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Background: Due to lower operational costs, health maintenance organizations (HMOs) may prioritize Helicobacter pylori stool antigen testing (HpStAg) for the non-invasive diagnosis of H. pylori infection over 13C-urea breath tests (13C-UBTs). The aim of our study was to compare the accuracy of the diagnostic tests for H. pylori ., Methods: We performed histology, rapid urease test (RUT), 13C-UBT and HpStAg on consecutive patients referred for gastroscopy. Monoclonal stool antigen test was performed using the LIAISON Meridian chemiluminescent immunoassay. Histology was examined with hematoxylin and eosin, and additional stains were performed at the pathologist's discretion. For the assessment of 13C-UBT, we compared concordant histology and RUT. HpStAg was compared to the concordant results of two of the three remaining tests., Results: 103 patients were included (36 males (35.0%), age 50.1 ± 18.4 years). The indication for gastroscopy was dyspepsia in 63 (61.2%). Agreement between RUT and histology was 95.9%. For 13C-UBT and HpStAg, respectively, H. pylori positivity was 30% (30/100) and 27.16% (22/81); sensitivity was 97% and 70%; specificity was 100% and 94.4%; accuracy was 98% and 86%; positive predictive value (PPV) was 100% and 86.4%; negative predictive value (NPV) was 93% and 86%. No demographic, clinical, or endoscopic predictors of HpStAg accuracy were identified using logistic regression., Conclusions: 13C-UBT performs better than HpStAg at our institution. When interpreting results, clinicians should consider test limitations.

Background: We examined corticosteroid use among Israeli patients with Inflammatory Bowel Disease (IBD), focusing on demographic, disease-related, and psychosocial factors. The objective was to contribute to the development of strategies minimizing corticosteroid dependence and improving patient outcomes, given the adverse effects associated with prolonged corticosteroid use., Methods: A comprehensive analysis was conducted on data collected from adult IBD patients attending six gastroenterological outpatient clinics in Israel. The data collected encompassed disease characteristics, demographic information, service level characteristics, social data, and steroid use. Statistical analyses were performed to associate these variables with steroid use., Results: Out of 402 patients, 26 % had been treated with corticosteroids in the previous year, with a majority of these having only one treatment course. Of patients treated with steroids, 57% (n-44) met steroid dependent/excess criteria. Steroid use was more common in patients diagnosed with ulcerative colitis (UC) compared to those with Crohn's disease. Factors such as a diagnosis of UC, male gender, elevated C-reactive protein and fecal calprotectin, and decreased albumin and hemoglobin were associated with steroid use., Conclusion: Corticosteroid use among Israeli IBD patients was associated with disease-related factors and some demographic characteristics. The results highlight the need for continued research to inform strategies aimed at reducing corticosteroid dependence in managing IBD, thereby improving patient outcomes., Competing Interests: Conflict of interest None., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Goals and Background: Gluten-free diet (GFD) includes a higher intake of sugars and fats. Previous studies have investigated its effect on body mass index (BMI) in celiac disease (CD) patients but had contradictive conclusions. Thus, we conducted a systematic review and meta-analysis examining the effect of GFD on BMI in CD patients., Study: Systematically, we conducted literature research using Medline, Scopus, and Embase, and we identified 1565 potential studies/abstracts. Only studies of patients with CD under a GFD with recorded BMI before and after dietary intervention were included. Subgroup analyses based on study design and BMI categories were performed. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (Cls) for the number of patients in each BMI group according to the World Health Organization (WHO) definitions after GFD using fixed and random effect meta-analysis., Results: The analysis included 10 studies and 38 sub-studies/data sets, which encompassed 2450 patients from 5 countries. We found nonsignificant odds for changing the BMI group (pooled OR 0.972, 95% CI: 0.858-1.101, P=0.65) after GFD. However, looking specifically at BMI subgroups, we found higher odds for BMI category change after GFD in underweight patients (OR 0.588, 95% CI: 0.479-0.723, P <0.001), and overweight patients,25

Background : Local excision by transanal endoscopic microsurgery (TEM) is considered an acceptable treatment for rectal adenomas with high-grade dysplasia (HGD). This study aims to assess the likelihood of harboring an invasive carcinoma in preoperatively diagnosed HGD polyps and evaluate the risk factors for tumor recurrence in patients with final HGD pathology. Methods : Data from patients who underwent TEM procedures for adenomatous lesions with HGD from 2005 to 2018 at the Rabin Medical Center, Hasharon Hospital, were analyzed. Collected data included patient demographics, preoperative workup, tumor characteristics and postoperative results. Follow-up data including recurrence assessment and further treatments were reviewed. The analysis included two subsets: preoperative pathology of HGD (sub-group 1) and postoperative final pathology of HGD (sub-group 2) patients. Results : Forty-five patients were included in the study. Thirty-six patients had a preoperative diagnosis of HGD, with thirteen (36%) showing postoperative invasive carcinoma. Thirty-two patients had a final pathology of HGD, and three (9.4%) experienced tumor recurrence. Large tumor size (>5 cm) was significantly associated with recurrence ( p = 0.03). Conclusions : HGD rectal polyps are associated with a significant risk of invasive cancer. Tumor size was a significant factor in predicting tumor recurrence in patients with postoperative HGD pathology. The TEM procedure is an effective first-line treatment for such lesions.

