- Email: [email protected]
Can the Preprocurement Pancreas Suitability Score Predict Ischemia-Reperfusion Injury and Graft Survival After Pancreas Transplantation?
Can the Preprocurement Pancreas Suitability Score Predict Ischemia-Reperfusion Injury and Graft Survival After Pancreas Transplantation? G. Woeste, C. Moench, I.A. Hauser, H. Geiger, E. Scheuermann, and W.O. Bechstein ABSTRACT Background. Ischemia-reperfusion injury (IRI) is common after pancreas transplantation, leading to pancreatitis or thrombosis with the need for relaparotomy or even graft loss. Optimal donor selection may reduce the postoperative morbidity of IRI. The Eurotransplant preprocurement pancreas suitability score (P-PASS) seeks to identify ideal donors with a value ⬍17. Owing to the organ shortage the waiting time for pancreas transplantation is increasing, a problem that may be addressed with the use of extended-criteria donors. We analyzed our pancreas transplantations regarding postoperative complications according to the P-PASS. To reflect IRI we used the peak C-reactive protein (CRP) levels during the first 3 postoperative days. Methods. From January 2009 to July 2010, we transplanted 52 pancreas grafts, including, 50 simultaneous pancreas-kidney transplantations (SPK), 1 after a kidney graft, and 1 alone. For 3 SPK donors the P-PASS was not available. All transplantations were performed using systemic venous and enteric drainage. The immunosuppression protocol included antibody induction with antithymocyte globulin and maintenance therapy with steroids, tacrolimus, and mycophenolate mofetil. The peak CRP in the first 3 postoperative days was used as a marker for IRI. Results. The mean P-PASS of our donors was 16.4 ⫾ 2.6 (range, 12–22). We compared 24 patients receiving organs from “ideal” donors (P-PASS ⬍17; ID) with 25 receiving grafts from extended-criteria donors (P-PASS ⱖ17; ED). There was no significant difference in the incidence of graft loss among ID versus ED grafts (20.8% vs 20.0%; P ⫽ 1.0). Comparing the rates of postoperative complications of patients, we did not observe a significant difference in graft thrombosis (4.2% vs 16.0%; P ⫽ .349), relaparotomy (29.2% vs 40.0%; P ⫽ .551), a pancreatic fistula (37.5% vs 28.0%; P ⫽ .543), or the length of hospital stay (36.5 ⫾ 19.2 vs 37.4 ⫾ 20.8 days; P ⫽ .875), respectively. Regarding IRI, there was no significant difference in peak CRP values (14.1 ⫾ 5.5 vs 16.2 ⫾ 6.0 mg/dL; P ⫽ .211). Conclusion. This single center analysis failed to show that P-PASS significantly predicted pancreas graft survival, postoperative morbidity, or IRI severity. These findings suggested a chance to increase the donor pool using extended-criteria donors. imultaneous pancreas-kidney transplantation (SPK) has become a preferred procedure for patients suffering from type 1 diabetes mellitus and end-stage renal disease.1,2 During the past few years the technical success rate has markedly improved owing to better surgical techniques, organ procurement and preservation, and immunosuppression protocols.3–5 However graft pancreatitis and thrombosis remain major problems that can lead to graft loss.6,7 The main cause of these problems is microvascular damage
S
From the Department of General and Visceral Surgery, Goethe-University, Frankfurt, Germany; and Department of Nephrology, Goethe-University, Frankfurt, Germany. Address correspondence to Guido Woeste, MD, Department of Surgery, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. E-mail: guido.woeste@ kgu.de
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.09.021
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
4202
Transplantation Proceedings, 42, 4202– 4205 (2010)
PANCREAS SUITABILITY SCORE AS PREDICTOR
