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BackgroundAbdominal obesity is a risk factor for Barrett's esophagus independent of GERD symptoms, but little is understood about the biological mechanisms between obesity and the carcinogenic pathway of esophageal adenocarcinoma.AimsTo evaluate whether ghrelin and leptin may partially explain the association between obesity and Barrett's esophagus.MethodsWe conducted a case-control study using patients with a new diagnosis of Barrett's esophagus (cases) and two control groups frequency matched to cases for age, gender, and geographic region: (1) patients with gastroesophageal reflux disease (GERD) and (2) a sample of the general population. We generated odds ratios using logistic regressions to evaluate quartiles of serum ghrelin or serum leptin, adjusting for known risk factors for Barrett's esophagus. We evaluated potential interaction variables using cross products and ran stratified analyses to generate stratum-specific odds ratios.ResultsA total of 886 participants were included in the analysis. Higher ghrelin concentrations were associated with an increased risk of Barrett's esophagus, when compared to the population controls, but not the GERD controls. Ghrelin concentrations were not associated with the frequency of GERD symptoms, but ghrelin's relationship with Barrett's esophagus varied significantly with the frequency of GERD symptoms. Leptin concentrations were positively associated with at least weekly GERD symptoms among the population controls and were inversely associated with Barrett's esophagus only among the GERD controls. Adjusting for waist circumference did not change the main associations.ConclusionHigher levels of ghrelin were associated with an increased risk of Barrett's esophagus among the general population. In contrast, leptin was positively associated with frequent GERD symptoms, but inversely associated with the risk of Barrett's esophagus among the GERD controls.

Background & aimsAbdominal obesity and increasing body mass index are risk factors for esophageal adenocarcinoma and its main precursor, Barrett's esophagus; however, there are no known biological mechanisms for these associations or regarding why only some patients with gastroesophageal reflux disease develop Barrett's esophagus. We evaluated the association between Barrett's esophagus and multimers of an adipose-associated hormone, adiponectin.MethodsWe conducted a case-control study evaluating the associations between adiponectin (total, high-molecular-weight, and low-/medium-molecular-weight) and Barrett's esophagus within the Kaiser Permanente Northern California population. Patients with a new diagnosis of Barrett's esophagus (cases) were matched to patients with gastroesophageal reflux disease (GERD) without Barrett's esophagus and to population controls.ResultsComplete serologic and epidemiologic data were available for 284 cases, 294 GERD controls, and 285 population controls. Increasing adiponectin levels were a risk factor for Barrett's esophagus among patients with GERD (total adiponectin fourth vs first quartile odds ratio [OR], 1.96; 95% confidence interval [CI], 1.17-3.27; high-molecular-weight adiponectin OR, 1.65; 95% CI, 1.00-2.73; low-/medium-molecular-weight adiponectin OR, 2.18; 95% CI, 1.33-3.56), but not compared with population controls. The associations were significantly stronger among patients reporting frequent GERD symptoms and among smokers (P values interaction < .01).ConclusionsAdiponectin levels are associated positively with the risk of Barrett's esophagus among patients with GERD and among smokers, but not among population controls without GERD symptoms. Higher adiponectin concentrations either independently may contribute to the aberrant healing of esophageal injury into Barrett's esophagus or be a marker for other factors.

This document is a correction notice for an article titled "Ghrelin and Leptin Have a Complex Relationship with Risk of Barrett's Esophagus" published in Digestive Diseases & Sciences. The correction addresses an error in the co-author's name, which was originally written as "James E. Graham" instead of "James L. Graham." The correction has been made to the author group. The original article has been updated to reflect this correction. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Stuart J. Thomas, Lucy Almers, Jennifer Schneider, James L. Graham, Peter J. Havel, and Douglas A. Corley. [Extracted from the article]

Background: Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear.Methods: Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% CIs for self-reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random-effects meta-analysis.Results: Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00-1.80; I2  = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05-1.55; I2  = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I2  = 34.9%). Regurgitation symptoms modified the diabetes-EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19-2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74-1.43). No consistent association was found between diabetes and BE.Conclusions: Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer. [ABSTRACT FROM AUTHOR]

Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease ( GERD) are major risk factors associated with Barrett's esophagus ( BE) and esophageal adenocarcinoma ( EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length ( LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett's and Esophageal Adenocarcinoma Consortium ( BEACON). Telomere length was measured in leukocyte DNA samples by Q- PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population-based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study-specific odds ratios ( ORs) and 95% confidence intervals ( CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients ( OR 0.57; 95% CI: 0.35-0.93), compared to population-based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC. [ABSTRACT FROM AUTHOR]

