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Exocrine pancreatic insufficiency (EPI) is highly prevalent among individuals with cystic fibrosis (CF). Individuals diagnosed with EPI are often labeled as having "pancreas insufficient cystic fibrosis (PI-CF)" while those with normal exocrine function are labeled as "pancreas sufficient CF (PS-CF)." This diagnosis of EPI relies on clinical and laboratory features and management involves consumption of pancreas enzyme replacement therapy. In this review, we discuss the nuances of diagnosis and management of EPI in CF. We also present emerging evidence on the effects of CFTR modulating agents on the management of EPI, and speculate that these medications may lead to greater heterogeneity in management of EPI in CF moving forward., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Patients with Cystic Fibrosis (CF) are at increased risk of acute (AP) and chronic (CP) pancreatitis, and their complications. The extent of remaining healthy pancreatic parenchyma determines the risk of developing future episodes of pancreatitis, as well as pancreatic exocrine or endocrine insufficiency. Pancreatitis may be the presenting symptom of CF, and genetic testing is especially important in pediatrics. AP and recurrent AP are managed with intravenous fluid hydration and pain control, in addition to early refeeding and treatment of complications. With the use of modulator therapy in CF, pancreatic function may be restored to some extent. CP related pain is managed with analgesics and neuromodulators, with surgery if indicated in specific situations including TPIAT as a possible type of surgical intervention. Long-term sequelae of CP in patients with CF include exocrine pancreatic insufficiency treated with pancreatic enzyme replacement therapy, fat-soluble vitamin deficiencies and associated metabolic complications such as bone disease/osteoporosis, pancreatogenic diabetes, and less commonly, pancreatic cancer. We review the presentation and etiologies of pancreatitis in CF patients as well as the management of AP and CP primarily in children., (© 2024 Wiley Periodicals LLC.)

Background: Pancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and postoperative outcomes. We investigated its impact on nutritional status, body composition, and postoperative outcomes in patients with pancreatic head cancer undergoing neoadjuvant therapy (NAT)., Methods: We analyzed 136 patients with pancreatic head cancer who underwent NAT prior to intended pancreaticoduodenectomy (PD) between 2015 and 2022. Nutritional and anthropometric indices (body mass index [BMI], albumin, prognostic nutritional index [PNI], Glasgow prognostic score, psoas muscle index, subcutaneous adipose tissue index [SATI], and visceral adipose tissue index) and postoperative outcomes were compared between the occlusion (n = 78) and non-occlusion (n = 58) groups, in which 61 and 44 patients, respectively, ultimately underwent PD., Results: The occlusion group showed significantly lower post-NAT BMI, PNI, and SATI (p = 0.011, 0.005, and 0.015, respectively) in the PD cohort. The occlusion group showed significantly larger main pancreatic duct, smaller pancreatic parenchyma, and greater duct-parenchymal ratio (p < 0.001), and these morphological parameters significantly correlating with post-NAT nutritional and anthropometric indices. Postoperative 3-year survival and recurrence-free survival (RFS) rates were significantly poorer (p = 0.004 and 0.013) with pancreatic ductal occlusion, also identified as an independent postoperative risk factor for overall survival (hazard ratio [HR]: 2.31, 95% confidence interval [CI] 1.08-4.94, p = 0.030) and RFS (HR: 2.03, 95% CI 1.10-3.72, p = 0.023), in multivariate analysis., Conclusions: Pancreatic ductal occlusion may be linked to poorer postoperative outcomes due to PEI-related malnutrition., (© 2024. The Author(s).)

Background: An increasing number of patients are achieving long-term survival after pancreatoduodenectomy, meaning that risk assessments of endocrine and exocrine pancreatic insufficiency are needed. Herein, we investigated the risk factors for pancreatic insufficiency after pancreatoduodenectomy by incorporating pancreatic morphologic changes and perioperative factors., Methods: Patients who underwent pancreatoduodenectomy between January 2015 and December 2020 were enrolled in this single-center retrospective study. Clinicopathologic, surgical, and pancreatic morphologic factors were collected, and risk factors for exocrine pancreatic insufficiency and endocrine pancreatic insufficiency were analyzed. Exocrine pancreatic insufficiency was defined as steatorrhea requiring pancreatic enzymes and new onset steatosis, and endocrine pancreatic insufficiency was defined as postoperative new-onset diabetes mellitus. Multivariate analysis was performed., Results: Among the 206 patients enrolled, 14% and 24% developed endocrine pancreatic insufficiency and exocrine pancreatic insufficiency, respectively. Multivariate analysis revealed residual pancreatic stent 1 year postoperatively, lymph node metastasis, and postoperative pancreatic atrophy (P-atrophy) as independent risk factors for exocrine pancreatic insufficiency, whereas preoperative glycated hemoglobin levels, residual pancreatic stent, and postoperative main pancreatic duct dilatation were risk factors for endocrine pancreatic insufficiency. Subgroup analysis of pancreatic ductal adenocarcinoma revealed that exocrine pancreatic insufficiency in patients with pancreatic ductal adenocarcinoma was caused by preoperative decreased pancreatic function (high glycated hemoglobin and a low postoperative pancreatic fistula rate), whereas the high incidence of POPF influenced the development of exocrine pancreatic insufficiency in patients without pancreatic ductal adenocarcinoma., Conclusion: Postoperative pancreatic atrophy and main pancreatic duct dilatation are risk factors for exocrine pancreatic insufficiency I and endocrine pancreatic insufficiency, respectively, and residual pancreatic stent affects both types of pancreatic dysfunction. Improving the surgical approach and stent management may help prevent these late complications., (Copyright © 2024 Elsevier Inc. 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.)

Background: Approximately 85% of patients with cystic fibrosis (CF) have exocrine pancreatic insufficiency (EPI) with 10% requiring supplemental nighttime enteral tube feedings. Administration of pancreatic enzyme replacement therapy (PERT) with nighttime feedings is fraught with challenges. RELiZORB (Alcresta Therapeutics, Inc), an in-line lipase cartridge, delivers PERT continuously with enteral feedings. Outcomes related to the use of this in-line lipase cartridge are lesser known. This project evaluated anthropometrics related to in-line lipase cartridge use among pediatric patients with CF already receiving oral PERT therapy prior to nighttime enteral feedings., Methods: Retrospective chart review was performed on 29 patients with CF and EPI receiving supplemental tube feedings and utilizing in-line lipase cartridge for a continuous 12 month period between 2015 and 2019. Anthropometrics were evaluated 12 months before and after initiation of in-line lipase cartridge., Results: Compared with mean height z score at 6-months pre-in-line lipase cartridge, mean height z score at 6-months post-in-line-lipase cartridge (adjusted mean difference [AMD] = 0.2540; 95% CI = [0.0487, 0.4592]; P = 0.0153) and mean height z score at 12-months post-in-line lipase cartridge (AMD = 0.2684; 95% CI = [0.0203, 0.5166]; P = 0.0340) were significantly higher. Mean weight z score at 12-months post-in-line-lipase-cartridge neared statistical significance compared with 6-months pre-in-line lipase cartridge (AMD = 0.2816; 95% CI = [-0.0003, 0.5634]; P = 0.0502) when excluding seven patients with advanced lung disease (forced expiratory volume in the first second of expiration of 40%). Weight-for-length or body mass index did not significantly differ compared with pre-in-line lipase cartridge., Conclusion: Use of in-line lipase cartridge with enteral feeds improved anthropometrics, especially height, in pediatric patients with CF., (© 2024 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Competing Interests: Declaration of competing interest The author declares that she has no competing interests.

