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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