No Barrett's-No Cancer: A Proposed New Paradigm for Prevention of Esophageal Adenocarcinoma.

Esophageal adenocarcinoma is inflammation-associated cancer with a recognizable preneoplastic stage, Barrett's. Barrett's describes the metaplastic transformation of esophageal squamous mucosa into columnar epithelium that typically results secondary to mucosal damage caused by acidic gastroduodenal reflux. Continued acid reflux may then result in mucosal inflammation which results in progressive inflammation-induced genetic instability that may eventuate in esophageal adenocarcinoma. Barrett's is the only recognized precursor lesion to esophageal carcinoma. Barrett's mucosa is unique among preneoplastic lesions; ablation therapy results in restitution of a squamous epithelium reducing or eliminating accumulated genetic instabilities and resetting the biological clock progressing toward invasive cancer. However, recurrence of Barrett's after ablation is common. We propose that both Barrett's and recurrence of Barrett's after ablation can be prevented and discuss how current approaches to therapy for gastroesophageal reflux disease, for Barrett's screening, chemoprevention, and ablation therapy all might be reconsidered. We propose (1) improved approaches to Barrett's prevention, (2) universal Barrett's screening by linking Barrett's screening to colon cancer screening, (3) ablation of all Barrett's mucosa along with (4) acid-suppressive-antireflux therapy tailored to prevent development of Barrett's or the recurrence of Barrett's after ablation therapy. We propose that ultimately, treatment decisions for gastroesophageal reflux disease and prevention of Barrett's and esophageal carcinoma should be based on assessing and maintaining esophageal mucosal integrity. This will require development and verification of specific measurements that reliably correlate with prevention of Barrett's. We outline the new research and technical advances needed to cost-effectively achieve these goals.

Erosive Esophagitis Portends a Benign Clinical Course in the Majority of Patients.

INTRODUCTION: Indefinite proton pump inhibitor (PPI) therapy and endoscopic evaluation for Barrett's esophagus is recommended for erosive esophagitis (EE). However, the clinical course of EE remains undefined. METHODS: Adults with EE on esophagogastroduodenoscopy (EGD) were identified at Mayo Clinic Rochester between January 2003 and September 2005. Patients with repeat EGD performed after index endoscopy were included. Patients with a history of upper gastrointestinal surgery, esophageal cancer, achalasia, or Barrett's on initial EGD were excluded. RESULTS: Of 219 patients identified, 98 had LA grade A, 72 LA grade B, and 49 LA grade C esophagitis. Persistent EE was found in 27% on repeat endoscopy. No patients progressed to more severe grades of esophagitis. While discontinuation of PPI was associated with persistent esophagitis, long-term healing of esophagitis occurred in the majority of patients despite discontinuation of PPI. Grade A or B esophagitis and the absence of hiatal hernia were also independent predictors of esophagitis healing on multivariate analysis. The rate of Barrett's esophagus was similar among patients with LA grade A/B and C esophagitis on initial EGD (5% vs. 14%, p = 0.6). CONCLUSION: The majority of patients with EE demonstrated healing at follow-up endoscopy regardless of continued PPI use. A small proportion developed Barrett's esophagus, including those with LA grade A and B esophagitis, highlighting a potential role for repeat endoscopy in all grades of EE. A more conservative long-term PPI strategy may be reasonable in patients with LA grade A or B esophagitis in the absence of hiatal hernia.

The Influence of Antireflux Surgery on Esophageal Cancer Risk in England: National Population-based Cohort Study.

