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The Ultimate Gift
A
newsletter from the transplant team
at Rhode Island Hospital
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Pancreas Transplantation
Since the first performance of pancreatic transplantation in humans
by Kelly and his associates at the University of Minnesota in 1966
the procedure has come of age. As of June 2005, the International
Pancreas Transplant Registry (www.iptr.umn.edu)
had recorded more than 19,600 pancreatic transplants, out of which
more than 14,300 were done in the United States. Traditionally pancreatic
transplants have been performed in the patient with diabetic nephropathy
requiring kidney transplantation. These patients already require
chronic immunosuppression and a functioning pancreas transplant
provides the most efficacious method for achieving a normal glucose
and hemoglobin A1C. In this setting there are two options, either
performing a simultaneous pancreas and kidney transplantation (SPK)
where one cadaver donor provides both the kidney and the pancreas;
or pancreas after a previously performed kidney transplant (PAK).
More contentious is pancreas transplant alone (PTA) in a patient
with no diabetic nephropathy, where the trade off of achieving normoglycaemia
with the possible complications of chronic immunosuppression has
to be weighed closely.
Currently the whole organ obtained from a cadaver donor is used.
The organ is placed in the pelvis opposite to the kidney transplant
and receives its blood supply through the iliac vessels. In addition
to the endocrine output of insulin secretion the pancreas allograft
also produces the exocrine secretion of bicarbonate and a rich mixture
of digestive enzymes. It is the need of draining this secretion,
which is responsible for most of the post-operative surgical complications
associated with this procedure. The pancreas allograft can either
be drained into the small intestine or the bladder. The urinary
output of the amylase in bladder-drained cases provides a sensitive
indicator for early detection of rejection of the pancreatic allograft.
However there is an increased incidence of late urological complications
after bladder drainage of the pancreas allograft, including severe
hematuria, and a proportion requires conversion to enteric drainage.
The improvement in immunosuppression, and consequent reduction in
rejection rates, as well as more frequent use of percutaneous allograft
biopsy for diagnosing rejection, has swung the trend towards primary
enteric drainage.
A relatively newer surgical innovation has been portal venous drainage
of the pancreas allograft. The traditional systemic venous drainage
achieves euglycemia at the expense of hyperinsulinemia. Portal venous
drainage replicates the physiological state and due to the first
pass effect achieves euglycemia with normal insulin levels. There
is also some indication that there may be an immunological advantage
as well for the portal-drained pancreata, but the difference is
small. Patient survival at one year for 2005 to 2005 U.S. cadaveric
pancreas transplants was at least 94% in all categories (SPK 95%;
PAK 94%; PTA 98%). Pancreas graft survival rate at one year (1996
to 2005 data, U.S. cadaveric SPK) was 84.7%; kidney graft survival
was 92%. For solitary pancreas transplants pancreas graft survival
at one year was 78.5% for PAK and 78.2% for PTA.
Indications for pancreas transplantation:
- Presence of insulin-requiring diabetes mellitus
- Ability to withstand surgery and immunosuppression
- Adequate cardiopulmonary function
- Absence of organ system failure (other than kidney: Degree of
nephropathy for SPK creatinine clearance < 30mL/min; for PAK
> 40 mL/min.)
- Emotional and psychosocial suitability
- Presence of two or more diabetic complications:
- Proliferative retinopathy
- Nephropathy (hypertension, proteinuria, decreased glomerular
filtration rate)
- Peripheral or autonomic neuropathy
- Microangiopathy
- Accelerated atherosclerosis
- Glucose hyperlability, hypoglycemia unawareness
Absolute contraindications
- Insufficient cardiovascular reserve (coronary angiography with
uncorrectable or untreatable coronary artery disease, or recent
myocardial infarction)
- Active infection
- History of malignancy treated within the past three years (excluding
non-melanoma skin cancer)
- Positive HIV serology
- Positive hepatitis B surface antigen serology
- Active, untreated peptic ulcer disease
- Ongoing substance abuse (drug or alcohol)
- Major ongoing untreated psychiatric illness
- Recent history of medical noncompliance
- Inability to provide informed consent
- Any systemic illness that would severely limit life expectancy
or compromise recovery
- Significant, irreversible hepatic or pulmonary dysfunction
- Positive lymphocytotoxic cross-match
Relative contraindications
- Age less that 18, or greater than 50 years
- Recent retinal hemorrhage
- Symptomatic cerebrovascular or peripheral vascular disease
- Absence of appropriate social support network
- Extreme obesity (greater that 150% ideal body weight)
- Active smoking
- Severe, untreatable peripheral vascular (aorto-iliac) disease
Risk factors
- History of myocardial infarction, congestive heart failure or
previous open-heart surgery
- History of major amputation or peripheral bypass graft
- History of cerebrovascular event or carotid endarterectomy
- History of hypercoagulable syndrome
Pancreas Transplantation at Rhode Island Hospital
Our transplant program received approval to start SPK and PAK transplants
in June 2005, when we started to list diabetic patients who had
stable kidney allografts for PAK transplants and also suitable diabetic
patients on the kidney waiting list for SPK transplants. The New
England Organ Bank does not maintain a separate list for SPK recipients
and only provides an opportunity for a SPK when the patient reaches
the top 12 of the entire region kidney list. This would mean a wait
of three to four years depending on the blood group of the patient.
The first PAK transplant was done at Rhode Island Hospital on October
24, 2005. Since then a total of 13 pancreas transplants (11 PAK
and 2 SPK) have been done in 12 patients. In two cases (one PAK
and one SPK) grafts were lost because of thrombosis occurring on
post-transplant days one and eight. The patient with the PAK transplant
thrombosis underwent a second pancreas transplant, four and a half
months later, which has been working well for the past year. The
remaining 11 pancreas allografts are working well with hemoglobin
A1C in the range of 4.5 to 6, over a follow-up of 2 to 21 months.
The patient and graft survival for one year is 100% and 84% respectively.
There have been three deaths on the waiting list, emphasizing the
high cardiovascular risk factors due to previous end-stage renal
disease and continuing diabetes.
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