The Diabetes Control and Complications Trial (DCCT) demonstrated in patients with type 1 diabetes mellitus (T1DM) that intensive insulin therapy may slow the rate of secondary complications of diabetes at the expense of causing life-threatening, iatrogenic hypoglycemia. Pancreas transplantation (PTX) is the most effective treatment for glycemic control and forestalling microvascular end-organ damage in T1DM. Compared to insulin-based treatment of T1DM, functional pancreata result in euglycemia; do not cause hypoglycemia; and lead to improvements of retinopathy, peripheral neuropathy, and progression of native diabetic nephropathy (DN) or recurrence of DN in the transplanted kidney.

Currently, PTX is not only the first choice for organ replacement in T1DM but also in patients with type 2 diabetes mellitus with BMI ≤28 mg/kg per m² and also in patients undergoing pancreatectomy for malignancy localized to the pancreas or chronic pancreatitis with irreversible damage.

• Simultaneous kidney-pancreas transplant (SPK)
• Pancreas after kidney transplant (PAK)
• Pancreas transplant alone (PTA)

• Since the first SPK transplant in 1966, the outcomes, surgical technique, immunosuppression, and complications of pancreas transplant modalities have evolved and improved. In the past 30 yr, more than 31,000 PTX procedures have been performed in the United States. The success in survival of PTX and recipients is the result of better procurement techniques, changes in pancreas exocrine drainage from the urinary bladder to the small intestine and advances in immunosuppression.
• The introduction in the 1980s of OKT3 and calcineurin inhibitors such as cyclosporine was pivotal in improving PTX outcomes. With the introduction of rabbit antithymocyte globulin in the late 1990s (replacing OKT3) and tacrolimus (replacing cyclosporine), there has been an additional reduction in PTX loss in the first 90 days posttransplant and in PTX rejection. Similarly, the survival of the kidney (native or transplant) has improved due to reduction of nephrotoxicity and chronic immune injury.

The exam of PTX recipients is no different from that of other organ recipients. PTX is surgically placed in the right lower quadrant of the abdomen. Abdominal pain is a common sign of rejection, graft thrombosis (complicating 5% to 10% of PTX), and pancreatitis (complicating 3% of PTX). Fever is common in viral infections of the PTX (e.g., cytomegalovirus, adenovirus) or intraabdominal bacterial infections. An anastomotic leak is a rare and serious complication, contributing to 4% of graft failures. The diagnosis is suggested by peritonitis, fever, and leukocytosis and is confirmed by imaging studies.

• Acute rejection
• Surgical complications
• Transplant pancreatitis
• Viral infection: CMV, adenovirus, Coxsackie virus, and mumps virus
• Posttransplant lymphoproliferative lymphoma occurs more commonly in pancreatic transplants compared to kidney transplants

In bladder-drained PTX, urologic complications include urethral stenosis and hemorrhagic cystitis, recurrent urinary tract infections, severe metabolic acidosis, and volume depletion from exocrine sodium bicarbonate loss in urine. These complications often require surgical conversion from bladder drainage to enteric drainage.

• Graft monitoring:
  1. Amylase and lipase levels (lipase, more specific)
  2. Fasting blood glucose level
  3. Fasting C-peptide level
  4. A1c level
  5. Bladder-drained PTX: Urinary amylase may be helpful
• Specific tests:
  1. Viral polymerase chain reaction: Cytomegalovirus, adenovirus, BK virus, mumps
  2. PTX biopsy
  3. Bacterial cultures as indicated: Blood, urine, peritransplant collections
• Elevated fasting glucose or A1c levels or low fasting C-peptide level predict poor graft survival. In these circumstances, the risks associated with treatment of graft rejection may outweigh its benefits

Surgical conversion: Pancreatic graft bladder drainage to enteric drainage

• Acute rejection: Acute immunosuppression with antithymocyte globulin, intravenous pulse glucocorticoids, antiproliferative agents (mycophenolate-based drugs or mammalian target of rapamycin inhibitors, e.g., everolimus or rapamycin), and calcineurin inhibitor (i.e., tacrolimus)
• Chronic or maintenance immunosuppression: Generally, a regimen comprising calcineurin inhibitor (i.e., tacrolimus), antiproliferative agents (mycophenolate-based drugs or mammalian target of rapamycin inhibitors, e.g., everolimus or rapamycin), and glucocorticoids

Admission to an intensive care unit or dedicated transplant organ floor, depending on severity of clinical presentation. Management may require consultations to infectious diseases and urology where appropriate.