Search

Introduction: Type 1 and type 2 diabetes mellitus (DM) are often accompanied by mild forms of pancreatic exocrine insufficiency (PEI). The prevalence rates of PEI in diabetic patients are unclear and variable depending on the testing modality and the studies published. The clinical consequences of PEI in diabetics are also not well defined., Aim: We aimed to determine the prevalence of PEI in a diabetic cohort using the faecal elastase-1 (FE-1) assay as a screening test and to validate a patient-reported symptom-based scoring system, the (PEI-S) for diagnosing PEI within this patient population., Methods: Two hundred and three diabetic patients attending diabetic and gastroenterology outpatients of a university hospital without previously known PEI were recruited for the study. Demographic parameters, PEI score (PEI-S), and glycated hemoglobin (HBA1c) were documented in standardized data sheets, and a stool sample was obtained. A FE-1 value < 200 μg/g and or a PEIS of > 0.6 was used as the screening cut-off for PEI., Results: One hundred sixty-six patients returned faecal samples. The prevalence of PEI, as measured by low FE-1, was 12%. Smoking was associated with an increased risk of developing PEI in this diabetic population. No other independent risk factors were identified. The PEI-S system did not differentiate between people with diabetes having a normal and low FE1., Conclusion: 12% of this mixed, real-life cohort of type 1 and 2 DM patients had undiagnosed PEI, as defined by an FE-1 score of less than 200 μg/g. While this may appear low, given the rising prevalence of type 2 DM worldwide, there is likely an unrecognized burden of PEI, which has long-term health consequences for those affected. The PEI-S, a symptom-scoring system for patients with PEI, did not perform well in this patient group., (© 2024. The Author(s).)

Exocrine pancreatic insufficiency (EPI) is a condition caused by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption of nutrients. Clinical manifestations of EPI may include steatorrhea, weight loss, diarrhea, and abdominal pain. Although direct testing is the most sensitive and specific for EPI, these tests are invasive, time consuming, expensive, and not well standardized. Fecal elastase (FE-1) has been shown to be an indirect marker of the exocrine secretory capacity of the pancreas and has become the most commonly employed indirect test for diagnosis of EPI. Measurement of fecal elastase consists of two main phases, a preanalytical phase and analytical phase. The preanalytical phase involves stool collection, storage and handling. The second phase is the analytical phase, which includes the actual assay processes and products used to produce a result. For FE-1 this includes sample extraction and measurement on an immunoassay. Each step in the process can influence the result and contribute to heterogeneity in FE-1 measurement, potentially impacting clinical diagnosis and management. Thus, this paper provides an overview of the preanalytical and analytical factors that can affect measurement and interpretation of FE-1 results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

In mild cases, it is difficult to diagnose pancreatic exocrine insufficiency (PEI). There is no gold standard method for the diagnosis of PEI. A reliable method is needed for preliminary diagnosis of PEI. The PEI-TEST was applied to the patients with nonspecific gastrointestinal complaints. Serum amylase, lipase, serum trypsinogen, and fecal elastase 1 (FE-1) were analyzed from each patient. According to the PEI-TEST, PEI was present in 42 (47.7%) and PEI was not present in 46 (52.3%) patients. No significant difference was observed between the 2 groups with regard to age, gender and amylase, lipase, serum trypsinogen, and FE-1. When an FE-1 value of <200 µg/dL was considered as indicating PEI, the sensitivity and specificity of the test were found to be 47.4% and 52.2%, respectively. Although it is promising that PEI-TEST is a validated test in our country and suitable for our society, it is not suitable for pediatric patients., 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.

The existence of alpha-1 antitrypsin variants with apparently unremarkable phenotypes and serum concentrations, contrasting with a clinical picture suggestive of a severe deficiency, led us to investigate whether in these cases there was a reduction or even suppression of the capacity of alpha-1 antitrypsin to inhibit elastase. To this end, in two different laboratories, we adapted and validated a method for measuring the functional activity of alpha-1 antitrypsin, based on spectrophotometric kinetic analysis of the inhibition by serum alpha-1 antitrypsin of the hydrolytic activity of porcine pancreatic elastase on a chromogenic substrate. This method has proved to be robust, reproducible and transferable and made possible to define, on the basis of an analysis of a hospital population, a functionality index with a confidence interval comprised between 0.87 and 1.2, allowing to identify subjects likely to have a functional deficiency of alpha-1 antitrypsin, whether this deficiency being of a genetic origin without any quantitative or phenotypic translation, or whether being acquired under the effect of external agents (cigarette smoke or viruses).

Tendon exhibits the capacity to be stretched and to return to its original length without suffering structural damage in vivo, a capacity known as elastic recoil. Collagen fibres are aligned longitudinally and elastin fibres mostly run parallel to collagen fibres in tendon. However, their interactions and contributions to tendon elastic behaviours are not well understood. The present study examined functional roles of collagen and elastin in tendon elastic behaviours using a variety of mechanical tests. We prepared three types of fascicle specimens from mouse tail tendon: fascicles freshly isolated, those digested with elastase in PBS to selectively remove elastin, and those incubated in PBS without elastase. A quasi-static tensile test demonstrated that elastase-treated fascicles had higher tangent moduli and strength compared to fresh and PBS fascicles. Cyclic stretching tests showed that fresh and PBS fascicles could withstand cyclic strain at both small and large amplitudes, but elastase-treated fascicles could only behave elastically to a limited degree. Fibre-sliding analysis revealed that fresh fascicles could be elongated both through stretching of collagen fibers and through movement of the fibres. However, elastase-treated fascicles could be stretched only via fibre stretching. This evidence suggests that normal tendons can be extended through both fibre stretching and fibre sliding, whereas tendons without elastin can only extend as much as collagen fibers can withstand. Accordingly, collagen fibres mainly contribute to tendon elastic behaviours by furnishing rigidity and elasticity, whereas elastin provides tendon viscoelasticity and also enables sliding of collagen fibres during elastic behaviours. STATEMENT OF SIGNIFICANCE: The present study revealed distinct mechanical functions of collagen and elastin fibres in elastic behaviours of mouse tail tendon fascicle using a variety of mechanical tests at both microscopic and macroscopic levels. It was demonstrated that collagen mainly governs tendon fascicle rigidity and elasticity, but only possesses limited extensibility, whereas elastin contributes to viscoelasticity and collagen fibre sliding, enabling elastic recoil behaviour against relatively large deformation. By their interactions, tendon can be elongated without suffering major structural damage and withstand a large magnitude of tensile force in response to mechanical loading. Such information should be particularly useful in designing collagen-based biomaterials such as artificial tendons, in that previous studies have merely considered collagen without incorporation of elastin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background/aims:  Pancreatic steatosis (PS) is a pathology associated with metabolic syndrome (MS), endocrin and exocrine disfunctions of the pancreas, and fatty liver. The data on the frequency of PS are very limited. We aimed to evaluate the frequency of PS detected by transabdominal ultrasonography (TAU) in gastroenterology clinics located in different geographical regions of Turkey and the factors associated with it., Materials and Methods:  Volunteers were evaluated by TAU for PS and hepatosteatosis (HS), and its degree. Pancreatic stiffness was evaluated by ultrasonographic shear wave elastography (SWE). All demographic, physical, and biochemical parametres were measured., Results:  A total of 1700 volunteers from 14 centers throughout Turkey were included in the study. Mean age was 48.03 ± 20.86 years (56.9% female). Prevalance of PS was detected in 68.9%. In the PS group, age, body mass index (BMI), waist circumference, systolic blood pressure, fasting blood glucose (FBG), lipid levels, insulin resistance, diabetes mellitus, hypertension, MS frequency, and pancreatic SWE score were increasing, and fecal elastase level was decreasing in correlation with the degree of PS. The frequency of HS was 55.5%. Hepatosteatosis [odds ratio (OR): 9.472], increased age (OR: 1.02), and BMI (OR: 1.089) were independent risk factors for the occurrence of PS. Lean-PS rate was 11.8%. The lean-PS group was predominantly female and younger than non-lean PS. Also it has lower blood pressure, FBG, liver enzymes, lipid levels, and HS rates., Conclusion:  The frequency of PS was found 68.9% in Turkey. Its relationship was determined with age, BMI, HS, MS (and its components), pancreatic stiffness, and fecal elastase level.

