肝移植联合腺病毒介导的单纯疱疹病毒胸苷激酶/更昔洛韦治疗肝细胞癌的研究探索  

Study on liver transplantation combined with adenovirus-mediated delivery of herpes simplex virus thymidine kinase/ganciclovir in treatment of hepatocellular carcinoma

作　　者：王振顺 刘召波 林栋栋[1] 李宁[2] WANG Zhenshun;LIU Zhaobo;LIN Dongdong;LI Ning(Department of General Surgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,P.R.China;Department of General Surgery,Beijing Youan Hospital,Capital Medical University,Beijing 100069,P.R.China)

机构地区：[1]首都医科大学宣武医院普通外科,北京100053 [2]首都医科大学附属北京佑安医院普通外科中心,北京100069

出　　处：《中国普外基础与临床杂志》2023年第1期53-59,共7页Chinese Journal of Bases and Clinics In General Surgery

基　　金：“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项(项目编号:2017ZX10203205-006-003)。

摘　　要：目的分析肝移植(liver transplantation,LT)联合腺病毒介导的单纯疱疹病毒胸苷激酶/更昔洛韦(adenovirus-mediated delivery of herpes simplex virus thymidine kinase/ganciclovir,ADV-TK/GCV)治疗肝细胞癌的临床疗效,希望能使更多超米兰标准的肝细胞癌患者从中获益。方法收集笔者团队2007年至今采用LT治疗的肝细胞癌患者的临床病理资料,根据是否联合ADV-TK/GCV将患者分为单纯LT组和LT+ADV-TK/GCV组,比较总体肝细胞癌患者及其中超米兰标准患者行单纯LT和LT+ADV-TK/GCV治疗后的5年累积总生存率和无复发生存率,同时采用Cox回归多因素分析影响肝细胞癌患者LT术后长期总生存时间和无复发生存时间的危险因素。结果本研究共收集到符合纳入条件的肝细胞癌患者216例,其中单纯LT组134例、LT+ADV-TK/GCV组82例,单纯LT组和LT+ADV-TK/GCV组累积5年总生存率分别为52.9%和48.5%、累积无复发生存率分别为41.5%和44.5%。216例肝细胞癌患者中超米兰标准患者162例,超米兰标准患者中单纯LT者101例、LT+ADV-TK/GCV者61例。所有肝细胞癌患者和超米兰标准肝细胞癌患者的单纯LT组和LT+ADV-TK/GCV组的基线资料比较差异均无统计学意义(P>0.05)。对所有肝细胞癌患者分析的5年总生存率和无复发生存率比较差异均无统计学意义(P>0.05);对超米兰标准肝细胞癌患者的生存分析发现,LT+ADV-TK/GCV患者的5年总生存率优于单纯LT患者(χ^(2)=4.11,P=0.047),但未发现二者的5年无复发生存率比较差异有统计学意义(以27个月生存时间为界,P=0.46、P=0.06)。Cox回归多因素分析影响肝细胞癌患者LT术后总生存率和无复发生存率的危险因素发现,患者的年龄小、累积肿瘤直径大及术前TNM分期晚降低LT术后患者无复发生存概率(P<0.05),而未发现联合ADV-TK/GCV治疗对长期无复发生存率的影响(P>0.05);同时发现累积肿瘤直径越小、术前TNM分期早、术前血清甲胎蛋白≤400μg/Objective To evaluate the therapeutic effect of liver transplantation(LT)combined with adenovirusmediated delivery of herpes simplex virus thymidine kinase/ganciclovir(ADV-TK/GCV)in treatment of patients with hepatocellular carcinoma(HCC),so as to benefit more patients with HCC beyond the Milan criteria.Methods The clinicopathologic data of patients with HCC underwent LT by the author team since 2007 were collected and analyzed.The patients were assigned into simple LT group and LT+ADV-TK/GCV group.The 5-year cumulative overall survival rate and relapse free survival rate of all LT patients and the patients with LT beyond the Milan criteria by simple LT and LT+ADV-TK/GCV therapy were compared.Meanwhile,Cox regression was used to analyze the risk factors affecting long-term overall survival rate and relapse free survival rate of all patients with HCC after LT.Results A total of 216patients eligible for inclusion were collected in this study,including 134 patients in the simple LT group and 82 patients in the LT+ADV-TK/GCV group,162 of whom beyond the Milan criteria,including 101 patients underwent the simple LT and 61 patients underwent the LT+ADV-TK/GCV.There were no statistical differences in the baseline data between the simple LT and LT+ADV-TK/GCV in all patients and patients beyond the Milan criteria(P>0.05).There were no statistical differences in 5-year overall survival rate and relapse free survival rate of all patients with HCC(P>0.05).The 5-year cumulative overall survival rate of the LT+ADV-TK/GCV group was better than that of the simple LT group in the patients beyond the Milan criteria(χ^(2)=4.11,P=0.047),but it was not found that the 5-year cumulative relapse free survival rate had statistical difference(27-month survival time as the critical value,P=0.46,P=0.06).Cox regression multivariate analysis results showed that the larger cumulative tumor diameter,the preoperative elevated serum alpha fetoprotein(>400μg/L),later TNM stage,and without combination of ADV-TK/GCV therapy increased the probabili

关 键 词：肝移植 腺病毒介导的单纯疱疹病毒胸苷激酶/更昔洛韦 米兰标准 长期生存 

分 类 号：R735.7[医药卫生—肿瘤]