Extended pancreas donor program -the EXPAND study rationale and study protocol

详细信息    查看全文

• 作者：Andrea Proneth (1)
  Andreas A Schnitzbauer (1) (2)
  Florian Zeman (3)
  Johanna R Foerster (1)
  Ines Holub (1)
  Helmut Arbogast (4)
  Wolf O Bechstein (2)
  Thomas Becker (5)
  Carsten Dietz (6)
  Markus Guba (4)
  Michael Heise (7)
  Sven Jonas (8)
  Stephan Kersting (9)
  Jürgen Klempnauer (10)
  Steffen Manekeller (11)
  Volker Müller (12)
  Silvio Nadalin (13)
  Bj?rn Nashan (14)
  Andreas Pascher (15)
  Falk Rauchfuss (16)
  Michael A Str?hlein (17)
  Peter Schemmer (18)
  Peter Schenker (19)
  Stefan Thorban (20)
  Thomas Vogel (21)
  Axel O Rahmel (22)
  Richard Viebahn (19)
  Bernhard Banas (23)
  Edward K Geissler (1)
  Hans J Schlitt (1)
  Stefan A Farkas (1)
  
• 关键词：Pancreas transplantation ; Organ allocation ; Extended donor criteria ; Rejection
• 刊名：Transplantation Research
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：2
• 期：1
• 全文大小：399KB
• 参考文献：1. Sollinger HW, Odorico JS, Becker YT, D'Alessandro AM, Pirsch JD: One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. / Ann Surg 2009, 250:618-30.
  2. White SA, Shaw JA, Sutherland DE: Pancreas transplantation. / Lancet 2009, 373:1808-817. CrossRef
  3. Becker BN, Brazy PC, Becker YT, Odorico JS, Pintar TJ, Collins BH, Pirsch JD, Leverson GE, Heisey DM, Sollinger HW: Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease. / Kidney Int 2000, 57:2129-135. CrossRef
  4. Ojo AO, Meier-Kriesche HU, Hanson JA, Leichtman A, Magee JC, Cibrik D, Wolfe RA, Port FK, Agodoa L, Kaufman DB, Kaplan B: The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. / Transplantation 2001, 71:82-0. CrossRef
  5. Tyden G, Bolinder J, Solders G, Brattstrom C, Tibell A, Groth CG: Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation. / Transplantation 1999, 67:645-48. CrossRef
  6. Ojo AO, Meier-Kriesche HU, Arndorfer JA, Leichtman AB, Magee JC, Cibrik DM, Wolfe RA, Port FK, Agodoa L, Kaufman DB, Kaplan B: Long-term benefit of kidney-pancreas transplants in type 1 diabetics. / Transplant Proc 2001, 33:1670-672. CrossRef
  7. Biesenbach G, Konigsrainer A, Gross C, Margreiter R: Progression of macrovascular diseases is reduced in type 1 diabetic patients after more than 5 years successful combined pancreas-kidney transplantation in comparison to kidney transplantation alone. / Transpl Int 2005, 18:1054-060. CrossRef
  8. Giannarelli R, Coppelli A, Sartini M, Aragona M, Boggi U, Vistoli F, Rizzo G, Del Prato S, Mosca F, Marchetti P: Effects of pancreas-kidney transplantation on diabetic retinopathy. / Transpl Int 2005, 18:619-22. CrossRef
  9. Koznarova R, Saudek F, Sosna T, Adamec M, Jedinakova T, Boucek P, Bartos V, Lanska V: Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. / Cell Transplant 2000, 9:903-08.
  10. Kennedy WR, Navarro X, Goetz FC, Sutherland DE, Najarian JS: Effects of pancreatic transplantation on diabetic neuropathy. / N Engl J Med 1990, 322:1031-037. CrossRef
  11. Loss M, Drewitz KP, Apfelbacher CJ, van Rosmalen MD, Rahmel A, Schlitt HJ, Loss J: Why offered pancreases are refused in the allocation process-a descriptive study using routine data from eurotransplant. / Transplantation 2013, 95:1134-141. CrossRef
  12. Vinkers MT, Rahmel AO, Slot MC, Smits JM, Schareck WD: How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors. / Transplant Proc 2008, 40:1275-278. CrossRef
  13. Burke GW 3rd, Kaufman DB, Millis JM, Gaber AO, Johnson CP, Sutherland DE, Punch JD, Kahan BD, Schweitzer E, Langnas A, Perkins J, Scandling J, Concepcion W, Stegall MD, Schulak JA, Gores PF, Benedetti E, Danovitch G, Henning AK, Bartucci MR, Smith S, Fitzsimmons WE: Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results. / Transplantation 2004, 77:1269-275. CrossRef
  14. Mineo D, Sageshima J, Burke GW, Ricordi C: Minimization and withdrawal of steroids in pancreas and islet transplantation. / Transpl Int 2009, 22:20-7. CrossRef
  15. Boggi U, Mosca F, Vistoli F, Signori S, Del Chiaro M, Bartolo TV, Amorese G, Coppelli A, Marchetti P, Mariotti R, Rondini L, Del Prato S, Rizzo G: Ninety-five percent insulin independence rate 3 years after pancreas transplantation alone with portal-enteric drainage. / Transplant Proc 2005, 37:1274-277. CrossRef
  16. Krieger NR, Odorico JS, Heisey DM, D'Alessandro AM, Knechtle SJ, Pirsch JD, Sollinger HW: Underutilization of pancreas donors. / Transplantation 2003, 75:1271-276. CrossRef
