Successful pancreas transplantation restores normal control of glucose metabolism and obviates the need for insulin therapy in patients with diabetes mellitus. Improved control of blood glucose levels in diabetes undoubtedly reduces the risk of secondary complications such as retinopathy, peripheral vascular disease and nephropathy. However, in considering the indications for pancreas transplantation, these advantages have to be weighed carefully against the risks posed both by the transplant procedure itself and by the immunosuppressive therapy required to prevent graft rejection. For most patients with diabetes, the additional risks associated with pancreas transplantation and immunosuppression are such that the operation can only be justified when kidney transplantation for diabetic nephropathy is also being undertaken. The only additional risks of pancreas transplantation in such patients relate to the transplant operation itself. In the USA, around half of all diabetic patients undergoing kidney transplantation also receive a pancreas transplant. In most cases, the kidney and pancreas are obtained from the same donor, so-called ‘simultaneous pancreas and kidney transplantation’ (SPKT). Sometimes pancreas transplantation is performed in patients who have already undergone successful kidney transplantation — ‘pancreas after kidney transplantation’ (PAKT). Occasionally, pancreas transplantation alone (PTA) can be justified, for example to treat labile diabetes or hypoglycaemic unawareness.
Careful patient selection is essential to avoid excessive mortality and morbidity. The procedure is usually reserved for those patients with type I diabetes who are relatively young (under the age of 50 years) and do not have advanced coronary artery disease or peripheral vascular disease. Echo-cardiography and coronary angiography are mandatory during assessment of recipient suitability for transplantation.
Most centres now perform transplantation of the whole pancreas together with a segment of duodenum, essentially as pioneered by Lillehei in1966. Segmental pancreas transplantation is still performed occasionally, especially in France. SPKT is usually performed through a midline incision. The pancreas graft is placed intraperitoneally in the pelvis, usually on the right, and the kidney graft is placed either intraperitoneally or extraperitoneally on the left side. The donor vessels of the pancreas graft are anastomosed to the recipient iliac vessels and the exocrine secretions are dealt with by anastomosing the graft duodenum to either the bladder (urinary drainage) or the small bowel (enteric drainage). The pancreas graft functions immediately after revascularisation, although supplementary insulin may be required for a few days. Technical complications usually occur early and include vascular thrombosis of the graft (5—10 per cent) and anastomotic leaks. Wound infection occurs in around 10 per cent of patients and intra-abdominal infection is relatively common. The specific complications of enteric drainage include intra-abdominal sepsis and gastrointestinal haemorrhage (anastomotic). Bladder drainage of the exocrine pancreas may result in the following complications:
• bladder/duodenal anastomotic leaks;
• cystitis (due to effect of pancreatic enzymes);
• urethritis/urethral stricture;
• reflux pancreatitis;
• urinary tract infection;
• metabolic acidosis (due to loss of bicarbonate in the urine).
Urinary drainage of the pancreas has the advantage that urinary amylase levels can be used to monitor for graft rejection. However, after bladder drainage, urinary complications are common and, in around 20 per cent of cases, are severe enough to require conversion to enteric drainage. Many centres now prefer primary enteric drainage after SPKT. Acute rejection after SPKT usually involves both the kidney and pancreas graft and serum creatinine can be used, therefore, as a surrogate marker for pancreas graft rejection. Urinary drainage is still preferable after PTA and PAKT because it allows pancreas graft rejection to be monitored by serial measurement of urinary amylase. A fall in urinary amylase is indicative of acute rejection. Measurement of blood glucose levels are less useful as an early indicator of rejection. Acute graft rejection is common but usually responds to treatment with steroids.
Results of pancreas transplantation
The results of pancreas transplantation have improved significantly over the last decade. After SKPT, the 1-year patient survival rate is greater than 90 per cent, and the 1-year graft survival rate for pancreas and kidney grafts, respectively, is 80 and 90 per cent. Most deaths are due to cardiovascular complications or overwhelming infection. Patient and kidney graft survival after SKPT in patients with diabetic nephropathy are at least as good as after kidney transplant alone in this group. The results of PTA are not as good as after SKPT (1-year pancreas graft survival 70 per cent) because acute rejection is more difficult to monitor in the absence of a kidney allograft. The aim of pancreas transplantation is to provide freedom from insulin treatment and to improve the quality of life. The extent to which pancreas transplantation halts the progression of the secondary complications of diabetes is still unclear.
Transplantation of isolated pancreatic islets
Treatment of diabetes by transplantation of isolated islets of Langerhans is a more attractive concept than vascularised pancreas transplantation because major surgery and the potential complications of transplanting exocrine pancreas are avoided. Pancreatic islets for transplantation are obtained by mechanically disrupting the pancreas after injection of collagenase into the pancreatic duct. The islets are then purified from the dispersed tissue by density gradient centrifugation and can be delivered into the recipient liver (the optimal site for transplantation) by injection into the portal vein. Islet transplantation has been performed in diabetics receiving immunosuppression because of a kidney transplant. Although some degree of islet cell function occurs initially this is not sustained. Obtaining a critical mass of islet tissue for transplantation is problematic and isolated pancreatic islets are particularly susceptible to graft rejection. Attempts have been made to protect isolated islet cells from rejection by encapsulating them inside semipermeable membranes. The protective membranes are designed with a pore size that allows insulin to pass through but prevents antibodies and leucocytes from reaching the islets, thereby avoiding the need for immunosuppressive therapy. A major attraction of this approach is that islets isolated from animals can be used, and bioartificial pancreas grafts containing xenogeneic islets are currently under evaluation.
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