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The Role of Pancreas Transplantation in the Long Term Management of Diabetes

The Role of Pancreas Transplantation in the Long Term Management of Diabetes. Christopher Johnson MD Professor of Surgery Division of Transplant Surgery Medical College of Wisconsin. Learning objectives:.

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The Role of Pancreas Transplantation in the Long Term Management of Diabetes

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  1. The Role of Pancreas Transplantation in the Long Term Management of Diabetes Christopher Johnson MD Professor of Surgery Division of Transplant Surgery Medical College of Wisconsin

  2. Learning objectives: 1. This talk will increase your understanding about the rationale (including risk/benefit assessment) for pancreas transplantation in the management of diabetes. 2. This talk will allow you to better appreciate some of technical and immunological challenges associated with pancreas transplantation 3. This talk will help you to better anticipate therapy options for diabetic patients who have chronic kidney disease.

  3. no disclosures

  4. Tight control reduces end organ damage but increases the risk (2-3 fold) of severe hypoglycemic episodes (1). 1DCCT. The Diabetes Control and Complications Trial Research Group The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. N Engl J Med 1993; 329: 977–986.

  5. Retinopathy Neuropathy DCCT trial (1441 patients randomized to intensive insulin vs. conventional insulin) designed to examine the effect of tight control on 2° complications (followed > 6yrs) Prevalence of neuropathy Incidence progression

  6. A successful pancreas transplant completely normalizes blood sugar control However, it requires life long immunosuppression

  7. Types of pancreas transplants: • Kidney/Pancreas (pts undergoing kidney transplantation) • Pancreas after kidney (already on IS) • Pancreas transplant alone (severe life-threatening complications of DM) • Islet after kidney (no surgical procedure) • Islet transplant (no surgical procedure but requires IS)

  8. Combined kidney/pancreas transplant is the most common scenario for pancreas transplantation:

  9. Indications for Simultaneous Kidney and Pancreas Transplant: • Presence of ESRD (or eGFR < 20 ml/min) • Presence of diabetes: type 1 or 2 (meeting age (< 55) and BMI criteria (<30) • Lack of major complications and/or severe cardiovascular disease which limits life expectancy

  10. Figure 13: Unadjusted 1-year, 3-year, 5-year and 10-year pancreas graft survival by transplant type

  11. Reversal of Lesions of Diabetic Nephropathy after Pancreas Transplantation Fioretto, Paola; Steffes, Michael W.; Sutherland, David E.R.; Goetz, Frederick C.; Mauer, Michael. NEJM 339:69-75 July 9, 1998 Number 2

  12. Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure Survival estimates for patients with kidney graft function at 1 year. Abbreviations: LD, living donor; CAD, cadaveric. Am J Kid Disease 41:464-470. 2003

  13. Figure 2: Waiting list death rates by diagnosis, 1999–2008.

  14. Diabetics who receive k/p gain more life-years than k-alone or non-diabetics:

  15. k/p transplants are equally successful for type 1 and type 2 diabetes: data from SRTR 2010

  16. What is the role of pancreas transplant in type 2 diabetes? • Diabetes affects 10% of the population • 90-95% is type 2 • Distinction between type 1 and 2 not always clear cut C –peptide is not accurate in renal failure c

  17. suggested criteria:

  18. Organ Procurement: Simultaneous Liver and Pancreas Removal

  19. Back table dissection:

  20. More back table dissection…

  21. Back table Reconstruction of Pancreatic Allograft

  22. Arterial “Y” Graft of Donor Iliac Artery Portal Vein Mobilization

  23. Bladder Drainage with Systemic Venous Anastomosis Enteric Drainage with Portal Venous Anastomosis

  24. Trends in maintenance immunosuppression therapy prior to discharge for simultaneous kidney-pancreas transplantation 1994-2003 American Journal of Transplantation 2005;5(Part 2):874-886

  25. Incidence of rejection during first year among simultaneous kidney-pancreas recipients American Journal of Transplantation 2005;5(Part 2):874-886

  26. ADVANCES IN PANCREAS TRANSPLANTATION. Transplantation. 77(9) Supplement:S62-S67, May 15, 2004. Burke G, Ciancio G, Sollinger H

  27. Surgical Aspects of Pancreas Transplantation: • Post-Transplant Complications • Early post-operative complications (Bleeding, infection) • Venous Thrombosis • Reperfusion pancreatitis • Pancreas is a relatively low-flow organ • Unrecognized inherited hypercoagulable state • in the recipient • Transplant Pancreatitis • Mild - transient amylase elevation for 48-96h • Severe – fat necrosis, infected peripancreatic fluid • Kidney (urine leak, ureteral stricture)

  28. Radiologic tools for transplant evaluation:

  29. Splenic vein thrombosis:

  30. Fluid collection on CT:

  31. Diagnosis of Pancreatic Allograft Rejection (is difficult) Drachenberg CB, Papadimitriou JC, Klassen DK, et.al: Evaluation of pancreas transplant needle biopsy. Reproducibility and revision of histologic grading system. Transplantation 1997;63(11):1579-1586. Drachenberg C, Klassen D, Bartlett S, Hoehn-Saric E, Schweitzer E, Johnson L, Weir J and Papadimitriou J: Histologic grading of pancreas acute allograft rejection in percutaneous needle biopsies. Transplant Proc 1996;28(1):512-513

  32. PAK and PTA have higher rate of immunologic graft loss after 1 year

  33. Indications for isolated pancreas transplant (PAK or PTA): • Frequent and/or severe hypoglycemic events • consistent failure of insulin-based management to prevent acute and chronic complications (poor control). • clinical and/or emotional problems associated with the use of exogenous insulin therapy that are so severe as to be incapacitating

  34. Isolated Pancreas Transplant: Recipient • Selection Criteria • IDDM, age > 18 years with an upper age limit of ? • Ability to withstand surgery and immunosuppression • Psychosocial stability/ social support/ compliance/ • commitment to long-term follow-up • Diabetic secondary complications • Hyper-lability/ Hypoglycemic Unawareness • Financial resources (USA) • Absence of any exclusionary criteria: • - renal function • - coronary disease

  35. Mortality risk/benefit of PAK and PTA: Mortality after transplant: Mortality on waiting list: SPK spk American Journal of Transplantation 2004; 4: 2018–2026

  36. Islet Isolation 1. Organ Procurement 2. Distension with Collagenase 3. Digestion & Mechanical Separation 4. Purification of Islets 5. Quantification

  37. The “Edmonton Protocol” Efficient Isolation Procedure Reliable Collagenase Steroid Free Immunosuppressive Protocol IL-2R Blockade Tacrolimus Sirolimus

  38. Only 31% remained insulin independent at 2 years N Engl J Med 2006;355:1318-30.

  39. Failed islet transplants are associated with sensitization to HLA antigens:

  40. Whole Pancreas Transplantation Pancreatic Islet Cell Transplantation + +

  41. Successful islet transplants decrease progression of nephropathy and retinopathy Preservation of renal function Decreased progression of retinopathy

  42. Conclusions: • Pancreas transplants when successful, normalize glucose metabolism and increase quality (and quantity) of life. • “Good risk” diabetics (type 1 or 2) with renal failure should receive either a living donor kidney transplant or a combined kidney/pancreas transplant

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