title: The role of hepatic ischemia-reperfusion injury and liver parenchymal quality on cancer recurrence.
abstract: Hepatic ischemia/reperfusion (I/R) injury is a common clinical challenge. Despite accumulating evidence regarding its mechanisms and potential therapeutic approaches, hepatic I/R is still a leading cause of organ dysfunction, morbidity, and resource utilization, especially in those patients with underlying parenchymal abnormalities. In the oncological setting, there are growing concerns regarding the deleterious impact of I/R injury on the risk of post-surgical tumor recurrence. This review aims at giving the last updates regarding the role of hepatic I/R and liver parenchymal quality injury in the setting of oncological liver surgery, using a "bench-to-bedside" approach. Relevant medical literature was identified by searching PubMed and hand scanning of the reference lists of articles considered for inclusion. Numerous preclinical models have depicted the impact of I/R injury and hepatic parenchymal quality (steatosis, age) on increased cancer growth in the injured liver. Putative pathophysiological mechanisms linking I/R injury and liver cancer recurrence include an increased implantation of circulating cancer cells in the ischemic liver and the upregulation of proliferation and angiogenic factors following the ischemic insult. Although limited, there is growing clinical evidence that I/R injury and liver quality are associated with the risk of post-surgical cancer recurrence. In conclusion, on top of its harmful early impact on organ function, I/R injury is linked to increased tumor growth. Therapeutic strategies tackling I/R injury could not only improve post-surgical organ function, but also allow a reduction in the risk of cancer recurrence.
authors.affiliation: Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, University of Geneva, 4 rue Gabrielle-Perret-Gentil, 1211, Geneva, Switzerland, lorenzo.orci@hcuge.ch.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Orci
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lacotte
authors.forename: Graziano
authors.initials: G
authors.lastname: Oldani
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Gilles
authors.initials: G
authors.lastname: Mentha
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008099:Liver / Q000293:injuries* / Q000473:pathology*; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery*; D009364:Neoplasm Recurrence, Local / Q000209:etiology* / Q000503:physiopathology / Q000556:secondary; D009366:Neoplasm Seeding; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A