Abeer Alsarraj

Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett's oesophagus: a case-control study

Objective Abdominal obesity has been associated with increased risk of Barretts oesophagus (BE) but the underlying mechanism is unclear. We examined the association between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the risk of BE. Design A case-control study among eligible patients scheduled for elective oesophagastroduodenoscopy (EGD) and in a sample of patients eligible for screening colonoscopy recruited at the primary care clinic. All cases with definitive BE and a random sample of controls without BE were invited to undergo standardised mid-abdomen non-contrast computerised axial tomography images, which were analysed by semiautomated image segmentation software. The effect of VAT and SAT surface areas and their ratio (VAT to SAT) on BE were analysed in logistic regression models. Results A total of 173 BE cases, 343 colonoscopy controls and 172 endoscopy controls underwent study EGD and CT scan. Participants with BE were more than twice as likely to be in the highest tertile of VAT to SAT ratio (OR: 2.42 (1.51 to 3.88) and adjusted OR 1.47 (0.88 to 2.45)) than colonoscopy controls, especially for those long (≥3 cm) segment BE (3.42 (1.67 to 7.01) and adjusted OR 1.93 (0.92 to 4.09)) and for white men (adjusted OR 2.12 (1.15 to 3.90)). Adjustment for gastroesophageal reflux disease (GERD) symptoms and proton pump inhibitors (PPI) use attenuated this association, but there was a significant increase in BE risk even in the absence of GERD or PPI use. Conclusions Large amount of visceral abdominal fat relative to subcutaneous fat is associated with a significant increase in the risk of BE. GERD may mediate some but not all of this association.

Antibiotic Resistance of Helicobacter pylori Among Male United States Veterans

BACKGROUND & AIMS The most recent information published on resistance of Helicobacter pylori to antibiotics in a large population in the United States is more than 10 years old. We assessed the susceptibility of H pylori to antibiotics among patients in a large metropolitan hospital, as well as demographic, clinical, and lifestyle factors associated with antimicrobial resistance. METHODS We performed a cross-sectional study of a random sample of 656 patients (90.2% men) from a cohort of 1559 undergoing esophagogastroduodenoscopy with collection of gastric biopsies from 2009 through 2013 at the Houston Veterans Affairs Medical Center. We performed culture analyses of gastric tissues to detect H pylori. The minimum inhibitory concentrations of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were determined by the Epsilometer test. Logistic regression analysis was performed to estimate the association between risk factors and antimicrobial resistance. RESULTS Biopsies from 135 subjects (20.6%) tested positive for H pylori; 128 of these were from men (94.8%). Only 65 strains were susceptible to all 5 antibiotics. The prevalence of resistance to levofloxacin was 31.3% (95% confidence interval [CI], 23.1%-39.4%), to metronidazole it was 20.3% (95% CI, 13.2%-27.4%), to clarithromycin it was 16.4% (95% CI, 9.9%-22.9%), and to tetracycline it was 0.8% (95% CI, 0.0%-2.3%). No isolate was resistant to amoxicillin. Clarithromycin resistance increased from 9.1% in 2009-2010 to 24.2% in 2011-2013. In multivariate analysis, prior treatment of H pylori infection and use of fluoroquinolones were significantly associated with clarithromycin and levofloxacin resistance, respectively. CONCLUSIONS H pylori resistance to clarithromycin increased between 2009 and 2013; resistance to metronidazole remains high in infected men in the United States. The high frequency of resistance to levofloxacin is a new and concerning finding.

Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated With an Increased Risk of Barrett's Esophagus in White Men