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.

Background: Low faecal elastase-1 (FE-1) results are suggestive of pancreatic insufficiency, but watery diarrhoea may lead to falsely low results., Methods: FE-1 results reported on watery samples over a three-year period were reviewed. Results in watery samples were compared to those from a formed sample. The follow-up of patients in whom an FE-1 result ≤199 ug/g stool (Schebo ELISA) was reported on a watery sample was also reviewed., Results: In total, 288 watery samples were identified. All results (19/19) ≥200 ug/g in watery samples were also ≥200 ug/g when measured in a formed sample from the same patient. There were 41 results ≤199 ug/g in watery samples, of which 29 (71%) were ≥200 ug/g when measured in a formed sample. Thirty-seven patients with a single FE-1 value ≤199 ug/g from a watery sample were followed up. Pancreatic Enzyme Replacement Therapy (PERT) was commenced in 15 patients. This was inappropriate in at least one patient. Reporting practice was subsequently changed to not report FE-1 values ≤199 ug/g in watery samples. This change was assessed after 12 months. Repeat samples were received from 15/56 (27%) of patients. Overall, 10/15 (67%) of samples were ≥200 ug/g on repeat. PERT was not commenced inappropriately in any of these patients., Conclusions: There is value in measuring FE-1 in watery samples, as 144/288 (50%) of watery samples analysed were ≥200 ug/g, enabling a diagnosis of exocrine pancreatic insufficiency to be excluded. Not reporting FE-1 values ≤199 ug/g in a first-time watery stool samples appears clinically safe and has potentially reduced inappropriate diagnoses and prescribing.

Objective: The aim: To conduct a comparative analysis of parameters of the structural and functional state of the liver and pancreas in patients with chronic pancreatitis in comorbidity with treated etiologically chronic viral hepatitis C, depending on the results of testing according to the international CAGE questionnaire., Patients and Methods: Materials and methods: 100 ambulatory patients with CP with concomitant HCV, treated etiotropically, were examined. All patients were examined ac-cording to generally accepted algorithms. To establish the role of alcohol on the formation of CP and the condition of patients with treated HCV, latent craving for alcohol was verified using the international CAGE questionnaire. The study of the density of the liver parenchyma and the liver of the patients was carried out not only according to the ultrasound data in the B-mode, but also with the simultaneous measurement of the shear wave elastography (SWE) method on the Ultima PA scanning ultrasound device with the further determination of the median of the parameters, which characterizes the stiffness in kilopascals (kPa). Determination of the presence and depth of pancreatic exocrine insufficiency (PEI) was carried out by the content of fecal elastase-1 (FE-1), which was determined by the enzyme immunoassay method., Results: Results: Screening-testing of patients with CP on the background of etiotropically treated HCV using the CAGE scale made it possible to state that 65.0% of such patients had a hidden craving for alcohol, and 21.0% of this cohort were women, which needs to be taken into account in the management of such patients. It has been proven that in the group of patients with CAGE≥2.0, the level of functional and structural changes in the liver and liver was significantly more severe (according to the deepening of the PEI, a decrease in fecal α-elastase by 13.01%, according to an increase in the total index of the coprogram by 15.11% and the total US-indicator of the pancreas structure by 28.06%, and the total US-indicator of the liver structure - by 40.68% (p<0.05) and corresponded to the average degree of severity of the process in panceas according to the criteria of the Marseille-Cambridge classification, and in the group with CAGE<2.0 - only a mild degree., Conclusion: Conclusions: The negative effect of the factor of increased alcohol use according to CAGE was proven by increasing the density of the echostructure of the liver by 5.73% (p<0.05), and the liver by 5.16% (p<0.05). According to the results of the correlation analysis of the dependence of the structural state of the liver and PW of the studied patients on the value of the CAGE scale, which was R=0.713, p<0.05, and R=0.686, p<0.05, respectively, it was established that there is a strong direct dependence of the structural state of the liver and PW from the value of the CAGE questionnaire, which proved an independent, reliably significant role of alcohol consumption for patients with a comorbid course of CP and HCV.

Background: Pancreatic elastase-1 (PE1) can be measured to assess exocrine activity of the pancreas. A semi-automated particle-enhanced, open-channel turbidimetric immunoassay has been introduced by Bühlmann (fPELA turbo, Bühlmann Laboratories AG, Schoenenbuch, Switzerland). Published evaluation data is lacking. We therefore verified performance of the assay on the Binding Site Optilite benchtop analyser and undertook a sample comparison with the DiaSorin PE1 assay on the Liaison., Methods: Accuracy, imprecision, lower limit of quantitation (LLoQ) and linearity of the Bühlmann fPELA turbo assay on the Binding Site Optilite analyser was ascertained. Comparison with the DiaSorin Liaison PE1 assay was also undertaken. Difference between assays was evaluated using the Wilcoxon signed-rank test and method comparison was undertaken using Spearman's rank correlation (rs), Bland-Altman and Passing-Bablok regression analyses., Results: The fPELA turbo assay was linear between 5 and 2500 μg/g. The LLoQ was 5 µg/g. Intra- and inter-assay imprecision was <6%. There was a good agreement (rs = 0.92) and no significant bias (5.8 µg/g, P = 0.29) present between the Bühlmann fPELA turbo and DiaSorin PE1 assays., Conclusion: The Bühlmann fPELA turbo assay performs well on the Binding Site Optilite analyser. Faecal elastase results are commutable between with Bühlmann fPELA turbo and DiaSorin Liaison PE1 assays.

Background and Aims: Pancreatic resection is associated with pancreatic exocrine insufficiency (PEI) leading to nutritional consequences. The Pancreatic Nutrition Clinic was established to diagnose and manage PEI through standardised nutritional assessment. In this prospective observational study, we aimed to define the rate of PEI, diabetes mellitus and nutritional abnormalities in patients who underwent pancreatic resection., Methods: All Pancreatic Nutrition Clinic patients were included for analysis. Clinical data were prospectively obtained at initial assessment. Biochemical data included micronutrient levels, faecal elastase-1 and haemoglobin A1c. Bone mineral density and nutritional assessment were undertaken., Results: Ninety-eight patients were included. Fifty-nine per cent (58/98) had undergone a pancreatoduodenectomy. Ninety-three patients had a faecal elastase-1 result, 65% (60/93) of which had a faecal elastase-1 less than 200 μg/g of faeces. Seventy-five patients (76%) of the total population required PERT, and thirty-nine (40%) were classified as malnourished using the patient-generated subjective global assessment tool. Seventy-two per cent (70/97) had a biochemical deficiency of one or more micronutrients. Thirty-eight people (39%) had diabetes mellitus. Of the seventy-eight patients with a bone mineral density scan available for analysis, 29% (23/78) had osteoporosis and 49% (38/78) osteopenia., Conclusions: Pancreatic exocrine insufficiency, micronutrient deficiency, bone disease, diabetes mellitus and malnutrition are highly prevalent in patients who have undergone pancreatic resection., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2022 IAP and EPC. All rights reserved.)

