eMedicine Specialties > Transplantation > Surgery

Pancreas Transplantation: Treatment & Medication

Author: Dixon B Kaufman, MD, PhD, Director of Pancreas Transplantation, Professor, Department of Surgery, Division of Transplantation, Feinberg School of Medicine, Northwestern University
Contributor Information and Disclosures

Updated: Nov 11, 2009

Treatment

Surgical Care

The timing of allocation of the pancreas to a specific patient relative to the procurement of the organ has important implications. Determining donor human leukocyte antigen (HLA) typing, serologies, and crossmatch results with patients on the pancreas transplantation waiting list will permit the ideal situation of allocating the cadaveric pancreas (plus kidney, with SPK transplantation) prior to procurement of the organs. This sequence of events has several advantages, as follows:

• Prior allocation allows the transplantation center performing the pancreas transplantation the choice to procure the pancreas as well. It allows patients to be admitted to the hospital and the reevaluation process to begin simultaneously with the procurement of organs, rather than sequentially.
• The cold-ischemia time of the pancreas prior to implantation is minimized. Pancreas allografts do not tolerate cold-ischemia as well as kidney allografts. Ideally, the pancreas should be revascularized within 24 hours from the time of cross-clamping at procurement.
• Finally, prior allocation also allows identification of 0-antigen mismatched donor-recipient pairs before procurement, which minimizes cold-ischemia time if the organs need to be transported across country.
• Pancreas transplantation surgery: The surgical techniques for pancreas transplantation are diverse, and no standard methodology is used by all programs. The principles are consistent, however, and include providing adequate arterial blood flow to the pancreas and duodenal segment, adequate venous outflow of the pancreas via the portal vein, and management of the pancreatic exocrine secretions. The native pancreas is not removed. Pancreas graft arterial revascularization typically is accomplished using the recipient right common or external iliac artery. The Y-graft of the pancreas is anastomosed end-to-side. Positioning of the head of the pancreas graft cephalad or caudad is not relevant with respect to successful arterial revascularization.
  • When the pancreas transplantation is performed simultaneously with kidney transplantation, it is not uncommon for the kidney transplantation to be performed first. The kidney is based on the recipient left iliac vessels. Both organs may be transplanted through a midline incision and placed intraperitoneal.
  • Occasionally, considering placement of pancreas transplantation based on the left iliac vessels is necessary because of previously placed kidney transplantation on the right side. In this sequential pancreas-after-kidney transplantation procedure, the intra-abdominal approach is used. Mobilization of the left iliac vessels medial to the sigmoid colon is somewhat more challenging.
  • Most programs have had good experience with enteric drainage of the pancreas transplantation alone. Markers for rejection include clinical signs and symptoms of pancreas graft pancreatitis and measurement of serum amylase or lipase levels coupled with biopsy. The pancreas is sometimes drained into the bladder if a pancreas transplantation alone or pancreas-after-kidney transplantation is performed in order to measure urinary amylase levels as a method of detecting rejection.
  • Two choices are available for venous revascularization—systemic and portal. No clinically relevant difference in glycemic control has been documented. Currently, approximately 15% of pancreas transplantations are performed with portal venous drainage and the remainder with systemic venous drainage.
    • Systemic venous revascularization commonly involves the right common iliac vein or the right external iliac vein following suture-ligation and division of the hypogastric veins.
    • If portal venous drainage is used, dissecting out the superior mesenteric vein (SMV) at the root of the mesentery is necessary. The pancreas portal vein is anastomosed end-to-side to a branch of the SMV. This may influence the methodology of arterial revascularization using a long Y-graft placed through a window in the mesentery to reach the right common iliac artery. Portal venous drainage of the pancreas is more physiologic with respect to immediate delivery of insulin to the recipient liver. This results in diminished circulating insulin levels relative to that in systemic venous-drained pancreas grafts.
    • Handling the exocrine drainage of the pancreas is the most challenging aspect of the transplantation procedure. Several methods exist. Very few programs use duct injection. Pancreatic exocrine drainage is handled by means of anastomosis of the duodenal segment to the bladder or anastomosis to the small intestine. Currently, approximately 80% of pancreas transplantations are performed with enteric drainage; the remaining 20% are performed with bladder drainage.
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      Solitary pancreas transplantation with enteric drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.

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      Solitary pancreas transplantation with enteric drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.

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      Solitary pancreas transplantation with bladder drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.

      [ CLOSE WINDOW ]

      

      Solitary pancreas transplantation with bladder drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.

