术后辅助化疗对肝内胆管癌预后影响的多中心回顾性研究  

Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study

作　　者：林起柱 刘红枝 周伟平 程张军[3] 楼健颖[4] 郑树国 毕新宇 王剑明[7] 郭伟[8] 李富宇[9] 王坚[10] 郑亚民[11] 李敬东[12] 程石[13] 曾永毅 Lin Qizhu;Liu Hongzhi;Zhou Weiping;Cheng Zhangjun;Lou Jianying;Zheng Shuguo;Bi Xinyu;Wang Jianming;Guo Wei;Li Fuyu;Wang Jian;Zheng Yamin;Li Jingdong;Cheng Shi;Zeng Yongyi(Department of Hepatobiliary Surgery,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou 350002,China;Department of Hepatobiliary SurgeryⅢ,the Third Affiliated Hospital of Naval Medical University,Shanghai 200438,China;Department of Hepatobiliary and Pancreatic Surgery,Zhongda Hospital,Southeast University,Nanjing 210009,China;Department of Hepatobiliary Surgery,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China;Department of Hepatobiliary Surgery,the Southwest Hospital of Army Medical University,Chongqing 400038,China;Department of Hepatobiliary Surgery,Cancer Hospital,Peking Union Medical University,Chinese Academy of Medical Sciences,Beijing 100021,China;Department of Hepatobiliary Surgery,Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China;Department of Hepatobiliary Surgery,Beijing Friendship Hospital Affiliated to Capital Medical University,Beijing 100050,China;Department of Hepatobiliary Surgery,West China Hospital,Sichuan University,Chengdu 610041,China;Department of Hepatobiliary Surgery,Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200127,China;Department of Hepatobiliary Surgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China;Department of Hepatobiliary Surgery,Tiantan Hospital Affiliated to Capital Medical University,Beijing 100070,China)

机构地区：[1]福建医科大学孟超肝胆医院肝胆外科,福州350002 [2]海军军医大学第三附属医院肝外三科,上海200438 [3]东南大学附属中大医院肝胆胰外科,南京210009 [4]浙江大学医学院附属第二医院肝胆胰外科,杭州310009 [5]陆军军医大学西南医院胆道外科,重庆400038 [6]中国医学科学院北京协和医学院肿瘤医院肝胆外科,北京100021 [7]华中科技大学同济医学院附属同济医院胆胰外科,武汉430030 [8]首都医科大学附属北京友谊医院普外科,北京100050 [9]四川大学华西医院胆道外科,成都610041 [10]上海交通大学医学院附属仁济医院胆胰外科,上海200127 [11]首都医科大学宣武医院普外科,北京100053 [12]川北医学院附属医院肝胆外科,南充637000 [13]首都医科大学附属北京天坛医院普外科,北京100070

出　　处：《中华外科杂志》2023年第4期305-312,共8页Chinese Journal of Surgery

摘　　要：目的探讨术后辅助化疗对肝内胆管癌(ICC)患者根治性切除术后生存的影响及辅助化疗的可能获益人群。方法回顾性收集2011年12月至2017年12月中国13家医院654例术后病理学诊断为ICC的患者的临床和病理学资料。根据纳入及排除标准,共纳入455例患者,男性278例,女性177例;年龄[M(IQR)]59(16)岁(范围:23~88岁)。其中接受术后辅助化疗69例(化疗组),未接受术后辅助化疗386例(未化疗组)。采用倾向性评分匹配(PSM)法对化疗组和未化疗组的组间差异进行均衡,采用Kaplan-Meier法绘制PSM前后的生存曲线,并使用Log-rank检验比较组间总体生存(OS)与无复发生存(RFS)的差异。采用Cox单因素分析确定根治性切除术后ICC患者OS的预后因素。然后对P<0.10的预后因素进行多变量Cox比例风险模型分析,以确定潜在的独立预后因素。根据纳入的研究变量及AJCC分期系统对人群进行分层,并使用Kaplan-Meier法进行亚组分析,探讨辅助化疗的可能获益人群。结果经1∶1 PSM后,两组均得到69例患者,组间基线资料的差异无统计学意义(P值均>0.05)。PSM后Cox多因素分析结果显示,淋巴结是否转移(HR=3.06,95%CI:1.52~6.16,P=0.039)、切缘宽度(HR=0.56,95%CI:0.32~0.99,P=0.044)及是否接受辅助化疗(HR=0.51,95%CI:0.29~0.91,P=0.022)是影响ICC患者OS的独立预后因素。Kaplan-Meier法分析结果显示,化疗组较未化疗组的OS时间更长(P<0.05);而化疗组及未化疗组RFS时间的差异无统计学意义(P>0.05)。亚组分析结果显示,女性、无乙肝病毒感染、癌胚抗原<9.6μg/L、CA19-9≥200 U/ml、术中出血量<400 ml、肿瘤最大径>5 cm、无微血管侵犯、淋巴结转移阳性、AJCCⅢ期的患者可从辅助化疗中获益(P值均<0.05)。结论辅助化疗能延长ICC患者根治性切除术后的OS时间,肿瘤最大径>5 cm、淋巴结转移阳性、AJCCⅢ期、无微血管侵犯的患者更可能从辅助化疗中获益。Objectives To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC)and identify patients who may benefit from it.Methods The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 were collected retrospectively in 13 hospitals in China.According to inclusion and exclusion criteria,455 patients were included in this study,including 69 patients(15.2%)who received adjuvant chemotherapy and 386 patients(84.8%)who did not receive adjuvant chemotherapy.There were 278 males and 177 females,with an age of 59(16)years(M(IQR))(range:23 to 88 years).The propensity score matching(PSM)method was used to balance the difference between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group.The Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS)and recurrence free survival(RFS)between the two groups.Univariate analysis was used to determine prognostic factors for OS.Then,multivariate Cox proportional hazards models were performed for prognostic factors with P<0.10 to identify potential independent risk factors.The study population was stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy.Results After 1∶1 PSM matching,69 patients were obtained in each group.There were no significant differences in baseline data between the two groups(all P>0.05).After PSM,the Cox multivariate analysis showed that lymph node metastasis(HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin(HR=0.56,95%CI:0.32 to 0.99,P=0.044)and adjuvant chemotherapy(HR=0.51,95%CI:0.29 to 0.91,P=0.022)were independent prognostic factors for OS.Kaplan-Meier analysis showed that the median OS time of the adjuvant chemotherapy group was significant

关 键 词：胆管肿瘤 肝切除术 辅助化疗 预后 倾向评分匹配 多中心回顾性 

分 类 号：R735.7[医药卫生—肿瘤]