肝内胆管结石肝切除术后发生肝内胆管癌的危险因素分析

Risk factors analysis of intrahepatic cholangiocarcinoma after hepatectomy for hepatolithiasis

目的:探讨肝内胆管结石肝切除术后发生肝内胆管癌(ICC)的危险因素。方法:采用回顾性病例对照研究方法。收集2010年1月至2011年12月海军军医大学东方肝胆外科医院收治的1071例行肝切除术治疗肝内胆管结石患者的临床病理资料;男379例,女692例;年龄为(53±12)岁,年龄范围为12~86岁。患者入院后均完成详细术前检查。对于区域性结石,行解剖性肝切除术。对于弥漫性结石,切除局限于肝段或肝叶的区域性毁损病灶,必要时行肝胆管切开取石术和(或)胆道镜取石。当肝门部胆管存在严重狭窄影响胆道引流时,行肝胆管空肠吻合术、胆管狭窄成形术等。观察指标:(1)术前检查、手术和术后情况。(2)随访情况。(3)影响肝切除术后5年内发生ICC的危险因素分析。采用门诊和电话方式进行随访,了解患者肝切除术后发生ICC情况。随访时间截至2019年12月。正态分布的计量资料以±s表示,偏态分布的计量资料以M(范围)表示。计数资料以绝对数或百分数表示。连续性变量转换为分类变量时根据临床常用参考值或受试者工作特征曲线最佳截断值进行转换。危险因素分析采用二元Logisitic回归模型,单因素分析结果中P<0.10的因素纳入多因素分析。结果:(1)术前检查、手术和术后情况。1071例患者术前检查:结石相关症状持续时间为8.2年(0~27.0年),CA19-9为(163±87)U/mL,癌胚抗原为(5.0±2.1)μg/L,左半肝、右半肝、双侧肝叶、肝总管或胆总管结石分别为545、245、228、53例,226例伴有胆管狭窄,172例伴有肝段萎缩。1071例患者中,595例行解剖性肝切除术,272例行局部非解剖性肝切除术,143例行胆管切开取石术,61例行胆肠吻合术。26例患者术后影像学检查示残留狭窄胆管,74例术后残留胆管结石。(2)随访情况:1071例患者均获得术后随访,随访时间为(8.6±1.5)年。1071例患者中,92例发生ICC,发生率为8.590%(92/1071);其中32例、66例、90例患者术后3、5、8年内发生ICC,发生率分别为2.988%(32/1071)、6.162%(66/1071)、8.403%(90/1071)。(3)影响肝切除术后5年内发生ICC的危险因素分析。构建术前结石相关症状持续时间与术后5年内发生ICC的受试者工作特征曲线,依据约登指数最大原则,以术前结石相关症状持续7年为最佳截断值,将术前结石相关症状持续时间转换为分类变量进行后续分析。单因素分析结果显示:术前结石相关症状持续时间、合并代谢性疾病、肝段萎缩、术后残留胆管结石是影响肝内胆管结石患者肝切除术后5年内发生ICC的相关因素(优势比=2.939,2.654,1.903,2.361,95%可信区间为1.582~5.460,1.145~6.154,1.068~3.390,1.118~4.987,P<0.05)。将P<0.10的临床病理因素纳入多因素分析,其结果显示:术前结石相关症状持续时间>7年、合并代谢性疾病、肝段萎缩和术后残留胆管结石是影响肝内胆管结石患者肝切除术后5年内发生ICC的独立危险因素(优势比=2.843,2.469,1.922,2.202,95%可信区间为1.523~5.309,1.042~5.851,1.064~3.472,1.021~4.747,P<0.05)。结论:肝内胆管结石肝切除术后存在发生ICC的风险;术前结石相关症状持续时间>7年,合并代谢性疾病,肝段萎缩和术后残留胆管结石是影响肝内胆管结石患者肝切除术后5年内发生ICC的独立危险因素。