Objectives: To analyze the evolution of clinical and anthropometric characteristics of children and adolescents with cystic fibrosis (CF) over 24 months, including the period of the COVID-19 pandemic., Methods: A longitudinal study with data collection from May 2018 to November 2020 in physical and electronic records from a pediatric reference center, including individuals with CF aged up to 18 years., Results: The sample encompassed 72 individuals. Weight (p < 0.01), height (p < 0.01), and body mass index (BMI) (p = 0.043) were higher in 2020 than in 2018. There were no significant changes in BMI-Z (p = 0.977) and in percentiles of weight (p = 0.540), height (p = 0.458), and BMI percentile (p = 0.454) between both periods. Pancreatic insufficiency was observed in 91.7% of patients in 2020, and there were twice as many confirmed cases of diabetes compared to 2018. There was a 9.7% increase in individuals colonized by the oxacillin-sensitive Staphylococcus aureus (OSSA) (p = 0.039) and an 11.1% reduction in non-colonized individuals (p = 0.008)., Conclusion: Although there was an increase in weight, height, and BMI from 2018 to 2020, there were no significant changes in BMI-Z and in percentiles of weight, height, and BMI percentile, suggesting that the anthropometric aspects of nutritional status did not change in this period of 2 years. Moreover, there was an increase in the prevalence of individuals colonized by OSSA and a reduction in the prevalence of individuals non-colonized with any bacteria., (© 2024 Wiley Periodicals LLC.)

