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Cervical inlet patches (CIP) are common endoscopic findings with uncertain pathogenesis and clinical significance. We aimed to perform a systematic review and prospective study of clinical data and endoscopic findings related to CIP. It was a prospective single-center study conducted between 10/01/2017 and 9/01/2018. Forty patients with histopathologically confirmed CIP were compared with 222 individuals in the reference group. The systematic review was executed in accordance with the PRISMA guideline. Alcohol consumption tended to be higher among patients with CIP (3.0 ± 4.6 vs. 1.9 ± 5.0 standard drinks/week CIP patients and reference group, respectively; p 0.001). Dysphagia was more frequent among patients with CIP (25% vs. 1.4%, CIP patients and reference group, respectively; p 0.001), and sore throat and hoarseness were less frequent in patients with CIP (17.5% vs. 26.6% CIP patients and reference group, respectively; p 0.01). In the multivariate regression analysis, the only risk factor of CIP occurrence was dysphagia (OR 21.9, 95%CI 4.9-98.6; p 0.001). Sore throat and hoarseness were a reverse-risk factor of CIP diagnosis (OR 0.3, 95%CI 0.1-0.93; p = 0.04). Clinical data and coexisting endoscopic findings were not related to CIP. In the presented study, dysphagia was related to CIP occurrence, and sore throat and hoarseness tended to be less frequent among patients with CIP.

Precancerous conditions for esophageal (EA) and gastric adenocarcinoma (GA) are Barrett's esophagus (BE) and atrophic gastritis (AG), respectively. The surveillance of which is crucial in the detection of early lesions.The study aimed to assess whether one-time esophagogastroduodenoscopy (EGD) in searching for precancerous conditions would be effective in a low-to-moderate esophageal and gastric cancer risk population.5984 individuals who underwent diagnostic EGD in 3 endoscopic centers from 03.2018 to 10.2019 were analyzed to assess the age of patients with precancerous conditions and cancers. Age distribution of patients with malignant gastric and esophageal tumors registered in the national cancer registry (KRN) from 2014 to 2017 was analyzed.The risk of diagnosis of EA and GA raised in comparison with individuals at age40 at age 60-64 (OR 12.1; 95%CI 1.5-98.6), gastric and esophageal dysplasia at age 55-59 (OR 3.6; 95%CI 1.3-9.7), and BE and AG at age 40-44 (OR 1.6; 95%CI 1.04-2.4). The number of procedures per one cancer that could be potentially avoided was 236, 235, 290, 360, 394, and 344 for age groups 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 respectively. The assessed ratio of potential benefits and harms was 47, 38, 31, 28, and 32 for age groups 40-49, 50-54, 55-59, 60-64, and 65-69 respectively.The one-time EGD in searching for precancerous conditions could be potentially applicable in individuals between 40 and 69 years of age.

Background Nonalcoholic fatty liver disease (NAFLD) awareness is low. NAFLD diagnosis and management by gastroenterologists (GEs) and general practitioners (GPs) in Poland were evaluated. Methods RESTORE was an observational, noninterventional, retrospective cross-sectional survey performed among GEs and GPs with at least 3 years' experience. Computer-assisted web interviews were completed. GEs provided information from patient records. Results Mean experience was 14.2 (95 GEs) and 22.6 (115 GPs) years. Mean patient numbers with liver disorders consulted per month were 36 (13%; GEs) and 51 (6%; GPs); ~50% were patients with NAFLD. All GEs/GPs used ultrasound; most evaluated transaminases and gamma-glutamyl transferase. More GEs used other imaging techniques and a larger spectrum of laboratory tests than GPs. Physician-identified NAFLD key symptoms were similar for GEs/GPs. GEs noticed less obvious symptoms (abdominal discomfort, drowsiness, fatigability, lack of energy) vs. GPs (abdominal pain/discomfort, dyspepsia). Common comorbidities in NAFLD were similar in GE/GP responses. NAFLD interventions by GEs/GPs (% patients) were diet/lifestyle/pharmacological interventions (54%/59%), diet/lifestyle changes alone (41%/31%) or pharmacological interventions alone (5%/10%). The top three criteria for supportive pharmacological selection were efficacy, tolerability and quality of life improvement for GEs/GPs. The five supportive treatments most commonly prescribed by GEs/GPs were essential phospholipids, ursodeoxycholic acid, timonacic, silybinin/silymarin and ornithine + choline. Information from patient records (n = 380) confirmed GEs responses. Conclusions NAFLD is not a silent disease as physicians and patients reported many, albeit nonspecific, symptoms. This cross-sectional survey provides important insights into clinical management of NAFLD by GEs and GPs in Poland.

