**5.3. The impact of procurement practices and techniques**

**5. Outcomes**

**5.1. Whole organ pancreas transplant outcomes**

168 Organ Donation and Transplantation - Current Status and Future Challenges

great increase in acceptance and success.

**5.2. Islet cell transplant outcomes**

Vascularized pancreas transplantation outcomes have improved considerably over time. Although changes to immunosuppression and post-transplantation care can partly account for this, advances in retrieval surgery and organ preservation, in addition to better donor selection, are significant contributors [90, 91]. When exploring pancreas transplantation outcomes, it is paramount to account for the type of transplant performed, as these are associated with differential graft success and survival rates. More specifically, outcomes must be considered based on whether a simultaneous pancreas-kidney (SPK), pancreas after kidney (PAK) transplant, or pancreas transplant alone (PTA) was performed. An exploration of general pancreas transplantation outcomes is beyond the scope of this chapter, as the focus is on the specific impact of retrieval and preservation practices. Overviews investigating trends and recipient outcomes following pancreas transplantation have been published by others, including Dean et al., and Gruessner et al. [90–94]. In brief, the current expected 5-year graft and patient survival rates for pancreas (SPK) transplantation range from 73 to 82% and 89 to 93%, respectively, in the US, UK, Eurotransplant region, and Australia/New Zealand [91, 94–96]. Outcome differences are seen between SPKs, which have historically provided better results, and PTAs and PAKs, due to important variations in the type(s) of recipients for each transplant type, technical differences in the transplantation procedure, and a differential ability to diagnose and treat rejection episodes [91]. SPK transplantation is by far the most commonly performed type of pancreas transplant but islet cell transplantation has also seen a

Like its forebear, islet cell transplantation outcomes have improved considerably over time. The most impactful change was seen with advances in immunosuppression, clearly shown by the success of the Edmonton trial [97], one that revolutionized the progress of the cellular transplant. Other factors have also continued to impact the field, including post-transplantation care, advances in retrieval surgery and organ preservation, in addition to better donor selection. In brief, the most recent presentation from the Collaborative Islet transplant registry (CITR), presented the combined world islet cell transplant data where they reported that over 1055 allogeneic islet transplants have now been reported by 50 islet transplantation centers in Australia, Europe, North America, and Asia. Of these cases, islet transplant alone (ITA) was the most frequent procedure (n = 858) followed by islet after kidney (IAK) and simultaneous islet and kidney transplantation (SIK) (n = 197) [98]. More recently, according to outcomes of the Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia, the primary end point of HbA1c < 7.0% was achieved by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred [99]. This trial clearly demonstrated the significant improvements achieved in the outcomes of islet cell transplantation and its impact on those patients suffering from hypoglycemic unawareness.

Pancreas procurement techniques can significantly impact subsequent transplantation outcomes, and can also prove the difference between organ utilization and discard. In particular, there is ample evidence that factors such as *en bloc* retrieval, retrieval technique and graft handling, type(s) of instruments utilized, and perfusion routes are all important determinants of graft function and transplant-related morbidity. Ensuring that pancreas retrieval is performed by an experienced pancreatic transplant surgeon can significantly minimize such retrieval-related complications and risks [100].

Pancreatic damage during retrieval is not uncommon, and may deem the organ unusable certainly for whole organ transplant. Although the rates are different between centers and of course depends upon the level of training of the surgeons performing the retrievals, a large UK registry analysis showed a greater than 50% rate of surgical damage in retrieved pancreata; furthermore, approximately 10% of grafts were subsequently discarded due to damage sustained at retrieval in this analysis [37]. This was further seen as a significant loss as the grafts were also not utilized for islet cell transplantation due to extended cold ischemic times as a result of ongoing referrals. Within the same series, parenchymal and/or vascular (arterial) damage at procurement contributed to significantly higher rates of subsequent graft loss if the pancreas proceeded to transplantation [37]. In order to minimize surgical retrieval damage it is best to ensure that the staff performing the surgery are at a more senior level, and therefore our unit always sends a senior experienced surgeon to all pancreas retrieval surgeries to ensure adequate training of junior staff and optimize graft quality.

Graft thrombosis is the most important technical cause of whole organ pancreatic allograft loss. Pancreas retrieval and surgical technique is a significant etiologic factor in the incidence of graft thrombosis [101–104]. Graft pancreatitis, which in itself is a significant risk factor for graft thrombosis, is another potentially catastrophic complication associated with morbidity and graft loss that is partly attributable to retrieval technique [100]. Excessive graft handling and poor retrieval surgical technique, including damage to the inferior pancreaticoduodenal artery, are commonly accepted causes of graft pancreatitis in the recipient. [100] The same contributing factors also have an impact on the organs when they are used for islet cell isolation [9].

*En bloc* procurement of the liver and pancreas is associated with better recipient outcomes owing to faster organ retrieval and therefore shorter warm ischemia times [58, 100]. Interestingly, in the aforementioned UK registry analysis between 2008 and 2012, although the vast majority of liver and pancreas retrievals were not performed *en bloc*, there was a trend favoring the *en bloc* approach with respect to reduced pancreatic retrieval injury [37].

*In situ* perfusion routes, in particular the utilization of dual aorto-portal perfusion in preference to aortic-only perfusion, can impact both whole organ and cellular allograft outcomes. Dual perfusion is potentially associated with increased retrieval-related pancreatic injury through a combination of flush injury (increased perfusion volumes), and/or an obstruction of pancreatic portal venous outflow secondary to catheter placement within the inferior or superior mesenteric veins [52, 58]. This ultimately impacts on the pancreas that is retrieved for whole pancreas or cellular transplantation as it can cause a significant increase in edema, and may be associated with a higher rate of graft pancreatitis in whole organ, and poorer isolation results due to collagenase dilution in the islet isolation process. Importantly, an aortic-only perfusion technique does not seem to compromise hepatic allograft outcomes, especially in the standard criteria DBD donors from which pancreata are usually retrieved, and therefore should be considered by retrieval surgeons in these circumstances especially in centers that retrieve grafts for both whole and cellular transplantation [34, 58].

The comparative utility of each preservation fluid must also be considered in the context of additional donor and transplant-related factors. One important consideration when considering any possible superior preservation effects of UW is the expected pancreatic graft cold ischemic time (CIT). UW may especially be beneficial when CIT is greater than or equal to 12 hours [106, 108]. Furthermore, as already mentioned previously, pancreas retrieval is usually undertaken in the multi-organ donor setting. The perfusion/preservation fluid utilized must therefore not compromise any abdominal organ additionally procured, especially the liver. There is conflicting evidence regarding the relative efficacy of UW, HTK, Celsior, and IGL-1 for liver preservation. Some authors suggest that HTK results in inferior graft survival in comparison to UW, whilst others have reported similar survival but a reduction in postliver transplantation biliary strictures when HTK is utilized [109, 110]. Overall, current cumulative evidence does not suggest a significant difference between these four fluids, and further

Pancreas Retrieval for Whole Organ and Islet Cell Transplantation

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

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**5.5. Donation after circulatory death (DCD) vs. donation after brain death (DBD)** 

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 trans-

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

research in this area is required [34].

plantation [84, 115].

**transplantation and the importance of donor selection**

Furthermore, the specific instrument-type employed for pancreatic dissection is an important determinant of the amount of pancreatic bleeding upon reperfusion in the recipient [46]. We have shown that ultrasonic shear (e.g. Harmonic Scalpel) utilization during pancreas retrieval allows the sealing of peri-pancreatic vessels that are otherwise easily missed, thereby contributing to less bleeding and a reduced blood transfusion requirement after transplantation within the recipient [41].