Background: Relieving gastrointestinal symptoms is a research priority in cystic fibrosis. Emerging evidence highlights effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on gastrointestinal function, including pancreatic sufficiency. This study explores ivacaftor licensing and treatment on recorded pancreatic enzyme replacement therapy (PERT) prescription in the US and UK CF registries., Methods: Retrospective longitudinal registry study of recorded pancreatic PERT use between 2008 and 2017. Interrupted time series analysis in propensity-matched cohorts estimated annual change and step change according to ivacaftor eligibility before and after licensing year, 2012. Generalised estimating equations assessed adjusted risk of PERT use in individuals treated with ivacaftor after 2012 compared to untreated individuals., Results: In the US CF registry, the difference in annual change in prevalence of PERT use post-2012 between eligible cases and ineligible controls was -5.0 per 1000 people/year (95 %CI -7.6; -2.3, p = 0.001). The step change and annual change in prevalence of PERT use in eligible cases was not significantly different to controls in the UK CF registry. Relative to the relationship in 2013, ivacaftor treatment in the US CF registry was associated with a lower adjusted risk ratio of PERT use compared to untreated individuals by 2016 (0.97, 95 %CI 0.96; 0.99), which was not observed in the UK CF registry., Conclusions: Licensing of ivacaftor was followed by a lower prevalence of PERT use in the eligible US population compared to pre-licensing period, as well as lower risk of PERT use in those who received treatment. Inconsistencies in US and UK CF registries were observed., Competing Interests: Declaration of competing interest A.R. Smyth has research grants (paid to the University of Nottingham) from Vertex Pharmaceuticals and payment for an advisory board (paid to the University of Nottingham) from Viatris Pharmaceuticals, all outside the current work. A.R. Smyth has patents issued (Camara M, Williams P, Barrett D, Halliday N, Knox A, Smyth A, Fogarty A, Barr H, Forrester D. Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof. US2016131648-A1; https://pubchem.ncbi.nlm.nih.gov/patent/US-2016131648-A1 Outside the current work, A.R. Smyth reports participation on a Data Safety Monitoring Board for the North American Cystic Fibrosis Foundation Therapeutic Development Network., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: The aim of this study was to study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC)., Materials and Methods: Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016-2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk, and pancreatic enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching (PSM) of patients with EPI versus patients without an EPI diagnosis., Results: The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years. After PSM, PDAC risk among patients with EPI was twice as high compared with patients without EPI (aHR, 1.97; 95% CI, 1.66-2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (adjusted odds ratio, 4.25; 95% CI, 2.99-6.04). Only 58% (n = 13, 390) of patients with EPI received PERT. No difference was observed in PDAC risk between patients with EPI on PERT and those not on PERT (aHR, 1.10; 95% CI, 0.95-1.26; P = 0.17)., Conclusions: Despite a low prevalence, patients with EPI may have a higher risk of PDAC, and majority with EPI were not on PERT. PERT did not impact incident PDAC risk after an EPI diagnosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients undergoing pancreatectomy are at risk for pancreatic exocrine insufficiency and malnutrition. However, the incidence of these complications and the associated risk factors have not been sufficiently examined. This study aimed to investigate the changes in pancreatic morphology, pancreatic exocrine function, and long-term nutritional status after pancreatectomy., Methods: We assessed the nutritional status, pancreatic morphologic parameters, and pancreatic exocrine function in patients undergoing pancreaticoduodenectomy and distal pancreatectomy. Nutritional status was evaluated on the basis of body weight change, body mass index, and skeletal muscle mass. Pancreatic parenchymal texture at the time of surgery, remnant volume of the pancreatic parenchyma, and diameter of the pancreatic duct were measured. Exocrine function was measured using the N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test and the clinical signs of steatorrhea and nonalcoholic steatohepatitis. We then investigated potential causal relationships., Results: Seventy patients were included in the study. Moderate and severe malnutrition were diagnosed in 19 (27%) and 15 patients (21%), respectively. Most patients with malnutrition before surgery were also found to be malnourished postoperatively. Body weight and skeletal muscle mass decreased after pancreatectomy in most patients, even in the longer term. Subclinical and clinical pancreatic exocrine insufficiency was found in 36 (51%) and 25 patients (36%), respectively, and pancreatic ductal adenocarcinoma, pancreaticoduodenectomy, dilated pancreatic duct, low preoperative body mass index, and pancreatic exocrine insufficiency grade were found to contribute to postoperative malnutrition., Conclusion: Pancreatic ductal adenocarcinoma, dilated pancreatic duct, pancreaticoduodenectomy, low preoperative body mass index, and pancreatic exocrine insufficiency were risk factors for postoperative malnutrition., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Intestinal inflammation with contradictory data on faecal calprotectin (fCP) levels is documented in patients with cystic fibrosis (CF). The aim of this study was to longitudinally evaluate fCP in a cohort of children with CF and their relationship with clinical variables., Design: Prospective observational study to assess evolution of fCP levels, primary aimed at improving fat absorption. Along 1.5 years of follow-up (November 2016-May 2018) with four study visits pertaining to a pilot study (two of four) and to a clinical trial (two of four), the study outcomes were measured., Setting: Six European CF centres in the context of MyCyFAPP Project., Subjects: Children with CF and pancreatic insufficiency (2-18 years old)., Main Outcome Measurements: fCP levels, pulmonary function (percentage of forced expiratory volume in 1 s (FEV 1 %)) and coefficient of fat absorption (CFA). Additionally, in the last two visits, gastrointestinal (GI) symptoms were evaluated through the PedsQL-GI Questionnaire. Linear mixed regression models were applied to assess association between fCP and FEV 1 , CFA and GI symptoms., Results: Twenty-nine children with CF and pancreatic insufficiency were included. fCP levels were inversely associated with total modified specific PedsQL-GI score (p=0.04) and positively associated with diarrhoea (p=0.03), but not with CFA. Along the four study visits, fCP significantly increased (from 62 to 256 µg/g) and pulmonary function decreased (from 97% to 87%), with a significant inverse association between the two study outcomes (p<0.001)., Conclusions: In children with CF, fCP levels are inversely associated with pulmonary function and thus the specificity of fCP as a marker of intestinal inflammation in paediatric patients with CF warrants further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nonalcoholic fatty liver disease (NAFLD) occurs in 10% to 40% of patients after pancreatic resection. Pancreatic exocrine insufficiency (PEI) is thought to be closely associated with NAFLD; however, the mechanism of NAFLD is not clearly understood. We perform a systematic review and meta-analysis to better understand the risk factors of NAFLD., Methods: A systematic literature search was performed in the MEDLINE database. Studies focused on the risk factors associated with NAFLD in patients undergoing pancreatectomy. The odds ratios (ORs) denoting the association of risk factors with NAFLD after resection were curated., Results: Of 814 published articles, 26 studies met the inclusion criteria. Combined, these studies included clinical data on 4055 patients. The pooled incidence of NAFLD was 29% (23%-35%). Among the various risk factors analyzed, the following had a significant likelihood of NAFLD on forest plot analysis: female gender (OR, 2.44), pancreatic ductal adenocarcinoma (OR, 2.11), portal vein or superior mesenteric vein resection (OR, 1.99), dissection of nerve plexus around the superior mesenteric artery (OR, 1.93), and adjuvant chemotherapy (OR, 1.58). Only 2 studies investigated 2 different measurements of quantitative PEI, which could not be used for analysis. Owing to heterogeneity of studies, pancreatic remanent volume, which is considered a marker for PEI could not be evaluated. Pancreatic enzyme replacement therapy (PERT) was not associated with NAFLD., Conclusion: Numerous factors are associated with NAFLD after pancreatectomy. Previous research shows that PEI may be associated with NAFLD; however, this could not be compared in our meta-analysis. Further research is required to study the role of PERT in NAFLD., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps., Competing Interests: Declaration of competing interest No conflicts of interest exist., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation., Methods: First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz., Results: No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly., Conclusion: Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the long-term consequences of necrotising pancreatitis, including complications, the need for interventions and the quality of life., Design: Long-term follow-up of a prospective multicentre cohort of 373 necrotising pancreatitis patients (2005-2008) was performed. Patients were prospectively evaluated and received questionnaires. Readmissions (ie, for recurrent or chronic pancreatitis), interventions, pancreatic insufficiency and quality of life were compared between initial treatment groups: conservative, endoscopic/percutaneous drainage alone and necrosectomy. Associations of patient and disease characteristics during index admission with outcomes during follow-up were assessed., Results: During a median follow-up of 13.5 years (range 12-15.5 years), 97/373 patients (26%) were readmitted for recurrent pancreatitis. Endoscopic or percutaneous drainage was performed in 47/373 patients (13%), of whom 21/47 patients (45%) were initially treated conservatively. Pancreatic necrosectomy or pancreatic surgery was performed in 31/373 patients (8%), without differences between treatment groups. Endocrine insufficiency (126/373 patients; 34%) and exocrine insufficiency (90/373 patients; 38%), developed less often following conservative treatment (p<0.001 and p=0.016, respectively). Quality of life scores did not differ between groups. Pancreatic gland necrosis >50% during initial admission was associated with percutaneous/endoscopic drainage (OR 4.3 (95% CI 1.5 to 12.2)), pancreatic surgery (OR 3.2 (95% CI 1.1 to 9.5) and development of endocrine insufficiency (OR13.1 (95% CI 5.3 to 32.0) and exocrine insufficiency (OR6.1 (95% CI 2.4 to 15.5) during follow-up., Conclusion: Acute necrotising pancreatitis carries a substantial disease burden during long-term follow-up in terms of recurrent disease, the necessity for interventions and development of pancreatic insufficiency, even when treated conservatively during the index admission. Extensive (>50%) pancreatic parenchymal necrosis seems to be an important predictor of interventions and complications during follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Exocrine pancreatic insufficiency (EPI) is common in pancreatic ductal adenocarcinoma (PDAC) and may lead to significant nutrition compromise. In the setting of cancer cachexia and gastrointestinal toxicities of cancer treatments, untreated (or undertreated) EPI exacerbates weight loss, sarcopenia, micronutrient deficiencies, and malnutrition. Together, these complications contribute to poor tolerance of oncologic therapies and negatively impact survival. Treatment of EPI in PDAC involves the addition of pancreatic enzyme replacement therapy, with titration to improve gastrointestinal symptoms. Medical nutrition therapies may also be applicable and may include fat-soluble vitamin replacement, medium-chain triglycerides, and, in some cases, enteral nutrition. Optimizing nutrition status is an important adjunct treatment approach to improve quality of life and may also improve overall survival., (© 2024 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Fat digestion and absorption play crucial roles in maintaining energy homeostasis and supporting essential physiological functions. The initial stage of fat digestion occurs in the stomach, where gastric lipase begins the hydrolysis of triglycerides. However, most fat digestion takes place in the small intestine via pancreatic enzymes and bile salts. Emulsification of fat by bile acids facilitates enzymatic action, breaking down triglycerides into free fatty acids and monoglycerides, which are then able to be absorbed by enterocytes. Fat malabsorption can result from various underlying conditions, such as exocrine pancreatic insufficiency, bile acid disorders, or intestinal diseases. The clinical manifestations of fat malabsorption include steatorrhea, malnutrition, and deficiencies of fat-soluble vitamins. Diagnostic approaches involve assessing fecal fat levels, imaging studies, and various functional tests to identify the specific etiology. This review article will describe the normal physiologic process of fat digestion and absorption and discuss various pathophysiology that can lead to fat malabsorption within the gastrointestinal tract as well as their respective diagnostic testing modalities. Effective digestion of fat is essential for overall health, because it allows for absorption of many essential nutrients, plays an integral role in cellular and structural function, and supplies energy to the body. When this is dysfunctional, disorders of malabsorption can occur. This article will give a brief overview of the physiologic process of fat digestion and absorption in healthy individuals as well as review important pathophysiology that can lead to fat malabsorption within the gastrointestinal tract and current diagnostic testing modalities., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Surgical resection is the mainstay of treatment for patients with tumors of the pancreas. There are a number of well-recognized complications that account for the significant morbidity associated with the operation, including exocrine pancreatic insufficiency (EPI). Patients with pancreatic cancer commonly have evidence of EPI prior to surgery, and this is exacerbated by an operation, the extent of the insult being dependent on the indication for surgery and the operation performed. There are accumulating data to demonstrate that treatment of EPI with pancreatic enzyme replacement (PERT) enhances clinical outcomes after surgery by reducing critical complications; this in turn may enhance oncological outcomes. Data would indicate that quality of life (QoL) is also improved after surgery when enzymes are prescribed. To date, many surgeons and clinicians have not appreciated the need for PERT or the benefits it may bring to their patients; therefore, education of clinicians remains a significant opportunity. In turn, patient education about consumption of the correct dose of enzymes at the appropriate time is key to an optimal outcome. In addition, because of the complex nature of the regulation of pancreatic exocrine function, there is evidence to support the presence of EPI following operations performed on other gastrointestinal (GI) organs, including the esophagus, stomach, and small intestine. The aim of this review is to document the existing published evidence in relation to EPI and its treatment with PERT following GI surgery., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Exocrine pancreatic insufficiency (EPI) stems from a deficiency of functional pancreatic enzymes with consequent maldigestion and malnutrition. EPI shares clinical symptoms and manifestations with other disorders and is a considerable burden to individuals affected. In this narrative review, we analyzed the literature to identify relevant publications on living with EPI with the scope of individuating evidence gaps, including those related to symptoms, health-related quality of life (HRQoL), emotional functioning, disease burden, presence of comorbidities, and the use of pancreatic enzyme replacement therapy (PERT). Abdominal pain emerged as one of the most prominent symptoms. HRQoL was affected in EPI, but no articles examined emotional functioning. Comorbidities reported involved other pancreatic disorders, diabetes, gastrointestinal disorders, sarcopenia and osteopenia, cardiovascular disorders, bacterial overgrowth, and nutritional deficiencies. PERT was found to be effective in improving EPI symptoms and was well tolerated by most individuals. Our review revealed a dearth of literature evidence on patients' experience with EPI, such as emotional functioning and disease burden. We also revealed that studies on long-term effects of PERT are missing, as are studies that would help advance the understanding of the disease and its progression, risk/mitigating factors, and comorbidities. Future studies should address these identified gaps., (© 2024. The Author(s).)

