Pancreas Transplantation Ahmad Bashar Abdulkarim , MD, PhD, FACS - - PDF document

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Pancreas Transplantation

Ahmad Bashar Abdulkarim, MD, PhD, FACS Transplant Surgery

Avera Health Center Sioux Falls, SD

Pancreas Transplantation

Facts:

• Diabetes patients with chronic kidney disease (CKD)

experience excessive morbidity and mortality

• Simultaneous pancreas and kidney (SPK)

Simultaneous pancreas and kidney (SPK) transplantation has been shown to significantly improve quality of life, and increase life expectancy

• f uremic diabetes patients

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Pancreas Transplantation

Facts:

• One-year and 5-year pancreas graft survival rates are

now comparable with those of kidney, liver, and heart transplants

• Half life of an SPK is about 14 years

Pancreas Transplantation

• Indications

A- Simultaneous kidney and pancreas transplant (SPK): ESRD secondary to diabetic nephropathy. B- Pancreas Transplant alone (PTA): * Brittle diabetics Brittle diabetics * Frequent episodes of DKA * Hypoglycemic unawareness

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Pancreas Transplantation

• Contraindications

A- Malignancy: A- Malignancy: * Screening * Free of recurrence for 2 years before the transplant; this will eliminate about 2/3 of recurrences

• Malignant melanomas, breast Ca, and

Colon Ca with higher tumor stages; nodal Colon Ca with higher tumor stages; nodal involvement (5 years)

• Carcinoma in situ; skin, small incidental

renal cell carcinoma (no waiting time)

Pancreas Transplantation

• Contraindications

B- Infections Viruses: HIV: [HAART] Small series show

comparable outcomes.

Grossi, PA et al, Transplantation, 2012; 12(4): 1039-1045

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Pancreas Transplantation

B- Infections Viruses: HBsAg+: KTx; Similar pt and graft

survival but higher risk of dying of hepatic failure

PTx; Few reports with encouraging

results when using Lamivudine for the first year post transplantation.

Reddy et al, Clin Am J Soc Neph 2011 6(6): 1481-7 Akalin E, Clin Transplant 2005, 19(3): 364-6

Pancreas Transplantation

B- Infections Viruses: HepC: No significant effect on graft

• r patient survival, small reports.

Miguel M et al, Transplantation 2010; 90(1):61-67

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Results of SPK Transplantation in The USA

Pancreas Transplantation

T1DM vs T2DM T1DM vs.T2DM

• Obesity, and later age of onset, for example, often blur

the diagnosis between T1DM vs. T2DM.

• C-peptide (renal failure/gastroparesis.. False elevation)

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Pancreas Transplantation

T2DM T2DM

The pathophysiology of T2DM includes genetic causes of chronic inflammation and insulin resistance leading to hyperinsulinemia, which ultimately results in beta-cell exhaustion.

T1DM

Patients classically suffer autoimmune-mediated damage to beta cells leading to decreased (or absent) insulin secretion.

Pancreas Transplantation

Given the increasing prevalence of T2DM in most western Given the increasing prevalence of T2DM in most western countries, and Given that T2DM is among the leading causes of kidney disease, Therefore, pancreas transplantation may be underutilized in this population. Currently,

• 8% of SPKs in the USA are performed for T2DM, and 5% and

1% for PAK and PTA, respectively

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Pancreas Transplantation

Indications for SPK in T2DM Indications for SPK in T2DM

• BMI <28
• Insulin dependence (<1 unit/kg/day)
• C peptide >2ng/ml

Pancreas Transplantation

• Types:

A- Simultaneous pancreas and kidney transplant (SPK). B- Pancreas after kidney (PAK) C- Pancreas transplant alone (PTA) D- Islet Transplantation

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Pancreas Transplantation

D O ti Donor Operation

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Pancreas Transplantation

Recipient Operation

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Pancreas Transplantation

• Types of Pancreas Functions

A- Exocrine:

• Amylase
• Lipase
• Bicarbonate…..

B- Endocrine:

• Insulin
• Glucagon
• Somatostatin….

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Pancreas Transplantation

• Types of Pancreas Functions

A- Exocrine:

• Amylase
• Lipase
• Bicarbonate….

B- Endocrine:

• Insulin Pancreas Islet Transplant
• Glucagon…..

Pancreas Transplantation

Islet Transplantation Indication

This therapy is only suitable in its current form for patients with unstable glycemic control that cannot be corrected by standard conventional and intensive insulin therapies

Shapiro, N Engl J Med, 2000, 343 (4):230

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Pancreas Transplantation

Islet Transplantation

Not currently considered for islet transplantation 1- Patients with good glycemic control 2- Children are not currently considered for islet transplantation

Shapiro, N Engl J Med, 2000, 343 (4):230

Pancreas Transplantation

Islet Transplantation vs. Insulin Pump

Hgb A1c Corrected Varies Diabetic Nephropathy Progression No effect

Shapiro, Curr opin organ transplant, 2011, 16(6): 627 Thompson, Transplantation 2011, 91(3): 373

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Pancreas Transplantation

• Types: (Based on drainage of donor duodenum)

