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Hiatus hernia (HH) is a prevalent endoscopic finding in clinical practice, frequently co-occurring with esophageal disorders, yet the prevalence and degree of association remain uncertain. We aim to investigate HH's frequency and its suspected association with esophageal disorders. We reviewed endoscopic reports of over 75,000 consecutive patients who underwent gastroscopy over 12 years in two referral centers. HH was endoscopically diagnosed. We derived data on clinical presentation and a comprehensive assessment of benign and malignant esophageal pathologies. We performed multiple regression models to identify esophageal sequela associated with HH. The overall frequency of HH was (16.8%); the majority (89.5%) had small HHs (<3 cm). Female predominance was documented in HH patients, who were significantly older than controls (61.1±16.5 vs. 52.7±20.0; P < 0.001). The outcome analysis of esophageal pathology revealed an independent association between HH, regardless of its size, and erosive reflux esophagitis (25.7% vs. 6.2%; OR = 3.8; P < 0.001) and Barrett's esophagus (3.8% vs. 0.7%; OR = 4.7, P < 0.001). Furthermore, following rigorous age and sex matching, in conjunction with additional multivariable analyses, large HHs were associated with higher rates of benign esophageal strictures (3.6% vs. 0.3%; P < 0.001), Mallory Weiss syndrome (3.6% vs. 2.1%; P = 0.01), and incidents of food impactions (0.9% vs. 0.2%; P = 0.014). In contrast, a lower rate of achalasia was noted among this cohort (0.55% vs. 0%; P = 0.046). Besides reflux-related esophageal disorders, we outlined an association with multiple benign esophageal disorders, particularly in patients with large HHs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gastroesophageal reflux disease (GERD) is a condition that occurs when reflux of gastric contents into the esophagus causes symptoms and/or complications. The prevalence of GERD in Western societies has been estimated at 30%, making it one of the most commonly encountered disorders in primary care. The spectrum of GERD includes typical symptoms of esophageal reflux (heartburn and/or regurgitation); esophageal injury (erosive esophagitis; stricture; Barrett esophagus; and, rarely, adenocarcinoma); and extraesophageal symptoms, such as hoarseness and chronic cough. Proper diagnosis and treatment of GERD includes symptom control, exclusion of other disorders, avoiding overuse of medications and invasive testing, and minimizing complications., Competing Interests: Disclosures: All relevant financial relationships have been mitigated. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0087.

Introduction: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD., Methods: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts., Results: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts., Discussion: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD., (Copyright © 2023 by The American College of Gastroenterology.)

Objective: Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett's oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance., Design: We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC)., Results: We found that 58 of 77 short-segment ( < 3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p<0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer., Conclusion: SS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance., Competing Interests: Competing interests: RCF and MOD are named on patents for Cytosponge and associated technology, licensed to Covidien GI solutions (now Medtronic). RCF and MOD are shareholders of Cyted Ltd., a company working on early detection technology. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Although bile reflux plays an important role in the development of Barrett's esophagus, the relationship between endoscopic findings of bile reflux and Barrett's esophagus remains unclear., Objective: This study evaluated whether endoscopic evidence of bile reflux was associated with the presence of Barrett's esophagus., Methods: A retrospective analysis of a prospectively maintained database comprising consecutive patients who underwent screening esophagogastroduodenoscopy was conducted. Endoscopic evidence of bile reflux was defined as the presence of bile-stained fluid in the gastric fundus. We performed multivariate analysis to identify predictive factors that differed significantly between patients with and without Barrett's esophagus., Results: Of 4021 patients, 922 (23%) had Barrett's esophagus, and 1000 (25%) showed endoscopic findings of bile reflux. Multivariate analysis revealed endoscopic evidence of bile reflux as the strongest independent factor associated with the presence of Barrett's esophagus (odds ratio [OR] 5.65, 95% confidence interval [CI] 4.71-6.76) in relation to the presence of hiatal hernia (OR 3.30, 95% CI 2.70-4.04) and male gender (OR 1.54, 95% CI 1.24-1.91)., Conclusions: Endoscopic evidence of bile reflux was independently associated with the presence of Barrett's esophagus. This finding might help identify patients at future risk of Barrett's esophagus who could benefit from increased endoscopy surveillance., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: The aim of this study was to characterize baseline morphologic features of crypts in nondysplastic Barrett's esophagus and correlate them with DNA content abnormalities and risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC)., Methods: The morphologic features of nondysplastic crypts in baseline biopsy specimens from 212 BE patients (2956 biopsy specimens) were graded histologically using a 4-point scale (crypt atypia levels, 0-3). DNA content abnormalities were detected using flow cytometry., Results: In patients who had dysplasia in their baseline biopsy specimens, dysplasia was associated significantly with increasing grades of crypt atypia in the background nondysplastic Barrett's esophagus (P < .001). In a subset of patients without dysplasia at baseline (N = 149), a higher grade of crypt atypia was associated with longer Barrett's esophagus segment length (5.5 vs 3.3 cm; P = .0095), and a higher percentage of cells with 4N DNA content (3.67 ± 1.27 vs 2.93 ± 1.22; P = .018). Crypt atypia was associated with the development of any neoplasia (low-grade dysplasia and HGD/EAC). Although no significant association was noted between the grade of crypt atypia and increased 4N, aneuploidy, or progression to HGD/EAC, only patients with grade 2 or 3 crypt atypia showed increased 4N, aneuploidy, or progression to HGD/EAC., Conclusions: Patients with Barrett's esophagus likely develop dysplasia via a progressive increase in the level of crypt atypia before the onset of dysplasia, and these changes may reflect some alteration of DNA content., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Although the risk of cancer progression in a Barrett's esophagus (BE) is very low, worrying about cancer is known as an important factor affecting HRQoL. The aim of this study was to determine the proportion of BE patients with high levels of worry for cancer, to compare outcomes of patients endoscopically treated for BE neoplasia (DBE), non-dysplastic BE patients (NDBE) and patients with reflux symptoms, and to examine associated factors. We performed a cross sectional, exploratory, self-administered questionnaire study using the cancer worry scale, and the reflux disease questionnaire. A total of 192 DBE patients, 213 NDBE patients and 111 refractory reflux symptom patients were included from October 2019 until July 2021, 76.8% of BE participants were male and aged 66.9 years. High cancer worry was reported in 40.6% of the DBE patients and 36.2% of NDBE patient. Reflux patients scored statistically significant worse with 56.6% stated high cancer worry. Positive correlations were found between reflux symptoms and cancer worry in NDBE patients and reflux patients. In DBE patients' negative correlations were found between higher cancer worry and younger age as well as a family history of esophageal carcinoma. A clinically significant group of BE patients reported high cancer worry, which was associated with reflux symptoms in NDBE patients and a younger age and a (family) history of esophageal carcinoma diagnosis in BE patients treated for (early) neoplasia. Physicians should communicate about the actual cancer risk, which leads to greater patient understanding and therefore may have a positive impact on health outcomes., (© 2024. The Author(s).)