OBJECTIVE: To evaluate how antireflux surgery influences the risk of esophageal cancer in patients with gastroesophageal reflux disease (GERD) and Barrett esophagus. BACKGROUND: GERD is a major risk factor for esophageal adenocarcinoma, and the United Kingdom has the highest incidence of esophageal adenocarcinoma globally. METHODS: Hospital Episode Statistics database was used to identify all patients in England aged over 18 years diagnosed with GERD with or without Barrett Esophagus from 2000 to 2012, with antireflux surgery being the exposure investigated. The Clinical Practice Research Datalink (CPRD) was used to provide a sensitivity analysis comparing proton pump inhibitor therapy and antireflux surgery. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards model with inverse probability weights based on the probability of having surgery to adjust for selection bias and confounding factors. RESULTS: (i) Hospital Episode Statistics analysis; among 838,755 included patients with GERD and 28,372 with Barrett esophagus, 22,231 and 737 underwent antireflux surgery, respectively. In GERD patients, antireflux surgery reduced the risk of esophageal cancer (HR = 0.64; 95% CI 0.52-0.78). In Barrett esophagus patients, the corresponding HR was (HR = 0.47; 95% CI 0.12-1.90).(ii) CPRD analysis; antireflux surgery was associated with decreased point estimates of esophageal adenocarcinoma in patients with GERD (0% vs. 0.2%; P = 0.16) and Barrett esophagus (HR = 0.75; 95% CI 0.21-2.63), but these were not statistically significant. CONCLUSION: Antireflux surgery may be associated with a reduced risk of esophageal cancer risk, however it remains primarily an operation for symptomatic relief.

Melatonin in Prevention of the Sequence from Reflux Esophagitis to Barrett's Esophagus and Esophageal Adenocarcinoma: Experimental and Clinical Perspectives.

Melatonin is a tryptophan-derived molecule with pleiotropic activities which is produced in all living organisms. This "sleep" hormone is a free radical scavenger, which activates several anti-oxidative enzymes and mechanisms. Melatonin, a highly lipophilic hormone, can reach body target cells rapidly, acting as the circadian signal to alter numerous physiological functions in the body. This indoleamine can protect the organs against a variety of damaging agents via multiple signaling. This review focused on the role played by melatonin in the mechanism of esophagoprotection, starting with its short-term protection against acute reflux esophagitis and then investigating the long-term prevention of chronic inflammation that leads to gastroesophageal reflux disease (GERD) and Barrett's esophagus. Since both of these condition are also identified as major risk factors for esophageal carcinoma, we provide some experimental and clinical evidence that supplementation therapy with melatonin could be useful in esophageal injury by protecting various animal models and patients with GERD from erosions, Barrett's esophagus and neoplasia. The physiological aspects of the synthesis and release of this indoleamine in the gut, including its release into portal circulation and liver uptake is examined. The beneficial influence of melatonin in preventing esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals as well as the usefulness of melatonin and its precursor, L-tryptophan in prophylactic and supplementary therapy against esophageal disorders in humans, are also discussed.

Recurrence of Barrett's Esophagus is Rare Following Endoscopic Eradication Therapy Coupled With Effective Reflux Control.

OBJECTIVES: Recent data suggest that effective control of gastroesophageal reflux improves outcomes associated with endoscopic eradication therapy (EET) for Barrett's esophagus (BE). However, the impact of reflux control on preventing recurrent intestinal metaplasia and/or dysplasia is unclear. The aims of the study were: (a) to determine the effectiveness and durability of EET under a structured reflux management protocol and (b) to determine the impact of optimizing anti-reflux therapy on achieving complete eradication of intestinal metaplasia (CE-IM). METHODS: Consecutive BE patients referred for EET were enrolled and managed with a standardized reflux management protocol including twice-daily PPI therapy during eradication. Primary outcomes were rates of CE-IM and IM or dysplasia recurrence. RESULTS: Out of 221 patients enrolled (46.0% with high-grade dysplasia/intramucosal carcinoma, 34.0% with low-grade dysplasia, and 20.0% with non-dysplastic BE) an overall CE-IM of 93% was achieved within 11.6±10.2 months. Forty-eight patients did not achieve CE-IM in 3 sessions. After modification of their reflux management, 45 (93.7%) achieved CE-IM in a mean of 1.1 RFA sessions. Recurrence occurred in 13 patients (IM in 10(4.8%), dysplasia in 3 (1.5%)) during a mean follow-up of 44±18.5 months. The only significant predictor of recurrence was the presence of a hiatal hernia. Recurrence of IM was significantly lower than historical controls (10.9 vs. 4.8%, P=0.04). CONCLUSIONS: The current study highlights the importance of reflux control in patients with BE undergoing EET. In this setting, EET has long-term durability with low recurrence rates providing early evidence for extending endoscopic surveillance intervals after EET.

