Search

Background/objectives: Chronic pancreatitis (CP) is associated with increased risk of calcium-oxalate kidney stones, likely due to enteric hyperoxaluria. However, the risk of kidney stones for patients with CP after total pancreatectomy with islet autotransplantation (TPIAT) is unknown. We aimed to evaluate kidney stone risk in patients with CP after TPIAT., Methods: A retrospective analysis of 629 patients who underwent TPIAT was conducted to identify patients who developed kidney stones post-TPIAT. Kaplan-Meier analysis estimated time to first event. An Anderson-Gill proportional-hazards analysis of all kidney stone events described key clinical associations., Results: Mean age at TPIAT was 33 years (SD 15.3, range 3-69); 69.8 % (n = 439) were female. The estimated chance of any kidney stone episodes by 5 years post-TPIAT was 12.8 % (95 % CI: 8.8-16.6 %); by 10 years, 23.2 % (CI: 17.5-28.6 %); by 15 years, 29.4 % (CI: 21.8-36.2 %). Significant associations with kidney stones post-TPIAT included older age (HR 1.25 per 10 years), smoking history (HR 1.72), mild chronic kidney disease (HR 1.96), renal cysts (HR 3.67), pre-TPIAT kidney stones (HR 4.06), family history of kidney stones (HR 4.10), and Roux-en-Y reconstruction (HR 2.68). Of the 77 patients who developed kidney stones, 34 (44.1 %) had recurrent episodes. Of 143 total kidney stone events, 35 (24.5 %) required stone removal, 79 (55.2 %) resolved spontaneously, and 29 (20.3 %) were missing this data., Conclusions: Patients with CP post-TPIAT commonly have kidney stones: nearly 3 in 10 have ≥1 kidney stone episodes within 15 years. Clinicians should be aware of this risk and counsel patients on prevention., Competing Interests: Declaration of competing interest MDB discloses research support from Viacyte, Dexcom; and consulting/advisory board relationships with Vertex. SJS serves as a consultant to UpToDate, Mirum, Renexxion, and WIC., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Total pancreatectomy and islet autotransplantation (TPIAT) for pancreatitis may induce risk for essential fatty acid deficiency (EFAD) due to exocrine pancreatic insufficiency and intestinal alterations. The prevalence of EFAD post-TPIAT is currently unknown., Methods: We abstracted essential fatty acid (EFA) profiles (n = 332 samples) for 197 TPIAT recipients (72% adult, 33% male). Statistical analyses determined the prevalence of, and associations with, EFAD post-operatively. EFAD was defined as a Triene-to-Tetraene ratio ≥0.05 if <18 years old, or ≥0.038 if ≥18 years old., Results: Prevalence of EFAD was 33%, 49%, and 53.5% at 1, 2, and ≥3 years. At 1-year post-TPIAT, older age at transplant ( P = 0.03), being an adult versus a child ( P = 0.0024), and obstructive etiology ( P = 0.0004) were significant predictors of EFAD. Only 6% of children had EFAD 1-year post-TPIAT versus 46% of adults. The alpha-linolenic acid levels were lower with lower body mass index at transplant ( P = 0.011). EFAD was associated with the presence of other intestinal diseases ( P < 0.0001)., Conclusions: One-third of individuals had EFAD 1-year post-TPIAT, highlighting the need for systematic monitoring. Older age at transplant increased risk and adults were more affected than children. Other diagnoses affecting intestinal health may further increase risk for EFAD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care ( n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group ( p = 0.027). A1AT increased after IAT in all groups ( p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period., Competing Interests: MB declares research support from Dexcom and Viacyte; consulting/DSMB membership with Vertex, Insulet, and consulting for Emerging Therapy Solutions. BJH holds equity in and serves as a paid executive officer and director of Diabetes Fee, Inc., a company that may commercially benefit from the results of this research. This interest has been reviewed and managed by the University of Minnesota in accordance with its Conflict of Interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abdel-Karim, Hodges, Herold, Pruett, Ramanathan, Hering, Dunn, Kirchner, Beilman and Bellin.)

Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n = 52, age 3-11 years) versus adolescents (n = 82, age 12-18 years). For MMTT, children consumed Boost HP and we sampled C-peptide and glucose repeatedly over 2 h. The trajectory of outcomes before and after TPIAT was compared between children and adolescents using data from pre-TPIAT and 3, 6 months, 1, 2, 3, and 4 years post-TPIAT and mixed linear models with a random effect for child. Cox regression was used to analyze time outcomes (e.g., time to first off insulin). Islet mass transplanted, measured as islet equivalents (IEQ), was higher in adolescents (p = .003) but IEQ/kg was higher in young children (p < .001) because of their lower weight. AUC C-peptide in young children increased somewhat over 4 years, but was stable in adolescents (p = .0013). AUC glucose increased more in adolescents over time post-TPIAT (p = .0024). Islet function by AUC C-peptide:AUC glucose ratio was better preserved in young children (p < .001). Adolescents were less likely to wean off insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of young age in islet graft survival after TPIAT. The greater likelihood of insulin independence in young children may be driven by better islet survival after transplant., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence., Methods: We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT., Results: We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females., Conclusion: Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment., Clinical Trial Notation: This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997)., Competing Interests: Declaration of competing interest MDB discloses support from Insulet (DSMB membership), Viaycte (research support), and Dexcom (research support)., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation., Methods: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP., Results: Children more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14-22 versus 11 days; IQR 8-14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT., Conclusions: Pancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children., Competing Interests: Declaration of competing interest MDB discloses the following: research support from Viacyte and Dexcom; advisory role (DSMB) for Insulet. LFL discloses the following: research support from Abbvie, consultant for Abbvie, speaker for Abbvie and Nestle. SJS discloses funding from Gilead and UpToDate. VKS is a consultant for Abbvie and Nestle, and he receives research support from Orgenesis and Theraly., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Total pancreatectomy with islet autotransplantation (TPIAT) involves pancreatectomy, splenectomy, and reinjection of the patient's pancreatic islets into the portal vein. This process triggers a local inflammatory reaction and increase in portal pressure, threatening islet survival and potentially causing portal vein thrombosis. Recent research has highlighted a high frequency of extreme thrombocytosis (platelets ≥1000 × 109/L) after TPIAT, but its cause and association with thrombotic risk remain unclear., Methods: This retrospective single-site study of a contemporary cohort of 409 pediatric and adult patients analyzed the frequency of thrombocytosis, risk factors for thrombosis, and antiplatelet and anticoagulation strategies., Results: Of 409 patients, 67% developed extreme thrombocytosis, peaking around postoperative day 16. Extreme thrombocytosis was significantly associated with infused islet volumes. Thromboembolic events occurred in 12.2% of patients, with portal vein thromboses occurring significantly earlier than peripheral thromboses. Portal vein thromboses were associated with infused islet volumes and portal pressures but not platelet counts or other measures. Most thromboembolic events (82.7%) occurred before the postoperative day of maximum platelet count. Only 4 of 27 (14.8%) of portal vein thromboses occurred at platelet counts ≥500 × 109/L. Perioperative heparin was given to all patients. Treatment of reactive thrombocytosis using aspirin in adults and hydroxyurea in children was not associated with significantly decreased thromboembolic risk., Conclusions: These results suggest that post-TPIAT thrombocytosis and portal vein thromboses may be linked to the islet infusion inflammation, not directly to each other, and further reducing this inflammation may reduce thrombosis and thrombocytosis frequencies simultaneously., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Gastrointestinal bleeding (GIB) is an uncommon complication after abdominal