Mendelian randomization analysis reveals the impact of physical and occupational activities on the risk of gastroesophageal reflux disease and Barrett's esophagus.

BACKGROUND: Recent studies have indicated that participating in physical activity may provide a safeguard against gastroesophageal reflux disease (GERD). Nevertheless, the precise links between physical and occupational activity and the occurrence of GERD and Barrett's esophagus (BE) are still uncertain. METHODS: Conducting univariate and multivariate Mendelian randomization investigations to examine the causal relationship between exposures and outcomes. Genetic variation simulation was used in randomized experiments. Data on physical and occupational activity were obtained from the UK Biobank and GWAS catalog. In the meantime, data on GERD and BE were extracted from a high quality meta-analysis. RESULTS: The results of univariate Mendelian randomization analysis using multiple methods suggest a causal relationship between strenuous sports or other forms of exercise (as a protective factor) and GERD/BE. At the same time, three types of occupational related physical activities, including heavy manual or physical work, shift work and walking or standing work, are risk factors for GERD/BE and have a causal relationship with them. These results were reconfirmed through multivariate Mendelian randomization analysis, which excluding the influence of other potential confounding factors. CONCLUSIONS: The findings indicated that strenuous sports or other forms of exercise could lower the likelihood of GERD/BE, while excessive physical strain in the workplace, prolonged periods of standing or walking, and shift work could raise the risk of GERD/BE. Acknowledging this risk and implementing suitable measures can contribute to the prevention of GERD and BE, thus mitigating the associated health burden.

Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN) in World Trade Center exposed firefighters: a case-control observational study protocol.

BACKGROUND: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms. METHODS: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life. DISCUSSION: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care. TRIAL REGISTRATION: Name of Primary Registry: "Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)". Trial Identifying Number: NCT05216133 . Date of Registration: January 31, 2022.

Sleeve-Dor Fundoplication - An Innovative Surgical Technique to Avoid the Epidemic Long Term de Novo Gastroesophageal Reflux and Barrett´s Esophagus After Sleeve Gastrectomy for Obesity.

BACKGROUND: Sleeve gastrectomy (SG) in current literature showed an increased risk of "de novo" gastroesophageal reflux disease (GERD) and increased risk for Barrett's esophagus in longer follow-up series, with a possibility of esophageal adenocarcinoma in this population. Adding primarily an anterior Dor Fundoplication to SG (Sleeve-Dor) may protect the patient for future and can potentially avoid these chronic complications for patients with obesity. METHODOLOGY: A standard SG is performed laparoscopically, and a small redundance of the fundus is maintained as a wrap, and this will be fixed to the right crura without dissection of the anatomy of the hiatus. The resulted anterior 180° Dor fundoplication is usually sufficient to relieve or to avoid reflux symptomatic. DISCUSSION: Based on our preliminary and literature experiences, the SG with anterior Dor fundoplication (Sleeve-Dor) procedure could provide favorable safety profile, satisfactory reflux control and good bariatric outcomes. The complication rate is lower compared to published for Nissen Sleeve or Sleeve-Rossetti technique, with no leaks or major complications recorded to date. Sleeve-Dor procedure may be a potential primary and standard surgery for morbidly obese patients, especially for patients with preoperative GERD symptoms without major findings at endoscopy.

[Barrett's Esophagus: Update on the Diagnosis and Treatment. Review]. / Esófago de Barrett: Actualización en el diagnóstico y tratamiento.

Barrett's esophagus (BE) is the condition in which a metaplastic columnar mucosa predisposed to neoplasia replaces the squamous mucosa of the distal esophagus. The current guidelines recommends that diagnosis requires the finding of intestinal metaplasia (IM) with goblet cells of at least 1 cm in length. BE affects approximately 1% of the general population and up to 14% of patients with gastroesophageal reflux disease (GERD). BE is a precursor of esophageal adenocarcinoma (EAC), which has increased in western countries. The main risk factors described for EAC associated with BE are male sex, age > 50 years, central obesity and tobacco use. Annual risk of EAC in patients with BE without dysplasia, low grade (LGD) and high-grade dysplasia is 0,1-0,3%, 0,5% y 5-8%, respectively. Treatment of non-dysplastic BE consists mainly of a healthy lifestyle change, chemoprevention with proton pump inhibitors and surveillance endoscopy every 3 to 5 years. It is recommended that from the presence of LGD patients are referred to an expert center for confirmation of the diagnosis, stage and thus define their management. In patients with BE and dysplasia or early-stage cancer, endoscopic therapy with resection and ablation is successful in about 90% of the patients. The main adverse event is esophageal stricture, which is managed endoscopically.

