Survival Outcomes Following R0 Liver Resection For Intrahepatic Cholangiocarcinoma With Different Causative Risk Factors

Objective:The impact of different causative factors on prognosis after RO liver resection for intrahepatic cholangiocarcinoma (ICC) is unknown. This study was to evaluate the surgical outcomes of ICC patients with different underlying risk factors, and investigate risk factor associated with surgical prognosis for patients who underwent liver resection with different causative factors.Methods:The clinical data of 731 consecutive patients undergoing RO liver resection for ICC patients at the Eastern Hepatobiliary Surgery Hospital between November 2004 and February 2010 were prospectively collected. According to the different risk factors, these patients were divided into the HBV-related ICC group (HBV-ICC, n=519), the hepatolithiasis-related ICC group (stone-ICC, n=87), the HBV and hepatolithiasis related ICC group (HBV/stone-ICC, n=45) and the other etiologies related ICC group (other-ICC, n=80). Overall survival (OS) and time to recurrence (TTR) were used as primary endpoints. The overall survival (OS) and tumor recurrence rates were compared by the Kaplan-Meier method and the log-rank test. Independent risk factors were identified by Cox regression univariate and multivariate analysis. A propensity score matching (PSM) was used to eliminate the baseline differences in clinicopathological charateristic between these groups, continuous variables were compared with the paired t-test or Mann-Whitney U test, as appropriate, and categorical variables were compared with the χ2 test or Fisher’s exact test, All reported P values were two-sided, and P values of less than 0.05 were considered to indicate statistical significance, Data analysis was performed using SPSS 19.0 and R software v.2.10.1.Results:The follow-up time was censored on August 31,2014. The median follow-up time was 25.4 months. The 5 year OS and tumor recurrence rates were 32.7%,16.3%, 17.7%, and 22.6%; 75.4%,90.3%,83.0%, and 80.9% in the HBV-, stone-, HBV/stone- and other-ICC groups, respectively. Comparisons among these four groups were conducted by the log rank test, Only comparison between the HBV-ICC and stone-ICC groups showed significant differences no matter in OS and tumor recurrence rates (P<0.001 for both), other comparisons were not significantly different (P>0.05). Considering the different distribution in sex, CA19-9, ALP, tumor number, LN metastasis and tumor macroscopic type, PSM was used to create a new cohort which was consisted of 75 stone-ICC patients and 75 HBV-ICC patients. Comparison between clinical baseline in the new cohort didn’t show significant difference. The 1-,3- and 5-year OS and recurrence rates in stone-ICC and HBV-ICC were 52.7%,30.5% and 19.2% vs.70.7%,44.7% and 34.6%, respectively (P=0.027), and 60.4%,77.3% and 88.6% vs.37.6%,67.9% and 69.9%, respectively (P =0.017). Therefore, we found that HBV-ICC group did achieve better surgical prognosis than stone-ICC group regardless of clinicopathological characteristic bias. Cox multivariate analysis in HBV-ICC and stone-ICC cohort (n=606) showed that stone-ICC was an independent risk factor no matter for OS and TTR (hazard ratio [HR]:1.603,95% confidence interval [CI],1.241-2.071; 1.573,1.234-2.006, respectively). In the HBV-ICC group (n＝519), multivariate analysis showed CA19-9>39 U/mL (HR:1.382,95% CI, 1.098-1.741; 1.363,1.093-1.699, respectively), tumor size>5 cm (HR:1.357,95% CI, 1.081-1.705; 1.329,1.069-1.653, respectively), multiple tumors (HR:1.832,95% CI, 1.447-2.321; 1.690,1.342-2.129, respectively), local invasion (HR:1.519,95% CI, 1.066-2.164; 1.463,1.035-2.067, respectively), and lymph node metastasis (HR:1.693,95% CI,1.291-2.220; 1.627,1.256-2.108, respectively) were independent risk factors of OS and tumor recurrence. The stone-ICC patients (n=87) had similar risk factors as the HBV-ICC patients, but with the exceptions that tumor size>5 cm was not an independent risk factor, and surgical margin<1 cm (HR:2.335,95% CI,1.153-4.731; 2.004,1.082-3.708, respectively) was an independent risk factor of OS and tumor recurrence.Conclusion:Different causative risk factors affected the prognosis of ICC patients following R0 liver resection. Patients with HBV-ICC had better survival outcomes than those with stone-ICC. The prognostic difference was associated with the biological malignant behavior rather than the stage of the tumor.