Intraoperative revision of margins from frozen sections could increase overall survival (OS) in patients with perihilar cholangiocarcinoma (CCA), according to a study recently published in Annals of Surgical Oncology.

“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 authors wrote.

This meta-analysis included 1955 patients previously diagnosed with CCA reported in 10 different retrospective observational studies. The researchers found that those patients that had initially positive margins (R1) and underwent a revision, determining a definite R0 (R1R0) had comparable OS to those with initial R0, with a hazard ratio (HR) of 0.93, 95% CI 0.72–1.19, P =.56, I2 =84%.

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Moreover, individuals with R1 either revised or not, exhibited considerably lower OS than those with R1 (HR 0.52, 95% CI 0.34-0.79, P =.002, I2 =0%).

“Overall, the results support routine frozen section analysis of both proximal and distal biliary margins during the resection of perihilar [CCA] with additional resection when safe and feasible,” the authors said.

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The anatomical location of CCA makes its complete resection a challenging procedure. Anatomopathological analysis of intraoperative frozen sections aims to aid in the surgeon’s approach with a rate of inaccurate margin assessment of just 3.1%, making it a feasible routine practice for these cases. Despite that limited data exist on the re-resection of positive margins, the study hypothesizes this conduct could be beneficial for the patient since the greatest predictor for OS is a margin-negative resection.

Although limited, data suggest postsurgical complications are no different in patients that underwent re-resection. Furthermore, previous publications reported that submucosal invasion of CCA could be of 5 mm or more, yielding special importance to the length of ductal resection.

Regardless, the authors point out that some exclusions may apply. For example, further resecting negative borders may not be a better outcome in patients with metastasis to lymph nodes or other organs. Likewise, a negative bile duct margin will only be meaningful if the other margins are also negative.


Lenet T, Gilbert R, Smoot R, et al. 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. Ann Surg Oncol. Published online June 25, 2022. doi:10.1245/s10434-022-12041-x