Pediatric Islet Autotransplantation: Indication, Technique, and Outcome

Abstract

Chronic pancreatitis is a rare disease in childhood. However, when severe, a total pancreatectomy may be the only option to relieve pain and restore quality of life. An islet autotransplant performed at the time of pancreatectomy can prevent or minimize the postsurgical diabetes that would otherwise result from pancreatectomy alone. In this procedure, the resected pancreas is mechanically disrupted and enzymatically digested to separate the islets from the surrounding exocrine tissue, and the isolated islets are infused into the portal vein and engraft in the liver. Because patients are receiving their own tissue, no immunosuppression is required. Islet autotransplant is successful in two thirds of children-these patients are insulin independent or require little insulin to maintain euglycemia. Factors associated with a more successful outcome include a younger age at transplant (<13 years), more islets transplanted, and lack of prior surgical procedures on the pancreas (partial pancreatectomy or surgical drainage procedures).

β-Cell Dysfunction in Chronic Pancreatitis

“…Recently, it is demonstrated that severe histopathological changes were associated with lower islet yield for auto transplantation indicating greater islet destruction in severely inflamed and fibrotic pancreas [6,7]. On the other hand, islets that were autotransplanted into the liver via portal vein were found to have improved functions with time [8]. This suggests that islet autotransplantation early in the progression of symptomatic disease can retain b-cell function.…”

Near-Euglycemia Can Be Achieved Safely in Pediatric Total Pancreatectomy Islet Autotransplant Recipients Using an Adapted Intravenous Insulin Infusion Protocol

“…It should be noted that the islet yield for many patients was moderate to high (4,830 -3,692 IEQ/kg), and these transplanted islets may contribute to better glycemic control. [1][2][3][4][5] The rationale for targeting a physiologic glucose range in our transplant recipients is to avoid hyperglycemia-induced b-cell loss. This concept is supported by a large body of animal studies as well as ongoing work in clinical islet transplant recipients at our institution.…”

“…The surgical procedure of TPIAT was performed as previously described, 1 with minor modifications to the gastrointestinal reanastamosis. In brief, a TP, partial duodenectomy, Roux-en-Y duodenojejunostomy, choledochojejunostomy, and splenectomy were performed.…”

“…In this procedure, the islets are isolated from the remainder of the pancreas, infused back into the portal vein, and subsequently engraft in the liver sinusoids where they release insulin in response to ambient blood glucose (BG). 1 Approximately 40% of children discontinue insulin therapy after TPIAT, with islet mass being the most important measurable predictor of subsequent diabetes risk. [2][3][4][5][6] During isolation, islets are stripped of their native arteriolar blood supply.…”

Accuracy of Continuous Glucose Monitoring in Patients After Total Pancreatectomy with Islet Autotransplantation

“…All participants underwent total pancreatectomy as previously described [28][29][30] along with infusion of the patient's own islet cells into a tributary of the portal vein, or if elevated portal pressures prevented infusion of all the islets intraportally, the remaining islets were transplanted into the peritoneal cavity. Immediately after surgery, all patients were started on a continuous intravenous (IV) insulin infusion protocol with the goal of maintaining BG in the range of 80-125 mg/dL.…”