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Pancreas Transplantation

By Martin Hertl, MD, PhD, Harvard Medical School;Massachusetts General Hospital ; Paul S. Russell, MD, Harvard Medical School;Massachusetts General Hospital

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Patient Education

Pancreas transplantation is a form of pancreatic beta-cell replacement that can restore normoglycemia in diabetic patients.

Because the recipient exchanges risks of insulin injection for risks of immunosuppression, eligibility is limited mostly to

  • Patients who have type 1 diabetes with renal failure and who are thus candidates for kidney transplantation

More than 90% of pancreas transplantations include transplantation of a kidney.

At many centers, repeated failure to control glycemia with standard treatment and episodes of hypoglycemic unawareness are also eligibility criteria.

Relative contraindications include age > 55 and significant atherosclerotic cardiovascular disease, defined as a previous MI, coronary artery bypass graft surgery, percutaneous coronary intervention, or a positive stress test; these factors dramatically increase perioperative risk.

Options include

  • Simultaneous pancreas-kidney (SPK) transplantation

  • Pancreas-after-kidney (PAK) transplantation

  • Pancreas-alone transplantation

The advantages of simultaneous pancreas-kidney transplantation are one-time exposure to induction immunosuppression, potential protection of the newly transplanted kidney from adverse effects of hyperglycemia, and the ability to monitor rejection in the kidney; the kidney is more prone to rejection than the pancreas, where rejection is difficult to detect.

The advantage of pancreas-after-kidney transplantation is the ability to optimize HLA matching and timing of kidney transplantation using a living donor.

Pancreas-alone transplantation offers an advantage to patients who do not have end-stage renal disease but have other severe diabetic complications, including labile glucose control.

Pancreas donors

Donors are usually recently deceased patients who are aged 10 to 55 and have no history of glucose intolerance or alcohol abuse.

For simultaneous pancreas-kidney transplantation, the pancreas and kidney come from the same donor, and the same restrictions for kidney donation apply.

A few (< 1%) segmental transplantations from living donors have been done, but this procedure has substantial risks for the donor (eg, splenic infarction, abscess, pancreatitis, pancreatic leak and pseudocyst, secondary diabetes), which limit its widespread use.

Procedure

The donor is anticoagulated, and a cold preservation solution is flushed into the celiac artery. The pancreas is cooled in situ with iced saline slush, then removed en bloc with the liver (for transplantation into a different recipient) and the 2nd portion of the duodenum containing the ampulla of Vater. The iliac artery is also removed.

The donor pancreas is positioned intraperitoneally and laterally in the lower abdomen.

In simultaneous pancreas-kidney transplantation, the pancreas is placed into the right lower quadrant of the recipient’s abdomen and the kidney into the left lower quadrant. The native pancreas is left in place. The donor iliac artery is used for reconstruction on the back table to reconstruct the splenic artery and superior mesenteric artery of the pancreas graft. This technique results in one artery for connection to the recipient blood vessels. The final anastomoses are made between the donor iliac artery and one of the recipient's iliac arteries and between the donor portal vein and recipient iliac vein. Thus, endocrine secretions drain systemically, causing hyperinsulinemia; sometimes the donor pancreatic venous system is anastomosed to a portal vein tributary to re-create physiologic conditions, although this procedure is more demanding and its benefits are unclear. The duodenum is sewn to the bladder dome or to the jejunum for drainage of exocrine secretions.

Immunosuppression regimens vary but typically include immunosuppressive Igs, a calcineurin inhibitor, a purine synthesis inhibitor, and corticosteroids, which can be slowly tapered over 12 mo (see Table: Immunosuppressants Used to Treat Transplant Rejection).

Complications

Rejection

Despite adequate immunosuppression, acute rejection develops in 40 to 60% of patients, primarily affecting exocrine, not endocrine, components.

Compared with kidney transplantation alone, simultaneous pancreas-kidney transplantation has a greater risk of rejection, and rejection episodes tend to occur later, to recur more often, and to be corticosteroid-resistant. Symptoms and signs are nonspecific (see Table: Manifestations of Pancreas Transplant Rejection by Category).

After simultaneous pancreas-kidney transplantation and pancreas-after-kidney transplantation, pancreas rejection is best detected by an increase in serum creatinine because pancreas rejection almost always accompanies kidney rejection. After pancreas-alone transplantation, a stable urinary amylase concentration in patients with urinary drainage excludes rejection; a decrease suggests some form of graft dysfunction but is not specific to rejection. Early detection is therefore difficult.

Diagnosis is confirmed by ultrasound-guided percutaneous or cystoscopic transduodenal biopsy.

Treatment is with antithymocyte globulin.

Manifestations of Pancreas Transplant Rejection by Category

Rejection Category

Manifestations

Hyperacute

Pancreatic necrosis, fever, hyperglycemia

Accelerated

Pancreatitis, hyperglycemia, elevated amylase and lipase

Acute

Same as those for accelerated

Chronic

Hyperglycemia, mildly elevated amylase and lipase

Other complications

Early complications affect 10 to 15% of patients and include wound infection and dehiscence, gross hematuria, intra-abdominal urinary leak, reflux pancreatitis, recurrent UTI, small-bowel obstruction, abdominal abscess, and graft thrombosis.

Late complications relate to urinary loss of pancreatic sodium bicarbonate (NaHCO3−), causing volume depletion and non-anion gap metabolic acidosis. Hyperinsulinemia does not appear to adversely affect glucose or lipid metabolism.

Prognosis

Overall, 1-yr survival rates are

  • Patients: > 90%

  • Grafts: 78%

Whether survival is higher than that of patients without transplantation is unclear; however, the primary benefits of the procedure are freedom from insulin therapy and stabilization or some amelioration of many diabetic complications (eg, nephropathy, neuropathy).

Graft survival is

  • Simultaneous pancreas-kidney transplantation: 95%

  • Pancreas-after-kidney transplantation: 74%

  • Pancreas-alone transplantation: 76%

The rate of immunologic graft loss for pancreas-after-kidney transplantation and pancreas-alone transplants is higher, possibly because such a transplanted pancreas lacks a reliable monitor of rejection; in contrast, rejection after simultaneous pancreas-kidney transplantation can be monitored using established indicators of rejection for the transplanted kidney.

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