Optimizing management of patients with pancreatic exocrine insufficiency.
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ABSTRACT:
SUBMITTER: Arvanitakis M
PROVIDER: S-EPMC9944529 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Optimizing management of patients with pancreatic exocrine insufficiency.
Arvanitakis Marianna M Hadefi Alia A Viesca Michael Fernandez Y MFY
Hepatobiliary surgery and nutrition 20230109 1
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Project description:European evidence-based guidelines for the treatment and management of chronic pancreatitis (CP) have been made available following the harmonizing diagnosis and treatment of CP across Europe (HaPanEU) initiative by the United European Gastroenterology (UEG). The aim of this study was to evaluate adherence to the guideline recommendations in the management of patients with pancreatic exocrine insufficiency (PEI) at Karolinska University Hospital in Stockholm. UEG guideline recommendations were evaluated and categorized into 55 different quality indicators (QIs). Data from a retrospective cohort of CP patients being treated at Karolinska University Hospital were evaluated with regard to overall adherence as well as adherence to specific QIs. A total number of 118 patients out of 956 patients diagnosed with CP were eligible for inclusion with mean overall adherence of 61.9% to the defined QIs. A significant difference in mean overall adherence was shown between patients diagnosed with CP prior to 1 January 2016 and following 1 January 2016 (59.3% and 67.7% respectively, p = 0.004), with linear regression analysis also demonstrating improvement correlating to date of diagnosis (p = 0.002). In conclusion, diagnosis and treatment of PEI improved after the HaPanEU guidelines became available and is continuously improving; however, there is room for further improvement.
| S-EPMC8233716 | biostudies-literature
Project description:Exocrine pancreatic insufficiency (EPI) is a clinically defined syndrome based on the physician's assessment of a patient's maldigestion. However, current clinical definitions are inadequate in determining (1) the threshold of reduced pancreatic digestive enzyme secretion that determines "pancreatic insufficiency" in an individual patient; (2) the role of pancreatic function tests; (3) effects of differing metabolic needs, nutrition intake, and intestinal function/adaptation (4) when pancreatic enzyme replacement therapy is needed; and (5) how to monitor and titrate multiple therapies. Experts and key opinion leaders were invited to PancreasFest 2021 to discuss and help clarify mechanistic issues critical to defining EPI and to address misconceptions and barriers limiting advancements in patient care. Clinically EPI is defined as inadequate delivery of pancreatic digestive enzymes to meals to meet nutritional needs and is reversed with appropriate treatment. A new mechanistic definition of EPI was proposed that includes the disorders essence and character: (1) EPI is a disorder caused by failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of a series of individual snacks and meals over time to meet nutritional and metabolic needs, given (a) the specific macronutritional and micronutritional needs; (b) nutrient intake; (c) exocrine pancreatic function; and (d) intestinal anatomy, function, diseases, and adaptative capacity. (2) EPI is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, by gastrointestinal symptoms of nutrient maldigestion and by improvement or correction of nutritional state with lifestyle changes, disease treatment, optimized diet, dietary supplements, and/or administration of adequate pancreatic enzyme replacement therapy. EPI is complex and individualized and multidisciplinary approaches are needed to optimize therapy. Better pancreas function tests and biomarkers are needed to diagnose EPI and guide treatment.
| S-EPMC11307793 | biostudies-literature
Project description:BackgroundExocrine pancreatic insufficiency (EPI) is a serious condition characterized by a lack of functional exocrine pancreatic enzymes and the resultant inability to properly digest nutrients. EPI can be caused by a variety of disorders, including chronic pancreatitis, pancreatic cancer, and celiac disease. EPI remains underdiagnosed because of the nonspecific nature of clinical symptoms, lack of an ideal diagnostic test, and the inability to easily identify affected patients using administrative claims data.ObjectivesTo develop a machine learning model that identifies patients in a commercial medical claims database who likely have EPI but are undiagnosed.MethodsA machine learning algorithm was developed in Scikit-learn, a Python module. The study population, selected from the 2014 Truven MarketScan® Commercial Claims Database, consisted of patients with EPI-prone conditions. Patients were labeled with 290 condition category flags and split into actual positive EPI cases, actual negative EPI cases, and unlabeled cases. The study population was then randomly divided into a training subset and a testing subset. The training subset was used to determine the performance metrics of 27 models and to select the highest performing model, and the testing subset was used to evaluate performance of the best machine learning model.ResultsThe study population consisted of 2088 actual positive EPI cases, 1077 actual negative EPI cases, and 437 530 unlabeled cases. In the best performing model, the precision, recall, and accuracy were 0.91, 0.80, and 0.86, respectively. The best-performing model estimated that the number of patients likely to have EPI was about 12 times the number of patients directly identified as EPI-positive through a claims analysis in the study population. The most important features in assigning EPI probability were the presence or absence of diagnosis codes related to pancreatic and digestive conditions.ConclusionsMachine learning techniques demonstrated high predictive power in identifying patients with EPI and could facilitate an enhanced understanding of its etiology and help to identify patients for possible diagnosis and treatment.
