Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral Subtype

Tao Wei; Jianfeng Lu; Xue-Lian Xiao; Matthew Weiss; Irinel Popescu; Hugo P Marques; Luca Aldrighetti; Shishir K Maithel; Carlo Pulitano; Todd W Bauer; Feng Shen; George A Poultsides; Oliver Soubrane; Guillaume Martel; Bas Groot Koerkamp; Endo Itaru; Yi Lv; Xu-Feng Zhang; Timothy M Pawlik; International Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma Study Groups; U.S. Extrahepatic Biliary Malignancy Consortium

doi:10.1245/s10434-023-14502-3

Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral Subtype

Ann Surg Oncol. 2024 Feb;31(2):1232-1242. doi: 10.1245/s10434-023-14502-3. Epub 2023 Nov 6.

Authors

Tao Wei^{1

2}, Jianfeng Lu², Xue-Lian Xiao^{1

3}, Matthew Weiss⁴, Irinel Popescu⁵, Hugo P Marques⁶, Luca Aldrighetti⁷, Shishir K Maithel⁸, Carlo Pulitano⁹, Todd W Bauer¹⁰, Feng Shen¹¹, George A Poultsides¹², Oliver Soubrane¹³, Guillaume Martel¹⁴, Bas Groot Koerkamp¹⁵, Endo Itaru¹⁶, Yi Lv¹, Xu-Feng Zhang^{17

18}, Timothy M Pawlik^{19

20}; International Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma Study Groups; U.S. Extrahepatic Biliary Malignancy Consortium

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.
² Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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.
⁴ Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
⁵ Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania.
⁶ Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal.
⁷ Department of Surgery, Ospedale San Raffaele, Milan, Italy.
⁸ Department of Surgery, Emory University, Atlanta, GA, USA.
⁹ Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia.
¹⁰ Department of Surgery, University of Virginia, Charlottesville, VA, USA.
¹¹ Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
¹² Department of Surgery, Stanford University, Stanford, CA, USA.
¹³ Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France.
¹⁴ Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
¹⁶ Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan.
¹⁷ Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. xfzhang125@xjtu.edu.cn.
¹⁸ Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA. xfzhang125@xjtu.edu.cn.
¹⁹ Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Tim.Pawlik@osumc.edu.
²⁰ 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. Tim.Pawlik@osumc.edu.

PMID: 37930500
DOI: 10.1245/s10434-023-14502-3

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.

Keywords: Hepatocellular carcinoma; Hilar cholangiocarcinoma; Intrahepatic cholangiocarcinoma; Overall survival; Resection.

MeSH terms

Bile Duct Neoplasms* / pathology
Bile Ducts, Intrahepatic / pathology
Carcinoma, Hepatocellular* / surgery
Cholangiocarcinoma* / pathology
Humans
Liver Neoplasms* / pathology
Prognosis