Aims: To investigate the potential association of chronic use of omeprazole with the occurrence of osteoporotic fractures (OF) in community-dwelling elderly subjects., Methods: The cohort consisted of community-dwelling residents aged >65 years registered with a large health maintenance organization in Israel between January 2002 and December 2016. Data were retrospectively collected from the electronic medical files on demographics, parameters known to be associated with OF, diagnoses of osteoporotic hip, wrist, and vertebral fractures, and chronic use of omeprazole (>11 prescriptions/year). Time to OF/death/end of study was calculated from the beginning of the study (2002). The risk of fractures in the chronic users of omeprazole was analyzed by multivariate Cox proportional hazard regression model., Results: In total, 46 805 subjects were included (41% men), mean age 83.4±6.4 years, of whom 10 272 (21.9%) were chronic users of omeprazole. During 14 years of follow-up, OF were diagnosed in 414 (4.0%) omeprazole users and 1007 (2.8%) omeprazole nonusers (p < 0.001). In a Cox regression model adjusted for age and gender only, chronic use of omeprazole was associated with a 16% excess of OF. However, when parameters known to be associated with OF were entered into the multivariate Cox regression model, chronic use of omeprazole was not found to be an independent risk factor for OF, either overall (adjusted hazard ratio = 0.965, 95% confidence interval 0.86-1.08, P = .55) or specifically, in the ≥85 years age group (adjusted hazard ration = 0.780, 95% confidence interval 0.635-0.958, P < .05) in which an inverse correlation between omeprazole use and OF, was demonstrated., Conclusions: Chronic use of omeprazole was not associated with the occurrence of OF in elders., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease., Methods: In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data., Findings: We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet., Interpretation: Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA., Funding: None., Competing Interests: Declaration of interests GLN is an employee of Werfen. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE)., Methods: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation., Results: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively., Conclusion: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: Subjects with a positive Fecal Occult Blood Test (FOBT) that are non-compliant with colonoscopy are at increased risk for colorectal cancer (CRC). Yet, in clinical practice, many remain non-compliant., Aims: To evaluate whether machine learning models (ML) can identify subjects with a positive FOBT predicted to be both non-compliant with colonoscopy within six months and harbor CRC (defined as the "target population")., Methods: We trained and validated ML models based on extensive administrative and laboratory data about subjects with a positive FOBT between 2011 and 2013 within Clalit Health that were followed for cancer diagnosis up to 2018., Results: Out of 25,219 included subjects, 9,979(39.6%) were non-compliant with colonoscopy, and 202(0.8%) were both non-compliant and harbored cancer. Using ML, we reduced the number of subjects needed to engage from 25,219 to either 971 (3.85%) to identify 25.8%(52/202) of the target population, reducing the number needed to treat (NNT) from 124.8 to 19.4 or to 4,010(15,8%) to identify 55.0%(52/202) of the target population, NNT = 39.7., Conclusion: Machine learning technology may help healthcare organizations to identify subjects with a positive FOBT predicted to be both non-compliant with colonoscopy and harbor cancer from the first day of a positive FOBT with improved efficiency., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The association between long-term omeprazole use and gastric cancer (GC) risk is controversial. The aim of this study was to investigate the incidence of GC in elderly community-dwelling omeprazole chronic users with/without aspirin compared to non-users., Methods: The registry of a large health management organization was searched for all community-dwelling members aged ≥65 years from January 2002 to December 2016. Data on demographics, background parameters, and chronic omeprazole and aspirin use (>11 prescriptions/year) were retrieved. Those diagnosed with new-onset GC during the study period (from January 2003) were identified., Results: Of 51 405 subjects who met the inclusion criteria, 197 were diagnosed with GC during a mean follow-up period of 8.74 ± 4.16 years. This group accounted for 0.7% of PPI chronic users (72/11 008) and 0.3% (125/40 397) of nonusers (P < 0.001). GC risk was directly associated with omeprazole chronic use [hazard ratio (HR) 2.03, 95% confidence interval (CI): 1.51-2.73, P < 0.001] and inversely associated with aspirin chronic use (HR 0.55, 95% CI: 0.40-0.75, P < 0.001). Each year of omeprazole use increased GC risk by 9%, and each year of aspirin use decreased GC risk by 10% among omeprazole chronic users. The lowest rate of GC was found in omeprazole nonusers/ aspirin chronic users, and the highest, in omeprazole chronic users/aspirin nonusers., Conclusion: Higher GC rate was associated with omeprazole chronic use and inversely associated with aspirin chronic use relative to omeprazole nonuse in community-dwelling elderly., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: There is no gold standard to assess adherence to gluten-free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence., Methods: Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis., Results: The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8-11.7) years, and median (IQR) duration on GFD of 2.5 (2-5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms., Conclusions: Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Ultrasound-guided percutaneous liver biopsy (UPLB) is currently performed mainly to determine if new hepatic space occupying lesions (SOL) represent benign, primary malignant, or metastatic disease. This study sought to investigate the outcome of UPLB in this setting., Methods: In a retrospective study, patients with a new hepatic SOL who underwent UPLB during 1/2006-12/2016 were included and followed to 12/2018. Clinical data and pathology reports were reviewed. Mortality within 60 days and no change in patients' management following UPLB were defined as medically futile., Results: Included 140 patients, 50% male, mean age 68.8 ± 11.5 years; 112 patients died, all of malignant disease. 32 patients (23%) died within 60 days of UPLB. Median post-UPLB survival was 151 days. Survival was significantly shorter in patients with >1 hepatic lesion (n = 108) or an extrahepatic malignant lesion (n = 77) (p = 0.0082, p = 0.0301, respectively). On Cox Proportional Hazards analysis, significant predictors of mortality within 60 days of UPLB were: age as a continuous variable, (HR 1.070, 95% CI 1.011-1.131, p = 0.018), serum albumin <2.9 g/dL, (HR 4.822 95% CI 1.335-17.425, p = 0.016) and serum LDH >1500 U/L (HR 9.443, 95% CI 3.404-26.197, p < 0.0001)., Conclusions: In patients with these features or with disseminated disease, liver biopsy should be carefully reconsidered., Competing Interests: Declaration of competing interest The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Local excision of large rectal polyps can be an alternative for radical rectal resection with total mesorectal excision. We aim to report the functional and oncological outcomes of transanal endoscopic microsurgery (TEM) for patients with large rectal polyps., Methods: All demographic and clinical data of patients who underwent TEM for rectal polyp of 5 cm or more at the Hasharon Hospital from 2005 to 2018 were retrospectively reviewed., Results: Twenty-eight patients were included. The mean age was 66 years. The mean polyp size was 6.2 cm (range: 5-8.5 cm) with a mean distance of 8.3 cm from the anal verge. Peritoneal entry during TEM was observed in five patients and additional laparoscopy after the completion of the TEM was performed in four patients. There were no major perioperative complications. Seven patients had minor complications. Final pathology revealed T1 carcinoma in five patients and T2 carcinoma in three patients. Re-TEM was performed in one patient with involved margins with adenoma. After a median follow-up of 64 months, one patient had local recurrence., Conclusion: TEM is an acceptable technique for the treatment of large polyps with minor complications and a reasonable recurrence rate. TEM may be considered regardless of the size of the rectal polyp., Competing Interests: None

Background and Aim: Minimal data are available regarding the performance of video capsule endoscopy (VCE) in patients who underwent bariatric surgery. We aimed to report indications, feasibility, and safety of VCE performed after bariatric surgery, specifically focusing on diagnosis rates of Crohn's disease (CD) in this population., Methods: A retrospective analysis of all VCE procedures was performed between January 2015 and December 2019. All patients who underwent bariatric surgery prior to VCE were included. Indication for VCE, ingestion methods, completion rates, retention rates, and endoscopic findings were recorded., Results: A total of 1,255 patients underwent VCE examination during the study period, of which 31 (2.5%) underwent bariatric surgery prior to VCE. The most common bariatric surgery was laparoscopic sleeve gastrectomy (16 patients, 51.6%), and the most common indication for VCE was evaluation of iron deficiency anemia (14 patients, 45.1%). The majority of patients ingested the capsule independently, without endoscopic assistance (20, 64.5%). Although a patency capsule was not used in our cohort, no events of capsule retention were documented. Mean transit time was 4.32 h. Only 4 events of incomplete examination were recorded. Over a median follow-up of 27.5 months (IQR 13.0-34.2), 10 patients (31.2%) had a final diagnosis of CD with a median Lewis score of 225 (IQR 135-900)., Conclusion: VCE is a feasible and safe procedure after bariatric surgery. Oral ingestion does not carry risk of retention. It is an effective means of diagnosis of small-bowel CD in this population., (© 2022 S. Karger AG, Basel.)