Does physical activity protect against the development of gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma? A review of the literature with a meta-analysis.

Physical activity affects the functioning of the gastrointestinal system through both local and systemic effects and may play an important role in reducing the risk of esophageal adenocarcinoma. This review assesses the biological mechanisms and epidemiological evidence for the relationship between physical activity and the development of esophageal adenocarcinoma and its precursor diseases: gastroesophageal reflux disease (GORD) and Barrett's esophagus. A search of PubMed, Medline, Embase, and CINAHL was conducted from their inceptions to 25th March 2017 for analytical studies that examined associations between recreational and/or occupational levels of physical activity and the risk of GORD, Barrett's esophagus, and esophageal adenocarcinoma. Where appropriate, a meta-analysis of effects was undertaken. Seven studies were included (2 cohort, 5 case control). For GORD, there were three case-control studies with 10 200 cases among 78 034 participants, with a pooled estimated OR of 0.67 (95% CI 0.57-0.78) for high versus low levels of recreational physical activity. In Barrett's esophagus, there was a single case-control study, which reported no association, OR 1.19 (95% CI 0.82-1.73). For esophageal adenocarcinoma, there were three studies (two prospective cohort, one case control) with 666 cases among 910 376 participants. The largest cohort study reported an inverse association for high versus low levels of recreational physical activity, RR 0.68, 95% CI 0.48-0.96. The remaining two studies reported no associations with either occupational or combined recreational and occupational activity. Heterogeneity in the measurement of exposure (recreational, occupational, and both) made a pooled estimate for esophageal adenocarcinoma inappropriate. Although limited, there is some evidence that higher levels of recreational physical activity may reduce the risk of both GORD and esophageal adenocarcinoma, but further large cohort studies examining the type, intensity and duration of activities that may be beneficial are needed.

Proceedings from an international conference on ablation therapy for Barrett's mucosa: Brittany, France, 31 August - 2 September 1997.

The increasing incidence of adenocarcinoma of the lower esophagus and cardia arising in Barrett's metaplastic epithelium continues to be of great concern because medical and surgical efforts to reverse the process have been disappointing. A potential answer to the problem is removal of the metaplastic epithelium. Modern technology has introduced physical and chemical modalities which facilitate ablation of the neo-epithelium endoscopically. These techniques have been used in several centers, and preliminary results are encouraging. This report summarizes the proceedings of an international symposium on ablative therapy held in Brittany, France in August 1997.Twenty-eight speakers contributed to the talks on the pathology, pathogenesis, current therapy experimental studies and clinical experience of ablation of Barrett's esophagus.

Dietary magnesium, calcium:magnesium ratio and risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma: a population-based case-control study.