Introduction: Sleeve gastrectomy is the most commonly performed bariatric operation globally. The main complication is GERD. In the medium term, it can increase the incidence of Barrett's esophagus (BE), which is a risk factor for esophageal adenocarcinoma. Following conventional sleeve gastrectomy, BE is noted in up to 16% of patients postoperatively. Recently, Nissen sleeve gastrectomy (NSG) has been shown to reduce the frequency of postoperative GERD compared to conventional sleeve gastrectomy. This study aims to evaluate the impact of NSG on the incidence and remission of BE in the long term., Material and Method: This bicentric retrospective study included 692 patients who received NSG from September 2013 to July 2021. All patients underwent preoperative upper GI endoscopy and were then scheduled to receive upper GI endoscopy between 1 and 2 years and then between 3 and 5 years postoperatively. BE was systematically confirmed by biopsies., Results: Seventy-four patients had endoscopic suspicion of BE, which was confirmed on 54/692 patients by histology. The BE lesions consisted of 18.5% intestinal metaplasia and 75.9% fundal metaplasia. Among these 54 patients, 38 underwent endoscopic investigation within 2 years postoperatively. The biopsies showed healed BE in 25/38 patients (64.1%). At 5 years, two patients had proven BE. Concerning the incidence of BE post NSG: 234 performed the follow-up endoscopy within 2 years. The incidence of de novo BE is nil., Conclusion: The NSG is associated with healing of known BE in approximately two-thirds of patients at 2-year follow-up. This is consistent with the GERD improvement that has been shown with NSG., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Helicobacter pylori eradication therapy may worsen gastroesophageal reflux disease that is a significant risk factor for Barrett's esophagus. However, the relationship between eradication therapy and Barrett's esophagus remains controversial. This study evaluated the impact of Helicobacter pylori eradication on the lengthening of Barrett's esophagus., Materials and Methods: We conducted a retrospective analysis of consecutive patients who successfully underwent Helicobacter pylori eradication between 2004 and 2017. Endoscopic images obtained before and after eradication therapy were compared for Barrett's esophagus length according to the Prague C&M criteria and the presence of reflux esophagitis based on the Los Angeles classification., Results: A total of 340 patients were analyzed (mean age: 66.9 ± 12.9 years) for a median follow-up of 55 months (interquartile range: 29.8-89.3). At the initial endoscopic assessment, 187 patients (55%) had a hiatal hernia, and all patients had gastric atrophy (C-0 to I: 2%, C-II to III: 47%, O-I to III: 51%). Reflux esophagitis was detected in 7 patients (2%) before eradication and in 21 patients (6%) afterward, which was a significant increase (p = 0.007). Barrett's esophagus was identified in 69 patients (20%) before eradication, with a median length of C0M1. Elongation after treatment was observed in only 2 patients (0.6%). We observed no significant increase in either the prevalence (p = 0.85) or the median length (p = 0.5) of Barrett's esophagus., Conclusions: Only 0.6% of patients exhibited Barrett's esophagus lengthening after Helicobacter pylori eradication therapy, suggesting no significant impact of the treatment on the development or elongation of Barrett's esophagus., (© 2024 S. Karger AG, Basel.)

Background: Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance., Aims: We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort., Methods: EAC and GEJAC patients from 1976 to 2019 were identified using ICD 9 and 10 diagnostic codes from the Rochester Epidemiology Project (REP). Clinical data and survival status were abstracted. Poisson regression was used to calculate incidence rate ratios (IRR). Survival analysis and Cox proportional models were used to assess predictors of survival., Results: We included 443 patients (287 EAC,156 GEJAC). The incidence of EAC and GEJAC during 1976-2019 was 1.40 (CI 1.1-1.74) and 0.83 (CI 0.61-1.11) per 100,000 people, respectively. There was an increase in the incidence of EAC (IRR = 2.45, p = 0.011) and GEJAC (IRR = 3.17, p = 0.08) from 2000 to 2004 compared to 1995-1999, plateauing in later time periods. Most patients had associated BE and presented at advanced stages, leading to high 5-year mortality rates (66% in EAC and 59% in GEJAC). Age and stage at diagnosis were predictors of mortality., Conclusion: The rising incidence of EAC/GEJAC appears to have plateaued somewhat in the last decade. However, both cancers present at advanced stages with persistently poor survival, underscoring the need for early detection., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Repair of giant paraesophageal hernia (PEH) is associated with a considerable hernia recurrence rate by objective measures. This study analyzed a large series of laparoscopic giant PEH repair to determine factors associated with anatomical recurrence., Method: Data was extracted from a single-surgeon prospective database of laparoscopic repair of giant PEH from 1991 to 2021. Upper endoscopy was performed within 12 months postoperatively and selectively thereafter. Any supra-diaphragmatic stomach was defined as anatomical recurrence. Patient and hernia characteristics and technical operative factors, including "composite repair" (360° fundoplication with esophagopexy and cardiopexy to right crus), were evaluated with univariate and multivariate analysis., Results: Laparoscopic primary repair was performed in 862 patients. The anatomical recurrence rate was 27.3% with median follow-up of 33 months (IQR 16, 68). Recurrence was symptomatic in 45% of cases and 29% of these underwent a revision operation. Hernia recurrence was associated with younger age, adversely affected quality of life, and were associated with non-composite repair. Multivariate analysis identified age < 70 years, presence of Barrett's esophagus, absence of "composite repair", and hiatus closure under tension as independent factors associated with recurrence (HR 1.27, 95%CI 0.88-1.82, p = 0.01; HR 1.58, 95%CI 1.12-2.23, p = 0.009; HR 1.72, 95%CI 1.2-2.44, p = 0.002; HR 2.05, 95%CI 1.33-3.17, p = 0.001, respectively)., Conclusion: Repair of giant PEH is associated with substantial anatomical recurrence associated with patient and technique factors. Patient factors included age < 70 years, Barrett's esophagus, and hiatus tension. "Composite repair" was associated with lower recurrence rate., (© 2023. The Author(s).)

Purpose of Review: Barrett's esophagus (BE) is associated with chronic gastroesophageal reflux disease and is a known precursor to esophageal adenocarcinoma. While endoscopic surveillance strategies and the role for endoscopic eradication therapy have been well established, there has been much interest in identifying chemopreventive agents to disrupt or halt the metaplasia-dysplasia-carcinoma sequence in patients with BE., Recent Findings: No pharmacological agent has held more hope in reducing the risk of neoplastic progression in BE than proton pump inhibitors (PPIs). However, data supporting PPIs for chemoprevention have largely been from observational cohort and case-control studies with mixed results. In this review, we revisit the literature and highlight the role of PPIs in patients with BE as it pertains to chemoprophylaxis against the progression of BE to dysplasia and esophageal adenocarcinoma., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Esophageal adenocarcinoma incidence has increased significantly despite surveillance endoscopy for Barrett's esophagus (BE) and gastric acid supression medications. This prospective, cohort study's aims were to determine the long-term efficacy of proton-pump inhibitors twice daily (PPI-BID) with cryotherapy (CRYO) for complete ablation of BE., Materials and Methods: Consecutive BE patients were managed with a PPI-BID, CRYO ablation, follow-up protocol. Primary outcomes were to determine complete ablation rate of intestinal metaplasia (IM) or dysplasia/carcinoma, and factors affecting recurrence., Results: Sixty-two patients were enrolled: advanced disease (11%), low-grade or indefinite dysplasia (26%), non-dysplastic BE (63%). In 58 completing CRYO, eradication was confirmed in 100% on surveillance endoscopy. Adverse events (5%) were minor (mild pain 4%). IM recurred in 9% after a mean of 52 months, all successfully re-ablated. No second recurrence occurred. The primary predictor of recurrence was noncompliance with PPI-BID. BE or cardia IM recurred in 35% of those taking proton pump inhibitors once daily or less compared with 0% in those on PPI-BID or dexlansoprazole daily ( p <.001)., Conclusions: Minimizing acid reflux with at least PPI-BID combined with CRYO ablation appears to be the optimal cost-effective and safe BE treatment for any stage to minimize progression to adenocarcinoma by addressing both the stimulus that causes BE and the presence of goblet cells.