Background: The association between proton pump inhibitor (PPI) use and increased risk of dementia is controversial., Aim: Investigating this issue in a large population of community-dwelling elders., Methods: Our database was retrospectively searched for all community-dwelling patients aged ≥65 years who newly diagnosed with dementia/cognitive decline (DCD) between January 2002 - December 2012. Receiving ≥11 prescriptions of PPIs/year was categorized as PPI users. Clinical data were collected from the medical files. Risk of DCD in PPI users was analyzed by Cox regression models., Results: Included 48,632 elders of whom 8,848 were diagnosed with DCD (18.2%). PPI use was documented in 10,507, of whom 1,959 were subsequently diagnosed with DCD (18.6%). Among 38,125 non-PPI users, 6,889 (18.1%) were diagnosed with DCD. The hazard ratio for occurrence of DCD in PPI users compared to non-users was 0.85 (95% CI: 0.81-0.89, P <0.001) in an un-adjusted Cox regression model and 0.83 in a Cox regression model adjusted for age and sex (95% CI: 0.79-0.87, P <0.001). Multivariate Cox regression accounting for background diseases, marital status, and socioeconomic state yielded a hazard ratio of 0.77 (95% CI: 0.73-0.81, P <0.001)., Conclusion: PPI use wasn't associated with DCD development in chronic PPI users., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Juvenile polyposis syndrome (JPS), has diverse phenotypes., Aim: To assess mutation rate, clinical features and genotype-phenotype correlation among Israeli JPS kindreds from different ethnicities., Methods: Patients' data were extracted retrospectively from 5 centers., Results: Thirty five kindreds (49 patients) were included. Thirty one (89%) Jewish [10 (32%) Ashkenazi; 9 (29%) Sephardi; 11 (35%) non-Russia former Soviet-Union countries (NRFSU), one (3%) unknown]. 40/49 individuals from 27 families underwent genetic testing. Among them 34, from 21 families (85, 78%, respectively) had a pathogenic mutation: BMPR1A n = 15 (71%), SMAD4 n = 6 families (29%). While no SMAD4 mutation was described among Jewish families from NRFSU, 7 NRFSU families carried a founder mutation comprising a large genomic deletion of BMPR1A. GI involvement was reported in 42 patients (86%): colonic polyps (n = 40, 95%, > 50 polyps n = 14, 35%) and 12 underwent colonic resection. Fourteen patients (34%) had gastric or small bowel involvement (n = 5) and 4\14 underwent gastrectomy due to polyp burden. Families from NRFSU had more gastric involvement (66.7% vs. 22.2%- Sephardic and 20%- Ashkenazi Jews; p = 0.038), with more gastric polyps (p = 0.017)., Conclusions: We demonstrated a high rate of mutation detection in the heterogeneous population of Israel. Patients from NRFSU with BMPR1A mutation had high rate of gastric involvement., (© 2022. The Author(s).)

Introduction: The association of anemia with dementia in elders is controversial. We examined the potential association of anemia with dementia in a large population of elders., Methods: Historical-prospective registry-based study. Included 36,951 community-dwelling elders (65-113 years) that were followed during 2002-2012. Anemia of all kinds was defined according to Clalit Health Services (CHS) definitions: hemoglobin (HGB) <14 g/dL men, <12 g/dL women; and World Health Organization (WHO): HGB <13 g/dL men, <12 g/dL women. Anemia was categorized as mild (HGB 11-13 g/dL men, 11-12 g/dL women) or moderate-severe (HGB <8-10.9 g/dL men and women). Background data, laboratory values, and diagnosis of dementia and cognitive decline (DCD) were reviewed., Results: During the 10-year follow-up period, DCD was newly diagnosed in 7,180 subjects (19.4%). Subjects with DCD had a higher rate of anemia than those without DCD. Time to development of DCD was 1.5 years shorter in those with than without anemia. On multivariate Cox regression analysis adjusted for age and sex, the hazard ratio (HR) for DCD was 1.45 (95% CI: 1.37-1.54) by CHS and 1.51 (95% CI: 1.41-1.61) WHO anemia criteria. The more severe the anemia, the greater the risk of DCD development (HGB 13-14 g/dL [men only], HR = 1.20 [95% CI: 1.09-1.32]; mild anemia, HR = 1.38 [95% CI: 1.28-1.49]; moderate-severe anemia, HR = 1.64 [CI: 1.41-1.90]). Every decrease in 1 standard deviation of HGB (1.4 g/dL) increased the DCD risk by 15%. A competing risk model has weakened the association of anemia with DCD risk., Conclusions and Implications: Anemia in community-dwelling elders appears to be associated with an increased DCD risk in a dose-response manner. Application of the WHO anemia criteria in men may miss patients with mild anemia that places them at DCD risk. Further research should look at anemia as a cause of reversible dementia., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Routine screening for establishing Lynch syndrome (LS) in young individuals diagnosed with adenomas is not recommended due to its low yield, and limited sensitivity of the employment of immunohistochemistry for DNA mismatch-repair proteins on polyps. Hence we aimed to evaluate the yield of germline mutational analysis in diagnosis of LS in a young Israeli cohort with colorectal adenomatous polyps., Methods: Data were retrospectively collected on consecutive patients, age ≤ 45 years, who underwent colonoscopy with removal of at least one adenoma during 2015-2020, and subsequently genetic testing by multigene panel or LS-Jewish founder mutation panel., Results: Overall, 92 patients were included (median age 35 years, range 23-45 years), of whom 79 (85.8%) underwent multigene panel genotyping, and 13 (14.2%) analysis for Jewish founder LS gene mutations. Altogether, 18 patients were identified with pathogenic mutations in actionable genes, including LS-associated genes in 6 (6.5%), BRCA2 in 2 (2.5%), GREM1 in 1(1.2%), and low-penetrance genes- APC I1307K and CHEK2- in 9 (11.4%) patients. Compared with non-LS patients, LS-carriers had a significantly higher median PREMM5 score (2.6 vs. 1.3; P = 0.04)., Conclusions: Young individuals diagnosed with adenomatous polyps should be offered genetic testing when fulfilling clinical guidelines for LS, but weight should also be given to adenoma characteristics in the PREMM5 score., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Ltd.)

Background: Transanal endoscopic microsurgery (TEM) is considered the procedure of choice for rectal adenomas non-amendable for endoscopic excision and for early rectal cancer. TEM may gain more importance in patients who are considered unfit for major surgery. The option of spinal anaesthesia may offer many advantages for patients undergoing TEM while maintaining the principles of complete tumour excision. The aim of this study is to report the outcome of patients undergoing TEM under spinal anaesthesia., Methods: Demographic and clinical data pertaining patients undergoing TEM under spinal anaesthesia between 2004 and 2015 were retrospectively collected., Results: A total of 158 TEM procedures were recorded in the study period. Twenty-three patients (15%) underwent the procedure under spinal anaesthesia and were included in the study; 13 of them were male and ten were female. The mean age of the patients was 69.1 ± 10.6 years. Seventeen (74%) rectal lesions were adenomas, two (9%) were adenocarcinoma and four (17%) had involved margins after polypectomy. The mean tumour size was 2.1 cm (range, 0.5-3). Distance from the anal verge was 7.7 ± 2.2 cm. Seventeen (74%) lesions were in the posterior wall. The operative time was 73 min (range, 46-108) No adverse anaesthesia-related events were recorded, and the post-operative pain was reduced. The median time of hospitalisation was 2 days (range, 1-4). No major complications were noted, and the minor complications were treated conservatively. The surgical margins were free of tumour in all cases., Conclusion: TEM under spinal anaesthesia had short duration of surgery, no increase in operative and post-operative complications or hospital length of stay. Avoiding the use of general anaesthesia, in such challenging procedure, may open new opportunities for patients determined to be unfit for general anaesthesia., Competing Interests: None

