Search

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]

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]

OBJECTIVES:Diabetes mellitus (DM) has been associated with an increased risk of colorectal cancer (CRC). The American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008 recommend that clinicians be aware of an increased CRC risk in patients with smoking and obesity, but do not highlight the increase in CRC risk in patients with DM. To provide an updated quantitative assessment of the association of DM with colon cancer (CC) and rectal cancer (RC), we conducted a meta-analysis of case-control and cohort studies. We also evaluated whether the association varied by sex, and assessed potential confounders including obesity, smoking, and exercise.METHODS:We identified studies by searching the EMBASE and MEDLINE databases (from inception through 31 December 2009) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias.RESULTS:DM was associated with an increased risk of CC (summary RR 1.38, 95% CI 1.26-1.51; n=14 studies) and RC (summary RR 1.20, 95% CI 1.09-1.31; n=12 studies). The association remained when we limited the meta-analysis to studies that either controlled for smoking and obesity, or for smoking, obesity, and physical exercise. DM was associated with an increased risk of CC for both men (summary RR 1.43, 95% CI 1.30-1.57; n=11 studies) and women (summary RR 1.35, 95% CI 1.14-1.53; n=10 studies). For RC, there was a significant association between DM and cancer risk for men (summary RR 1.22, 95% CI 1.07-1.40; n=8 studies), but not for women (summary RR 1.09, 95% CI=0.99-1.19; n=8 studies).CONCLUSIONS:These data suggest that DM is an independent risk factor for colon and rectal cancer. Although these findings are based on observational epidemiological studies that have inherent limitations due to diagnostic bias and confounding, subgroup analyses confirmed the consistency of our findings across study type and population. This information can inform risk models and specialty society CRC screening guidelines. [ABSTRACT FROM AUTHOR]

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]

