肝门部胆管癌的外科治疗及预后分析

Surgical treatment and prognosis analysis of hilar cholangiocarcinoma

目的:探讨肝门部胆管癌的外科治疗效果及预后因素。方法:本研究为双向专病队列研究。回顾性收集2005年8月至2022年12月南京医科大学第一附属医院肝胆中心连续收治的首诊为肝门部胆管癌并接受外科手术切除的510例患者资料。男性324例,女性186例,年龄[ M(IQR)]63(13)岁(范围:25~85岁)。入院时肝功能Child-Pugh分级为A级343例(67.3%),B级167例(32.7%)。其中372例(72.9%)患者伴有黄疸症状,入院时总胆红素为126.3(197.6)μmol/L(范围:5.4~722.8 μmol/L),247例(48.4%)术前行经皮经肝穿刺胆道引流或内镜下鼻胆管引流减黄治疗,减黄组术前中位胆红素水平由186.4 μmol/L降至85.5 μmol/L。通过多因素Logistic回归识别根治性切除(R0切除)的影响因素,采用Cox比例风险模型筛选总体生存和无复发生存的预后因素。 结果:510例患者中,Bismuth-Corlett Ⅲ~Ⅳ型366例(71.8%),其中86.1%(315/366)行半肝及以上切除;Ⅰ~Ⅱ型144例,其中81.9%(118/144)行单纯肝外胆管切除。510例患者的中位生存时间为22.8个月,1、3、5、10年总体生存率分别为72.2%、35.6%、24.8%、11.0%;中位无复发生存期为15.2个月,无复发生存率分别为66.0%、32.4%、20.9%、11.0%。R0切除率为64.5%(329/510),R0切除患者1、3、5、10年总体生存率分别为82.5%、48.6%、34.4%、15.2%。Clavien-Dindo并发症分级系统Ⅲ级及以上并发症发生率为26.1%(133/510),30 d内病死率为4.3%(22/510)。多因素Logistic回归分析结果提示,Bismuth-Corlett Ⅰ~Ⅲ型( P=0.009)、半肝及以上切除( P=0.001)及不伴有血管侵犯的T1~T2期患者更易获得R0切除[T2期比T1期: OR=1.43(0.61~3.35), P=0.413;T3期比T1期, OR=2.57(1.03~6.41), P=0.010;T4期比T1期: OR=3.77(1.37~10.38), P<0.01]。术前胆红素水平、Child-Pugh分级、肿瘤最大径、手术切缘、T分期、N分期、神经浸润和病理学分级是pM0期患者总体生存和无复发生存的独立预后因素( P值均<0.05)。 结论:根治性手术切除是肝门部胆管癌患者获得长期生存的必要条件。行半肝及以上切除、区域淋巴结清扫,必要时合并血管切除重建可提高R0切除率。

Objective To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods This is an ambispective cohort study.From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected.In the cohort,there were 324 males and 186 females,with an age of(M(IQR))63(13)years(range:25 to 85 years).The liver function at admission was Child-Pugh A(343 cases,67.3%)and Child-Pugh B(167 cases,32.7%).Three hundred and seventy-two(72.9%)patients had jaundice symptoms and the median total bilirubin was 126.3(197.6)μmol/L(range:5.4 to 722.8μmol/L)at admission.Two hundred and fourty-seven cases(48.4%)were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation.The median bilirubin level in the drainage group decreased from 186.4μmol/L to 85.5μmol/L before operation.Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS)and disease-free survival(DFS).Results Among 510 patients who underwent surgical resection,Bismuth-Corlett typeⅢ-Ⅳpatients accounted for 71.8%,among which 86.1%(315/366)underwent hemi-hepatectomy,while 81.9%(118/144)underwent extrahepatic biliary duct resection alone in Bismuch-Corlett typeⅠ-Ⅱpatients.The median OS time was 22.8 months,and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8%and 11.0%,respectively.The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9%and 11.0%,respectively.The R0 resection rate was 64.5%(329/510),and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%,48.6%,34.4%,15.2%,respectively.The morbidity of Clavien-Dindo gradeⅢ-Ⅴcomplications was 26.1%(133/510)and the 30-day mortality was 4.3%(22/510).Multivariate Logistic regression indicated that Bismuth-Corlett typeⅠ-Ⅲ(P=0.009),hemi-hepatectomy and extended resection(P=0.001),T1 and T2 patients without vascular invasion(T2 vs.T1:OR=1.43(0.61-3.35),P=0.413;T3 vs.T1:OR=2.57(1.03-6.41),P=0.010;T4 vs.T1,OR=3.77(1.37-10.38),P<0.01)were more likely to obtain R0 resection.Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis.Conclusions Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients.Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.