Abaza Ronney, Miocinovic Ranko, Keck Rick W, Selman Steven H
Department of Urology, Ohio State University Medical Center and James Cancer Hospital, Columbus and University of Toledo College of Medicine, Toledo, Ohio.
J Urol. 2009 Apr;181(4):1901-6. doi: 10.1016/j.juro.2008.11.089. Epub 2009 Feb 23.
Tumor spillage from bladder perforation during transurethral bladder tumor resection or cystectomy risks seeding the peritoneum with transitional cell carcinoma. We determined the lowest effective mitomycin C dose to prevent tumor implantation and the potential efficacy of delayed therapy. Additionally, we investigated the effect of tumor debulking combined with intraperitoneal mitomycin C.
Using our established murine model of intraperitoneal transitional cell carcinoma implantation mitomycin C was instilled at decreasing concentrations to find the lowest effective dose. To evaluate the effectiveness of delayed therapy mitomycin C was administered on day 3 or 7 after tumor implantation. Finally, surgical debulking of established tumors with or without mitomycin C was performed.
All control animals had disseminated carcinomatosis. The lowest effective intraperitoneal mitomycin C dose to prevent implantation was 0.3125 mg/m(2). Administration of mitomycin C on day 3 after instillation resulted in tumor-free status in 50% of the animals, although no rats were tumor-free when treated on day 7. Tumor debulking only for established disease cured 40% of the animals, whereas debulking combined with mitomycin C had a 100% cure rate.
Intraperitoneal mitomycin C prevents tumor growth after transitional cell carcinoma implantation. Delayed therapy is not as effective as immediate treatment but cure is still possible, particularly when combined with surgical debulking, in a rat model.
经尿道膀胱肿瘤切除术或膀胱切除术期间膀胱穿孔导致肿瘤溢出,有使腹膜播散移行细胞癌的风险。我们确定了预防肿瘤种植的最低有效丝裂霉素C剂量以及延迟治疗的潜在疗效。此外,我们研究了肿瘤减瘤联合腹腔内注射丝裂霉素C的效果。
使用我们建立的腹腔内移行细胞癌种植小鼠模型,以递减浓度滴注丝裂霉素C以找到最低有效剂量。为了评估延迟治疗的效果,在肿瘤种植后第3天或第7天给予丝裂霉素C。最后,对已形成的肿瘤进行手术减瘤,有或没有丝裂霉素C。
所有对照动物均发生播散性癌病。预防种植的最低有效腹腔内丝裂霉素C剂量为0.3125mg/m²。滴注后第3天给予丝裂霉素C,50%的动物无肿瘤,而在第7天治疗时没有大鼠无肿瘤。仅对已形成的疾病进行肿瘤减瘤可治愈40%的动物,而减瘤联合丝裂霉素C的治愈率为100%。
腹腔内注射丝裂霉素C可预防移行细胞癌种植后的肿瘤生长。在大鼠模型中,延迟治疗不如立即治疗有效,但仍有可能治愈,特别是与手术减瘤联合使用时。