组织培养加药物敏感性测定在表浅膀胱癌术后丝裂霉素灌注化疗中的指导作用

Mitomycin intravesical chemotherapy for superficial bladder carcinoma guided by histo-culture drug response assay

目的探讨组织培养加药物敏感性测定在指导表浅膀胱癌术后丝裂霉素（MMC）膀胱灌注化疗中的应用价值。方法原发表浅膀胱移行细胞癌患者41例。男30例，女11例。平均年龄55岁。TNM分期：Ta10例、T131例。病理分级：G19例、G222例、G310例。采用经尿道电切或膀胱部分切除术保留膀胱。肿瘤标本依次行三维组织培养和改良噻唑盐（MTT）法药物敏感性测定。生长抑制率〉70％为高度敏感，50％～70％为中度敏感，〈50％为不敏感。41例患者术后均行MMC标准膀胱灌注化疗。无复发随访时间5年，中途复发者则随访结束。结果41例患者癌组织经1g／L浓度MMC作用2h后不敏感13例，其中T11例、T112例（P=0．009），G11例、G27例、G35例（P=0．101）。灌注化疗后随访3～5年，复发16例（39％），其中Ta1例、T115例（P=0．059），G210例、G36例（P=0．016）。对MMC不敏感组的复发率为77％（10／13），敏感组仅为21％（6／28，P=0．004）。单因素Kaplan-Meier生存分析和Log-rank检验结果显示，平均无肿瘤复发时间不敏感组为16．5个月，敏感组为49．2个月（P〈O．001）。多因素Cox回归分析显示对MMC敏感性是独立预后因子（P=0．008）。此法预测MMC膀胱灌注化疗效果的准确率为78％。结论利用组织培养药物敏感性测定方法指导表浅膀胱癌术后MMC灌注化疗，可提高疗效，降低肿瘤复发率。

Objective To evaluate the efficacy of mitomycin （MMC） intravesical chemotherapy for superficial bladder carcinoma by in vitro chemosensitivity using histoculture drug response assay （HDRA）. Methods Forty one cases of superficial bladder transitional cell carcinoma（TCC） were obtained, including 30 males and 11 females with mean age of 55 years. Of them, 10 cases were Ta and 31 were T1 according to TNM stage system （UICC 2002） while 9 cases were G1 , 22 were G2 and 10 were G3 （WHO1973）. All cases had no chemotherapy history before operation and were operated to retain bladder. Tumor specimens were cultured by three-dimensional histoculture. HDRA with im proved MTT assay was utilized for chemosenstivity test of MMC with 1 g/L concentration and 2 hours exposure. Growth inhibition rate （GI） exceeding 70% was defined as high-sensitive while less than 50% GI was defined as insensitive, others were moderate-sensitive. All cases were performed standard intravesical chemotherapy with MMC 40 mg plus 40 ml saline. Every case was followed up every 3 months. The patients were followed up for 5 years or untill recurrence. Results The MMC chem osensitivity was different among 41 patients. Thirteen cases were insensitive including 1 of Ta, 12 of T1 （P=0. 009） and 1 of G1 , 7 of G2 , 5 of G3 （P=0. 101）. Total recurrence rate was 39%（16/41） after 3 to 5 years＇ follow-up. There were 1 of Ta, 15 of T1（P=0.059） and 10 of G2, 6 of G3（P= 0. 016）. Insensitive group recurrence rate was 77 % （10/13） while sensitive group was 21% （6/28, P= 0. 004）. Patients in sensitive group showed a longer median time（49.2 months） than patients in insensitive group （16.5 months, P〈0. 001） according to Kaplan Meier analysis with Log rank test. The MMC chemosensitivity was independent prognostic factor examed by Cox regression analysis （P = 0. 008）. There was a 78% correlation rate of chemosensitivity by HDRA to clinical effect of MMC intravesical chemotherapy. Conclusion HDRA could evaluate MMC intravesical chemotherapy for superficial bladder TCC, improve therapeutic effect and lower tumor recurrence rate.