Objective:To investigate the risk factors for intrahepatic cholangiocarcinoma(ICC)after hepatectomy for hepatolithiasis.Methods:The retrospective case-control study was conducted.The clinico-pathological data of 1071 patients who underwent hepatectomy for hepatolithiasis at the Eastern Hepatobiliary Surgery Hospital of Navy Medical University between January 2010 and December 2011 were collected.There were 379 males and 692 females,aged(53±12)years,with the range of 12-86 years.Patients completed preoperative examinations.For regional hepatolithiasis,the anatomical hepatectomy was performed.For diffused hepatolithiasis,regional damaged lesions which confined to liver segment or lobe were resected.Hepaticolithotomy or cholangio-lithotomy was performed if necessary.When severe stricture of hilar bile duct affects biliary drainage,cholangiojejunostomy or biliary stricture plasty was performed.Observation indicators:(1)preoperative examination,surgical and postoperative situations;(2)follow-up;(3)risk factors analysis of ICC within the 5 years after hepatectomy for hepatolithiasis.Follow-up using outpatient examination and telephone interview was performed to detect the incidence of ICC after hepatectomy up to December 2019.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were described as M(range).Count data were described as absolute numbers or percentages.Continuous variables were converted into categorical variables according to the common clinical values or the best cut-off value of receiver operating characteristic curve.Binary logistic regression model was used for risk factors analysis.The factors with P<0.10 in univariate analysis were included for the multivariate analysis.Results:(1)Preoperative examination,surgical and postoperative situations.Results of preoperative examination:duration of hepatolithiasis-related symptoms of the 1071 patients was 8.2 years(range,0-27.0 years),the levels of CA19-9 and CEA were(163±87)U/mL and(5.0±2.1)μg/L,and stones located at left liver,right liver,bilateral sides,common hepatic duct or common bile duct were detected in 545,245,228,53 patients.There were 226 patients complicated with biliary stricture and 172 with segmental atrophy.Of the 1071 patients,595 underwent anatomical hepatectomy,272 underwent regional non-anatomical hepatectomy,143 underwent cholangiolithotomy,and 61 underwent cholangiojejunostomy.Results of postoperative imaging examination showed residual biliary stricture in 26 patients and residual biliary stones in 74 patients.(2)Follow-up:1071 patients were followed up for(8.6±1.5)years.Of the 1071 patients,92 developed ICC,with an incidence of 8.590%(92/1071).There were 32,66,90 patients developing ICC within 3,5,8 years after hepatectomy,with the incidence of 2.988%(32/1071),6.162%(66/1071),8.403%(90/1071).(3)Risk factors analysis of ICC within the 5 years after hepatectomy for hepatolithiasis.The receiver operating characteristic curve of duration of hepatolithiasis-related symptoms for ICC within the 5 years after hepatectomy was constructed,and duration of hepatolithiasis-related symptoms was converted into categorical variable for following analysis using 7 years as the cut-off value based on Youden index.Results of univariate analysis showed that duration of hepatolithiasis-related symptoms>7 years,complication with metabolic diseases,segmental atrophy,postoperative residual stones were related factors for ICC within the 5 years after hepatectomy(odds ratio=2.939,2.654,1.903,2.361,95%confidence interval:1.582-5.460,1.145-6.154,1.068-3.390,1.118-4.987,P<0.05).Results of multivariate analysis based on factors with P<0.10 in the univariate analysis showed that duration of hepatolithiasis-related symptoms>7 years,complication with metabolic diseases,segmental atrophy,postoperative residual stones were independent risk factors for ICC within the 5 years after hepatectomy(odds ratio=2.843,2.469,1.922,2.202,95%confidence interval:1.523-5.309,1.042-5.851,1.064-3.472,1.021-4.747,P<0.05).Conclusions:There was risk of developing ICC after hepatectomy for cholelithiasis.The duration of hepatolithiasis-related symptoms>7 years,complication with metabolic diseases,segmental atrophy and postoperative residual stones are independent risk factors for ICC development within 5 years after hepatectomy.