    • The bladder-drained pancreas transplantation was a very important modification introduced in about 1985. This technique significantly improved the safety of the procedure by minimizing occurrence of intra-abdominal abscess from leakage of enteric-drained pancreas grafts.
    • With the successful application of the new immunosuppressant agents and the reduction of the incidences of rejection, enteric drainage of the pancreas transplantations has enjoyed a successful rebirth. Enteric drainage of pancreas grafts is physiologic with respect to the delivery of pancreatic enzymes and bicarbonate into the intestines for reabsorption. Enterically drained pancreases can be constructed with or without a Roux-en-Y. The enteric anastomosis can be made side-to-side or end-to-side with the duodenal segment of the pancreas. The risk of intra-abdominal abscesses is extremely low, and avoidance of the bladder-drained pancreas has significant implications with respect to the potential complications that include the following: bladder infection, cystitis, urethritis, urethral injury, balanitis, hematuria, metabolic acidosis, and the frequent requirement for enteric conversion.

Diet

Following successful pancreas transplantation, no dietary restrictions are required. In fact, the diet can be liberalized to include virtually anything because blood sugar control is restored to normal.

Activity

Following successful pancreas transplantation, few activity restrictions are needed. Extreme contact sports probably should be avoided to prevent accidental trauma to the newly placed intra-abdominal organs.

Medication

All pancreas transplant recipients require life-long immunosuppression to prevent a T-cell alloimmune rejection response. The Food and Drug Administration (FDA) has approved several new immunosuppressive agents, and several others currently are in clinical trials.

Two broad classifications of immunosuppressive agents exist—intravenous induction/antirejection agents and maintenance immunotherapy agents. No consensus exists as to the single best immunosuppressive protocol, and each transplant program utilizes various combinations of agents slightly differently.

The goals are to prevent acute or chronic rejection, minimize drug toxicity, minimize rates of infection and malignancy, and achieve the highest possible rates of patient and graft survival.

Immunosuppressant agents for induction immunotherapy

Induction immunotherapy consists of a short course of intensive treatment with intravenous agents. Antilymphocyte antibody induction therapeutic agents are varied and include polyclonal antisera, mouse monoclonals, and so-called humanized monoclonals. Polyclonal antisera, such as antilymphocyte globulin (ALG), antilymphocyte serum (ALS), and antithymocyte globulin (ATG) are equine, goat, or rabbit antisera directed against human lymphoid cells. The effects significantly lower and almost abolish circulating lymphoid cells critical to rejection response.

The agents are very effective at prophylaxis against early acute rejection, which is especially beneficial in managing the recipient with delayed graft function. The agents provide an effective immunologic cover during a period where the calcineurin inhibitors either are delayed or administered in subtherapeutic doses until graft function improves. Induction agents are used less often if immediate graft function occurs, such as recipients of living kidney donors, especially HLA-ID grafts.

Daclizumab (Zenapax)

Humanized monoclonal antibody that specifically binds to and blocks interleukin-2 (IL-2) receptor on surface of activated T cells.

Basiliximab (Simulect)

Chimeric monoclonal antibody that specifically binds to and blocks the IL-2 receptor on the surface of activated T cells.

Antithymocyte globulin, rabbit (Thymoglobulin)

A purified immunoglobulin solution produced by the immunization of rabbits with human thymocytes is used to treat acute rejection.

Alemtuzumab (Campath)

A humanized monoclonal antibody against the CD52 antigen. The anti-CD52 antibody induces lympholysis from complement-mediated lysis or other effector mechanisms.

Maintenance immunosuppression agents

Several immunosuppressive agents currently are in use for maintenance immunotherapy in kidney transplant recipients. Optimal maintenance immunosuppressive protocol has not been developed. Maintenance immunosuppressive agents are required for life.

Prednisone (Sterapred)

Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Azathioprine (Imuran)

Active component of azathioprine is 6-mercaptopurine. Acts as purine analog that interacts with DNA and inhibits lymphocyte cell division.

Mycophenolate (CellCept, Myfortic)

Inhibitor of enzyme inosine monophosphate dehydrogenase (IMPDH). Results in inhibition of lymphocyte proliferation. Used for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.

Cyclosporine (Sandimmune, Neoral)

Calcineurin inhibitors that diminish IL-2production in activated T cells. These agents bind to the intracellular immunophilin cyclophilin, interfering with the action of calcineurin, which inhibits nuclear translocation of the nuclear factor of activated T cells (NFAT).

Tacrolimus (Prograf)

Calcineurin inhibitor that diminishes IL-2 production in activated T cells. Binds to intracellular immunophilin, FKBP, interfering with the action of calcineurin, which inhibits nuclear translocation of the NFAT. FDA approved for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.

Sirolimus (Rapamune)

Inhibits lymphocyte proliferation by interfering with signal transduction pathways. Binds to immunophilin FKBP to block action of mTOR. FDA approved for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.

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