Liver transplantation is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. This has necessitated the adoption of innovative technologies and strategies to protect these higher-risk grafts from the deleterious effects of traditional preservation and ischaemia reperfusion injury (IRI). The advent of normothermic machine perfusion (NMP) and rapid growth in the clinical adoption of this technology has accelerated efforts to utilise NMP as a platform for therapeutic intervention to optimise donor livers. In this review we will explore the emerging preclinical data related to ameliorating the effects of IRI, protecting the microcirculation and reducing the immunogenicity of donor organs during NMP. Exploiting the window of opportunity afforded by NMP, whereby the liver can be continuously supported and functionally assessed while therapies are directly delivered during the preservation period, has clear logistical and theoretical advantages over current preservation methods. The clinical translation of many of the therapeutic agents and strategies we will describe is becoming more feasible with widespread adaptation of NMP devices and rapid advances in molecular biology and gene therapy, which have substantially improved the performance of these agents. The delivery of novel therapeutics during NMP represents one of the new frontiers in transplantation research and offers real potential for successfully tackling fundamental challenges in transplantation such as IRI.

Simultaneous pancreas-kidney transplantation (SPK) is one of the treatment options for type 1 diabetes mellitus with end-stage renal failure. Solid organ transplant recipients are more susceptible to developing post-transplant cancers, including renal cell carcinoma compared to the general population. While the incidence of renal cell carcinoma is up to 10 times higher in kidney-only transplant recipients, reports of renal cell cancers in renal grafts after SPK transplantation are rare and successful nephron sparing partial nephrectomy has not yet been reported in literature. We present herein the case report of two patients, aged 47 and 54 years old, who underwent a successful partial nephron-sparing graft nephrectomy for clear cell and papillary renal cell carcinoma ten and fourteen years after his SPK transplant respectively. Both patients made a full recovery after surgery and maintained good renal function in the respective 12-month and 9-month postoperative period.