Background: Using Mendelian randomization (MR) approach, our objective was to determine whether there was a causal association between dietary factors and gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), or esophageal cancer (EC)., Methods: Genome-wide association study (GWAS) data for eighteen types of dietary intake were obtained from the UK Biobank. GWAS data for GERD, BE, and EC were sourced from the FinnGen consortium. We performed univariable and multivariable MR analysis to assess the cause effect between dietary factors and esophageal diseases. MR results were expressed as odds ratios (OR) with 95% confidence intervals (CI)., Results: Raw vegetable intake was associated with a lower risk of GERD (OR = 0.478; P = 0.011). On the contrary, cooked vegetable intake increased the risk of GERD (OR = 1.911; P = 0.024). Bread intake was associated with increased odds of BE (OR = 6.754; P = 0.007), while processed meat intake was associated with reduced risk of BE (OR = 0.210; P = 0.035). We also observed evidence that increased consumption of dried fruit (OR = 0.087; P = 0.022) and salt added to food (OR = 0.346; P = 0.045) could prevent EC. The results of multivariable MR showed that the protective effect of consumption of salt added to food on EC was no longer significant after adjusting for the consumption of dried fruit., Conclusion: Vegetable consumption was associated with GERD, whereas consumption of bread and processed meat was associated with BE. Dried fruit intake was associated with a lower risk of EC, and the protective effect of consumption of salt added food on EC may also be mediated by consumption of dried fruit. Future research should be performed to investigate the mechanisms behind these cause-and-effect relationships to reduce the burden of disease caused by dietary habits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

'Esophageal cancer' (EC) is a highly aggressive and deadly complex disease. It comprises two types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with Barrett's esophagus (BE) being the only known precursor. Recent research has revealed that microRNAs (miRNAs) play a crucial role in the development, prognosis and treatment of EC and are involved in various human diseases. Biological databases have become essential for cancer research as they provide information on genes, proteins, pathways and their interactions. These databases collect, store and manage large amounts of molecular data, which can be used to identify patterns, predict outcomes and generate hypotheses. However, no comprehensive database exists for EC and miRNA relationships. To address this gap, we developed a dynamic database named 'ESOMIR (miRNA in esophageal cancer) (https://esomir.dqweilab-sjtu.com)', which includes information about targeted genes and miRNAs associated with EC. The database uses analysis and prediction methods, including experimentally endorsed miRNA(s) information. ESOMIR is a user-friendly interface that allows easy access to EC-associated data by searching for miRNAs, target genes, sequences, chromosomal positions and associated signaling pathways. The search modules are designed to provide specific data access to users based on their requirements. Additionally, the database provides information about network interactions, signaling pathways and region information of chromosomes associated with the 3'untranslated region (3'UTR) or 5'UTR and exon sites. Users can also access energy levels of specific miRNAs with targeted genes. A fuzzy term search is included in each module to enhance the ease of use for researchers. ESOMIR can be a valuable tool for researchers and clinicians to gain insight into EC, including identifying biomarkers and treatments for this aggressive tumor. Database URL https://esomir.dqweilab-sjtu.com., (© The Author(s) 2023. Published by Oxford University Press.)

BACKGROUND Barrett's esophagus (BE) is a metaplastic change in the normal esophageal squamous epithelium and is a well-recognized precursor of esophageal adenocarcinoma (EAC). Nowadays, focal radiofrequency ablation is a valid technique for BE treatment by inducing a superficial and focal thermic destruction of metaplastic tissues. According to the literature, the most frequent patient-related adverse events of this procedure are esophageal iatrogenic stenosis, mucosal laceration or perforation of the esophagus, chest pain, and odynophagia/dysphagia. Postoperative heart rhythm abnormalities have been reported very rarely. CASE REPORT A 74-year-old patient with HE was treated by radiofrequency ablation (RFA) with the Barrx™ catheter system. He had 2 symptomatic episodes of atrial flutter in the immediate postoperative period requiring an external electrical cardioversion to induce a return to sinus cardiac rhythm. After atrial flutter ablation, 2 more radiofrequency procedures were performed, without adverse events. A laparoscopic Nissen fundoplication was carried out with complete endoscopic and histologic eradication of BE after 12-month follow-up. To the best of our knowledge, this is the first reported case of atrial flutter after esophageal RFA. Different mechanisms acting on an anatomic predisposing substrate can potentially play a role in starting atrial flutter, and include inflammation, autonomic activation, and myocardial injury. CONCLUSIONS The occurrence of this new type of adverse effect could potentially modify indications and postoperative monitoring of RFA treatment for BE. Endoscopists should know the possibility of this procedural complication in high-risk patients and they should propose alternative techniques or implement close cardiac monitoring in the postoperative period.