Evidence suggests a role of Mg and the ratio of Ca:Mg intakes in the prevention of colonic carcinogenesis. The association between these nutrients and oesophageal adenocarcinoma - a tumour with increasing incidence in developed countries and poor survival rates - has yet to be explored. The aim of this investigation was to explore the association between Mg intake and related nutrients and risk of oesophageal adenocarcinoma and its precursor conditions, Barrett's oesophagus and reflux oesophagitis. This analysis included cases of oesophageal adenocarcinoma (n 218), Barrett's oesophagus (n 212), reflux oesophagitis (n 208) and population-based controls (n 252) recruited between 2002 and 2005 throughout the island of Ireland. All the subjects completed a 101-item FFQ. Unconditional logistic regression analysis was applied to determine odds of disease according to dietary intakes of Mg, Ca and Ca:Mg ratio. After adjustment for potential confounders, individuals consuming the highest amounts of Mg from foods had significant reductions in the odds of reflux oesophagitis (OR 0·31; 95 % CI 0·11, 0·87) and Barrett's oesophagus (OR 0·29; 95 % CI 0·12, 0·71) compared with individuals consuming the lowest amounts of Mg. The protective effect of Mg was more apparent in the context of a low Ca:Mg intake ratio. No significant associations were observed for Mg intake and oesophageal adenocarcinoma risk (OR 0·77; 95 % CI 0·30, 1·99 comparing the highest and the lowest tertiles of consumption). In conclusion, dietary Mg intakes were inversely associated with reflux oesophagitis and Barrett's oesophagus risk in this Irish population.

Adherence to WCRF/AICR lifestyle recommendations for cancer prevention and the risk of Barrett's esophagus onset and evolution to esophageal adenocarcinoma: results from a pilot study in a high-risk population.

PURPOSE: While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett's esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle. METHODS: Established risk factors for BE and EAC development and adherence to WCRF guidelines were assessed in 107 consecutive patients undergoing an upper gastrointestinal endoscopy for symptoms suggesting gastroesophageal reflux (GERD) and a suspected diagnosis of BE/dysplasia on BE. Patients were divided according to histology: those with GERD without metaplasia, with non-dysplastic BE, with low-grade dysplasia, with high-grade dysplasia or with early EAC. The four groups were expressed as an ordered categorical variable of disease progression. An ordered logit model was estimated to identify the independent predictors of disease progression. RESULTS: Adherence to WCRF guidelines was identified as independent protective factor (OR 0.51, 95 % CI 0.37-0.67) of disease progression. Disease progression was associated with reduced adherence to guidelines on physical activity (from 48.2 to 5.3 %, p = 0.001), sedentary habits (from 33.3 to 0 %, p = 0.03), fruit consumption (from 37.0 to 5.6 %, p = 0.02) and processed meat consumption (from 51.9 to 10.5 %, p = 0.002). CONCLUSION: Adherence to WCRF guidelines has a protective factor in BE onset and its evolution to EAC.

Reduced Risk of Barrett's Esophagus in Statin Users: Case-Control Study and Meta-Analysis.

BACKGROUND: Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett's esophagus. AIM: The purpose of this study was to examine the association between statin use and the presence of Barrett's esophagus in patients having their first gastroscopy. METHODS: We have performed a case-control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett's esophagus. Male Barrett's cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case-control studies. RESULTS: Regular statin use was associated with a significantly lower incidence of Barrett's esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37-0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21-0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett's was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett's, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett's esophagus [pooled adjusted OR 0.63 (95 % CI 0.51-0.77)]. CONCLUSIONS: Statin use is associated with a reduced incidence of a new diagnosis of Barrett's esophagus.

Rat Reflux Model of Esophageal Cancer and Its Implication in Human Disease.

OBJECTIVES: The epidemiologic shift in esophageal cancer from squamous cell carcinoma to esophageal adenocarcinoma coincided with popularization of proton pump inhibitors and has focused attention on gastroesophageal reflux disease as a causative factor in this shift. The aim of this study is to review the literature on the rat reflux model in an effort to elucidate this phenomenon. METHODS: An extensive online literature review (PubMed) was carried out to identify all seminal contributions to the study of esophageal adenocarcinoma using the rat reflux model. RESULTS: The rat reflux model is a validated reproducible model for the development of Barrett's esophagus and esophageal adenocarcinoma. Esophageal reflux of an admixture of gastric acid and duodenal juice induces Barrett's esophagus followed by adenocarcinoma. A high-pH environment created by surgical gastrectomy or proton pump inhibitor therapy in combination with a high-fat diet seems to potentiate the development of Barrett's esophagus and adenocarcinoma. Early surgical intervention to prevent reflux reduces the progression toward esophageal adenocarcinoma. Anti-inflammatory, antioxidant, and nitrate-trapping agents reduce the incidence of tumorigenesis. CONCLUSIONS: As in the rat so also in humans, reflux of an admixture of gastric acid and duodenal juice in a high-pH environment induces the development of Barrett's esophagus followed by esophageal adenocarcinoma. This has led to the hypothesis that to prevent Barrett's esophagus and subsequent esophageal adenocarcinoma in humans, the reflux of an admixture of acid and bile must be controlled before the development of Barrett's esophagus by methods other than acid-suppression therapy.