surgery. Given the unique risks in the total pancreatectomy with islet autotransplant (TPIAT) population, we aimed to describe this population's incidence of postoperative GIB., Methods: Prospectively collected data on patients who underwent a TPIAT from 2001 to 2018 at the University of Minnesota were reviewed for postoperative GIB. Each GIB patient was matched to a control patient and compared for medical, medication, and social history and for clinical outcomes., Results: Sixty-eight patients developed a GIB (12.4%) at median time after surgery of 17 months. Etiologies included the following: anastomotic ulcer (35%), Clostridium difficile (4%), gastric or duodenal ulcers (9%), esophagitis/gastritis (10%), hemorrhoids (3%), inflammatory bowel disease (4%), Mallory-Weiss tears (1%), and unknown (29%). During diagnostic workup, 87% had an endoscopic procedure and 3% underwent imaging. Seven patients required an operation (10%), 1 required an open embolization (1%), and 13 required endoscopic treatments (19%). Patients with a GIB were more likely to die (15% vs 5%, P = 0.055)., Conclusions: Twelve percent of patients developed a GIB after TPIAT. One third of those had an undefined etiology despite endoscopy. The need for intervention was high (30%)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown., Methods: We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes., Results: Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005)., Conclusions: Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed., Competing Interests: L.F.F. is a consultant for Medtronic and Abbvie and a speaker for Nestle. S.C. did not declare conflict of interest related to the article. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children-digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Context: Body composition in total pancreatectomy with islet autotransplantation (TPIAT) has never been studied., Objective: Determine whether presurgical body composition is associated with islet function and insulin sensitivity after TPIAT., Methods: In 88 adults undergoing TPIAT (median age 41.0 years, IQR 32.8-48.0), beta-cell function and insulin sensitivity were assessed using mixed meal tolerance test and frequent sample intravenous glucose tolerance test before surgery and 12 and 18 months afterward. Body composition was measured by dual x-ray absorptiometry. Analyses used linear and logistic regression., Results: Before surgery, 8 individuals (9.1%) were underweight, 40 (45.5%) normal weight, 20 (22.7%) overweight, and 20 (22.7%) obese. Overweight/obese patients had higher area under the curve C-peptide and lower insulin sensitivity index. Baseline body weight was positively associated with first-phase insulin secretion (AIRg) at 12 months (average 38.5 [SE 17.1] mU/L/min higher per extra kg; P = 0.03) and 18 months (38.3 [18.5]; P = 0.04), while baseline lean mass was inversely associated with AIRg at 12 months (-0.05 [0.02] per extra kg; P = 0.01) and 18 months (-0.05 [0.02]; P = 0.03). Percent gynoid fat was inversely associated with disposition index at 18 months (-206.0 [97.2] per extra percent; P = 0.04). Percent body fat and percent gynoid fat were associated with glucose effectiveness index at 18 months (1.9 × 10-3 [0.9 × 10-3] per extra percent; P = 0.04 and -1.96 × 10-3 [0.8 × 10-3]; P = 0.02, respectively). Insulin independence was not significantly associated with body weight or composition., Conclusions: Half of these chronic pancreatitis patients were overweight/obese; underweight was uncommon. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples ( n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p ( P = 0.03), hsa-miR-148a-3p ( P = 0.04) and hsa-miR-221-3p ( P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p ( P = 0.04) and hsa-miR-7-5p ( P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p ( P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p ( P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg ( r = -0.20, P = 0.02). Also, hsa-miR-200c ( r = 0.18, P = 0.03) and hsa-miR-221-3p ( r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.

Background and Aims: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield., Methods: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders., Results: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement., Conclusions: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT., Competing Interests: Declaration of competing interest M. Bellin discloses research funding from Viacyte and Dexcom, and medical advisory role (DSMB) for Insulet., (Copyright © 2020. Published by Elsevier B.V.)

