**5.4. The impact of perfusion and preservation fluids**

Pancreas preservation by cold storage using University of Wisconsin solution has been the mainstay method used for pancreas transplantation over the past two decades. Other solutions, such as HTK, Celsior, and SCOT 15, struggled to demonstrate any advantage for shortterm preservation periods. But the advent of clinical islet transplantation and the larger use of controlled DBD donors have prompted the transplantation community to develop methods for increasing pancreas graft quality while preventing ischemic reperfusion damage especially in the cellular arena. It has been thought that oxygenation by 1- or 2-layer methods during pancreas preservation, as well as the use of perfluorocarbons, may increase islet yield. Based on the former methods, there is a renewed interest in machine perfusion and oxygenation in pancreas preservation for pancreas transplantation and islet cell preparation [105].

A recent systematic review and meta-analysis by our group compared the outcomes of whole organ pancreas transplantation based on the *in situ* perfusion and subsequent preservation fluid utilized (UW, HTK, or Celsior) [81]. Ischemia-reperfusion injury of the pancreas, as reflected by post-operative peak lipase levels, was significantly lower when UW was employed as a perfusion/preservation fluid in comparison to HTK, but there was no significant difference in peak amylase. This pancreatic ischemia-reperfusion injury may translate to lower clinical graft pancreatitis rates when UW is used in comparison to HTK, although this is not a universal finding [106]. No significant disparity was observed in biochemical injury markers or graft pancreatitis rates between UW and Celsior [81].

As discussed above, post-transplantation graft thrombosis is a significant cause of graft loss. Thrombotic graft loss rates do not differ based on whether UW, HTK, or Celsior is used for *in situ* perfusion and preservation of the pancreas [81]. Furthermore, cumulative graft survival after first post-transplantation month does not favor UW over HTK, although a distinct trend favoring UW emerges at the 1-year mark [81, 106, 107]. A US registry analysis provided further evidence for this, showing a significant association between HTK perfusion/preservation and graft loss, in comparison to UW [108]. In comparison, the use of Celsior is associated with similar 1-year graft survival rates to UW [64, 76].

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 research in this area is required [34].

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

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

Pancreas preservation by cold storage using University of Wisconsin solution has been the mainstay method used for pancreas transplantation over the past two decades. Other solutions, such as HTK, Celsior, and SCOT 15, struggled to demonstrate any advantage for shortterm preservation periods. But the advent of clinical islet transplantation and the larger use of controlled DBD donors have prompted the transplantation community to develop methods for increasing pancreas graft quality while preventing ischemic reperfusion damage especially in the cellular arena. It has been thought that oxygenation by 1- or 2-layer methods during pancreas preservation, as well as the use of perfluorocarbons, may increase islet yield. Based on the former methods, there is a renewed interest in machine perfusion and oxygenation in pancreas preservation for pancreas transplantation and islet cell preparation [105].

A recent systematic review and meta-analysis by our group compared the outcomes of whole organ pancreas transplantation based on the *in situ* perfusion and subsequent preservation fluid utilized (UW, HTK, or Celsior) [81]. Ischemia-reperfusion injury of the pancreas, as reflected by post-operative peak lipase levels, was significantly lower when UW was employed as a perfusion/preservation fluid in comparison to HTK, but there was no significant difference in peak amylase. This pancreatic ischemia-reperfusion injury may translate to lower clinical graft pancreatitis rates when UW is used in comparison to HTK, although this is not a universal finding [106]. No significant disparity was observed in biochemical injury

As discussed above, post-transplantation graft thrombosis is a significant cause of graft loss. Thrombotic graft loss rates do not differ based on whether UW, HTK, or Celsior is used for *in situ* perfusion and preservation of the pancreas [81]. Furthermore, cumulative graft survival after first post-transplantation month does not favor UW over HTK, although a distinct trend favoring UW emerges at the 1-year mark [81, 106, 107]. A US registry analysis provided further evidence for this, showing a significant association between HTK perfusion/preservation and graft loss, in comparison to UW [108]. In comparison, the use of Celsior is associated with

retrieve grafts for both whole and cellular transplantation [34, 58].

170 Organ Donation and Transplantation - Current Status and Future Challenges

**5.4. The impact of perfusion and preservation fluids**

markers or graft pancreatitis rates between UW and Celsior [81].

similar 1-year graft survival rates to UW [64, 76].

within the recipient [41].