caused by ischemia followed by reperfusion (IRI),8,9 which have been addressed with various treatments.10,11 However, little is known about the impact of IRI on the occurrence of graft pancreatitis. The problem of organ shortage and increasing waiting time may be alleviated with less than ideal donors. Careful donor selection can reduce posttransplantation morbidity.12–14 The Eurotransplant Pancreas Advisory Committee retrospectively validated a donor quality score to recognize a suitable pancreas donor, the preprocurement pancreas suitability score (P-PASS).15 We analyzed the P-PASS in relation to the incidence of early postoperative complications and evidence of IRI among all pancreas transplantations performed at our center. METHODS
Using the following nine parameters available at the time of donor reporting, the Eurotransplant Pancreas Advisory Committee defined the P-PASS: age, body mass index, intensive care unit stay, cardiac arrest, serum sodium, serum amylase and lipase, and (nor)adrenaline and dobutamine dopamine use. An organ donor with a P-PASS of ⬍17 was suggested to represent an “ideal donor,” who is threefold more likely to be accepted by transplant surgeons in Eurotransplant.15 All 52 pancreas transplantations performed at our institution between January 2004 and July 2010 were evaluated for this retrospective study: 50 SPK, 1 pancreas after kidney transplantation, and 1 pancreas transplantation alone. We reviewed the medical records for donor characteristics and postoperative courses with special attention to IRI and complications regard the pancreas graft. Complete data to calculate the P-PASS was available for 49 patients (94.2%), including 20 women and 29 men. The overall mean age was 42.4 ⫾ 7.5 years, mean duration of diabetes 27.0 ⫾ 8.2 years, and mean duration of dialysis 25.1 ⫾ 29.2 months, with 13 patients transplanted preemptively before the need for dialysis. As described previously, the peak CRP over the first 3 postoperative days was used as a marker for IRI.16 We analyzed our findings according to the P-PASS. All pancreas transplantations were performed using systemic venous and enteric drainage. The immunosuppressive protocol consisted of antibody induction with antithymocyte globulin (Thymoglobulin; Genzyme, Neu-Isenburg, Germany) and maintenance therapy using steroids, tacrolimus (Prograf; Astellas, Munich, Germany), and mycophenolate mofetil (CellCept; Roche, Grenzach-Wyhlen, Germany). For the statistical analyses, we used the chi-square and Fisher exact tests for categoric variables and the MannWhitney U test for continuous variables. Graft survival was calculated by using the Kaplan-Meier method with log-rank comparisons of differences in survival rates. A P value of ⬍.05 was considered to be significant. Analyses were performed using PASW Statistics 18 (SPSS, Chicago, IL, USA).
4203
RESULTS
The mean P-PASS of all pancreas donors was 16.4 ⫾ 2.5 (range, 12–22). We compared 24 patients receiving organs from “ideal donors” (P-PASS ⬍17; ID) with 25 patients with grafts from extended criteria donors (P-PASS ⱖ17; ED). The cold ischemia times for the pancreas graft were 10.3 ⫾ 2.5 hours from ideal donors and 10.9 ⫾ 3.9 hours for extended donors (P ⫽ .508). The overall incidence of relaparotomy was 17/52 (32.7%), including 7/24 (29.2%) in the ID and 10/25 (40.0%) in the ED group (P ⫽ .551). The most frequent reason for another operation was graft thrombosis in 1/24 ID (4.2%) and 4/25 ED (16%) patients (P ⫽ .249). The times to relaparotomy in the ID versus ED groups were 13.0 ⫾ 14.4 days versus 10.1 ⫾ 11.9 days, respectively (P ⫽ .655). A clinically relevant pancreatic fistula occurred in 9/24 (37.5%) versus 7/25 (28.0%) recipients (P ⫽ .543). There was no significant difference in the length of hospital stay between the groups (Table 1). Regarding IRI, as indicated by peak CRP, there was no significant difference between ID (14.1 ⫾ 5.5 mg/dL) and ED (16.2 ⫾ 6.0 mg/dL). The pancreas graft survivals at 1, 3, and 6 months were 87.5%, 79.2%, and 79.2%, respectively, for ID and 84%, 84%, and 84% for ED (Fig 1). DISCUSSION
