微血管侵犯对肝内胆管癌根治性切除病人预后影响研究:基于多中心的倾向评分匹配分析

The prognostic impact of microvascular invasion on the prognosis of patients undergoing radical resection of intrahepatic cholangiocarcinoma:A multicenter propensity score matching analysis

目的分析微血管侵犯(MVI)对肝内胆管癌(ICC)根治性切除病人预后的影响。方法采用倾向评分匹配(PSM)及回顾性队列研究方法。搜集自2011年12月至2017年12月国内13家医疗中心(海军军医大学东方肝胆外科医院、浙江大学医学院附属第二医院、福建医科大学孟超肝胆医院、陆军军医大学西南医院、中国医学科学院北京协和医学院肿瘤医院、华中科技大学同济医学院附属同济医院、首都医科大学附属北京友谊医院、四川大学华西医院、上海交通大学医学院附属仁济医院、首都医科大学宣武医院、川北医学院附属医院、首都医科大学附属天坛医院、东南大学附属中大医院)收治的初诊为ICC病人的临床病理资料。其中男性202例,女性299例;中位年龄为57(49~64)岁,年龄范围为23~88岁。根据术后病理学诊断是否合并MVI分为MVI组和NonMVI组,其中MVI组61例、Non-MVI组440例。观察指标:(1)PSM前后两组病人基线资料比较。(2)生存分析:采用Kaplan-Meier法进行总体生存(OS)及无瘤生存(DFS)分析,COX回归分析影响ICC预后的独立危险因素。(3)MVI影响因素分析:Logistic回归分析MVI发生的独立危险因素。结果 (1)共纳入501例ICC根治性切除术后病人,MVI发生率为12.2%。经1∶1 PSM后,MVI组和Non-MVI组分别获得61例,两组之间基线资料差异无统计学意义(所有P>0.05)。(2)PSM前COX多因素分析结果显示:性别、肿瘤最大径、MVI、术后辅助治疗为OS的独立危险因素(HR=0.74,95%CI 0.58~0.94,P=0.013;HR=1.43,95%CI 1.11~1.83,P=0.006;HR=1.87,95%CI 1.35~2.58,P<0.01;HR=0.69,95%CI 0.50~0.97,P=0.031)。性别、切缘距离、病理学分型、肿瘤最大径、卫星灶、微血管侵犯为DFS的独立危险因素(HR=0.80,95%CI 0.64~1.01,P=0.061;HR=1.40,95%CI 1.10~1.77,P=0.005;HR=1.51,95%CI 1.08~2.12,P=0.017;HR=1.35,95%CI 1.07~1.71,P=0.013;HR=1.74,95%CI 1.21~2.52,P=0.003;HR=2.36,95%CI 1.73~3.21,P<0.01)。经1∶1 PSM,COX多因素分析结果显示:Child-Pugh分级、MVI为OS的独立危险因素(HR=1.75,95%CI 1.03~2.99,P=0.039;HR=1.84,95%CI 1.17~2.90,P=0.008)。病理学分型、MVI为DFS的独立危险因素(HR=1.93,95%CI 1.08~3.44,P=0.027;HR=2.64,95%CI 1.64~4.24,P<0.01)。(3)Kaplan-Meier分析显示,PSM前后MVI组总存活率和无瘤存活率显著低于Non-MVI组(所有P<0.05)。(4)PSM前,MVI组与Non-MVI组病人的复发率分别为88.5%、62.5%(P<0.01)。PSM后,MVI组与Non-MVI组病人的复发率分别为88.5%和50.8%(P<0.01)。(5)Logistic多因素分析结果显示,ECOG评分<2分(OR=0.49,95%CI 0.27~0.87,P=0.014),Child-Pugh分级(OR=0.49,95%CI 0.25~0.97,P=0.041),肿瘤分化程度(OR=1.85,95%CI 1.01~3.39,P=0.046),肿瘤最大径(OR=2.19,95%CI 1.18~4.08,P=0.014)及神经侵犯(OR=2.18,95%CI 1.03~4.59,P=0.41)是MVI的独立影响因素。结论 MVI与ICC侵袭性特征及肿瘤复发相关,MVI是ICC根治术后预后不良的独立危险因素。