BACKGROUND AND AIM The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

Obstruction of the upper gastrointestinal tract, caused by blocked passage in the oesophagus, stomach or duodenum, is an important clinical and diagnostic problem in gastroenterological practice. The typical symptoms are dysphagia, postprandial vomiting, epigastric pain and weight loss. Post-inflammatory oesophageal lesions associated with reflux oesophagitis are the most common cause of obstruction. Other common causes include foreign bodies, neoplasms, chemical burns of the oesophagus and radiation-induced stenosis. In more than 2/3 cases, foreign bodies are localised in the proximal part of the oesophagus, but anatomical abnormalities, such as a Schatzki ring or post-inflammatory stenosis, increase the risk of food bolus impaction in the distal part of the oesophagus. Radiotherapy of head and neck tumours may cause stenosis, which affects more than 7% of patients treated this way. For the stomach and duodenum, 50–80% of obstruction cases are associated with neoplastic processes, with gastric cancer and pancreatic adenocarcinoma accounting for 35% and 15–25% of these cases, respectively. Mild causes of peripyloric obstruction include gastric and duodenal peptic ulcer, peritoneal adhesions, gastric polyps and Crohn’s disease. Symptoms of temporary pylorus obstruction can be caused by large, gastric hyperplastic pedunculated polyps. Therapeutic endoscopy is the most commonly used method for upper gastrointestinal tract obstruction. Depending on the cause, it involves foreign body removal, balloon enteroscopy, stenting with self-expanding metallic stents, and, in the case of treatment failure, surgical resection or palliative gastrojejunostomy.

Purpose Heterotopic gastric mucosa in the upper esophagus (cervical inlet patches - CIP) may be easily missed during esophagogastroduodenoscopy (EGD) due to low awareness of this usually, but not invariably, benign lesion. Narrow-band imaging (NBI) emphasizes contrast between normal esophageal mucosa and CIP. The purpose of this study was to investigate how NBI use and enhanced attention of operator during inspection of upper esophagus impacts cervical inlet patch detection rate (CIPDR). Materials and methods This is a prospective, randomized study in which we enrolled 1000 patients, qualified for diagnostic EGD. The trial was divided into two parts; the first, when 6 operators performed EGD with standard attention (SA), and the second, when the same operators were asked to step up with attention at CIP (enhanced attention - EA). In both parts of the study, patients were randomized to NBI and white light endoscopy (WLE) in 1:1 ratio. The study is registered in ClinicalTrials.gov (No. NCT03015571). Results Differences in CIPDR between WLE and NBI in SA and EA were not statistically different (5.6% vs 7.6%; p ​= ​0.3, and 7.6% vs 11.6%; p ​= ​0.1, respectively). In multivariate regression analysis, the only factors improving CIPDR were NBI with EA (NBIEA, OR 3.31; 95%CI 1.57–6.98; p ​= ​0.003) and sedation (OR 1.97; 95%CI 1.27–3.05; p ​= ​0.002). Conclusions The use of NBI combined with EA significantly improves CIPDR.

This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2012. It contains 46 recommendations for the diagnosis and treatment, both pharmacological and surgical, of Crohn's disease in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality and strength of the available recommendations. The degree of expert support for the proposed statement, assessment of the quality of evidence and the strength of the recommendation was assessed on a 6-point Likert scale. Voting results, quality and strength ratings with comments are included with each statement.