Statin use is associated with a decreased risk of Barrett's esophagus.

BACKGROUND & AIMS: Statins have been associated with a reduced risk of esophageal adenocarcinoma, but little is known about their effect on development of Barrett's esophagus. We evaluated the association between statins and risk of Barrett's esophagus. METHODS: We conducted a case-control study among eligible patients scheduled for elective esophagogastroduodenoscopy and patients eligible for screening colonoscopy, recruited from primary care clinics at a Veterans Affairs center. We compared 303 patients with Barrett's esophagus with 2 separate sex-matched control groups: 606 elective endoscopy controls and 303 primary care controls without Barrett's esophagus. Use of statins and other lipid-lowering medications was ascertained by reviewing filled prescriptions in electronic pharmacy records during a 10-year period before the Barrett's esophagus diagnosis date for patients and study endoscopy date for controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) using conditional multivariable logistic-regression models among 276 patients and 828 controls further matched on age. RESULTS: A smaller proportion of Barrett's esophagus patients filled statin prescriptions (57.4%) than endoscopy controls (64.9%; P = .029) or primary care controls (71.3%; P < .001). Controls had longer durations of statin prescriptions filled than patients (28.6 vs 22.1 months; P = .001). Statin use was associated with a significantly lower risk of Barrett's esophagus (adjusted OR = 0.57; 95% CI: 0.38-0.87) compared with the combined control groups. The risk of Barrett's esophagus was especially lower with statin use among obese patients (OR = 0.26; 95% CI: 0.09-0.71), as was the risk for Barrett's esophagus segments ≥ 3 cm (OR = 0.13; 95% CI: 0.06-0.30). We found no significant association between Barrett's esophagus and nonstatin lipid-lowering medications (P = .452). CONCLUSIONS: In a case-control study of veterans, statin use was associated with a reduced risk of Barrett's esophagus. The greatest level of risk reduction was observed for obese patients and for long-segment Barrett's esophagus.

Medical Prevention of Barrett's Esophagus: Effects of Statins, Aspirin, Non-aspirin NSAIDs, Calcium, and Multivitamins.

BACKGROUND: Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease (GERD) that is a precursor to esophageal adenocarcinoma. There is limited information regarding whether medications can reduce the risk of developing BE. AIM: We analyzed medical records at a large veterans hospital to determine the effects of statins, aspirin, non-aspirin NSAIDs, calcium, or multivitamins on the risk of developing BE. METHODS: In this retrospective case-control study, 250 patients with biopsy-confirmed Barrett's esophagus were compared with 250 controls with acid-peptic symptoms but no endoscopic BE. Medication histories were reviewed for the use of the above substances prior to endoscopic evaluation. Logistic and linear regression was used to determine predictors of the outcomes. RESULTS: Mean age at diagnosis was significantly older in the Barrett's population compared with controls (61.2 vs. 56.7 years, P < 0.001), with no difference in mean BMI (29.1 vs. 29.0, respectively). On multivariate analysis, independently significant factors for risk of BE were found with multivitamins (OR 0.41, P = 0.001), statins (OR 0.53, P = 0.003), age (OR 1.033/year, P = 0.001), and Hispanic ethnicity (OR 0.38, P = 0.007). Furthermore, statin use was associated with less long-segment (3 cm or longer) BE and was inversely correlated with continuous BE length. CONCLUSIONS: GERD patients with BE are less likely to use multivitamins and statins, as well as less likely to be of Hispanic ethnicity. Additionally, statins were inversely associated with BE length. Prospective studies of this topic are indicated.