Pancreas transplantation is the only treatment for type 1 diabetes mellitus that consistently establishes an insulinindependent normoglycemic state.17 The markedly improved results since the early 1990s have led to SPK being considered the procedure of choice for selected uremic diabetic patients with moderate end-organ complications.18 The combination of type 1 diabetes and dialysis leads to a tenfold increase in cardiovascular risk; the need for pretransplant dialysis significantly increases mortality among SPK recipients.19 –21 Therefore the best time for SPK is before the onset of dialysis, offering a survival benefit.22 However, only a small fraction of SPK cases are performed preemptively: 22% in the USA and 26% at our center.23 Because the number of patients awaiting pancreas transplantation is growing owing to the increased incidence of type 1 diabetes and because of the donor shortage the waiting time for a suitable graft is rising.24 To achieve the proven benefits of SPK for an increasing number of diabetic subjects, we must expand the pancreas donor pool by Table 1. Complications Following Pancreas Transplantation Comparing Grafts from Ideal Donors (ID) and Extended-Criteria Donors (ED)
Peak CRP (mg/dL) Pancreas graft loss Graft thrombosis Pancreatic fistula Relaparotomy Length of stay (d)
ID (n ⫽ 24)
ED (n ⫽ 25)
P Value
14.1 ⫾ 5.5 20.8% 1/24 (4.2%) 9/24 (37.5%) 7/24 (29.2%) 36.5 ⫾ 19.2
16.2 ⫾ 6.0 20.0% 4/25 (16%) 7/25 (28.0%) 10/25 (40.0%) 37.4 ⫾ 20.8
.211 1.0 .349 .543 .551 .875
4204
WOESTE, MOENCH, HAUSER ET AL
Therefore, there is a chance to expand the donor pool with extended criteria donors without increasing IRI and graft failure rates. Additional methods to reduce IRI are mandatory to decrease surgical complication and technical failure rates, especially when accepting extended-criteria donors.
REFERENCES
Fig 1. Pancreas graft survival in the first year after transplantation for grafts from ideal donors (P-PASS ⬍17, dash line) and extended-criteria donors (P-PASS ⱖ17, solid line).
accepting grafts from extended-criteria donors. However, several donor parameters have been shown to have negative impacts on graft survival.12,13,25,26 Vinkers et al created the P-PASS by analyzing the parameters of the donors accepted for pancreas transplantation.15 Using this score, those authors showed that pancreas grafts from donors with a P-PASS of ⱖ17 displayed a significantly greater rate of graft failure.27 Therefore, expanding the donor pool with organs from those donors may impair graft and patient survival. In contrast, the singlecenter experience of Schenker et al revealed a higher relaparotomy and pancreas graft failure rates within the first month that correlated with P-PASS; but there was no association with long-term patient or graft outcomes.28 The present study also failed to show a difference in graft survival; the higher incidence of relaparotomy and pancreas graft thrombosis among the ED group did not reach statistical significance. The degree of IRI may represent one key mechanism for the evolution of graft dysfunction and postoperative graft thrombosis by impairing the microcirculation.10 Although the peak CRP measured after transplantation has been shown to be a marker for IRI after pancreas transplantation, our experience did not show a significant difference between the 2 donor groups’ suggesting that IRI did not significantly correlate with the P-PASS.16 Additional factors may affect the IRI other than donor characteristics. In conclusion, the P-PASS may help a physician to decide whether a donor is an “ideal” or “extended-criteria” one, but it predicted neither IRI nor long-term graft survival.
1. Gruessner AC, Sutherland DE: Pancreas transplant outcomes for United States (US) cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR). Clin Transpl 45, 2008 2. Morath C, Schmied B, Mehrabi A, et al: Simultaneous pancreas-kidney transplantation in type 1 diabetes. Clin Transplant 23(suppl 21):115, 2009 3. Bechstein WO, Malaise J, Saudek F, et al: Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in primary simultaneous pancreas-kidney transplantation: 1-year results of a large multicenter trial. Transplantation 77:1221, 2004 4. Malaise J, De RA, Squifflet JP, et al: Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond. Acta Chir Belg 108:673, 2008 5. Stratta RJ, Lo A, Shokouh-Amiri MH, et al: Improving results in