Aims: Treatment of pancreatic exocrine insufficiency (PEI) following pancreatoduodenectomy (PD) improves quality of life, clinical outcomes, and survival. However, diagnosing PEI following PD is challenging owing to the difficulties with current tests and often non-specific symptoms. This work aims to quantify the true rate of long-term PEI in patients following a PD., Methods: Patients underwent a PEI screen approximately one to two years following PD for oncologic indication, including the 13 C Mixed triglyceride breath test ( 13 CMTGT), faecal elastase 1 (FE-1) and the PEI Questionnaire (PEI-Q). Four reviewers with expertise in PEI reviewed the results blinded to other decisions to classify PEI status; disagreements were resolved on consensus., Results: 26 patients were recruited. Of those with valid test results, these were indicative of PEI based on pre-specified thresholds for 60 % (15/25) for the 13 CMTGT, 82 % (18/22) for FE-1, and 88 % (22/25) for the PEI-Q. After discussion between reviewers, the consensus PEI prevalence was 81 % (95 % CI: 61-93 %; 21/26), with 50 % (N = 13) classified as having severe, 23 % (N = 6) moderate, and 8 % (N = 2) mild PEI., Discussion: Since no ideal test exists for PEI, this collation of diagnostic modalities and blinded expert review was designed to ascertain the true rate of long-term PEI following PD. This required our cohort to survive a year, travel to hospital, and undergo a period of starvation and PERT hold, and therefore there is likely to be recruitment bias towards fitter, younger patients with less aggressive pathology. Despite this, over 80 % were deemed to have PEI, with over 90 % of these being considered moderate or severe., Competing Interests: Decleration of competing ineterest No authors have any financial or personal relationships with other people or organizations that could inappropriately influence (bias) their work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Thirty-nine percent of people with type 1 diabetes may have lowered pancreatic elastase levels, correlated with exocrine pancreatic insufficiency (EPI or PEI). EPI is treated with oral supplementation of pancreatic enzymes. Little is known about the glycemic impact of pancreatic enzyme replacement therapy (PERT) in people with diabetes. This article demonstrates a method of assessing glycemic variability (GV), glycemic outcomes, and other changes in an individual with type 1 diabetes using open-source automated insulin delivery (AID)., Method: Macronutrient, PERT intake, and EPI-related symptoms were self-tracked; diabetes data were collected automatically via an open-source AID system. Diabetes data were uploaded via Nightscout to Open Humans and downloaded for analysis alongside self-tracked data (food, PERT). Glycemic outcomes, macronutrients, PERT dosing, and a variety of GV metrics following meals were evaluated for one month before and one month after PERT commencement. Breakfast was assessed independently across both time periods., Results: In an n = 1 individual using an open-source AID, time in range was already above goal and improved further after PERT commencement. Glucose rate of change and excursions >180 mg/dL were reduced; mean high blood glucose index was reduced overall and more so specifically at breakfast following PERT commencement., Conclusions: GV can aid in assessing response to new-onset medications, as was demonstrated in this article for n = 1 individual with type 1 diabetes (using an open-source AID) after commencing PERT for newly identified EPI. GV may be useful for evaluating the efficacy of new-onset medications for people with insulin-requiring diabetes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Exocrine pancreatic insufficiency (EPI) is a common manifestation of chronic pancreatitis (CP) and autoimmune pancreatitis (AIP). This study aimed to estimate the presence of EPI in patients with CP or AIP using alternative clinical markers., Materials and Methods: A machine learning analysis employing a decision tree model was conducted on a retrospective training cohort comprising 57 patients with CP or AIP to identify EPI, defined as fecal elastase-1 levels less than 200 μg/g. The outcomes were then confirmed in a validation cohort of 26 patients., Results: Thirty-nine patients (68%) exhibited EPI in the training cohort. The decision tree algorithm revealed body mass index (≤21.378 kg/m 2 ) and total protein level (≤7.15 g/dL) as key variables for identifying EPI. The algorithm's performance was assessed using 5-fold cross-validation, yielding area under the receiver operating characteristic curve values of 0.890, 0.875, 0.750, 0.625, and 0.771, respectively. The results from the validation cohort closely replicated those in the training cohort., Conclusions: Decision tree analysis revealed that EPI in patients with CP or AIP can be identified based on body mass index and total protein. These findings may help guide the implementation of appropriate treatments for EPI., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic pancreatitis (CP) is often associated with exocrine pancreatic insufficiency (EPI), which may increase risk for fat-soluble vitamin depletion. Although vitamin D deficiency is widespread among the general population, vitamins A, E, and K deficiencies may more uniquely present in patients with CP. Yet, it is unclear whether fat-soluble vitamin status should be routinely monitored in all patients with CP or limited to those with EPI. The purpose of this review is to describe the laboratory status of vitamins A, E, and K in adult patients with CP and their association with exocrine pancreatic function. Five primary, observational studies met the inclusion criteria for qualitative synthesis. Biochemical deficiencies in fat-soluble vitamins were observed across trials but results varied with respect to whether EPI increased risk. Challenges related to the diagnosis and treatment of EPI along with potential confounders may contribute to the heterogeneity among study results. Although more studies are needed to determine the influence of pancreatic enzyme replacement therapy on fat-soluble vitamin status as well as effective vitamin repletion strategies, clinicians should consider periodically screening for deficiencies in all patients with CP regardless of EPI to avoid associated health effects of vitamin depletion., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Background: Untreated pancreatic exocrine insufficiency (PEI) results in substantial patient harm. Upper gastrointestinal surgery (bariatric metabolic surgery and oesophagogastric resection) affects the delicate physiology of pancreatic exocrine function and may result in PEI. The aim of this study was to assimilate the literature on incidence, diagnosis, and management of PEI after bariatric metabolic surgery and oesophagogastric resection., Methods: A systematic review of PubMed, MEDLINE, and Embase databases identified studies investigating PEI after non-pancreatic upper gastrointestinal surgery. Meta-analyses were undertaken for incidence of PEI and benefit of pancreatic enzyme replacement therapy., Results: Among 1620 patients from 24 studies included in quantitative synthesis, 36.0% developed PEI. The incidence of PEI was 23.0 and 50.4% after bariatric metabolic surgery and oesophagogastric resection respectively. Notably, the incidence of PEI was 44% after biliopancreatic diversion with duodenal switch and 66.2% after total gastrectomy. The most common diagnostic test used was faecal elastase 1 (15 of 31 studies), with less than 200 µg/g being diagnostic of PEI. A total of 11 studies considered the management of pancreatic exocrine insufficiency, with 78.6% of patients responding positively to pancreatic enzyme replacement when it was prescribed., Conclusion: PEI is common after non-pancreatic upper gastrointestinal surgery and patients may benefit from enzyme replacement therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Aim: The aim of the research was to study the features of pancreatic exocrine insufficiency (EPI) in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM) at COVID-19., Patients and Methods: Materials and Methods: 72 patients with NAFLD and COVID-19 were examined. The patients have been divided into two groups: group 1 included 42 patients with NAFLD and insulin resistance (IR); group 2 consisted of 30 patients with NAFLD in the combination with type 2 DM. EPI was detected by 13С-mixed triglyceride breath test (13С-MTBT) in all the patients., Results: Results: The result of 13С-MTBT indicates EPI in the examined subjects of the 2 group. A significant decrease in the maximum concentration of 13СО2 between 150 and 210 min was also diagnosed in group 1 patients. research (up to 8.2 ± 0.9% - p < 0.05), however, the total concentration of 13СО2 at the end of 360 min. the study reached only 27.7 ± 1.1% (p < 0.05)., Conclusion: Conclusions: Based on the results of laboratory-instrumental methods of research, patients with NAFLD and type 2 diabetes with COVID-19 were diagnosed with severe EPI. The results of 13С-MTBT in NAFLD and IR with COVID-19 indicate a decrease in the functional reserves of the pancreas and the formation of its EPI.