Rebamipide Alters the Esophageal Microbiome and Reduces the Incidence of Barrett's Esophagus in a Rat Model.

BACKGROUND: Barrett's esophagus (BE) is characterized by a distinct Th2-predominant cytokine profile. However, antigens that shift the immune response toward the Th2 profile are unknown. AIM: We examined the effects of rebamipide on the esophageal microbiome and BE development in a rat model. METHODS: BE was induced by esophagojejunostomy in 8-week-old male Wistar rats. Rats were divided into control and rebamipide-treated group receiving either a normal or a 0.225 % rebamipide-containing diet, respectively, and killed 8, 16, 24, and 32 weeks after the operation. PCR-amplified 16S rDNAs extracted from esophageal samples were examined by terminal-restriction fragment length polymorphism (T-RFLP) analysis to assess microbiome composition. The dynamics of four bacterial genera (Lactobacillus, Clostridium, Streptococcus, and Enterococcus) were analyzed by real-time PCR. RESULTS: The incidences of BE in the control and rebamipide group at 24 and 32 weeks were 80 and 100, and 20 and 33 %, respectively. T-RFLP analysis of normal esophagus revealed that the proportion of Clostridium was 8.3 %, while that of Lactobacillales was 71.8 %. The proportions of Clostridium increased and that of Lactobacillales decreased at 8 weeks in both groups. Such changes were consistently observed in the control but not in the rebamipide group. Clostridium and Lactobacillus expression was lower and higher, respectively, in the rebamipide group than in the control group. CONCLUSIONS: Rebamipide reduced BE development and altered the esophageal microbiome composition, which might play a role in BE development.

Aspirin and nonsteroidal anti-inflammatory drug use and the risk of Barrett's esophagus.

BACKGROUND: The use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of esophageal adenocarcinoma; however, it is unknown where these agents may act in the proposed pathway from normal mucosa to Barrett's esophagus to esophageal adenocarcinoma. AIM: The aim of the study was to evaluate the association between aspirin and NSAID use and Barrett's esophagus in a case-control study within a large community-based population. METHODS: We conducted a case-control study of aspirin/NSAID use and Barrett's esophagus within the Kaiser Permanente Northern California population. Cases had a new diagnosis of Barrett's esophagus between October 2002 and September 2005; controls were members without a diagnosis of Barrett's esophagus. RESULTS: Persons with Barrett's esophagus were less likely to use aspirin than population controls [odds ratio (OR) 0.59, 95 % confidence interval (CI) 0.39-0.87]; a stronger association was found among cases and controls with reflux symptoms (OR 0.49, 95 % CI 0.32-0.75; p value interaction = 0.004). Similar associations were found with the use of either aspirin and/or non-aspirin NSAIDs (OR 0.53, 95 % CI 0.35-0.81), although NSAID use alone was not significantly associated with Barrett's esophagus (OR 0.74, 95 % CI 0.47-1.16). The strength of the association was highest among persons with at least moderate-to-high total medication intake. CONCLUSIONS: Regular use of aspirin or NSAIDs was associated with a decreased risk of Barrett's esophagus, particularly among persons with gastroesophageal reflux disease symptoms. These findings have implications for chemoprevention, as some of the previously described protective association between aspirin/NSAIDs and esophageal adenocarcinoma may be explained by events that occur prior to the development of Barrett's esophagus.

Improving the diagnosis and management of GORD in adults.