Background and Aim: Empirical therapy for Helicobacter pylori infection is limited by increasing antibiotic resistance and suboptimal eradication rates. Studies of the relative effectiveness of susceptibility-guided therapy have produced conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine whether susceptibility-guided therapy is superior to empirical therapy for H. pylori infection., Methods: We searched articles listed in PubMed, MEDLINE, EMBASE, and Web of Science through May 25, 2020, RCTs comparing susceptibility-guided versus empirical therapy for H. pylori infection. Outcomes, including effectiveness and safety, were analyzed in a meta-analysis., Results: Our final analysis included 16 studies, comprising 2374 patients who received susceptibility-guided therapy and 2451 patients who received empirical treatment. In previously untreated subjects, susceptibility-guided therapy was slightly more effective than empirical therapy (intent to treat risk ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21; P < 0.0001, I 2  = 75%). Susceptibility-guided therapy was superior to first-line clarithromycin-based triple therapy only when clarithromycin resistance exceeded 20% (RR, 1.18; 95% CI, 1.07-1.30; P = 0.001, I 2  = 81%). Susceptibility-guided therapy was not more effective than empirical quadruple therapy (RR, 1.02; 95% CI, 0.92-1.13; P = 0.759, I 2  = 80%). Three RCTs were performed exclusively among previously treated subjects, and were highly heterogeneous., Conclusions: Our findings suggest that susceptibility-guided treatment may be slightly superior to empirical first line triple therapy. Susceptibility- guided treatment does not appear to be superior to empirical first-line quadruple therapy or empirical rescue therapy., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Due to the increasing resistance of Helicobacter pylori, there is a need for novel antibiotic treatment protocols. We aimed to perform a systematic review and meta-analysis in order to determine the effectiveness and safety of rifabutin triple therapy for H. pylori infection., Methods: We performed a systematic review of prospective clinical trials with a treatment arm consisting of proton pump inhibitor, amoxicillin, and rifabutin and a meta-analysis of randomized controlled trials (RCTs)., Results: Thirty-three prospective studies including 44 datasets were identified. Meta-analysis of four RCTs for rescue treatment found no difference between treatment groups (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.437-1.791, I 2  = 68.1%, P = 0.733). Only one RCT compared rifabutin therapy with control for first-line treatment of H. pylori infection (OR 3.78, 95% CI 2.44-5.87, P < 0.0001). Treatment was more likely to be successful in Asian versus non-Asian populations (81.0% vs 72.4%, P = 0.001) and when daily amoxicillin dose was ≥ 3000 mg or proton pump inhibitor dose was ≥ 80 mg or treatment duration was 14 days (80.6% vs 66.0%, P = 0.0001). The overall event rate for adverse effects was 24.8% (729/2937) (95% CI 0.23-0.26), and the pooled OR for adverse effects in the treatment versus control group was 0.93 (95% CI 0.50-1.75) (I 2  = 79.76, P = 0.82)., Conclusion: Evidence for the effectiveness of rifabutin for the first-line treatment of H. pylori infection in adults is limited, and studies comparing rifabutin with conventional first-line treatments are lacking., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim of the Study: To compare [¹¹C] choline PET/CT findings between patients with cirrhosis and normal liver controls., Methods: Included 11 patients with cirrhosis and 14 controls. All underwent a dynamic [11C] choline PET/CT. The maximal standard uptake values (SUVmax), the area under the curve (AUC) and kinetic parameters (K1 and K2), clinical and laboratory data, were compared between groups., Results: Patients mean age was 68.4 ± 10.7 and controls, 69.7 ± 7.3 years. Mean SUVmax was higher in patients than controls (right lobe, 10.06 ± 12 vs. 6.3 ± 1.6, P = 0.011; left lobe, 8.6 ± 11.6 vs. 5.4 ± 0.9, P = 0.024; spleen 17.99 ± 27.8 vs. 13.4 ± 2.6, P = 0.027; kidney, 35.9 ± 59.5 vs. 19.3 ± 4.8, P = 0.025) and also AUC values (right lobe, 13,538 ± 20,020 vs. 8427.3 ± 1557.9, P = 0.026; left lobe 12,304 ± 18,871 vs. 6878.9 ± 1294.3, P = 0.024; spleen, 12,875 ± 17,930 vs. 8263.9 ± 1279.2, P = 0.023; kidney, 24,623 ± 36,025 vs. 13,667 ± 3873.9, P = 0.032). No difference in kinetic parameters was found. No correlations between severity of clinical signs and imaging-derived parametric data were found among patients with cirrhosis., Conclusions: [11C] choline PET/CT may serve as a noninvasive biomarker for patients with cirrhosis., Competing Interests: Declaration of Competing Interest No potential conflicts of interest were disclosed., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Intestinal metaplasia (IM) is an intermediate step in the progression from premalignant to malignant stages of gastric cancer (GC). The Popeye domain containing ( POPDC ) gene family encodes three transmembrane proteins, POPDC1, POPDC2, and POPDC3, initially described in muscles and later in epithelial and other cells, where they function in cell-cell interaction, and cell migration. POPDC1 and POPDC3 downregulation was described in several tumors, including colon and gastric cancers. We questioned whether IM-to-GC transition involves POPDC gene dysregulation. Gastric endoscopic biopsies of normal, IM, and GC patients were examined for expression levels of POPDC1-3 and several suggested IM biomarkers, using immunohistochemistry and qPCR. Immunostaining indicated lower POPDC1 and POPDC3 labeling in IM compared with normal tissues. Significantly lower POPDC1 and POPDC3 mRNA levels were measured in IM and GC biopsies and in GC-derived cell lines. The reduction in focal IM was smaller than in extensive IM that resembled GC tissues. POPDC1 and POPDC3 transcript levels were highly correlated with each other and inversely correlated with LGR5 , OLFM4 , CDX2 , and several mucin transcripts. The association of POPDC1 and POPDC3 downregulation with IM-to-GC transition implicates a role in tumor suppression and highlights them as potential biomarkers for GC progression and prospective treatment targets.

Aim: Data on cardiovascular outcomes in elderly using proton pump inhibitors (PPI) are scant. We aimed to test the association between PPI use and the occurrence of first-time ischemic stroke (FTIS) among elderly., Methods: The electronic database of a centrally located district branch of a large health maintenance organization in Israel was retrospectively screened (2002-2016) for community-dwelling individuals (≥65-95 years) for demographics and co-morbidities. Follow-up was until FTIS, death or end of study. Findings were analyzed by PPI use and occurrence of FTIS., Results: 29,639 subjects (without history of stroke and use of antiplatelet aggregation drugs) mean age of 82.2 ± 5.5 years (range: 65-95 years, 38% male) were analyzed: 8,600 (29%) used PPIs. Mean follow up was 10.58 years (SD ± 5.44). Similar total and annual occurrence rates of FTIS were depicted in PPI users and non-users (20.9% vs. 21% and 2% vs. 2.1%, respectively). On a Cox regression analysis, upon adjustment for age, gender and cardiovascular disease related risk factors, PPI use was significantly associated with lower rates of FTIS (HR 0.73, 95% C.I. 0.69-0.77, p < 0.001). The risk for FTIS was significantly lower in subjects using PPI at any dose and for any time period compared to non-users (HR 0.9, 95% C.I. 0.85-0.96 for 7-48 yearly prescriptions and HR 0.51, 95% C.I. 0.46-0.55 for ≥49 yearly prescriptions)., Conclusions: PPI use was associated with lower rates of FTIS in community-dwelling elders. Prospective large-scale studies are needed to fully elucidate the effect of PPI in this aging population., (© 2020 The British Pharmacological Society.)