solitary pancreas transplantation with portal-enteric drainage, thymoglobin induction, and tacrolimus/mycophenolate mofetil-based immunosuppression. Transpl Int 16:154, 2003 6. Steurer W, Malaise J, Mark W, et al: Spectrum of surgical complications after simultaneous pancreas-kidney transplantation in a prospectively randomized study of two immunosuppressive protocols. Nephrol Dial Transplant 20(suppl 2):ii54, 2005 7. Troppmann C: Complications after pancreas transplantation. Curr Opin Organ Transplant 15:112, 2010 8. Benz S, Bergt S, Obermaier R, et al: Impairment of microcirculation in the early reperfusion period predicts the degree of graft pancreatitis in clinical pancreas transplantation. Transplantation 71:759, 2001 9. Schaser KD, Puhl G, Vollmar B, et al: In vivo imaging of human pancreatic microcirculation and pancreatic tissue injury in clinical pancreas transplantation. Am J Transplant 5:341, 2005 10. Fertmann JM, Wimmer CD, Arbogast HP, et al: Single-shot antithrombin in human pancreas-kidney transplantation: reduction of reperfusion pancreatitis and prevention of graft thrombosis. Transpl Int 19:458, 2006 11. Woeste G, Wullstein C, Meyer S, et al: Octreotide attenuates impaired microcirculation in postischemic pancreatitis when administered before induction of ischemia. Transplantation 86:961, 2008 12. Humar A, Ramcharan T, Kandaswamy R, et al: The impact of donor obesity on outcomes after cadaver pancreas transplants. Am J Transplant 4:605, 2004 13. Odorico JS, Heisey DM, Voss BJ, et al: Donor factors affecting outcome after pancreas transplantation. Transplant Proc 30:276, 1998 14. Wullstein C, Woeste G, De VE, et al: Acceptance criteria of pancreas grafts: how do surgeons decide in Europe? Transplant Proc 37:1259, 2005 15. Vinkers MT, Rahmel AO, Slot MC, et al: How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors. Transplant Proc 40:1275, 2008 16. Wullstein C, Drognitz O, Woeste G, et al: High levels of C-reactive protein after simultaneous pancreas-kidney transplantation predict pancreas graft–related complications and graft survival. Transplantation 77:60, 2004 17. Sutherland DE, Gruessner RW, Gruessner AC: Pancreas transplantation for treatment of diabetes mellitus. World J Surg 25:487, 2001
PANCREAS SUITABILITY SCORE AS PREDICTOR 18. Odorico JS, Sollinger HW: Technical and immunosuppressive advances in transplantation for insulin-dependent diabetes mellitus. World J Surg 26:194, 2002 19. Gruessner RW, Sutherland DE, Gruessner AC: Mortality assessment for pancreas transplants. Am J Transplant 4:2018, 2004 20. Tuomilehto J, Borch-Johnsen K, Molarius A, et al: Incidence of cardiovascular disease in type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland. Diabetologia 41:784, 1998 21. Varma R, Garrick R, McClung J, et al: Chronic renal dysfunction as an independent risk factor for the development of cardiovascular disease. Cardiol Rev 13:98, 2005 22. Pruijm MT, de Fijter HJ, Doxiadis II, et al: Preemptive versus non-preemptive simultaneous pancreas-kidney transplantation: a single-center, long-term, follow-up study. Transplantation 81:1119, 2006
4205 23. Gruessner AC, Sutherland DE, Gruessner RW: Pancreas transplantation in the United States: a review. Curr Opin Organ Transplant 15:93, 2010 24. Passa P: Diabetes trends in Europe. Diabetes Metab Res Rev 18(suppl 3):S3, 2002 25. Kapur S, Bonham CA, Dodson SF, et al: Strategies to expand the donor pool for pancreas transplantation. Transplantation 67:284, 1999 26. Krieger NR, Odorico JS, Heisey DM, et al: Underutilization of pancreas donors. Transplantation 75:1271, 2003 27. Vinkers MT, Rahmel AO, Slot MC, et al: Influence of a donor quality score on pancreas transplant survival in the Eurotransplant area. Transplant Proc 40:3606, 2008 28. Schenker P, Vonend O, Ertas N, et al: Preprocurement pancreas allocation suitability score does not correlate with longterm pancreas graft survival. Transplant Proc 42:178, 2010
S