Although low-grade dysplasia (LGD) in Barrett's esophagus (BE) is a histopathological diagnosis based on different histological abnormalities, it is still problematic for different reasons. Patients without confirmed diagnosis of LGD undergo unnecessary and intensified follow-up where the risk of progression is low in the majority of cases. In contrast, the presence of confirmed LGD indicates a high risk of progression. In this article we try to address these reasons focusing on re-confirmation of LGD diagnosis, interobserver agreement, and persistent confirmed LGD. The progression risk of LGD to high-grade dysplasia and esophageal adenocarcinoma will also be reviewed., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Background & Aims: Antibiotic exposure leads to changes in the gut microbiota. Our objective was to evaluate the association between antibiotic exposure and esophageal adenocarcinoma (EAC) risk., Methods: We performed a nested case-control study using data from the Veterans Health Administration from 2004 through 2020. The case group consisted of patients who received an incident diagnosis of EAC. For each case, up to 20 matched controls were selected using incidence density sampling. Our primary exposure of interest was any oral or intravenous antibiotic use. Our secondary exposures included cumulative number of days of exposure and classification of antibiotics by various subgroups. Conditional logistic regression was used to estimate the crude and adjusted odds ratios (aORs) for the risk of EAC associated with antibiotic exposure., Results: The case-control analysis included 8226 EAC cases and 140,670 matched controls. Exposure to any antibiotic was associated with an aOR for EAC of 1.74 (95% confidence interval [CI], 1.65-1.83) vs no antibiotic exposure. Compared with no antibiotic exposure, the aOR for EAC was 1.63 (95% CI, 1.52-1.74; P < .001) for cumulative exposure to any antibiotic for 1 to 15 days; 1.77 (95% CI, 1.65-1.89; P < 0 .001) for 16 to 47 days; and 1.87 (95% CI, 1.75-2.01; P < .001) for ≥48 days, respectively (P for trend < .001)., Conclusion: Exposure to any antibiotic is associated with an increased risk of EAC, and this risk increases as the cumulative days of exposure increase. This novel finding is hypothesis-generating for potential mechanisms that may play a role in the development or progression of EAC., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Barrett's esophagus (BE) is the replacement of the usual esophageal mucosa by a simple columnar epithelium with the presence of goblet cells (GC) of intestinal type. It has been related to different risk factors such as gastroesophageal reflux disease (GERD), inappropriate consumption of irritating foods, smoking and overweight. There are CC mimic cells, known as blue cells (BC), which make the diagnosis of BE difficult, due to the lack of a precise definition of the nature and location of the gastroesophageal junction and the microscopic variations in this area., Objective: To identify morphologically and with histochemical techniques Alcian blue (AA) and periodic acid-Schiff (PAS) between GC and BC., Material and Methods: Retrolective cross-sectional analytical study where 45 samples of patients diagnosed with BE were included., Results: The morphological characteristics are similar in both cell varieties. PAS staining was 100%, unlike AA staining, with only 16 cases with staining, corresponding to 35.55%., Conclusions: PAS staining has a high sensitivity and specificity for the identification of GC, this being a fundamental pillar for the correct diagnosis of BE. The presence of BC detected by AA does not exclude the diagnosis of BE, since both cell types can coexist., (Licencia CC 4.0 (BY-NC-ND) © 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD) symptomatology, and future prescriptions of proton pump inhibitors in clinical practice. A total of 922 patients (546 women and 376 men; mean age 54.3 [SD 18.4] years) who underwent gastroscopy between 2012 and 2015 were analyzed. Patient questionnaire regarding symptoms were compared with endoscopy findings. A medical chart review was done that focused on the prescription of PPIs, additional gastroscopies, and GERD surgery in a 3-year period before the index gastroscopy and in a 6-year period afterward. In patients naïve to PPI prescriptions (n = 466), Hill grade III was significantly associated with esophagitis (AOR 2.20; 95% CI 1.00-4.84) and > 2 PPI prescriptions 6 year after the index gastroscopy (AOR 1.95; 95% CI 1.01-3.75), whereas Hill grade IV was significantly associated with esophagitis (AOR 4.41; 95% CI 1.92-10.1), with Barrett's esophagus (AOR 12.7; 95% CI 1.45-112), with reported heartburn (AOR 2.28; 95% CI 1.10-4.74), and with >2 PPI prescriptions (AOR 2.16; 95% CI 1.02-4.55). In patients 'non-naïve' to PPI prescription (n = 556), only Hill grade IV was significantly associated with esophagitis, reported heartburn, and with >2 PPI prescriptions. The gastroscopic classification in Hill grades III and IV is important in clinical practice because they are associated with esophagitis, Barrett's esophagus, symptoms of GERD, and prescriptions of PPIs, whereas a differentiation between Hill grades I and II is not., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Esophageal inlet patch (IP) with heterotopic gastric mucosa is an incidental finding on esophagogastroduodenoscopy (EGD). Although IP is thought to be embryologic in nature, IP has been associated with Barrett's esophagus (BE)., Aims: The aim of this study was to compare prevalence, symptoms, demographic factors, and esophageal testing in patients with IP and BE., Methods: We retrospectively analyzed endoscopic findings of EGDs, high-resolution esophageal manometry and esophageal pH impedance studies from January 2010 to January 2021 at a single academic medical center. Patients were grouped by presence or absence of IP and BE., Results: Of 27,498 patients evaluated, 1.3% had endoscopic evidence of IP and 4.9% had BE. Of 362 patients with IP, 17.1% had BE; of 1356 patients with BE, 4.6% had IP. Both IP and BE patients presented primarily with heartburn and/or regurgitation. Patients with BE and/or IP were older and had higher BMI than those without (p < 0.001). Mean lower esophageal sphincter pressure was lower and mean acid exposure time (AET) was higher in patients with IP and/or BE than those without (p < 0.05)., Conclusions: Our study reports an IP prevalence of 1.3%, with 17.1% patients having concomitant BE; and a BE prevalence of 4.9%, with 4.6% also having IP. Patients with IP alone presented with similar symptoms to patients with concomitant BE. Esophageal function testing showed that patients with either IP or BE had decreased LES pressures and increased esophageal AET. During endoscopy, patients found to have one of these findings should be carefully examined for the other., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We define mixed esophageal disease (MED) as a disorder of esophageal structure and/or function that produces variable signs or symptoms, simulating-fully or in part other well-defined esophageal conditions, such as gastroesophageal reflux disease, esophageal motility disorders, or even neoplasia. The central premise of the MED concept is that of an overlap syndrome that incorporates selected clinical, endoscopic, imaging, and functional features that alter the patient's quality of life and affect natural history, prognosis, and management. In this article, we highlight MED scenarios frequently encountered in medico-surgical practices worldwide, posing new diagnostic and therapeutic challenges. These, in turn, emphasize the need for better understanding and management, aiming towards improved outcomes and prognosis. Since MED has variable and sometimes time-evolving clinical phenotypes, it deserves proper recognition, definition, and collaborative, multidisciplinary approach, be it pharmacologic, endoscopic, or surgical, to optimize therapeutic outcomes, while minimizing iatrogenic complications. In this regard, it is best to define MED early in the process, preferably by teams of clinicians with expertise in managing esophageal diseases. MED is complex enough that is increasingly becoming the subject of virtual, multi-disciplinary, multi-institutional meetings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recent guidelines recommend screening for patients with chronic gastroesophageal reflux disease who have three or more additional risk factors for Barrett's esophagus (BE). Failure to screen high-risk individuals represents a missed opportunity in esophageal adenocarcinoma prevention and early detection. We aimed to determine the frequency of upper endoscopy and prevalence of BE and esophageal cancer in a cohort of United States veterans who possessed four or more risk factors for BE. All patients at VA New York Harbor Healthcare System with at least four risk factors for BE between 2012 and 2017 were identified. Procedure records were reviewed for upper endoscopies performed between January 2012 and December 2019. Multivariable logistic regression was used to determine risk factors associated with undergoing endoscopy and factors associated with BE and esophageal cancer. 4505 patients with at least four risk factors for BE were included. 828 patients (18.4%) underwent upper endoscopy, of which 42 (5.1%) were diagnosed with BE and 11 (1.3%) with esophageal cancer (10 adenocarcinoma; 1 squamous cell carcinoma). Among individuals who underwent upper endoscopy, risk factors associated with undergoing endoscopy included obesity (OR, 1.79; 95% CI, 1.41-2.30; P < 0.001) and chronic reflux (OR, 3.86; 95% CI, 3.04-4.90; P < 0.001). There were no individual risk factors associated with BE or BE/esophageal cancer. In this retrospective analysis of patients with 4 or more risk factors for BE, fewer than one-fifth of patients underwent upper endoscopy, supporting the need for efforts aimed at improving BE screening rates., (Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus 2023.)

