术前血清学联合影像学检查预测肝内胆管癌根治性切除术后患者生存获益的研究  

Combined preoperative serological and imaging examinations in predicting survival benefits of patients after radical resection of intrahepatic cholangiocarcinoma

作　　者：陈家璐 于小鹏 唐玥 陈晨[3] 邱应和 吴泓[5] 宋天强[6] 何宇 毛先海[8] 翟文龙[9] 程张军[10] 李敬东[11] 梁宵[12] 孙传东[13] 马凯[13] 林瑞新 汤地[15] 耿智敏[3] 汤朝晖[1] 全志伟[1] CHEN Jialu;YU Xiaopeng;TANG Yue;CHEN Chen;QIU Yinghe;WU Hong;SONG Tianqiang;HE Yu;MAO Xianhai;ZHAI Wenlong;CHENG Zhangjun;LI Jingdong;LIANG Xiao;SUN Chuandong;MA Kai;LIN Ruixin;TANG Di;GENG Zhimin;TANG Zhaohui;QUAN Zhiwei(Department of General Surgery,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Department of Oncology,Shanghai Sixth People's Hospital,Shanghai 200030,China;Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Department of Biliary Tract Surgery,Eastern Hepatobiliary Surgery Hospital,Naval Medical University,Shanghai 200433,China;Center of Liver Surgery and Liver Transplantation,West China Hospital,Sichuan University,Chengdu 610041,China;Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Hospital,Tianjin 300060,China;Department of Hepatobiliary Surgery,the First Affiliated Hospital of Army Medical University,Chongqing 400038,China;Department of Hepatobiliary Surgery,Hunan Provincial People's Hospital,Changsha 410005,China;Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Hepatobiliary Surgery,Zhongda Hospital,Southeast University,Nanjing 210009,China;Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637000,China;Department of Hepatobiliary and Pancreatic Surgery,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou 310020,China;Department of Hepatobiliary and Pancreatic Surgery,Affiliated Hospital of Qingdao University,Qingdao,Shandong 266003,China;Department of Hepatobiliary and Pancreatic Surgery,the Second Norman Bethune Hospital of Jilin University,Changchun 130041,China;Department of General Surgery,the Seventh Affiliated Hospital,Sun Yatsen University,Shenzhen,Guangdong 528403,China)

机构地区：[1]上海交通大学医学院附属新华医院普通外科,上海200092 [2]上海市第六人民医院肿瘤科,上海200030 [3]西安交通大学第一附属医院肝胆外科,陕西西安710061 [4]中国人民解放军海军军医大学东方肝胆外科医院胆道外科,上海200433 [5]四川大学华西医院肝脏外科与肝脏移植中心,四川成都610041 [6]天津医科大学附属肿瘤医院肝胆肿瘤科,天津300060 [7]中国人民解放军陆军军医大学西南医院肝胆外科,重庆400038 [8]湖南省人民医院肝胆外科,湖南长沙410005 [9]郑州大学第一附属医院肝胆胰外科,河南郑州450052 [10]东南大学附属中大医院肝胆外科,南京210009 [11]川北医学院附属医院肝胆外科,四川南充637000 [12]浙江大学医学院附属邵逸夫医院肝胆胰外科,浙江杭州310020 [13]青岛大学附属医院肝胆胰外科,山东青岛266003 [14]吉林大学白求恩第二医院肝胆胰外科,吉林长春130041 [15]中山大学附属第七医院普外科,广东深圳528403

出　　处：《中国普通外科杂志》2023年第8期1156-1166,共11页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(81772521);上海交通大学医学院附属新华医院院级临床研究培育基金资助项目(17CSK06);上海交通大学医学院多中心临床研究基金资助项目(DLY201807)。

摘　　要：背景与目的:肝内胆管癌(ICC)起病隐匿、侵袭性高,患者往往确诊时已失去了最佳手术时机,接受手术者5年生存率也极低。早期判断患者根治性切除术的生存获益至关重要。本研究依据术前影像学联合血清学指标对ICC根治性切除患者生存获益实行预测,以期对临床判断是否适宜行根治性切除提供指导与参考。方法:回顾性收集2010年1月—2021年12月于中国13家三甲医院行根治性切除的821例ICC患者的影像学与血清学检测资料。影像学指标包括:发现肝脏肿块、肝内胆管扩张、门静脉侵犯、淋巴结侵犯、腹水及结石;血清学指标包括:血红蛋白、白细胞计数、淋巴细胞计数、中性粒细胞计数、甲胎蛋白(AFP)、癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、CA125、丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)、白蛋白(ALB)及凝血酶原时间(PT)。通过单因素与多因素Cox回归筛选目标变量,用目标变量构建CoxPH模型并绘制列线图,用Kaplan-Meier生存分析验证评分与患者预后的关系,通过受试者工作特征(ROC)曲线及校准曲线对模型预测效能进行评估。结果:影像学发现腹水、肝内胆管扩张、淋巴结侵犯与血清学指标CEA>5μg/L、CA19-9>37 U/mL、CA125>40 U/mL是独立预后因素(均P<0.05)。用该六个变量构建CoxPH模型,根据该模型所区分的高风险组患者术后1、3、5年生存率均明显低于低风险组患者(均P<0.05);所构建的列线图具有较好的区分度及有效性。ROC曲线显示,模型1、3、5年预测的曲线下面积分别为0.711、0.721、0.782;模型1、3、5年预测效能均高于独立指标的预测效能。结论:由CA125、腹水、肝内胆管扩张、淋巴结侵犯、CEA、CA19-9这六个术前指标组成的预后模型能较好地对患者进行高低风险分层,并对ICC患者根治性切除术后生存获益进行较精准的个体化预测,对临床医生判断患者是否适宜行根治性切除具有指导意Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is characterized by its insidious onset and high invasiveness,often resulting in patients losing the optimal timing for surgery upon diagnosis,leading to poor 5-year survival rates following surgery.Early prediction of survival benefits from radical resection is crucial.This study was performed to predict survival benefits in ICC patients undergoing radical resection based on preoperative imaging and serum markers to provide guidance and references for clinical decisions regarding the suitability of radical resection.Methods:The imaging and serological data of 821 ICC patients who underwent radical resection in 13 tertiary-grade A-class hospitals in China from January 2010 to December 2021 were retrospectively collected.Imaging data included the presence of liver mass,intrahepatic bile duct dilation,portal vein invasion,lymph node invasion,ascites,and stones.Serum markers had hemoglobin,white blood cell count,lymphocyte count,neutrophil count,alpha-fetoprotein(AFP),carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),CA125,alanine aminotransferase(ALT),total bilirubin(TBIL),albumin(ALB),and prothrombin time(PT).Target variables were selected through univariate and multivariate Cox regression analysis,and using these variables,a CoxPH model was constructed,and a nomogram was also visualized.Survival curves were plotted using Kaplan-Meier analysis to validate the relationship between the scores and patient outcomes.The model's predictive performance was assessed through receiver operating characteristics(ROC)and calibration curves.Results:The independent prognostic factors were imaging indicators of ascites,intrahepatic bile duct dilation,lymph node invasion,and serum markers with CEA>5μg/L,CA19-9>37 U/mL,and CA125>40 U/mL(all P<0.05).The CoxPH model built using the 6 variables demonstrated that patients in the high-risk group identified by the model had significantly lower 1-,3-,and 5-year survival rates compared to the low-risk group(all P<0.05).

关 键 词：胆管肿瘤 胆管 肝内 预后 列线图 

分 类 号：R735.8[医药卫生—肿瘤]