摘要目的 分析肝胆管结石相关性肝内胆管癌(HICC)患者的外科治疗及预后分析.方法 采用回顾性病例对照研究方法.收集2011年1月至2015年12月陆军军医大学第一附属医院收治的109例HICC患者的临床病理资料;男40例,女69例;平均年龄为55岁,年龄范围为29～ 81岁.患者术前行影像学和实验室检查,依据检查结果及术中情况决定手术方案:根治性手术、姑息性手术、单纯活组织检查.观察指标:(1)手术情况.(2)随访情况.(3)影响HICC患者术后生存的危险因素分析.采用电话或门诊方式进行随访,了解患者生存情况,随访时间截至2018年1月.采用Shapiro-Wilk检验进行正态性检验,正态分布的计量资料以Mean±SD表示,组间比较采用t检验;偏态分布的计量资料以M(范围)表示,组间比较采用Wilcoxon秩和检验.分类变量采用x2检验.采用Kaplan-Meier法绘制生存曲线和计算累积生存率,单因素分析采用Log-rank检验,将P＜0.05的指标纳入COX回归模型以逐步向前法进行多因素分析.结果 (1)手术情况:109例HICC患者行手术治疗.109例患者肝胆管结石及肿瘤分布部位:结石位于左半肝58例、右半肝26例、双侧25例;肿瘤位于左半肝65例、右半肝31例、双侧13例.手术方式:51例患者行根治性手术(联合胆肠吻合38例、区域淋巴结清扫33例、血管重建3例、胰十二指肠切除2例),其中半肝切除33例、非半肝切除18例.46例患者行姑息性手术(肿瘤局部切除13例、胆肠吻合19例、胃肠吻合9例、空肠造瘘13例、单纯胆道引流5例、其他12例,部分患者联合多种手术方式).12例患者行单纯活组织检查.109例患者侵犯转移:肝内转移22例、血管侵犯52例、淋巴结转移55例、肝外侵犯转移58例,其中64例患者合并多种侵犯转移.109例患者手术时间为(359± 170) min,术中出血量为(556±382) mL,53例进行术中输血.术后35例患者发生并发症,主要为肺部感染、胸腹腔积液、腹腔出血、腹腔感染、胆汁漏、脏器衰竭等,其中经相关治疗后29例患者好转或痊愈,6例死亡(肺部重症感染3例、肝衰竭1例、感染性休克1例、消化道出血l例).109例患者肿瘤组织病理学特点:肿块型50例、管周浸润型49例、管内生长型10例;按肿瘤分化程度分类:高分化22例、中分化50例、低分化37例.(2)随访情况:107例患者获得随访,随访时间为1 ～ 84个月,中位随访时间为51个月.患者术后中位生存时间为25.0个月(17.9～32.1个月),1、3、5年总体生存率分别为78.7％、39.4％、9.8％.根治性手术患者1、3、5年生存率分别为86.3％、61.8％、20.6％,姑息性手术患者上述指标分别为88.4％、19.1％、0,单纯活组织检查患者上述指标分别为34.6％、0、0,3者预后情况比较,差异有统计学意义(x2=43.237,P＜0.05).(3)影响HICC患者术后生存的危险因素分析.①单因素分析结果显示:结石病程、肝硬化、手术方式、肿瘤直径、肿瘤大体分型、肿瘤分化程度、肝内转移、血管侵犯、淋巴结转移、肝外侵犯转移、中性粒细胞百分比、总胆红素、直接胆红素、白蛋白(Alb)、CA19-9是影响HICC患者手术预后的相关因素(x2=5.764,8.768,43.273,4.086,11.995,21.910,15.436,6.469,17.181,35.307,24.676,10.69l,11.367,5.808,3.907,P＜0.05).②多因素分析结果提示:手术方式为单纯活组织检查、结石病程≥60个月、肝硬化、肿瘤分化程度为低分化、血管侵犯、肝外侵犯转移、Alb＜ 35g/L是影响HICC患者手术预后的独立因素(风险比=3.317,1.809,1.917,1.882,1.761,2.283,0.502,95％可信区间为1.263～ 8.712,1.132～2.892,1.061～3.463,1.291 ～ 2.744,1.087～2.852,1.220～4.271,0.304～0.827,P＜0.05).结论 部分长期罹患肝胆管结石病患者可进展为HICC;手术切除是HICC患者首选治疗方法.该病肿瘤恶性程度高,常合并有肝内外及淋巴结转移,预后较差.手术方式为单纯活组织检查、结石病程≥60个月、肝硬化、肿瘤分化程度为低分化、血管侵犯、肝外侵犯转移、Alb＜35g/L是影响HICC患者预后的独立危险因素.