Various measures of esophagogastroduodenoscopy (EGD) quality have been proposed so far and the examination time was one of the first. The aim of the study was to compare the procedure time with novel novel quality measures - composite detection rate (CDR) and endoscopist biopsy rate (EBR).It was prospective observational study. A total of 880 diagnostic EGDs conducted from 01.2019 to 07.2019 have been enrolled in the study.Median EGD time was 4.2 min. Procedures of longer duration were marked with higher CDR (26.3% vs. 11.8%; P 0.0001), higher EBR (44.9% vs. 12.3%; P 0.0001), and better upper gastrointestinal neoplasm (UGN) detection (1.8% vs. 0%; P = 0.004) in comparison with procedures of shorter duration. The procedures were divided into 4 groups based on the time quartiles (group 13.3 min; group 2 3.3-4.2 min; group 3 4.2-5.3 min; group 45.3 min). The odds ratios of groups 2, 3, and 4 for biopsy rate were 2.42 (95% CI, 1.33-4.55), 4.33 (95% CI, 2.46-7.94), and 5.51 (95% CI, 3.18-10.03), respectively, in comparison with group 1. The odds ratios of groups 2, 3, and 4 for CDR were 3.18 (95% CI, 2.03-4.97), 5.46 (95% CI, 3.51-8.50), and 23.44 (95% CI, 14.3-38.4), respectively, in comparison with group 1.The procedure time is related to novel metrics - CDR and EBR. It is also related to UGN. Based on our findings it could be concluded that EGD should not last less than 4.2 min.

Current guidelines provide weak recommendations to treat small (2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification.We conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location.In our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and 8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% CONCLUSION: Using a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (1 cm) in the tail of the pancreas should be sampled under EUS-guidance.

Background: The COVID-19-pandemic poses challenges to the medical system and especially to endoscopic staff and patients. National, European and International societies provided recommendations on how to safely perform endoscopic procedures during the current pandemic. Until now, the effect of the current pandemic on tertiary endoscopy centers has not been reported. Objective: The aim of this was to analyze the influence of the early SARS-CoV2-pandemic on endoscopic care and work flow in 2 European tertiary endoscopy units. Methods: Data from 2 tertiary endoscopy units (Katowice and Munich) were retrospectively collected during the early pandemic and compared to an equivalent pre-pandemic period. Data include procedures, complications, benchmarks, and influence on endoscopy training. Results: During the early pandemic, we noted a highly significant decrease (49.1%) in the overall number of all endoscopies with a significant increase in therapeutic procedures. Besides, there were no significant differences in the number of urgent endoscopic retrograde cholangiopancreatography or interventional endoscopic ultrasound procedures. The exceptional situation reduced endoscopic procedures performed by trainees significantly. Conclusions: The SARS-CoV2-pandemic halved the endoscopy service of 2 tertiary centers while maintaining an urgent therapeutic service. Recommended personal safety measures in endoscopy proved to be efficient and safe in preventing SARS-CoV2 infection of staff or spreading. Unnecessarily, the SARS-CoV2 pandemic prevented routine endoscopy training.

The diagnosis of atrophic gastritis (AG) and intestinal metaplasia (IM) is a crucial screening and surveillance strategy for gastric adenocarcinoma.The main objective was to assess the performance of endoscopic diagnosis of gastric precancerous conditions in a real‑life scenario.A total of 2099 gastroscopies with biopsy to evaluate gastritis performed in 3 endoscopic centers from March 2018 to October 2019 were retrospectively analyzed. Endoscopic data regarding gastritis, atrophy, and intestinal metaplasia were compared with histopathological reports.The endoscopic diagnosis sensitivity was 69.5% for AG and 19.4% for IM. The specificity of endoscopic detection of AG was 69.5% and of IM, 97.9%. The endoscopic detection of gastritis was a risk factor for AG and IM diagnosis (odds ratio [OR], 5.1; 95% CI, 1.9-14.1 and OR, 14.5; 95% CI, 5.9-35.8, respectively) and the patient's age was a risk factor for AG, IM, dysplasia, and advanced stage of AG (ASAG) diagnosis (OR, 1.05; 95% CI, 1.04-1.06; OR, 1.035; 95% CI, 1.03-1.04; OR, 1.04; 95% CI, 1.02-1.06; and OR, 1.05; 95% CI, 1.02-1.09, respectively). The age threshold of 45 or 40 years with endoscopically diagnosed gastritis for obtaining biopsy would result in 96.3% and 95% ASAG or dysplasia diagnosis sensitivity, and in the reduction of the number of biopsies by 20.2% and 20.5%, respectively.The application of the age threshold with or without an endoscopic diagnosis of gastritis could reduce the number of mapping biopsies to detect advanced stages of atrophic gastritis or dysplasia with high sensitivity.

