Histotripsy of Renal Implanted VX-2 Tumor in a Rabbit Model: Investigation of Metastases

OBJECTIVE To compare the number and density of lung metastases in histotripsy-treated and control subjects. Histotripsy is a noninvasive, nonthermal, pulsed ultrasound technology that produces targeted mechanical tissue fractionation. Histotripsy ablation of renal implanted VX-2 tumor has been previously demonstrated; however, concerns have been raised that mechanical forces associated with histotripsy might result in unwanted metastatic dissemination of tumor. METHODS VX-2 tumor was implanted into the left kidneys of New Zealand White rabbits. Twenty rabbits were treated with histotripsy on day 13; 8 were maintained as controls. All rabbits underwent left nephrectomy on day 14. Lungs were harvested and processed for histopathologic inspection on day 19. Whole-mount coronal lung sections were examined to determine the number of metastases and metastatic density. RESULTS Tumors grew after implantation in all 28 cases and were localized with ultrasound in 19 of 20 subjects before treatment. Histology confirmed fractionation of tumor in all treatment rabbits. The number of lung metastases (88.7 vs 72.5; P = .29) and the metastatic density (8.9 vs 7.0 mets/cm(2); P = .22) were not statistically different between treatment and control rabbits. CONCLUSION Histotripsy of renal implanted VX-2 tumor in an in-vivo rabbit model did not produce a statistically significant increase in number or density of lung metastasis. Data suggesting a trend toward increased metastases after histotripsy are overwhelmed by the high baseline rate of metastases in this aggressive tumor model. Further investigation using less aggressive tumor models is indicated to clarify this relationship. UROLOGY 80: 724-729, 2012. (c) 2012 Elsevier Inc.