Gastro-oesophageal reflux disease (GORD) is defined as a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Many patients with GORD complications such as oesophagitis, and up to a third of patients with Barrett's oesophagus have no reflux or heartburn symptoms. Conversely, patients can be symptomatic even when normal reflux levels are found and there is an absence of mucosal damage. Significant GORD symptoms occur at least once a week in 8.8-26% of Europeans, with equal prevalence of symptoms in men and women. The frequency and severity of symptoms do not accurately predict the degree of oesophageal damage. If patients with GORD also describe symptoms of dyspepsia this should be considered first with H. py/oritesting or direct referral for gastroscopy if the patient is over 55 given the risk of gastric cancer in these patients. Oesophageal disease can account for up to 20% of cases of chronic cough. Symptoms of GORD occur in more than 45% of patients with asthma, and erosive oesophagitis on endoscopy has a 50% higher likelihood of a diagnosis of asthma. GORD is a risk factor for Barrett's oesophagus and oesophageal adenocarcinoma. The risk increases with duration, severity and frequency. Endoscopy should not be routinely offered at initial presentation unless the patient has dysphagia or other symptoms suggestive of upper GI cancer. Smoking cessation and weight loss are beneficial in reducing GORD symptoms. Abdominal obesity causes GORD by elevating intra-abdominal pressure, which promotes reflux and the development of hiatus hernia. GORD symptoms are increased by 70% among daily smokers who have been smoking for more than 20 years.

Protective role of gluteofemoral obesity in erosive oesophagitis and Barrett's oesophagus.

OBJECTIVE: Abdominal obesity has been associated with erosive oesophagitis (EO) and Barrett's oesophagus (BO). As gluteofemoral obesity protects against diabetes mellitus and cardiovascular disease, we hypothesised that gluteofemoral obesity would be inversely associated with EO and BO. DESIGN: We conducted a cross-sectional study on 822 male colorectal cancer screenees who were recruited to also undergo upper endoscopy. An additional 80 patients with BO clinically detected by upper endoscopy referred for clinical indications were recruited shortly after their diagnoses of BO. Logistic regression was used to estimate the effects of abdominal obesity (waist circumference), gluteofemoral obesity (hip circumference) and waist-to-hip ratio (WHR) on EO and BO (vs neither condition). RESULTS: There were 225 cases of either BO or EO and 675 controls. After adjustment for potential confounders, a positive association was observed between waist circumference and BO and/or EO, which became stronger with further adjustment for hip circumference. In contrast, hip circumference was inversely associated with BO and/or EO. Compared with the lowest quartile of WHR, the adjusted ORs were 1.32 (95% CI 0.747 to 2.33) for the 2nd quartile, 1.54 (95% CI 0.898 to 2.63) for the 3rd quartile, and 2.68 (95% CI 1.57 to 4.55) for the highest quartile. Similar results were obtained for BO and EO treated as separate outcomes. CONCLUSIONS: In a population of older, mostly overweight men, the distribution of obesity is associated with the presence of EO and BO. Abdominal obesity appears to increase the risk of these outcomes, whereas gluteofemoral obesity may be protective.

Durability and predictors of successful radiofrequency ablation for Barrett's esophagus.