INTRODUCTION Plastic biliary stents embedded by endoscopy as definitive or temporary treatment of benign and malignant conditions have been used for over 30 years. These stents are commonly available, inexpensive and easy to implant. OBJECTIVES To evaluate the patency duration of plastic stents and assess complications associated with their use, and to determine the time required for the replacement of stents depending on the indication for the biliary stenting. PATIENTS AND METHODS This was a retrospective cohort study that included patients with plastic biliary stents implanted from 2012 to 2013 with 5-year follow up in a single tertiary referral gastroenterological center. Performance of stenting was assessed from medical records, direct contact with patients or their family members and information derived from the Central Death Register. RESULTS The analysis included 830 procedures of biliary stenting performed in 346 patients. The indications for stenting of the biliary tract were: choledocholithiasis in 120 patients (34.7%), benign stricture in 70 patients (20.2%) and malignant stricture in 156 patients (45.1%). In these conditions the mean duration of stent patency was 110, 106 and 55 days, respectively (P

Background Esophagogastroduodenoscopy (EGD) is commonly used diagnostic method with no widely accepted quality measure. We assessed quality indicator—composite detection rate (CDR)—consisting of detection of at least one of the following: cervical inlet patch, gastric polyp and post-ulcer duodenal bulb deformation. The aim of the study was to validate CDR according to detection rate of upper gastrointestinal neoplasms (UGN). Methods It was a multicenter, prospective, observational study conducted from January 2019 to October 2019. The endoscopic reports from 2896 symptomatic patients who underwent diagnostic EGD were analyzed. The EGDs were performed in three endoscopy units located in tertiary university hospital, private outpatient clinic and local hospital. Results 64 UGNs were detected. The mean CDR was 21.9%. The CDR correlated with UGN detection rate (R = 0.49, p = 0.045). Based on CDR quartiles, operators were divided into group 1 with CDR 26%. Detection rate of UGN was significantly higher in the group 4 in comparison to group 1 (OR 4.4; 95% CI 2.2 − 9.0). In the multivariate regression model, patient age, male gender and operator’s CDR > 26% were independent risk factors of UGN detection (OR 1.03; 95% CI 1.01 − 1.05, OR 2; 95% CI 1.2 − 3.5, and OR 5.7 95% CI 1.5 − 22.3, respectively). Conclusions The CDR is associated with the detection of upper gastrointestinal neoplasms. This parameter may be a useful quality measure of EGD to be applied in general setting.

Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G&gt, T. Two known heterozygous missense variants&mdash, c.2188G&gt, A, p.(Val730Ile) and c.8353A&gt, C, p.(Asn2785His)&mdash, in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G&gt, T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.

Summary Background Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. Methods The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice–web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39). Findings Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the seladelpar 200 mg group. Mean changes from baseline in alkaline phosphatase were −2% (SD 16) in the placebo group, −53% (14) in the seladelpar 50 mg group, and −63% (8) in the seladelpar 200 mg group. Changes in both seladelpar groups versus placebo were significant (p vs placebo), with no significant difference between the two seladelpar groups (p=0·1729). All five patients who received seladelpar for 12 weeks had normal alkaline phosphatase values at the end of treatment, based on a central laboratory ULN for alkaline phosphatase of 116 U/L. The most frequently reported adverse events were pruritus (16%; one patient on placebo, four on seladelpar 50 mg, and one on seladelpar 200 mg), nausea (13%; one patient on placebo, three on seladelpar 50 mg, and one on seladelpar 200 mg), diarrhoea (10%; two patients on placebo, one on seladelpar 50 mg, and one on seladelpar 200 mg), dyspepsia (8%; two patients on seladelpar 50 mg and one on seladelpar 200 mg), muscle spasms (8%; three patients on seladelpar 200 mg), myalgia (8%; one patient on placebo and two on seladelpar 200 mg), and dizziness (8%; one patient on placebo and two on seladelpar 50 mg). Interpretation Seladelpar normalised alkaline phosphatase levels in patients who completed 12 weeks of treatment. However, treatment was associated with grade 3 increases in aminotransferases and the study was stopped early. The effects of seladelpar should be explored at lower doses. Funding CymaBay Therapeutics.