Introduction: Cystic fibrosis transmembrane conductance regulator modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with cystic fibrosis (CF) on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function., Methods: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms., Results: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p &lt; 0.001), mean body weight by 3.51 kg (p &lt; 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p &lt; 0.001). Only 1 patient, initially pancreatic insufficient (4.5%, p &lt; 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 μg/g to 442.1 μg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p &lt; 0.001) and stools frequency by 1.18 per day (p &lt; 0.001)., Conclusion: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: Patients with chronic pancreatitis (CP) often report a poor quality of life and may be disabled. Our study identifies clinical characteristics, predictors and outcomes in CP patients with disability., Methods: A review of established CP patients followed in our Pancreas Center between January 1, 2016 and April 30, 2021. Patients were divided into 2 groups based on disability. Univariate analysis was performed to identify differences in demographics, risk factors, comorbidities, complications, controlled medications, and resource utilization. Multivariate analysis was conducted to identify predictors for disability., Results: Out of 404 CP patients, 18% were disabled. These patients were younger (53.8 vs. 58.8, P =0.001), had alcoholic CP (54.1% vs. 30%; P <0.001), more recurrent pancreatitis (83.6% vs. 61.1%; P =0.001), chronic abdominal pain (96.7% vs. 78.2%; P =0.001), exocrine pancreatic insufficiency (83.6% vs. 55.5%; P <0.001), concurrent alcohol (39.3% vs. 23.3%; P =0.001) and tobacco abuse (42.6% vs. 26%; P =0.02), anxiety (23% vs. 18.2%; P <0.001), and depression (57.5% vs. 28.5%; P <0.001). A higher proportion was on opiates (68.9% vs. 43.6%; P <0.001), nonopiate controlled medications (47.5% vs. 23.9%; P <0.001), neuromodulators (73.3% vs. 44%; P <0.001), and recreational drugs (27.9% vs. 15.8%; P =0.036). Predictors of disability were chronic pain (OR 8.71, CI 2.61 to 12.9, P < 0.001), celiac block (OR 4.66, 2.49 to 8.41; P <0.001), neuromodulator use (OR 3.78, CI 2.09 to 6.66; P <0.001), opioid use (OR3.57, CI 2.06 to 6.31; P < 0.001), exocrine pancreatic insufficiency (OR3.56, CI 1.89 to 6.82; P <0.001), non-opioid controlled medications (OR 3.45, CI 2.01 to 5.99; P <0.001), history of recurrent acute pancreatitis (OR 2.49, CI 1.25 to 4.77; P <0.001), depression (OR 2.26, CI 1.79 to 3.01; P <0.001), and active smoking (OR1.8, CI 1.25 to 2.29; P <0.001)., Conclusion: CP patients with disability have unique characteristics and predictors, which can be targeted to reduce disease burden and health care expenditure in this population., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT)., Methods: A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured., Results: 101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT., Conclusion: For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Pancreatic exocrine insufficiency (PEI) is common after gastric resection for cancer or ulcers but is under-recognized and undertreated. Although pancreatic enzyme replacement therapy (PERT) is the mainstay of PEI management, robust evidence supporting its use after gastric surgery is limited., Areas Covered: In the absence of guideline recommendations specific for patients with pancreatic insufficiency after gastrectomy, a panel of experts from different geographical regions convened in a virtual meeting to discuss their approach to patient management., Expert Opinion: Pancreatic insufficiency after gastrointestinal surgery is not a simple post-surgical complication as several factors contribute to its development. Although the pancreas is unimpaired after gastrectomy, it cannot function normally in the altered environment. Pancreatic insufficiency can be challenging to diagnose in gastrectomy patients due to nonspecific symptoms and the absence of a simple diagnostic test. Fecal elastase appears to be the default test, although it is not sufficiently sensitive nor reliable for diagnosing or monitoring PEI. Patients with maldigestion symptoms after gastrectomy are treated pragmatically: those with clinical suspicion of pancreatic insufficiency receive a trial of PERT and are monitored for symptom improvement. There is a clear need for high-quality evidence from clinical trials to guide the management of this patient population.

Being an underdiagnosed and under or insufficiently treated condition, surgical pancreatic exocrine insufficiency (PSP) is the condition in which pancreatic enzymes are insufficient for digestion because of gastrointestinal (GI) surgery involving the upper GI tract, biliary ducts, or the pancreas, and and leading to potential malnutrition and deterioration in quality of life. Age, obesity, history of tobacco use, family history of diabetes, surgery due to a malignant tumor, presence of steatorrhea, jaundice, weight loss, and intraoperative findings of hard pancreatic texture have been associated with a higher risk of PSP. Pancreatoduodectomy (PD) has demonstrated an increased risk of developing PSP, with a prevalence between 19-100%. Distal pancreatectomy (DP) and central pancreatectomy (CenP) are associated with less risk of PSP, with a prevalence of 0-82% and 3.66-8.7%, respectively. In patients with chronic pancreatitis (CP), PSP was associated with 80% in Partington-Rochelle procedure, 86% in Frey procedure, 80% in duodenum preserving pancreatic head procedure, >60% in PD and 27.5-63% in DP. Fecal elastase-1 (FE-1) is a generally accepted tool for diagnosis. Treatment is recommended to start as soon as a diagnosis is achieved, or clinical suspicion is high. Pancreatic enzyme replacement therapy improves symptoms of malabsorption, facilitates weight gain, and ultimately improves patients' quality of life. Starting dosage is between 10,000-50,000 units in snacks and 50,000-75,000 units in main meals, administered throughout food intake, though further data specifically on PSP are needed. Follow-up in PSP is recommended on an on-demand basis, where malnutrition should be assessed.

Bariatric surgery (BS) is currently the most effective treatment for severe obesity, requiring ongoing multidisciplinary follow-up to ensure proper progress and nutrition post-procedure. Despite its favourable safety profile, it is not exempt from complications, one of which being exocrine pancreatic insufficiency (EPI). The underlying pathophysiological mechanisms of EPI after BS are multifactorial, including poorly synchronized pancreatic enzyme secretion with the passage of nutrients (pancreaticocibal or postcibal asynchrony), insufficient pancreatic stimulation and bacterial overgrowth. We conducted a short literature review of the topic through a case of a patient who underwent BS in our centre and subsequently developed EPI and severe malnutrition. EPI initially was attributed to the surgery, but after a comprehensive evaluation, an unexpected cause was revealed., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The morbidity and mortality of pancreatic cancer surgery has seen substantial improvement due to the standardization of surgical techniques, the optimization of perioperative multidisciplinary management and the organization of specialized care systems. The identification and treatment of postoperative functional and nutritional sequelae have thereby become major issues in patients who undergo pancreatic surgery. This review addresses the functional sequelae of pancreatic resection for cancerous and pre-cancerous lesions (excluding chronic pancreatitis). Its aim is to specify the prevalence and severity of sequelae according to the type of pancreatic resection and to document, where appropriate, the therapeutic management. Exocrine pancreatic insufficiency (ExPI) is observed in nearly one out of three patients at one year after surgery, and endocrine pancreatic insufficiency (EnPI) is present in one out of five patients after pancreatoduodenectomy (PD) and one out of three patients after distal pancreatectomy (DP). In addition, digestive functional disorders may appear, such as delayed gastric emptying (DGE), which affects 10 to 45% of patients after PD and nearly 8% after DP. Beyond these functional sequelae, pancreatic surgery can also induce nutritional and vitamin deficiencies secondary to a lack of uptake for certain vitamins or to the loss of absorption site in the duodenum. In addition to the treatment of ExPI with oral pancreatic enzymes, nutritional management is based on a high-calorie, high-protein diet with normal lipid intake in frequent small feedings, combined with vitamin supplementation adapted to monitored deficiencies. Better knowledge of the functional consequences of pancreatic cancer surgery can improve the overall management of patients., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