The Igls criteria assess islet function after islet allotransplant, based on C-peptide, insulin use, hemoglobin A1c, and severe hypoglycemia. However, these criteria as currently defined cannot be applied to total pancreatectomy islet autotransplant (TPIAT) patients. We tested modified criteria for assessing islet function in a large cohort of TPIAT patients (n = 379). Metabolic outcomes were assessed. We assigned Auto-Igls class to each patient as able and evaluated the utility, validity, and perioperative risk factors of Auto-Igls at 1-year post-IAT. We tested the association of Auto-Igls with independent measures of islet graft function, specifically continuous glucose monitoring (CGM) data or acute C-peptide response to glucose (ACRglu) from intravenous glucose tolerance tests. An Auto-Igls class was assigned to 264 patients (69%). Among patients who could not be classified, most were missing exact insulin dose. Seventy-three percent of TPIAT recipients were classified as optimal or good at 1 year. The only significant predictor of Auto-Igls class was islet mass transplanted (P < 0.0001). Auto-Igls class was associated with percent time in range (70-140 mg/dl) on CGM (P = 0.02) and ACRglu (P < 0.0001). Modified Igls classification for IAT permits simple, comprehensive assessment of metabolic outcomes after TPIAT and is associated with other islet functional measures., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Objective: When total pancreatectomy with islet autotransplantation (TPIAT) is performed for chronic pancreatitis, the pancreas and most of the duodenum are removed, with Roux-en-Y reconstruction of the gastrointestinal tract. Enteroendocrine cells in the intestines and pancreas secrete hormones coordinating digestion and motility, but anatomic reconstruction alters transit of nutrients to these cells. We hypothesized that TPIAT leads to changes in enteroendocrine hormones., Methods: Glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and pancreatic polypeptide (PP) were measured from mixed-meal tolerance tests of 34 clinical trial participants before and 18 months after TPIAT. Area under the curve of GLP-1 and PYY-stimulated responses were calculated by trapezoidal method, and the PP response was measured as the stimulated max minus baseline (ΔPP)., Results: Area under the curve of GLP-1 and PYY increased significantly after TPIAT (GLP-1 average +553.1 pg/mL per minute, P = 0.004; PYY average +4647.9 pg/mL per minute, P = 0.02). ΔPP trended toward lower after TPIAT (average, -52.2 pg/mL, P = 0.06)., Conclusions: In this novel study of enteroendocrine hormones in TPIAT patients, stimulated levels of GLP-1 and PYY were significantly higher after versus before TPIAT. ΔPP was lower after TPIAT, but not significantly. These hormone changes have potential clinical implications that warrant further research.

Metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT) are influenced by the islet mass transplanted. Preclinical and clinical studies indicate that insulin and C-peptide levels measured after intravenous administration of the beta cell secretagogue arginine can be used to estimate the available islet mass. We sought to determine if preoperative arginine stimulation test (AST) results predicted transplanted islet mass and metabolic outcomes in pediatric patients undergoing TPIAT. We evaluated the association of preoperative C-peptide and insulin responses to AST with islet isolation metrics using linear regression, and with postoperative insulin independence using logistic regression. Twenty-six TPIAT patients underwent preoperative AST from 2015 to 2018. The acute C-peptide response to arginine (ACRarg) was correlated with isolated islet equivalents (IEQ; r = 0.59, P = 0.002) and islet number (IPN; r = 0.48, P = 0.013). The acute insulin response to arginine (AIRarg) was not significantly correlated with IEQ (r = 0.38, P = 0.095) or IPN (r = 0.41, P = 0.071). Neither ACRarg nor AIRarg was associated with insulin use at 6 months postoperatively. Preoperative C-peptide response to arginine correlates with islet mass available for transplant in pediatric TPIAT patients. AST represents an additional tool before autotransplant to provide counseling on likely islet mass and to inform quality improvements of islet isolation techniques., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetes distress (DD), or psychological fatigue associated with diabetes management, is common in type 1 and 2 diabetes mellitus and is associated with poor glycemic control. Diabetes distress has never been evaluated in patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for chronic pancreatitis. We analyzed DD after TPIAT in 260 patients (average age 34.3 [standard deviation 15], 75.5% F) undergoing TPIAT between 2006 and 2014. Each patient completed 