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

3/24/2015 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 of uremic diabetes patients 1

3/24/2015 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 2

3/24/2015 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 3

3/24/2015 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 or patient survival, small reports. Miguel M et al, Transplantation 2010; 90(1):61-67 4

3/24/2015 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) 5

3/24/2015 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 6

3/24/2015 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 7

3/24/2015 Pancreas Transplantation D Donor Operation O ti 8

3/24/2015 9

3/24/2015 10

3/24/2015 Pancreas Transplantation Recipient Operation 11

3/24/2015 Pancreas Transplantation • Types of Pancreas Functions A- Exocrine: -Amylase -Lipase -Bicarbonate….. B- Endocrine: -Insulin -Glucagon -Somatostatin…. 12

3/24/2015 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 13

3/24/2015 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 14

3/24/2015 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 15

3/24/2015 Pancreas Transplantation Bladder-drained Pancreas 16

3/24/2015 Pancreas Transplantation Systemic-enteric Pancreas Systemic-enteric SPK 17

3/24/2015 18

3/24/2015 19

3/24/2015 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. 20

3/24/2015 Systemic vs. Portal Drainage Hyperinsulinemia has been associated with: • Insulin resistance as a result of increased hepatic I li i t lt f i d h ti 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. 21

3/24/2015 Systemic vs. Portal Drainage • A beneficial effect on pancreas graft acceptance t (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 22

3/24/2015 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 23

3/24/2015 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 system t Pancreas Tx Volume (contin.) • Better diabetes education • Regional waiting list rules • More stringent donor selection • Greater scrutiny of center outcomes 24

3/24/2015 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 occurring in nearly equal frequency Neiderhaus, AJT 2013 25

3/24/2015 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 • This highlights the need for early diagnosis and Thi hi hli h h d f l di i d 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 of 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 26

3/24/2015 Acute Rejection • A pancreas allograft biopsy allows the surgeon to A ll f bi ll h accurately identify and define rejection, and should be incorporated into the portfolio of pancreas transplant monitoring Acute Rejection • Other clinical parameters for rejection: O h li i l f j i -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 27