There is cumulative evidence that pancreatic exocrine insufficiency (PEI) is under-recognised and can occur in patients with 'at-risk' conditions. Thus, we aimed to assess the current practice and yield of requesting faecal elastase (FEL-1), an indicator of PEI, in patients with 'at-risk' conditions. We prospectively recruited patients attending secondary care clinics with diabetes mellitus (DM), people living with HIV (PLHIV) and inpatients admitted to hospital with high alcohol intake (HAI). All patients underwent testing with FEL-1. Those patients with PEI (FEL-1 <200 μg/g) were contacted and offered a follow-up review in gastroenterology clinic. In total, 188 patients were recruited (HAI, n=78; DM, n=64; and PLHIV, n=46). Previous FEL-1 testing had not been performed in any of the patients. The return rate of samples was 67.9% for patients with HAI, 76.6% for those with DM and 56.5% for those with PLHIV. The presence of PEI was shown in 20.4% of patients with DM, 15.4% of patients with PLHIV and 22.6% in those with HAI. Diarrhoea and bloating were the most reported symptoms in followed-up patients with low FEL-1 (31.8% and 22.7% of patients, respectively). Follow-up computed tomography (CT) scans in those patients with PEI identified chronic pancreatitis changes in 13.6% and pancreatic atrophy in 31.8% of patients. These results suggest that there is a lack of testing for PEI in 'at-risk' groups. Our findings also suggest that using FEL-1 to test for PEI in patients with DM, PLHIV and HAI has a significant impact, although further studies are required to validate these findings., (© Royal College of Physicians 2023. All rights reserved.)

Purpose of Review: The diagnosis and management of exocrine pancreatic dysfunction (EPD) can be challenging. EPD classically results from conditions that cause loss of pancreatic acinar cell function and decreased digestive enzyme production. However, several conditions may contribute to signs or symptoms of EPD with otherwise normal pancreatic exocrine function. A thoughtful approach to considering these conditions, along with their specific therapies, can guide a tailored management approach., Recent Findings: An EPD severity classification schema has been proposed, which emphasizes a shift towards a more restrictive prescription of pancreas enzyme replacement therapy (PERT) for patients with milder EPD. In contrast, PERT use has been associated with a measurable survival benefit among individuals with EPD and pancreatic cancer, so the prescription of PERT may be more liberal in this population. Recent publications in the cystic fibrosis population offer pearls guiding the titration and optimization of PERT., Summary: Among individuals with severe EPD, PERT is an effective therapy. Among individuals with milder EPD, although PERT is effective, there may be opportunities to provide additional and potentially more effective therapies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Complications in chronic pancreatitis (CP) can be grouped in inflammatory (ICC) and fibrotic (FCC) clusters and pancreatic insufficiency cluster (PIC). However, the association between etiological risk factors and the development of complication clusters remains obscure. In this study, the impact of the etiology and disease duration on disease onset and development of complications was investigated., Methods: This cross-sectional study recruited patients with CP from Mannheim/Germany (n = 870), Gieβen/Germany (n = 100) und Donetsk/Ukraine (n = 104). Etiological risk factors, disease stage, age at disease onset, complications, need for hospitalization and surgery were noted., Results: In 1074 patients diagnosed with CP, main risk factors were alcohol and nicotine abuse. An earlier onset of the disease was observed upon nicotine abuse (-4.0 years). Alcohol abuse was only associated with an earlier onset of the definite stage of CP. Alcohol abuse was the major risk factor for the development of ICC (p < 0.0001, multiple regression modeling). Abstinence of alcohol reduced ICC, whereas abstinence of nicotine showed no association. PIC correlated with efferent duct abnormalities and the disease duration. In contrast, FCC was mainly dependent on the disease duration (p < 0.0001; t-test). The presence of any complication cluster correlated with the need for surgery (p < 0.01; X 2 -test). However, only ICC correlated with a prolonged hospital stay (p < 0.05; t-test)., Conclusions: ICC is mainly dependent on alcohol abuse. In contrast, FCC and PIC are mainly dependent on the disease duration. The etiology and disease duration can be used as predictors of the course of disease to provide individual treatment and surveillance strategies., Competing Interests: Declaration of competing interest None., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Chronic diarrhea, defined as diarrhea persisting for more than 4 weeks, affects up to 5% of the population regardless of patient age, sex, race, or socioeconomic status. The impact on patient health and quality of life is substantial, and diagnosis and management of these patients have significant economic consequences for health care services. The differential diagnosis of chronic diarrhea is broad, with etiologies including infections, endocrinopathies, maldigestive/malabsorptive conditions, and disorders of gut-brain interaction. The considerable overlap of symptoms across this spectrum makes accurate diagnosis problematic and may lead to delays in diagnosis or misdiagnosis. In this narrative review, we consider the differential diagnosis of chronic diarrhea, focusing on irritable bowel syndrome with diarrhea and exocrine pancreatic insufficiency, two conditions that may present similarly but have very different underlying causes and require significantly different management strategies. We outline a 4-step diagnostic strategy and propose a straightforward algorithm to assist in efficiently differentiating irritable bowel syndrome from exocrine pancreatic insufficiency and other causes of chronic diarrhea. We anticipate that these aids will improve diagnostic accuracy, which ultimately should lead to improvements in patients' health-related quality of life and reduce the societal burden on health care services., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The prevalence of celiac disease (CD) is approximately 1% in the US. Studies have shown possible association between exocrine pancreatic insufficiency (EPI) and CD, with numerous hypothesized biological mechanisms including small bowel mucosal damage causing disruption of enteric-mediated hormonal secretion such as cholecystokinin and loss of enterokinase. The overall prevalence of EPI in CD remains unknown. We performed systematic review and metanalysis and examined the prevalence of EPI in patients who were first diagnosed with CD versus those who had been on treatment with gluten-free diet (GFD). Results  Six studies were included in the analysis totaling 446 CD patients (Avg age 44.1 years; 34% Males). One hundred and forty-four patients had newly diagnosed CD, and 302 patients had known CD with at least 9 months treatment with GFD. Four studies examined newly diagnosed CD patients. The individual rates of EPI in new CD patients ranged from 10.5 to 46.5%. The pooled prevalence of EPI in newly diagnosed CD patients was 26.2% (95% CI 8.43-43.92%, Q = 2.24, I 2  = 0%). Five studies examined CD patients on GFD. The rate of EPI ranged from 1.9% to 18.2%. The prevalence of EPI in patients treated with GFD is 8% (95% CI 1.52-14.8%, Q = 4.42, I 2  = 9.59%). Patients with newly diagnosed CD are significantly more likely to have EPI compared to those patients treated with GFD (p = 0.031). CD patients on GFD with persistent symptoms have a significantly higher rate of EPI (28.4%) compared to CD patients on GFD who are asymptomatic (3%) (p < 0.001)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients undergoing pancreatic surgery are at risk of pancreatic exocrine insufficiency (PEI) and needing pancreatic enzyme replacement therapy (PERT)., Methods: This study included 254 patients undergoing pancreatic surgery for oncologic indications. A 13 C mixed triglyceride breath test was performed immediately preoperative and postoperative. This test analyzes the pancreatic remnant lipase activity measuring 13 CO 2 in breath samples after a test meal with 1.3-distearyl-( 13 C-Carboxyl)octanol-glycerol. Cumulative percent dose recovery after 6 h of less than 23% confirms PEI. In addition, PEI was compared between pathology subgroups., Results: In 197 patients undergoing pancreaticoduodenectomy, cPDR-6h decreased significantly from a median of 32.84% before to 15.80% after surgery (p < 0.0001). This decrease in exocrine function was significant in all pathology subgroups except in pancreatic neuroendocrine tumors. Exocrine function decreased most in pancreatic ductal adenocarcinoma (PDAC). In addition, the percentage of patients needing PERT because of PEI increased from 25.9% to 68.0% postoperative (p < 0.001). Overall, patients with an MPD diameter of more than 3 mm had a higher risk of developing postoperative PEI: 62.7% compared to 37.3% (p = 0.009), OR = 3.11. In contrast, the majority of the 57 patients undergoing a distal pancreatectomy did not experience any significant change in exocrine function., Conclusions: The vast majority of patients undergoing pancreaticoduodenectomy for oncologic indications experience a significant drop in exocrine function, are at high risk of developing pancreatic exocrine insufficiency and consequently need to be treated with pancreatic enzyme replacement therapy. Therefore, systematic screening for pancreatic exocrine insufficiency is needed after pancreaticoduodenectomy., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Improvements in survival after pancreaticoduodenectomy has increased the number of patients potentially at risk of pancreatic insufficiency., Aims: We studied long-term (> 1 year) pancreatic functions (endocrine and exocrine) after pancreaticoduodenectomy and aimed to recognize the impact of various clinicopathological factors and postoperative complications on pancreatic functions., Methods: All patients who underwent pancreaticoduodenectomy at least 1 year prior were recruited from July 2020 to December 2021. Endocrine function was assessed using HbA1c, fasting blood sugar and postprandial blood sugar levels. Pancreatic exocrine function was assessed clinically with history of steatorrhea and objectively with quantitative estimation of fecal elastase-1 levels in stool samples. Volume of remnant pancreas, parenchymal thickness and duct diameter were assessed by computed tomography. Quality of life assessment was done using SF-36 questionnaire., Results: Of the 106 patients assessed, 64 patients met the inclusion criteria. Endocrine insufficiency was noted in 51.6%, and 34.3% had new onset diabetes mellitus. The incidence of pancreatic exocrine insufficiency was 87.5% and severe insufficiency was found in 62.5% of patients. Twenty-nine (45.3%) patients had both exocrine and endocrine insufficiency. Patients with CRPOPF had higher risk of severe exocrine insufficiency (5 vs. 2, OR 1.57(0.28-8.81) p = 0.6). The SF-36 scores were lower than general population especially in role limitation due to physical health, role limitation due to emotional problems, energy/fatigue, general health perception and health change domains., Conclusion: Post-pancreaticoduodenectomy patients have a high frequency of pancreatic insufficiency and should be screened for same. The post-operative pancreatic fistula increases the risk of pancreatic exocrine insufficiency., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: We aimed to assess the prevalence of pancreatic exocrine insufficiency (PEI) in Indian patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) using a unique diagnostic criterion., Methods: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration &lt;100 μg/gm stool., Results: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration &lt;100 μg/gm stool., Conclusions: Pancreatic exocrine insufficiency (PEI) was found to be prevalent in nearly one-fourth of Indian patients with diabetes, using composite diagnostic criteria., (© Journal of the Association of Physicians of India 2011.)

