Surgical Treatment And Prognostic Analysis Of Hepatolithiasis-associated Intrahepatic Cholangiocarcinoma

ObjectiveHepatolithiasis is one of the common bile duct diseases in the southwest of China which is relatively rare in western countries,but more common in east Asia and southeast Asia area.Because of the complicated condition,it can arise the residual and recurrent hepatolithiasis after treatment.even if some patients underwent the surgery treatment for many times,the end-stage ones still progress to biliary cirrhosis,portal hypertension and intrahepatic cholangiocarcinoma.It is a serious health hazard,therefore hepatolithiasis has become one of the main factors of benign biliary disease death in our country.There is evidence that the occurrence of hepatolithiasis and intrahepatic cholangiocarcinoma has a close relationship.Intrahepatic cholangiocarcinoma occurs accounts for about 2% to 10% on the basis of hepatolithiasis.In recent years hepatolithiasis-associated intrahepatic cholangiocarcinoma has attracted more attention because of its atypical clinical symptoms and poor early diagnosis rate.This study analyzed the surgical treatment and prognostic analysis of hepatolithiasis-associated intrahepatic cholangiocarcinoma in order to further standardize the treatment plan and help improve the long-term curative effect.MethodsThe clinicopathological data of 109 patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma was collected,who were admitted to Department of Hepatobiliary Surgery,Southwest Hospital of The Army Medical University from January 2011 to December 2015,and the disease was confirmed by pathological examination after operation.The patients underwent imaging and laboratory examinations before operation,and the treatment plan was formulated according to preoperative evaluation.Observation indexes:(1)Preoperative situation: general condition(sex,age,course of hepatolithiasis)?clinical manifestations and previous treatment?supplementary examination;(2)Surgical treatment(operative methods,operative time,intraoperative bleeding volume,invasion and metastasis,pathological features of tumors,postoperative complications);(3)Postoperative follow-up(survival time and cumulative survival rate);(4)Prognostic analysis of hepatolithiasis-associated intrahepatic cholangiocarcinoma patients after surgical treatment(univariate analysis and multivariate analysis).Follow-up was conducted by telephone or outpatient medical record to acquire the survival condition of the patients.The follow-up period was up to January 2018.The normality test was done by Shapiro-Wilk,the measurement data of normal distribution were expressed as?x±s,and comparison between groups was evaluated with the t test,measurement data with skewed distribution were expressed as M(range),and comparison between groups was analyzed using the Wilcoxon rank-sum test.The classified variables were analyzed by ?2 test.Kaplan-Meier method was used to draw the survival curve and calculate cumulative survival rate.Log-rank test was used for univariate analysis.The index(p<0.05)was incorporated into Cox regression model for multivariate analysis in the forward wald.Results1.Preoperative situation: General condition: of the 109 patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma,40 were males and 69 were females,aged from 29 to 81 years old,with a median age of 54 years old.The course of hepatolithiasis ranged from 5 to 480 months,and 42 cases are more than 5 years.Clinical manifestations: preoperative abdominal pain,fever,jaundice,short-term significant weight loss and recurrent cholangitis were 99 cases,39 cases,46 cases,43 cases and 26 cases,respectively.Previous treatment of hepatolithiasis: 62 cases had a history of biliary tract surgery,including 10 cases with hepatectomy,17 cases with choledochojejunostomy,and 40 cases with exploration of bile duct and stone extraction,and twenty cases had underwent two or more operations.Supplementary examination: the detection rates of stones and tumors by ultrasound,CT/MRI were 88.24%/48.24%,78.30%/62.26%,79.61%/58.25%,respectively.2.Surgical treatment: All the 109 patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma had underwent surgical treatment.Operative methods: radical operation was performed in 51 cases(38 cases of combined choledochojejunostomy,33 cases of regional lymph node dissection,3 cases of vascular reconstruction,2 cases of pancreaticoduodenectomy),palliative operation in 46 cases(13 cases of local resection of tumors,19 cases of choledochojejunostomy,9 cases of gastrointestinal anastomosis,13 cases of jejunostomy,5 cases of simple biliary drainage,12 cases of other operations,some patients combined with a variety of surgical methods),and biopsy alone in 12 cases.The operation time of 109 patients was(359±170)minutes,the amount of bleeding was(556±382)mL,and 53 patients received intraoperative blood transfusion.Invasion and metastasis: intrahepatic metastasis occurred in 22 cases,perihepatic vascular invasion in 52 cases,lymph node metastasis in 55 cases,extrahepatic invasion and metastasis in 58 cases.Histopathological characteristics of tumors: mass type in 50 cases,peritubular infiltration type in 49 cases,intratubular growth type in 10 cases;according to the degree of differentiation of tumors,22 cases were well differentiated,50 cases were moderately differentiated and 37 cases were poorly differentiated.Postoperative complications occurred in 35 patients,including pulmonary infection,abdominal infection,bile leakage,etc.6 patients died.3.Postoperative follow-up: 107 patients were followed up with a follow-up rate of 98.17%.The overall median survival time was 25.0 months(17.9-32.1 months),the survival rates of 1,3 and 5 years were 78.7%,39.4% and 9.8% respectively.The 1-,3-and 5-year survival rates of radical surgery group were 86.3%,61.8% and 20.6% respectively.The above indexes of palliative surgery patients were 88.4%,19.1% and 0 respectively,and simple biopsy patients were 34.6%,0 and 0 respectively.The difference was statistical ly significant(?2= 43.237,P < 0.05).4.Prognostic analysis of hepatolithiasis-associated intrahepatic cholangiocarcinoma patients after surgical treatment: The results of univariate analysis showed that course of disease,cirrhosis,operative method,tumor size,gross classification,differentiation degree,intrahepatic metastasis,perihepatic vascular invasion,lymph node metastasis,extrahepatic invasion and metastasis,percentage of neutrophils,TBil,DBil,Alb and CA19-9 are the related factors affecting the prognosis of hepatolithiasis-associated intrahepatic cholangiocarcinoma patients after surgical treatment(?2=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).The results of multivariate analysis showed that operative method,course of disease,cirrhosis,differentiation degree,perihepatic vascular invasion,extrahepatic invasion and metastasis,Alb are independent prognostic factors.(HR=3.317,1.809,1.917,1.882,1.761,2.283,0.502;95% confidence interval:1.263-8.712,1.132-2.892,1.061-3.463,1.291-2.744,1.807-2.852,1.220-4.271,0.304-0.827,p<0.05).Conclusion Some patients with chronic hepatolithiasis can progress to hepatolithiasis-associated intrahepatic cholangiocarcinoma,surgical resection is the first choice,However,due to the high degree of malignancy,there is usually a combination of invasion and metastasis,resulting in poor prognosis.Operative method,course of disease?60 months,cirrhosis,tumors of differentiation,perihepatic vascular invasion,extrahepatic invasion and metastasis,Alb<35g/L are independent risk factors affecting the poor prognosis of patients with HICC after surgical treatment.