| S-EPMC7299452 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed late, leading to a high mortality rate. Early detection facilitates better treatment options. The aim of this UK-based case-control study was to determine whether two validated tests for pancreatic exocrine insufficiency (PEI), namely, the 13C-mixed triglyceride breath test (13C-MTGBT) and a faecal elastase (FE-1) test, can discriminate between patients with resectable PDAC versus healthy volunteers (HVs) along with a comparison group with chronic pancreatitis (CP). Discrimination between disease states and HVs was tested with receiver operator characteristic (ROC) curves. In total, 59 participants (23 PDAC (16 men), 24 HVs (13 men) and 12 CP (10 men)) were recruited, with a similar age in each population, and a combined median (IQR) age of 66 (57-71). The areas under the ROC curve for discriminating between PDAC and HVs were 0.83 (95% CI: 0.70-0.96) for the 13C-MTGBT, and 0.85 (95% CI: 0.75-0.95) for the FE-1 test. These were similar to CP vs. HV. In conclusion, PEI occurs in resectable PDAC to a similar extent as in CP; further large-scale, prospective studies using these tests in the primary care setting on high-risk groups are warranted.
| S-EPMC10741412 | biostudies-literature
Project description:Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.
| S-EPMC4155341 | biostudies-literature
Project description:BackgroundPancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta-analysis.MethodsScopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer.ResultsA total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55-86%), being significantly higher when tumours were located in the pancreatic head (relative risk = 3.36, 1.07-10.54; p = 0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37-6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life.Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.
| S-EPMC7724551 | biostudies-literature
Project description:Background and Aims:Fecal elastase-1 (FE-1) as a screening test for exocrine pancreatic insufficiency (EPI) is gaining popularity in clinical practice. The role of imaging in patients with FE-1-related suspicion of EPI remains unclear. The aim of this study was to characterize endoscopic ultrasound (EUS) findings for patients with low FE-1. Methods:A retrospective cross-sectional study was performed in 40 patients who had low FE-1 and underwent EUS to evaluate the pancreas. We obtained data on demographic and lifestyle factors, EUS findings, and histopathology results. We compared these variables between patients with FE-1 < 100 mcg/g vs. 100-200?mcg/g. Results:Most patients (82.5%) established one or more new diagnoses from EUS. Diagnoses included: definitive chronic pancreatitis (n = 29, 72.5%), fatty pancreas (n = 9, 22.5%), and pancreatic solid mass or cyst (n = 9, 22.5%). Half (n = 4) of the solid or cystic lesions were neoplastic. All patients with a solid pancreatic mass also had concurrent chronic pancreatitis. There were no significant differences in EUS findings or demographic or lifestyle factors between groups with FE-1 < 100 mcg/g vs. 100-200?mcg/g. Conclusion:Chronic pancreatitis is the most common EUS finding in patients with low FE-1 levels. EUS appears helpful in determining the cause of EPI in most patients with low FE-1 and may detect unsuspected pancreatic neoplasia.
| S-EPMC6710758 | biostudies-literature
Project description:E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.
| S-EPMC406522 | biostudies-literature
Project description:Background/objectivesThe epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis.MethodsScopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests.ResultsQuantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests.ConclusionsThe prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.
| S-EPMC6584228 | biostudies-literature
Project description:Exocrine pancreatic insufficiency (EPI) is a malabsorptive syndrome resulting from insufficient secretion of pancreatic digestive enzymes. EPI is treated with pancreatic enzyme replacement therapy (PERT), but the persistence of clinical signs, especially diarrhea, is common after treatment. We used untargeted metabolomics of serum to identify metabolic disturbances associated with EPI and generate novel hypotheses related to its pathophysiology. Fasted serum samples were collected from dogs with EPI (n = 20) and healthy controls (n = 10), all receiving PERT. Serum metabolomes were generated using UPLC-MS/MS, and differences in relative metabolite abundances were compared between the groups. Of the 759 serum metabolites detected, 114 varied significantly (p < 0.05, q < 0.2) between dogs with EPI and healthy controls. Differences in amino acids (arginate, homoarginine, 2-oxoarginine, N-acetyl-cadaverine, and α-ketoglutaramate) and lipids (free fatty acids and docosahexaenoylcarnitine) were consistent with increased proteolysis and lipolysis, indicating a persistent catabolic state in dogs with EPI. Relative abundances of gut microbial metabolites (phenyllactate, 4-hydroxyphenylacetate, phenylacetyl-amino acids, catechol sulfates, and o-cresol-sulfate) were altered in dogs with EPI, consistent with disruptions in gut microbial communities. Increased kynurenine is consistent with the presence of intestinal inflammation in dogs with EPI. Whether these metabolic disturbances participate in the pathophysiology of EPI or contribute to the persistence of clinical signs after treatment is unknown, but they are targets for future investigations.
| S-EPMC10376357 | biostudies-literature