From the Department of General and Visceral Surgery, Goethe-University, Frankfurt, Germany; and Department of Nephrology, Goethe-University, Frankfurt, Germany. Address correspondence to Guido Woeste, MD, Department of Surgery, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. E-mail: guido.woeste@ kgu.de
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.09.021
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
4202
Transplantation Proceedings, 42, 4202– 4205 (2010)
PANCREAS SUITABILITY SCORE AS PREDICTOR
caused by ischemia followed by reperfusion (IRI),8,9 which have been addressed with various treatments.10,11 However, little is known about the impact of IRI on the occurrence of graft pancreatitis. The problem of organ shortage and increasing waiting time may be alleviated with less than ideal donors. Careful donor selection can reduce posttransplantation morbidity.12–14 The Eurotransplant Pancreas Advisory Committee retrospectively validated a donor quality score to recognize a suitable pancreas donor, the preprocurement pancreas suitability score (P-PASS).15 We analyzed the P-PASS in relation to the incidence of early postoperative complications and evidence of IRI among all pancreas transplantations performed at our center. METHODS
Using the following nine parameters available at the time of donor reporting, the Eurotransplant Pancreas Advisory Committee defined the P-PASS: age, body mass index, intensive care unit stay, cardiac arrest, serum sodium, serum amylase and lipase, and (nor)adrenaline and dobutamine dopamine use. An organ donor with a P-PASS of ⬍17 was suggested to represent an “ideal donor,” who is threefold more likely to be accepted by transplant surgeons in Eurotransplant.15 All 52 pancreas transplantations performed at our institution between January 2004 and July 2010 were evaluated for this retrospective study: 50 SPK, 1 pancreas after kidney transplantation, and 1 pancreas transplantation alone. We reviewed the medical records for donor characteristics and postoperative courses with special attention to IRI and complications regard the pancreas graft. Complete data to calculate the P-PASS was available for 49 patients (94.2%), including 20 women and 29 men. The overall mean age was 42.4 ⫾ 7.5 years, mean duration of diabetes 27.0 ⫾ 8.2 years, and mean duration of dialysis 25.1 ⫾ 29.2 months, with 13 patients transplanted preemptively before the need for dialysis. As described previously, the peak CRP over the first 3 postoperative days was used as a marker for IRI.16 We analyzed our findings according to the P-PASS. All pancreas transplantations were performed using systemic venous and enteric drainage. The immunosuppressive protocol consisted of antibody induction with antithymocyte globulin (Thymoglobulin; Genzyme, Neu-Isenburg, Germany) and maintenance therapy using steroids, tacrolimus (Prograf; Astellas, Munich, Germany), and mycophenolate mofetil (CellCept; Roche, Grenzach-Wyhlen, Germany). For the statistical analyses, we used the chi-square and Fisher exact tests for categoric variables and the MannWhitney U test for continuous variables. Graft survival was calculated by using the Kaplan-Meier method with log-rank comparisons of differences in survival rates. A P value of ⬍.05 was considered to be significant. Analyses were performed using PASW Statistics 18 (SPSS, Chicago, IL, USA).
4203
RESULTS
The mean P-PASS of all pancreas donors was 16.4 ⫾ 2.5 (range, 12–22). We compared 24 patients receiving organs from “ideal donors” (P-PASS ⬍17; ID) with 25 patients with grafts from extended criteria donors (P-PASS ⱖ17; ED). The cold ischemia times for the pancreas graft were 10.3 ⫾ 2.5 hours from ideal donors and 10.9 ⫾ 3.9 hours for extended donors (P ⫽ .508). The overall incidence of relaparotomy was 17/52 (32.7%), including 7/24 (29.2%) in the ID and 10/25 (40.0%) in the ED group (P ⫽ .551). The most frequent reason for another operation was graft thrombosis in 1/24 ID (4.2%) and 4/25 ED (16%) patients (P ⫽ .249). The times to relaparotomy in the ID versus ED groups were 13.0 ⫾ 14.4 days versus 10.1 ⫾ 11.9 days, respectively (P ⫽ .655). A clinically relevant pancreatic fistula occurred in 9/24 (37.5%) versus 7/25 (28.0%) recipients (P ⫽ .543). There was no significant difference in the length of hospital stay between the groups (Table 1). Regarding IRI, as indicated by peak CRP, there was no significant difference between ID (14.1 ⫾ 5.5 mg/dL) and ED (16.2 ⫾ 6.0 mg/dL). The pancreas graft survivals at 1, 3, and 6 months were 87.5%, 79.2%, and 79.2%, respectively, for ID and 84%, 84%, and 84% for ED (Fig 1). DISCUSSION
