Urethral-sparing histotripsy of the prostate in a canine model

To evaluate the feasibility and healing response to urethral-sparing prostate histotripsy using a canine model of benign prostatic hypertrophy.

Histotripsy was performed on 10 canines using a 750-kHz piezoelectric ultrasound transducer targeting the prostatic parenchyma while avoiding the urethra. Periprocedure prostatic urethral integrity was evaluated with serial cystourethroscopy. Evolution of histotripsy treatment effect and subjects' response to urethral sparing was evaluated with serial ultrasound and laboratory evaluation, respectively. The dogs were euthanized acutely or chronically and findings were confirmed histologically.

Bilateral treatment was possible in 8/10 subjects, whereas unilateral treatment was performed in 2/10. Failure to spare the urethra was observed in 2/18 treatments-one acutely and one chronically, despite normal cystourethroscopy for the first week. Modest prostatic volume reduction was seen in subjects survived to 8 weeks post histotripsy. Laboratory studies revealed transient perioperative increases in mean white blood cell count, C-reactive protein, and lactate dehydrogenase. On histology, 80% of successful urethral sparing treatment cavities were completely epithelialized, containing simple fluid with minimal cellular debris at 8 weeks despite no communication with the urethra.

Urethral-sparing histotripsy of the prostate is feasible and well tolerated in a canine model, resulting in modest volume reduction and prompt resorption of homogenized tissue debris. Human studies to evaluate the clinical utility and symptomatic response of urethral sparing are needed.