Introduction: The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is estimated as 2-46% among patients without known pancreatic diseases. An association between NAFPD and non-alcoholic fatty liver disease (NAFLD) has been proposed, as well as an association between NAFPD and pancreatic exocrine insufficiency (PEI)., Patients and Methods: Patients with histologically confirmed NAFLD were included in the study. The control group consisted of individuals included in a surveillance screening program. Magnetic resonance imaging (MRI) of the pancreas was performed in all patients and fat measurement was made using 2-point Dixon imaging. Fecal elastase-1 (FE-1) was performed to evaluate pancreatic exocrine function. Additionally, a 13 C-mixed triglyceride breath test (13 C-MTG-BT) was performed in patients with FE-1 < 200 μg/g., Results: Imaging signs of NAFPD were present in 17 (71%) patients; 11 (85%) from the NAFLD group and 6 (55%) from the control group. FE-1 < 200 μg/g was found in six (25%) patients (four in the NAFLD group and two in the control group); however, none of them had clinical symptoms of PEI. Therefore, in five out of six patients with low FE-1, a 13 C-MTG-BT was performed, showing normal results (>20.9%) in all tested patients. Furthermore, the serum nutritional panel was normal in all patients with low FE-1. A systematic review identified five studies relevant to the topic., Conclusion: NAFPD was found in 85% of patients with NAFLD and in 55% of control patients. We did not diagnose PEI in either group. A literature review showed PEI in 9-56% of patients with NAFPD.

Purpose: Chronic pancreatitis (CP) leads to diabetes and pancreatic exocrine insufficiency (PEI). PEI may lead to maldigestion and malnutrition, which may cause fat-soluble vitamin deficiency, sarcopenia and abnormal bone density. We aim to study the prevalence of osteoporosis, sarcopenia and vitamin deficiency among CP patients., Methods: Long-term (4-5 years) follow-up was implemented on CP patients. We recorded CP duration, BMI, smoking, alcohol consumption and medication. We determined the serum values for A, D and E vitamins, albumin, creatinine, haemoglobin, calcium and magnesium. Bone density measurement was taken from the proximal femur and lumbar spine. CT/MRI scans were used to measure for psoas muscle area., Results: A total of 33 patients (median age 62 [39-81] years, 61% male) were included. None of these patients had earlier diagnosis of osteopathy, and none of them had known vitamin deficiency or were sarcopenic. Nineteen patients (57%) had pancreatic exocrine insufficiency and of these seven patients (37%) had no pancreatic enzyme replacement therapy (PERT) and one (5%) had inadequate enzyme therapy. During the study, osteoporosis was diagnosed in 20% and possible sarcopenia in 48% of patients. PEI and inadequate PERT was associated with low E vitamin levels (75% vs. 0%, p = 0.012), higher risk of osteoporosis (43% vs. 5.6%, p = 0.013) and sarcopenia (80% vs. 36%, p = 0.044)., Conclusion: This study demonstrates that chronic pancreatitis is associated with osteoporosis, sarcopenia and vitamin deficiency. If untreated, pancreatic exocrine insufficiency is associated with increased risk of these outcomes. This highlights the importance of identifying and treating PEI in CP patients., (© 2023. The Author(s).)

We present the case of a 59-year-old man with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two years later, he consulted for diarrhea and steatorrhea of 2-3 months of evolution with significant weight loss. Stool cultures and study of parasites were negative. Thyroid and celiac profile, cytomegalovirus viremia and colonoscopy, were normal. Fecal calprotectin and fecal clearance of alpha-1-Antitrypsin were normal but with almost undetectable fecal elastase (<15 ug/g). Pancreatic magnetic resonance reveals a generalized atrophy of the pancreas without other parenchymal or ductal alterations. The patient had no risk factors for chronic pancreatitis and was diagnosed with exocrine pancreatic insufficiency (EPI) associated with chronic graft-versus-host disease (GVHD). GVHD is caused by an immune-mediated reaction by donor T cells recognizing foreign antigens from the recipient. GVHD occurs in 80% of patients after allo-HSCT. Diarrhea is one of the most frequent manifestations, most often due to intestinal damage, opportunistic infections or chemoradiation effects.

Introduction: Although abdominal pain is the most prevalent and disabling symptom in patients with chronic pancreatitis (CP), there are also patients who have painless CP., Patients and Methods: We performed a retrospective analysis of patients with a diagnosis of CP. A total of 279 patients with definite CP with completed demographic and clinical data were included in the final analysis., Results: There were 75 (26.9%) patients with painless CP. These patients had a significantly higher mean age at diagnosis, 61.7 years, than the 52.5 years of patients with pain ( p  < 0.001). Painless and painful CP had similar rates of diabetes mellitus (DM) (28.4% vs. 31.6%) and pancreatic exocrine insufficiency (PEI) (50.0% vs. 52.3%). Painless CP had lower rates of alcoholic etiology, 36.0%, than the 52.5% in painful CP ( p  < 0.05). Patients older than 55 at the time of CP diagnosis were associated with painless CP with an adjusted odds ratio (aOR) of 3.27 [95% confidence interval (CI): 1.62-6.60]. Alcoholic etiologies were not associated with painless CP, aOR of 0.51 (95% CI: 0.25-0.91)., Conclusion: Patients with painless CP had a significantly higher mean age than patients with painful CP and increased aOR for those older than 55 at CP diagnosis. Painless and painful CP patients had similar rates of DM and PEI, confirming the necessity of routine follow up in all patients with CP.

