Pancreas Transplantation



Pancreas Transplantation

Introduction

• Currently, pancreas transplantation is considered a therapeutic option for patients with all stages of DM, even those with advanced extrapancreatic complications.

• More than 15,000 pancreas transplants were reported to the International Pancreas Transplant Registry (IPTR) between 1966 and 2000.

• SPK transplantation is by far the most common approach.

Current Status of Pancreas Transplantation

• Combined or simultaneous pancreas-kidney (SPK).

o 1-year patient survival rate of 95%

o 1-year graft survival rate of 82%

• Pancreas after kidney (PAK) transplantation.

o 1-year patient survival rate of 94%

o 1-year graft survival rate of7 4%

• Pancreas transplant alone (PTA).

o 1-year patient survival rate of 100% in PTA recipients

o 1-year graft survival rate of 76%

Indications for Pancreas Transplantation

| |Patients with type 1 DM who have |

|PTA |Recurrent, acute, severe metabolic complications (ketoacidosis) requiring medical intervention. |

| |Acute complications despite repeated trials with exogenous insulin replacement. |

| |Incapacitating clinical and emotional problems associated with exogenous insulin therapy. |

| |Patients with type 1 DM |

|SPK |In conjunction with impending or established ESRD. |

|Or |20-50 years of age. |

|PAK |Creatinine clearance approximates 25-30 mL/m2/min. or Significant uremic symptoms. |

Benefits of Pancreas Transplantation

• Restores euglycemia.

• Improves quality of life in patients with insulin-dependent diabetes.

• Slows the progression of end-organ complications.

|Peripheral Neuropathy |Cardiovascular Disease |

|Cardiac Dysautonomia |Microvascular Disease |

|Gastric Dysautonomia |Diabetic Retinopathy |

|Urinary Dysautonomia |Diabetic Nephropathy |

|Macrovascular Disease | |

Contraindications

|Absolute contraindications |Relative Contraindications |

|HIV infection |Cardiovascular disease |

|Disseminated or untreated cancer |Treated malignancy |

|Severe psychiatric disease |Substance abuse history |

|Unresolvable psychosocial problems |Chronic liver disease |

|Persistent substance abuse |Structural genitourinary abnormality or recurrent urinary tract |

|Severe mental retardation |infection |

|Un-reconstructable coronary artery disease or refractory |Past psychosocial abnormality |

|congestive heart failure |Aortoiliac disease |

Pretransplant Evaluation for Pancreas Transplant Candidates

|Blood Work |Electrolyte panel, phosphate, magnesium, uric acid |

| |Pancreatic enzymes: amylase, lipase |

| |Lipid profile, Liver function tests |

| |CBC with differential count, sedimentation rate |

| |Coagulation profile*: PT, PTT, INR |

| |Serologies: RPR, HIV, HAV IgG, HBV surface antigen, HBV core antibody and surface antibody, HCV antibody, CMV, |

| |EBV |

|Cardiovascular Consultation and |12-lead ECG, Chest x-ray, Echocardiogram Exercise treadmill test, thallium stress test |

|Evaluation |Ultrasound of the carotid arteries |

| |Doppler studies to detect vascular disease such as arterial duplex studies with lower extremity segmental |

| |pressures |

| |Deep vein thrombosis (nuclear medicine) such as contrast venography |

| |Letter of clearance for surgery from cardiologist |

|Renal Consultation and Evaluation |Urinalysis, 24-hour urine for creatinine clearance |

| |Glomerular filtration rate, Urine microalbumin, total protein |

|Endocrinology Consultation and Evaluation|Cortisol level, thyroid studies (T3, T4, TSH), FANA, ANA |

| |Bone mineral density |

Procedures for Pancreas Transplantation

| |Systemic-Bladder Technique |Portal-Enteric Technique |

|Venous outflow and insulin drainage |Iliac vein |Portal vein |

|Exocrine drainage |urinary bladder |Enteric |

|Advantages |Fewer complications |More physiologic |

|Assessment of pancreatic function |via urinary amylase levels |ostomy drainage amylase levels |

|Disadvantages |Hyperinsulinemia | |

|Contraindications |neutropenic bladder dysfunction | |

Postoperative Management

Early

• Infection and thrombosis prophylaxis.

• Prevention of acute rejection ( Immunosuppressive therapy

o Induction therapy with an antilymphocyte agent

o Triple-agent immunosuppression with: ( standard maintenance regimen

▪ Calcineurin inhibitor (CsA or TAC).

▪ Antiproliferative agent (azathioprine [AZA] or MMF.

▪ Corticosteroids is the.

▪ CsA or TAC trough levels and CD2 or CD3 counts (depending on the induction agent used) are monitored daily until:

• Discharge from the hospital. or

• Completion of induction therapy.

• Monitoring of graft function. ( blood glucose, amylase, HbA1c, and C-peptide levels

• Patients are given antibiotics during surgery and for 2-5 days after transplantation.

• Anticoagulation beginning a few weeks before transplantation then low-molecular-weight dextran during the first week after surgery.

• Frequent monitoring of fluid and electrolyte balance, cardiac parameters, and metabolic function.

• Administration of albumin and IV fluids with or without bicarbonate prevents dehydration and corrects the metabolic acidosis.

• Symptomatic management (metoclopramide, cisapride, domperidone).

• Administration of calcium channel blockers may decrease the incidence of posttransplant pancreatitis.

Delayed Graft Function

Factors associated with delayed graft function:

• Prolonged duration of cold ischemic preservation time of the donor organ

• Donor hyperglycemia or hyperamylasemia.

• Increased donor age is associated with poorer posttransplant outcomes.

Complications

• Graft thrombosis.

• Arterial thrombosis may involve the splenic artery, the superior mesenteric artery (SMA) or both.

• Infection

o Bacterial, viral, fungal.

o Pancreatitis can occur in the immediate postoperative period as a result of damage to the pancreas during cold ischemic preservation or from handling of the organ during surgery.

o Cystitis and urethritis.

o Intrapancreatic abscess

• Anastomotic Leak

Rejection

Hyperacute rejection (extremely rare)

• Occurs immediately in the operating room upon vascularization of the graft.

• Caused by the presence of preformed circulating cytotoxic antibodies in the recipient's blood.

• Pancreas becomes grossly edematous and ischemic.

• Results in immediate graft loss.

Acute rejection

• Occurs from approximately 1 week to 3 months after transplantation.

• Cellular immune response involving mononuclear, cytotoxic, helper T cells, monokines, and lymphokines.

• Only type of rejection that can be treated.

• Treatment

• Hospitalization.

• Aggressive immunosuppressive therapy.

• Pulsed corticosteroid therapy and/or antilymphocyte agents are administered.

Chronic Rejection

• Occur at any time after approximately 3 months after transplantation.

• Mediated by T cells and B cells.

• Leads to insidious, progressive loss of graft function.

• Manifested clinically by:

o Hyperglycemia.

o Low C-peptide levels.

• Confirmed by biopsy ( dense septal fibrosis and acinar cell loss.

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