  17. Gruessner RW, Sutherland DE, Gruessner AC: Mortality assessment for pancreas transplants. / Am J Transplant 2004, 4:2018-026. CrossRef
  18. Nakamura T, Onozato W, Mitomi H, Naito M, Sato T, Ozawa H, Hatate K, Ihara A, Watanabe M: Retrospective, matched case–control study comparing the oncologic outcomes between laparoscopic surgery and open surgery in patients with right-sided colon cancer. / Surg Today 2009, 39:1040-045. CrossRef
  19. Bodingbauer M, Pakrah B, Steininger R, Berlakovich G, Rockenschaub S, Wekerle T, Muehlbacher F: The advantage of allocating kidneys from old cadaveric donors to old recipients: a single-center experience. / Clin Transplant 2006, 20:471-75. CrossRef
  20. Cohen B, Smits JM, Haase B, Persijn G, Vanrenterghem Y, Frei U: Expanding the donor pool to increase renal transplantation. / Nephrol Dial Transplant 2005, 20:34-1. CrossRef
  21. Watson CJ, Rudge C: Current practices of donor pancreas allocation in the UK: future implications for pancreas and islet transplantation. / Transpl Int 2005, 18:1388. author reply 1389 CrossRef
  22. Ridgway D, Manas D, Shaw J, White S: Preservation of the donor pancreas for whole pancreas and islet transplantation. / Clin Transplant 2010, 24:1-9. CrossRef
  23. Ridgway DM, White SA, Kimber RM, Nicholson ML: Current practices of donor pancreas allocation in the UK: future implications for pancreas and islet transplantation. / Transpl Int 2005, 18:828-34. CrossRef
  24. Muthusamy AS, Vaidya AC, Sinha S, Roy D, Elker DE, Friend PJ: Alemtuzumab induction and steroid-free maintenance immunosuppression in pancreas transplantation. / Am J Transplant 2008, 8:2126-131. CrossRef
  25. Salvalaggio PR, Schnitzler MA, Abbott KC, Brennan DC, Irish W, Takemoto SK, Axelrod D, Santos LS, Kocak B, Willoughby L, Lentine KL: Patient and graft survival implications of simultaneous pancreas kidney transplantation from old donors. / Am J Transplant 2007, 7:1561-571. CrossRef
  26. Andreoni KA, Brayman KL, Guidinger MK, Sommers CM, Sung RS: Kidney and pancreas transplantation in the United States, 1996-005. / Am J Transplant 2007, 7:1359-375. CrossRef
  27. Desschans B, Van Gelder F, Van Hees D, de Rocy J, Monbaliu D, Aerts R, Coosemans W, Pirenne J: Evolution in allocation rules for renal, hepatic, pancreatic and intestinal grafts. / Acta Chir Belg 2008, 108:31-4.
  28. Fernandez LA, Di Carlo A, Odorico JS, Leverson GE, Shames BD, Becker YT, Chin LT, Pirsch JD, Knechtle SJ, Foley DP, Sollinger HW, D'Alessandro AM: Simultaneous pancreas-kidney transplantation from donation after cardiac death: successful long-term outcomes. / Ann Surg 2005, 242:716-23. CrossRef
  29. Neidlinger NA, Odorico JS, Sollinger HW, Fernandez LA: Can 'extreme' pancreas donors expand the donor pool? / Curr Opin Organ Transplant 2008, 13:67-1. CrossRef
  30. Singh RP, Rogers J, Farney AC, Moore PS, Hartmann EL, Reeves-Daniel A, Adams PL, Gautreaux M, Stratta RJ: Outcomes of extended donors in pancreatic transplantation with portal-enteric drainage. / Transplant Proc 2008, 40:502-05. CrossRef
  31. Barth RN, Janus CA, Lillesand CA, Radke NA, Pirsch JD, Becker BN, Fernandez LA, Thomas Chin L, Becker YT, Odorico JS, D'Alessandro AM, Sollinger HW, Knechtle SJ: Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. / Transpl Int 2006, 19:885-92. CrossRef
  32. Boggi U, Vistoli F, Signori S, Del Chiaro M, Amorese G, Vanadia Bartolo T, Croce C, Sgambelluri F, Marchetti P, Mosca F: Outcome of 118 pancreas transplants with retroperitoneal portal-enteric drainage. / Transplant Proc 2005, 37:2648-650. CrossRef
  33. Schadde E, D'Alessandro AM, Knechtle SJ, Odorico J, Becker Y, Pirsch J, Sollinger H, Fernandez LA: Alemtuzumab induction and triple maintenance immunotherapy in kidney transplantation from donors after cardiac death. / Transpl Int 2008, 21:625-36. CrossRef
  34. Gruessner AC, Sutherland DE: Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. / Clin Transplant 2005, 19:433-55. CrossRef
  35. Schenker P, Vonend O, Ertas N, Wunsch A, Viebahn R: Preprocurement pancreas allocation suitability score does not correlate with long-term pancreas graft survival. / Transplant Proc 2010, 42:178-80. CrossRef
  36. Gruessner AC, Sutherland DE: Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. / Clin Transpl 2005, 4:433-55. CrossRef
  37. Stegall MD, Dean PG, Sung R, Guidinger MK, McBride MA, Sommers C, Basadonna G, Stock PG, Leichtman AB: The rationale for the new deceased donor pancreas allocation schema. / Transplantation 2007, 83:1156-161. CrossRef
  
