PLoS ONE (Jan 2019)

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

  • Graziano Oldani,
  • Andrea Peloso,
  • Florence Slits,
  • Quentin Gex,
  • Vaihere Delaune,
  • Lorenzo A Orci,
  • Yohan van de Looij,
  • Didier J Colin,
  • Stéphane Germain,
  • Claudio de Vito,
  • Laura Rubbia-Brandt,
  • Stéphanie Lacotte,
  • Christian Toso

DOI
https://doi.org/10.1371/journal.pone.0224890
Journal volume & issue
Vol. 14, no. 11
p. e0224890

Abstract

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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.