Login to Access Video or Poster Abstract: MP100-02
Sources of Funding: The Urology Care Foundation, The Focused Ultrasound Foundation, NIH K01EB015745S_x000D_

Introduction

Boiling histotripsy (BH) is a focused ultrasound (US) technique that produces non-thermal mechanical ablation of targeted tissues. Our group has been developing BH as a non-invasive treatment for renal carcinoma (RCC). Previously, we have demonstrated the feasibility of BH ablation of RCC in vivo in the Eker rat RCC model. Here in we accessed the long-term effects of BH ablation and the evolution of the homogenized lesion over time._x000D_

Methods

Eker rats (n=15) were monitored for de novo RCCs with serial US. When tumors were ≥6 mm, rats underwent transcutaneous BH using a 1.5 MHz transducer (10-20 ms pulses, ~30kW/cm²) under US guidance targeting ~50% of the tumor. Following treatment, rats were provided with ketoprofen analgesia and monitored for complications. Serial US (Days 0, 1, 2, 7, 14, 28 and 56) was performed to assess the evolution of treatment within the targeted tumor. Rats were survived for 7 (n=5), 14 (n=5) or 56 (n=5) days. At euthanasia, necropsy was performed to assess for collateral damage and both kidneys underwent gross and histologic assessment._x000D_

Results

BH was successful in all cases producing hyperechoic bubbles within the targeted tumor which gave way to hypoechoic regions consistent with mechanical disruption. On serial post-BH US we observed an evolution of these heterogeneous hypoechoic regions within the tumor into well-circumscribed, nearly anechoic cavities by day 7. Subsequently, the cavities decreased in size and were mostly re-absorbed with apparent contour deformities on day 14, with no apparent cavity by Day 28. Histologically, day 7 tumors demonstrated sharply demarcated lesions containing homogenized cell debris that appeared to be devoid of all cellular features by day 14. Day 56 kidneys appeared completely healed. Rats appeared well post-BH with minimal pain and did not require analgesia beyond 24 hours. Hematuria was noted in 33% (n=5) of rats which resolved in all but one within 24 hours and in all by day 2. One rat required humane euthanasia on day 1 for a large perinephric hematoma. _x000D_

Conclusions

BH is a promising non-invasive treatment for RCC, producing desired tumor ablation with minimal collateral damage. Treatment appears well tolerated with rapid healing. Further studies will assess long-term tumor control while optimizing pulse parameters and image guidance to improve efficacy and safety._x000D_

Funding

The Urology Care Foundation, The Focused Ultrasound Foundation, NIH K01EB015745S_x000D_