Pancreas transplantation is the only treatment for type 1 diabetes mellitus that consistently establishes an insulinindependent normoglycemic state.17 The markedly improved results since the early 1990s have led to SPK being considered the procedure of choice for selected uremic diabetic patients with moderate end-organ complications.18 The combination of type 1 diabetes and dialysis leads to a tenfold increase in cardiovascular risk; the need for pretransplant dialysis significantly increases mortality among SPK recipients.19 –21 Therefore the best time for SPK is before the onset of dialysis, offering a survival benefit.22 However, only a small fraction of SPK cases are performed preemptively: 22% in the USA and 26% at our center.23 Because the number of patients awaiting pancreas transplantation is growing owing to the increased incidence of type 1 diabetes and because of the donor shortage the waiting time for a suitable graft is rising.24 To achieve the proven benefits of SPK for an increasing number of diabetic subjects, we must expand the pancreas donor pool by Table 1. Complications Following Pancreas Transplantation Comparing Grafts from Ideal Donors (ID) and Extended-Criteria Donors (ED)
Peak CRP (mg/dL) Pancreas graft loss Graft thrombosis Pancreatic fistula Relaparotomy Length of stay (d)
ID (n ⫽ 24)
ED (n ⫽ 25)
P Value
14.1 ⫾ 5.5 20.8% 1/24 (4.2%) 9/24 (37.5%) 7/24 (29.2%) 36.5 ⫾ 19.2
16.2 ⫾ 6.0 20.0% 4/25 (16%) 7/25 (28.0%) 10/25 (40.0%) 37.4 ⫾ 20.8
.211 1.0 .349 .543 .551 .875
4204
WOESTE, MOENCH, HAUSER ET AL
Therefore, there is a chance to expand the donor pool with extended criteria donors without increasing IRI and graft failure rates. Additional methods to reduce IRI are mandatory to decrease surgical complication and technical failure rates, especially when accepting extended-criteria donors.
REFERENCES
Fig 1. Pancreas graft survival in the first year after transplantation for grafts from ideal donors (P-PASS ⬍17, dash line) and extended-criteria donors (P-PASS ⱖ17, solid line).
accepting grafts from extended-criteria donors. However, several donor parameters have been shown to have negative impacts on graft survival.12,13,25,26 Vinkers et al created the P-PASS by analyzing the parameters of the donors accepted for pancreas transplantation.15 Using this score, those authors showed that pancreas grafts from donors with a P-PASS of ⱖ17 displayed a significantly greater rate of graft failure.27 Therefore, expanding the donor pool with organs from those donors may impair graft and patient survival. In contrast, the singlecenter experience of Schenker et al revealed a higher relaparotomy and pancreas graft failure rates within the first month that correlated with P-PASS; but there was no association with long-term patient or graft outcomes.28 The present study also failed to show a difference in graft survival; the higher incidence of relaparotomy and pancreas graft thrombosis among the ED group did not reach statistical significance. The degree of IRI may represent one key mechanism for the evolution of graft dysfunction and postoperative graft thrombosis by impairing the microcirculation.10 Although the peak CRP measured after transplantation has been shown to be a marker for IRI after pancreas transplantation, our experience did not show a significant difference between the 2 donor groups’ suggesting that IRI did not significantly correlate with the P-PASS.16 Additional factors may affect the IRI other than donor characteristics. In conclusion, the P-PASS may help a physician to decide whether a donor is an “ideal” or “extended-criteria” one, but it predicted neither IRI nor long-term graft survival.
