Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

* This is a professional Version *

Pancreas Transplantation

by Martin Hertl, MD, PhD, Paul S. Russell, MD

Pancreas transplantation is a form of pancreatic β-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; > 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 SPK 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 PAK 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.

Donors are usually recently deceased patients who are aged 10 to 55 and have no history of glucose intolerance or alcohol abuse. For SPK, the pancreas and kidney come from the same donor, and the same restrictions for kidney donation apply (see Kidney Transplantation). 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 SPK, 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.

Complications

Despite adequate immunosuppression, acute rejection develops in 60 to 80% of patients, primarily affecting exocrine, not endocrine, components. Compared with kidney transplantation alone, SPK 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 Manifestations of Transplant Rejection by Category).

After SPK and PAK, 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.

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 NaHCO 3 , 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 95% for SPK, 74% for PAK, and 76% for pancreas-alone transplantation. The rate of immunologic graft loss for PAK and pancreas-alone transplants is higher, possibly because such a transplanted pancreas lacks a reliable monitor of rejection; in contrast, rejection after SPK can be monitored using established indicators of rejection for the transplanted kidney.

Pancreatic Islet Cell Transplantation

Islet cell transplantation (into the recipient's liver) has theoretical advantages over pancreas transplantation; the most important is that the procedure is less invasive. A secondary advantage is that islet cell transplantation appears to help maintain normoglycemia in patients who require total pancreatectomy for pain due to chronic pancreatitis. Nevertheless, the procedure remains developmental, although steady improvements appear to be occurring.

Its disadvantages are that transplanted glucagon-secreting αcells are nonfunctional (possibly complicating hypoglycemia) and several pancreata are usually required for a single islet cell recipient (exacerbating disparities between graft supply and demand and limiting use of the procedure).

Indications are the same as those for pancreas transplantation. Simultaneous islet cell–kidney transplantation may be desirable after the technique is improved.

Procedure

A pancreas is removed from a brain-dead donor; collagenase is infused into the pancreatic duct to separate islets from pancreatic tissue. A purified islet cell fraction is infused percutaneously into the portal vein by direct puncture of that vein or via a branch of the mesenteric vein. Islet cells travel into hepatic sinusoids, where they lodge and secrete insulin .

Results are best when 2 cadavers are used, with each supplying 2 or 3 infusions of islet cells, followed by an immunosuppressive regimen consisting of an anti-IL-2 receptor antibody (daclizumab), tacrolimus, and sirolimus (Edmonton protocol); corticosteroids are used sparingly because they cause hyperglycemia. Immunosuppression must be continued lifelong or until islet cell function ceases.

Rejection is poorly defined but can be detected by deterioration in blood glucose control and an increase in glycosylated hemoglobin (HbA 1c ); treatment of rejection is not established. Procedural complications include percutaneous hepatic puncture with bleeding, portal vein thrombosis, and portal hypertension.

Successful islet cell transplantation maintains short-term normoglycemia, but long-term outcomes are unknown; additional injections of islet preparations may be necessary to obtain longer-lasting insulin independence.


Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • No US brand name
  • RAPAMUNE
  • PROGRAF

* This is a professional Version *