This study aimed to investigate the chemical composition of essential oils isolated from Acca sellowiana (feijoa) leaves and stems and elaborate on their relevance as natural anti-aging, coupled with molecular-docking studies. The isolated oils were analysed using gas chromatography-mass spectrometry analysis and investigated for inhibitory effects against acetylcholinesterase, β-secretase, collagenase, elastase and tyrosinase. Molecular-modelling study was performed using MOE-Dock program to evaluate binding interactions of major components with the above-mentioned targets. The leaf oil revealed the predominance of caryophyllene oxide (24.3 %), linalool (7.9 %), and spathulenol (6.6 %), while the stem oil was presented by caryophyllene oxide (38.1 %), α-zingiberene (10.1 %) and humulene oxide II (6.0 %). The stem oil expressed superior inhibitory activities against acetylcholinesterase (IC 50 =0.15±0.01 μg/mL), β-secretase (IC 50 =3.99±0.23 μg/mL), collagenase (IC 50 =408.10±20.80 μg/mL), elastase (IC 50 =0.17±0.01 μg/mL) and tyrosinase (IC 50 =8.45±0.40 μg/mL). The valuable binding interactions and docking scores were observed for caryophyllene oxide and α-zingiberene with acetylcholinesterase. Besides, α-zingibirene followed by linalool and τ-cadinol revealed tight fitting with collagenase and elastase. Additionally, linalool, spathulenol and τ-cadinol showed the best binding energy to tyrosinase. This study provides valuable scientific data on A. sellowiana as potential candidates for the development of natural antiaging formulations. The current study provided scientific evidence for the potential use of feijoa essential oils in antiaging formulations and as an adjuvant for the prophylaxis against Alzheimer disease., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Fecal pancreatic elastase 1 (FPE1) is an established screening test for pancreatic exocrine insufficiency (PEI), a condition that is underdiagnosed and if not treated may cause significant morbidity. The aim of this study was to compare a new FPE1 machine based CLIA kit to an ELISA assay which is considered the de facto gold standard in our laboratory for FPE1 measurement., Methods: Levels of FPE1 from the 227 stool samples were analyzed by the ScheBo ELISA kit and the CLIA Liaison XL system simultaneously with the same cutoff values for both assays. Performance of the Liaison XL system was assessed by calculating sensitivity, specificity, and accuracy., Results: The comparison between the Liaison XL system performance and the ScheBo ELISA kit as reference revealed a sensitivity, specificity, and accuracy of 86.8%, 94.3%, and 92.1%, respectively, using a cutoff of 100 µg FPE1/g stool. When the cutoff is 200 µg FPE1/g stool the sensitivity, specificity, and accuracy were 86.6%, 97.1%, and 90.7%, respectively. Furthermore, linear correlation of FPE1 levels between the two assays were found to be significant by Pearson's correlation coefficient test (R = 0.85, p-values < 0.0001)., Conclusions: The Liaison XL system showed good laboratory performance with our pre-determined cutoff values when compared to our previous assay. An important advantage of this system is its semi-automated mechanism that enables large scale analysis of FPE1. In addition to that, the Liaison XL system is ideal for both qualitative and quantitative analysis of FPE1 allowing for its application to the clinical setting.

Objectives: We describe the methodology of Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency (PAPPEI), a prospective, observational, multicenter cohort study. The objectives of PAPPEI are to estimate the incidence rate of post-acute pancreatitis (AP) pancreatic exocrine insufficiency (PEI), define factors that determine the development of post-AP PEI, and evaluate the impact of post-AP PEI on nutritional status and quality of life., Methods: Enrollment started in June 2017 in 3 expert academic centers in the United States. Data were collected during hospitalization (baseline) at 3 and 12 months after enrollment. Fecal elastase-1 was used to assess PEI. Study questionnaires are completed by patient interview and review of electronic medical records. Blood is obtained to evaluate vitamin deficiencies and nutritional markers., Results: As of August 2020, 77 subjects have completed the baseline evaluation. The median age was 58 years (interquartile range, 39-67 years), 38% were male, and 90% were white. The etiology of AP was biliary in 39 subjects (51%), and 51 subjects (66%) had mild AP. Three- and 12-month follow-up data have been collected in 29 and 13 subjects, respectively., Conclusion: The PAPPEI study aims to expand our understanding of post-AP PEI incidence, including its impact on nutritional status and quality of life., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Neutrophils release web like-structures known as neutrophil extracellular traps (NETs) that ensnare and kill microorganisms. These networks are constituted of a DNA scaffold with associated antimicrobial proteins, which are released to the extracellular space as an effective mechanism to fight against invading microorganisms. In parallel with this beneficial role to avoid microbial dissemination and wall off infections, accumulating evidence supports that under certain circumstances, NETs can exert deleterious effects in inflammatory, autoimmune, and thrombotic pathologies. Research on NET properties and their role in pathophysiological processes is a rapidly evolving and expanding field. Here, we describe a combination of methods to achieve a successful in vitro NET visualization, semiquantification, and isolation.

Backgrounds: We aimed to monitor pancreatic exocrine function longitudinally in relation to the development of islet autoimmunity (IA) and type 1 diabetes (T1D) in at-risk children with a first-degree relative with T1D, who were followed prospectively in the Environmental Determinants of Islet Autoimmunity (ENDIA) study., Methods: Fecal elastase-1 (FE-1) concentration was measured longitudinally in 85 ENDIA children from median age 1.0 (IQR 0.7,1.3) year. Twenty-eight of 85 children (progressors) developed persistent islet autoantibodies at median age of 1.5 (IQR 1.1,2.5) years, of whom 11 went on to develop clinical diabetes. The other 57 islet autoantibody-negative children (non-progressors) followed similarly were age and gender-matched with the progressors. An adjusted linear mixed model compared FE-1 concentrations in progressors and non-progressors., Results: Baseline FE-1 did not differ between progressors and non-progressors, or by HLA DR type or proband status. FE-1 decreased over time in progressors in comparison to non-progressors (Wald statistic 5.46, P = .02); in some progressors the fall in FE-1 preceded the onset of IA., Conclusions: Pancreatic exocrine function decreases in the majority of young at-risk children who progress to IA and T1D., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Prior to the use of cystic fibrosis (CF) modulator therapy, exocrine pancreatic insufficiency in CF was thought to be irreversible. Improvement in pancreatic function on ivacaftor has been reported in open label studies in 1-5 year olds. The mechanism by which ivacaftor might improve exocrine pancreatic function is unclear. Although the effect of ivacaftor on pancreatic function may be more significant in younger children, evidence is mounting that there may still be potential for improvement in older children on long term therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Pancreatic exocrine insufficiency (PEI) is found in 30-50% of diabetes mellitus (DM). Insulin resistance is triggering factor in both DM and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to investigate frequency of PEI in NAFLD, and relationship of fecal pancreatic elastase (PE) levels with liver histology and pancreatic fat., Methods: Ninety-seven biopsy proven NAFLD patients and 50 controls were enrolled. Pancreas exocrine functions were measured by PE. Magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) was used to quantify fat., Results: NAFLD patients had significantly lower PE levels than controls (297 [204-517] vs. 500 [298-678] μg/g, p < 0.01). PEI (PE < 200 μg/g) ratio of NAFLD patients (22.7%, n = 22) was higher than PEI ratio of controls (6%, n = 3) (p = 0.011). Among diabetic (n = 35) NAFLD patients, 9 (25.7%) exhibited PEI, compared to 13 (21%) of non-diabetics. There was no significant difference in patients with and without DM in terms of PEI (p = 0.592). Among NASH (n = 68) patients 16 (23.5%) exhibited PEI, compared to (20.7%) of non-NASH (p = 0.76). Multiple analysis revealed NAFLD as a predictor of PEI independent of age, sex and DM (OR = 4.892, p = 0,021). Mean pancreas MRI-PDFF was significantly higher in diabetics (13.7% ± 3.6% vs. 8.7% ± 5.1%, p = 0.001). There was no significant pancreas MRI-PDFF difference between NASH and non-NASH (P = 0.95). Mean pancreas MRI-PDFF was significantly higher in patients with PEI (13.7% ± 3.4% vs. 8.9% ± 5.2%, P < 0.01)., Conclusion: This is the first study demonstrating the high frequency of PEI in NAFLD independent of DM. Moreover, increasing pancreatic steatosis appears to be associated with higher frequency of PEI in NAFLD., Competing Interests: Declaration of competing interest We confirm that there are no financial or other relations that could lead to a conflict to interest. We also verify that all authors had access to the data and a role in writing the manuscript., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice., Objectives: The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy., Methods: Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy., Results: One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%., Conclusions: In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