The development of and adherence to quality indicators in gastroenterology, as in all of medicine, is increasing in importance to ensure that patients receive consistent high-quality care. In addition, government-based and private insurers will be expecting documentation of the parameters by which we measure quality, which will likely affect reimbursements. Barrett’s esophagus remains a particularly important disease entity for which we should maintain up-to-date guidelines, given its commonality, potentially lethal outcomes, and controversies regarding screening and surveillance. To achieve this goal, a relatively large group of international experts was assembled and, using the modified Delphi method, evaluated the validity of multiple candidate quality indicators for the diagnosis and management of Barrett’s esophagus. Several candidate quality indicators achieved >80% agreement. These statements are intended to serve as a consensus on candidate quality indicators for those who treat patients with Barrett’s esophagus. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD).METHODS:We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations.RESULTS:In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients.CONCLUSIONS:In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research. [ABSTRACT FROM AUTHOR]

Background Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may be affected by bias and confounding. Methods We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided. Results The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1 kg/m² increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses. Conclusions People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Results from studies examining the association between alcohol consumption and the risk of Barrett's esophagus have been inconsistent. We assessed the risk of Barrett's esophagus associated with total and beverage-specific alcohol consumption by pooling individual participant data from five case-control studies participating in the international Barrett's and Esophageal Adenocarcinoma Consortium.METHODS:For analysis, there were 1,282 population-based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and 1,169 patients with Barrett's esophagus (cases). We estimated study-specific odds ratios (ORs) and 95% confidence intervals (95% CI) using multivariable logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking status, and GERD symptoms. Summary risk estimates were obtained by random-effects models. We also examined potential effect modification by sex, BMI, GERD symptoms, and cigarette smoking.RESULTS:For comparisons with population-based controls, although there was a borderline statistically significant inverse association between any alcohol consumption and the risk of Barrett's esophagus (any vs. none, summary OR=0.77, 95% CI=0.60-1.00), risk did not decrease in a dose-response manner (Ptrend=0.72). Among alcohol types, wine was associated with a moderately reduced risk of Barrett's esophagus (any vs. none, OR=0.71, 95% CI=0.52-0.98); however, there was no consistent dose-response relationship (Ptrend=0.21). We found no association with alcohol consumption when cases were compared with GERD controls. Similar associations were observed across all strata of BMI, GERD symptoms, and cigarette smoking.CONCLUSIONS:Consistent with findings for esophageal adenocarcinoma, we found no evidence that alcohol consumption increases the risk of Barrett's esophagus. [ABSTRACT FROM AUTHOR]

Background: Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. Methods: Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. Results: Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index. Conclusions: This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10−10) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10−9) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10−9) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective: Barrett's oesophagus is a precursor lesion of oesophageal adenocarcinoma, a cancer that, in the USA, has increased in incidence over 600% during the past 40 years. Barrett's oesophagus and oesophageal adenocarcinoma are much more common among men than among women; this finding is unexplained and most earlier studies lacked sufficient numbers of women to evaluate sex-specific risk factors. We leveraged the power of an international consortium to assess sexspecific relationships between body mass index (BMI), abdominal circumference and Barrett's oesophagus. Design: Four case-control studies provided a total of 1102 cases (316 women, 786 men) and 1400 population controls (436 women, 964 men) for analysis. Study-specific estimates, generated using individual participant data, were combined using random effects meta-analysis. Results: Waist circumference was significantly associated with Barrett's oesophagus, even after adjustment for BMI; persons in the highest versus the lowest quartiles of waist circumference had approximately 125% and 275% increases in the odds of Barrett's oesophagus among men and women, respectively (OR 2.24, 95% CI 1.08 to 4.65, I²=57; OR 3.75, 95% CI 1.47 to 9.56, I²=0). In contrast, there was no evidence of a significant association between BMI and the risk of Barrett's oesophagus, with or without adjustment for waist circumference. Conclusions: Waist circumference, independent of BMI, was found to be a risk factor for Barrett's oesophagus among both men and women. Future studies examining the biological mechanisms of this association will extend our knowledge regarding the pathogenesis of Barrett's oesophagus. [ABSTRACT FROM AUTHOR]

Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios ( ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes ( OR 0.66; 95% confidence interval [ CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett's esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined ( OR 0.61; 95% CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control. [ABSTRACT FROM AUTHOR]