BACKGROUND & AIMS Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD) and also might contribute to the development of Barretts esophagus (BE), although results are inconsistent. We examined the effects of waist-to-hip ratio (WHR) and body mass index (BMI) on the risk of BE and investigated whether race, GERD symptoms, or hiatus hernia were involved. METHODS We conducted a case-control study using data from eligible patients who underwent elective esophagogastroduodenoscopy; 237 patients had BE and the other 1021 patients served as endoscopy controls. We also analyzed data and tissue samples from enrolled patients who were eligible for screening colonoscopies at a primary care clinic (colonoscopy controls, n = 479). All patients underwent esophagogastroduodenoscopy, completed a survey, and had anthropometric measurements taken. WHR was categorized as high if it was 0.9 or greater for men or 0.85 or greater for women. Data were analyzed with logistic regression. RESULTS There was no association between BMI and BE. However, more patients with BE had a high WHR (92.4%) than endoscopy controls (79.5%) or colonoscopy controls (84.6%) (P < .001 and P = .008, respectively). In adjusted analysis, patients with BE were 2-fold more likely to have a high WHR than endoscopy controls (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.1-3.5), this association was stronger for patients with long-segment BE (OR, 2.81; 95% CI, 1.0-7.9). A high WHR was associated significantly with BE only in whites (OR, 2.5; 95% CI, 1.2-5.4), but not in blacks or Hispanics. GERD symptoms, hiatus hernia, or gastroesophageal valve flap grade could not account for the association. CONCLUSIONS High WHR, but not BMI, is associated with a significant increase in the risk of BE, especially long-segment BE and in whites. The association is not caused by GERD symptoms or hiatus hernia.

Circulating Inflammatory Cytokines and Adipokines Are Associated With Increased Risk of Barrett's Esophagus: A Case–Control Study

BACKGROUND & AIMS Obesity is associated with Barretts esophagus (BE) and with changes in circulating levels of adipokines (leptin and adiponectin) and cytokines. Although studies have reported that adipokines and inflammatory cytokines are necessary for the development of BE, their role is controversial. METHODS We performed a case-control study; cases (n = 141) were patients who underwent esophagogastroduodenoscopy and were found to have BE, which was based on endoscopy and histology, and controls (n = 139) were primary care patients eligible for screening colonoscopies who agreed to undergo esophagogastroduodenoscopy. We examined the association between BE and circulating levels of adipokines and cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, and IL-12p70; tumor necrosis factor-α; and interferon-γ). Cases and controls were compared by calculating odds ratios (ORs) and 95% confidence intervals (CIs) and using unadjusted and multiple logistic regression, adjusting for age, sex, race, waist-hip ratio, use of proton pump inhibitors and nonsteroidal anti-inflammatory drugs, and Helicobacter pylori infection. RESULTS The adjusted ORs for BE were 2.62 (95% CI, 1.0-6.8), 5.18 (95% CI, 1.7-15.7), and 8.02 (95% CI, 2.79-23.07) for the highest quintile vs the lowest quintile of levels of IL-12p70, IL-8, and leptin, respectively, but the OR was not significant for IL-6 (2.39; 95% CI, 0.84-6.79). The adjusted OR for BE was 0.14 for highest quintile of IL-10 compared with lowest quintile (95% CI, 0.05-0.35) and 0.03 for IL-1β ≥ median vs none detected (95% CI, 0.006-0.13). Higher levels of IL-8 and leptin and lower levels of IL-10 and IL-1β were associated with the presence of long-segment (≥3 cm) and short-segment BE. There were no differences between cases and controls in levels of interferon-γ, tumor necrosis factor-α, adiponectin, or insulin. CONCLUSIONS BE is associated with circulating inflammatory cytokines and leptin and low levels of anti-inflammatory cytokines. These findings could partly explain the effect of obesity on BE.

Helicobacter pylori-negative gastritis: prevalence and risk factors.

OBJECTIVES:Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis.METHODS:Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire.RESULTS:Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P=0.06).CONCLUSIONS:We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known.

Association between Helicobacter pylori and Barrett's esophagus: a case-control study.

OBJECTIVES:The estimated association between Helicobacter pylori and Barretts esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association.METHODS:We conducted a case–control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders.RESULTS:We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35–0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63).CONCLUSIONS:The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week).

Fat mass by bioelectrical impedance analysis is not associated with increased risk of Barrett esophagus.

Goal: To evaluate whether the association between obesity and Barrett esophagus (BE) is due to total body fatness, abdominal obesity, or both. Background: BE risk seems to be more strongly related to central obesity than total obesity. However, no studies have investigated the association between total obesity and BE using direct measures of total body fatness. Study: We conducted a case-control study among patients scheduled for elective esophagogastroduodenoscopy, and a sample of patients eligible for screening colonoscopy recruited from primary care clinics. BE cases were patients with specialized intestinal metaplasia, whereas controls had no endoscopic or histopathologic BE. All patients underwent a study esophagogastroduodenoscopy and had body measurements taken. Fat mass and fat-free mass were estimated from bioelectrical impedance analysis (BIA). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression. Results: There were 70 BE cases, 229 endoscopy controls, and 118 primary care controls. BMI and BIA-derived fat mass were highly correlated; however, we found no association between BMI, fat mass, and BE (vs. all controls: BMI, OR/1 SD=1.01; 95% CI, 0.76-1.34; fat mass, OR=1.02; 95% CI, 0.77-1.36). Waist-to-hip ratio was significantly associated with increased BE risk (vs. all controls: OR/1 SD=1.45; 95% CI, 1.03-2.04). We found similar results when we analyzed the control groups separately. Conclusion: Waist-to-hip ratio, but not fat mass or BMI, was associated with increased BE risk. This study provides strong evidence that BE is related to body size and composition through central adiposity and not through total body fatness.

