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Sarcopenia defined as degenerative loss of skeletal muscle mass associated with aging, represents an objective parameter to measure frailty and to estimate patient’s physiologic reserves. It is a robust predictor of post-operative complications in transplantation and major oncologic surgeries. There is no data regarding the prevalence of sarcopenia in chronic pancreatitis or its impact on the outcome of patients undergoing TPIAT for CP. We sought to estimate the prevalence of sarcopenia, its impact on post-operative morbidity and prediction of islet yield and metabolic outcomes in patients undergoing TPIAT. Adult patients undergoing TPIAT between 2008 and 2018 were identified from our prospectively maintained database and were included if they had CT within 6 months before TPIAT. Skeletal muscle index (SMI) was evaluated by pre-operative CT at the level of L3 vertebra. Sarcopenia was defined as SMI

OBJECTIVES Chronic pancreatitis (CP) is an infrequent but debilitating complication associated with CFTR mutations. Total pancreatectomy with islet autotransplantation (TPIAT) is a treatment option for CP that provides pain relief and preserves β-cell mass, thereby minimizing the complication of diabetes mellitus. We compared outcomes after TPIAT for CP associated with CFTR mutations to CP without CTFR mutations. METHODS All TPIATs performed between 2002 and 2014 were retrospectively reviewed: identifying 20 CFTR homozygotes (cystic fibrosis [CF] patients), 19 CFTR heterozygotes, and 20 age-/sex-matched controls without CFTR mutations. Analysis of variance and χ tests were used to compare groups. RESULTS Baseline demographics were not different between groups. Postoperative glycosylated hemoglobin and C-peptide levels were similar between groups, as were islet yield and rate of postoperative complications. At 1 year, 40% of CF patients, 22% of CFTR heterozygotes, and 35% of control patients were insulin independent. CONCLUSION Total pancreatectomy with islet autotransplantation is a safe, effective treatment option for CF patients with CP, giving similar outcomes for those with other CP etiologies.

Background/Objectives Total pancreatectomy and islet autotransplant (TP-IAT) is a potential treatment for children with severe refractory chronic pancreatitis. Cultures from the resected pancreas and final islet preparation are frequently positive for microbes. It is unknown whether positive cultures are associated with adverse outcomes in pediatric patients. Methods We reviewed the medical records of children (n = 86) who underwent TP-IAT from May 2006–March 2015 with emphasis on demographics, previous pancreatic interventions, culture results, islet yield, hospital days, posttransplant islet function, and posttransplant infections. We compared outcomes in patients with positive (n = 57) and negative (n = 29) cultures. Results Patients with positive cultures had higher rates of previous pancreas surgery ( P = 0.007) and endoscopic retrograde cholangiopancreatography ( P P = 1.00) or prolonged hospital length of stay ( P = 0.29). Patients with positive final islet preparation culture showed increased rates of graft failure at 2 years posttransplant ( P = 0.041), but not when adjusted for islet mass transplanted ( P = 0.39). Conclusions Positive cultures during pediatric TP-IATs do not increase the risk of posttransplant infections or prolong hospital length of stay. Endocrine function depends on islet mass transplanted.

We investigated the impact of patient age and disease duration on islet isolation results, diabetes outcomes, and pain outcomes after total pancreatectomy with islet autotransplant (TPIAT) performed in 64 patients with hereditary pancreatitis due to PRSS1 gene mutation.We evaluated the association of patient age and disease duration on islet isolation results and opioid use at 1 year using logistic regression and on graft function using 1-way analysis of variance.Islet mass was negatively associated with increasing age and longer disease duration, with a 13% reduction (95% confidence interval [CI], 3%-22%) and 22% (95% CI, 14%-29%) reduction in islet equivalents per kilogram body weight (IEQ/kg) for each 5 years of age and disease duration, respectively. Full graft function was associated with younger age and shorter duration of disease (P0.01). Persistent opioid use (15% of patients at 1 year) increased with age (P = 0.05) and disease duration (P = 0.04).The TPIAT outcomes were adversely impacted by older age and prolonged disease. In particular, islet mass is lower and risk of diabetes high in older patients with prolonged disease. This should be considered when counseling this subgroup of TPIAT recipients on expected outcomes.

Human islet isolation and autotransplantation [autologous islet transplant (AUTX)] is performed to prevent or ameliorate brittle diabetes after total pancreatectomy performed for benign disease. The success or failure of the transplant can be associated with a profound impact on the individual's quality of life and even survival. AUTX offers unique insights into the effects of pancreas quality, islet number, isolation technique and alternate site engraftment on transplant efficacy. Herein, we review islet isolation with a focus on potential pathways to further optimize the endocrine outcome of AUTX, and compare and contrast differences in islet processing for AUTX and allotransplantation (allogeneic islet transplant).New knowledge of human islet biology and issues surrounding the engraftment process offer opportunities for innovative approaches toward optimizing islet cell transplantation.Improving the rate and durability of insulin independence in the often-times marginal dose model of AUTX may provide new insight toward improving the efficiency and durability of single donor islet (allogeneic islet transplant).

BACKGROUND The optimal enzyme blend that maximizes human islet yield for transplantation remains to be determined. In this study, we evaluated eight different enzyme combinations (ECs) in an attempt to improve islet yield. The ECs consisted of purified, intact or truncated class 1 (C1) and class 2 (C2) collagenases from Clostridium histolyticum (Ch), and neutral protease (NP) from Bacillus thermoproteolyticus rokko (thermolysin) or Ch (ChNP). METHODS We report the results of 249 human islet isolations, including 99 deceased donors (research n=57, clinical n=42) and 150 chronic pancreatitis pancreases. We prepared a new enzyme mixture (NEM) composed of intact C1 and C2 collagenases and ChNP in place of thermolysin. The NEM was first tested in split pancreas (n=5) experiments and then used for islet autologous (n=21) and allogeneic transplantation (n=10). Islet isolation outcomes from eight different ECs were statistically compared using multivariate analysis. RESULTS The NEM consistently achieved higher islet yields from pancreatitis (P

Background Using standard density gradient (SDG) ranges for human islet purification frequently results in islet loss and transplantation of lower islet mass. Measuring the densities of islet and acinar tissue beforehand to customize the gradient range for the actual COBE 2991 cell processor (COBE) purification is likely to maximize the recovery of islets. We developed an analytical test gradient system (ATGS) for predicting pancreatic tissue densities before COBE purification to minimize islet loss during purification. Methods Human islets were isolated from deceased donor (n=30) and chronic pancreatitis pancreata (n=30). Pancreatic tissue densities were measured before purification by the ATGS, and the density gradient range for islet purification in a COBE was customized based on density profiles determined by the ATGS. The efficiency of custom density gradients (CDGs) to recover high islet yield was compared with predefined SDGs. Results Pancreatic tissue densities from autografts were significantly higher than in allograft preparations. In allograft purifications, a higher proportion of islets were recovered using ATGS-guided CDGs (85.9%±18.0%) compared with the SDG method (69.2%±27.0%; P=0.048). Acinar contamination at 60%, 70%, and 80% cumulative islet yield for allografts was significantly lower in the CDG group. In autograft purifications, more islets were recovered with CDGs (81.9%±28.0%) than SDGs (55.8%±22.8%; P=0.03). CDGs effectively reduced islet loss by minimizing islet sedimentation in the COBE bag. Conclusions Using ATGS-guided CDGs maximizes the islet recovery for successful transplantations by reducing acinar contamination in allograft preparations and by reducing sedimentation of islets in the COBE bag in autograft preparations.