The aim of this study was to evaluate hepatic vaspin mRNA in morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to look for its relationships with metabolic and histopathological features. The study included 56 severely obese women who underwent intraoperative wedge liver biopsy during bariatric surgery. Hepatic vaspin mRNA was assessed by quantitative real-time PCR. Vaspin mRNA found in all included patients was markedly higher in patients with body mass index (BMI) ≥ 40 kg/m2 (4.59 ±3.09 vs. 0.44 ±0.33; p = 0.05). An evident but statistically insignificant difference in vaspin mRNA levels was observed between patients with and without hepatocyte ballooning (4.77 ±4.23 vs. 0.45 ±0.29, respectively), with and without steatosis (4.80 ±4.20 vs. 0.41 ±0.29, respectively), without and with fibrosis (0.25 ±0.80 vs. 6.23 ±7.2, respectively), and those without and with lobular inflammation (0.27 ±1.0 vs. 5.55 ±10.1, respectively). There was marked difference in vaspin mRNA between patients with simple steatosis/borderline nonalcoholic steatohepatitis (NASH) compared to those with definite NASH (0.24 ±0.96 vs. 10.5 ±10.4). Adiposity is an undoubted confounding factor influencing vaspin levels. Hepatic vaspin mRNA seems to be markedly elevated in morbidly obese patients with more advanced NAFLD and when hallmarks of NASH were observed. Pointing to non-linear mRNA levels within the NAFLD spectrum and an evident increase in patients with fibrosis and definite NASH, the detrimental action of vaspin cannot be excluded.

The aim of this study was to investigate hepatic chemerin mRNA, serum chemerin concentration, and immunohistochemical staining for chemerin and and chemokine receptor-like 1 (CMKLR1) in hepatic tissue in 56 morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to search for a relationship with metabolic and histopathological features. Chemerin mRNA was assessed by quantitative real-time PCR, chemerin, and CMKLR1 immunohistochemical expression with specific antibodies, while serum chemerin concentration was assessed with commercially available enzyme-linked immunosorbent assays. Serum chemerin concentration reached 874.1 ±234.6 ng/ml. There was no difference in serum chemerin levels between patients with BMI < 40 kg/m2 and ≥ 40 kg/m2. Serum chemerin concentration tended to be higher in patients with hepatocyte ballooning, greater extent of steatosis, and definite nonalcoholic steatohepatitis (NASH). Liver chemerin mRNA was observed in all included patients and was markedly, but insignificantly, higher in those with BMI ≥ 40 kg/m2, hepatocyte ballooning, greater extent of steatosis, and definite NASH. Hepatic chemerin mRNA might be a predictor of hepatic steatosis, hepatocyte ballooning, and NAFLD activity score (NAS) but seemed not to be a primary driver regulating liver necroinflammatory activity and fibrosis. The lack of association between serum chemerin and hepatic chemerin mRNA may suggest that adipose tissue but not the liver is the main source of chemerin in morbidly obese women.

Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants—c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)—in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.

Gastric antral vascular ectasia (GAVE) is a rare vasculopathy that associates several diseases, most commonly liver cirrhosis. It usually presents as an occult gastrointestinal bleeding leading to profound iron deficiency anemia. We hypothesized that GAVE is local mucosal pathology dependent on genetic mechanisms, and the purpose of the study was to characterize miRNAs expression in gastric tissue of patients with cirrhosis and GAVE.Thirteen patients with GAVE and cirrhosis and 35 healthy subjects were recruited. Microarray analysis and comparative microRNA study was done by quantitative polymerase chain reaction (qPCR). The microarray scores were grouped with use of the hierarchical clusterization analysis and miRNA target prediction was done with TargetScan 6.2 algorithm and Gene Ontology analysis (DIANA-miRPath).Concentration of miR-3677 in GAVE-affected mucosa was higher by 72% in comparison with GAVE-free mucosa of patients with cirrhosis (33.7 vs. 35.6 PCR cycles; p .001) and by 45% in comparison with normal mucosa (33.7 vs. 34.9 PCR cycles; p .05). According to Gene Ontology analysis miR-3677 was related to angiopoietin-like protein 4 (ANGPTL4) gene.GAVE in liver cirrhosis is associated with increased expression of miR-3667 that may be linked with ANGPTL4 gene.