Background: Several small studies reported high risk of progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) patients who undergo solid organ transplantation (SOT) and implied that this may be due to immunosuppressant use. However, the major shortcoming of these studies was the lack of a control population. Therefore, we aimed to determine the rates of neoplastic progression in BE patients who underwent SOT and compare to that in controls and identify the predictors of progression., Methods: This was a retrospective cohort study of BE patients seen in Cleveland Clinic and affiliated hospitals between January 2000 and August 2022. Demographics, endoscopic and histological findings, history of SOT and fundoplication, immunosuppressant use, and follow-up were abstracted., Results: The study population consisted of 3466 patients with BE, of which 115 had SOT (lung 35, liver 34, kidney 32, heart 14, and pancreas 2) and 704 patients on chronic immunosuppressants but no history of SOT. During a median follow-up of 5.1 years, there was no difference in the annual risk of progression between the three groups (SOT=0.61%, no SOT but on immunosuppressants= 0.82%, and no SOT/no immunosuppressants= 0.94%, p=0.72). On multivariate analysis, immunosuppressant use (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.04-1.82, p=0.025) but not SOT (OR 0.39, 95%CI 0.15-1.01, p=0.053) was associated with neoplastic progression in BE patients., Conclusion: Immunosuppression is a risk factor for progression of BE to HGD/EAC. Therefore, close surveillance of BE patients on chronic immunosuppressants needs to be considered., (© 2023. The Society for Surgery of the Alimentary Tract.)

Half of Barrett's esophagus (BE) surveillance endoscopies do not adhere to guideline recommendations. In this multicenter prospective cohort study, we assessed the clinical consequences of nonadherence to recommended surveillance intervals and biopsy protocol. Data from BE surveillance patients were collected from endoscopy and pathology reports; questionnaires were distributed among endoscopists. We estimated the association between (non)adherence and (i) endoscopic curability of esophageal adenocarcinoma (EAC), (ii) mortality, and (iii) misclassification of histological diagnosis according to a multistate hidden Markov model. Potential explanatory parameters (patient, facility, endoscopist variables) for nonadherence, related to clinical impact, were analyzed. In 726 BE patients, 3802 endoscopies were performed by 167 endoscopists. Adherence to surveillance interval was 16% for non-dysplastic (ND)BE, 55% for low-grade dysplasia (LGD), and 54% of endoscopies followed the Seattle protocol. There was no evidence to support the following statements: longer surveillance intervals or fewer biopsies than recommended affect endoscopic curability of EAC or cause-specific mortality (P > 0.20); insufficient biopsies affect the probability of NDBE (OR 1.0) or LGD (OR 2.3) being misclassified as high-grade dysplasia/EAC (P > 0.05). Better adherence was associated with older patients (OR 1.1), BE segments ≤ 2 cm (OR 8.3), visible abnormalities (OR 1.8, all P ≤ 0.05), endoscopists with a subspecialty (OR 3.2), and endoscopists who deemed histological diagnosis an adequate marker (OR 2.0). Clinical consequences of nonadherence to guidelines appeared to be limited with respect to endoscopic curability of EAC and mortality. This indicates that BE surveillance recommendations should be optimized to minimize the burden of endoscopies., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objective: Presenting chronic obstructive pulmonary disease (COPD) patients frequently report concurrent symptoms of gastroesophageal reflux disease (GERD). Few studies have shown a correlation between GERD and COPD. We aimed to examine the correlation between GERD and COPD as well as secondary related reflux complications, such as esophageal stricture, esophageal cancer, and Barrett's esophagus. Methods : This population-based analysis included 7,159,694 patients. Patients diagnosed with GERD with and without COPD were compared to those without GERD. The enrollment of COPD included centrilobular and panlobular emphysema and chronic bronchitis. Risk factors of COPD or GERD were used for adjustment. Bivariate analyses were performed using the chi-squared test or Fisher exact test (2-tailed) for categorical variables as appropriate to assess the differences in the groups. Results : Our results showed that COPD patients had a significantly higher incidence of GERD compared to those without COPD (27.8% vs. 14.1%, p < 0.01). After adjustment of demographics and risk factors, COPD patients had a 1.407 times higher risk of developing non-erosive esophagitis ( p < 0.01), 1.165 higher risk of erosive esophagitis ( p < 0.01), 1.399 times higher risk of esophageal stricture ( p < 0.01), 1.354 times higher risk of Barrett's esophagus without dysplasia ( p < 0.01), 1.327 times higher risk of Barrett's esophagus with dysplasia, as well as 1.235 times higher risk of esophageal cancer than those without COPD. Conclusions : Based on the evidence from this study, there are sufficient data to provide convincing evidence of an association between COPD and GERD and its secondary reflux-related complications.

We herein report two cases of early esophageal adenocarcinoma derived from non-Barrett's columnar epithelium. Both patients, a 65-year-old woman and 60-year-old man, had elevated lesions on white-light imaging. Magnifying endoscopy revealed slightly irregular surface and vessel patterns, and both patients were successfully treated with endoscopic submucosal dissection. Histopathologically, both lesions comprised of well-differentiated gastric mucin phenotype adenocarcinoma. One lesion was accompanied by ectopic gastric mucosa, but the other was speculated to be ectopic gastric mucosa according to the tumor locus at the upper thoracic esophagus. Despite its rarity, endoscopists should consider the existence of adenocarcinoma derived from non-Barrett's columnar epithelium.

Purpose of Review: The aim of this paper is to review and assess the appropriateness of eradication of nondysplastic Barrett's esophagus. Dysplasia in Barrett's esophagus is a known predictor for the development of esophageal cancer, and is currently the best marker in aiding the decision making regarding treatment options. Current data supports endoscopic eradication therapy for most patients with dysplastic Barrett's. The controversy, however, lies in the management of nondysplastic Barrett's and when to recommend ablation versus ongoing surveillance., Recent Findings: There have been increasing efforts to identify factors that can help predict which patients with nondysplastic Barrett's esophagus are at increased risk for cancer progression, and to quantify that risk. While there is currently varying data and literature supporting this, a more objective risk score is likely to soon become available and accepted, in an effort to differentiate between low and high risk nondysplastic Barrett's, and better aid in decision making regarding surveillance versus endoscopic eradication. This article reviews the current data on Barrett's esophagus and its risk for cancer progression, and it outlines several factors which impact progression that should be considered in the management approach to nondysplastic Barrett's esophagus., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

With the development of endoscopic technology, an increasing number of patients with esophageal disease are being diagnosed, although the underlying pathogenesis of many esophageal diseases remains unclear. In recent years, a large number of studies have demonstrated that the occurrence and development of various intestinal diseases were related to intestinal flora. As a result, researchers have shifted their focus towards investigating esophageal flora to better understand the pathogenesis, early diagnosis, and treatment of esophageal diseases. This paper reviewed the normal esophageal flora and the changes of esophageal flora under different esophageal disease states. It was observed that there are distinct differences in the composition of esophageal microflora among Gastroesophageal Reflux, Barrett's esophagus, eosinophilic esophagitis and normal esophagus. The normal esophageal flora was dominated by gram-positive bacteria, particularly Streptococcus , while the esophageal flora under esophagitis was dominated by gram-negative bacteria. Furthermore, the diversity of esophageal flora is significantly decreased in patients with esophageal cancer. Several potential microbial biomarkers for esophageal cancer have been identified, among which Fusobacterium nucleatum showed a close association with esophageal squamous cell carcinoma's pathological stage and clinical stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zou, Feng, Cai, Qian and Xu.)