Background: Gastroesophageal reflux disease (GERD) is a common disorder. Overall, ≤35% of GERD patients fail the standard dose of proton-pump-inhibitor (PPI) treatment. Due to the high prevalence and low satisfaction rate with treatment failure, there is an unmet need for new treatment. Our aim was to evaluate whether the use of the transcutaneous electrical stimulation system (TESS) can reduce esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI., Methods: We enrolled 10 patients suffering from heartburn and regurgitation with an abnormal esophageal-acid exposure (off PPIs) who failed standard-dose PPI. After the placement of a wireless esophageal pH capsule, all patients were treated with TESS. The primary end point was the reduction in the baseline (pretreatment) 24-hour percent total time pH <4 and/or DeMeester score by 50%., Results: Seven GERD patients (five females and two males, aged 49.3 ± 10.1 years) completed the study. At baseline, the mean percent total time pH <4 was 12.0 ± 4.9. Following TESS, the mean percent total time pH <4 dropped to 5.5 ± 3.4, 4.5 ± 2.6, 3.7 ± 2.9, and 4.4 ± 2.5 on Days 1, 2, 3, and 4, respectively. At baseline, the mean DeMeester score was 39.0 ± 18.5. After TESS, the mean DeMeester score dropped to 15.8 ± 9.2, 13.2 ± 6.8, 11.2 ± 9.4, and 12.0 ± 6.8 on Days 1, 2, 3, and 4, respectively., Conclusion: TESS is a safe and potentially effective modality in reducing esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI. A larger and prospective controlled study is needed to verify these preliminary results., (© The Author(s) 2021. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Postcolonoscopy colorectal cancer (PCCRC) can arise from missed cancers, missed premalignant lesions, incomplete resection, and new cancers with an accelerated route to cancer. 1 ., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Goals: The goal of this study was to examine the impact of prior treatment with a nitroimidazole antibiotic on the success of Helicobacter pylori treatment., Background: Prior nitroimidazole exposure may increase the likelihood of nitroimidazole-resistant H. pylori. Current H. pylori treatment guidelines recommend that, in the absence of susceptibility testing, patients with prior nitroimidazole exposure should not be treated with a nitroimidazole antibiotic. Data to support this recommendation are lacking., Study: We searched the Clalit Health Services database to identify subjects 25 to 60 years old who underwent a first-ever C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved., Results: A total of 1386 subjects (34.8% male individuals, age 40.7±10.7 y) received a nitroimidazole-containing regimen including 282 (20.4%) with prior nitroimidazole exposure. Successful eradication was achieved in 58.9% and 73.8% of subjects with and without prior nitroimidazole exposure, respectively (odds ratio, 0.51; 95% confidence interval, 0.39-0.67; P<0.0001). Nitroimidazole exposure adversely impacted the success of triple therapy with nitroimidazole, proton pump inhibitor, and amoxicillin or clarithromycin (39.4% vs. 63.4% and 54.4% vs. 73.6%, P<0.01, respectively), but not quadruple therapy. Following multivariate analysis, nitroimidazole exposure was significantly associated with eradication failure (odds ratio, 1.89; 95% confidence interval, 1.43-2.50; P<0.0001). A greater time elapsed from nitroimidazole exposure, and a lower cumulative nitroimidazole dose were observed in subjects with successful eradication (P<0.0001 for both)., Conclusion: Nitroimidazole exposure may adversely impact the success of nitroimidazole-based triple therapy, but not quadruple therapy. Clinicians should conduct a thorough patient drug history before administering empiric treatment for H. pylori infection.

Lactose intolerance is a common condition caused by lactase deficiency and may result in symptoms of lactose malabsorption (bloating, flatulence, abdominal discomfort, and change in bowel habits). As current data is limited, the aim of our study was to assess the efficacy of probiotics with a β-galactosidase activity on symptoms of lactose malabsorption and on the lactose hydrogen breath test (LHBT). The study group comprised eight symptomatic female patients with a positive LHBT. Patients were treated for 6 months with a probiotic formula with β-galactosidase activity (Bio-25, Ambrosia-SupHerb, Israel). All patients completed a demographic questionnaire as well as a diary for the assessment of symptom severity and frequency at entry, every 8 weeks, and at the end of the treatment period. Measurements of hydrogen (H 2 ) levels (parts per million, ppm) at each of these time points were also performed. End points were a decrease of 50% in symptom severity or frequency, and the normalization (decrease below cutoff point of 20 ppm) of the breath test. Mean age and mean body mass index (BMI) were 36.4 ± 18.6 years and 23.2 kg/m 2 , respectively. Compared to baseline scores, the frequency of most symptoms, and the severity of bloating and flatulence, improved after treatment. Normalization of LHBT was obtained in only two patients (25%). In this pilot study, Bio-25, a unique formulation of probiotics with β-galactosidase activity, demonstrated symptom resolution in most patients with lactose malabsorption. A larger randomized trial is warranted to confirm these preliminary findings.

Background: The approach to surgical resection of multiple rectal lesions when endoscopic polypectomy is unsuccessful has historically been radical rectal resection with total mesorectal excision. This approach is fraught with high morbidity and mortality. We explored the possibility of performing one transanal endoscopic microsurgery procedure to resect multiple synchronous rectal lesions., Materials and Methods: A retrospective analysis of all adult patients undergoing transanal endoscopic microsurgery at a single institution between 2004 and 2015. Clinical, demographic, and pathologic data were analyzed for all patients with synchronous rectal lesions that were excised via one transanal endoscopic microsurgery procedure., Results: Of the 158 patients who underwent transanal endoscopic microsurgery during the study period, 14 (8.8%) had two or more synchronous rectal lesions resected. The mean tumor size was 2.5 cm (range 0.5-3.5). The mean distance from the anal verge for the upper/proximal lesions: 10 ± 2.5 cm, and for the lower/distal lesions: 7 ± 2 cm. Mean operative time was 112 minutes (range 75-170). Median hospitalization time was 3 days (range 2-4). Two patients had urinary retention. No other complications were noted. All the transanal endoscopic microsurgery specimens were with clear margins., Conclusion: Transanal endoscopic microsurgery is a safe and feasible procedure for patients with multiple rectal lesions. We demonstrate no increase in surgical time, completeness of specimen resection, no increase in complications or hospital length or stay when compared to patients undergoing transanal endoscopic microsurgery for a single lesion.

Introduction: Suppression of gastric acid secretion with proton-pump inhibitors (PPI) is an integral part of the treatment of Helicobacter pylori infection. Esomeprazole has been shown to be superior to other PPIs when used in the context of triple therapy; however, comparative data for PPI efficacy in quadruple therapy are lacking. Current guidelines recommend H. pylori eradication with quadruple therapy in areas with high clarithromycin resistance., Objective: To determine whether esomeprazole is more effective than other PPIs in the context of quadruple therapy for H. pylori eradication., Methods: We retrospectively identified 25- to 60-year-old subjects with a positive 13C-urea breath test and no prior laboratory or endoscopic test for H. pylori infection. Pharmacy dispensation data were retrieved., Results: A total of 7,896 subjects including 2,856 (36.2%) males, aged 40.4 ± 10.6 years, were identified. Of those, 78.1% received omeprazole, 20.1% received lansoprazole, 1.5% received esomeprazole, and 0.34% received pantoprazole together with antibiotics for H. pylori eradication. Esomeprazole was associated with a greater proportion of successful eradication (85.0 vs. 77.5%, esomeprazole vs. omeprazole, OR 1.64; 95% CI 0.99-2.72; p = 0.05). A nonsignificant trend favored esomeprazole over omeprazole among subjects receiving quadruple therapy (90.0 vs. 82.0%, respectively, OR 1.98; 95% CI 0.68-5.72; p = 0.16). Independent predictors of treatment success included older age and quadruple therapy., Conclusion: Esomeprazole is more beneficial than other PPIs for H. pylori eradication. Studies with larger subgroups are necessary to confirm our findings among subjects receiving quadruple therapy., (© 2020 S. Karger AG, Basel.)