abstractsObjective To analyze the surgical treatment and prognostic factors of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (HICC).Methods The retrospective case-control study was conducted.The clinicopathological data of 109 patients with HICC who were admitted to the First Affiliated Hospital of Army Medical University between January 2011 and December 2015 were collected,including 40 males and 69 females,aged from 29 to 81 years,with an average age of 55 years.The patients underwent imaging and laboratory examinations before operation,and then the operation plan was worked out according to the results of examination and intraoperative conditions,including radical operation,palliative surgery and simple biopsy.Observation indicators:(1) surgical situations;(2) follow-up;(3) analysis of risk factors affecting postoperative survival of HICC patients.The follow-up using telephone interview and outpatient examination was performed to detect patients' survival up to January 2018.The normality test was done by ShapiroWilk.Measurement data with normal distribution were represented as Mean±SD and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range) and comparison between groups was analyzed using the Wilcoxon rank sum test.Categorical variables were analyzed using the chi-square test.The survival curve and cumulative survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis was done using the Log-rank test.The indexes with P＜ 0.05 were incorporated into COX regression model for multivariate analysis in the forward wald.Results (1) Surgical situations:109 patients with HICC underwent surgery.Distribution of hepatolithiasis and HICC in the 109 patients:the stones of 58,26 and 25 patients were located in the left liver,right liver and bilateral sides,respectively.The tumors of 65,31 and 13 patients were located in the left liver,right liver and bilateral sides,respectively.Operation methods:radical operation was performed in 51 cases (combined choledochojejunostomy in 38 cases,regional lymph node dissection in 33 cases,vascular reconstruction in 3 cases and pancreaticoduodenectomy in 2 cases),including 33 with hemihepatectomy and 18 with non-hemihepatectomy.Palliative surgery was performed in 46 cases (local resection of tumors in 13 cases,choledochojejunostomy in 19 cases,gastrointestinal anastomosis in 9 cases,jejunostomy in 13 cases,simple biliary drainage in 5 cases,other operations in 12 cases,some patients combined with a variety of surgical methods),and simple biopsy was performed in 12 cases.Invasion and metastasis in the 109 patients:intrahepatic metastasis occurred in 22 cases,vascular invasion in 52 cases,lymph node metastasis in 55 cases,extrahepatic invasion and metastasis in 58 cases (64 cases were complicated with multiple invasion and metastasis).The operation time and volume of intraoperative blood loss of 109 patients were respectively (359± 170)minutes and (556±382)mL,and 53 patients received intraoperative blood transfusion.Postoperative complications occurred in 35 patients,including pulmonary infection,pleural and peritoneal effusion,abdominal hemorrhage,abdominal infection,bile leakage and organ failure.Twenty-nine of the 35 patients were improved or recovered after treatment,and 6 died (3 died of severe pulmonary infection,1 died of liver failure,1 died of septic shock and 1 died of gastrointestinal hemorrhage).Histopathological characteristics of tumors in the 109 patients:mass type,peritubular infiltration type and intratubular growth type were detected respectively in 50,49 and 10 cases;according to the degree of tumor differentiation,high-differentiated,moderate-differentiated and low-differentiated tumors were detected in 22,50 and 37 cases,respectively.(2) Follow-up:107 patients were followed up for 1-84 months,with a median followup time of 51 months.The median survival time was 25.0 months (range,17.9-32.1 months).The 1-,3-and 5-year overall survival rates were 78.7％,39.4％ and 9.8％,respectively.The 1-,3-and 5-year survival rates were 86.3％,61.8％,20.6％ in patients with radical surgery and 88.4％,19.1％,0 in patients with palliative surgery and 34.6％,0,0 in patients with simple biopsy,respectively,showing a statistically significant difference (x2 =43.237,P＜0.05).(3) Analysis of risk factors affecting postoperative survival of HICC patients:① the results of univariate analysis showed that course of stone,cirrhosis,operation method,tumor diameter,tumor gross classification,degree of tumor differentiation,intrahepatic metastasis,vascular invasion,lymph node metastasis,extrahepatic invasion and metastasis,percentage of neutrophils,total bilirubin (TBiL),direct bilirubin (DBiL),albumin (Alb) and CA19-9 were the related factors affecting the prognosis of HICC patients after surgical treatment (x2 =5.764,8.768,43.273,4.086,11.995,21.910,15.436,6.469,17.181,35.307,24.676,10.691,11.367,5.808,3.907,P＜0.05).② The results of multivariate analysis showed that simple biopsy as operation method,course of stone ≥ 60 months,cirrhosis,low-differentiated tumor,vascular invasion,extrahepatic invasion and metastasis and Alb ＜ 35 g/L were independent factors affecting the prognosis of HICC patients after surgical treatment (hazard ratio =3.317,1.809,1.917,1.882,1.761,2.283,0.502,95％ confidence interval:1.263-8.712,1.132-2.892,1.061-3.463,1.291-2.744,1.087-2.852,1.220-4.271,0.304-0.827,P＜0.05).Conclusions Some patients with chronic hepatolithiasis can progress to HICC,and surgical resection is the first choice.However,due to the high malignancy,there is usually a combination of invasion and mnetastasis,resulting in poor prognosis.The simple biopsy as operation method,course of stone ≥ 60 months,cirrhosis,low-differentiated tumor,perihepatic vascular invasion,extrahepatic invasion and metastasis,Alb ＜ 35 g/L are independent risk factors affecting the prognosis of HICC patients after surgical treatment.