The impact of short-term machine perfusion on the risk of cancer recurrence after rat liver transplantation with donors after circulatory death

PLoS One. 2019 Nov 25;14(11):e0224890. doi: 10.1371/journal.pone.0224890. eCollection 2019.

Abstract

Hypothermic and normothermic ex vivo liver perfusions promote organ recovery after donation after circulatory death (DCD). We tested whether these perfusions can reduce the risk of hepatocellular carcinoma (HCC) recurrence in a 1h-DCD syngeneic transplantation model, using Fischer F344 rats. DCD grafts were machine perfused for 2h with hypothermic perfusion (HOPE) or normothermic perfusion (NORMO), and transplanted. After reperfusion, we injected HCC cells into the vena porta. On day 28 after transplantation, we assessed tumour volumes by MRI. Control rats included transplantations with Fresh and non-perfused DCD livers. We observed apoptotic-necrotic hepatocyte foci in all DCD grafts, which were more visible than in the Fresh liver grafts. Normothermic perfusion allowed a faster post-transplant recovery, with lower day 1 levels of transaminases compared with the other DCD. Overall, survival was similar in all four groups and all animals developed HCCs. Total tumor volume was lower in the Fresh liver recipients compared to the DCD and DCD+HOPE recipients. Volumes in DCD+NORMO recipients were not significantly different from those in the Fresh group. This experiment confirms that ischemia/reperfusion injury promotes HCC cell engraftment/growth after DCD liver transplantation. Using the present extreme 1h ischemia model, both hypothermic and normothermic perfusions were not effective in reducing this risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism
  • Blood Circulation*
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Female
  • Graft Survival
  • Liver Neoplasms / therapy*
  • Liver Transplantation*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Oxygen / metabolism
  • Perfusion
  • Rats, Inbred F344
  • Reperfusion Injury / pathology

Substances

  • Oxygen

Grants and funding

This study was supported by grants from the Swiss National Science Foundation (PP00P3_139021), the Geneva Cancer League (ref 1509), the Minkoff Foundation, the Artères Foundation, and the Insuleman Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.