© 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.

INTRODUCTION Most patients with malignant biliary obstruction are suited only for palliation by endoscopic drainage with plastic stents (PS) or self-expandable metal stents (SEMS). OBJECTIVE To compare the clinical outcome and costs of biliary stenting with SEMS and PS in patients with malignant biliary strictures. PATIENTS AND METHODS A total of 114 patients with malignant jaundice who underwent 376 endoscopic retrograde biliary drainage (ERBD) were studied. RESULTS ERBD with the placement of PS was performed in 80 patients, with one-step SEMS in 20 patients and two-step SEMS in 14 patients. Significantly fewer ERBD interventions were performed in patients with one-step SEMS than PS or the two-step SEMS technique (2.0±1.12 vs. 3.1±1.7 or 5.7±2.1, respectively, P

INTRODUCTION The etiology of autoimmune hepatitis (AIH) is unclear, with molecular mimicry between host and viral/drug antigens being the most plausible mechanism initiating the immune cascade that induces hepatocyte injury. Finding a serologic parameter that closely relates to the liver histology would be beneficial for monitoring AIH activity and optimizing treatment. OBJECTIVES We studied serum interleukin (IL)-17 levels and IL‑17 activators (IL‑6 and transforming growth factor β1 [TGF-β1]) in treatment-naive and immunosuppressed patients with AIH. We also analyzed the relationships between these cytokines and histological inflammation scores. PATIENTS AND METHODS A total of 44 patients with confirmed AIH were enrolled to the study (22 treatment-naive patients and 22 patients in clinical remission after at least 3 years of immunosuppression). Liver biopsies were performed, and the histological grading of inflammatory activity was performed by a single pathologist. The control group comprised 30 healthy age- and sex‑matched subjects. Serum IL‑17, IL‑6, and TGF‑β1 levels were measured by a quantitative sandwich enzyme immunoassay. RESULTS Serum IL‑17, IL‑6, and TGF‑β1 levels were higher in treatment-naive patients compared with controls (23.2 pg/ml vs 15.3 pg/ml, P = 0.0001; 5.20 pg/ml vs 1.42 pg/ml, P = 0.0001; and 40.5 ng/ml vs 30.1 ng/ml, P = 0.04; respectively). In treatment-naive patients, serum IL‑17 negatively correlated with hepatic inflammation (r = -0.63, P = 0.01). A reduced serum IL‑17 concentration correlated with an increased TGF‑β1 concentration in patients in clinical remission (r = -0.51, P = 0.03). CONCLUSIONS Serum IL‑17 levels may be a useful parameter for assessing disease activity in patients with AIH.

INTRODUCTION The etiology of autoimmune hepatitis (AIH) is unclear, with molecular mimicry between host and viral/drug antigens being the most plausible mechanism initiating the immune cascade that induces hepatocyte injury. Finding a serologic parameter that closely relates to the liver histology would be beneficial for monitoring AIH activity and optimizing treatment. OBJECTIVES We studied serum interleukin (IL)-17 levels and IL‑17 activators (IL‑6 and transforming growth factor β1 [TGF-β1]) in treatment-naive and immunosuppressed patients with AIH. We also analyzed the relationships between these cytokines and histological inflammation scores. PATIENTS AND METHODS A total of 44 patients with confirmed AIH were enrolled to the study (22 treatment-naive patients and 22 patients in clinical remission after at least 3 years of immunosuppression). Liver biopsies were performed, and the histological grading of inflammatory activity was performed by a single pathologist. The control group comprised 30 healthy age- and sex‑matched subjects. Serum IL‑17, IL‑6, and TGF‑β1 levels were measured by a quantitative sandwich enzyme immunoassay. RESULTS Serum IL‑17, IL‑6, and TGF‑β1 levels were higher in treatment-naive patients compared with controls (23.2 pg/ml vs 15.3 pg/ml, P = 0.0001; 5.20 pg/ml vs 1.42 pg/ml, P = 0.0001; and 40.5 ng/ml vs 30.1 ng/ml, P = 0.04; respectively). In treatment-naive patients, serum IL‑17 negatively correlated with hepatic inflammation (r = -0.63, P = 0.01). A reduced serum IL‑17 concentration correlated with an increased TGF‑β1 concentration in patients in clinical remission (r = -0.51, P = 0.03). CONCLUSIONS Serum IL‑17 levels may be a useful parameter for assessing disease activity in patients with AIH.

