The clinicopathological factors associated with prognosis of patients with resectable perihilar cholangiocarcinoma A systematic review and meta-analysis

The refinement in surgical techniques combined with the preoperative management has improved the resectability rate of perihilar cholangiocarcinoma (pCCA). However, the prognosis of pCCA with curative resection is still dismal. This meta-analysis was performed to investigate the prognostic clinicopathological factors in resectable pCCA. PubMed, the Cochran Library, ScienceDirect, and Web of Science were searched systematically to identify reports focusing on studying the prognostic clinicopathological factors in resectable pCCA. The hazard ratios (HRs) and its 95% confidence interval (95% CI) from the identified studies using Cox proportional hazard regression model were extracted for overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) analysis. Three prospective and 35 retrospective cohort studies including 5681 resectable pCCA were included in the pooled analysis. Among more than 20 clinicopathological factors associated with negative survival of pCCA, only 6 were included in quantitative analysis which showed that lymph node involvement was associated with a reduced OS (HR=2.04; 95% CI: 2.10-2.62), DSS (HR=1.80; 95% CI: 1.39-2.34), DFS (HR=4.38; 95% CI: 1.89-10.14), negative resection margin (HR=2.04; 95% CI: 1.73-2.41), operative transfusion (HR=1.82; 95% CI: 1.06-3.11), and T3 or T4-stage (HR=2.04; 95% CI: 2.04-2.53) were poor prognostic factors of OS, and poor or moderate differentiation was also an adverse prognostic factor of OS (HR=2.71; 95% CI: 1.80-4.07) and DSS (HR=1.74; 95% CI: 1.25-2.44). The overall median resectability rate (95CI%), R0 resection (95CI%), and 5-year OS (95CI%) in Eastern and Western countries were 74.9 (66.4-78.4) % and 41.3 (32.6-80.8) %, 70.7 (65.6-80.8) % and 75.9 (64.0-80.4) %, and 33.0 (29.7-39.7) % and 25.5 (20.0-31.6) %, respectively. Negative resection margin, lymph node involvement, poor or moderate differentiation grade was identified as the negative predictor factors of resectable pCCA. Operative transfusion and T3/T4 stage were also associated with a reduced survival of resectable pCCA.