Ex situ Perfusion of Pancreas for Whole-Organ Transplantation: Is it Safe and Feasible? A Systematic Review

Abstract

Introduction: Pancreas transplantation is currently one of the best treatments proposed in highly selected patients with unstable and brittle type 1 diabetes. The objective of pancreas transplantation is to restore normoglycemia and avoid the occurrence of complications associated with diabetes. Graft pancreatitis and thrombosis, arising from ischemia reperfusion injuries, are major causes of graft loss in the postoperative period. Ex situ perfusion, in hypothermic or normothermic settings, allowed to improve ischemic reperfusion injury in other organ transplantations (kidney, liver, or lung). The development of pancreatic graft perfusion techniques would limit these ischemic reperfusion injuries. Objective: Evaluation of the safety and feasibility of ex situ perfusion of pancreas for whole-organ transplantation. Methods: English literature about pancreas perfusion was analyzed using electronic database Medline via PubMed (1950-2018). Exclusion criteria were studies that did not specify the technical aspects of machine perfusion and studies focused only on pancreas perfusion for islet isolation. Results: Hypothermic machine perfusion for pancreas preservation has been evaluated in nine studies and normothermic machine perfusion in ten studies. We evaluated machine perfusion model, types of experimental model, anatomy, perfusion parameters, flushing and perfusion solution, length of perfusion, and comparison between static cold storage and perfusion. Conclusions: This review compared ex vivo machine perfusion of experimental pancreas for whole-organ transplantation. Pancreas perfusion is feasible and could be a helpful tool to evaluate pancreas prior to transplantation. Pancreas perfusion (in hypothermic or normothermic settings) could reduce ischemic reperfusion injuries, and maybe could avoid pancreas thrombosis and reduce morbidity of pancreas transplantation.

Pancreas Ex-Situ Preservation and Evaluation. Development of a Normothermic Machine Perfusion System

“…40 mmHg is a low pressure suitable for the pancreas graft and found by us to be enough to provide a perfusion and not to be injurious to the microcirculation over a prolonged period of perfusion. Our observation is in keeping with the available studies that low perfusion pressures are associated with viable pancreas grafts during machine perfusion 10 . The ideal pressure level has not yet been established but a U.K group, Kumar et al proposed an even lower perfusion pressure of 25 mmHG reporting excellent preservation of parenchyma while maintaining good blood flow 16 .…”

“…It is a technology already clinically established, in France, normothermic regional perfusion is mandatory in DCD organ procurement with the first pancreas transplantation now performed post this 5 . NP has proven to be effective in kidney [6][7] , liver [8][9][10] , lung 11 and heart 12 transplantation with published clinical studies. The exciting possibilities of NP are being expanded with multiple groups exploring ex-situ injection of drugs and or cellular therapies with the goal of organ resuscitation prior to transplantation 9 .…”

“…The exciting possibilities of NP are being expanded with multiple groups exploring ex-situ injection of drugs and or cellular therapies with the goal of organ resuscitation prior to transplantation 9 . Data on NP in pancreatic transplantation are few published animal and non-transplanted human graft studies with all being preclinical 10 . Our transplantation research group has been focused on establishing NP for both experimental and clinical uses.…”

Breaking the limits of experimental pancreas transplantation: Working toward the clinical ideal graft

“…Preservation of the pancreas is critical to prevent the two major early complications of pancreas transplant, namely thrombosis and graft pancreatitis. These complications are causes of graft loss in the postoperative period and can occur in 25-50% of cases (8). The standard method to preserve human pancreas is hypothermic preservation by static cold storage (SCS).…”

“…Ex vivo machine perfusion (EVMP) has provided benefits over SCS in other organ transplants (8). It consists of a pump-generated flow through the organ in a circuit allowing recirculation of a preservation solution through the vasculature at various temperatures.…”