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction.

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

Comparison of focal cryoballoon ablation with 10- and 8-second doses for treatment of Barrett's esophagus-related neoplasia: results from a prospective European multicenter study (with video).

BACKGROUND AND AIMS: Focal cryoballoon ablation (FCBA) is currently being investigated for the treatment of Barrett's esophagus (BE)-related neoplasia in a European multicenter study (Euro-Coldplay study). After inclusion of 28 of 107 patients, the initial dose of 10 seconds was lowered to 8 seconds. The current study aimed to compare the efficacy and safety of a single FCBA treatment session with 10 seconds versus 8 seconds. METHODS: Treatments were performed at 7 European BE referral centers. All 28 patients treated with 10 seconds were compared with 28 consecutive patients treated with 8 seconds. The gastroesophageal junction was ablated circumferentially followed by all visible BE. To assess efficacy and safety, 3 expert adjudicators, blinded to physician and dose, compared pre- and post-treatment images. Primary outcomes were median BE surface regression and stricture rate after single-session FCBA. RESULTS: We included 56 patients (10-second cohort, n = 28; 8-second cohort, n = 28) with a median BE length of C0M2 (Prague classification). Baseline characteristics did not significantly differ between the cohorts. The median BE surface regression after a single FCBA session was comparable for 10 seconds and 8 seconds (80% [95% confidence interval {CI}, 75-90] and 80% [95% CI, 66-90], respectively; P = .65). Strictures requiring dilation were seen in 19% (95% CI, 4-33) and 15% (95% CI, 4-30) of the 10-second and 8-second groups, respectively (P = 1.00). Two patients in the 10-second group developed a severe stricture requiring >3 dilations. CONCLUSIONS: In patients with limited BE, single-session FCBA with 8 seconds showed similar BE surface regression as compared with 10 seconds and may theoretically result in fewer and less severe strictures. Therefore, we suggest using 8 seconds as the standard dose for FCBA. (Clinical trial registration number: NL7253.).

Effect of gastro-esophageal reflux symptoms on the risk of Barrett's esophagus: A systematic review and meta-analysis.

BACKGROUND AND AIM: Gastro-esophageal reflux (GER) is the main predisposing factor for Barrett's esophagus (BE). A more precise estimate of the association of GER symptoms with the risk of BE would be important to prioritize endoscopic screening. We conducted a systematic review and meta-analysis to examine this issue. METHODS: MEDLINE, EMBASE, and EMBASE Classic were searched to identify cross-sectional studies that reported the prevalence of BE based on presence of GER symptoms. The prevalence of BE was compared according to presence or absence of GER symptoms using an odds ratio (OR), with a 95% confidence interval (CI). Specificity and sensitivity of GER symptoms for predicting BE was calculated. RESULTS: Of 10,463 citations evaluated, 19 studies reported the prevalence of BE in 43,017 subjects. The pooled OR among individuals with weekly GER symptoms compared with those without was 1.67 (95% CI 1.30-2.15) for endoscopically suspected BE, and 2.42 (95% CI 1.59-3.68) for histologically confirmed BE. No significant association was found between weekly GER symptoms and the presence of short segment BE (OR 1.30; 95% CI 0.86-1.97), whereas a strong association was present with long segment BE, with an OR of 6.30 (95% CI 2.26-17.61). CONCLUSIONS: Gastro-esophageal reflux symptoms are associated with an increased odds of BE, with a further increase when weekly symptoms are present. Overall, GER symptoms showed low sensitivity and specificity for predicting BE; however, a strong association was found between weekly GER symptoms and long segment BE, but not short segment BE, suggesting that it may be worth considering screening individuals with weekly GER symptoms to rule out long segment BE.

Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia.

We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.

Barrett Esophagus: A Review.

Importance: Barrett esophagus is characterized by the replacement of normal esophageal squamous cell epithelium with columnar metaplasia and affects approximately 5% of people in the US and approximately 1% worldwide. Approximately 3% to 5% of patients with Barrett esophagus will be diagnosed with esophageal adenocarcinoma in their lifetime. Observations: Barrett esophagus affects approximately 2.3% to 8.3% of people with gastroesophageal reflux disease (GERD) and approximately 1.2% to 5.6% of people without GERD. Characteristics associated with Barrett esophagus include older age (prevalence of approximately 1.1% in individuals older than 50 years compared with 0.3% in those 50 years or younger), male sex, and smoking (prevalence of approximately 12% in people who smoke cigarettes compared with 1.1% in those who do not smoke cigarettes). The histopathology of Barrett esophagus progresses from metaplasia to dysplasia and, without treatment, can progress to adenocarcinoma. People with Barrett esophagus have approximately a 0.2% to 0.5% annual rate of developing esophageal adenocarcinoma. Management of Barrett esophagus primarily consists of acid-suppressive medications to reduce underlying GERD symptoms and surveillance endoscopy every 3 to 5 years. In patients with Barrett esophagus and dysplasia or early cancer, endoscopic therapy consisting of resection and ablation successfully treats 80% to 90% of patients. Conclusions and Relevance: Barrett esophagus affects approximately 5% of people in the US and approximately 1% worldwide and is associated with an increased risk of esophageal adenocarcinoma. First-line therapy for Barrett esophagus consists of proton-pump inhibitors for control of reflux symptoms, but their role in chemoprevention is unclear. Surveillance with upper endoscopy is recommended by practice guidelines to monitor for progression to esophageal adenocarcinoma, but randomized clinical trials are lacking.

Barrett's Esophagus: A Comparison Study between Two Cohorts of Gastroesophageal Reflux Disease.

INTRODUCTION: Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease (GERD). It is seen among 15% of GERD patients as per a population-based study by Ronkainen et  al. Barrett's has malignant potential and annual progression to carcinoma depends on the presence or absence of dysplasia. There are various risk factors for the development of BE. We compared two symptomatic cohorts of GERD patients from the same geographical area who were evaluated for the presence of Barrett's and various factors that can contribute to Barrett's Materials and methods: Cross-sectional study. Two GERD cohorts, one from Kottayam and the other from Trivandrum were taken. The presence of Barrett's and the factors contributing to the development of Barrett's were analyzed between the two groups. Since biopsy data of all patients were not available, endoscopically suspected esophageal metaplasia (ESEM) was taken as Barrett's Results: 415 patients were enrolled for the study (203 from Trivandrum and 212 from Kottayam). 192 females (99 from Trivandrum and 93 from Kottayam), and 223 males (104 from Trivandrum and 119 from Kottayam). Barrett's esophagus and especially long-segment Barrett's were significantly more common in Kottayam than Trivandrum (68 vs 22 and 36 vs 9) (p-value <0.001). Among the factors that were traditionally thought to contribute to the development of Barrett's esophagus, age (>50 years) was not statistically significant among the two cohorts (mean age of Trivandrum was 48 years and Kottayam was 49 years). Duration of GERD symptoms was significantly more in the Trivandrum cohort compared to Kottayam (p-value <0.001). Hiatus hernia and body mass index (BMI) were more common in Kottayam. There were no statistically significant differences in erosive esophagitis and antral gastritis (%age?) between the two cohorts. CONCLUSION: Both Trivandrum and Kottayam belong to the same geographical area and are separated by a distance of only 150 km. The Kottayam cohort is more prone to develop distal esophageal carcinoma as the BE is more in Kottayam. This data also suggests the need for GERD registries so that high-risk population can be targeted and early intervention can lead to a decrease in the incidence of distal esophageal carcinomas.