Objectives: Helicobacter pylori (H. pylori) guidelines, including the recent ACG clinical guideline, recommend avoiding clarithromycin-based triple therapy (TT-C) among patients with past macrolide exposure. Data to support this recommendation are scarce, and the impact of macrolide exposure on quadruple therapies is unclear. We aimed to determine the impact of macrolide exposure on the efficacy of H. pylori treatment in our region., Methods: We searched the Clalit Health Services database to identify subjects aged 25-60 years who underwent the first-ever C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved., Results: We identified 7,842 subjects (36.1% male individuals, age: 40.3 ± 10.5 years), including 3,062 (39.0%) with previous macrolide exposure. The efficacy of TT-C was 74.3% and 82.4% among subjects with and without macrolide exposure, respectively (odds ratio (OR), 0.62; 95% confidence interval (CI), 0.55-0.70; P < 0.0001). TT success was adversely affected by exposure to clarithromycin (55.5%; OR, 0.31; 95% CI, 0.24-0.39; P < 0.0001), roxythromycin (74.4%; OR, 0.65; 95% CI, 0.58-0.74; P < 0.0001), and erythromycin (73.9%; OR, 0.72; 95% CI, 0.57-0.89; P < 0.01) but not by exposure to azithromycin. A greater time elapsed because exposure to clarithromycin and roxythromycin was associated with higher eradication (OR, 1.007; 95% CI, 1.002-1.012; P < 0.01 and OR, 1.004; 95% CI, 1.002-1.006; P < 0.0001). A higher dose of clarithromycin and roxythromycin was associated with a lower likelihood of successful eradication (OR, 0.99988; 95% CI, 0.99982-0.99996; P < 0.01 and OR, 0.99981; 95% CI, 0.99971-0.99992; P < 0.001). The efficacies of sequential and concomitant therapies were 82.7% and 81.3%, respectively, and were not significantly affected by macrolide exposure., Conclusions: TT-C is adversely affected by previous exposure to macrolide antibiotics. Sequential, concomitant, and bismuth-based treatment may be preferred in this setting.

This study sought to determine the prevalence of significant liver disease in those subjects with serum alanine aminotransferase levels in the range between the current and the newly suggested upper limit of normal (termed the delta range). The files of the previous study subjects (who underwent at least one alanine aminotransferase measurement in 2002 and followed to 2012) were reviewed for a diagnosis of chronic liver disease; aspartate aminotransferase/platelet ratio index, FIB-4 and alanine aminotransferase/aspartate aminotransferase ratio were used to evaluate liver fibrosis. The prevalence of significant liver disease, by diagnoses and fibrosis scores was compared between subjects with alanine aminotransferase levels in the delta range (men, 42-45 IU/L; women, 26-34 IU/L) and in the newly suggested normal range (men, 15-42 IU/L; women, 10-26 IU/L). The cohort included 49,634 subjects (41% male, mean age 83±6 years) of whom 2022 were diagnosed with chronic liver disease including 366 with cirrhosis. Compared to subjects with alanine aminotransferase levels in the newly suggested normal range, subjects with alanine aminotransferase levels in the delta range had a significantly higher rate of chronic liver disease (men, 15.3% vs. 4.9%; women, 7.8% vs. 3.3%) and of cirrhosis specifically (men, 4.2% vs. 0.9%; women, 1.5% vs. 0.4%) and also had higher mean fibrosis scores (P <0.001 for all). Lowering the current upper limit of normal of serum alanine aminotransferase may help to identify elderly patients at risk of significant liver disease., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Only a minority of patients with a positive fecal occult blood test (FOBT) undergo a follow-up second diagnostic procedure, thus minimizing its contribution for colorectal cancer (CRC) prevention. We aimed to obtain a precise estimation of this problem and also assess the diagnostic yield of CRC and adenomas by colonoscopy in these patients., Methods: Literature searches were conducted for "compliance" OR "adherence" AND "fecal occult blood test" OR "fecal immunohistochemical test" AND "colonoscopy." Comprehensive meta-analysis software was used., Results: The search resulted in 42 studies (512,496 patients with positive FOBT), published through December 31, 2017. A funnel plot demonstrates a moderate publication bias. Compliance with any second procedure, colonoscopy, or combination of double-contrast barium enema with or without sigmoidoscopy in patients with a positive FOBT was 0.725 with 95% confidence interval (CI) 0.649-0.790 ( p  = 0.000), 0.804 with 95% CI 0.740-0.856 ( p  = 0.000) and 0.197 with 95% CI 0.096-0.361 ( p  = 0.000), respectively. The diagnostic yield for CRC, advanced adenoma and simple adenoma was 0.058 with 95% CI 0.050-0.068 ( p  = 0.000), 0.242 with 95% CI 0.188-0.306 ( p  = 0.000) and 0.147 with 95% CI 0.116-0.184 ( p  < 0.001), respectively., Discussion: Compliance with diagnostic evaluation after a positive FOBT is still suboptimal. Therefore, measures to increase compliance need to be taken given the increased risk of CRC in these patients.

Background: Threshold values for 13 C-urea breath test (13C-UBT) positivity may be affected by various sociodemographic, host, bacterial, and laboratory factors. Manufacturer recommended cutoffs for 13C-UBT assays may not be applicable in all settings. Optimizing 13C-UBT cutoffs may have profound public health ramifications. We aimed to determine the optimal threshold for 13C-UBT positivity in our population., Methods: Consecutive test samples collected at our central laboratory from patients undergoing a first-time 13C-UBT between 1 January 2010 and 31 December 2015 were included. The difference between values at 30 minutes and at baseline (T30-T0) was expressed as delta over baseline (DOB). Cluster analysis was performed on the 13C-UBT test results to determine the optimal cutoff point with minimal interclass variance., Results: Two lakhs thirty four thousand eight hundred thirty one patients (87 291 (37.2%) male, age 39.9 ± 19.9) underwent a first-time 13C-UBT, including 124 701 (53.1%) negative and 110 130 (46.9%) positive tests, using the manufacturer-recommended cutoff of 3.5 DOB. Cluster analysis determined an optimized cutoff of 2.74 DOB, representing an additional 2180 (0.93%) positive subjects who had been previously categorized as negative according to the manufacturer-specified cutoff of 3.5 DOB. Mean positive and negative DOB values were 19.54 ± 14.95 and 0.66 ± 0.51, respectively. The cutoffs for male and female subjects were 2.23 and 3.05 DOB, respectively. Threshold values for <45-year-olds, 45-60-year-olds and >60-year-olds were 2.67, 2.55, and 2.93 DOB, respectively. Of the 2180 (0.93%) patients with DOB 2.73-3.49, 289 (13.3%) performed a subsequent 13C-UBT and 140 (48.4%) remained positive when tested at 20.3 ± 14.4 months., Conclusions: Major referral laboratories should optimize threshold values for 13C-UBT positivity for their geographical location. Different cutoff values should be applied for male and female subjects., (© 2018 Wiley Periodicals, Inc.)