Objectives: Patients with inflammatory bowel disease (IBD) frequently have extraintestinal manifestations. The goal of this pilot study was to assess exocrine pancreatic function in cases with suspicion for or an established diagnosis of IBD., Methods: Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD, in both newly diagnosed and established cases. Demographic, clinical, and laboratory parameters were entered into a database and analyzed., Results: Among the 74 children, 49 were newly diagnosed and 25 had an established diagnosis of IBD. A majority had the diagnosis of Crohn disease (CD) (n = 48; 32 new and 16 established cases) with male predominance (64.6%). Altogether, 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). Twenty-four of the 48 CD children (50%) had abnormal ePFT. In those with ulcerative colitis (UC), 18 of the 26 (62.9%) had abnormal ePFT. The highest abnormality rate was in lipase enzyme activity. Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). Peak protein concentration in collected pancreatic fluid was significantly lower in children with CD who had abnormal ePFT ( P = 0.013)., Conclusions: This pilot study revealed a relatively high prevalence of EPI in children with IBD through use of ePFT. EPI can result in maldigestion, with decreased capacity to digest fat. Further prospective studies are needed to assess need and efficacy of pancreatic enzyme replacement therapy in children with IBD and abnormal ePFT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Pancreatic exocrine insufficiency occurs as a clinical consequence of chronic pancreatitis leading to fat maldigestion, malabsorption and malnutrition. Fecal elastase-1 is a laboratory-based test used for the diagnosis or exclusion of pancreatic exocrine insufficiency. The aim of the study was to observe the value of fecal elastase-1 in children with pancreatitis as an indicator of pancreatic exocrine insufficiency. This was a cross-sectional descriptive study conducted from January 2017 through June 2018. Thirty children with pain abdomen as control and 36 patients with pancreatitis as cases were included. An ELISA technique which recognizes human pancreatic elastase-1 from spot stool sample was employed for the test. Fecal elastase-1 activity in spot stool samples in acute pancreatitis (AP) ranged from 198.2-500μg/g with a mean of 342.1±136.4μg/g, acute recurrent pancreatitis (ARP) ranged from 15-500μg/g with a mean of 332.8±194.5μg/g and chronic pancreatitis (CP) ranged from 15-492.8μg/g with a mean of 222.2±197.1μg/g was obtained. In controls, fecal elastase-1 ranged from 28.4-500μg/g with a mean of 398.8±114.9μg/g. Disease severity was classified as mild to moderate pancreatic insufficiency (fecal elastase-1 100 to 200μg/g stool) was found in AP (14.3%) and CP (6.7%) cases. The severe pancreatic insufficiency (fecal elastase-1<100μg/g stool) was observed in ARP (28.6%) and CP (46.7%) cases. Malnutrition was observed in severe pancreatic insufficiency cases. This study result showed that fecal elastase-1 can be used as a measure of pancreatic exocrine function in children with pancreatitis.

Introduction: The diagnosis of pancreatic exocrine insufficiency (PEI) is challenging. The 13 C mixed triglyceride breath test ( 13 C MTGT) has emerged as a promising diagnostic method. However, there is need to assimilate high quality evidence to understand its accuracy and address variation in the conduct of the test. This systematic review aims to appraise the existing literature on the methodology and accuracy of the 13 C MTGT., Methods: A systematic literature search of PUBMED, MEDLINE, and EMBASE databases identified articles describing the use of the 13 C MTGT in the analysis of pancreatic function in adults. Data extraction addressed each methodological step in detail. These were combined in a narrative synthesis. For quantitative analysis, those studies within this search that assessed the accuracy of the 13 C MTGT were selected., Results: 37 studies were included for qualitative review, 6 assessed sensitivity and specificity of the 13 C MTGT against another measure of PEI and were included in quantitative synthesis. Areas with a majority consensus were pre-test overnight fasting, a test meal with a lipid load of at least 10 g, within-test control of exercise and dietary intake, breath sampling every 30 min and the preference of isotope ratio mass spectrometry (IRMS) for analysis. Good evidence suggests there is no benefit to extend the total timeframe of breath sampling beyond 6 h. Areas of uncertainty are a) Duration of PERT cessation b) the addition of metoclopramide, c) the ideal test meal and d) if the time frame can be shortened. Quantitative analysis among 6 studies demonstrated a pooled sensitivity and specificity of the 13 C MTGT for diagnosing PEI of 0.84 (95% CI: 0.73-0.91) and 0.87 (95% CI: 0.79-0.93) respectively., Conclusion: There is yet to emerge a clear standard of breath test methodology that is validated for all causes of PEI and suitable for routine use. The accuracy of the 13 C MTGT for diagnosing PEI is encouraging when compared to other measures. We present a suggested set protocol based on the current literature and identify areas that need further, high quality evidence. With refinement, the 13 C MTGT could become a valuable, non-invasive PEI diagnostic tool that could be used outside of specialist centres., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Exocrine pancreatic insufficiency (EPI) is a critical host factor in determining the composition of the gut microbiota. Diseases that cause exocrine insufficiency can affect the gut microbiome, which can potentiate disease progression and complications. To date, the relationship of exocrine insufficiency in various pancreatic (PA) pathologies, in chronic pancreatitis (CP), with dysbiotic changes in the intestinal microbiota (IM) has not been reliably studied. The available data are heterogeneous and contradictory, which determines the need for further research., Aim: To conduct a comparative analysis of the taxonomic composition of the intestinal microbiota in patients with CP of various etiologies, without or with the presence of EPI of varying severity, as well as patients with severe EPI with a history of surgical intervention (SI) on the pancreas., Materials and Methods: A total of 85 patients were included in the study. Patients were divided into groups according to the severity of EPI: Group 1 ( n =16) - patients with CP without EPI; Group 2 ( n =11) - patients with CP and mild EPI; Group 3 ( n =17) - patients with severe CP and EPI; Group 4 ( n =41) - severe EPI in persons with a history of SI on the pancreas. Verification of CP was carried out according to clinical, anamnestic and instrumental data. The degree of EPI was determined by the level of pancreatic elastase-1 (PE-1) feces. Informed consent for the study was obtained for each patient, an anamnesis was collected, physical and laboratory examinations were performed, and a stool sample was obtained. DNA was extracted from each stool sample, the taxonomic composition of BM was determined by sequencing the bacterial 16S rRNA genes, followed by bioinformatic analysis., Results: We followed the changes in the gut microbiota from a group of patients with CP without EPI to a group with severe EPI, in those who underwent SI. At the level of the phylum, the IM of all groups showed the dominance of Firmicutes , with the lowest representation in the severe EPI group, both with SI and CP, and the growth of the Actinobacteria , Verrucomicrobiota and Fusobacteria types. The differential representation of childbirth varied: in patients with severe EPI and CP, compared with mild, statistically significant genera - Akkermansia , Ruminococcus gauvreauii group and Holdemanella ; compared with CP without exocrine insufficiency, Prevotella , Ruminococcus gauvreauii group , Peptostreptococcus and Blautia dominated. The CP group with mild EPI was dominated by the following genera: Lachnospiraceae&#95;ND 2004 group , Faecalitale a, Fusobacterium , Catenibacterium , Roseburia , Atopobium , Cloacibacillus , Clostridium innococum group , Ruminococcus torques group . All groups showed a low diversity of taxa with a predominance of opportunistic flora, including participants in oncogenesis., Conclusion: The results of the study show that patients with CP of various etiologies and patients with severe EPI who underwent specific intervention on the pancreas have intestinal microbiota dysbiosis, the severity of which is significantly influenced by the degree of EPI.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes., Methods: We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included., Results: Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7)., Conclusions: CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)