The standard technique for pancreas preservation for transplantation is Static Cold Storage (SCS). In this experimental study, we compare SCS to Hypothermic Machine Perfusion (HMP) of the pancreas to assess if the latter could safely prolong the ischaemia period prior to transplantation. We worked in 2 phases, first with organ preservation for 24hours and second, preservation for either 2 or 6hours before allotransplantation. In phase 1, exocrine injury markers were found to be non‐significantly lower, in the HMP group (n=3) versus SCS (n=3) after 24hours of preservation; amylase (p=0.2), lipase (p=0.3) and lactate dehydrogenase (p=0.1). In phase 2, 14 recipient diabetic pigs (after total pancreatectomy) received allotransplantations with n=4 and n=4 pancreases after HMP for 2 and 6hours versus n=3 and n=3 pancreases after SCS for 2 and 6hours respectively. There were no differences in recipient survival (p=0.7), mean survival was 14 days (0‐53 days). All recipients had allograft function defined as detectable C‐peptide and independent normoglycemia. We have not highlighted vascular thrombosis in all allotransplantations. This study reports the first successful pancreas allotransplantation after HMP preservation for up to 6 hours with no evidence of graft thrombosis.

Tacrolimus, the cornerstone immunosuppression after simultaneous pancreas and kidney transplantation, may exert nephrotoxic and diabetogenic effects. We therefore prospectively compared in an open‐label, randomised, monocentric, 5‐year follow‐up study, a tacrolimus‐ and a sirolimus‐based immunosuppressive regimen. Randomisation using the block method allowing a blind allocation was done at the time of surgery. All patients received anti‐thymocyte globulin and maintenance therapy with tacrolimus, mycophenolate mofetil and steroids. At month 3, tacrolimus was continued or replaced by sirolimus. The primary endpoint was kidney and pancreas graft survival at one and five years. Fifty patients were included in final analysis in each group. At one year, difference for kidney and pancreas graft survival between sirolimus and tacrolimus were 0 % (CI 90 % [‐4.61 %, 4.61 %]) and 6 % (CI 90 % [‐6.32 %, 18.32 %]) respectively. There was neither difference in renal and pancreas graft survival at 5 years. Thirty‐four patients (68 %) in the sirolimus group versus 3 (6 %) in the tacrolimus group needed definitive withdrawal of the study drug. Despite non‐inferiority of sirolimus compared to tacrolimus for kidney and pancreas graft survival, the high rate of sirolimus discontinuation does not favour its use as cornerstone therapy after SPK. NCT00693446

The pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the pancreas linked to ischemia-reperfusion injury involves the activation of innate immune cell subsets such as macrophages and neutrophils, following tissue damage and release of damage-associated molecular patterns and pro-inflammatory cytokines. Macrophages and neutrophils favor tissue invasion by other immune cells, have deleterious effects or functions, and promote tissue fibrosis. However, some innate cell subsets may promote tissue repair. This outburst of sterile inflammation promotes adaptive immunity activation via antigen exposure and activation of antigen-presenting cells. Better controlling sterile inflammation during pancreas preservation and after transplantation is of utmost interest in order to decrease early allograft loss (in particular thrombosis) and increase long-term allograft survival. In this regard, perfusion techniques that are currently being implemented represent a promising tool to decrease global inflammation and modulate the immune response.