ObjectiveTo analyze the effect of microvascular invasion(MVI)on the prognosis of patients undergoing radical resection of intrahepatic cholangiocarcinoma(ICC).MethodsThe propensity score matching(PSM)and retrospective cohort study was conducted. The clinicopathological data of 501 patients with ICC who were admitted to 13 medical centers between December 2011 and December 2017,including Eastern Hepatobiliary Surgery Hospital of Navy Military Medical University,Second Hospital Affiliated to Zhejiang University School of Medicine,Mengchao Hepatobiliary Hospital of Fujian Medical University,First Hospital Affiliated to Army Military Medical University,Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College,Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Beijing Friendship Hospital Affiliated to Capital Medical University,West China Hospital of Sichuan University,Renji Hospital Affiliated to Shanghai Jiaotong University School of medicine,Xuanwu Hospital Affiliated to Capital Medical University,Affiliated Hospital of North Sichuan Medical College,Beijing Tiantan Hospital Affiliated to Capital Medical University,Zhongda Hospital Southeast University. There were 202 males and 299 females,age from 23 to 88 years,with a median age of 57 years. According the postoperative pathological diagnosis,61 patients with MVI were divided into MVI group and 440 patients without MVI were divided into Non-MVI group. Observation indicators:(1)Comparison of baseline data comparison between the two groups before and after PSM;(2)Kaplan-Meier method was used for overall survival(OS)and disease-free survival(DFS)analysis. COX regression analysis of risk factors for ICC prognosis;(3)Logistic regression analysis of risk factors for MVI.Results(1)A total of 501 patients with ICC were included,and the incidence of MVI was 12.2%. There were122 patients left after 1∶1 PSM,including 61 in the MVI group and 61 in the Non-MVI group. No significant differences were observed in the baseline data between the two groups(all P>0.05).(2)Before PSM,the results of multivariate analysis showed that gender,tumor diameter,microvascular invasion,and postoperative adjuvant therapy were independent risk factors for OS(HR=0.74,95% CI 0.58-0.94,P=0.013;HR=1.43,95% CI 1.11-1.83,P=0.006;HR=1.87,95% CI 1.35-2.58,P<0.01;HR=0.69,95% CI 0.50-0.97,P=0.031);while gender,surgery margin,pathological classification,tumor diameter,satellite nodule,and microvascular invasion were independent risk factors for DFS(HR=0.80,95% CI 0.64-1.01,P=0.061;HR=1.40,95% CI 1.10-1.77,P=0.005;HR=1.51,95% CI 1.08-2.12,P=0.017;HR=1.35,95% CI 1.07-1.71,P=0.013;HR=1.74,95% CI 1.21-2.52,P=0.003;HR=2.36,95% CI 1.73-3.21,P<0.01).After PSM,the results of multivariate analysis showed that the Child-Pugh classification and microvascular invasion were independent risk factors for OS(HR=1.75,95% CI 1.03-2.99,P=0.039;HR=1.84,95% CI 1.17-2.90,P=0.008);while pathological classification and microvascular invasion were independent risk factors for DFS(HR=1.93,95% CI1.08-3.44,P=0.027;HR=2.64,95% CI 1.64-4.24,P<0.01).(3)Kaplan-Meier analysis showed that significant difference in the OS and DFS between the two groups(all P<0.05).(4)Before PSM,the recurrence rates of MVI group and Non-MVI group were 88.5% and 62.5%,respectively(P<0.01). After PSM,the recurrence rates of those two groups were 88.5% and 50.8%,respectively(P<0.01).(5)The results of Logistic multivariate analysis showed that the ECOG score<2 points(OR=0.49,95% CI 0.27-0.87,P=0.014),Child-Pugh classification(OR=0.49,95% CI 0.25-0.97,P=0.041),tumor differentiation(OR=1.85,95% CI 1.01-3.39,P=0.046),tumor diameter(OR=2.19,95% CI 1.18-4.08,P=0.014)and neuroinvasion(OR=2.18,95% CI 1.03-4.59,P=0.41)were independent risk factors for MVI.ConclusionMicrovascular invasion is associated with tumor aggressive characteristics and higher recurrence rate. It is an independent risk factor affecting the prognosis of ICC patients.