肾素-血管紧张素系统拮抗剂对非肌层浸润性膀胱癌的预后影响

Influence of Renin-angiotensin System Blockage on Recurrence of Non-muscle-invasive Bladder Cancer

目的探讨血管紧张素转化酶抑制剂(ACEIs)和血管紧张素受体拮抗剂(ARBs)对非肌层浸润性膀胱癌(NMIBC)患者术后预后的影响。方法回顾性分析2009年1月至2011年12月收治的388例NMIBC患者的临床资料,术前因高血压服用ACEIs/ARBs者为用药组,术前未用ACEIs/ARBs者为对照组,再按高血压因素分层。总结两组患者病理组织学特征和临床特征,分析患者术后复发的独立危险因素。结果所有纳入的患者均为非肌层浸润后膀胱尿路上皮癌,行经尿道膀胱肿瘤切除术后均完成膀胱维持灌注化疗,其中306例术后完成了即刻膀胱灌注化疗,82例患者术后未行即刻膀胱灌注化疗。161例患者确诊高血压,其中,107例术前服用ACEIs/ARBs(用药组),54例未服用ACEIs/ARBs。对照组281例,包括54例高血压患者,227例非高血压患者。两组患者在年龄、性别、吸烟状态、肿瘤分期分级、肿瘤数量、肿瘤直径以及是否行膀胱即刻灌注化疗等方面比较差异无统计学意义,按血压、用药(ACEIs/ARBs)因素分层后上述指标差异仍无统计学意义。中位随访时间60月,用药组中36例复发,对照组中129例复发,两组肿瘤无复发生存时间分别为(48.43±23.50)月、(41.15±23.64)月,差异有统计学意义(P=0.007),5年肿瘤无复发生存率分别为66.36%、54.09%,差异有统计学意义(P=0.027)。Cox多因素回归分析显示,未服用ACEIs/ARBs[标准偏回归系数(β)=0.174]是影响NMIBC术后复发的独立危险因素(P<0.05),排在肿瘤直径≥3cm(β=0.193)、吸烟(β=0.191)、G3期肿瘤(β=0.181)之后,且权重排位不受血压影响。结论服用ACEIs/ARBs可改善NMIBC患者预后,降低术后复发率。

Objective To investigate the effects of angiotensin-converting enzyme inhibitors（ACEIs）and angiotensin receptor blockers（ARBs）on the recurrence of non-muscle-invasive bladder cancer（NMIBC）.Methods Clinical data of 388 patients with NMIBC undergoing transurethral resection of bladder tumor during Jan.2009 to Dec.2011 were retrospectively reviewed.Recurrence-free survival was analyzed,and the risk factors of recurrence were explored by Cox multivariate regression analysis.Results All patients were managed with postoperative intravesical chemotherapy,but 82 of them only received maintenance instillation without immediate instillation.There were 161 patients diagnosed of hypertension,107 of them were treated with ACEIs or ARBs.No significant differences in age,sex,history of smoking,pathological stage,pathological grade,tumor diameter and postoperation immediate instillation were observed between the patients treated with（drug-use group）or without ACEIs/ARBs（control group）.There was also no statistically significant difference among aforementioned indexes after the stratification by hypertension and medication（ACEIs/ARBs）.During a median follow up of 60 months,there were 36 and 129 patients found recurrence in drug-use group and control group,respectively.The recurrence free survival times of the patients treated with and without ACEIs/ARBs were（48.43±23.50）and（41.15±23.64）months,respectively（P=0.007）.The 5-year recurrence-free survival rate was 66.36%in drug-use group and 54.09%in the controls（P=0.027）.Multivariate regression analysis revealed that no ACEIs/ARBs treatment[standardized regression coefficient（β）=0.174]was independent risk factor of recurrence（P〈0.05）.The weight of no ACEIs/ARBs treatment was behind to no immediate instillation（β=0.131）,tumor multiplicity（β=0.128）,tumor diameter≥3 cm（β=0.193）,grade 3 tumor（β=0.181）,and smoking status（β=0.191）.Conclusion The administration of ACEIs/ARBs may decrease the recurrence of NMIBC after transurethral resection of bladder tumor.