丝裂霉素膀胱热灌注化疗治疗高复发浅表性膀胱癌的初步临床研究

Clinical studies of HIVEC with MMC in highly recurrent superficial TCC of the bladder

目的:探讨丝裂霉素(MMC)膀胱腔内热灌注化疗治疗高复发浅表性膀胱移行细胞癌(TCC)的有效性。方法:选择高复发性TCC患者18例,男16例,女2例,年龄41～80岁,平均59.4岁。Ⅰ级、Ⅱ级各9例,病理分期均为T1期。复发次数3～12次,平均4.1次;最后1次复发间隔3～12个月,平均6.2个月;复发肿瘤个数1～20个,平均6.5个。所有患者入院后先行经尿道膀胱肿瘤电切术,术后随机分为两组,对照组9例,术后24h内膀胱灌注MMC 20mg,治疗45min,3天1次共4次;实验组9例,术后3天行MMC膀胱腔内热灌注化疗:先给予杜冷丁+非那根肌注,留置三腔导尿管,生理盐水600ml中加入MMC 80mg,治疗温度45℃,流速150ml/min,通过动力泵泵入膀胱,将进水管连接热交换器,进行膀胱体外循环治疗45min,3天1次共4次。治疗前后2天复查血常规、肝肾功能。治疗后2年内每3个月复查膀胱镜,2年后每6个月复查膀胱镜,了解肿瘤有无局部复发;同时检查X线、B超,了解肿瘤有无远处转移。结果:实验组男7例,女2例,平均年龄61.2岁;对照组男9例,平均年龄57.6岁。实验组与对照组治疗前的肿瘤复发次数、肿瘤个数、肿瘤复发时间差异无统计学意义(P>0.05)。实验组入水温度44.7～45.2℃,出水温度43.5～44.0℃,温度差(入水温度-出水温度)小于2℃。患者治疗期间耐受性和依从性良好,无一例因出现严重并发症而退出治疗。治疗期间主要不良反应为尿频、尿急、尿痛,排尿不适,症状在治疗后3天～2周内消失。患者均获得平均20个月的随访,均健在,无盆腔淋巴结转移及远处转移。对照组7例出现局部复发,复发时间平均6.4个月,肿瘤个数1～5个,平均2.6个;实验组局部复发3例,复发时间平均10个月,复发个数1～2个,平均1.7个。两组治疗后复发间期比较,实验组治疗后复发间期较对照组显著延长(P<0.05)。结论:对于高复发浅表性TCC患者,MMC膀胱热灌注化疗可减少肿瘤复发机会,使肿瘤复发时间延长,数目减少,可增强MMC治疗TCC的临床效果。

Objective： To investigate the efficacy and toxicity of hyperthermic intravesical chemotherapy （HIVEC） with mitomycin C as an adjuvant treatment, after complete transurethral resection（TURB） of highly re= current superficial transitional cell carcinoma（TCC） of the bladder. Methods： Between 2008 and 2009, 18 patients were enrolled. These patients suffering from highly recurrent superficial （Ta-T1） TCC of the bladder, after a com- plete TURBT, were randomly assigned to experimental group and controll group. Night patients was experimental group. Experimental group receive HIVEC with mitomycin C. A new system, BR-TRGY-I, was used. Two the- mometers were located inside the perfusion catheter in the inflow and outflow drug solution. The goal temperature was 45 ~C. The drug solution was constantly pumped into the bladder with 150 ml/min. A drug solution consisted of 80 mg mitomycin-C dissolved in 600 ml of normal saline. The treatment was concluded after a total period of 45 minutes of effective heating （mean inflow solution temperature greater than 41 ℃ ）. HIVEC was administered in four 3-day cycles. The other night patients, which underwent the perfusion of common temperature drug solution, served as control group. The follow-up protocol consisted of cystoscopy every 3 months thereafter. Results： The combined chemo-thermotherapy was tolerated relatively well. Most treatment side effects were localized and tran- sient. After a mean follow-up of 20 months, 66.7% of these patients were recurrence free in experimental group. Three（33. 3%） recurrences were seen in a mean period of 10 months in these patients and were treated with TURBT. While seven（77.7%） recurrences were seen in a mean period of 6.4 months in control group. No disease-related mortality had occurred. The results demonstrate a highly significant difference in recurrence time of tumors in the experimental group and control group. Conclusions= HIVEC is an active treatment in patients with highly recurrent superficial TCC of the bladder.