Background & Aims: Identifying dysplasia of Barrett's esophagus (BE) in the electronic medical record (EMR) requires manual abstraction of unstructured data. Natural language processing (NLP) creates structure to unstructured free text. We aimed to develop and validate an NLP algorithm to identify dysplasia in BE patients on histopathology reports with varying report formats in a large integrated EMR system., Methods: We randomly selected 600 pathology reports for NLP development and 400 reports for validation from patients with suspected BE in the national Veterans Affairs databases. BE and dysplasia were verified by manual review of the pathology reports. We used NLP software (Clinical Language Annotation, Modeling, and Processing Toolkit; Melax Tech, Houston, TX) to develop an algorithm to identify dysplasia using findings. The algorithm performance characteristics were calculated as recall, precision, accuracy, and F-measure., Results: In the development set of 600 patients, 457 patients had confirmed BE (60 with dysplasia). The NLP identified dysplasia with 98.0% accuracy, 91.7% recall, and 93.2% precision, with an F-measure of 92.4%. All 7 patients with confirmed high-grade dysplasia were classified by the algorithm as having dysplasia. Among the 400 patients in the validation cohort, 230 had confirmed BE (39 with dysplasia). Compared with manual review, the NLP algorithm identified dysplasia with 98.7% accuracy, 92.3% recall, and 100.0% precision, with an F-measure of 96.0%., Conclusions: NLP yielded a high degree of sensitivity and accuracy for identifying dysplasia from diverse types of pathology reports for patients with BE. The application of this algorithm would facilitate research and clinical care in an EMR system with text reports in large data repositories., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Esophageal lesions ranging from erosive esophagitis to Barrett's esophagus (BE) eventually develop months-years after sleeve gastrectomy (SG), representing a significant post-surgical issue in GI practice. Roux-en-Y gastric bypass (RYGB) conversion is a widespread and effective method of managing reflux and esophageal complications following SG. Although some studies using a limited sample size have demonstrated that RYGB performed as a primary procedure may regress BE presumably by reducing reflux, whether the same may apply to RYGB performed as revision surgery after SG has scarcely been addressed in the literature. Though histological regression of BE following primary RYGB occurs in 51.9% of patients, with regression of Barrett's dysplasia in 50% of cases, revisional RYGB yields a remission rate as high as 81.8% for Barrett's metaplasia and 100% for dysplastic lesions, although the number of subjects in the published studies are very small. We report two patients who developed GERD and BE following SG with complete regression 12 months after conversion to RYGB in both subjects, confirming the substantially greater proportion of BE resolution in patients undergoing RYGB as revision surgery following SG., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose:  to review recent literature concerning long-term health issues and transitional care in esophageal atresia (EA) patients. PubMed, Scopus, Embase and Web of Science databases were screened for studies regarding EA patients aged more than or equal to 11 years, published between August 2014 and June 2022. Sixteen studies involving 830 patients were analyzed. Mean age was 27.4 years (range 11-63). EA subtype distribution was: type C (48.8%), A (9.5%), D (1.9%), E (0.5%) and B (0.2%). 55% underwent primary repair, 34.3% delayed repair, 10.5% esophageal substitution. Mean follow-up was 27.2 years (range 11-63). Long-term sequelae were: gastro-esophageal reflux (41.4%), dysphagia (27.6%), esophagitis (12.4%), Barrett esophagus (8.1%), anastomotic stricture (4.8%); persistent cough (8.7%), recurrent infections (4.3%) and chronic respiratory diseases (5.5%). Musculo-skeletal deformities were present in 36 out of 74 reported cases. Reduced weight and height were detected in 13.3% and 6% cases, respectively. Impaired quality of life was reported in 9% of patients; 9.6% had diagnosis or raised risk of mental disorders. 10.3% of adult patients had no care provider. Meta-analysis was conducted on 816 patients. Estimated prevalences are: GERD 42.4%, dysphagia 57.8%, Barrett esophagus 12.4%, respiratory diseases 33.3%, neurological sequelae 11.7%, underweight 19.6%. Heterogeneity was substantial (> 50%).   Conclusion: EA patients must continue follow-up beyond childhood, with a defined transitional-care path by a highly specialized multidisciplinary team due to the multiple long-term sequelae., What Is Known: • Survival rates of esophageal atresia patients is now more than 90% thanks to the improvements in surgical techniques and intensive care, therefore patients' needs throughout adolescence and adulthood must be taken into account., What Is New: • This review, by summarizing recent literature concerning long term sequelae of esophageal atresia, may contribute to raise awareness on the importance of defining standardized protocols of transitional and adulthood care for esophageal atresia patients., (© 2023. The Author(s).)

Goals: We aimed to evaluate factors associated with patient adherence to recommended surveillance guidelines during the first 3 years after endoscopic eradication of Barrett's esophagus (BE) with high-grade dysplasia (HGD) or T1a carcinoma in situ (CIS) and the relationship between adherence and detection of recurrence., Background: While surveillance endoscopies after treatment of BE with HGD or T1a CIS are an important component of therapy, it is unclear whether these high-risk patients are adhering to recommended surveillance guidelines., Materials and Methods: A total of 123 BE patients who underwent radiofrequency ablation±endoscopic mucosal resection for biopsy-proven HGD, or CIS between January 2010 and November 2018 underwent retrospective review for adherence to surveillance guidelines, patient factors related to adherence, and recurrence of dysplasia or CIS at 12, 24, and 36 months., Results: Of 123 BE patients (89 HGD and 34 CIS), adherence during the first year following treatment was 26.97% for HGD patients and 41.18% for CIS patients, with increasing adherence rates in subsequent years. Patients who received 3 to 4 surveillance endoscopies in the first year posttreatment had significantly higher rates of recurrence detection than patients who received 0 to 2 surveillance endoscopies over this interval ( P =0.01). No patient factors were found to impact adherence significantly., Conclusions: Adherence to recommended surveillance intervals after endoscopic treatment of BE with HGD or CIS is low, with poor adherence during the first year associated with decreased detection of recurrence. Future studies are needed to evaluate risk factors and develop a potential intervention for poor adherence in this high-risk population., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current surveillance for Barrett's esophagus (BE), consisting of four-quadrant random forceps biopsies (FBs), has an inherent risk of sampling error. Wide-area transepithelial sampling (WATS) may increase detection of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). In this multicenter randomized trial, we aimed to evaluate WATS as a substitute for FB., Methods: Patients with known BE and a recent history of dysplasia, without visible lesions, at 17 hospitals were randomized to receive either WATS followed by FB or vice versa. All WATS samples were examined, with computer assistance, by at least two experienced pathologists at the CDx Diagnostics laboratory. Similarly, all FBs were examined by two expert pathologists. The primary end point was concordance/discordance for detection of HGD/EAC between the two techniques., Results: 172 patients were included, of whom 21 had HGD/EAC detected by both modalities, 18 had HGD/EAC detected by WATS but missed by FB, and 12 were detected by FB but missed by WATS. The detection rate of HGD/EAC did not differ between WATS and FB ( P  = 0.36). Using WATS as an adjunct to FB significantly increased the detection of HGD/EAC vs. FB alone (absolute increase 10 % [95 %CI 6 % to 16 %]). Mean procedural times in minutes for FB alone, WATS alone, and the combination were 6.6 (95 %CI 5.9 to 7.1), 4.9 (95 %CI 4.1 to 5.4), and 11.2 (95 %CI 10.5 to 14.0), respectively., Conclusions: Although the combination of WATS and FB increases dysplasia detection in a population of BE patients enriched for dysplasia, we did not find a statistically significant difference between WATS and FB for the detection of HGD/EAC as single modality., Competing Interests: The study was financially supported by CDx Diagnostics, Inc. CDx Diagnostics supported the study personnel cost and provided the study brushes. The sponsor had no role in the design and conduct of the study or collection, management, analysis, and interpretation of the data. The sponsor was provided with a draft prior to submission and did submit feedback to the authors.R. Bisshops has received consultancy fees from CDx Diagnostics. G. de Hertogh’s employer, the University of Leuven, received payments for involvement as central pathology reader in the study. R. Kariv is supported by a grant from Pfizer. P.D. Siersema is supported by grants from Pentax, MicroTech, the Enose company, and Motus GI. K. Ragunath has received consultancy fees from CDX Diagnostics. J. Bergman, P. Bhandari, L. Correale, G. Fernández-Esparrach, R. Haidry, C. Hassan, P. Leclercq, A. Lemmers, S.L. Meijer, H. Messmann, M. Munoz-Navas, H. Neuhaus, O. Pech, A. Probst, A. Repici, E.J. Schoon, S. Seewald, S.N. van Munster, and B.L.A.M. Weusten declare that they have no conflict of interest., (Thieme. All rights reserved.)