• 作者单位：Andrea Proneth (1)
  Andreas A Schnitzbauer (1) (2)
  Florian Zeman (3)
  Johanna R Foerster (1)
  Ines Holub (1)
  Helmut Arbogast (4)
  Wolf O Bechstein (2)
  Thomas Becker (5)
  Carsten Dietz (6)
  Markus Guba (4)
  Michael Heise (7)
  Sven Jonas (8)
  Stephan Kersting (9)
  Jürgen Klempnauer (10)
  Steffen Manekeller (11)
  Volker Müller (12)
  Silvio Nadalin (13)
  Bj?rn Nashan (14)
  Andreas Pascher (15)
  Falk Rauchfuss (16)
  Michael A Str?hlein (17)
  Peter Schemmer (18)
  Peter Schenker (19)
  Stefan Thorban (20)
  Thomas Vogel (21)
  Axel O Rahmel (22)
  Richard Viebahn (19)
  Bernhard Banas (23)
  Edward K Geissler (1)
  Hans J Schlitt (1)
  Stefan A Farkas (1)
  
  1. Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
  2. Department of General and Visceral Surgery, Goethe-University Hospital and Clinics, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
  3. Centre for Clinical Studies, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
  4. Department of Surgery, Ludwig Maximilian’s University, University Hospital Grosshadern, Marchioninistrasse 15, 81377, Munich, Germany
  5. Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Arnold-Heller-Strasse 3, 24105, Kiel, Germany
  6. Department of Visceral, Thoracic and Vascular Surgery, University Hospital Marburg, Baldingerstrasse, 35043, Marburg, Germany
  7. Department of General ,Visceral and Transplantation Surgery, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
  8. Department of Visceral ,Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany
  9. Department of General, Thoracic and Vascular Surgery, University of Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
  10. Visceral and Transplantation Surgery, Hannover Medical School, General, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
  11. Department of Surgery, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany
  12. Department of Surgery, University Hospital Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany
  13. Department of General ,Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany
  14. Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
  15. Department of General, Visceral and Transplantation Surgery, Charité-University Medicine Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
  16. Department of General ,Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07747, Jena, Germany
  17. Cologne-Merheim Medical Center, Department of Abdominal, Vascular, and Transplant Surgery, Witten/Herdecke University, Ostmerheimer Strasse 200, 51109, Cologne, Germany
  18. Clinic for General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
  19. Department of Surgery, Knappschafts-Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892, Bochum, Germany
  20. Klinikum Rechts der Isar, Department of Surgery, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany
  21. Department of General Surgery, University Hospital of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany
  22. Eurotransplant International Foundation, 2301CH, Leiden, The Netherlands
  23. Department of Internal Medicine II, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
  

文摘

Background Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients. Methods/Design This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation. Discussion The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future. Trial registration Trial registered at: NCT01384006