Islet Cell And Pancreatic Transplantation

The dream of every patient with type 1 DM is to permanently rid themselves of the need to administer exogenous insulin on a daily basis. Islet cell and pancreatic transplantation has the potential to achieve this aim.

Islet cell transplantation

The concept of transplanting pieces or extracts of pancreas in patients with diabetes is over a century old. By the 1980s, reports of successful allogeneic islet transplantation with the use of conventional immunosup-pression and purified human islets from cadaveric donors began to appear. However, the overall rates of success internationally were reported to be less than 10%. In 2000, Shapiro and co-workers in Edmonton reported a 100% success rate in seven patients. The Edmonton patients were highly selected and a novel steroid-free immunosuppression regimen was used consisting of pre- and post-transplant daclizumab (an anti-interleukin 2 receptor monoclonal antibody), maintenance sirolimus and low-dose tacrolimus. An adequate mass of freshly isolated islets usually from two sequential donors was freshly transplanted by embolization into the liver through a small catheter placed under fluoroscopic guidance into the main portal vein. In an extended series of 32 consecutive patients with type 1 DM treated in Edmonton, the 1-year rate of sustained insulin independence was 85%. At present, the Edmonton protocol, or variants thereof, is being subjected to trials at several other international centers, with some centers already reporting successful cases. Clearly, there are many hurdles to overcome before islet cell transplantation can be a more universal technique not least of which is the skill in preparing the islets and the availability of donor pancreases.

Whole-pancreas transplantation

Until the advent of successful islet cell transplantation, whole-pancreas transplantation was the only technique that could consistently restore endogenous secretion of insulin responsive to normal mechanisms of feedback control. Many thousand (over 15 000 up to 2001) pancreatic transplantations have been performed worldwide, the majority of which have been simultaneous pancreas-kidney transplants (SPKs). Some centers, for example the Minnesota group, have been enthusiastic advocates of pancreas transplants alone (PTA) for selected patients. Surgical techniques have improved greatly over the past few decades and have incorporated both enteric and bladder drainage of the exocrine pancreas. Significant advances in immunosuppressive regimens, particularly with the introduction of the use of tacrolimus as an immunosuppressant, have contributed to better outcomes for transplanted patients. For SPK recipients the actuarial survival of patients and of functional pancreas grafts with complete independence from insulin are 94% and 89% at 1 year and 81% and 67% at 5 years, respectively. The results for PTA grafts remain inferior to SPK grafts with pancreas graft survival being significantly lower.

SPK remains an excellent treatment option for diabetic patients in advanced renal failure, while PTA may transform the lives of those with rapidly advancing microvascular complications or serious hypoglycemic unawareness, although life-long immunosuppression will remain an issue. Undoubtedly, further progress will be made especially with regard to immunosuppressive regimens; however, the problem of a shortage of cadaver organs will always exist, although some centers have employed the use of living donor segmental pancreas transplants.

It is speculated that further success with islet cell transplantation may reduce the need for SPK or PTA transplantation and improved diabetes treatments may obviate the need for both.

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