title: Histotripsy focal ablation of implanted prostate tumor in an ACE-1 canine cancer model.
abstract: OBJECTIVE
  Histotripsy is a nonthermal ablative focused ultrasound technology with possible future applications for prostate cancer focal therapy. We used the ACE-1 prostate tumor model and evaluated the feasibility of treating prostate tumors with histotripsy.
  
  
  METHODS
  A total of 10 immunosuppressed (cyclosporine treated) canine subjects received transrectal ultrasound guided percutaneous intraprostatic injection of ACE-1 canine prostate cancer cells. Prostates were serially imaged with transrectal ultrasound to monitor tumor growth. Subjects were sham treated (3) or underwent transabdominal histotripsy of the prostate, which targeted implanted tumor and adjacent parenchyma using a 750 kHz piezoelectric ultrasound therapy transducer. Prostates were examined histologically to confirm tumor and the histotripsy treatment effect.
  
  
  RESULTS
  ACE-1 tumors were visualized on transrectal ultrasound in all 10 subjects within 2 weeks of tumor injection. Lesions demonstrated growth in the prostatic capsule, glandular lobules, fibrous septa and periurethral stroma with significant desmoplastic reaction and areas of central necrosis on histology. Lymph node and/or pulmonary metastases developed in 4 subjects. Ultrasound tumor localization and initiation of cavitation during histotripsy therapy were feasible in all treated subjects. Histologically there was evidence of homogenization of tumor and prostatic parenchyma in all 4 acute subjects with necrosis and hemorrhage in the 3 chronic subjects.
  
  
  CONCLUSIONS
  This study shows the feasibility of histotripsy destruction of prostate tumors in a canine ACE-1 model. It suggests a potential role for histotripsy based focal therapy for prostate cancer. Further studies are needed to better characterize the effects of histotripsy on malignant tissues.
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Schade
authors.forename: Jill
authors.initials: J
authors.lastname: Keller
authors.forename: Kim
authors.initials: K
authors.lastname: Ives
authors.forename: Xu
authors.initials: X
authors.lastname: Cheng
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rosol
authors.forename: Evan
authors.initials: E
authors.lastname: Keller
authors.forename: William W
authors.initials: WW
authors.lastname: Roberts
mesh_terms: D055011:Ablation Techniques / Q000379:methods; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male; D009368:Neoplasm Transplantation; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology*