Current Opinion in Organ Transplantation:
PANCREAS TRANSPLANTATION: Edited by Walter mark
Donor risk factors, retrieval technique, preservation and ischemia/reperfusion injury in pancreas transplantation
Maglione, Manuela; Ploeg, Rutger J.a,b; Friend, Peter J.a,b
aOxford Transplant Centre
bNuffield Department of Surgical Sciences, University of Oxford, Churchill Hospital, Roosevelt Drive, Oxford, UK
Correspondence to Manuel Maglione, Oxford Transplant Centre, Churchill Hospital, Roosevelt Drive, OX3 7LJ Oxford, UK. Tel: +44 7803 876219; e-mail: firstname.lastname@example.org,email@example.com
Purpose of review: Pancreas transplantation is still hampered by a high incidence of early graft loss, and organ quality concerns result in high nonrecovery/discard rates. Demographic donor characteristics, surgical retrieval strategy, preservation fluid and ischemia time are crucial factors in the process of organ selection and are discussed in this review.
Recent findings: The donor shortage is driving an increasing utilization of nonideal organs which would previously have been identified as unsuitable. Recent literature suggests that organs from extended criteria donors – older (>45 years), BMI >30 kg/m2, and donation after cardiac death (DCD) – can achieve the same graft and patient survival as those from standard criteria donors, with the proviso that the accumulation of risk factors and long ischemic times should be avoided. Visual assessment of the pancreas is advisable before declining/accepting a pancreas. University of Wisconsin represents the gold standard solution; however, histidine–tryptophan–ketoglutarate and Celsior result in equal outcomes if cold ischemia time (CIT) is less than 12 h. Currently in pancreas transplantation, there is no proven effective ischemia/reperfusion injury prophylaxis than trying to keep CIT as short as possible.
Summary: Demographic risk factors, inspection of the pancreas by an experienced surgeon and predicted CIT are crucial factors in deciding whether to accept a pancreas for transplantation. However, there is a need for an improved evidence base to determine where to set the ‘cut-off’ for unsuitable pancreatic grafts.
Simultaneous pancreas kidney (SPK) transplantation represents the treatment of choice for most diabetic patients suffering from end-stage renal disease. Similarly, pancreas transplantation alone (PTA) may be indicated in patients with poor blood glucose control and recurrent life-threatening hypoglycaemic episodes . Despite the published benefits of pancreas transplantation, clinicians are often reluctant to refer patients for this procedure (particularly PTA) due to its complexity and risks. Pancreas transplantation is still hampered by a high burden of early nonimmunological graft losses due to thrombosis, pancreatitis, leakage from the duodenal anastomosis and bleeding [International Pancreas Transplant Registry (IPTR), http://www.iptr.umn.edu]. Surgical complications are associated with reduced long-term graft survival [2,3] and pancreatic graft loss results in a three-fold increased risk ratio for recipient death [4▪]. As a result transplant units are reluctant to accept higher-risk organs resulting in much higher nonrecovery/discard rates compared to other abdominal donor organs [5,6▪▪,7]. In this review, we address the clinical dilemma that faces a transplant surgeon on call, focusing on aspects which influence the decision as to whether or not to accept a pancreas, such as demographic donor risk factors, retrieval technique and preservation, and on ischemia/reperfusion injury (IRI).
DEMOGRAPHIC DONOR RISK FACTORS
Accurate donor selection is crucial in pancreas transplantation . Regarding demographic variables an ideal donor can be defined as a donation after brain death (DBD) donor, between 10 and 40 years of age, with a BMI less than 27.5 kg/m2 and a cause of brain death other than cerebrovascular . Recent IPTR data confirm the importance of donor demographics, with significantly better long-term graft function associated with donors that were young or had a cause of death other than cerebrovascular [10▪▪]. In response to the increasing incidence of nonstandard donors and a high nonrecovery rate, the Eurotransplant Pancreas Advisory Committee introduced the Pre-Procurement-Pancreas-Suitability-Score (P-PASS) that is based on donor parameters available at the time of reporting. Parameters included are age, BMI, ICU stay, cardiac arrest, sodium, amylase, lipase, and catecholamine dose. Total points range from 9 to 28. Retrospective analysis of pancreas donors reported in Eurotransplant demonstrated a three-fold more likelihood to discard the organ if the score was above 17 . Even though this score has been developed to assess the chance of acceptance for transplantation, several centres tested whether it could also predict graft survival. Results are conflicting, with retrospective Eurotransplant registry data showing significantly higher 1-year graft survival in SPK recipients with a P-PASS less than 17 , and single-centre analyses reporting no differences in the incidence of IRI and for 1-year or long-term graft survival [12–14].
Review of the Scientific Registry of Transplant Recipients resulted in the development of the Pancreas-Donor-Risk-Index (P-DRI), a measure of organ quality aiming at predicting 1-year graft survival [15▪]. Factors such as sex, age, race, BMI, height, cause of death, serum creatinine and donation after circulatory death (DCD) are included, as well as preservation time. The median donor has a P-DRI of 1 and is defined as male, 28 years of age, nonblack, BMI of 24 kg/m2, with a height of 173 cm, DBD with a cause of death other than cerebrovascular, serum creatinine less than 2.5 mg/dl and 12 h cold ischemia time (CIT). Age above 45 years, BMI higher than 30 kg/m2 and DCD increase the P-DRI up to 1.56, 1.17 and 1.39, respectively, resulting in higher risk ratio for graft failure. Although the P-DRI represents a valuable tool for donor selection, different single-centre studies challenge these findings reporting equal outcomes with donors older than 45 years of age, and also successful transplantation of paediatric organs [16–19]. Similarly, recent reports show good outcomes using donors with a BMI higher than 30 kg/m2[20▪]. Pancreatic grafts from DCD donors – currently limited to controlled DCD – have also dramatically increased . An analysis of more than 1000 pancreatic grafts transplanted in the UK showed no difference between DCD and DBD in the 1-year patient and graft survival. However, this mirrors a more conservative selection for DCD donors (younger donors, lower BMI, higher incidence of trauma as cause of death). Furthermore, aiming at short ischaemic times, DCD organs were significantly more likely to be locally transplanted [6▪▪]. Similarly, Cambridge showed comparable results between the DCD and DBD transplants; again, cerebrovascular causes of death were less frequent and CIT significantly shorter in the DCD group. Interestingly, the time from withdrawal of treatment to cold perfusion ranged from 16 to 110 min, exceeding by far the threshold of 60 min proposed in the UK and 45 min in the USA . The recently published DCD experience from Madison, Wisconsin, confirms European findings with excellent 1, 3 and 10-year graft survival. The longer mean CIT, compared to European studies, was balanced by the very short mean time from withdrawal of treatment to cold perfusion, pointing at the importance of avoiding accumulation of risk factors in these donors [9,23▪].
There are two retrieval strategies in DBD donation: rapid dissection of vasculature and organs in the cold after flush-out (mandatory if the donor is unstable)  or warm dissection before cold perfusion [25▪]. Whereas the first technique has the major advantage of shortening the procurement procedure, the second technique gives the possibility of a thorough inspection of possible anatomical variations. Although impaired hepatic microcirculation has been associated with liver hilum preparation during the warm phase  there is no evidence to favour either one of these techniques. Key points of pancreas retrieval are to inspect the organ before perfusion to decide whether it is transplantable, to identify abnormalities in the hepatic arterial supply, to avoid traumatic injury to the pancreas during retrieval, and to procure an intact iliac bifurcation (without excessive traction that can cause intimal dissection) for back-table arterial reconstruction. Following general abdominal inspection opening of the lesser sac permits visual and tactile assessment of the pancreas. Pancreases with extensive fibrosis/calcification, intra-lobular fat and severe oedema should be discarded, whereas peri-pancreatic fat often surrounds a suitable pancreas. An aberrant/accessory right hepatic artery originating from the superior mesenteric artery (SMA) has to be recognized but is only a contraindication for simultaneous liver and pancreas procurement if it is of very narrow calibre and runs through the pancreatic parenchyma. For successful liver transplantation a vessel of typical calibre can be divided outside the pancreas and anastomosed to the stump of the gastroduodenal artery (GDA) . The majority of accessory arteries run behind the pancreas and can be dissected and removed with a patch of proximal SMA patch leaving the distal SMA stump for back-table reconstruction of the pancreatic arterial inflow.
If small bowel is retrieved (for a different recipient to the pancreas) the SMA and the superior mesenteric vein (SMV) can be transected at the insertion point of the mid-colic vessels immediately distally to the uncinate process allowing enough vascular length for the intestinal graft without harming pancreatic arterial supply [28,29]. According to centre preferences abdominal organs can be retrieved either en bloc and separated on the back table [24,28], or in one after the other, with the liver first, followed by intestine, pancreas and kidneys [25▪]. In both cases (no evidence favours one strategy) it is of prime importance that the pancreas is retrieved without parenchymal injuries or capsular breaches. Typically these occur by dissecting the GDA (upper margin of the pancreatic head), stapling the mesenteric axis (uncinate process protruding into the mesentery) and by dissecting the pancreas free from all peritoneal attachments and retroperitoneal connective tissue. This is best performed by using the spleen as a handle to minimize surgical trauma of the organ. The excised pancreas comprises the duodenal C, the pancreas itself and the spleen. The three arteries supplying the graft (SMA, splenic artery and GDA) should be intact and the two latter marked with a 6-0 prolene. The iliac bifurcation (Y-graft) should be packed in a separate bag with preservation solution. In addition to these caveats, external cooling of the pancreas by ice slush placed into the lesser sac is recommended to further reduce the core temperature. Portal perfusion should be performed after completely transecting the portal vein or after venting the splenic or inferior mesenteric vein to avoid congestion of the pancreas .
The retrieval technique for DCD organs differs in the timing of the cross clamping, which is either done by ‘super rapid recovery’ through laparotomy and immediate cannulation of the aorta or by immediate cannulation of the femoral artery. This to keep the ischemia time following cessation of cardiorespiratory function and the recommended 5 min observation period prior to declaration of death as short as possible [30▪].
Whilst in kidney  and liver transplantation , there is current debate regarding static cold storage and hypothermic machine perfusion, preservation of the pancreas is achieved by simple cold storage . The three solutions used are in the order of frequency: University of Wisconsin; histidine–tryptophan–ketoglutarate (HTK); Celsior solution . The current ‘gold standard’ for preservation of the pancreas graft is University of Wisconsin solution, which was, in fact, originally developed by Belzer and Southard as a preservation solution for pancreas transplantation . Other solutions such as HTK and Celsior were originally developed as cardioplegic solutions [36,37] but have been increasingly utilized in the perfusion/preservation of abdominal organs. As the exact composition of the solution goes beyond the scope of this manuscript we refer to recent reviews dealing with this topic [34,38,39]. Comparison of University of Wisconsin with HTK shows conflicting data. In a retrospective single-centre study including 308 organs there were no differences in University of Wisconsin or HTK perfused/preserved grafts regarding patient and graft survival [40▪▪]. These observations are supported by two retrospective studies [41,42] and by a small prospective randomized multicentre study showing no advantage in graft survival of University of Wisconsin compared to HTK . Two retrospective studies contrast these reports. In a United Network for Organ Sharing database analysis Stewart et al. reported HTK solution to be associated with a higher risk of graft loss already during the first month following transplantation, especially if CIT exceeded 12 h, and a single-centre analysis describes a four-fold higher thrombosis rate with HTK . There is, however, consensus regarding equal results using University of Wisconsin or HTK if CIT is less than 12 h. Even though high-volume flush of HTK is recommended by the manufacturer, results of these studies suggest a higher incidence of graft pancreatitis, if the HTK volume exceeds 5 l. Less common is the use of Celsior. In a prospective, randomized study Boggi et al. reports similar safety profiles between University of Wisconsin and Celsior. In line with this study Manrique et al. shows similar 2-year graft and patient survival for University of Wisconsin and Celsior perfused/preserved pancreases.
The pancreas is highly susceptible to ischemic periods. This is reflected also in the increased incidence of pancreatitis following haemorrhagic shock and cardiac by-pass surgery [48,49]. So far there are no reliable early markers for pancreatic IRI. Serum amylase, lipase and C-reactive protein levels do not correlate well with the intensity of pancreatitis until after a few days after transplantation.
Postischemic microcirculatory failure is considered the hallmark of pancreatic IRI [50–52]. With venous thrombosis of the transplanted graft accounting for the highest number of early graft losses major efforts in experimental pancreas transplantation are focussed on agents aimed at increasing postreperfusion blood flow. These include nitric oxide , anticoagulation prophylaxis  and prevention of neutrophil adhesion . However, none of these strategies has yet been tested in prospective randomized trials. Recently, a single-centre experience with prophylactic high-dose application (3000 IU) of antithrombin reported lower thrombosis rates and significantly reduced serum amylase and lipase in treated patients . Antiadhesive prophylaxis with a recombinant P-selectin antagonist (YSPSL) has been recently tested in human kidney transplantation showing prevention of inflammatory gene transcription without, however, decreasing delayed graft function [57,58]. Further results are needed to estimate the value of these strategies. Remote ischaemic preconditioning is a promising new approach; originally applied in paediatric cardiac surgery , this has been shown to prevent IRI in experimental pancreas transplantation [60,61]. A current randomized controlled trial is now testing this approach evaluating the influence of a short period of blood flow occlusion of the lower extremity prior to organ recovery on kidney, liver and pancreas graft survival (clincaltrials.gov number NCT00975702).
Current donor scoring systems may help transplant surgeons to achieve uniform practice and improve utilization of higher-risk organs but these are not reliable in identifying a ‘cut-off’ for suitable vs. nonsuitable organs. As surgical assessment of the graft (probably the most important determinant in organ selection process) is not included, nonstandard organs should always be visually inspected by an experienced pancreas transplantation surgeon before deciding the nonrecovery. Prolonged life expectancy associated with a functioning SPK compared to patients remaining on the waiting list [17,62,63], increased quality of life  and psychological issues of the potential recipient should also influence the decision-making. Available evidence suggests the need to avoid an accumulation of demographic donor risk factors. Higher-risk organs should probably be transplanted only if CIT can be kept below 12 h.
The quality of evidence for the best retrieval strategy and optimum perfusion solution is poor; however, there is a broad agreement about the necessity to minimize CIT, since the pancreas is probably the most susceptible abdominal organ to IRI. Currently there is no specific treatment for IRI and prevention is clearly more likely to be effective than treatment.
The authors confirm that this manuscript has not been published or accepted for publication in its current or a substantially similar form elsewhere, and that it is not under consideration by another publisher.
Conflicts of interest
The authors have no conflict of interest to declare.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 124).
1. White SA, Shaw JA, Sutherland DE. Pancreas transplantation. Lancet 2009; 373:1808–1817.
2. Banga N, Hadjianastassiou VG, Mamode N, et al. Outcome of surgical complications following simultaneous pancreas-kidney transplantation. Nephrol Dial Transplant 2012; 27:1658–1663.
3. Page M, Rimmelé T, Ber CE, et al. Early relaparotomy after simultaneous pancreas–kidney transplantation. Transplantation 2012; 94:159–164.
4▪. Gruessner AC. 2011 update on pancreas transplantation: comprehensive trend analysis of 25,000 cases followed up over the course of twenty-four years at the International Pancreas Transplant Registry (IPTR). Rev Diabet Stud 2011; 8:6–16.
Retrospective analysis of the outcome of more than 25 000 pancreas and pancreas–kidney transplantations performed in the USA over the past 45 years.
5. Tuttle-Newhall JE, Krishnan SM, Levy MF, et al. Organ donation and utilization in the United States: 1998–2007. Am J Transplant 2009; 9:879–893.
6▪▪. Muthusamy AS, Mumford L, Hudson A, et al. Pancreas transplantation from donors after circulatory death from the United kingdom. Am J Transplant 2012; 12:2150–2156.
This article summarizes the current UK experience with pancreas transplantations from DCD donors. Stringent DCD donor selection and short CIT result in similar 1-year graft and patient survival between DBD and DCD grafts.
7. Vinkers MT, Rahmel AO, Slot MC, et al. How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors. Transplant Proc 2008; 40:1275–1278.
8. Sutherland D, Gruessner R, Dunn D, et al. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 2001; 233:463–501.
9. Fridell JA, Rogers J, Stratta RJ. The pancreas allograft donor: current status, controversies, and challenges for the future. Clin Transplant 2010; 24:433–449.
10▪▪. Gruessner AC, Sutherland DE, Gruessner RW. Long-term outcome after pancreas transplantation. Curr Opin Organ Transplant 2012; 17:100–105.
Based on IPTR data this article shows the direct correlation between 1-year graft survival and long-term outcome of the pancreatic graft.
11. Vinkers MT, Rahmel AO, Slot MC, et al. Influence of a donor quality score on pancreas transplant survival in the Eurotransplant area. Transplant Proc 2008; 40:3606–3608.
12. Woeste G, Moench C, Hauser IA, et al. Can the preprocurement pancreas suitability score predict ischemia-reperfusion injury and graft survival after pancreas transplantation? Transplant Proc 2010; 42:4202–4205.
13. Schenker P, Vonend O, Ertas N, et al. Preprocurement pancreas allocation suitability score does not correlate with long-term pancreas graft survival. Transplant Proc 2010; 42:178–180.
14. Foltys DB, Kaths JM, Zimmermann T, et al. Ten years of simultaneous pancreas-kidney transplantation: a retrospective single-center analysis of prospectively obtained data. Transplant Proc 2011; 43:3267–3269.
15▪. Axelrod DA, Sung RS, Meyer KH, et al. Systematic evaluation of pancreas allograft quality, outcomes and geographic variation in utilization. Am J Transplant 2010; 10:837–845.
First description of the P-DRI aiming at uniform and improve organ acceptance by estimating the risk of graft failure.
16. Singh RP, Rogers J, Farney AC, et al. Outcomes of extended donors in pancreatic transplantation with portal-enteric drainage. Transplant Proc 2008; 40:502–505.
17. Salvalaggio PR, Schnitzler MA, Abbott KC, et al. Patient and graft survival implications of simultaneous pancreas kidney transplantation from old donors. Am J Transplant 2007; 7:1561–1571.
18. Boggi U, Del Chiaro M, Signori S, et al. Pancreas transplants from donors aged 45 years or older. Transplant Proc 2005; 37:1265–1267.
19. Fernandez LA, Turgeon NA, Odorico JS, et al. Superior long-term results of simultaneous pancreas-kidney transplantation from pediatric donors. Am J Transplant 2004; 4:2093–2101.
20▪. Fridell JA, Mangus RS, Taber TE, et al. Growth of a nation part I: impact of organ donor obesity on whole-organ pancreas transplantation. Clin Transplant 2011; 25:E225–E232.
This article describes good results with donors having BMI above 30 kg/m2.
21. Domínguez-Gil B, Haase-Kromwijk B, Van Leiden H, et al. Current situation of donation after circulatory death in European countries. Transpl Int 2011; 24:676–686.
22. Qureshi MS, Callaghan CJ, Bradley JA, et al. Outcomes of simultaneous pancreas-kidney transplantation from brain-dead and controlled circulatory death donors. Br J Surg 2012; 99:831–838.
23▪. Bellingham JM, Santhanakrishnan C, Neidlinger N, et al. Donation after cardiac death: a 29-year experience. Surgery 2011; 150:692–702.
This article reports the single-centre experience with organ transplantation from DCD donors including the outcome of 72 pancreas transplantations which is comparable with DBD pancreatic grafts.
24. Brockmann JG, Vaidya A, Reddy S, Friend PJ. Retrieval of abdominal organs for transplantation. Br J Surg 2006; 93:133–146.
25▪. Wunderlich H, Brockmann JG, Voigt R, et al. DTG procurement guidelines in heart beating donors. Transpl Int 2011; 24:733–757.