Objectives: The aim of this study was to investigate if pancreatic steatosis measured by proton density fat fraction (PDFF) is associated with exocrine pancreatic function defined by fecal elastase concentrations., Materials and Methods: A total of 1458 volunteers (777 women; age range, 21-88 years) underwent magnetic resonance imaging of the pancreas, and organ fat content was quantified by using confounder corrected PDFF. Exocrine pancreatic function was categorized by fecal elastase levels using defined cutoffs: greater than 200 μg/g normal function (n = 1319) and 200 μg/g or less impaired function (n = 139). Statistical analysis to correlate pancreatic fat content with fecal elastase included linear regression, and analyses were adjusted for known confounders for pancreatic steatosis, such as age, sex, and body mass index., Results: Overall mean (±standard deviation) of pancreatic fat content was 7.50% ± 3.78%. Pancreatic fat content was significantly higher in subjects with impaired pancreatic exocrine function (9.36% ± 4.95%) compared with subjects with normal function (7.30% ± 3.59%; P < 0.01). Linear regression analyses showed an inverse correlation between pancreatic fat and fecal elastase levels over the whole study population (beta, -7.19 [standard error, 1.39]; P < 0.01) as well as in the subgroup of subjects with normal function (-4.26 [1.32]; P < 0.01). Among subjects with impaired pancreatic exocrine function, a trend toward an inverse relation was detected (-1.28 [0.84]; P < 0.13)., Conclusions: An inverse correlation between PDFF of the pancreas and fecal elastase suggests an association between pancreatic steatosis and impaired pancreatic exocrine function.

The exocrine structure is significantly affected by diabetes because of endocrine structure-function disorder within the pancreas. Exocrine pancreatic dysfunction (EPD) is the general name of the malabsorption process resulting from inadequate production, release, decreased activation, and/or insufficient degradation of enzymes required for digestion from pancreatic acinar cells. It is important to diagnose patients early and correctly, since there may be both macro- and micro-nutrient deficiency in EPD. In this paper, EPD, the diabetes-EPD relationship, and the predictive, effective factors affecting the emergence of EPD are briefly explained and summarized with contemporary literature and our experienced based on clinical, lab, and radiological findings., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Aims: Altered pancreatic exocrine function can be observed in patients with type 1 or type 2 diabetes. In the present study, we evaluated the potential nutritional consequences of this dysfunction., Methods: Serum concentrations of nutritional markers, including albumin, cholesterol, triacylglycerol, vitamins A, D, and E, were assessed in a cohort of 468 patients (137 with type 1 diabetes and 331 with type 2 diabetes), after exclusion of the patients with a CRP > 10 mg/l. These patients were compared with 47 patients with diseases of the exocrine pancreas and diabetes (type 3c diabetes or pancreatogenic diabetes). Fecal elastase-1 and chymotrypsin concentrations were measured and patients with type 1 and type 2 diabetes were divided into three groups according to whether zero (group NN), one (group LN), or both (group LL) concentrations were decreased., Results: Several markers differed significantly between the groups of patients, including BMI, albumin, phosphorus, and fat-soluble vitamins. Patients with pancreatogenic diabetes had markedly more profound alterations than patients with type 1 or type 2 diabetes and altered exocrine function. However, patients with type 1 or type 2 diabetes and decreased concentrations of both elastase-1 and chymotrypsin had lower albumin, phosphorus, and vitamin A than patients with normal pancreatic exocrine function., Conclusions: Modest nutritional alterations were found in patients with type 1 or type 2 diabetes and altered exocrine function. Patients with type 1 or type 2 diabetes and altered exocrine function may thus deserve to be screened for nutritional deficiencies.

Objectives: Pancreatic insufficiency in children is usually associated with diseases such as cystic fibrosis, Shwachman-Diamond syndrome, or chronic pancreatitis. Fecal elastase-1 is a reliable laboratory test for the diagnosis of exocrine pancreatic insufficiency (EPI). Transient pancreatic insufficiency has been rarely described and data on this entity are lacking in the medical literature. In this retrospective study we report 17 cases of transient pancreatic insufficiency presented mainly with failure to thrive and/or diarrhea., Methods: We followed 43 children (age range 1 month-18 years) with low fecal elastase-1 in our institution between the years 2009 and 2017. We followed growth and laboratory results (particularly, complete blood count, albumin, transaminases, celiac serology, sweat test, and fat-soluble vitamins). Elastase levels <200 mg/g were considered as pancreatic insufficiency., Results: Twenty-six were excluded due to missing data, a comorbidity or being syndromatic. Enrolled children (17) were all otherwise healthy.The median age at diagnosis was 3 years (range 0.2-15 years), 11 girls and 6 boys. Their main presenting symptoms were failure to thrive and/or diarrhea. Median fecal elastase-1 levels were 71 mg/g (range 18-160). Median time for normalization was 6 months (range 1-48 months). Abdominal sonography, celiac serology, and sweat test were normal for all patients. Most patients were treated with pancreatic enzymes until resolution., Conclusions: Transient EPI without clear etiology should be in the differential diagnosis of EPI after ruling out known etiologies. The resolving course pattern may be attributed to an unidentified infectious agent. Further studies to assess the etiology are mandated.

Background: Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis (CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency (PEI), which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting results., Aim: To investigate serum zinc levels in patients with CP of various etiologies., Methods: Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the M-ANNHEIM classification system into the following etiological subcategories: alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal (fecal elastase 1 > 200 μg/g), mildly reduced (100-200 μg/g) and severely reduced (fecal elastase 1 < 100 μg/g)., Results: A total of 150 patients were included in the analysis. Zinc deficiency (< 11 μmol/L) was present in 39 (26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency (FE-1 < 200 μg/g). Older age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients < 40 years of age [OR: 3.8, 95%CI (1.08-13.4); P = 0.04]; [OR 6.26, 95%CI (1.94-20.2), P > 0.002]. Smoking and number of pack-years were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher compared to those who had never smoked. Gender, body mass index, etiology of CP, presence of diabetes mellitus, levels of glycated hemoglobin (HbA1c), bone mineral density, alcohol intake and presence of PEI were not associated with low zinc levels., Conclusion: Zinc deficiency is common in patients with CP and is significantly associated with age ≥ 60, smoking and the number of pack-years, but not with PEI., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.

