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Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral Subtype

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

Abstract

Background

Intrahepatic cholangiocarcinoma (ICC) constitutes a group of heterogeneous malignancies within the liver. We sought to subtype ICC based on anatomical origin of tumors, as well as propose modifications of the current classification system.

Methods

Patients undergoing curative-intent resection for ICC, hilar cholangiocarcinoma (CCA), or hepatocellular carcinoma (HCC) were identified from three international multi-institutional consortia of databases. Clinicopathological characteristics and survival outcomes were assessed.

Results

Among 1264 patients with ICC, 1066 (84.3%) were classified as ICC-peripheral subtype, whereas 198 (15.7%) were categorized as ICC-perihilar subtype. Compared with ICC-peripheral subtype, ICC-perihilar subtype was more often associated with aggressive tumor characteristics, including a higher incidence of nodal metastasis, macro- and microvascular invasion, perineural invasion, as well as worse overall survival (OS) (median: ICC-perihilar 19.8 vs. ICC-peripheral 37.1 months; p < 0.001) and disease-free survival (DFS) (median: ICC-perihilar 12.8 vs. ICC-peripheral 15.2 months; p = 0.019). ICC-perihilar subtype and hilar CCA had comparable OS (19.8 vs. 21.4 months; p = 0.581) and DFS (12.8 vs. 16.8 months; p = 0.140). ICC-peripheral subtype tumors were associated with more advanced tumor features, as well as worse survival outcomes versus HCC (OS, median: ICC-peripheral 37.1 vs. HCC 74.3 months; p < 0.001; DFS, median: ICC-peripheral 15.2 vs. HCC 45.5 months; p < 0.001).

Conclusions

ICC should be classified as ICC-perihilar and ICC-peripheral subtype based on distinct clinicopathological features and survival outcomes. ICC-perihilar subtype behaved more like carcinoma of the bile duct (i.e., hilar CCA), whereas ICC-peripheral subtype had features and a prognosis more akin to a primary liver malignancy.

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Acknowledgment

T.W. and X.-F.Z. were supported by Shaanxi Science Foundation for Distinguished Young Scholars (2021JC-36), Shaanxi Innovative Research Team for Science and Technology (2022TD-53), and the “Young Talent Support Plan” of Xi’an Jiaotong University, China.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Tao Wei MD, Xue-Lian Xiao MD, Yi Lv MD & Xu-Feng Zhang MD, PhD

  2. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Tao Wei MD & Jianfeng Lu MD

  3. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Xue-Lian Xiao MD, Xu-Feng Zhang MD, PhD & Timothy M. Pawlik MD, PhD, MPH, MTS, MBA

  4. Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA

    Matthew Weiss MD

  5. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania

    Irinel Popescu MD

  6. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal

    Hugo P. Marques MD

  7. Department of Surgery, Ospedale San Raffaele, Milan, Italy

    Luca Aldrighetti MD

  8. Department of Surgery, Emory University, Atlanta, GA, USA

    Shishir K. Maithel MD

  9. Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia

    Carlo Pulitano MD

  10. Department of Surgery, University of Virginia, Charlottesville, VA, USA

    Todd W. Bauer MD

  11. Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China

    Feng Shen MD

  12. Department of Surgery, Stanford University, Stanford, CA, USA

    George A. Poultsides MD

  13. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France

    Oliver Soubrane MD

  14. Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada

    Guillaume Martel MD

  15. Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Bas Groot Koerkamp MD

  16. Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan

    Endo Itaru MD

  17. Department of Surgery, Oncology, Health Services Management and Policy, Wexner Medical Center, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Columbus, OH, USA

    Timothy M. Pawlik MD, PhD, MPH, MTS, MBA

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  1. Tao Wei MD
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  19. Timothy M. Pawlik MD, PhD, MPH, MTS, MBA
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Consortia

International Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma Study Groups

U.S. Extrahepatic Biliary Malignancy Consortium

Corresponding authors

Correspondence to Xu-Feng Zhang MD, PhD or Timothy M. Pawlik MD, PhD, MPH, MTS, MBA.

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Dr. Guillaume Martel—speaker’s honorarium from Incyte Biosciences.

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Wei, T., Lu, J., Xiao, XL. et al. Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral Subtype. Ann Surg Oncol 31, 1232–1242 (2024). https://doi.org/10.1245/s10434-023-14502-3

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  • DOI: https://doi.org/10.1245/s10434-023-14502-3

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