[Management of complicated Barrett's esophagus. Observational study carried out in a regional hospital]. / Prise en charge de l'œsophage de Barrett compliqué. Étude observationnelle réalisée dans un centre hospitalier régional.

The incidence of Barrett's esophagus, complication of gastroesophageal reflux disease, is rising in western countries. It is the same for esophageal adenocarcinoma, of which it is the main contributing factor. This retrospective study seeks to report the incidence of these pathologies observed in a regional hospital center and to describe their management. In 5 years, 354 Barrett's esophagus are detected and 34 of them are complicated by high-grade dysplasia or adenocarcinoma. Endoscopic resection is performed in 24 of these patients. The histological analysis of which leads to the conclusion of adenocarcinoma in 20 patients and high-grade dysplasia in the 14 others. The complications of endoscopic and surgical resections are detailed. Their frequency and severity remain low, comparable to data in the literature.

L'incidence de l'œsophage de Barrett, complication du reflux gastro-œsophagien, est en croissance dans les pays occidentaux. Il en est de même de l'adénocarcinome œsophagien dont il est le principal facteur favorisant. Cette étude rétrospective s'attache à rapporter l'incidence de ces pathologies, observées dans un centre hospitalier régional, et à détailler leur prise en charge. En 5 ans, 354 œsophages de Barrett sont détectés et 34 d'entre eux sont compliqués de dysplasie de haut grade ou d'adénocarcinome. Une résection endoscopique est réalisée chez 24 de ces malades. Les analyses histologiques permettent de conclure à un adénocarcinome chez 20 malades et une dysplasie de haut grade chez les 14 restants. Les complications des résections endoscopiques et chirurgicales sont détaillées. Leur fréquence et leur gravité restent faibles, comparables aux données de la littérature.

Global prevalence of Barrett's oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis.

OBJECTIVES: Chronic gastro-oesophageal reflux might lead to the development of Barrett's oesophagus (BO) or even oesophageal adenocarcinoma. There has been no definitive systematic review and meta-analysis of data to estimate global prevalence of BO or oesophageal adenocarcinoma in individuals with gastro-oesophageal reflux. DESIGN: We searched MEDLINE, Embase and Embase Classic to identify cross-sectional surveys that reported prevalence of BO or oesophageal adenocarcinoma in adults with gastro-oesophageal reflux. We extracted prevalence for all studies, both for endoscopically suspected and histologically confirmed cases. We calculated pooled prevalence according to study location, symptom frequency and sex, as well as ORs with 95% CIs. RESULTS: Of the 4963 citations evaluated, 44 reported prevalence of endoscopically suspected and/or histologically confirmed BO. Prevalence of BO among individuals with gastro-oesophageal reflux varied according to different geographical regions ranging from 3% to 14% for histologically confirmed BO with a pooled prevalence of 7.2% (95% CI 5.4% to 9.3%), whereas pooled prevalence for endoscopically suspected BO was 12.0% (95% CI 5.5% to 20.3%). There was heterogeneity in many of our analyses. Prevalence of BO was significantly higher in men, both for endoscopically suspected (OR=2.1; 95% CI 1.6 to 2.8) and histologically confirmed BO (OR=2.3; 95% CI 1.7 to 3.2). Dysplasia was present in 13.9% (95% CI 8.9% to 19.8%) of cases of histologically confirmed BO, 80.7% of which was low-grade. CONCLUSION: The prevalence of Barrett's oesophagus among individuals with gastro-oesophageal reflux varied strikingly among countries, broadly resembling the geographical distribution of gastro-oesophageal reflux itself. Prevalence of BO was significantly higher in men.

Forkhead box F1 induces columnar phenotype and epithelial-to-mesenchymal transition in esophageal squamous cells to initiate Barrett's like metaplasia.