Background and Aim: There is lack of data on functional and morphological recovery after an attack of acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in children. This study aims to evaluate the functional impairment and morphological changes in the pancreas after recovery., Methods: All consecutive patients presenting with AP (n = 61) or ARP (n = 35), as per standard diagnostic criteria, were enrolled. After 2 months of pancreatitis, fecal elastase-1 (FE-1) (μg/g) and 2-h oral glucose tolerance test to calculate oral disposition index (DI o ) (mmol/L) (β-cell function) were performed. Morphological changes were assessed by endoscopic ultrasound and transabdominal ultrasound. Patients with chronic pancreatitis (CP) (n = 27) and healthy children (HC) (n = 26) were included as controls for functional parameters., Results: At a median follow up of 12 (4-44) and 11 (2-108) months, 66.7% and 75.9% (P = 0.57) of AP and ARP demonstrated exocrine insufficiency (FE-1 < 200), respectively. Mean (SD) FE-1 was 183.64 ± 150.94 (AP), 135.70 ± 103.80 (ARP), 46.56 ± 30.20 (CP), and 240.00 ± 181.83 (HC) (P < 0.001; anova) (AP vs CP, ARP vs CP, and CP vs HC; P < 0.001). Prediabetes due to insulin resistance was seen in 16.6% and 22.6% (P = 0.56) of AP and ARP. Median (interquartile range) DI o (mmol/L) was comparable between AP (4.20 [2.36, 8.3]) and HC (5.20 [2.89, 8.68]), but was low in ARP (2.97 [1.80, 5.12]), which was comparable with CP (1.91 [1.20, 2.83]). Endoscopic ultrasound demonstrated morphological changes in 25% and 37% (P = 0.34) of AP and ARP, respectively., Conclusion: There was high frequency of biochemical evidence of exocrine insufficiency. β-Cell function (DI o ) was preserved among AP but was poor in ARP. Nearly one-third showed morphological changes in imaging., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Study Aims: We aimed to demonstrate the association between fecal elastase levels and Rosemont categories in patients with chronic changes in pancreas detected with endoscopic ultrasound., Patients and Methods: Patients were selected consecutively from endosonography examinations performed for upper gastrointestinal subepithelial lesions and for pancreas evaluation. Pancreas imaging findings were categorized according to the Rosemont criteria using echoendoscope. Patients who were indeterminate of, suggestive of, and consistent with chronic pancreatitis were included in the study. Fecal elastase measurements were performed after the patients were qualified to participate in the study according to endosonography findings., Results: Seventy patients were included in the study. 54 of them were male. Mean age of the patients was 51.7 ± 10.2 year. There were 36 patients in the indetermine group for chronic pancreatitis. Mean fecal elastase level was 507.1 ± 14.6 μ g/g in the indeterminate group. There were 24 patients in the suggestive group of chronic pancreatitis. Mean fecal elastase level was 400.4 ± 121.4 μ g/g in the suggestive group of chronic pancreatitis. There were 10 patients, in the consistent group with chronic pancreatitis. Mean fecal elastase level was 134.8 ± 86.1. The difference between the three groups of fecal elastase values was statistically significant compared with Kruskal Wallis test. Ordinal logistic regression analysis showed that there was a significant relation between endosonografic categories and fecal elastase values with Nagelkerke value of 0.704., Conclusions: Fecal elastase levels of each of the endosonographic categories were significantly different from each other. Also, fecal elastase values can predict chronic changes in pancreas detected with endoscopic ultrasound.

Background: The optimal nutritional therapy in the field of pancreatic surgery is still debated., Methods: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group., Results: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement., Conclusion: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background/aims: Pancreatic steatosis (PS) is a generally used term to define accumulation of fat in the pancreas. In theory PS may be able to affect the exocrine function of pancreas. In this study we aimed to determine the effect of PS on exocrine pancreas function., Materials and Methods: Forty-three patients with PS determined by 3 tesla magnetic resonance imaging (MRI) and 48 patients without PS were included in this study. Patients with PS were classified as group 1 and control patients were classified as group 2. Fecal elastase-1 levels were determined. Fecal elastase-1 levels <200 μg/g were defined as exocrine pancreatic insufficiency (EPI). Patients with PS were further grouped according to severity and anatomic distribution of steatosis based on findings of 3 tesla MRI., Results: Fecal elastase-1 levels was significantly lower in group 1 compared to group 2 (319.76±45.7 vs 549.31±69.4, respectively, p=0.003). Proportion of patients with EPI was significantly higher in group 1 than group 2 (35.5% vs 12% p=0.042). There were no significant differences in terms of severity or the anatomic distribution of PS in patients with PS with EPI based on MRI (p=0.052, p=0.198, p=0.405) Conclusion: Current study demonstrates that PS can cause EPI.

The Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment was prepared on the initiative of the Russian "Pancreatic Club" on the Delphi method. His goal was to clarify and consolidate the opinions of specialists on the most relevant issues of diagnosis and treatment of exo- and endocrine insufficiency after surgical interventions on the pancreas. An interdisciplinary approach is provided by the participation of leading gastroenterologists and surgeons.

Background & Aims: Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in detection of EPI., Methods: We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase-1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta-analysis., Results: We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta-analysis. The assay for elastase-1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58-0.89) and specificity value of 0.88 (95% CI, 0.78-0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79-0.99) and specificity value of 0.88 (95% CI, 0.59-0.97), compared to quantitative fecal fat estimation. In patients with low pre-test probability of EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and a false-positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre-test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives)., Conclusions: In a systematic review and meta-analysis of studies that compared fecal level of elastase-1 for detection of EPI, we found that normal level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200 mcg/g) has a high false-positive rate., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Traditionally, elastase has been used to study exocrine activity of the pancreas in patients with chronic pancreatitis and cystic fibrosis, and calprotectin as a marker for gut-wall inflammation in patients with inflammatory bowel disease. The aim of the study was to find out whether elastase and calprotectin could be used as inflammatory markers for radiation-induced gut wall injury of the distal bowel., Material and Methods: Adult male mice were exposed to two, three, or four fractions of 6 Gy or 8 Gy irradiation to the sigmoid and rectum of the large bowel, using a linear accelerator. Fecal samples were collected from mice at 1, 3, and 6 weeks post-irradiation. The fecal levels of elastase and calprotectin were analyzed using ELISA., Results: Three and 6 weeks after irradiation, we found a dose-effect relationship between dose of ionizing radiation and the fecal level of elastase; that is significantly higher levels of elastase were observed in mice that had received a high irradiation dose. We also found that irradiated mice hosted in the same cage had a comparable level (either high or low) of elastase. No significant differences were observed from the calprotectin data., Conclusions: We found a clear association between the dose of ionizing radiation to the distal colon and the level of elastase in the fecal samples.

Objective: The function of the exocrine pancreas is decreased in patients with type 1 diabetes but it is not known when this defect develops. The current study set out to determine whether the reduced exocrine function becomes manifest after the initiation of islet autoimmunity., Methods: The study was nested in the prospective Type 1 Diabetes Prediction and Prevention study where children with human leukocyte antigen (HLA)-conferred susceptibility are observed from birth. Elastase-1 levels were analyzed from stool samples collected at the time of seroconversion to islet autoantibody positivity and at diagnosis of type 1 diabetes, as well as from samples taken from matched control children of similar age., Results: Elastase levels were lower in case children at the time of the diagnosis of diabetes when compared to the control children. However, elastase concentrations did not differ between cases and controls at the time when autoantibodies appeared., Conclusion: The results suggest that the defect in the exocrine function develops after the appearance of islet autoantibodies. Further studies are needed to assess whether reduced elastase levels predict rapid progression of islet autoimmunity to clinical disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: As cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being increasingly adopted as the standard treatment for peritoneal surface malignancies, familiarity with this procedure's adverse events is also growing. Herein, we describe an unreported adverse event of exocrine pancreatic insufficiency (EPI) following CRS and HIPEC., Patients and Methods: Patients who underwent CRS and HIPEC between 9/2016 and 9/2017 were prospectively recruited. Fecal elastase-1 (FE1) and Clostridium difficile toxins were tested in all patients in the immediate postoperative period. Patients with diarrhea who had low FE1 were started on oral pancreatic enzyme replacement therapy (PERT) and their symptomatic progression was followed., Results: A total of 26 patients were included. Eleven patients (42.31%) developed postoperative refractory diarrhea, nine of whom had a low FE1 level. These patients were treated with PERT either directly or after completion of antibiotics course if C. difficile toxin was positive. Eight patients demonstrated symptomatic resolution of their diarrhea, and thus the diagnosis of EPI was established (30.77%). Patients with diarrhea had lower FE1 levels, and were more likely to have had a terminal ileum resection and had a longer hospital stay. Regression analysis identified the rapid rise of a patient's core temperature by >1°C within 15 minutes as the sole predictor of EPI occurrence., Conclusion: EPI is a potential adverse event following CRS and HIPEC and might be largely responsible for refractory diarrhea. In our patients with refractory diarrhea and low FE1, PERT provided immediate symptomatic relief. The biological basis of this phenomenon remains unclear and warrants further investigation., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency. He was treated with pancreatic enzyme supplementation with complete resolution of diarrhea. This case reinforces the importance of awareness and anticipation of unusual immune-related adverse events related to checkpoint inhibitors.