Background & Aims: Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett''s esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. Methods: We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. Results: Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. Conclusions: We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies. [Copyright &y& Elsevier]

Background & Aims: Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett''s esophagus. We investigated whether tobacco smoking and other factors increase risk for Barrett''s esophagus. Methods: We analyzed data from 5 case-control studies included in the international Barrett''s and Esophageal Adenocarcinoma Consortium. We compared data from subjects with Barrett''s esophagus (n = 1059) with those from subjects with gastroesophageal reflux disease (gastroesophageal reflux disease controls, n = 1332), and population-based controls (n = 1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for Barrett''s esophagus. Results: Subjects with Barrett''s esophagus were significantly more likely to have ever smoked cigarettes than the population-based controls (odds ratio [OR] = 1.67; 95% confidence interval [CI]: 1.04–2.67) or gastroesophageal reflux disease controls (OR = 1.61; 95% CI: 1.33–1.96). Increasing pack-years of smoking increased the risk for Barrett''s esophagus. There was evidence of a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (95% CI: 0.25–0.52). Conclusions: Cigarette smoking is a risk factor for Barrett''s esophagus. The association was strengthened with increased exposure to smoking until ∼20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to development of Barrett''s esophagus. [Copyright &y& Elsevier]

Background Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation. Methods We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided. Results The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and ≥10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar. Conclusions Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks. [ABSTRACT FROM AUTHOR]

Background & Aims: Little is known about the effects of alcohol use and sociodemographics on the risk of Barrett''s esophagus, a precursor to esophageal adenocarcinoma. We evaluated the association between alcohol use, alcohol type, sociodemographic profiles, other lifestyle factors, and the risk of Barrett''s esophagus. Methods: With the use of a case-control study within the Kaiser Permanente Northern California membership, patients with a new diagnosis of Barrett''s esophagus (n = 320) diagnosed between 2002 and 2005 were matched to persons with gastroesophageal reflux disease (GERD; n = 316) and to population controls (n = 317). We collected information using validated questionnaires during direct in-person interviews. Analyses used multivariate unconditional logistic regression. Results: Total alcohol use was not significantly associated with the risk of Barrett''s esophagus, although stratification by beverage type showed an inverse association for wine drinkers compared with nondrinkers (≥7 drinks of wine per week vs none: odds ratio, 0.44; 95% confidence interval, 0.20–0.99; multivariate analysis). Among population controls, those who preferred wine were more likely to have college degrees and regularly take vitamin supplements than those who preferred beer or liquor, although adjustment for these factors or GERD symptoms did not eliminate the inverse association between wine consumption and Barrett''s esophagus. Education status was significantly inversely associated with the risk of Barrett''s esophagus. Conclusions: There are associations between alcohol types, socioeconomic status, and the risk of Barrett''s esophagus. Although choice of alcoholic beverages was associated with several factors, multiple adjustments (including for GERD) did not eliminate the association between alcohol and Barrett''s esophagus. Further research to evaluate the associations among socioeconomic status, GERD, and Barrett''s esophagus is warranted. [Copyright &y& Elsevier]