Multiple genome-wide association studies (GWAS) have linked Forkhead Box F1 (FOXF1) to Barrett's esophagus (BE). Understanding whether FOXF1 is involved in initiation of Barrett's metaplasia could allow FOXF1 to be used for risk stratification and for therapy. Two-dimensional cell cultures and three-dimensional organoid cultures and well-annotated human biopsies were used to determine the role of FOXF1 in BE pathogenesis. Multiple established esophageal squamous and BE cell lines were tested in gain- and loss-of-function studies. Initiation of a BE-like metaplastic change was evaluated by measuring characteristic cytokeratins and global gene expression profiling and by culturing organoids. Epithelial-mesenchymal transition (EMT) was evaluated by immunostaining for E-cadherin, vimentin and Snail, and by cell motility assay. Columnar esophageal epithelium of BE patients exhibited higher expression of FOXF1 compared to normal squamous esophageal epithelium of GERD patients (P < 0.001). Acidic bile salts induced nuclear FOXF1 in esophageal squamous cells. FOXF1 overexpression in normal esophageal squamous cells: (a) increased columnar cytokeratins and decreased squamous cytokeratins, (b) converted squamous organoids to glandular organoids, and (c) switched global gene profiles to resemble that of human BE epithelium (P = 2.1685e - 06 for upregulated genes and P = 8.3378e - 09 for downregulated genes). FOXF1 inhibition in BE cell lines led to loss of BE differentiation markers, CK7, and mucin 2. Also, FOXF1 induced EMT and promoted cell motility in normal esophageal squamous epithelial cells. FOXF1-induced genes mapped to pathways such as Cancer, Cellular Assembly and Organization, DNA Replication, Recombination, and Repair. In conclusion, FOXF1 promotes a BE-like columnar phenotype and cell motility in esophageal squamous epithelial cells, which may have a critical role in BE development. FOXF1 should be studied further as a biomarker for BE and as a target for BE treatment.

Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial.

BACKGROUND: Treatment of dysplastic Barrett's oesophagus prevents progression to adenocarcinoma; however, the optimal diagnostic strategy for Barrett's oesophagus is unclear. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett's oesophagus. The aim of this study was to investigate whether offering this test to patients on medication for gastro-oesophageal reflux would increase the detection of Barrett's oesophagus compared with standard management. METHODS: This multicentre, pragmatic, randomised controlled trial was done in 109 socio-demographically diverse general practice clinics in England. Randomisation was done both at the general practice clinic level (cluster randomisation) and at the individual patient level, and the results for each type of randomisation were analysed separately before being combined. Patients were eligible if they were aged 50 years or older, had been taking acid-suppressants for symptoms of gastro-oesophageal reflux for more than 6 months, and had not undergone an endoscopy procedure within the past 5 years. General practice clinics were selected by the local clinical research network and invited to participate in the trial. For cluster randomisation, clinics were randomly assigned (1:1) by the trial statistician using a computer-generated randomisation sequence; for individual patient-level randomisation, patients were randomly assigned (1:1) by the general practice clinics using a centrally prepared computer-generated randomisation sequence. After randomisation, participants received either standard management of gastro-oesophageal reflux (usual care group), in which participants only received an endoscopy if required by their general practitioner, or usual care plus an offer of the Cytosponge-TFF3 procedure, with a subsequent endoscopy if the procedure identified TFF3-positive cells (intervention group). The primary outcome was the diagnosis of Barrett's oesophagus at 12 months after enrolment, expressed as a rate per 1000 person-years, in all participants in the intervention group (regardless of whether they had accepted the offer of the Cytosponge-TFF3 procedure) compared with all participants in the usual care group. Analyses were intention-to-treat. The trial is registered with the ISRCTN registry, ISRCTN68382401, and is completed. FINDINGS: Between March 20, 2017, and March 21, 2019, 113 general practice clinics were enrolled, but four clinics dropped out shortly after randomisation. Using an automated search of the electronic prescribing records of the remaining 109 clinics, we identified 13 657 eligible patients who were sent an introductory letter with 14 days to opt out. 13 514 of these patients were randomly assigned (per practice or at the individual patient level) to the usual care group (n=6531) or the intervention group (n=6983). Following randomisation, 149 (2%) of 6983 participants in the intervention group and 143 (2%) of 6531 participants in the usual care group, on further scrutiny, did not meet all eligibility criteria or withdrew from the study. Of the remaining 6834 participants in the intervention group, 2679 (39%) expressed an interest in undergoing the Cytosponge-TFF3 procedure. Of these, 1750 (65%) met all of the eligibility criteria on telephone screening and underwent the procedure. Most of these participants (1654 [95%]; median age 69 years) swallowed the Cytosponge successfully and produced a sample. 231 (3%) of 6834 participants had a positive Cytosponge-TFF3 result and were referred for an endoscopy. Patients who declined the offer of the Cytosponge-TFF3 procedure and all participants in the usual care group only had an endoscopy if deemed necessary by their general practitioner. During an average of 12 months of follow-up, 140 (2%) of 6834 participants in the intervention group and 13 (<1%) of 6388 participants in the usual care group were diagnosed with Barrett's oesophagus (absolute difference 18·3 per 1000 person-years [95% CI 14·8-21·8]; rate ratio adjusted for cluster randomisation 10·6 [95% CI 6·0-18·8], p<0·0001). Nine (<1%) of 6834 participants were diagnosed with dysplastic Barrett's oesophagus (n=4) or stage I oesophago-gastric cancer (n=5) in the intervention group, whereas no participants were diagnosed with dysplastic Barrett's oesophagus or stage I gastro-oesophageal junction cancer in the usual care group. Among 1654 participants in the intervention group who swallowed the Cytosponge device successfully, 221 (13%) underwent endoscopy after testing positive for TFF3 and 131 (8%, corresponding to 59% of those having an endoscopy) were diagnosed with Barrett's oesophagus or cancer. One patient had a detachment of the Cytosponge from the thread requiring endoscopic removal, and the most common side-effect was a sore throat in 63 (4%) of 1654 participants. INTERPRETATION: In patients with gastro-oesophageal reflux, the offer of Cytosponge-TFF3 testing results in improved detection of Barrett's oesophagus. Cytosponge-TFF3 testing could also lead to the diagnosis of treatable dysplasia and early cancer. This strategy will lead to additional endoscopies with some false positive results. FUNDING: Cancer Research UK, National Institute for Health Research, the UK National Health Service, Medtronic, and the Medical Research Council.

