Selection Of Surgical Procedures And Repeat Resection After Recurrence And Long-term Survival In Patients With Intrahepatic Cholangiocarcinoma

Part I.Selection of surgical procedures in patients with intrahepatic cholangiocarcinoma: A Propensity Score Matching and Stratified Analysis with 7th TNM systemBackground: Liver resection is the most important treatment for patients with intrahepatic cholangiocarcinoma(IHCC).However,the long-term prognoses between anatomical resection(AR)and non-anatomical resection(NAR)in IHCC remains to be determined.Methods: Data on 702 consecutive patients who underwent AR(n = 319)or NAR(n = 383)with curative intention for histopathologically proven IHCC between 2006 and 2010 were reviewed.Tumor recurrence and overall survival(OS)were the end point of this study and analyzed using the Kaplan-Meier method with the log-rank test and the Cox hazard regression model.The propensity score matching(PSM)analysis and the stratified analysis with 7th TNM system were used to identify the groups and subgroups of patients who benefited from AR or NAR.Results: The AR group had better long-term prognoses than the NAR group in the whole cohort(5-year tumor recurrence and OS rates: 71.6% vs.83.0%;34.7% vs.23.2%,both p < 0.001).After 1:1 PSM with 239 patients in each group,AR still conferred oncological advantages over NAR in 5-year recurrence and OS rates(73.1% vs.83.0%;33.5% vs.23.7%,p = 0.006,0.010).Multivariate analysis showed NAR to be an independent risk factor of OS and recurrence(hazard ratios: 1.386 and 1.444).Stratified analysis showed insignificant differences in long-term outcomes between AR and NAR in patients with ? 5 cm stage I tumors,or stage II and above tumors with vascular,periductal and local extrahepatic invasion and nodal metastasis.Conclusion: AR achieved better surgical outcomes than NAR,mainly in the subgroups of IHCC patients with > 5 cm stage I tumors,and stage II tumors without vascular invasion.Part II.Effectiveness of Repeat Hepatic Resection for Patients with Recurrent Intrahepatic Cholangiocarcinoma: Factors Associated with Long-term OutcomesBackground: Tumor recurrence after liver resection for intrahepatic cholangiocarcinoma(IHCC)is common.The effective treatment for recurrent IHCC remains to be established.This study evaluated the short-and long-term prognoses of patients after repeat hepatic resection for recurrent IHCC.Methods: Data of 72 patients who underwent R0 repeat hepatic resection for intrahepatic recurrent IHCC between 2005 and 2013 was analyzed.Tumor re-recurrence,recurrence-to-death survival(RTDS)and overall survival(OS)were calculated and compared using the Kaplan-Meier method and the log-rank test.Independent risk factors were identified by Cox regression analysis.Results: After repeat hepatic resection,surgical morbidity and mortality rates were 18.1% and 1.4%,respectively.The 1-,2-and 3-year re-recurrence rates were 53.2%,80.2% and 92.6%,respectively,and the corresponding RTDS rates were 82.9%,53.0%,and 35.3%,respectively.The 1-,3-and 5-year OS rates were 97.2%,67.0%,and 41.9%,respectively.Patients with a time to recurrence(TTR)of > 1 year from the initial hepatectomy achieved higher 1-,2-and 3-year RTDS rates than patients with a TTR of ? 1 year(92.5%,61.7% and 46.6% vs.70.4%,42.2% and 23.0%,P = 0.022).Multivariate analysis identified that recurrent tumor > 3 cm(hazard ratio: 2.346;95% confidence interval: 1.288-4.274),multiple recurrent nodules(2.304;1.049-5.059),cirrhosis(3.165;1.543-6.491),and a TTR of ? 1 year(1.872;1.055-3.324)were independent risk factors of RTDS.Based on the independent predictors of RTDS,a scoring system was developed for predicting RTDS after R0 repeat hepatic resection for recurrent IHCC.This scoring system was able to stratify patients into 3 prognostic subgroups with scores of 0,1 and ? 2,respectively,after repeat hepatic resection.The long-term prognoses of these 3 prognostic subgroups were different significantly,showing an increased re-recurrence rate and declined RTDS and OS rate with increasing of the scores.Conclusion: Repeat hepatic resection for recurrent IHCC was safe and produced long-term survival outcomes in selected patients based on prognostic stratification with the presence of the independent risk factors of RTDS.Part III.Actual more than 10-year survival after liver resection for patients with intrahepatic cholangiocarcinomaBackground: Hepatectomy is a potentially curative therapy for intrahepatic cholangiocarcinoma(IHCC),but overall surgical prognosis remains dismal and no study has reported 10-year actual postoperative survival.This study aims to document 10-year actual survival rates,identify the prognostic factors associated with 10-year survival,and characterize patient survived ? 10 years.Methods: Data of 251 IHCC patients who underwent curative surgery between 2003 and 2006 at the Eastern Hepatobiliary Surgery Hospital was analyzed.Survival curves were estimated by the Kaplan–Meier method.Cumulative incidences of recurrence and IHCC-related death were estimated using a competing risk analysis as defined by Fine and Gray.Independent risk factors associated with the cause-specific hazard of recurrence and IHCC-related death used univariate and multivariate Cox proportional hazard model.Results: 21 patients survived ? 10 years after surgery.The 5-,7-,and 10-year overall survival rates were 32.3%,22.3% and 8.4%,respectively.The 10-year cumulative incidence of IHCC-related death and recurrence were 80.9% and 85.7%,respectively.Multivariate analysis which based on competing risk survival analysis showed that tumor diameter > 5 cm was independently associated with IHCC-related death and recurrence(hazard ratios: 1.369 and 1.445),in addition to carcinoembryonic antigen(CEA)> 10 U/m L,carbohydrate antigen 19-9(CA19-9)> 39 U/m L,multiple tumors,vascular invasion,lymph node metastasis and local extrahepatic invasion.Patient who survived ? 10 years experienced recurrence later and were more likely to have lower levels of CEA,CA19-9 and alkaline phosphatase,less perioperative blood loss,solitary tumor,and smaller diameter without lymph node metastasis and local extrahepatic invasion.Conclusion: 10-year survival after liver resection for IHCC is possible and can be expected in approximately 8.4% of patients.Recurrence of IHCC might occur even after a 10-year recurrence-free period.Tumor diameter was also a risk factor of long-term prognoses.In addition,long-term follow-up after resection of IHCC is important which should be life-long.