Background: Serum alanine aminotransferase (ALT) levels below and above the reference range have been found to serve as a marker of liver injury and to predict all-cause mortality. The need to adjust the reference range by age, sex, or other parameters remains unclear. The current reference range of serum ALT in Israel is 0-34 IU/l for women and 0-45 IU/l for men. We aimed to test the applicability of the current reference range values of ALT in specific people - the elderly population., Methods: A retrospective design was used. The study population consisted of community-dwelling individuals aged at least 65 years who were tested for serum ALT in 2002 at a large health management organization and followed until the end of December 2012. Data were collected on demographics, laboratory tests, comorbidities, and mortality., Results: A total of 49 634 participants (59% women, mean age 83.2±6.3 years) were included. ALT levels between 16 and 25 IU/l were associated with the lowest mortality (hazard ratio=1), and values of less than 16 IU/l and more than 25 IU/l (unadjusted) were associated with higher mortality risk, yielding a U-shaped pattern.Highest mortality rates were also revealed at serum ALT levels more than 56 IU/l and less than 10 IU/l. A significant association of higher mortality risk was noted with lower mean values of hemoglobin, albumin, and total cholesterol, both for patients with lower serum ALT levels (<10 IU/l) and patients with higher serum levels (>56 IU/l)., Conclusion: Very low and very high levels of serum ALT within the current reference range are associated with an increased risk of death in community-dwelling individuals of at least 65 years old.

Background: There are continual efforts to identify factors which influence the success of first-line therapy for Helicobacter pylori ( H. pylori ) infection. The 13 C-urea breath test result (C13-UBT) utilizes H. pylori urease activity and is a highly accurate diagnostic assay. We aimed to determine whether the magnitude of C13-UBT result is related to treatment success., Methods: Adult patients who underwent a first-time 13 C-urea breath test between January 2010 and January 2016 were included. In order to isolate a naïve test-and-treat population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients > 45 years and those with a previous C13-UBT. Data were extracted from the Clalit Health Services laboratory database., Results: A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0 years) who underwent a first-time C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory posttreatment C13-UBT was performed in 18,375 (37.8%), and eradication was successful in 12,018 (65.4%). The mean C13-UBT recording was 20.6 ± 16.2 DOB in subjects with successful eradication and 19.5 ± 13.1 DOB in subjects with treatment failure (OR, 1.01; 95% CI 1.00-1.01, p < 0.01). Among patients in the upper quintile of C13-UBT measurement, eradication was achieved in 67.6%, compared to 62.6% in the lower quintile (OR, 1.22; 95% CI 1.11-1.35, p < 0.01). Subjects in the top 1 percentile (C13-UBT ≥ 70 DOB) achieved eradication in 75.0%, compared to 65.3% among subjects with C13-UBT < 70 DOB (OR, 1.59; 95% CI 1.05-2.41, p < 0.01)., Conclusions: The superiority in H. pylori eradication observed in subjects with a higher C13-UBT DOB is small but significant. Further studies should examine the physiological and microbiological basis for this finding.

Background: Patients' selection for transanal endoscopic microsurgery (TEM) depends on diagnostic modalities; however, there are still some limitations in the preoperative diagnosis of rectal lesions, and in some reports, up to third of the adenomas resected by TEM were found to be adenocarcinoma; therefore, salvage radical resection (RR) remains necessary for achieving oncological resection. Salvage RR may encounter some technical problems as the violation of the mesorectum and the scar formation. In this study, we aimed to report the outcome in patients undergoing salvage RR in terms of morbidity and oncological results., Materials and Methods: Demographic and clinical data pertaining to patients undergoing RR following TEM between 2004 and 2014 were retrospectively collected., Results: One hundred forty one TEM were performed in the study period, 53 (38%) for malignant rectal lesions. Indication for TEM: 15 (28%) benign adenoma, 25 (47%) early rectal cancer, and 13 (25%) had clinical complete response after neoadjuvant radiochemotherapy. Ten (19%) patients had no residual tumor in TEM specimen, 15 (28%) had T1, and 2 of them underwent salvage low anterior resection (LAR). Ten (19%) had T2, 4 had LAR, and 1 had abdominoperineal resection (APR). Five (9%) had a T3, 3 underwent LAR, and 2 had APR. Among the 13 (25%) after chemo-radiotherapy (CRT), 4 had salvage AR. The time from TEM to RR was 47 days (range32-70). Of 16 salvage surgeries, 8 (50%) were laparoscopic. The median operative time was 210 minutes (range165-360). Five patients had protective ileostomy. Rectal perforation occurred in 2 (12%) patients; both had a posterior location, one after CRT. Two (12%) postoperative small-bowl obstruction and three wound infections occurred. There was no perioperative mortality in any of the patients who underwent RR. The final pathology was no residual disease in 9, T3N1 in 1, T3N0 in 3, T2N1 in 1, and T2N0 in 2 patients. Eight (50%) had adjuvant chemotherapy., Conclusion: Laparoscopic total mesorectal excision following TEM seems to be safe, and with no negative impact of the completeness of the resection. The concern of intraoperative specimen perforation is real, and should be dealt with meticulous technique and careful dissection, particularly after CRT.

Background: Barrett's esophagus (BE) is a known complication of gastroesophageal reflux disease. In a previous study, we described a high prevalence of intestinal metaplasia (IM) in patients with an irregular Z line. However, the clinical importance of this finding is unclear., Goals: To evaluate the long-term development of BE and relevant complications in patients diagnosed with an irregular Z line, with or without IM, on routine esophago-gastro-duodenoscopy (EGD)., Methods: In our previously described cohort, 166 out of 2000 consecutive patients were diagnosed with an incidental irregular Z line. Of those with irregular Z line, 43% had IM. In this continuation study, patients' status was reassessed after a median follow-up of 70 months. Patients were divided into two groups: Patients with IM (IM-positive group) and without IM (IM-negative group). The incidence of long-term development of BE, dysplasia, and esophageal adenocarcinoma were compared between groups., Results: At least one follow-up EGD was performed in 102 (61%) patients with an irregular Z line. Endoscopic evidence of BE was found in eight IM-positive patients (8/50 [16%]) and in one IM-negative patient (1/52 [1.9%]). Two (4%) IM-positive patients developed BE with low-grade dysplasia. None of the patients developed high-grade dysplasia, or esophageal adenocarcinoma., Conclusions: Patients with irregular Z line do not develop major BE complication in more than 5 years of follow-up.

