Does Intraoperative Frozen Section and Revision of Margins Lead to Improved Survival in Patients Undergoing Resection of Perihilar Cholangiocarcinoma? A Systematic Review and Meta-analysis

Background Perihilar cholangiocarcinoma (PHC) is a rare malignancy that arises at the biliary confluence. Achieving a margin-negative resection (R0) is challenging given the anatomic location of tumors and remains the most important prognostic indicator of long-term survival. The objective of this study is to review the impact of intraoperative revision of positive biliary margins in PHC on oncologic outcomes. Patients and Methods Electronic databases were searched from inception to October 2021. Studies comparing three types of patients undergoing resection of PHC with intraoperative frozen section of the proximal and/or distal bile ducts were identified: those who were margin-negative (R0), those with an initially positive margin who had revised negative margins (R1R0), and those with a persistently positive margin with or without revision of a positive margin (R1). The primary outcome was overall survival (OS). Secondary outcomes included risk of postoperative complication. Results A total of 449 studies were screened. Ten retrospective observational studies reporting on 1955 patients were included. Patients undergoing successful revision of a positive proximal and/or distal bile duct margin (R1R0) had similar OS to those with a primary margin-negative resection (R0) [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.72–1.19, p = 0.56, I 2 = 84%], and significantly better OS than patients with a positive final bile duct margin (R1) (HR 0.52, 95% CI 0.34–0.79, p = 0.002, I 2 = 0%). There was no increase in the risk of postoperative complications associated with additional resection, although postoperative morbidity was inconsistently reported. Conclusions This review supports routine intraoperative biliary margin evaluation during resection of PHC with revision if technically feasible.