膀胱内灌注纤维蛋白溶解抑制药物对卡介苗预防膀胱癌复发的影响

Clinical investigation on the effect of intravesical instillation of antifibrinolytic agents with bacillus Calmette-Guerin on preventing bladder cancer recurrence

目的探讨纤维蛋白溶解抑制药物作为卡介苗(BCG)的佐剂与BCG联合膀胱内灌注治疗对BCG预防膀胱癌术后复发的影响.方法将行手术治疗后的326例浅表性膀胱移行细胞癌(BTCC)患者随机分成A组[66例,其中经尿道膀胱肿瘤电切术(TURBT)59例、膀胱部分切除术7例]、B组(64例,其中行TURBT 60例,膀胱部分切除术4例)、C组(65例,其中行TURBT 61例、膀胱部分切除术4例)、D组(64例,其中行TURBT 59例、膀胱部分切除术5例)及E组(67例,其中行TURBT 61例、膀胱部分切除术6例),A组患者术后定期膀胱内灌注BCG 100～120 mg+氨甲苯酸(PAMBA)0.1 g,B 组灌注BCG 50～60 mg+PAMBA 0.1 g,C组灌注BCG 100～120 mg+氨基己酸(EACA)2.0 g,D组灌注BCG50～60 mg+ EACA 2.0 g,E组灌注BCG 100～120 mg,每周1次,6次后每月1次.灌注后每3个月行膀胱镜检查. 结果术后随访4～69个月,平均28.5个月, A、B、C、D组膀胱癌的复发率分别为12%(7/59),10%(6/58),9%(5/54)和9%(5/56),低于E组的30%(17/57),差异均有统计学意义(χ2值分别为5.699,6.818,7.380,7.867,P值分别为0.017,0.009,0.007,0.005);BCG剂量减少的B、D组复发率与A组、C组比较,差异无统计学意义(P>0.05),毒副反应发生率B、D组分别为3%(2/60)、5%(3/59),较A、C组的11%(7/66)、13%(8/62)降低.结论纤维蛋白溶解抑制药物PAMBA、EACA可作为BCG的佐剂,与BCG联合膀胱内灌注治疗可增强BCG预防膀胱癌术后复发的疗效,BCG剂量减半后疗效不降低.

Objective To investigate the effect of intravesical instillation of antifibrinolytic agents with bacillus Calmette-Guerin （BCG） on preventing recurrence of surperficial bladder transitional cell carcinoma （BTCC） after surgical management. Methods A total of 326 cases of superficial BTCC undergoing transurethral resection of bladder tumor （TURBT） or partial cystectomy were divided into 5 groups. Then the different dosage BCG with or without antifibrinolytic agents was regular instilled into bladders （ once a week, then once a month after 6 times）. Group A including 66 cases received intravesical instillation of 100--120 mg BCG plus 100 mg para-aminomethyl benzoic acid （PAMBA）. Group B including 64 cases： instillation of 50----60 mg BCG plus 100 mg PAMBA; Group C including 65 cases： 100--120 mg BCG plus 2. 0 g epsilon-aminocarproic acid （EACA） ; Group D including 64 cases： 50----60 mg BCG plus 2.0 g EACA; Group E （control group） including 67 cases： 100--120 mg BCG. All the cases had been followed up for 4 to 69 months （ mean, 28.5 months）. Not only was cystoscopy performed every 3 monthes, but also iopsy was carried out to identify recurrence when necessary. Side effect was recorded after instillation. Results The rate of tumor recurrence of Group A, Group B, Group C and Group D was 12% ,10%, 9%, 9% respectively, which was significantly lower than that of Group E （30%） （X^2 =5. 699,6. 818,7. 380,7. 867,P =0. 017,0. 009,0. 007,0. 005）. And there was no significant difference of tumor recurrence rate between Group A and Group B or between Group C and Group D （ Group A and Group C： high dosage BCG plus antifibrinolytic agents, while Group B and Group D： low dosage BCG plus antifibrinolytic agents ） （ P 〉 0. 05 ）. But the side effects developing in Group B and Group D after BCG instillation were less than those in Group A and Group C. Conclusions The efficacy of BCG on prevention the recurrence of surperficial BTCC can be enhanced when combined with antifibrinolytic agents. Even if the dosage of BCG was reduced by half, the efficacy didn＇t changed. A new approach of low dosage BCG plus antifibrinolytic agents is recommended in the prophylaxis of recurrence of bladder cancer.