Introduction: Diagnosis of hepatocellular carcinoma (HCC) is considerably delayed, being frequently done in the non-curative stage of disease. The reason for delayed diagnosis is indolent course in early stages and/or unspecific symptoms indistinguishable from underlying cirrhosis. Hitherto methods used for screening of HCC have important limitations. TRIMprob is a non-invasive method, which showed utility in detection of cancers located in prostate, breast, or urinary bladder. Aim: To determine the diagnostic accuracy of TRIMprob in detecting HCC in cirrhotic liver. Material and methods: Forty-five patients were prospectively enrolled according to final clinical diagnosis into a group of cirrhosis and HCC or a group of cirrhosis without HCC. A control group consisted of 33 healthy subjects. Hepatocellular carcinoma was diagnosed by computed tomography (CT) or magnetic resonance (MR) and guided biopsy. The TRIMprob examination was performed in each patient. Three wave frequencies were used: 465, 930, and 1395 MHz. Results: In patients with HCC the intensity of return signal using wave a frequency of 465 MHz was significantly reduced in patients with HCC in comparison to healthy subjects (p < 0.0005), but not to cirrhotic patients without HCC. Moreover, cirrhosis was associated with significantly decreased TRIMprob signal in comparison to healthy liver (p < 0.002). In ROC analysis an optimal cut-off value for detection of HCC was 106 units, which yielded 80% sensitivity. Conclusions: TRIMprob identifies HCC with good sensitivity; however, the accuracy of this method to identify HCC in screening circumstances may be hindered by attenuation of the resonance interaction signal by cirrhosis itself.

We present a 22-year-old male who developed a severe erosive oesophagitis extending to the pharynx and oral cavity without obvious risk factors. Endoscopic image suggested viral aetiology that could not be confirmed by routine serological diagnostics of infections with cytomegalovirus, Epstein-Barr virus, and Herpes simplex virus. The histopathological evaluation also gave no definite clues to the aetiology of the inflammation. Treatment with acyclovir was ineffective, but gancyclovir therapy caused spectacular clinical improvement and healing of erosions. Two months later the patient presented febrile diarrhoea that was a symptom of ileocecal Crohn’s disease proven by endoscopy, enterography, and histopathology. It is the first report of severe viral oesophagitis preceding clinical manifestation of Crohn’s disease. This observation warrants further study towards the viral aetiology of oral, pharyngeal, and oesophageal erosions, frequently associated with Crohn’s disease.

Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Hepatitis C virus (HCV) may contribute to a broad spectrum of metabolic disturbances - namely, steatosis, insulin resistance (IR), increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), lipid metabolism abnormalities and atherosclerosis. HCV can directly or indirectly cause both IR and steatosis, but it is still not resolved whether this viral impact bears the same prognostic value as the metabolic counterparts. As the population exposed to HCV ages, the morbidity due to this disease is increasing. The rising epidemic of obesity contributes to higher prevalence of IR and T2DM. Our understanding of the mutual association between both disease states continues to grow, but is still far from complete. This review briefly discusses the most probable mechanisms involved in IR development in the course of CHC. Molecular mechanisms for the direct and indirect influence of HCV on intracellular insulin signaling are described. Subsequently, the consequences of IR/T2DM for disease progression and management are summarized.

This paper presents a case of a young patient with cyanosis and digital clubbing, until then an active, sporty person. He sought medical assistance due to the growing dyspnoea and the drop of effort tolerance. Initially the diagnostic process focused on the confirmation of the suspicion of pulmonary fibrosis or another interstitial lung disease as causes of the respiratory failure. Due to the atypical presentation of the symptoms, reaching the final diagnosis of digestive system disease with lung involvement required a more thorough multifaceted diagnostics of a number of systems and organs.

