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

Abstract

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.

Figures

Fig.1. Type of surgery vs. final pellet weight and IEQ/kg transplanted

A. Average of islet IEQs transplanted per kilogram body weight in patients who had transduodenal sphincteroplasty or no prior surgery (TDS/NPS, light grey bars), Whipple/Beger Procedure (WB, dark grey bars), distal pancreatectomy (DP, black bars) and lateral pancreaticojejunostomy (LPJ, lined bars). B. Final average islet pellet weight (gram) after islet isolation and before transplantation was measured in the different patient groups. There is a significant difference of islet yield among different groups as analyzed by the ANOVA test (p<0.001).

Fig.2. Elapsed time (minutes) from tissue excision to islet transplant

Longer time is needed to process pancreases from patient who had TDS/NPS (light grey bar), compared to patients who had WB (dark grey bar), DP (black bar) or LPJ (lined bar) procedures before TP-IAT.

Fig.3. Percentage of diabetes-free patients in each group before surgery (A) and at 6 months after surgery (B)

Data represent percentages of patients who do not need insulin to control their blood glucose levels. TDS/NPS (n=50, light grey bars), WB (n=14, dark grey bars), DP (n=8, black bars) and LPJ (n=4, lined bars).

Fig. 4. Diabetes management at 6 months post-operative

A. Average daily insulin requirement in patients that need insulin injection. B. Percentage of patients who were C-peptide positive at 6 months after surgery. C. Patients’ HbA1c levels after TP-IAT. TDS/NPS (light grey bars), WB (dark grey bars), DP (black bars) and LPJ (lined bars, n=2). C-peptide level in LPJ group only include 2 patients, the other 2 values were missing at 6 months). All other measurements include all patients in each group.