The endoscopist plays a critical role in the management of patients with congenital esophageal defects. This review focuses on esophageal atresia and congenital esophageal strictures and, in particular, the endoscopic management of comorbidities related to these conditions, including anastomotic strictures, tracheoesophageal fistulas, esophageal perforations, and esophagitis surveillance. Practical aspects of endoscopic techniques for stricture management are reviewed including dilation, intralesional steroid injection, stenting, and endoscopic incisional therapy. Endoscopic surveillance for mucosal pathology is essential in this population, as patients are at high risk of esophagitis and its late complications such as Barrett's esophagus., Competing Interests: Conflicts of interest The authors have no conflicts of interest or funding sources to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients with Barrett's esophagus (BE) and esophageal varices present a unique management dilemma. Endoscopic ablation and endoscopic resection are not suitable treatment options due to bleeding risk. Data are limited on successful eradication of BE and esophageal varices utilizing band ligation., Aims: To assess the outcomes of patients with BE and esophageal varices treated with banding., Methods: Retrospective analysis of patients with BE and esophageal varices who were treated with band ligation., Results: A total of eight patients were included in the case series. In all eight cases, BE and esophageal varices were successfully treated with band ligation alone. There were no bleeding, perforation or infectious complications in any patients undergoing banding for treatment of BE. Four patients had biopsy-proven dysplasia prior to treatment with band ligation. After band ligation, the 2 of 4 dysplastic cases that had repeat biopsies showed histologic resolution of the dysplasia. All patients who received banding for BE were followed at least yearly except for one patient lost to follow up. No interval esophageal cancers were reported in any patients with BE that were banded., Conclusions: Band ligation was used to treat BE pathology in eight patients with esophageal varices. Treatment of dysplasia through this method yielded negative biopsies both for dysplasia and BE on repeat endoscopy. This case series highlights the value of utilizing band ligation to address the management dilemma of BE in the context of esophageal varices., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Observational studies have reported that educational attainment has been related to the risk of esophageal cancer (EC) and its precancerous lesions. However, the causal relationship remains controversial. We aimed to apply the Mendelian randomization (MR) design to determine the causal associations between genetically predicted educational attainment and EC, Barrett's esophagus (BE), and gastroesophageal reflux disease (GERD), and to explore whether modifiable risk factors play a mediating role., Methods: Using summary statistics from genome-wide association studies (GWASs) based on European ancestry individuals of several years in education (EduYears, primary analysis, n = 293,723), college completion (College, secondary analysis, n = 95,427), EC ( n = 420,531), BE ( n = 361,194), and GERD ( n = 420,531), genetic associations between two education phenotypes and EC, BE, and GERD were tested by two-sample MR analyses. Then, two-step MR mediation analyses were used to assess the proportion of the aforementioned association that might be mediated by body mass index (BMI), major depressive disorder (MDD), smoking, drinking, carbohydrates, fat, and protein intake., Results: Genetically predicted EduYears was negatively associated with the risk of EC, BE, and GERD {odds ratio (OR), 0.64 [95% confidence interval (CI) 0.44-0.94], 0.86 (95% CI, 0.75-0.99), and 0.62 (95%CI, 0.58-0.67)}. EduYears was negatively associated with BMI, MDD, and smoking (range of OR: 0.76-0.84). There were positive associations between BMI, smoking with EC, BE, and GERD, as well as between MDD with GERD (range of OR: 1.08-1.50). For individual mediating effect, BMI and smoking mediated 15.75 and 14.15% of the EduYears-EC association and 15.46 and 16.85% of the EduYears-BE association. BMI, MDD, and smoking mediated 5.23, 4.98, and 4.49% of the EduYears-GERD association. For combined mediation, the aforementioned mediators explained 26.62, 28.38, and 11.48% of the effect of EduYears on EC, BE, and GERD. The mediating effects of drinking and dietary composition were not significant in the effect of education on EC, BE, and GERD., Conclusion: Our study supports that genetically predicted higher educational attainment has a protective effect on EC, BE, and GERD, and is partly mediated by reducing adiposity, smoking, and depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Yang, Zhang, Yin, Man and Lu.)

Shift work has adverse health effects such as diabetes, cardiovascular disease, sleep disturbance, depression, and breast cancer. Gastro-esophageal reflux disease (GERD) results in lesions such as reflux esophagitis (RE) and Barrett's esophagus. This study investigated the association between shift work and RE. A cohort study was conducted with 140,553 participants who were followed up at least once from 2012 to 2018. Type of working and shift types were collected using standardized questionnaires. Esophagogastroduodenoscopy (EGD) was performed by experienced endoscopists who were blinded to the aims of this study. According to the Los Angeles classification, RE was categorized based on the extent of esophageal mucosal breaks. During the 469,217.2 person-years of follow-up, 35,185 participants developed incident cases of RE. The multivariable adjusted hazard ratio (95% confidence intervals) for incident cases comparing shift work to fixed day work was 1.09 (1.04-1.13). This association was more strongly observed in the younger age group (18-39 years old) and the female group. In conclusion, shift work was significantly associated with the incidence of RE. Particularly, the results were more significant in the younger and female groups., (© 2023. The Author(s).)