1. Gruessner AC, Sutherland DE: Pancreas transplant outcomes for United States (US) cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR). Clin Transpl 45, 2008 2. Morath C, Schmied B, Mehrabi A, et al: Simultaneous pancreas-kidney transplantation in type 1 diabetes. Clin Transplant 23(suppl 21):115, 2009 3. Bechstein WO, Malaise J, Saudek F, et al: Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in primary simultaneous pancreas-kidney transplantation: 1-year results of a large multicenter trial. Transplantation 77:1221, 2004 4. Malaise J, De RA, Squifflet JP, et al: Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond. Acta Chir Belg 108:673, 2008 5. Stratta RJ, Lo A, Shokouh-Amiri MH, et al: Improving results in solitary pancreas transplantation with portal-enteric drainage, thymoglobin induction, and tacrolimus/mycophenolate mofetil-based immunosuppression. Transpl Int 16:154, 2003 6. Steurer W, Malaise J, Mark W, et al: Spectrum of surgical complications after simultaneous pancreas-kidney transplantation in a prospectively randomized study of two immunosuppressive protocols. Nephrol Dial Transplant 20(suppl 2):ii54, 2005 7. Troppmann C: Complications after pancreas transplantation. Curr Opin Organ Transplant 15:112, 2010 8. Benz S, Bergt S, Obermaier R, et al: Impairment of microcirculation in the early reperfusion period predicts the degree of graft pancreatitis in clinical pancreas transplantation. Transplantation 71:759, 2001 9. Schaser KD, Puhl G, Vollmar B, et al: In vivo imaging of human pancreatic microcirculation and pancreatic tissue injury in clinical pancreas transplantation. Am J Transplant 5:341, 2005 10. Fertmann JM, Wimmer CD, Arbogast HP, et al: Single-shot antithrombin in human pancreas-kidney transplantation: reduction of reperfusion pancreatitis and prevention of graft thrombosis. Transpl Int 19:458, 2006 11. Woeste G, Wullstein C, Meyer S, et al: Octreotide attenuates impaired microcirculation in postischemic pancreatitis when administered before induction of ischemia. Transplantation 86:961, 2008 12. Humar A, Ramcharan T, Kandaswamy R, et al: The impact of donor obesity on outcomes after cadaver pancreas transplants. Am J Transplant 4:605, 2004 13. Odorico JS, Heisey DM, Voss BJ, et al: Donor factors affecting outcome after pancreas transplantation. Transplant Proc 30:276, 1998 14. Wullstein C, Woeste G, De VE, et al: Acceptance criteria of pancreas grafts: how do surgeons decide in Europe? Transplant Proc 37:1259, 2005 15. Vinkers MT, Rahmel AO, Slot MC, et al: How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors. Transplant Proc 40:1275, 2008 16. Wullstein C, Drognitz O, Woeste G, et al: High levels of C-reactive protein after simultaneous pancreas-kidney transplantation predict pancreas graft–related complications and graft survival. Transplantation 77:60, 2004 17. Sutherland DE, Gruessner RW, Gruessner AC: Pancreas transplantation for treatment of diabetes mellitus. World J Surg 25:487, 2001
PANCREAS SUITABILITY SCORE AS PREDICTOR 18. Odorico JS, Sollinger HW: Technical and immunosuppressive advances in transplantation for insulin-dependent diabetes mellitus. World J Surg 26:194, 2002 19. Gruessner RW, Sutherland DE, Gruessner AC: Mortality assessment for pancreas transplants. Am J Transplant 4:2018, 2004 20. Tuomilehto J, Borch-Johnsen K, Molarius A, et al: Incidence of cardiovascular disease in type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland. Diabetologia 41:784, 1998 21. Varma R, Garrick R, McClung J, et al: Chronic renal dysfunction as an independent risk factor for the development of cardiovascular disease. Cardiol Rev 13:98, 2005 22. Pruijm MT, de Fijter HJ, Doxiadis II, et al: Preemptive versus non-preemptive simultaneous pancreas-kidney transplantation: a single-center, long-term, follow-up study. Transplantation 81:1119, 2006
4205 23. Gruessner AC, Sutherland DE, Gruessner RW: Pancreas transplantation in the United States: a review. Curr Opin Organ Transplant 15:93, 2010 24. Passa P: Diabetes trends in Europe. Diabetes Metab Res Rev 18(suppl 3):S3, 2002 25. Kapur S, Bonham CA, Dodson SF, et al: Strategies to expand the donor pool for pancreas transplantation. Transplantation 67:284, 1999 26. Krieger NR, Odorico JS, Heisey DM, et al: Underutilization of pancreas donors. Transplantation 75:1271, 2003 27. Vinkers MT, Rahmel AO, Slot MC, et al: Influence of a donor quality score on pancreas transplant survival in the Eurotransplant area. Transplant Proc 40:3606, 2008 28. Schenker P, Vonend O, Ertas N, et al: Preprocurement pancreas allocation suitability score does not correlate with longterm pancreas graft survival. Transplant Proc 42:178, 2010