Background: Fecal elastase-1 (E-1) levels in infants and young children may be expected to differ from those in adults and older children because of the immaturity of the gastrointestinal tract and the specificity of their diet. Despite the availability of data describing E-1 levels in the stools of preterm infants, older children, adults and subjects with malabsorption, there is still a lack of data regarding E-1 in healthy infants and toddlers. The aim of this cross-sectional study was to evaluate fecal E-1 concentrations in infants and children from 1 up to 24 months of age., Material and Methods: E-1 was measured in 160 healthy subjects aged 1-24 months (8 groups of 20: aged 1-3, 4-6 months, etc.) using an enzyme-linked immunosorbent assay (ELISA)., Results: Fecal E-1 concentrations ranged from 200 to 1695 μg/g of feces. No child had a fecal E-1 level below 200 μg/g of feces. Fecal E-1 concentrations did not significantly differ between age groups. However, fecal E-1 levels in the first 3 months were lower than in the second year of life (1-3 months vs 13-24 months, p=0.0230). A statistically significant correlation between the E-1 concentration and age was found (p=0.0007, r=0.2639; however, it does not affect the cut-off level of the reference values). The trend was rather exponential. Fecal E-1 values reached a plateau around the age of 6-10 months., Conclusions: Our study has shown that the fecal E-1 test can be reliably applied in infants and toddlers to confirm normal exocrine pancreatic function. However, within the first months of life fecal E-1 concentrations may be lower than later in life.

Elastase, collagenase, hyaluronidase and tyrosinase, are very interesting enzymes due to their direct implication in skin aging and as therapeutic hits. Different techniques can be used to study these enzymes and to evaluate the influence of effectors on their kinetics. Nowadays, analytical techniques have become frequently used tools for miniaturizing enzyme assays. The main intention of this article is to review chromatographic and electrophoretic tools that study the four enzymes above mentioned. More specifically, the use of high-performance liquid chromatography and capillary electrophoresis and their derivative techniques for monitoring these enzymes will be investigated. The advantages and limitations of these assays will also be discussed. The original use of microscale thermophoresis and thin layer chromatography in this domain will also be covered., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Morbid obesity is a lifelong disease, and all patients require complementary follow-up including nutritional surveillance by a multidisciplinary team after bariatric procedures. Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes and/or sodium bicarbonate. PEI is a known multifactorial complication after upper gastrointestinal surgery, and might constitute an important clinical problem due to the large number of bariatric surgical procedures in the world. Symptoms of PEI often overlap with sequelae of gastric bypass, making the diagnosis difficult. Steatorrhea, weight loss, maldigestion and malabsorption are pathognomonic for both clinical conditions. Altered anatomy after bypass surgery can make the diagnostic process even more difficult. Fecal elastase-1 (FE1) is a useful diagnostic test. PEI should be considered in all patients after bariatric surgery with prolonged gastrointestinal complaints that are suggestive of maldigestion and/or malabsorption. Appropriate pancreatic enzyme replacement therapy should be part of the treatment algorithm in patients with confirmed PEI or symptoms suggestive of this complication.

Background: An ability to predict the response to conventional non-surgical treatment of a periodontal site would be advantageous. However, biomarkers or tests devised to achieve this have lacked sensitivity. The aim of this study is to assess the ability of a novel combination of biomarkers to predict treatment outcome of patients with chronic periodontitis., Methods: Gingival crevicular fluid (GCF) and subgingival plaque were collected from 77 patients at three representative sites, one healthy (probing depth [PD] ≤3 mm) and two diseased (PD ≥6 mm), at baseline and at 3 and 6 months after treatment. Patients received standard non-surgical periodontal treatment at each time point as appropriate. The outcome measure was improvement in probing depth of ≥2 mm. Concentrations of active enzymes (matrix metalloproteinase [MMP]-8, elastase, and sialidase) in GCF and subgingival plaque levels of Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum were analyzed for prediction of the outcome measure., Results: Using threshold values of MMP-8 (94 ng/μL), elastase (33 ng/μL), sialidase (23 ng/μL), and levels of P. gingivalis (0.23%) and T. forsythia (0.35%), receiver operating characteristic curves analysis demonstrated that these biomarkers at baseline could differentiate healthy from diseased sites (sensitivity and specificity ≥77%). Furthermore, logistic regression showed that this combination of these biomarkers at baseline provided accurate predictions of treatment outcome (≥92%)., Conclusion: The "fingerprint" of GCF enzymes and bacteria described here offers a way to predict the outcome of non-surgical periodontal treatment on a site-specific basis.

Background and Aim: A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D., Methods: Patients aged over 40 years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3 months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool sample in which elastase concentration was measured by ELISA. A concentration of < 100 mcg/g stool represented severe and < 200 mcg/g mild to moderate PEI. Patients whose fecal elastase was < 200 mcg/g underwent testing for pancreatic pathology with an endoscopic ultrasound or abdominal CT., Results: Two hundred eighteen patients (mean age of 60 years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n = 10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis., Conclusion: One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Extended wavelength analyte-responsive fluorescent probes are highly desired for the imaging applications owing to their deep tissue penetration, and minimum interference from autofluorescence by biomolecules. Near infra-red (NIR) sensitive and self-quenching fluorescent probe based on the dye-peptide conjugate (SQ 1 PC) was designed and synthesized by facile and efficient one-pot synthetic route for the detection of Elastase activity. In the phosphate buffer solution, there was an efficient quenching of fluorescence of SQ 1 PC (86%) assisted by pronounced dye-dye interaction due to H-aggregate formation. Efficient and fast recovery of this quenched fluorescence of SQ 1 PC (> 50% in 30s) was observed on hydrolysis of this peptide-dye conjugate by elastase enzyme. Presently designed NIR sensitive self-quenching substrate offers the potential application for the detection of diseases related to proteases by efficient and fast detection of their activities., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Infections with parasites of the Leishmania donovani complex result in clinical outcomes that range from asymptomatic infection to severe and fatal visceral leishmaniasis (VL). Neutrophils are major players of the immune response against Leishmania, but their contribution to distinct states of infection is unknown. Gene expression data suggest the activation of the NETosis pathway during human visceral leishmaniasis. Thus, we conducted an exploratory study to evaluate NET-related molecules in retrospective sera from VL patients, asymptomatic individuals and uninfected endemic controls., Results: We demonstrate that VL patients and asymptomatic individuals exhibit differential regulation of molecules associated with neutrophil extracellular traps (NET). These differences were observed at the transcriptional level of genes encoding NET-associated proteins; in quantifications of cell free DNA and metalloproteinase 9; and in enzymatic activity of DNAse and elastase. Moreover, multivariate analysis resulted in class-specific signatures, and ROC curves demonstrate the ability of these molecules in discriminating asymptomatic infection from uninfected controls., Conclusion: Molecules that are associated with NETs are differentially regulated between distinct states of infection with L. infantum, suggesting that NETs might have distinct roles depending on the clinical status of infection. Although unlikely to be exclusive for VL, these signatures can be useful to better characterize asymptomatic infections in endemic regions of this disease.

