Pancreas transplant pearls

Pancreas transplantation is considered the treatment of choice for patients with refractory Type I Diabetes Mellitus. The first pancreas transplant was described in 1967 by Kelly et al. (pictured) and was performed with a simultaneous kidney transplant in a 28 year old woman with type 1 diabetes. Early efforts were associated with a high complication rate, but this has improved over time. Pancreas transplantation now usually occurs in three settings:

1. Simultaneous Pancreatic and Kidney transplant (SPK) from the same deceased donor
2. Pancreas after Kidney transplant (PAK): generally from two different deceased donors at two different time points
3. Pancreas transplant alone: for patients with severe Type I DM, but relatively spared kidney function.

Recurrent severe hypoglycaemic events are the most common indication. See Melissa’s review on outcomes here.

Some of the variation in surgical techniques and acute management strategies are discussed below.

Bladder vs enteric duct drainage
Bladder – advantages include the easy availability of urine amylase measurements which can be used as a marker of graft function. Biopsies can be relatively easily obtained across the bladder wall from cystoscopy. The major complication from the bladder-drainage technique is loss of bicarbonate-rich fluid causing metabolic acidosis and volume depletion. Additional problems include bladder leak, reflux pancreatitis, chemical cystitis/urethritis, bladder infections, bladder tumours, bladder calculi, urethral stricture, epididymitis, prostatitis, and prostatic abscesses.

Enteric – due to the relatively high risk of complications with bladder drainage, improvements in immunosuppresison and less need for frequent monitoring, enteric drainage has become the favoured method. Indeed, approximately 35% of bladder drained grafts ultimately require enteric conversion due to complications associated with bladder drainage. Currently, around 80% of SPK’s in the United States are performed with enteric drainage.

Systemic vs Portal drainage of pancreatic venous effluent

The Meeting Place, St. Pancras Station, London

Historically, systemic venous drainage has been the more common procedure, primarily due to easier technical considerations. Systemic venous drainage results in higher overall insulin levels (two to three times higher than with portal drainage), as the secreted blood does not have to pass through the liver first, in comparison to drainage into the portal system. There is limited, but conflicting, evidence over which method has the better outcome.

Immediate outcomes
In most cases of pancreatic transplantation glucose concentrations normalize immediately following implantation of the pancreas graft. However, delayed onset of normoglycaemia can result from size mismatch of the graft, arterial or venous graft thrombosis, graft injury during retrieval or transport, pancreatitis or acute rejection.
HbA1c is usually normal by one month after the operation.

C peptide levels can be measured as a surrogate of insulin levels. Also, if for some reason exogenous insulin reintroduction is required, the C peptide level can be used to monitor for recovery of endogenous insulin production from the graft.

In acute pancreatic rejection, inflammation tends to be directed towards the acinar tissue, rather than the islets in the initial stages of disease – therefore, loss of glycaemic control is a relatively late marker of acute rejection. In SPK patients, it is unusual (less than 15%) for pancreatic rejection to occur in the absence of concomitant kidney rejection; therefore a rising creatinine should ring alarm bells for both organs.

In those with bladder drainage, a fall in urinary amylase of 25% from baseline on two consecutive measurement more than 12 hours apart can signal underlying rejection. The fall in urinary amylase generally occurs 24-48 hours before the development of hyperglycaemia.

Hopefully some of these pearls will prove useful when next managing a new pancreatic transplant recipient on your service.

Finnian Mc Causland MD