Outcomes of Surgical Interventions in Patients with Intrahepatic Cholangiocarcinoma and Analysis of the Prognostic Factors
|School||Second Military Medical University|
|Keywords||intrahepatic cholangiocarcinoma surgical intervention HBV infection prognosis|
ObjectivesIntrahepatic cholangiocarcinoma (ICC) derives from cholangiocytes of smallintrahepatic bile ducts (including secondary bile ducts). ICC is the second most commonprimary liver cancer after hepatocellular carcinoma (HCC), with an increasing incidenceand mortality in recent years. Although surgical resection has been shown to improvelong-term survival for patients with ICC, the prognosis after resection is still poor and canonly be performed in10%to20%of ICC patients, and no clear improvement has beenmade in survival rate over the past10years. Up to now, however, surgical outcomes andthe prognostic factors have not been well-documented although there have been increasingstudies on surgery for ICC. Owing to most of the existing studies usually involve smallnumbers of cases, span over a study period of decades and in some studies patientinclusion was highly selective, so the results of overall survival differed in a wide range forthe small series of cases. Besides, the data in those literatures also showed that lymphaticmetastasis, cirrhosis, without HBV infection, tumor size＞5cm, multiple tumor numbersand positive margins were the independent predictors of poor survival. So there are manycontroversies in current surgical management of ICC and its prognostic factors have notbeen entirely analyzed. In this study, the outcomes in our over-thousand cases study of ICCpatients undergoing surgery were retrospectively investigated and to define whether therewere differences in survival advantage among difference surgical interventions. And wesought to clarify the role of independent prognostic factors for ICC.Materials and MethodsA retrospective study was undertaken of1333patients with mass-forming type ICCwho admitted to Eastern Hepatobiliary Surgery Hospital for surgical treatment fromJanuary2007to December2011. The diagnosis of mass-forming type ICC was confirmedby pathology. All the clinicopathological data were extracted from the patient’s medicalrecords, included age, genders, symptoms (epigastric pain or hepatomegaly), liver diseases, laboratory data and pathological features. ICC was staged according to the7th editionAJCC cancer staging manual. Using telephone or clinic reviews on patients forpostoperative follow-up. The possible prognostic factors were analyzed by the univariateand multivariate analysis using the Kaplan-Meier method and the Cox proportional hazardsmodel.Results(1) Of1333patients undergoing surgery,1281received tumor resection, with an overall respectability rate of96.1%; R0, R1and R2resections were obtained in464(34.8%),598(44.9%) and219(16.4%) patients, respectively. The remaining52(3.9%) patients hadlaparotomy and biopsy only because of unresectable disease. Lymph node metastasisoccurred in375patients, among whom154patients obtained complete lymph nodedissection and187patients lymph nodes biopsy only in addition to liver resection. Theremaining34patients with lymph node metastasis were among those who had onlyexploration.(2) The overall1-,3-and5-year survival rates for all the1333ICC patientswere58.2%，25.2%，17.0%, respectively, with a median survival time of14months. Theoverall and disease-free1-,3-and5-year survival rates for the1062patients with curativeresection (R0+R1) were68.6%,30.1%,20.4%and36.5%,16.9%,11.9%, respectively,with the median survival times of18and8months, respectively.(3) The overall1-,3-and5-year survival rates of patients who underwent R0resection were79.1%、42.6%and28.7%, respectively, with a median survival time of30months, which were much better forsurvival rates than patients who underwent R1resection (60.5%、20.1%and13.9%,respectively, with a median survival time of15months)(P＜0.001).The overall1-,3-and5-year survival rates of patients who underwent R2resection were20.5%,7.4%and0%,respectively, with a median survival time of6months, which were much better especiallyfor long-term survival rates than patients who underwent laparotomy (3.8%,0%and0%,respectively, with a median survival time of4months)(P＜0.001).(4) The overall1-,3-and5-year survival rates of154patients in lymph node dissection group were52.6%,12.5%and4.7%, respectively, with a median survival time of13months. And the overall1-,3-and5-year survival rates of187patients in lymph nodes biopsy group were22.5%,6.9%and0%, respectively, with a median survival time of6months. Patients in lymph nodedissection group had more favorable prognosis than lymph nodes biopsy group in earlysurvival rates, but the survival difference was not shown between them after3years (P＜0.001).(5) According to the results of univariate analysis, HBV infection, cirrhosis, the level of CA19-9and CEA, tumor size, tumor number, capsule formation, surgical margin,lymphatic metastasis, vasculature invasion and neural invasion were significantly differentvariables in survival.(6) Multivariate analysis confirmed the level of CA19-9(+)(＞39U/ml) and/or CEA(+)(＞10μg/L)(1.721，1.502-1.972), multiple tumor numbers (1.290，1.126-1.479), lymphatic metastasis (1.273，1.081-1.498), vasculature invasion (1.252，1.056-1.484) and positive margins (1.859，1.669-2.071) to be independent predictors ofpoor survival, while HBV infection (0.785，0.714-0.863) and cirrhosis (0.819，0.691-0.971)were identified as independently favorable prognosis indicators.Conclusions(1) The long-term overall survival rates of ICC following surgical resections are stilldiamal.(2) R0resection of ICC provides the best chance for prolonged survival, whereasR2resection could prolong the survial of late stage patients.(3) Complete lymph nodedissection could prolong the survial of patients with lymph node metastasis in earlysurvival time.(4) HBV infection and cirrhosis were identified as independently favorableprognosis indicators.(5) The level of CA19-9(+)(＞39U/ml) and/or CEA(+), multipletumor numbers, lymphatic metastasis, vasculature invasion and positive margins are theindependent risk factors for prognosis of ICC.