Determination of fecal pancreatic elastase content by ELISA is a reliable, noninvasive clinical test for assessing exocrine pancreatic function. Despite the widespread use of commercial tests, their exact molecular targets remain poorly characterized. This study was undertaken to clarify which human pancreatic elastase isoforms are detected by the ScheBo Pancreatic Elastase 1 Stool Test and whether naturally occurring genetic variants influence the performance of this test. Using recombinantly expressed and purified human pancreatic proteinases, we found that the test specifically measured chymotrypsin-like elastases (CELA) 3A and 3B (CELA3A and CELA3B), while CELA2A was not detected. Inactive proelastases, active elastases, and autolyzed forms were detected with identical efficiency. CELA3B elicited approximately four times higher ELISA signal than CELA3A, and we identified Glu 154 in CELA3B as the critical determinant of detection. Common genetic variants of CELA3A and CELA3B had no effect on test performance, with the exception of the CELA3B variant W79R, which increased detection by 1.4-fold. Finally, none of the human trypsin and chymotrypsin isoforms were detected. We conclude that the ScheBo Pancreatic Elastase 1 Stool Test is specific for human CELA3A and CELA3B, with most of the ELISA signal attributable to CELA3B. NEW & NOTEWORTHY The ScheBo Pancreatic Elastase 1 Stool Test is widely used to assess pancreatic exocrine function, yet its molecular targets have been poorly defined. We demonstrate that, among the human pancreatic proteinases, the test measures the elastase isoform CELA3B and, to a lesser extent, CELA3A. Genetic variants of the human CELA3 isoforms have no significant effect on test performance., (Copyright © 2017 the American Physiological Society.)

Background: Disease activity can be determined using clinical, endoscopic or histologic criteria in patients with ulcerative colitis (UC). Persistent disease activity is associated with poor outcomes. Histologic disease activity has been shown to be associated with relapse, colectomy and colorectal cancer. The ability to objectively evaluate microscopic disease activity using histology is important for both clinical practice and clinical trials. However, the operating properties of the currently available histologic indices remain unclear., Objectives: A systematic review was undertaken to identify and evaluate the development and operating characteristics of histologic disease activity indices used to assess disease activity in people with ulcerative colitis., Search Methods: We searched MEDLINE, EMBASE, PubMed, CENTRAL and the Cochrane IBD Review Group Specialized Trials Register from inception to 2 December 2016 for applicable studies. There were no language or document type restrictions., Selection Criteria: Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated a histologic index in patients with UC were considered for inclusion. Eligible patients were adults (> 18 years), diagnosed with UC using conventional clinical, radiographic, endoscopic and histologic criteria., Data Collection and Analysis: Two authors (MHM and CEP) independently reviewed the titles and abstracts of the studies identified from the literature search. A standardized form was used to assess eligibility of trials for inclusion and for data extraction.Two authors (MHM and CEP) independently extracted and recorded data, which included the number of patients enrolled, number of patients per treatment arm, patient characteristics including age and gender distribution, and the name of the histologic index. Outcomes (i.e. intra-rater reliability, inter-rater reliability, internal consistency, content validity, criterion validity, construct validity, responsiveness, and feasibility) were recorded for each trial., Main Results: In total, 126 reports describing 30 scoring indices were identified through the screening process. Eleven of the 30 scoring indices have undergone some form of index validation. Intra-rater reliability was assessed for eight scoring indices. Inter-rater reliability was evaluated for all 11 of the scoring indices. Three of the indices underwent content validation. Two of the included scoring indices assessed criterion validity. Six of the included scoring indices explored content validity. Two of the included scoring indices were tested for responsiveness., Authors' Conclusions: The Nancy Index and the Robarts Histopathology Index have undergone the most validation in that four operating properties including reliability, content validity, construct validity (hypothesis testing) and criterion validity have been tested. However, none of the currently available histologic scoring indices have been fully validated. In order to determine the optimal endpoint for histologic healing in UC, more research is required. The optimal index would need to be fully validated.

Objective: To validate preoperative dynamic CT and fecal elastase-1 level in predicting the development of pancreatic fistulae after pancreatoduodenectomy., Materials and Methods: For 146 consecutive patients, CT attenuation values of the nontumorous pancreatic parenchyma were retrospectively measured on precontrast, arterial and equilibrium phase images for calculation of enhancement ratios. CT enhancement ratios and preoperative fecal elastase-1 levels were correlated with the development of pancreatic fistulae using independent t-test, logistic regression models, ROC analysis, Youden method and tree analysis., Results: The mean value of enhancement ratio on equilibrium phase was significantly higher (p = 0.001) in the patients without pancreatic fistula (n = 107; 2.26±3.63) than in the patients with pancreatic fistula (n = 39; 1.04±0.51); in the logistic regression analyses, it was significant predictor for the development of pancreatic fistulae (odds ratio = 0.243, p = 0.002). The mean preoperative fecal elastase-1 levels were higher (odds ratio = 1.003, p = 0.034) in the pancreatic fistula patients than other patients, but there were no significant differences in the areas under the curve between the prediction values of CT enhancement ratios and fecal elastase-1 combined and those of CT enhancement ratios alone (P = 0.897, p = 0.917) on ROC curve analysis. Tree analysis revealed that the CT enhancement ratio was more powerful predictor of pancreatic fistula than fecal elastase-1 levels., Conclusion: The preoperative CT enhancement ratio of pancreas acquired at equilibrium phase regardless of combination with fecal elastase-1 levels might be a useful predictor of the risk of developing a pancreatic fistula following pancreatoduodenectomy.

Background: The clinical relevance of fibrosis with regard to tumor progression is supported by the correlation between fibrosis and poor outcomes. Fecal elastase-1 (FE-1) level has been used to assess exocrine dysfunction of the pancreas and to predict pancreas fibrosis. The aim of this study was to assess the impact of FE-1 on the survival of pancreatic cancer patients., Methods: Between January 2006 and December 2014, 136 patients with pancreatic adenocarcinoma underwent R0 resection at Gangnam Severance Hospital, Korea. Preoperative FE-1 levels were available in 94 patients who were enrolled in the study. Patients were classified into two groups according to preoperative FE-1: "normal" (≥200 μg/g) or "reduced" (<200 μg/g)., Results: Median preoperative FE-1 level was 130.1 μg/g (IQR 32.0; 238.3). 62 patients (66.0%) had reduced pancreatic function and 32 patients (34.0%) had normal pancreatic function. The two groups had significantly different disease-free survival (P < 0.001). On multivariate analysis, normal FE-1, no lymph node metastasis and completion of adjuvant chemotherapy were found to be independent prognostic factors for better DFS (P = 0.001, P = 0.017, P = 0.038, respectively)., Conclusion: FE-1 is a simple and non-invasive predictive clinical marker for prognosis of pancreatic cancer after attempted curative resection., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Dichelobacter nodosus is a fastidious, strictly anaerobic bacterium, an obligate parasite of the ruminant hoof, and the essential causative agent of virulent ovine footrot. The clinical disease results from a complex interplay between the pathogen, the environment, and the host. Sheep flocks diagnosed with virulent but not benign footrot in Australia may be quarantined and required to undergo a compulsory eradication program, with costs met by the farmer. Virulence of D. nodosus at least partially depends on the elaboration of a protease encoded by aprV2 and manifests as elastase activity. Laboratory virulence tests are used to assist diagnosis because clinical differentiation of virulent and benign footrot can be challenging during the early stages of disease or when the disease is not fully expressed due to unfavorable pasture conditions. Using samples collected from foot lesions from 960 sheep from 40 flocks in four different geographic regions, we evaluated the analytical characteristics of qPCR tests for the protease gene alleles aprV2 and aprB2 , and compared these with results from phenotypic protease (elastase and gelatin gel) tests. There was a low level of agreement between clinical diagnosis and quantitative PCR (qPCR) test outcomes at both the flock and sample levels and poor agreement between qPCR test outcomes and the results of phenotypic virulence tests. The diagnostic specificity of the qPCR test was low at both the flock and individual swab levels (31.3% and 18.8%, respectively). By contrast, agreement between the elastase test and clinical diagnosis was high at both the flock level (diagnostic sensitivity [DSe], 100%; diagnostic specificity [DSp], 78.6%) and the isolate level (DSe, 69.5%; DSp, 80.5%)., (Copyright © 2017 McPherson et al.)

