The role of hepatic ischemia-reperfusion injury and liver parenchymal quality on cancer recurrence

Dig Dis Sci. 2014 Sep;59(9):2058-68. doi: 10.1007/s10620-014-3182-7. Epub 2014 May 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Hypoxia / complications
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Liver / injuries*
  • Liver / pathology*
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery*
  • Neoplasm Recurrence, Local / etiology*
  • Neoplasm Recurrence, Local / physiopathology
  • Neoplasm Recurrence, Local / secondary
  • Neoplasm Seeding*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic
  • Reperfusion Injury / complications*
  • Reperfusion Injury / physiopathology
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A