Hourglass optimization in pancreas transplantation: A systematic review (HOP study)

Pancreas transplantation provides durable metabolic control for selected patients with insulin-dependent diabetes mellitus but remains uniquely vulnerable to early technical failure. Ischemia-reperfusion injury is central to graft loss, yet the relative impact of discrete, time-dependent intervals during donor management, procurement, and implantation is incompletely defined. This systematic review evaluates how procurement-related temporal variables influence early complications and pancreas graft survival.

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (no. 1303859). MEDLINE, Embase, Scopus, and Web of Knowledge were searched from January 1996 to February 2026 for studies reporting donor-related timing variables and pancreas transplant outcomes. Primary exposure variables included brain-death-to-procurement time, donation after circulatory death agonal and asystolic times, pancreas extraction time, cold ischemia time, and vascular anastomosis time. Primary outcomes were technical graft failure and pancreas graft loss.

Twelve studies met inclusion criteria. Prolonged brain-death-to-procurement time was paradoxically associated with improved long-term graft survival and reduced acute rejection, suggesting potential graft stabilization following brain death. In donation after circulatory death donors, functional warm ischemia and asystolic time-but not total time to death-were independently associated with increased graft loss, demonstrating a phase-specific vulnerability once circulation ceases. Pancreas extraction time showed inconsistent associations with postoperative complications and was not an independent predictor of graft survival. In contrast, cold ischemia time emerged as the most consistent and clinically significant determinant of outcome, with a nonlinear threshold effect: cold ischemia time ≥20-24 hours markedly increased technical failure, thrombosis, and early graft loss, whereas each additional hour incrementally worsened long-term survival. Anastomosis time was not independently associated with graft outcomes.

Pancreas graft outcomes are determined by the cumulative and phase-specific burden of ischemic injury accrued from donor management through implantation. Among all temporal variables, cold ischemia time remains the dominant modifiable risk factor, while minimizing asystolic and functional warm ischemia is critical in donation after circulatory death procurement. Emerging perfusion strategies may mitigate time-dependent injury and expand the donor pool. Optimizing each procurement interval remains essential to improving early technical success and durable graft survival in pancreas transplantation.