Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis: Breaking Down Barriers

Abstract

In full bloom, chronic pancreatitis (CP) is a very serious, debilitating disease typified by unrelenting, severe abdominal pain requiring daily narcotics. Malabsorption, diarrhea, significant weight loss, an inability to work and/or parent, depression, and very poor overall quality of life (QOL) are associated complications. Once thought to be caused chiefly by alcohol abuse, it is now appreciated that CP has many potential etiologies involving genetic and familial influences, developmental abnormalities, and trauma. Cystic fibrosis, pancreatic divisum, sphincter of Oddi abnormalities and gall bladder disease are common associations. Medical treatment varies widely, ranging from antioxidants and pancreatic enzyme replacement to pancreatic duct stents, surgical drainage, and partial pancreatectomy for involved areas. The most definitive treatment is total pancreatectomy with intrahepatic transplantation of the patient’s own islets after isolation from the resected pancreas (TP/IAT) to prevent diabetes. TP/IAT was first performed more than 37 years ago by Sutherland et al (1) and Najarian et al (2). Since then, hundreds of procedures have been performed, chiefly at the University of Minnesota, the University of Cincinnati, and Leicester General Hospital in the United Kingdom. In the past 1–2 decades, many new programs have begun. In the largest series of 409 consecutive recipients of TP/IAT, the results showed an 85% success rate for pain resolution or improvement (3). In those who received approximately greater than 300 000 autoislets (the normal number for a healthy pancreas is 1 million) or greater than 5000 islets/ kg, the results showed a 94% posttransplant rate for glycated hemoglobin levels less than 7.0% without using exogenous insulin treatment. This rate decreased to 86% and 71% when less than 5000 but greater than 2500 and less than 2500 islets/kg were used, respectively. Thus, transplantation of lesser numbers of autoislets leads to lesser degrees of success, although many of these recipients are able to maintain good glucose control with only oncedaily injections of 10–15 U of long-acting insulin. The duration of successful islet function and relatively good glucose control in some instances has exceeded 25 years, and, increasingly, young children undergo TP/IAT with impressive growth spurts after the transplant and a return to school and normal physical activities (4). One caveat is the as-yet-unsolved problem of a significant prevalence of unexplained hypoglycemia, even in the absence of exogenous insulin treatment, which is related to but probably not completely explained by defective glucagon responses to hypoglycemia from intrahepatic islets (5, 6). There are significant barriers to embracing this modality to treat chronic pancreatitis. Most people in the medical field are surprised when they are confronted by a new patient who reports they have undergone total pancreatectomy. TP/IAT recipients report not infrequently that they have been told by their doctors that no one can live without a pancreas. Other barriers include the facts that only a few highly experienced TP/IAT centers are available; reluctance of insurance companies that, even though willing to cover the costs of total pancreatectomy, are not willing to cover the costs of islet isolation; and the infrequency with which this procedure is discussed in standard textbooks of medicine and during continuing medical education courses. Many institutions that consider setting up TP/IAT programs are daunted by the expense of setting up islet isolation facilities. In recent years, however, there