OBJECTIVE: The incidence of esophageal adenocarcinoma has been increasing rapidly among many countries. Antioxidant intake is a potentially modifiable protective factor, although the results from individual studies are inconclusive. We conducted a systematic review and statistical synthesis of studies that evaluated the associations between vitamin C, vitamin E, or beta-carotene/vitamin A and the risk of esophageal adenocarcinoma or the adjacent gastric cardia (gastroesophageal junction) adenocarcinoma. METHODS: Studies were included if they reported (a) a measure of dietary antioxidant intake; (b) esophageal or cardia adenocarcinoma occurrence; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI), or sufficient data to permit their calculation. RESULTS: We identified 10 studies (1 cohort, 9 case-control; 1,057 esophageal and 644 cardia cases). Summary estimates stratified by cancer site suggested that higher intakes of vitamin C, beta-carotene/vitamin A, and vitamin E were inversely associated with the risk of esophageal adenocarcinoma (vitamin C, OR 0.49, 95% CI 0.39–0.62, Pheterogeneity= 0.10; beta-carotene, OR 0.46, 95% CI 0.36–0.59, Pheterogeneity= 0.82; vitamin E intake, OR 0.80, 95% CI 0.63–1.03, Pheterogeneity= 0.59). Beta-carotene intake was also inversely associated with the risk of cardia adenocarcinoma (OR 0.57, 95% CI 0.46–0.72, Pheterogeneity= 0.17). Dose effects were observed for most associations. CONCLUSIONS: Pooled results from observational studies suggest that antioxidant intake may be protective against esophageal adenocarcinoma; the data do not support a consistent association between antioxidant intake and the risk of cardia carcinoma. These findings suggest possible etiological differences between these two adjacent malignancies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Several large studies have shown a negative association between Helicobacter pylori ( H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux. METHODS: We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls). RESULTS: A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer ( H. pylori and body mass index [BMI] adjusted OR = 0.18 [CI 0.04–0.78]). This inverse association was seen only in overweight subjects (BMI ≥ 25, P value for interaction = 0.09). The effects of H. pylori and ghrelin were independent. CONCLUSION: Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common cause of morbidity and health-care utilization in many countries. Obesity is a potentially modifiable risk factor, but existing studies have conflicting results, possibly due to differences in study design, definitions, or populations. METHODS: We performed a systematic review and meta-analysis of studies identified using MEDLINE, the Web of Science electronic database, manual literature review, and a review of expert bibliographies. Studies were included if they: (1) evaluated obesity, body mass index (BMI), or another measure of body size; (2) included data on reflux symptoms, esophagitis, or a GERD-related hospitalization; and (3) reported a relative risk or odds ratio (OR) with confidence intervals or provided sufficient data to permit their calculation. RESULTS: We identified 20 studies that included 18,346 patients with GERD. Studies from the United States demonstrated an association between increasing BMI and the presence of GERD (95% confidence interval [CI]= 1.36–1.80, overweight, OR = 1.57, P value homogeneity = 0.51, 95% CI = 1.89–2.45, obese, OR = 2.15, P= 0.10). Studies from Europe provided heterogeneous results despite stratification for several factors; individual studies demonstrated both positive associations and no association. CONCLUSIONS: This analysis demonstrates a positive association between increasing BMI and the presence of GERD within the United States; this relationship became apparent only after stratification by country and level of BMI. These results support the evaluation of weight reduction as a potential therapy for GERD. Further studies are needed to evaluate potential mechanisms and any differences in this relationship among different study populations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Medications that may increase gastroesophageal reflux could be risk factors for esophageal adenocarcinoma; however, epidemiologic studies present conflicting results. We evaluated patients with a high-risk condition, Barrett's esophagus, to identify risk factors that may act early in the carcinogenic process. METHODS: We conducted a nested case-control study within a large integrated health-services organization. Electronic databases were used to identify incident diagnoses of Barrett's esophagus (cases); two controls were matched to each case. Electronic databases provided information on the use of medications that may induce reflux (nitrates, calcium channel blockers, xanthines, benzodiazepines, and beta agonists) and potential confounders. A supplemental mailed questionnaire evaluated additional potential confounders. RESULTS: We identified 421 cases and selected 842 controls. The association between any medication use and a Barrett's esophagus diagnosis was modified by age; an increased risk was observed only among subjects <70 yr of age (adjusted odds ratio [OR]= 2.6; 95% confidence interval [CI] 1.5–4.6). A Barrett's esophagus diagnosis was associated with asthma medication use (OR 5.8; 95% CI 2.2, 14.9), but not with the other medications studied. Subgroup analyses suggested that medication use was not independently associated with reflux symptoms and that adjustment for asthma symptoms substantially reduced the association between medication use and a Barrett's esophagus diagnosis. CONCLUSION: The use of medications that may induce reflux was associated with a Barrett's esophagus diagnosis among younger persons. This association was only observed with asthma medications; the analyses suggested the possibility of confounding by indication, whereby reflux may cause both asthma and Barrett's esophagus. [ABSTRACT FROM AUTHOR]