Guidelines and caveats for organ retrieval – including the pancreas – in DBD donors.
26. Klar E, Kraus T, Osswald BR, et al. Induction of impaired hepatic microcirculation by in situ hilus preparation in liver explantation. Zentralbl Chir 1995; 120:482–485.
27. Hevelke P, Grodzicki M, Nyckowski P, et al. Hepatic artery reconstruction prior to orthotopic liver transplantation. Transplant Proc 2003; 35:2253–2255.
28. Boggi U, Vistoli F, Del Chiaro M, et al. A simplified technique for the en bloc procurement of abdominal organs that is suitable for pancreas and small-bowel transplantation. Surgery 2004; 135:629–641.
29. Fridell JA, Mangus RS, Powelson JA, et al. Outcomes of pancreas allografts procured simultaneously with an isolated intestine allograft: single-center and national data. Transplantation 2012; 94:84–88.
30▪. Reich DJ, Mulligan DC, Abt PL, et al. ASTS recommended practice guidelines for controlled donation after cardiac death organ procurement and transplantation. Am J Transplant 2009; 9:2004–2011.
Recommendations for organ procurement in DCD (Maastricht III and IV) donors. References are rated by their level of scientific evidence.
31. Moers C, Smits J, Maathuis M, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 2009; 360:7–19.
32. Guarrera JV, Henry SD, Samstein B, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant 2010; 10:372–381.
33. Maathuis MH, Leuvenink HG, Ploeg RJ. Perspectives in organ preservation. Transplantation 2007; 83:1289–1298.
34. Fridell JA, Mangus RS, Powelson JA. Organ preservation solutions for whole organ pancreas transplantation. Curr Opin Organ Transplant 2011; 16:116–122.
35. Ploeg RJ, Goossens D, Sollinger HW, et al. The Belzer-UW solution for effective long-term preservation in canine pancreas transplantation. Transplant Proc 1989; 21:1378–1380.
36. Bretschneider HJ. Myocardial protection. Thorac Cardiovasc Surg 1980; 28:295–302.
37. Menasché P, Termignon JL, Pradier F, et al. Experimental evaluation of Celsior, a new heart preservation solution. Eur J Cardiothorac Surg 1994; 8:207–213.
38. Iwanaga Y, Sutherland DE, Harmon JV, Papas KK. Pancreas preservation for pancreas and islet transplantation. Curr Opin Organ Transplant 2008; 13:445–451.
39. Squifflet JP, LeDinh H, de Roover A, Meurisse M. Pancreas preservation for pancreas and islet transplantation: a minireview. Transplant Proc 2011; 43:3398–3401.
40▪▪. Fridell JA, Mangus RS, Powelson JA. Histidine-tryptophan-ketoglutarate for pancreas allograft preservation: the Indiana University experience. Am J Transplant 2010; 10:1284–1289.
This retrospective single center study comparing University of Wisconsin and HTK in pancreas transplantation highlights the equal efficacy of both solutions if CIT is below 10 h.
41. Potdar S, Malek S, Eghtesad B, et al. Initial experience using histidine-tryptophan-ketoglutarate solution in clinical pancreas transplantation. Clin Transplant 2004; 18:661–665.
42. Becker T, Ringe B, Nyibata M, et al. Pancreas transplantation with histidine-tryptophan-ketoglutarate (HTK) solution and University of Wisconsin (UW) solution: is there a difference? JOP 2007; 8:304–311.
43. Schneeberger S, Biebl M, Steurer W, et al
. A prospective randomized multicenter trial comparing histidine-tryptophane-ketoglutarate versus University of Wisconsin perfusion solution in clinical pancreas transplantation. Transpl Int 2009; 22:217–224.
44. Stewart Z, Cameron A, Singer A, et al. Histidine-tryptophan-ketoglutarate (HTK) is associated with reduced graft survival in pancreas transplantation. Am J Transplant 2009; 9:217–221.
