The Outcome of Local Excision of Rectal Adenomas with High-Grade Dysplasia by Transanal Endoscopic Microsurgery: A Single-Center Experience.

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.

The Effects of Gluten-free Diet on Body Mass Indexes in Adults with Celiac Disease: A Systematic Review and Meta-analysis of Observational Studies.

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

Factors associated with corticosteroid use in Crohn's disease and ulcerative colitis patients in Israel: A multicenter cross-sectional study.

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.

Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study.

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.

Gastric cancer risk in the elderly is associated with omeprazole use and inversely associated with aspirin use.

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 ±â€…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.

Different effects of chronic omeprazole use on osteoporotic fractures rate in the elderly.

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.

The use of artificial intelligence to identify subjects with a positive FOBT predicted to be non-compliant with both colonoscopy and harbor cancer.

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.

Gluten Immunogenic Peptides Are Not Correlated With Reported Adherence to Gluten-Free Diet in Children With Celiac Disease.

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.

Predictors of poor outcome following liver biopsy for the investigation of new hepatic space occupying lesion/s.

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.

Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

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.

Video Capsule Endoscopy after Bariatric Surgery: A Tertiary Referral Center Experience.

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.

The outcome of local excision of large rectal polyps by transanal endoscopic microsurgery.

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.

Association of Anemia with Dementia and Cognitive Decline among Community-Dwelling Elderly.

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.

Phenotypic diversity among juvenile polyposis syndrome patients from different ethnic background.

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.

Chronic omeprazole use in the elderly is associated with decreased risk of dementia and cognitive decline.

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.

Effect of the transcutaneous electrical stimulation system on esophageal-acid exposure in patients non-responsive to once-daily proton-pump inhibitor: proof-of-concept study.

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.

Transanal endoscopic microsurgery under spinal anaesthesia.

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.

Genetic testing for assessment of lynch syndrome in young patients with polyps.

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.

The Transition from Gastric Intestinal Metaplasia to Gastric Cancer Involves POPDC1 and POPDC3 Downregulation.

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.