OBJECTIVE: No prior studies have contrasted esophageal and gastric cardia carcinoma incidence rates among multiple ethnicities. We evaluated whether these adjacent cancers differ; such detailed demographic analyses would inform risk factor, screening, and intervention studies.METHODS: We contrasted incidence rates and temporal trends from the Surveillance, Epidemiology, and End Results (SEER) cancer registry data between 1992 and 1998 for five groups: non-Hispanic whites (Caucasians), white Hispanics (Hispanics), blacks, Asians/Pacific Islanders (Asians/PI), and Native Americans (NA).RESULTS: Caucasian males' esophageal adenocarcinoma rate (4.2 per 100,000 population/yr) was double that of Hispanics and four-fold higher than those of blacks, Asians/PI, and NA (p<0.01). Female rates were much lower than male rates for all ethnicities. Similar to esophageal adenocarcinoma, cardia adenocarcinoma rates were highest in Caucasian males (3.4 per 100,000 population/yr); however, the ethnic differences were much less and female rates were comparable for all almost all ethnicities (range 0.6–0.7 per 100,000 population/yr) except NA. Esophageal adenocarcinoma incidence rates increased significantly only in Caucasians (males 5.6%/yr, females 9%/yr;p<0.05) and cardia cancer rates did not increase for any ethnicity during this period. In contrast, esophageal squamous cell carcinoma incidence rates were highest in blacks (8.8 per 100,000 population/yr) and Asians/PI (3.9 per 100,000 population/yr) and rates were stable or declined for all ethnicities between 1992 and 1998.CONCLUSIONS: Esophageal and cardia carcinoma incidence rates vary much more markedly by ethnicity and gender than previously reported and the two sites differ from each other. Current putative risk factors do not adequately explain these large differences. These data have implications for risk factor, screening, and intervention studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Upper gastrointestinal tract (UGI) symptoms are frequent in patients infected with the human immuno-deficiency virus (HIV), but little published information exists about their characteristics or methods of evaluation. We evaluated the prevalence of nonesophageal UGI symptoms in a referral population, the utility of esophagogastroduodenoscopy (EGD) for diagnosis, and clinical predictors of abnormal endoscopic findings in patients infected with HIV. METHODS: All HIV-infected patients referred to the outpatient gastroenterology clinics were prospectively evaluated using recognized symptom questionnaires. EGD indications, results, and the patients' self-reported symptom scores were compared. HIV-infected patients undergoing EGD were compared with HIV-infected patients not receiving an EGD and with symptomatic non-HIV-infected patients undergoing EGD. RESULTS: A total of 201 patients completed 280 questionnaires. Among 93 patients who underwent endoscopy, severe symptoms occurring at least several times per week included: anorexia (70%), upper abdominal pain (34%), vomiting (32%), or a recent weight loss of approximately 15 lb (31%). Patients undergoing EGD had more frequent/severe symptoms, but did not have differences in overall well-being or mean GI symptom score. The frequency of substantial and treatable endoscopic findings among patients infected with HIV was comparable to that found in the non-HIV-infected control group. There were no independent symptoms predicting substantial or treatable disease on EGD. CONCLUSIONS: We conclude that: 1) upper gastrointestinal symptoms are common in HIV-infected patients referred for GI consultation; 2) symptomatic HIV patients have a high prevalence of both treatable and untreatable upper GI pathologies; 3) and physicians use symptom frequency and severity to select patients for EGD, but these factors correlate poorly with abnormalities on EGD. Given this discrepancy, longitudinal study is needed to determine whether treating endoscopic abnormalities improves UGI symptoms. [ABSTRACT FROM AUTHOR]

Objective: Endoscopy allows accurate risk stratification of patients presenting with gastrointestinal bleeding; frequently, however, it is not immediately available. Initial management and triage of patients thus depends on nonendoscopic information. We sought to risk stratify patients with upper gastrointestinal bleeding using variables available on initial presentation (i.e., before endoscopy). Methods: A retrospective observational study was performed using data from 335 admissions with an initial diagnosis of upper gastrointestinal hemorrhage. All patients underwent endoscopy and were evaluated for an adverse outcome during their hospitalization. An adverse outcome was defined as death, the need for any operation, recurrent hematemesis, recurrent melena after initial clearing, or a hematocrit falling despite transfusion. Results: Univariate analysis identified 17 distinct variables associated (p < 0.05) with an adverse outcome. A stepwise logistic regression identified five variables as independent predictors (p < 0.05) of an adverse outcome: an initial hematocrit <30%, initial systolic blood pressure < 100 mm Hg, red blood in the nasogastric lavage, history of cirrhosis or ascites on exam, and a history of vomiting red blood. We derived a decision rule based on patients having 0-5 of these independent predictors. This decision rule allowed identification of a large patient population with a <10% chance of an adverse outcome. Conclusion: Risk stratification is possible from information available at the time of initial presentation. If confirmed in other populations, these predictors can be used to identify patients who require a less intensive level of care. [ABSTRACT FROM AUTHOR]

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.