the role of pancreas transplantation in the long term management of diabetes christopher johnson md...
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The Role of Pancreas The Role of Pancreas Transplantation in the Long Transplantation in the Long
Term Management of Term Management of DiabetesDiabetes
Christopher Johnson MDChristopher Johnson MDProfessor of SurgeryProfessor of Surgery
Division of Transplant SurgeryDivision of Transplant SurgeryMedical College of WisconsinMedical College of Wisconsin
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Learning objectives:Learning objectives:
1. 1. This talk will increase your understanding about This talk will increase your understanding about the rationale (including risk/benefit assessment) the rationale (including risk/benefit assessment) for pancreas transplantation in the for pancreas transplantation in the management of diabetes.management of diabetes.
2. This talk will allow you to better appreciate 2. This talk will allow you to better appreciate some of technical and immunological some of technical and immunological challenges associated with pancreas challenges associated with pancreas transplantation transplantation
3. This talk will help you to better anticipate 3. This talk will help you to better anticipate therapy options for diabetic patients who have therapy options for diabetic patients who have chronic kidney disease.chronic kidney disease.
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no disclosuresno disclosures
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Tight control reduces end organ damage but Tight control reduces end organ damage but increases the risk (2-3 fold) of severe increases the risk (2-3 fold) of severe hypoglycemic episodes (1).hypoglycemic episodes (1).
1 DCCT. The Diabetes Control and Complications DCCT. The Diabetes Control and Complications Trial Research Group The Effect of Intensive Trial Research Group The Effect of Intensive Treatment of Diabetes on the Development Treatment of Diabetes on the Development and Progression of Long-Term Complications in and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. Insulin-Dependent Diabetes Mellitus. N Engl J N Engl J MedMed 1993; 1993; 329329: 977–986. : 977–986.
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DCCT trial (1441 patients randomized to DCCT trial (1441 patients randomized to intensive insulin vs. conventional insulin) intensive insulin vs. conventional insulin) designed to examine the effect of tight designed to examine the effect of tight
control on 2control on 2°° complications (followed > 6yrs) complications (followed > 6yrs)
RetinopathyRetinopathy NeuropathyNeuropathy
Incidence progression Prevalence of neuropathy
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A successful pancreas transplant A successful pancreas transplant completely normalizes blood completely normalizes blood
sugar controlsugar control
However, it requires life long immunosuppression
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Types of pancreas Types of pancreas transplants: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)
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Combined kidney/pancreas Combined kidney/pancreas transplant is the most common transplant is the most common
scenario for pancreas scenario for pancreas transplantation:transplantation:
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Indications for Simultaneous Indications for Simultaneous Kidney and Pancreas Kidney and Pancreas
Transplant:Transplant: Presence of ESRD (or eGFR < 20 Presence of ESRD (or eGFR < 20
ml/min)ml/min) Presence of diabetes: type 1 or 2 Presence of diabetes: type 1 or 2
(meeting age (< 55) and BMI criteria (meeting age (< 55) and BMI criteria (<30)(<30)
Lack of major complications and/or Lack of major complications and/or severe cardiovascular disease which severe cardiovascular disease which limits life expectancylimits life expectancy
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Figure 13: Unadjusted 1-year, 3-year, 5-year and 10-year pancreas graft survival by transplant type
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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
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Survival estimates for patients with kidney graft function at 1 year. Abbreviations: LD, living donor; CAD, cadaveric.
Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure
Am J Kid Disease 41:464-470. 2003
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Figure 2: Waiting list death rates by diagnosis, 1999–2008.
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Diabetics who receive k/p gain more Diabetics who receive k/p gain more life-years than k-alone or non-life-years than k-alone or non-
diabeticsdiabetics::
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k/p transplants are equally successful for type 1 and type 2 diabetes:
data from SRTR 2010
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What is the role of pancreas What is the role of pancreas transplant in type 2 transplant in type 2
diabetes?diabetes? Diabetes affects 10% of the Diabetes affects 10% of the
populationpopulation 90-95% is type 290-95% is type 2 Distinction between type 1 and 2 not Distinction between type 1 and 2 not
always clear cutalways clear cut
cC –peptide is not accurate in renal failure
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suggested criteria:suggested criteria:
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Organ Procurement: Simultaneous Liver and Pancreas Removal
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Back table dissection:Back table dissection:
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More back table dissection…More back table dissection…
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Back table Reconstruction of Pancreatic Allograft
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Arterial “Y” Graft of Donor Iliac Artery
Portal Vein Mobilization
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Bladder Drainage with Systemic VenousAnastomosis
Enteric Drainage with Portal VenousAnastomosis
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Trends in maintenance immunosuppression therapy prior to discharge for simultaneous kidney-pancreas transplantation 1994-2003American Journal of Transplantation 2005;5(Part 2):874-886
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Incidence of rejection during first year among simultaneous kidney-pancreas recipients
American Journal of Transplantation 2005;5(Part 2):874-886
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ADVANCES IN PANCREAS TRANSPLANTATION.Transplantation. 77(9) Supplement:S62-S67, May 15, 2004.
Burke G, Ciancio G, Sollinger H
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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)
Surgical Aspects of Pancreas Transplantation:
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Radiologic tools for transplant evaluation:
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Splenic vein thrombosis:
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Fluid collection on CT:
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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
Diagnosis of Pancreatic Allograft Rejection (is difficult)
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PAK and PTA have higher rate of PAK and PTA have higher rate of immunologic graft loss after 1 immunologic graft loss after 1
yearyear
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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
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Isolated Pancreas Transplant: Recipient Selection Criteria
IDDM, age > 18 years with an upper age limit of ?Ability to withstand surgery and immunosuppressionPsychosocial stability/ social support/ compliance/ commitment to long-term follow-upDiabetic secondary complicationsHyper-lability/ Hypoglycemic UnawarenessFinancial resources (USA)Absence of any exclusionary criteria: - renal function - coronary disease
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Mortality risk/benefit of PAK and PTA:
American Journal of Transplantation 2004; 4: 2018–2026
Mortality on waiting list: Mortality after transplant:
spkSPK
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Islet IsolationIslet Isolation1. Organ Procurement
2. Distension with Collagenase
3. Digestion & Mechanical Separation
4. Purification of Islets
5. Quantification
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The “Edmonton Protocol”The “Edmonton Protocol”
Efficient Isolation ProcedureEfficient Isolation Procedure Reliable CollagenaseReliable Collagenase Steroid Free Immunosuppressive Steroid Free Immunosuppressive
ProtocolProtocol IL-2R BlockadeIL-2R Blockade TacrolimusTacrolimus SirolimusSirolimus
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Only 31% remained insulin independent at 2 years
N Engl J Med 2006;355:1318-30.
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Failed islet transplants are associated with sensitization to
HLA antigens:
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Whole Pancreas Transplantation
+ +
Pancreatic Islet Cell Transplantation
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Successful islet transplants decrease Successful islet transplants decrease progression of nephropathy and progression of nephropathy and
retinopathyretinopathy
Preservation of renal function
Decreased progression of retinopathy
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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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Conclusions:
“Good risk” diabetics with a functioning kidney transplant (and problematic BS control) should be considered for pancreas after kidney
“Better risk” diabetics without kidney disease, but with life threatening manifestations should be considered for pancreas transplant alone
“Good” = age < 55, BMI < 30, insulin use < 1U/kg/day, no or minimal CAD, PVD