Human papillomavirus and the risk of Barrett’s esophagus

Human papillomavirus (HPV) is strongly associated with squamous esophageal cancer. The potential role of HPV in Barretts esophagus (BE) has been examined but remains unclear. The aim of the study was to determine the prevalence of HPV in esophageal and gastric tissues obtained from patients with and without BE. We designed a cross-sectional study was conducted with prospective enrollment of eligible patients scheduled for esophagogastroduodenoscopy (EGD). All participants had biopsies of endoscopic BE, squamous-lined esophagus, and stomach. Immunohistochemistry (IHC) on formalin-fixed and paraffin-embedded tissue was conducted using monoclonal antibodies. Polymerase chain reaction (PCR) for HPV was performed on DNA extracted from esophageal biopsies snapped frozen within 30 minutes after endoscopic capture. The Roche HPV Linear Array Assay with PGMY primers that has high sensitivity for detecting 37 types of HPV was used. A total of 127 subjects were included: 39 with definitive BE had IHC done on samples from non-dysplastic BE, squamous esophagus, gastric cardia, and gastric body; and 88 control patients without BE had IHC done on squamous esophageal samples, gastric cardia, and gastric body. HPV was not detected in any of the samples in either group. For confirmation, HPV DNA PCR was performed on randomly selected samples from 66 patients (both esophagus and BE from 13 patients with BE, and 53 esophagus from patients without BE); no sample had HPV DNA detected via PCR in the presence of adequate quality control. HPV infection does not play a role in the formation of non-dysplastic Barretts esophagus in men in the United States.

Dietary consumption of meat, fat, animal products and advanced glycation end-products and the risk of Barrett's oesophagus

Advanced glycation end‐products (AGEs) are found in high quantity in high‐fat foods and meat cooked at high temperature. AGEs have been shown to contribute to chronic inflammation and oxidative stress in humans.

Oral Bisphosphonates and the Risk of Barrett's Esophagus: Case–Control Analysis of US Veterans

OBJECTIVES:This study examined Barretts esophagus (BE) risk factors in veterans to determine the association between risk of BE and use of oral bisphosphonates.METHODS:We conducted a case–control study among eligible patients scheduled for an elective esophagogastroduodenoscopy (EGD) and a sample of patients eligible for screening colonoscopy recruited from primary care clinics from a single VA Medical Center. Cases with definitive BE were compared with controls; all underwent study EGD. Use of oral bisphosphonates was ascertained by reviewing filled prescriptions in electronic pharmacy records. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs), using multivariate logistic regression modeling while adjusting for sex, age, race, proton-pump inhibitor use, hiatal hernia, waist-to-hip ratio, Helicobacter pylori infection, and gastroesophageal reflux disorder (GERD) symptoms.RESULTS:There were 285 BE cases, 1,122 endoscopy controls, and 496 primary care controls. Alendronate and risedronate were the only oral bisphosphonates prescribed. The proportion of BE cases with filled prescription of oral bisphosphonates (4.6%) was greater than in endoscopy controls (1.6%) or primary care controls (2.9%). In the adjusted analysis, oral bisphosphonate use was significantly associated with BE risk (OR=2.33; 95% CI: 1.11–4.88) compared with the combined control groups. This association remained significant when BE cases were compared with endoscopy controls only (OR=2.74; 95% CI: 1.28–5.87) but was attenuated when compared with primary care controls only (OR=2.60; 95% CI: 0.99–6.84). The association was observed in patients with GERD symptoms (OR=3.29; 95% CI: 1.36–7.97) but not in those without GERD symptoms.CONCLUSION:Oral bisphosphonate use may increase the risk for BE, especially among patients with GERD.