Extraordinary Medicine
Pancreas Transplantation Cellular or the Whole Organ? Peter Stock, MD
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iabetes mellitus impacts more than 130 million people worldwide, and in the U.S. it has been reported that one of every eight health care dollars is directed to the treatment of diabetes and its secondary complications. The importance of tight control with intensive insulin therapy in preventing the development of the neuropathy, nephropathy, retinopathy, and cardiovascular disease was well documented in the Diabetes Control and Complication Trial (DCCT). Unfortunately, even tight control could not prevent the development of the secondary complications, and these severely impacted the quality of life and risk of life-threatening hypoglycemic events. Successful solid-organ pancreas transplantation has achieved insulin independence and stabilized the progression of many of the secondary complications of diabetes. Unfortunately, many of these complications have progressed too far by the time most health care providers feel that the risks of surgery and immunosuppressants are justified. However, the results of the surgical procedure have improved dramatically in the last five years, shifting the risk/benefit ratio in favor of pancreas transplantation. Nonetheless, it is clear that a number of patients cannot tolerate the rigors of the extensive surgical procedure. In addition, it is also evident that earlier intervention prior to the development of secondary complications will be facilitated by a less invasive approach. In these respects, islet transplantation has significant benefits over pancreas transplantation. With an increasing population of diabetic patients seeking beta-cell replacement, it is important that health care providers have a current knowledge of the risks and benefits associated with either cellular or solid-organ beta-cell
replacement. This information will be essential to help patients adequately gauge the risk/benefit ratio of either strategy. Both cellular (islet cell) and solidorgan pancreas transplantation have had increasing success in achieving insulin independence for many patients. Whether to pursue the more physiologically stressful solid-organ transplant or to choose islet-cell infusion is often a difficult choice. Obviously, the decision should be based on the current success rate for each procedure, as well as the ability of the recipients to tolerate the physiologic stress associated with these interventions. The success of solid-organ pancreas transplantation, as defined by insulin independence, has increased dramatically over the last several years. The better results are principally due to improved strategies in terms of preventing both the alloimmune and autoimmune responses against the transplanted organ. Current rejection rates following simultaneous pancreas/kidney transplants have decreased from more than 80 percent to less than 20 percent in the last five years. The immunosuppressive regimens employ a lymphocyte-depleting agent used at the time of transplant (induction therapy), followed by maintenance therapy with the calcineurin inhibitor (CI) tacrolimus and the antiproliferative agent mycophenolate mofetil (MMF). These strategies have permitted the elimination of the beta-cell toxic steroids from maintenance therapy. Using steroid-free regimens, the rejection rates of this previously very im-
18 San Francisco Medicine November 2006
munogenic transplant have been reported at less than 10 percent (Kaufman et al. 2002; Freise et al. 2002). This very low incidence of acute rejection of either the kidney or the pancreas has resulted in better long-term results. The three-year pancreas allograft survival reported by the International Pancreas Transplant Registry, as defined by insulin independence, approximates 80 percent for pancreases performed either simultaneously with a kidney transplant (SPK) or after a kidney transplant (PAK). Pancreas transplants performed in the preuremic Type I diabetic patient (PTA) historically have had poorer results. The reasons for these results in this group of patients as compared to SPK or PAK patients relate to both immunologic and technical complications. From a technical standpoint, the preuremic patient is more likely to clot off the pancreas, since the platelets function normally in this group as compared to the uremic transplant recipient. This technical hurdle has been overcome with the use of perioperative anticoagulation. The immunologic hurdles have been overcome with the better immunosuppressive regimens previously described. As a result, the outcomes following pancreas transplant alone in the preuremic recipient are now approximating the results following SPK and PAK. This has given many transplant centers the impetus to increase the frequency of pancreas transplant performed in the preuremic patient, which has the benefits of preventing not only the potentially life-threatening hypoglycemic
“It has been reported that one of every eight U.S. health care dollars is directed to the treatment of diabetes and its secondary complications.�
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