Classification of adenocarcinomas (AC) arising around or within the gastroesophageal junction (GEJ) is hampered by major morphologic and phenotypic overlaps. We reviewed the surgical pathology of esophagectomy specimens of 115 primary resected AC of the esophagus as defined by the 5th edition of the WHO classification regarding the anatomical site of the tumor, with corresponding categorization according to the Siewert AEG Classification and the preceding 4th edition of the WHO (discriminating esophageal adenocarcinomas/EAC and adenocarcinomas of the gastroesophageal junction/AdGEJ), and further histology findings. In addition, immunohistochemistry (IHC) for CDX2, CK7, CK20, MUC2, MUC5AC and MUC6 was performed. Sixty-eight cases were Siewert AEG type I and 47 cases Siewert AEG type II. Out of the AEG I tumors, 26 were classified as AdGEJ. Regardless of the classification system, more proximally located tumors showed less aggressive behavior with lower rates of lymph node metastases, lymphatic, venous and perineural invasion, better histological differentiation (p < 0.05 each) and were more frequently associated with pre-neoplastic Barrett's mucosa (p < 0.001). Histologically, the tumors displayed intestinal morphology in the majority of cases. IHC showed non-conclusive patterns with a frequent CK7+/CK20+ immunophenotype in all tumors, but also a gastric MUC5AC+ and MUC6+ phenotype in some proximal tumors. In conclusion, histology of the tumors and IHC failed to distinguish reliably between more proximal and more distal tumors. The presence of Barrett's mucosa rather than location alone, however, may help to further differentiating adenocarcinomas arising in this region and may be indicative for a particular biologic type., (© 2022. The Author(s).)

Female hormones and hormone replacement therapy (HRT) are thought to play a role in gastroesophageal reflux disease (GERD). Pregnancy, menopause, and HRT have all been reported as risk factors for GERD. 1-6 It has been suggested that estrogen and progesterone confer their effect on the gastrointestinal tract by increasing nitric oxide synthesis, a muscle relaxant which decreases smooth muscle tone of the lower esophageal sphincter and esophageal body predisposing patients to gastroesophageal reflux. 6-8 However, the exact mechanism that these hormones play in GERD remains to be elucidated because menopause, which is a risk factor for GERD, is associated with a decrease in estrogen and progesterone levels. Thus the exact relationship between the different hormonal therapies and GERD remains unclear. The aim of this study was to determine the role and possible risk that estrogen and progesterone HRT pose for the development of GERD in postmenopausal women. In addition, we aimed to assess the relationship between HRT in postmenopausal women and GERD complications, such as esophageal stricture and Barrett's esophagus., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Helicobacter pylori ( H. pylori ) infection is a risk factor for many diseases, including peptic ulcer disease and gastric cancer. While H. pylori eradication therapy can prevent these diseases, potentially unfavorable effects of eradication therapy have also been reported in some diseases, such as gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), inflammatory bowel disease (IBD), allergic diseases, and metabolic diseases. Consequently, both positive and negative impacts should be considered when assessing the effects of H. pylori eradication therapy., Aim: To compare the incidence of these diseases before and after H. pylori eradication and to comprehensively assess its effects., Methods: This retrospective cohort study used a Japanese nationwide health claims database (April 2009-March 2020), developed by the Japanese Ministry of Health, Labour and Welfare. The database contained almost all health insurance claims data issued in Japan, and specific health check-up data for individuals who took the check-ups. Descriptive statistics were used for the analyses. Patients who received primary eradication therapy were defined as those prescribed medi-cation for H. pylori eradication. New diagnoses, defined as incidence of upper gastrointestinal diseases and IBD, and prevalence of allergic diseases were compared before and after eradication. The incidence and prevalence of each disease were also compared between the 3-year period before eradication (from the 4 th to the 2 nd year prior to the year of eradication) and the 3-year period after eradication (from the 1 st to the 3 rd year after the year of eradication) based on the age category and calendar year and month. Changes in body mass index and proportion of patients with metabolic syndrome (MS) were examined before and after eradication., Results: We identified 5219731 patients who received primary eradication therapy. The 65-69 years age group had the greatest number of patients in both sexes. There was no significant increase in the incidence of GERD after eradication when considering the effects of aging and reporting period. However, the incidence of BE was higher in the 3-year period after eradication than in the 3-year period before eradication for all age categories (0.02%-0.10% vs < 0.01%-0.05%). The incidence of IBD and prevalence of allergic disease were also higher after eradication. In contrast, the incidence of gastric and duodenal ulcers and gastritis was reduced after eradication. In patients with at least one entry of health check-up data (1701111 patients), the percentage of patients with MS showed a slight increase following eradication (11.0% in the year of eradication and 12.2% after 5 years)., Conclusion: The results suggest that H. pylori eradication therapy reduces peptic ulcers and gastritis; however, it is associated with increased incidence of several other chronic diseases., Competing Interests: Conflict-of-interest statement: Sugano K received lecture fees from Takeda Pharma. Inc and he is an advisor of Phathom Co. Takeshima T is an employee of Milliman Inc., which provides consulting service for biomedical companies. Mizukami K and Murakami K declare that they have no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients., Methods: We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE-) and determined the prevalence of BE in EoE patients., Results: Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE- 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE-. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE-, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017)., Conclusion: Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy., (© 2023 S. Karger AG, Basel.)

Educational Objective: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus., Objective: Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H + /K + ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H + /K + ATPase proton pumps., Study Design: In vitro translational., Methods: BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing., Results: Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer., Conclusions: These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE., Level of Evidence: NA Laryngoscope, 133:59-69, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Dysregulation of toll-like receptor (TLR) signaling within the gastrointestinal epithelium has been associated with uncontrolled inflammation and tumorigenesis. We sought to evaluate the role of TLR4 in the development of gastroesophageal reflux-mediated inflammation and mucosal changes of the distal esophagus. Verified human esophageal Barrett's cells with high grade dysplasia (CPB) and esophageal adenocarcinoma cells (OE33) were treated with deoxycholic acid for 24 hours. Cells were pretreated with a TLR4-specific inhibitor peptide 2 hours prior to deoxycholic acid treatment. Inflammatory markers were evaluated using immunoblotting and enzyme-linked immunosorbent assay. A surgical reflux mouse model was generated by performing a side-to-side anastomosis between the second portion of the duodenum and the gastroesophageal junction. Control animals underwent laparotomy with incision and closure of the esophagus superior to the gastroesophageal junction (sham procedure). Esophageal sections were evaluated using hematoxylin and eosin staining and immunohistochemistry. Deoxycholic acid increased expression of inflammatory markers including intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin 8. Pretreatment with a TLR4 inhibitor significantly decreased deoxycholic acid-induced inflammatory marker expression. C3H/HeNCrl mice demonstrated a significant increase in mucosal hyperplasia and proliferation following DGEA compared to sham procedure. TLR4 mutant mice (C3H/HeJ) undergoing DGEA demonstrated an attenuated hyperplastic and proliferative response compared to C3H/HeNCrl mice. Inhibition of TLR4 signaling attenuates reflux-induced inflammation in vivo. These findings identify TLR4 inhibition as a potential therapeutic target to halt the progression of pathologic esophageal changes developing in the setting of chronic gastroesophageal reflux disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)