Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Urol. 2012 Nov;188(5):1957-64. doi: 10.1016/j.juro.2012.07.006. Epub 2012 Sep 20.
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.
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.
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.
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.
Histotripsy 是一种非热消融的聚焦超声技术,可能有未来用于前列腺癌局灶治疗的应用。我们使用 ACE-1 前列腺肿瘤模型,评估了 Histotripsy 治疗前列腺肿瘤的可行性。
总共 10 只免疫抑制(环孢素处理)的犬接受了经直肠超声引导的经皮前列腺内注射 ACE-1 犬前列腺癌细胞。通过经直肠超声对前列腺进行连续成像,以监测肿瘤生长。动物接受假手术(3 只)或经腹 Histotripsy 治疗,该治疗使用 750 kHz 压电超声治疗换能器靶向植入的肿瘤和相邻的实质。对前列腺进行组织学检查以确认肿瘤和 Histotripsy 治疗效果。
在肿瘤注射后 2 周内,所有 10 只动物的经直肠超声均可见 ACE-1 肿瘤。病变在前列腺包膜、腺小叶、纤维隔和尿道周围基质中生长,有明显的促结缔组织反应和中央坏死区,组织学上。4 只动物出现淋巴结和/或肺转移。在所有接受治疗的动物中,超声肿瘤定位和 Histotripsy 治疗期间空化的启动都是可行的。组织学上,在 4 只急性动物中,肿瘤和前列腺实质均有均质化的证据,3 只慢性动物中有坏死和出血。
本研究表明 Histotripsy 破坏犬 ACE-1 模型前列腺肿瘤的可行性。提示 Histotripsy 基的局灶治疗在前列腺癌中可能有一定作用。需要进一步的研究来更好地描述 Histotripsy 对恶性组织的影响。