1 or more diabetes distress scale (DDS) questionnaires from 1 to 7 years post-TPIAT (631 total). We examined changes in DD over 7 years and also patient characteristics associated with DD 1 year post-TPIAT (n = 189). One year after TPIAT, 151 of 189 (80%) reported no or low distress (DD<2). Diabetes distress increased over time by an average of 0.084 (SE 0.017) points per year, an average 0.59 point increase from years 1 to 7 (P < .0001). Insulin-dependent patients had significantly greater DD 1 year post-TPIAT compared to insulin-independent patients (P < .0001). Higher DD was associated with poorer glycemic control as indicated by HbA1c (P < .0001). Prevalence of DD is low but increases over time after TPIAT. Insulin dependence and poorer glycemic control are associated with higher levels of DD., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/objectives: Total pancreatectomy with islet autotransplantation (TPIAT) is considered for managing chronic pancreatitis in selected patients when medical and endoscopic interventions have not provided adequate relief from debilitating pain. Although more centers are performing TPIAT, we lack large, multi-center studies to guide decisions about selecting candidates for and timing of TPIAT., Methods: Multiple centers across the United States (9 to date) performing TPIAT are prospectively enrolling patients undergoing TPIAT for chronic pancreatitis into the Prospective Observational Study of TPIAT (POST), a NIDDK funded study with a goal of accruing 450 TPIAT recipients. Baseline data include participant phenotype, pancreatitis history, and medical/psychological comorbidities from medical records, participant interview, and participant self-report (Medical Outcomes Survey Short Form-12, EQ-5D, andPROMIS inventories for pain interference, depression, and anxiety). Outcome measures are collected to at least 1 year after TPIAT, including the same participant questionnaires, visual analog pain scale, pain interference scores, opioid requirements, insulin requirements, islet graft function, and hemoglobin A1c. Health resource utilization data are collected for a cost-effectiveness analysis. Biorepository specimens including urine, serum/plasma, genetic material (saliva and blood), and pancreas tissue are collected for future study., Conclusions: This ongoing multicenter research study will enroll and follow TPIAT recipients, aiming to evaluate patient selection and timing for TPIAT to optimize pain relief, quality of life, and diabetes outcomes, and to measure the procedure's cost-effectiveness. A biorepository is also established for future ancillary studies., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: 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., Methods: 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., Results: 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 (P < 0.01). Persistent opioid use (15% of patients at 1 year) increased with age (P = 0.05) and disease duration (P = 0.04)., Conclusions: 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.

Objectives: Approximately two thirds of patients will remain on insulin therapy after total pancreatectomy with islet autotransplant (TPIAT) for chronic pancreatitis. We investigated the relationship between measured pancreas volume on computerized tomography or magnetic resonance imaging and features of chronic pancreatitis on imaging, with subsequent islet isolation and diabetes outcomes., Methods: Computerized tomography or magnetic resonance imaging was reviewed for pancreas volume (Vitrea software) and presence or absence of calcifications, atrophy, and dilated pancreatic duct in 97 patients undergoing TPIAT. Relationship between these features and (1) islet mass isolated and (2) diabetes status at 1-year post-TPIAT were evaluated., Results: Pancreas volume correlated with islet mass measured as total islet equivalents (r = 0.50, P < 0.0001). Mean islet equivalents were reduced by more than half if any one of calcifications, atrophy, or ductal dilatation were observed. Pancreatic calcifications increased the odds of insulin dependence 4.0 fold (1.1, 15). Collectively, the pancreas volume and 3 imaging features strongly associated with 1-year insulin use (P = 0.07), islet graft failure (P = 0.003), hemoglobin A1c (P = 0.0004), fasting glucose (P = 0.027), and fasting C-peptide level (P = 0.008)., Conclusions: Measures of pancreatic parenchymal destruction on imaging, including smaller pancreas volume and calcifications, associate strongly with impaired islet mass and 1-year diabetes outcomes.

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 < 0.0001). Positive cultures were not associated with posttransplant infections (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., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)