Pancreas transplantation

INTRODUCTION

The discovery of insulin by Banting and Best nearly 100 years ago made diabetes a treatable disease. Further developments, including synthetic short- and long-acting insulin, portable blood sugar monitoring and insulin pumps, have all improved diabetes treatment. Despite this, many patients will suffer from the secondary complications of diabetes, including retinopathy, neuropathy, nephropathy and premature cardiovascular disease. Pancreas transplant offers the ability to restore normoglycaemia in type 1 and selected type 2 diabetics. It aims to replace β-cell function, reduce short- and long-term complications of diabetes and increase long-term survival. The first pancreas transplant was performed in 1966 and since then there have been >50 000 pancreas transplants worldwide. The development of modern induction and maintenance immunosuppression as well as improvements in surgical techniques have led to excellent outcomes following pancreas transplant. However, transplantation remains a major surgical procedure in a patient population with multiple comorbidities and therefore it is important to select the patients who are most likely to benefit.

Who is eligible for a pancreas transplant?

Of pancreas transplants in the UK, 90% are performed as part of a simultaneous pancreas and kidney (SPK) transplant [1]. This is the treatment of choice for patients with type 1 diabetes and diabetic nephropathy with an estimated glomerular filtration rate <20 mL/min/1.73 m². Transplantation can also be considered in type 2 diabetics with renal failure who have a body mass index <30 kg/m² with low insulin requirements. In patients who have already received a living or deceased kidney transplant, a pancreas after kidney transplant can be considered.

Pancreas transplant alone is reserved for patients with diabetes complicated by frequent, severe metabolic complications despite optimum insulin therapy. These patients have severe hypoglycaemic unawareness but normal or near-normal renal function. Patients must have had at least two severe hypoglycaemic episodes, as defined by the American Diabetes Association, within the last 24 months and be assessed by a diabetologist to have disabling hypoglycaemia [2].

The operation

The pancreas transplant operation is a major surgical undertaking and involves meticulous preparation of the pancreas graft prior to transplant. The donor iliac vessels are used to form a ‘Y-graft’ between the recipient’s common iliac artery and the splenic and superior mesenteric arteries of the pancreas. The portal vein is commonly (but not exclusively) anastomosed directly to the inferior vena cava (IVC). Following reperfusion, the duodenum is anastomosed to a loop of small bowel for drainage of the exocrine secretions (Figure 1). For pancreas transplant alone, the duodenum is sometimes anastomosed to the bladder so urinary amylase can be monitored (Figure 1).

What are the potential risks of a pancreas transplant?

The pancreas tolerates cold ischaemia poorly and can develop pancreatitis after transplantation. The pancreas is a highly vascularized organ and bleeding is not uncommon after implantation. There can also be a leak from the duodenal–jejunal anastomosis and thrombosis can form in either the arterial Y-graft or the portal vein. Any one of these complications results in a relaparotomy rate of 20–30%, necessitating graft pancreatectomy in up to 10–15% of recipients [3]. The 1-year mortality following pancreas transplant is 3% [1].

All transplant recipients need to take maintenance immunosuppression. This usually consists of a calcineurin inhibitor such as tacrolimus and an anti-metabolite such as mycophenolate. Some recipients receive low-dose steroids, but many are on steroid-sparing regimes. As a result of this immunosuppression, all transplant recipients have an increased risk of infection and malignancy compared with the general population. This is particularly pertinent for pancreas transplant alone, as the risks of hypoglycaemic coma have to be carefully weighed against the risks of surgery and immunosuppression.

What are the outcomes of pancreas transplantation?

In the UK, the 1- and 5-year pancreas graft survival is 90% and 81%, respectively [1]. In patients with renal failure, there is a clear survival benefit from SPK transplant. In Scotland, the 10-year survival of diabetic patients ages 45–64 years on dialysis is only 10%. For patients in the younger age group of 18–45 years, the 10-year survival is still only 50% [4]. Similar survival statistics are found elsewhere in Europe and in the USA [5, 6]. This compares with 1-, 5- and 10-year patient survival following listing for SPK transplant in patients ages 18–60 years of 97%, 86% and 76%, respectively [1]. Large registry studies have demonstrated that long-term patient survival is superior in type 1 diabetics that receive an SPK transplant compared with those who receive a deceased donor kidney transplant [7]. This survival advantage is less evident when compared with those who receive a living donor kidney transplant. This may be because the living donor transplant recipients tend to be transplanted earlier and have better kidney function, outweighing the disadvantage of continued diabetes and diabetic complications. However, a recent study showed that if one examines longer-term outcomes up to 30 years, SPK transplant conveys a survival advantage compared with a matched group of living donor kidney recipients after 10 years [8].

The outcomes for pancreas transplant alone are inferior to those for SPK and the 5-year graft survival in the UK is <50% [1]. This is most likely due to unrecognized pancreas rejection, as deranged blood sugars are a late sign in rejection and the pancreas is challenging to biopsy. Co-transplant of the kidney with the pancreas allows the kidney to act as a surrogate to detect rejection in the pancreas (which is concurrent 90% of the time).

A number of studies have looked at the effect of pancreas transplant on diabetic complications. With a functioning pancreas graft, the progression of diabetic complications is slowed or stopped [9]. A proportion of patients experience an improvement in the symptoms from diabetic neuropathy and retinopathy following transplant. Overall, patients report an improvement in quality of life following pancreas transplant. However, this is not the case if patients undergo transplant and the pancreas fails or is removed [10].

What are the alternative treatments?

For all patients being considered for pancreas transplant, medical treatment of diabetes should first be optimized. Pancreas transplant is reserved for those patients who have already developed irreversible damage from diabetes, such as diabetic nephropathy, or for patients with failed medical management of impaired awareness of hypoglycaemia. An alternative and lower-risk option to pancreas transplant for such patients is islet cell transplantation. Although islet cell transplant does not usually result in long-term insulin independence, >90% of recipients regain their awareness of hypoglycaemia [1]. For those patients who are deemed not fit enough for an SPK transplant, simultaneous islet kidney transplant or islets after kidney transplant can be considered. A summary of pancreas transplant and islet cell transplant options is illustrated in Figure 2.

CONFLICT OF INTEREST STATEMENT

None declared.

REFERENCES