Pancreas
transplantation
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 (Fig.
11.17). 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
• bladder/duodenal anastomotic leaks;
• cystitis (due to effect of pancreatic enzymes);
• urethritis/urethral stricture;
• reflux pancreatitis;
• urinary tract infection;
• haematuria;
• 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.