A- Bladder-drained B- Enteric-drained (Based on venous drainage) (Based on venous drainage) A- Systemic B- Portal

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Pancreas Transplantation

Bladder-drained Pancreas

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Pancreas Transplantation

Systemic-enteric Pancreas

Systemic-enteric SPK

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Portal vs. Systemic Drainage Pancreas Tx

Systemic vs. Portal Drainage

• Bypassing the liver causes peripheral

hyperinsulinemia and portal hypoinsulinemia hyperinsulinemia and portal hypoinsulinemia

(50% of insulin is degraded during the first pass)

– Hyperinsulinemia has been associated with:

• The development of atherosclerosis, both directly

(stimulation of arterial smooth muscle growth) and indirectly (development of dyslipidemia and y ( p y p hypertension).

• It has also been linked to increased conc. plasminogen

activator inhibitor (PAI-1), which predisposes vessels to formation of lipid-laden rather than cell-rich plaques.

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Systemic vs. Portal Drainage

Hyperinsulinemia has been associated with:

I li i t lt f i d h ti

• Insulin resistance as a result of increased hepatic

glucose production, reduced postprandial peripheral glucose disposal, reduced insulin-stimulated glucose storage …..

• Downregulates insulin receptors and postreceptor

pathways in the muscle and adipose tissues, thus causing insulin resistance causing insulin resistance

• Hypertension, CVD, weight gain, and, in women,

polycystic ovary syndrome

Systemic vs. Portal Drainage

Portal hypoinsulinemia leads to lipoprotein abnormalities that lead to development and abnormalities that lead to development and progression of atherosclerosis.

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Systemic vs. Portal Drainage

• A beneficial effect on pancreas graft

t acceptance

(Hypothesis: antigen delivery via the portal vein favorably alters antigen presentation with subsequent induction of immunologic hyporeactivity and even tolerance)

More studies are needed to prove the immunologic advantage in favor of portal vein drainage

Observations Observations

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Pancreas Tx Volume

• Rates of pancreas transplantation have declined,

despite improved pancreatic graft outcomes. Pancreas Transplant Volume

Kandaswamy R et al; AJT 2013(13) [Suppl 1}:47-72

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Pancreas Tx Volume

• Fewer patients are placed on the waiting list
• Changes in the rate of diabetic nephropathy

development

• Delayed progression of late-stage CKD
• Greater availability of better insulin-delivery

t system

Pancreas Tx Volume (contin.)

• Better diabetes education
• Regional waiting list rules
• More stringent donor selection
• Greater scrutiny of center outcomes

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Acute Rejection Acute Rejection

Pancreas Transplantation

Acute Rejection

• The incidence of rejection within 1-year post-

transplantation in a cohort of 162 patients of all pancreas transplant types, including many re- transplants undergoing for-cause biopsies, was 21%, with antibody mediated rejection (AMR) acute with antibody-mediated rejection (AMR), acute cellular rejection (ACR), and mixed rejection

• ccurring in nearly equal frequency

Neiderhaus, AJT 2013

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Pancreas Transplantation

Acute Rejection

• In their study, the majority of pancreas rejection

episodes were successfully reversed and graft function was maintained. However, 20% of grafts were lost within a year of diagnosis Thi hi hli h h d f l di i d

• This highlights the need for early diagnosis and

efficient surveillance

Acute Rejection

• Rejection of the pancreas may be discordant with the

kidney after SPK and there is a greater appreciation kidney after SPK and there is a greater appreciation

• f antibody-mediated rejection of the pancreas

allograft

• De-novo donor-specific antibody without graft

dysfunction remains an active area of study, and the treatment for this condition is unclear treatment for this condition is unclear

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Acute Rejection

A ll f bi ll h

• A pancreas allograft biopsy allows the surgeon to

accurately identify and define rejection, and should be incorporated into the portfolio of pancreas transplant monitoring

Acute Rejection

O h li i l f j i

• Other clinical parameters for rejection:
• hyperglycemia
• serum amylase/lipase
• C-peptide level
• hemoglobin A1C, or

g ,

• (if bladder drained) urinary amylase

are insufficient because they are either too late or nonspecific

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Acute Rejection

Th ili d ff i f ill

• The utility and cost–effectiveness of surveillance

biopsies have not yet been studied

• Contrary to prior assumptions, concordance in

pathology between kidney graft and pancreas graft biopsies after SPK transplantation is not 100% and grafts can exhibit differing types and degrees of grafts can exhibit differing types and degrees of

• rejection. Therefore, kidney biopsies alone for SPK

patients are insufficient to determine the pathologic status of the pancreatic graft

Acute Rejection

Di d l b d d l ff bi

• Discordant results between a duodenal cuff biopsy

and pancreas parenchymal biopsy also occur

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Trends in Immunosuppression Conclusion

• Pancreas Transplantation improves quality of life and

life expectancy in uremic diabetic patients life expectancy in uremic diabetic patients

• Improvement in surgical technique and rejection

screening have made long-term outcome comparable to other organ transplants; kidney, liver, and heart

• Islet transplantation still holds promise for treatment
• f brittle diabetics

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Thank You