OBJECTIVE: High iron stores are a proposed modifiable risk factor for esophageal adenocarcinoma, but minimal human data exist. We evaluated whether iron intake and iron stores were associated with Barrett's esophagus, a metaplastic change that is a strong risk factor for esophageal adenocarcinoma. METHODS: We conducted a case-control study within the Kaiser Permanente Northern California population. We identified all persons with a new diagnosis of Barrett's esophagus (cases); they were matched to persons with GERD (without Barrett's esophagus) and to population controls. Subjects completed examinations, dietary questionnaires, and testing for serum iron stores (ferritin and transferrin saturation). Analyses used unconditional logistic regression. RESULTS: We evaluated 319 cases, 312 GERD patients, and 313 population controls. Compared with population controls, Barrett's esophagus patients had lower dietary iron intakes (4th vs 1st quartiles, odds ratio [OR]= 0.37, 95% confidence interval [CI] 0.17–0.80), similar total iron intakes (including supplement use), and lower iron stores (4th vs 1st quartiles, ferritin OR = 0.24, 95% CI 0.14–0.40;% transferrin saturation OR = 0.66, 95% CI 0.41–1.04; P value trend <0.01 and 0.03, respectively). Similar associations were observed in comparisons with GERD controls and among subjects without clear sources of blood loss on endoscopy. CONCLUSIONS: Patients with Barrett's esophagus had lower dietary iron intakes and lower serum iron stores than controls in our population. These findings do not provide support for the current hypothesis that high iron stores or a high iron intake are risk factors for Barrett's esophagus, a potential early event in the carcinogenic sequence for esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present study evaluated the associations among antioxidants, fruit and vegetable intake, and the risk of Barrett's esophagus (BE), a potential precursor to esophageal adenocarcinoma. METHODS: We conducted a case–control study within the Kaiser Permanente Northern California population. Incident BE cases (N = 296) were matched to persons with gastroesophageal reflux disease (GERD) (GERD controls N = 308) and to population controls (N = 309). Nutrient intake was measured using a validated 110-item food frequency questionnaire. The antioxidant results were stratified by dietary versus total intake of antioxidants. RESULTS: Comparing cases to population controls, dietary intake of vitamin C and beta-carotene were inversely associated with the risk of BE (4th vs 1st quartile, adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.26–0.90; OR 0.56, 95% CI 0.32–0.99, respectively), and the inverse association was strongest for vitamin E (OR 0.25, 95% CI 0.11–0.59). The inverse trends for antioxidant index (total and dietary) and fruit and vegetable intake were statistically significant, while most total intakes were not associated with reduced risk. The use of antioxidant supplements did not influence the risk of BE, and antioxidants and fruits and vegetables were inversely associated with a GERD diagnosis. CONCLUSION: Dietary antioxidants, fruits, and vegetables are inversely associated with the risk of BE, while no association was observed for supplement intake. Our results suggest that fruits and vegetables themselves or associated undetected confounders may influence early events in the carcinogenesis of esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Barrett’s esophagus is a strong risk factor for esophageal adenocarcinoma, but little is known about its associations with body mass index (BMI) or abdominal obesity. Methods: We conducted a case-control study within the Kaiser Permanente Northern California population. Persons with a new diagnosis of Barrett’s esophagus (cases) were matched to subjects with gastroesophageal reflux disease (GERD) without Barrett’s esophagus and to population controls. Subjects completed questionnaires and an anthropometric examination. Results: We interviewed 320 cases, 316 patients with GERD, and 317 controls. There was a general association between Barrett’s esophagus and a larger abdominal circumference (independent of BMI) compared with population controls (odds ratio, 2.24; 95% confidence interval, 1.21–4.15; circumference, >80 cm vs <80 cm). There was a possible risk plateau, with increased risk evident only at circumferences >80 cm and no significant trend for further increases in circumference. There was a trend for association compared with patients with GERD (test for trend, P = .03). There was no association between Barrett’s esophagus and BMI. Abdominal circumference was associated with GERD symptom severity (odds ratio, 1.86; 95% confidence interval, 1.03–3.38; risk of severe weekly GERD, per 10-cm circumference); adjustment for GERD partially attenuated the association between Barrett’s esophagus and circumference. Conclusions: Waist circumference, but not BMI, had some modest independent associations with the risk of Barrett’s esophagus. The findings provide partial support for the hypothesis that abdominal obesity contributes to GERD, which may in turn increase the risk of Barrett’s esophagus. [Copyright &y& Elsevier]

A correction to the article "BOB CAT: A Large-Scale Review and Delphi Consensus for Management of Barrett's Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia" that was published in the journal in 2015 is presented.

Background& Aims: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett''s esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E2 in patients with BE with no dysplasia or low-grade dysplasia. Methods: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE2 (the primary end point). Results: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE2 was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P = .02 vs arm A). Conclusions: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903. [Copyright &y& Elsevier]

Background & Aims: Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations. Methods: We performed a pooled analysis of 6 population-based studies within the Barrett''s and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model. Results: Compared with nonusers, individuals who have used NSAIDs had a statistically significant reduced risk of EAC (OR, 0.68; 95% CI, 0.56–0.83); they also appeared to have a reduced risk of EGJA (OR, 0.83; 95% CI, 0.66–1.03). Similar reductions in risk were observed among individuals who took aspirin or nonaspirin NSAIDs. The highest levels of frequency (daily or more frequently) and duration (≥10 years) of NSAID use were associated with an approximately 40% reduction in risk of EAC, with ORs of 0.56 (95% CI, 0.43–0.73; P trend < .001) and 0.63 (95% CI, 0.45–0.90; P trend = .04), respectively. Conclusions: Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, our pooled analysis suggests a possible role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction. [Copyright &y& Elsevier]

Abstract: Background: Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. Methods: The authors pooled data from 12 case–control studies from the Barrett''s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. Results: For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P <0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P =0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P <0.01). Conclusions: Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases. [Copyright &y& Elsevier]