Transcript The Role of Pancreas Transplantation in the Long Term - wi

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:
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.
no disclosures
Tight control reduces end organ damage
but increases the risk (2-3 fold) of
severe hypoglycemic episodes (1).
1 DCCT. 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 InsulinDependent Diabetes Mellitus. N Engl J
Med 1993; 329: 977–986.
DCCT trial (1441 patients randomized to intensive
insulin vs. conventional insulin) designed to
examine the effect of tight control on 2°
complications (followed > 6yrs)
Retinopathy
Incidence
progression
Neuropathy
Prevalence of neuropathy
A successful pancreas transplant
completely normalizes blood sugar
control
However, it requires life long immunosuppression
Types of pancreas transplants:
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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)
Combined kidney/pancreas transplant is
the most common scenario for pancreas
transplantation:
Indications for Simultaneous Kidney
and Pancreas Transplant:
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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
Figure 13: Unadjusted 1-year, 3-year, 5-year and 10-year
pancreas graft survival by transplant type
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
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
Figure 2: Waiting list death rates by
diagnosis, 1999–2008.
Diabetics who receive k/p gain more lifeyears than k-alone or non-diabetics:
k/p transplants are equally successful for type 1
and type 2 diabetes:
data from SRTR
2010
What is the role of pancreas
transplant in type 2 diabetes?
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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
suggested criteria:
Organ Procurement: Simultaneous Liver and
Pancreas Removal
Back table dissection:
More back table dissection…
Back table Reconstruction of Pancreatic Allograft
Arterial “Y” Graft of Donor Iliac Artery
Portal Vein Mobilization
Bladder Drainage with Systemic Venous
Anastomosis
Enteric Drainage with Portal Venous
Anastomosis
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
Incidence of rejection during first year among simultaneous
kidney-pancreas recipients
American Journal of Transplantation 2005;5(Part 2):874-886
ADVANCES IN PANCREAS TRANSPLANTATION.
Transplantation. 77(9) Supplement:S62-S67, May 15, 2004.
Burke G, Ciancio G, Sollinger H
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)
Radiologic tools for transplant
evaluation:
Splenic vein thrombosis:
Fluid collection on CT:
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
PAK and PTA have higher rate of
immunologic graft loss after 1 year
Indications for isolated pancreas
transplant (PAK or PTA):
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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
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/
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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
Mortality risk/benefit of PAK and PTA:
Mortality on waiting list:
Mortality after transplant:
SPK
spk
American Journal of Transplantation 2004; 4:
2018–2026
Islet Isolation
1. Organ Procurement
2. Distension with
Collagenase
3. Digestion & Mechanical
Separation
4. Purification of Islets
5. Quantification
The “Edmonton Protocol”
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Efficient Isolation Procedure
Reliable Collagenase
Steroid Free Immunosuppressive
Protocol
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IL-2R Blockade
Tacrolimus
Sirolimus
Only 31% remained
insulin independent at 2
years
N Engl J Med 2006;355:1318-30.
Failed islet transplants are associated
with sensitization to HLA antigens:
Whole Pancreas Transplantation
Pancreatic Islet Cell Transplantation
+
+
Successful islet transplants decrease
progression of nephropathy and retinopathy
Preservation of renal
function
Decreased progression of
retinopathy
Conclusions:
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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
Conclusions:
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“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