• Fabio Giannone, Fabio Del Zompo, Antonio Saviano, Erwan Pencreach, Catherine Schuster, Thomas F Baumert, and Patrick Pessaux.
• Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France.
• Br J Surg. 2024 Oct 30; 111 (11).

BackgroundIntrahepatic cholangiocarcinoma is a public health threat because of its aggressiveness. Its genetic background differs from other biliary cancers. The aim of this study was to investigate the impact of genetic alterations on long-term outcomes.MethodsPubMed, MEDLINE, Scopus, and Cochrane Library databases were systematically searched for studies assessing long-term outcomes after resection of intrahepatic cholangiocarcinoma according to genetic mutational profiling until 31 May 2022. The main outcome was the impact of genetic alterations on long-term outcomes in these patients. HR (95% c.i.) was used for effect size. Publication bias was investigated.ResultsA total of 24 retrospective studies were included. KRAS, IDH1/2, and TP53 were identified as the only three genes whose mutation correlated with survival (HR: 2.476, 95% c.i. 1.67-3.671, P < 0.01 for KRAS; HR: 0.624, 95% c.i. 0.450-0.867, P < 0.01 for IDH1/2; and HR: 2.771, 95% c.i. 2.034-3.775, P < 0.01 for TP53). The prevalence of KRAS and IDH1/2 mutations differed between western and eastern studies (P < 0.001 for both genes).ConclusionDetermining the overall prevalence of the most common actionable and undruggable mutations may help to expand target therapy indications in the adjuvant setting. Inconsistent results have been found for some infrequent gene alterations; their rare involvement could potentially bias their prognostic meaning.© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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