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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

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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, I2 = 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, I2 = 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.

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Acknowledgments

We acknowledge Alexandra Davis for her help in designing and running the search strategy.

Author information

Authors and Affiliations

  1. Liver and Pancreas Surgical Unit, Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada

    Tori Lenet MD, Richard W. D. Gilbert MD, Guillaume Martel MD & Kimberly A. Bertens MD, MPH, FRCSC, FACS

  2. Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA

    Rory Smoot MD, Lavanya Yohanathan MD & Sean P. Cleary MD

  3. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ching-Wei D. Tzeng MD

  4. Division of Surgical Oncology, Oregon Health and Science University/Knight Cancer Institute, Portland, OR, USA

    Flavio G. Rocha MD

  5. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Tori Lenet MD, Guillaume Martel MD & Kimberly A. Bertens MD, MPH, FRCSC, FACS

  6. Multi-organ Transplant Center, Beaumont Health, Royal Oak, MI, USA

    Lavanya Yohanathan MD

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  1. Tori Lenet MD
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Correspondence to Kimberly A. Bertens MD, MPH, FRCSC, FACS.

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Appendices

Appendix 1: Search Strategy

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Appendix 2: Data Extraction Form

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Lenet, T., Gilbert, R.W.D., 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 29, 7592–7602 (2022). https://doi.org/10.1245/s10434-022-12041-x

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