Aim: To compare two tests for exocrine pancreatic function (EPF) for use in M-ANNHEIM staging for pancreatitis., Methods: One hundred and ninety four consecutive patients with acute pancreatitis (AP; n = 13), recurrent acute pancreatitis (RAP; n = 65) and chronic pancreatitis (CP; n = 116) were enrolled. EPF was assessed by faecal elastase-1 (FE-1) estimation and stool fat excretion by the acid steatocrit method. Patients were classified as per M-ANNHEIM stages separately based on the results of the two tests for comparison. Independent Student's t -test, χ 2 test, Kruskal-Wallis test, Mann-Whitney U test and McNemar's test were used as appropriate., Results: Sixty-one (52.5%) patients with CP had steatorrhoea when assessed by the acid steatocrit method; 79 (68.1%) with CP had exocrine insufficiency by the FE-1 test (χ 2 test, P < 0.001). The results of acid steatocrit and FE-1 showed a significant negative correlation (Spearman's rho = -0.376, P < 0.001). A statistically significant difference was seen between the M-ANNHEIM stages as classified separately by acid steatocrit and the FE-1. Thirteen (6.7%), 87 (44.8%), 89 (45.8%) and 5 (2.5%) patients were placed in M-ANNHEIM stages 0, I, II, and III respectively, with the use of acid steatocrit as against 13 (6.7%), 85 (43.8%), 75 (38.6%), and 21 (10.8%) respectively by FE-1 in stages 0, I, II, and III thereby altering the stage in 28 (14.4%) patients ( P < 0.001, McNemar's test)., Conclusion: FE-1 estimation performed better than the acid steatocrit test for use in the staging of pancreatitis by the M-ANNHEIM classification since it diagnosed a higher proportion of patients with exocrine insufficiency., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare.

Background/objectives: Chronic pancreatitis (CP) is characterized by abnormal pancreatic morphology and impaired endocrine and exocrine function. However, little is known about the relationship between pancreatic morphology and function, and also the association with the etiology and clinical manifestations of CP. The aim was to explore pancreatic morphology and function with advanced MRI in patients with CP and healthy controls (HC) METHODS: Eighty-two patients with CP and 22 HC were enrolled in the study. Morphological imaging parameters included pancreatic main duct diameter, gland volume, fat signal fraction and apparent diffusion coefficient (ADC) values. Functional secretin-stimulated MRI (s-MRI) parameters included pancreatic secretion (bowel fluid volume) and changes in pancreatic ADC value before and after secretin stimulation. Patients were classified according to the modified Cambridge and M-ANNHEIM classification system and fecal elastase was collected., Results: All imaging parameters differentiated CP patients from HC; however, correlations between morphological and functional parameters in CP were weak. Patients with alcoholic and non-alcoholic etiology had comparable s-MRI findings. Fecal elastase was positively correlated to pancreatic gland volume (r = 0.68, P = 0.0016) and negatively correlated to Cambridge classification (r = -0.35, P < 0.001). Additionally, gland volume was negatively correlated to the duration of CP (r = -0.39, P < 0.001) and baseline ADC (r = -0.35, P = 0.027). When stratified by clinical stage (M-ANNHEIM), the pancreatic gland volume was significantly decreased in the severe stages of CP (P = 0.001)., Conclusions: S-MRI provides detailed information about pancreatic morphology and function and represents a promising non-invasive imaging method to characterize pancreatic pathophysiology and may enable monitoring of disease progression in patients with CP., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Roux-en-Y gastric bypass (RYGB) causes several alterations in gastrointestinal function. We hypothesized that levels of three commonly used fecal tests change after RYGB., Methods: Fecal levels of calprotectin, elastase, and alpha-1-antitrypsin were determined in 122 patients without signs of gastrointestinal disease 1 to 2 years after RYGB. Medians, distribution of values, and the percentage of patients with levels above or below reference values were determined., Results: Median fecal calprotectin level was 163.5 (<30-1587) μg/g; in 87 % of patients, it was above the reference value (<50 μg/g). Median fecal elastase level was 444 (<15-647) μg/g; 13 % was below the reference value (>200 μg/g). Median fecal alpha-1-antitrypsin level was 0.51 (<0.20-2.20) mg/g, comparable to the reference values., Conclusions: Fecal calprotectin levels are significantly higher than the reference value in most patients after RYGB. Fecal elastase is significantly lower. This might indicate that the validity of fecal calprotectin testing is impaired after RYGB and the specificity for fecal elastase is decreased. Clinical awareness of altered fecal markers after RYGB is essential to prevent unnecessary diagnostic tests, such as colonoscopy. Fecal alpha-1-antitrypsin is not influenced by RYGB., Competing Interests: Compliance with Ethical StandardsConflict of InterestDennis CW Poland is a shareholder in the Col-Group, which is the producer of the Fe-Col®. The other authors have no conflicts of interest to disclose.Ethical ApprovalThe medical ethics committee of the Slotervaart Hospital/Reade in Amsterdam gave approval for this study (NL49803.048.14, P1437). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.Statement of Informed ConsentInformed consent was obtained from all individual participants included in the study.

Introduction: Identification of pancreatic exocrine insufficiency (PEI) is important in the management of chronic pancreatitis. The 72-h stool for fecal fat estimation (FFE) has long been considered a gold standard indirect test for the diagnosis of PEI. However, the test is cumbersome for both patients and laboratory personnel alike. In this study, we aimed to assess fecal elastase 1 (FE1) as an alternate to FFE for the diagnosis of PEI., Methods: In all, 87 consecutive patients diagnosed with chronic pancreatitis were included in this study. FFE and FE1 estimation was done for all the patients. For FE1, two cutoffs (<100 and <200 μg) were selected to define pancreatic exocrine insufficiency. The sensitivity, specificity, and positive and negative predictive values for the two cutoffs were estimated. Kappa statistics was used to assess degree of agreement between both tests., Results: All patients completed the study and were included in the analysis. The sensitivity, specificity, and positive and negative predictive value and PABAK (prevalence and bias adjusted kappa) for FE1 <100 μg was 84.9, 47.6, 83.6, 50, and 0.52, respectively. For FE1 <200 μg, it was 90.9, 9.5, 75.95, 25, and 0.43, respectively., Conclusion: FE1 is a sensitive test; however, it does not have a good agreement with FFE. FE1 may be used as screening test for PEI in patients with chronic pancreatitis.