**5.5. Donation after circulatory death (DCD) vs. donation after brain death (DBD) transplantation and the importance of donor selection**

With careful selection of donors, excellent whole organ pancreatic transplantation outcomes can be obtained even after DCD transplantation. The Pancreas Donor Risk Index (PDRI) is a tool that incorporates donor and preservation-related risk factors, including DCD donors, prolonged preservation time, and high body mass index (BMI), in a risk model for subsequent graft failure [111]. This model has been utilized in both the North American and European settings [111, 112]. It is important to note however that such models must not be used in isolation, and donor pancreata with one or more risk factors, including DCD donors, can still be used to achieve good outcomes. Indeed, our center's first DCD pancreas transplant was in 2007, and has been followed by a further six DCD pancreas transplants, all displaying good long-term graft function [84, 113]. Meta-analyses have shown equivalent graft and patient survival when comparing DBD and DCD pancreatic transplantation, although graft thrombosis rates are higher when DCD grafts are used [51, 114]. Importantly, this higher graft thrombosis rate can be abrogated when donor therapies such as systemic ante-mortem heparin administration are applied [51]. The use of younger donors, with a lower BMI, and low warm ischemic times, has contributed to the success of DCD whole organ pancreas transplantation [84, 115].

There has, however, been more reserved interest in DCD in pancreas for cellular transplantation as the perceived ischemic insult appears to have a much greater effect on the isolated islets for cellular transplantation than when the whole pancreas is transplanted. This is largely because the entire reserve of islets remains intact in the whole organ graft rather than being removed, and a smaller proportion is transplanted in the cellular graft [66, 99]. However, a number of encouraging studies have shown varying success. Albeit from a more advantageous DCD setting allowing earlier intervention including cannulation of the donor and antemortem heparin administration, which has, been shown to be a distinct advantage in this setting [51]. One such report from the Japanese Islet Registry reported their findings from 65 DCD islet isolations performed for 34 transplantations in 18 patients with T1DM. Despite the fact that all recipients remained free of severe hypoglycemia, only three patients achieved insulin independence for 14, 79, and 215 days. HbA1c levels and requirement of exogenous insulin were significantly improved in all patients [116]. In the more traditional DCD setting the Edmonton group have recently reported their findings comparing islet isolations from 15 DCD and 418 DBD donors performed between September 2008 and September 2014. Compared to DBD, pancreata from DCD were procured locally and donors required less vasopressive support (P < 0.001 and P = 0.023, respectively), but the other variables were similar between groups. The metabolic function was similar between DBD and DCD, as well as the mean decrease in insulin requirement at 1-month post-transplantation (DBD: 64.82%; DCD: 60.17% reduction, P = 0.517). These results support the broader use of DCD pancreata for islet isolation. However, a much larger DCD islet experience will be required to truly determine non-inferiority of both short and long-term outcomes [117].

at normal body temperature (normothermic), such risks must then be balanced against the need for adequate perfusion to sustain normal aerobic metabolism. An additional challenge during pancreatic MP is the need to adequately and safely account for the organ's exocrine

Pancreas Retrieval for Whole Organ and Islet Cell Transplantation

http://dx.doi.org/10.5772/intechopen.75151

173

As a result of these issues, most pancreatic MP studies have been conducted in the field of islet cell transplantation rather than the whole pancreas [120, 123]. Graft edema, is disadvantageous for both whole organ and cellular transplantation. However some groups have studied its use as it theoretically facilitates the enzymatic digestion of pancreatic acinar tissue [124]. Hypothermic MP can potentially be employed to increase human islet yield, viability, and insulin secretion despite an extended CIT (> 12 hours), possibly increasing the number of pancreata that can be used for successful islet isolation [125]. Cases of human islet transplantation following MP are yet to be published, however. Whole organ pancreas MP has been investigated in the context of extended criteria organs that were not utilized for human transplantation. Some authors have shown 6 hours of oxygenated hypothermic MP using UW machine perfusion solution increases the ATP content of DCD pancreata to reach a level that is similar to DBD pancreata at baseline [126]. Graft edema can be kept to a minimum if low pressure hypothermic MP is utilized, even for as long as 24 hours [127]. Subsequent *ex vivo* normothermic perfusion can be used to simulate reperfusion at transplantation after initial hypothermic MP, and has been shown to demonstrate adequate insulin secretion by such

Normothermic MP is an attractive alternative for whole pancreas preservation, and likely provides better graft viability assessment than hypothermic perfusion. Both endocrine and exocrine graft function can be assessed during perfusion by measuring C-peptide and/or insulin secretion and stimulation in response to glucose, and amylase and lipase release, respectively [122, 129]. Blood flow and resistance parameters can also be assessed using this technique, although this is also possible with hypothermic MP. However it is important to note that no defined cut-offs or validated protocols for human transplantation have been developed, and

Persufflation is a technique in which the pancreas is directly perfused with a humidified gas such as oxygen via the SMA and/or splenic arteries. Non-utilized human DBD pancreata have been perfused by this method, and subsequent graft assessment showed an increase in pancreatic ATP levels [130]. Porcine data from the same group showed significantly improved pancreatic histology after 24 hours of persufflation in comparison to utilization of the TLM [131]. Islet isolation after 24 hours of persufflation, including in human pancreata, is likely increased, compared to other methods such as the TLM [132]. This was confirmed in a later study, whereby islets of sufficient quantity and quality for transplantation were isolated from all five human pancreata that underwent persufflation using 40% humidified oxygen perfused at 10–25 mmHg [133]. Similar to MP however, pancreas persufflation has not yet been followed by clinical islet and/or whole organ pancreas transplantation although some

output, which is stimulated during normothermic perfusion [122].

pancreata [128].

**6.2. Persufflation**

will require significantly more pre-clinical work.

research is now underway by a limited number of groups.
