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. [email protected].
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. [email protected].
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. [email protected].
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. [email protected].

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