Background: Esomeprazole is commonly administered with food; however, clinical data to support this practice are lacking. We aimed to determine the effect of postprandial ingestion of esomeprazole on reflux symptoms among patients with gastroesophageal reflux disease (GERD)., Methods: Consecutive patients with GERD adequately controlled with esomeprazole 40 mg daily, entered a 2-week lead-in period during which esomeprazole was administered 30 min before breakfast. Patients were then randomized to continue preprandial ingestion or to ingest esomeprazole following a standardized meal. Outcomes included GERD frequency and severity indices, GERD-health-related quality of life (GERD-HRQL) questionnaire and Short Form 36 (SF-36)., Results: Thirty-two patients (17 [53.1%] men, aged 53.5 ± 17.2 years) were included, and 16 (50%) switched to postprandial ingestion of esomeprazole. GERD frequency and severity decreased in both groups (Δ9.0 ± 7.2 vs. Δ10.0 ± 8.1, p = 0.29; Δ6.6 ± 6.8 vs. Δ10.2 ± 7.4, p = 0.57 in postprandial group vs. controls, for frequency and severity, respectively). GERD-HRQL improved in both study groups to a similar degree (Δ10.7 ± 10.5 vs. Δ10.0 ± 13.8, p = 0.97). All SF-36 subscores increased in both groups to a similar degree. In a mixed linear model, there were no differences between the study groups in the changes observed in GERD frequency (p = 0.49), severity (p = 0.32), and GERD-HRQL (p = 0.98) during the study period., Conclusion: Switching to postprandial administration of esomeprazole is not associated with deterioration in reflux symptoms among patients with GERD. Esomeprazole seems to remain efficacious when administered after meals., (© 2018 S. Karger AG, Basel.)

Background/aims: Although the efficacy of first-line treatment for Helicobacter pylori infection should aim to be > 90%, it is unclear whether this target has been achieved in Israel. We aimed to determine the success rate of treatment for H. pylori and to describe temporal changes in our region. Methods: Adult patients who underwent a first-time -C13-urea breath test (C13-UBT) at Clalit Health Services between January 1, 2010 and December 31, 2015 were included. In order to isolate a naïve "test-and-treat" population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients ≥45 years and those with any previous C13-UBT., Results: A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0) who underwent at least one C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory post-treatment C13-UBT was performed in 37.8, 44.1, 46.6, and 45.9% following 1st, 2nd, 3rd, and 4th-line treatment respectively. Eradication was successful in 65.4% following first-line treatment, and eradication success improved during the study period (59.2, 63.3, 65.7, 66.0, 69.0, and 73.1% in 2010, 2011, 2012, 2013, 2014, and 2015 respectively; OR 1.11; 95% CI 1.09-1.13; p < 0.0001). Eradication was successful in 44.7% following second-line treatment, although eradication success did not significantly improve during the study period (OR 1.05; 95% CI 0.99-1.10; p = 0.09)., Conclusions: Despite the increasing success of first-line treatment for H. pylori infection over the study period, eradication rates remain suboptimal. Initiatives to implement the Toronto and Maastricht Consensus Reports should be advanced., (© 2018 S. Karger AG, Basel.)

Background: The prevalence of obesity is as high as one-third of the adult population in the ultrasound. Obese patients operated for rectal cancer are less likely to undergo sphincter-preserving surgery, and have an increased morbidity and mortality. We aim to report the outcomes of transanal-endoscopic-microsurgery (TEM) in obese patients with benign and malignant neoplasms., Materials and Methods: An analysis was carried out of all patients undergoing TEM at a single institution between 2004 and 2015. Clinical, demographic, and pathologic data were analyzed in respect to BMI; a dichotomous variable was created categorizing the patients in this retrospective case series as either obese (BMI≥30) or nonobese (BMI<30)., Results: Of the 158 patients who underwent TEM during the study period, 51 (32%) were obese and 107 (68%) were nonobese. No significant differences were found in terms of patients' demographics and tumor characteristics. There were no significant differences in operative time [105 min (range: 75-170) and 98 (range: 56-170), respectively, P=0.2], hospital length of stay [3 days (range: 2-6) and 4 (range: 2-12), respectively, P=0.48], or complication rates (20 and 23%, respectively, P=0.68)., Conclusion: TEM is a safe procedure for rectal neoplasms in the obese population. We found no difference in surgical time and completeness of specimen resection, and no increase in complications or length of stay in the hospital in obese versus nonobese patients. As for selected high risk patients, the TEM may be of benefit in obese patients with T1/T2N0M0 rectal cancer.

Background and Aims: The current guidelines for surveillance after polypectomy do not distinguish between diminutive (1-5 mm) and small (6-9 mm) polyps with low-grade dysplasia (LGD). We aimed to evaluate the risk for advanced neoplasia on follow-up colonoscopy., Methods: We retrospectively analyzed 443 patients whose worst finding at index colonoscopy was polypectomy of 1 to 5 or 6 to 9 mm polyps with LGD and those who underwent a follow-up colonoscopy., Results: During a mean follow-up of 32.0 months (interquartile range 13-48 months), advanced neoplasia was found in 26 patients (5.9%). Among all included patients (n = 443), advanced neoplasia was found in 13 of 310 patients (4.2%) of the 1- to 5-mm group versus 13 of 133 patients (9.8%) of the 6- to 9-mm group (hazard ratio [HR], 3.49; 95% confidence interval [CI], 1.6-7.6). Among the patients with 1 to 2 polyps resected (n = 313), advanced neoplasia was found in 8 of 231 patients (3.5%) of the 1- to 5-mm group versus 8 of 82 patients (9.8%) of the 6- to 9-mm group (HR 3.97; 95% CI, 1.47-10.7). Among the patients with ≥3 polyps resected (n = 130), advanced neoplasia was found in 5 of 79 patients (6.3%) of the 1- to 5-mm group versus 5 of 51 patients (9.8%) of the 6- to 9-mm group (HR 2.4; 95% CI, 0.7-8.36). Fair bowel preparation also was associated with the risk for advanced neoplasia at follow-up (HR 3.87, 95% CI, 1.70-8.82)., Conclusions: Our findings suggest that among patients with up to 9-mm adenomatous polyps, a polyp size of 6 to 9 mm, >2 polyps, and fair bowel preparation are associated with advanced neoplasia., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Goal: To identify factors influencing survival after percutaneous endoscopic gastrostomy (PEG) tube insertion in elderly patients with severe dementia., Background: Use of PEG in patients with dementia raises medical and ethical questions., Study: The cohort included 189 patients aged ≥64 years with severe dementia who underwent PEG tube insertion in 2002 to 2011 at a tertiary hospital and were followed through 2014. Data were collected on background diseases, laboratory tests conducted 14 (±10) days before and 90 (±10) days after PEG, and date of death. Multivariate Cox regression analysis was performed and cumulative survival curves plotted., Results: Mean baseline serum albumin level was significantly lower in patients who died ≤30 days after PEG (n=32, 16.9%) than patients who survived longer (2.9±0.5 vs. 3.3±0.5 g/dL, P<0.001), and significantly higher in patients who survived 1 year after PEG (n=96, 50.8%) than patients who died earlier (3.4±0.5 vs. 3.1±0.5 g/dL, P=0.002). No significant differences were found for the other laboratory parameters. After adjustment for background diseases, serum albumin level above the median (3.3 g/dL) was the only predictor of survival (hazard ratio 0.51; 95% confidence interval, 0.37-0.72; P<0.001). Patients with stable/increased serum albumin levels at 90 days after PEG (n=80, 42.3%) survived longer than patients with decreased levels. The only predictor of survival after adjustment for age and background diseases was a stable/increased albumin level at 90 days (hazard ratio 0.59; 95% confidence interval, 0.42-0.85; P=0.004)., Conclusions: Survival after PEG tube insertion is associated with a higher serum albumin level at baseline and a stable/increased serum albumin level during follow-up.