Barrett's esophagus after sleeve gastrectomy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Sleeve gastrectomy (SG) has become significantly more common in recent years. Gastroesophageal reflux disease (GERD) is a major concern in patients undergoing SG and is the major risk factor for Barrett's esophagus (BE). We aimed to assess the prevalence of BE in patients who had undergone SG. METHODS: We searched the major search engines ending in July 2020. We included studies on patients who had undergone esophagogastroduodenoscopy (EGD) after SG. The primary outcome was the prevalence of BE in patients who had undergone SG. We assessed heterogeneity using I2 and Q statistics. We used funnel plots and the classic fail-safe test to assess for publication bias. We used random-effects modeling to report effect estimates. RESULTS: Our final analysis included 10 studies that included 680 patients who had undergone EGD 6 months to 10 years after SG. The pooled prevalence of BE was 11.6% (95% confidence interval [CI], 8.1%-16.4%; P < .001; I2 = 28.7%). On logistic meta-regression analysis, there was no significant association between BE and the prevalence of postoperative GERD (ß = 3.5; 95% CI, -18 to 25; P = .75). There was a linear relationship between the time of postoperative EGD and the rate of esophagitis (ß = 0.13; 95% CI, 0.06-0.20; P = .0005); the risk of esophagitis increased by 13% each year after SG. CONCLUSIONS: The prevalence of BE in patients who had EGD after SG appears to be high. There was no correlation with GERD symptoms. Most cases were observed after 3 years of follow-up. Screening for BE should be considered in patients after SG even in the absence of GERD symptoms postoperatively.