BACKGROUND & AIMS: After radiofrequency ablation (RFA), patients may experience recurrence of Barrett's esophagus (BE) after complete eradication of intestinal metaplasia (CEIM). Rates and predictors of recurrence after successful eradication have been poorly described. METHODS: We used the US RFA Registry, a nationwide registry of BE patients receiving RFA, to determine rates and factors that predicted recurrence of intestinal metaplasia (IM). We assessed recurrence by Kaplan-Meier analysis for the overall cohort and by worst pretreatment histology. Characteristics associated with recurrence were included in a logistic regression model to identify independent predictors. RESULTS: Among 5521 patients, 3728 had biopsies 12 months or more after initiation of RFA. Of these, 3169 (85%) achieved CEIM, and 1634 (30%) met inclusion criteria. The average follow-up period was 2.4 years after CEIM. IM recurred in 334 (20%) and was nondysplastic or indefinite for dysplasia in 86% (287 of 334); the average length of recurrent BE was 0.6 cm. In Kaplan-Meier analysis, more advanced pretreatment histology was associated with an increased yearly recurrence rate. Compared with patients without recurrence, patients with recurrence were more likely, based on bivariate analysis, to be older, have longer BE segments, be non-Caucasian, have dysplastic BE before treatment, and require more treatment sessions. In multivariate analysis, the likelihood for recurrence was associated with increasing age and BE length, and non-Caucasian race. CONCLUSIONS: BE recurred in 20% of patients followed up for an average of 2.4 years after CEIM. Most recurrences were short segments and were nondysplastic or indefinite for dysplasia. Older age, non-Caucasian race, and increasing length of BE length were all risk factors. These risk factors should be considered when planning post-RFA surveillance intervals.

Nonsteroidal anti-inflammatory drugs and the risk of Barrett's esophagus.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested to protect against esophageal adenocarcinoma (EAC). This study examined the effect of NSAIDs on the risk of developing Barrett's esophagus (BE), the precursor lesion to EAC. METHODS: We conducted a case-control study among eligible patients scheduled for either elective esophagogastroduodenoscopy (EGD) or recruited from primary care clinics to undergo a study EGD. We compared 323 patients with BE (296 nondysplastic and 27 dysplastic) with 2 separate control groups: 1347 patients from the elective EGD group (endoscopy controls) and 502 patients from the primary care group (primary care controls) with no endoscopic or histopathologic BE. Use of aspirin products and 23 nonaspirin NSAIDs was ascertained from detailed, self-reported questionnaires. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models. RESULTS: There were no significant differences in self-reported NSAID use between all BE cases and all controls (58.2% vs 54.6%; P = .33); this was seen for aspirin products (43.0% vs 37.4%; P = .08) and nonaspirin NSAIDs (7.7% vs 8.9%; P = .46). These findings persisted in the multivariable model for any NSAIDs (adjusted OR, 0.89; 95% CI, 0.75-1.28), aspirin (adjusted OR, 1.16; 95% CI, 0.90-1.51), and nonaspirin NSAIDs (adjusted OR, 0.88; 95% CI, 0.55-1.39). Use of a combination of aspirin and nonaspirin NSAIDs was reported in 7.4% of cases and 8.3% of controls, and a nonsignificant inverse association with BE was seen (adjusted OR, 0.70; 95% CI, 0.44-1.11). There was no significant association between BE and daily NSAID use (adjusted OR, 1.03; 95% CI, 0.78-1.37). Similar findings were observed for comparisons involving nondysplastic or dysplastic BE cases, and endoscopy or primary care control groups separately or combined. CONCLUSIONS: The use of NSAIDs was not associated with a reduced risk of BE. It is likely that the protective mechanism of NSAIDs on EAC occurs subsequent to the development of BE.

Risk factors for Barrett's esophagus.

PURPOSE OF REVIEW: To summarize the emerging data on the risk factors for Barrett's esophagus and risk stratification tools. RECENT FINDINGS: Obesity, particularly abdominal obesity, is associated with Barrett's esophagus, likely because of both mechanical effects promoting gastroesophageal reflux and nonmechanical effects. Circulating peptides related to obesity alter the risk of Barrett's esophagus and may work synergistically with gastroesophageal reflux. Tobacco use is an underappreciated risk for Barrett's esophagus. A number of genetic variants have been associated with Barrett's esophagus, involving pathways in esophageal development. Risk stratification tools are becoming available that have modest discriminatory capability and good calibration. SUMMARY: The developing understanding of risk factors for Barrett's esophagus is shifting the clinical guidelines to a nuanced approach incorporating multiple risk factors to select patients for screening for Barrett's esophagus.