**5. Outcomes**

#### **5.1. Whole organ pancreas 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 great increase in acceptance and success.

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

retrieval-related complications and risks [100].

tion [9].

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

Pancreas Retrieval for Whole Organ and Islet Cell Transplantation

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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 surger-

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 isola-

*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

*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

favoring the *en bloc* approach with respect to reduced pancreatic retrieval injury [37].

ies to ensure adequate training of junior staff and optimize graft quality.

#### **5.2. Islet cell transplant outcomes**

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.