High grade dysplasia or esophageal adenocarcinoma in patients with a history of Roux-en-Y gastric bypass surgery: a case series.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is the favored bariatric option in patients with gastroesophageal reflux and Barrett's esophagus because it prevents reflux. Weight loss and decreased reflux following RYGB could theoretically minimize the risk of progression to cancer. We aimed to demonstrate the management of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) developing in patients after RYGB. METHODS: A prospectively maintained database was searched to identify cases of HGD and cancer in RYGB patients. Charts were reviewed for past history, endoscopic findings, endoscopic therapy, and pathology findings. RESULTS: There were five cases where HGD/EAC developed several years after RYGB. The prior bariatric surgery precluded curative esophagectomy, illustrating the management challenges. All but one of the patients were uniquely and successfully managed with endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). CONCLUSIONS: RYGB patients are still at risk of developing esophageal cancer. Patients at risk should be screened prior to RYGB and those with Barret's esophagus need to undergo rigorous endoscopic surveillance following surgery. If detected early, EMR and ESD are invaluable in managing those who progress.

Regression of Barrett's esophagus after magnetic sphincter augmentation: intermediate-term results.

BACKGROUND: Untreated gastroesophageal reflux disease (GERD) can lead to Barrett's esophagus and an increased risk for esophageal adenocarcinoma. Magnetic sphincter augmentation (MSA) is a safe and effective modality for the treatment of GERD. Preliminary research on short-term outcomes after MSA demonstrated significant regression of Barrett's. Further investigation is required to evaluate the long-term effect of this treatment. METHODS: A retrospective review of patients was conducted with biopsy-proven Barrett's esophagus who underwent MSA between 2007 and 2019. As a part of their preoperative evaluation, patients underwent esophagogastroduodenoscopy (EGD) with biopsies of the distal esophagus and gastroesophageal junction including any abnormal-appearing segments, pH testing, and a videoesophagram. Patients were categorized according to the length of Barrett's identified (ultrashort < 1 cm, short 1-3 cm, long > 3 cm). Improvement was defined as a decrease in length (e.g. long to short). RESULTS: There were 87 patients identified for study inclusion. 55 patients were male. The median body mass index was 26.95. The median age was 61.81 (49.79-68.29). Mean follow-up time was 2.35 ± (1.57) years. 7 (8.0%) of these patients began with long segment Barrett's, 58 (66.7%) began with short segment disease, and 22 (25.3%) began with an ultrashort segment. Within this cohort, 74 (85.06%) had undergone postoperative biopsy. 7 out of 74 patients (9.46%) showed improvement in their intestinal metaplasia and 45/74 (60.81%) showed complete regression. Fisher's exact test showed a significant decrease in Barrett's length following MSA (p = 0.002). No patients progressed to dysplasia or neoplasia. There was a statistically significant decrease in the median Demeester score from 34.00 to 13.70 after surgery (p < .001). CONCLUSION: MSA reduces esophageal acid exposure and can lead to reduction or resolution of Barrett's esophagus. MSA is also effective at preventing progression of metaplasia to dysplasia or neoplasia. This effect remains consistent even after 2 years of follow-up.

Dietary Habits and Risk of Esophagitis and Barrett's Esophagus: A Multicenter Italian Case-Control Study.

BACKGROUND: Barrett's esophagus (BE) and esophagitis share potentially modifiable risk factors such as obesity, smoking, and alcohol. The role of diet on BE and esophagitis is still debated. AIMS: The objective of this study was to examine the association between some dietary habits and the risk of BE and esophagitis in Italy. METHODS: A multicenter case-control study involving 1285 individuals was carried out in 12 areas. Patients with a new diagnosis of BE (320) or esophagitis (359) and a group of endoscopic controls (606) were included. Information on personal history and dietary habits was collected using a structured questionnaire. RESULTS: No clear monotonic significant dose-response relationship was found for most of the considered food items. Nevertheless, the most extreme consumption category of red meat, cold cuts, dairy products, and fried foods showed esophagitis risk excesses varying from 19 to 49%. A higher fat rich diet seemed to increase risk by 49% for BE and 94% for esophagitis. A downward tendency in esophagitis (- 27%) and BE risk (- 20%) was found associated with higher frequency of fresh fruit intake. In addition, a statistically significant twofold increased risk for both BE and esophagitis was found for subjects eating late evening snacks more than once every three days in comparison with the lowest intake category (no consumption). CONCLUSIONS: BE and esophagitis patients appeared to be more likely than controls to follow a diet rich in fats and poor in fruit and vegetables. Late evening snacks were found to be associated with both disorders.