Background Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population. Methods Subjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays. Results Nineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene. Conclusions Our cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders. Electronic supplementary material The online version of this article (doi:10.1186/s12920-016-0239-9) contains supplementary material, which is available to authorized users.

Background & Aims Endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. Methods Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. Results We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%–84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%–94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC ( P Conclusions We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

Purpose Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis causing significant mortality which requires rapid recognition for effective antibiotic therapy, whereas ascitic fluid cultures are frequently negative. The aim of this study was to evaluate the SBP diagnostic efficacy of procalcitonin (PCT) and macrophage inflammatory protein-1 beta (MIP-1β) measured in serum and peritoneal fluid. Material/methods Thirty-two participants with liver cirrhosis and ascites were included into the study (11 females and 21 males, mean age 49.5 ± 11.9 years). The peritoneal fluid and venous blood were collected for routine laboratory examinations and measurements of PCT and MIP-1β. Patients were divided into two groups according to the ascitic absolute polymorphonuclear leukocytes count (≥250 mm −3 and –3 ). Results Ascites was sterile in 22 participants and SBP was diagnosed in 10 patients. Serum and ascitic levels of PCT and MIP-1β did not correlate with clinical and routine laboratory parameters. MIP-1β in the ascitic fluid was significantly higher in patients with SBP (213 ± 279 pg/ml vs. 66.3 ± 49.8 pg/ml; p = 0.01). The sensitivity and specificity for diagnosis of SBP with ascitic MIP-1β were 80% and 72.7%, respectively (cut-off value 69.4 pg/ml) with AUROC 0.77 (95%CI 0.58–0.96). Serum levels of MIP-1β showed lower diagnostic yield. Serum and ascitic PCT levels were not different in patients with and without SBP. Conclusions MIP-1β concentration in ascitic fluid may distinguish patients with and without SBP with satisfactory sensitivity and specificity. Chemokines should be further explored for diagnostic use.

W niniejszej pracy przedstawiono uaktualnione zalecenia grupy ekspertow Polskiej Sieci Guzow Neuroendokrynnych dotyczące zasad postepowania w nowotworach neuroendokrynnych zolądka i dwunastnicy z uwzglednieniem gastrinoma . Omowiono epidemiologie, patogeneze i obraz kliniczny tych nowotworow. Przedstawiono zalecenia dotyczące zasad postepowania diagnostycznego, z uwzglednieniem diagnostyki biochemicznej, histopatologicznej oraz lokalizacyjnej. Uwzgledniono takze zasady postepowania terapeutycznego, w tym leczenie endoskopowe i chirurgiczne, oraz omowiono mozliwości leczenia farmakologicznego i radioizotopowego. Przedstawiono takze zalecenia odnośnie monitorowania chorych z NEN zolądka, dwunastnicy z uwzglednieniem gastrinoma .

Nowotwory neuroendokrynne (NENs) jelita grubego stanowią 20% wszystkich nowotworow neuroendokrynnych. Najczestszą ich lokalizacją jest odbytnica. Nowotwory neuroendokrynne jelita grubego są wykrywane coraz cześciej i liczba ta bedzie wzrastac z uwagi na powszechnośc wykonywania kolonoskopii, w tym badan przesiewowych oraz usuwanie wykrytych zmian. W pracy przedstawiono aktualne zalecenia dotyczące diagnostyki i terapii NEN jelita grubego, z uwzglednieniem diagnostyki biochemicznej, patomorfologicznej, nowych technik obrazowania oraz leczenia endoskopowego, chirurgicznego, farmakologicznego i radioizotopowego. Omowiono takze epidemiologie, charakterystyke kliniczną i monitorowanie leczenia.

Gastroesophageal varices are one of the most serious consequences of portal hypertension. One-third of patients with varices will develop variceal haemorrhage. Despite significant improvements in the outcomes of treatment, mortality due to bleeding from gastro-oesophageal varices still remains very high. These recommendations present optimal management of patients with non-bleeding and bleeding varices.

Thank you very much for your letter concerning our article. Our study is a small-scale investigating the differentially expressed miRNAs in the gastric antral vascular ectasia (GAVE)-affected gastr...