Tumor Serosal Invasion in Perihilar Cholangiocarcinoma: A Lethal But Overlooked Feature

Ryusei Yamamoto; Takashi Mizuno; Shunsuke Onoe; Nobuyuki Watanabe; Shoji Kawakatsu; Masaki Sunagawa; Junpei Yamaguchi; Atsushi Ogura; Taisuke Baba; Mihoko Yamada; Yoshie Shimoyama; Kennosuke Karube; Takahiro Imaizumi; Tomoki Ebata

doi:10.1097/SLA.0000000000006957

Tumor Serosal Invasion in Perihilar Cholangiocarcinoma: A Lethal But Overlooked Feature

Ann Surg. 2025 Oct 15. doi: 10.1097/SLA.0000000000006957. Online ahead of print.

Authors

Affiliations

¹ Division of Surgical Oncology, Department of Surgery.
² Department of Pathology and Laboratory Medicine.
³ Department of Advanced Medicine Nagoya University Graduate School of Medicine, Nagoya, Japan.

PMID: 41090947
DOI: 10.1097/SLA.0000000000006957

Abstract

Objective: To determine the clinicopathologic importance of tumor serosal invasion (SI) in perihilar cholangiocarcinoma (pCCA).

Background: SI is a well-established survival predictor in most gastrointestinal cancers, but its impact in pCCA remains unknown, despite the perihilar bile ducts being covered by the serosal surface of the hepatoduodenal ligament.

Methods: Data from patients who underwent resection for pCCA between 2004 and 2019 were retrospectively reviewed. SI was defined as tumor invasion on or within 0.1 mm of the serosal surface of the hepatoduodenal ligament. The clinicopathologic features of SI and non-SI patients were compared following classification with the current AJCC tumor classification system and invasive tumor thickness (ITT) system.

Results: Among 725 patients, 273 (37.7%) had SI. The incidences of postoperative peritoneal dissemination were 34.1% and 12.8% in SI and non-SI patients, respectively (P<0.001), and the overall recurrence rates were 81.0% and 58.6%, respectively (P<0.001). SI was an independent negative predictor of overall survival by multivariable analysis (hazard ratio: 1.49, P<0.001). The 5-year survival was significantly worse in the SI group (25.2%) than in the non-SI group (53.5%, P<0.001); moreover, the former was worse than that of 55 patients with AJCC pT4 tumors (40.0%, P=0.007) and 172 patients with ITTs>8 mm (39.5%, P<0.001) in the non-SI group.

Conclusions: SI was associated with significantly worse survival than non-SI due to increased postoperative peritoneal dissemination in pCCA patients, regardless of the tumor classification. Moreover, survival was worse in SI than in non-SI patients with AJCC pT4 tumors and ITTs>8 mm.

Keywords: hepatoduodenal ligament; perihilar cholangiocarcinoma; serosal invasion; tumor classification; tumor depth.