Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation.

Stresses encountered during human islet isolation lead to unavoidable ß-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, ß-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less ß-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.

Prior surgery determines islet yield and insulin requirement in patients with chronic pancreatitis.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TP-IAT) is safe and effective in the management of intractable pain associated with chronic pancreatitis (CP). Prevention of pancreatogenic diabetes after TP-IAT is related to islet yield from the diseased pancreas. The purpose of this study is to compare islet yield and insulin requirement in the 76 patients who underwent different surgical procedures before TP-IAT at the Medical University of South Carolina between 2009 and 2011. METHODS: Patients were grouped into four categories based on the operation they had before TP-IAT: transduodenal sphincteroplasty/no prior surgery (n=50), Whipple or Beger procedure (n=14), distal pancreatectomy (n=8), or lateral pancreaticojejunostomy (n=4). Islets were harvested from pancreases of those patients at our current good manufacturing practice facility. Total unpurified islets were transplanted into patients via portal vein infusion. Pancreatic fibrosis, islet yield, cell viability, and insulin requirement were measured. RESULTS: The pancreases of transduodenal sphincteroplasty/no prior surgery and Whipple or Beger procedure patients were less fibrotic and had higher islet yield compared with those who had distal pancreatectomy or lateral pancreaticojejunostomy. Higher islet yield also correlated with a greater diabetes-free rate and a lesser insulin requirement at the following intervals: preoperative, postoperative, and 6 months after TP-IAT. CONCLUSIONS: Prior surgery is strongly correlated with the extent of pancreatic fibrosis, islet yield, and insulin requirements in CP patients undergoing TP-IAT. The history of prior pancreatic resection and drainage procedures may be used to predict postoperative islet function and help to determine the optimal timing for TP-IAT in CP patients.