45. Alonso D, Dunn T, Rigley T, et al. Increased pancreatitis in allografts flushed with histidine-tryptophan-ketoglutarate solution: a cautionary tale. Am J Transplant 2008; 8:1942–1945.
46. Boggi U, Vistoli F, Del Chiaro M, et al. Pancreas preservation with University of Wisconsin and Celsior solutions: a single-center, prospective, randomized pilot study. Transplantation 2004; 77:1186–1190.
47. Manrique A, Jiménez C, Herrero ML, et al. Pancreas preservation with the University of Wisconsin versus Celsior solutions. Transplant Proc 2006; 38:2582–2584.
48. Warshaw AL, O’Hara PJ. Susceptibility of the pancreas to ischemic injury in shock. Ann Surg 1978; 188:197–201.
49. Fernández-del Castillo C, Harringer W, Warshaw AL, et al. Risk factors for pancreatic cellular injury after cardiopulmonary bypass. N Engl J Med 1991; 325:382–387.
50. Schaser K, Puhl G, Vollmar B, et al. In vivo imaging of human pancreatic microcirculation and pancreatic tissue injury in clinical pancreas transplantation. Am J Transplant 2005; 5:341–350.
51. Drognitz O, Obermaier R, Liu X, et al. Effects of organ preservation, ischemia time and caspase inhibition on apoptosis and microcirculation in rat pancreas transplantation. Am J Transplant 2004; 4:1042–1050.
52. Maglione M, Oberhuber R, Cardini B, et al. Donor pretreatment with tetrahydrobiopterin saves pancreatic isografts from ischemia reperfusion injury in a mouse model. Am J Transplant 2010; 10:2231–2240.
53. Hegyi P, Rakonczay Z. The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas. Antioxid Redox Signal 2011; 15:2723–2741.
54. Hackert T, Werner J, Uhl W, et al. Reduction of ischemia/reperfusion injury by antithrombin III after experimental pancreas transplantation. Am J Surg 2005; 189:92–97.
55. Preissler G, Eichhorn M, Waldner H, et al
. Intercellular adhesion molecule-1 blockade attenuates inflammatory response and improves microvascular perfusion in rat pancreas grafts. Pancreas 2012; 41:1112–1118.
56. Fertmann JM, Arbogast HP, Illner WD, et al. Antithrombin therapy in pancreas retransplantation and pancreas-after-kidney/pancreas-transplantation-alone patients. Clin Transplant 2011; 25:E499–508.
57. Gaber AO, Mulgaonkar S, Kahan BD, et al. YSPSL (rPSGL-Ig) for improvement of early renal allograft function: a double-blind, placebo-controlled, multicenter Phase IIa study. Clin Transplant 2011; 25:523–533.
58. Cheadle C, Watkins T, Ehrlich E, et al. Effects of antiadhesive therapy on kidney biomarkers of ischemia reperfusion injury in human deceased donor kidney allografts. Clin Transplant 2011; 25:766–775.
59. Cheung MM, Kharbanda RK, Konstantinov IE, et al. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol 2006; 47:2277–2282.
60. Oehmann C, Benz S, Drognitz O, et al. Remote preconditioning reduces microcirculatory disorders in pancreatic ischemia/reperfusion injury. Pancreas 2007; 35:e45–e50.
61. Nikeghbalian S, Mardani P, Mansoorian MR, et al. The effect of ischemic preconditioning of the pancreas on severity of ischemia/reperfusion-induced pancreatitis after a long period of ischemia in the rat. Transplant Proc 2009; 41:2743–2746.
62. Ojo AO, Meier-Kriesche HU, Hanson JA, et al. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation 2001; 71:82–90.
63. Wolfe RA, McCullough KP, Schaubel DE, et al. Calculating life years from transplant (LYFT): methods for kidney and kidney-pancreas candidates. Am J Transplant 2008; 8 (4 Pt 2):997–1011.
64. Nathan DM, Fogel H, Norman D, et al. Long-term metabolic and quality of life results with pancreatic/renal transplantation in insulin-dependent diabetes mellitus. Transplantation 1991; 52:85–91.
DCD; ischemia; nonstandard donor; pancreas transplantation; risk score
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