Significant decline in the prevalence of Barrett's esophagus among patients with gastroesophageal reflux disease.

Barrett's esophagus (BE), a premalignant condition for the development of esophageal adenocarcinoma (EAC), is a consequence of chronic gastroesophageal reflux disease (GERD). Although the incidence of EAC is increasing, a similar trend for BE is not clear. We aimed to evaluate the prevalence of newly diagnosed BE over time in a cohort of patients presenting with GERD symptoms. Information was prospectively collected between 1998 and 2015 for patients presenting to the endoscopy unit at a tertiary referral center for their index upper endoscopy for evaluation of GERD symptoms. Patients were asked to complete a validated GERD questionnaire that documents the onset of GERD symptoms (heartburn and acid regurgitation) and grades the frequency and severity of symptoms experienced. Demographic information, body mass index (BMI), and use of aspirin, nonsteroidal anti-inflammatory drugs, acid suppression therapy if any, smoking, family history, and endoscopic findings: erosive esophagitis, BE, and hiatal hernia were recorded. Patients evaluated during 1998-2003 (control) were compared with those presented in subsequent years (3-year cohorts) using chi-square test, and a multivariable logistic regression model was used to evaluate independent predictors. A total of 1109 patients were included in the analysis: mean age 56.9 years (standard deviation [SD] 12.8), 83% Caucasian, 93% male, and mean BMI 29.8 (SD 5.5). Overall, 226 (20.3%) patients were diagnosed with BE, with a mean BE length of 2.1 cm (SD 2.6). There was a significant decrease in the prevalence of BE over time from 24.3% in 1998-2003 to 13.5% in 2013-2015 (P = 0.002). During the same time period, a significant increasing trend in proton pump inhibitor (PPI) (41.7%; 1998-2003 vs. 80.2%; 2013-2015) (P < 0.001) and aspirin (ASA) use (23.7%; 1998-2003 vs. 25.9%; 2013-2015) (P = 0.034) was noted. There was also a significant reduction in cigarette smoking. In a multivariable logistic regression model for predicting the presence of newly diagnosed BE, there was a significant effect of timeframe even after adjusting for confounding variables. The results of our study indicate that there has been a steady and significant decline in the prevalence of BE in GERD patients over the last 2 decades. During this same time period, there has been an accompanying increase in the use of PPI, aspirin therapy, and a reduction in smoking, all modifiable risk factors potentially contributing to the decreasing prevalence of BE. Whether this decreasing prevalence of BE will lead to a reduction in EAC remains to be seen.

Does Sleeve Gastrectomy Expose the Distal Esophagus to Severe Reflux?: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to appraise the prevalence of gastroesophageal reflux disease (GERD), esophagitis, and Barrett's esophagus (BE) after sleeve gastrectomy (SG) through a systematic review and meta-analysis. BACKGROUND: The precise prevalence of new-onset or worsening GERD after SG is controversial. Subsequent esophagitis and BE can be a serious unintended sequalae. Their postoperative prevalence remains unclear. METHODS: A systematic literature search was performed to identify studies evaluating postoperative outcomes in primary SG for morbid obesity. The primary outcome was prevalence of GERD, esophagitis, and BE after SG. Meta-analysis was performed to calculate combined prevalence. RESULTS: A total of 46 studies totaling 10,718 patients were included. Meta-analysis found that the increase of postoperative GERD after sleeve (POGAS) was 19% and de novo reflux was 23%. The long-term prevalence of esophagitis was 28% and BE was 8%. Four percent of all patients required conversion to RYGB for severe reflux. CONCLUSIONS: The postoperative prevalence of GERD, esophagitis, and BE following SG is significant. Symptoms do not always correlate with the presence of pathology. As the surgical uptake of SG continues to increase, there is a need to ensure that surgical decision-making and the consent process for this procedure consider these long-term complications while also ensuring their postoperative surveillance through endoscopic and physiological approaches. The long-term outcomes of this commonly performed bariatric procedure should be considered alongside its weight loss and metabolic effects.