【摘要】 目的 探讨轻中度肾功能不全肌层浸润性膀胱癌患者应用含顺铂的新辅助化疗的有效性和安全性。方法 56例估算肾小球滤过率(estimated glomerular filtration rate, eGFR)为50～60 mL/min的肌层浸润性膀胱癌患者，其中新辅助化疗采用ddMVAC方案(剂量密集的甲氨蝶呤+长春新碱+多柔比星+顺铂)者31例为ddMVAC组，采用GC方案(吉西他滨+顺铂)者25例为GC组。完成2个周期新辅助化疗的患者行根治性膀胱切除术。新辅助化疗前、术前、术后次日检测患者血肌酐，计算eGFR,并分别计算术前、术后eGFR降低百分比。完成新辅助化疗患者术后随访1年，记录复发及转移情况，绘制Kaplan-Meier生存曲线，分析2组术后1年无病生存情况。2组新辅助化疗前及术后1年采用ELISA法检测血清血管内皮细胞生长因子(vascular endothelial growth factor, VEGF)、基质金属蛋白酶(matrix metalloproteinase, MMP)-2、MMP-9水平，采用流式细胞术检测CD4~+、CD8~+T淋巴细胞比率，计算CD4~+/CD8~+比值。结果ddMVAC组共26例完成新辅助化疗，GC组共21例完成新辅助化疗，ddMVAC组新辅助化疗完成比率(83.87%)与GC组(84.00%)比较差异无统计学意义(χ~2=0.983,P=0.388)。ddMVAC组体质量指数、吸烟史、组织病理T分期及新辅助化疗前血肌酐、eGFR与GC组比较差异均无统计学意义(P>0.05)。ddMVAC组术前eGFR降低百分比[(11.02±2.41)%]与GC组[(11.15±2.66)%]比较差异无统计学意义(t=-0.176,P=0.861),术后eGFR降低百分比[(15.20±4.17)%]低于GC组[(18.26±5.09)%](t=-2.266,P=0.028)。ddMVAC组新辅助化疗前血清VEGF、MMP-2、MMP-9水平，CD4~+、CD8~+T淋巴细胞比率及CD4~+/CD8~+比值与GC组比较差异均无统计学意义(P>0.05);ddMVAC组术后1年血清VEGF、MMP-2、MMP-9水平[(34.11±7.04)ng/L、(97.26±15.04)mg/L、(91.09±16.88)mg/L]及CD8~+T淋巴细胞比率[(26.88±5.72)%]均高于GC组[(29.63±6.30)ng/L、(87.01±16.73)mg/L、(81.40±15.02)mg/L、(20.63±5.01)%](P<0.05),CD4~+T淋巴细胞比率[(41.33±9.17)%]、CD4~+/CD8~+比值(1.46±0.38)均低于GC组[(47.82±9.39)%、1.90±0.44](P<0.05)。ddMVAC组术后1年无病生存率(84.62%)与GC组(90.48%)比较差异无统计学意义(χ~2=0.025,P=0.874)。结论 部分轻中度肾功能不全的肌层浸润性膀胱癌患者新辅助化疗采用ddMVAC方案和GC方案时患者耐受性和1年生存率无明显差异，GC方案对患者肾功能及免疫功能的影响较ddMVAC方案小。更多还原

【Abstract】 Objective To investigate the efficacy and safety of cisplatin-based neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer(MIBC)with mild to moderate renal insufficiency.Methods In 56 MIBC patients with estimated glomerular filtration rate (eGFR)of 50to 60 mL/min,31patients received large dose of methotrexate+vincristine+doxorubicin+cisplatin (ddMVAC group),and 25patients received gemcitabine+cisplatin (GC group).Radical cystectomy was performed after two neoadjuvant chemotherapy cycles were completed and the tumor volume was significantly reduced by imaging examination.The serum creatinine level was measured before neoadjuvant chemotherapy,before surgery,and the next day after surgery.The eGFR was calculated,and the eGFR reduction percentages declined before and after surgery were calculated.Those who completed neoadjuvant chemotherapy were followed up for 1year after surgery to record the recurrence and metastasis.Kaplan-Meier curves were drawn to analyze 1-year disease-free survival in two groups.The serum vascular endothelial growth factor(VEGF),matrix metalloproteinase(MMP)-2and MMP-9 were detected by ELISA before neoadjuvant chemotherapy and 1 year after surgery.CD4~+and CD8~+T lymphocyte rates were detected by flow cytometry and CD4~+/CD8~+ratio was caculated.Results Twenty-six patients in ddMVAC group and 21in GC group completed neoadjuvant chemotherapy,and there was no significant difference in the completion rate of neoadjuvant chemotherapy between ddMVAC group(83.87%)and GC group(84.00%）（χ~2=0.983,P=0.388).There were no significant differences in the body mass index,smoking history,histopathological T stage,and serum creatinine and eGFR before neoadjuvant chemotherapy between two groups(P>0.05).The eGFR percentage declined showed no significant difference between ddMVAC group[(11.02±2.41)%]and GC group[(11.15±2.66)%]before surgery(t=-0.176,P=0.861),and was lower in ddMVAC group[(15.20±4.17)%]than that in GC group[(18.26±5.09)%]after surgery(t=-2.266,P=0.028).The levels of serum VEGF,MMP-2and MMP-9,rates of CD4~+and CD8~+T lymphocytes,and CD4~+/CD8~+ratio showed no significant differences between two groups before neoadjuvant chemotherapy (P>0.05).The levels of serum VEGF,MMP-2and MMP-9,and the rate CD8~+T lymphocytes were higher in ddMVAC group[(34.11±7.04)ng/L,(97.26±15.04)mg/L,(91.09±16.88)mg/L,(26.88±5.72)%]than those in GC group[(29.63±6.30)ng/L,(87.01±16.73)mg/L,(81.40±15.02)mg/L,(20.63±5.01)%]1year after surgery(P<0.05),the rate of CD4~+T lymphocytes and CD4~+/CD8~+ratio were lower in ddMVAC group[(41.33±9.17)%,1.46±0.38]than those in GC group[(47.82±9.39)%,1.90±0.44](P<0.05),and the disease-free survival rate showed no significant difference between two groups (84.62%vs.90.48%）（χ~2=0.025,P=0.874).Conclusion For MIBC patients with mild to moderate renal insufficiency,ddMVAC and GC regimens have similar tolerance and 1-year survival rate,and GC regimen has less effect on renal function and immune function.更多还原