Negative Reflux Disease Research Articles

Comparison of acid-lowering drugs for endoscopy negative reflux disease: Systematic review and network Meta-Analysis.

The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score. We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated. Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.

Endoscopic correlation of clinical presentation of gastroesophageal reflux disease among patients referred for gastroscopy in a tertiary hospital

Gastroesophageal reflux disease (GERD) is a leading indication for gastroscopy and a common cause of serious complications among patients with dyspeptic symptoms. Ethnic variability, gender and geographical locations are some of the factors that determine severity index and complications of GERD. Upper gastrointestinal endoscopy is a reliable method used in confirming clinical suspicion of GERD. This study aimed to determine the endoscopic correlation of clinical presentations and frequency of complications among patients with clinical diagnosis of GERD referred for gastroscopy. Hospital-based cross sectional study conducted between 1stJanuary, 2013 to 31st December, 2016. Sociodemographic characteristics and clinical diagnosis of GERD were evaluated alongside endoscopic findings. Endoscopic findings of oesophagitis, strictures, Barrett’s oesophagus or oesophageal adenocarcinoma were classified as endoscopy positive while those with symptoms but with normal endoscopic finding were classified as endoscopy negative or Non-erosive reflux Disease. One thousand, five hundred and ninety seven patients were referred for gastroscopy within the study period of which 226 were GERD (14.2%) using the self-administered questionnaire. One hundred and seven (47.3%) were males, with M: F ratio of 1:1.1. Mean age 38.5, SD± 13.1, and range of 15-75 years. The peak age occurred within the fourth decade of life (32.7%). One hundred and seventy seven (78.3%) were endoscopy positive, while 49 (21.7%) were endoscopy negative GERD. Los Angeles grade B was the highest prevalence 41.2%. GERD is not uncommon in our study and younger age groups are particularly more affected. Erosive esophagitis is the commonest complication encountered.

What are the benefits and harms of short-term treatment with proton pump inhibitors, H2-receptor antagonists or prokinetics in people with gastro-esophageal reflux disease-like symptoms and endoscopy negative reflux disease?

What are the benefits and harms of short-term treatment with proton pump inhibitors, H2-receptor antagonists or prokinetics in people with gastro-esophageal reflux disease-like symptoms and endoscopy negative reflux disease?

Convenient Method of Measuring Baseline Impedance for Distinguishing Patients with Functional Heartburn from those with Proton Pump Inhibitor-Resistant Endoscopic Negative Reflux Disease

Background: Combined 24-h intraesophageal pH-multichannel intraluminal impedance (24MII-pH) used for assessing gastroesophageal reflux disease by measuring baseline impedance (BI) requires a 24-h measuring period. In the present study, we developed a quick method of measuring BI and evaluated its usefulness in classifying patients with proton pump inhibitor (PPI)-refractory non-erosive reflux diseases (NERD) as having functional heartburn (FH) or endoscopic-negative reflux disease (ENRD). Methods: Ninety-one NERD patients without esophageal motility disorder underwent 24MII-pH monitoring while on a PPI. The measurements of the mean nocturnal BI (MNBI) and short MNBI were assessed at 3 times (at about 1: 00, 2: 00, and 3: 00 am) for 10 min and 30 s respectively. The measurement of the simple mean BI (MBI) was performed once 30 s at about 11: 00 am. Results: Ninety-one patients were divided into 2 groups: 59 with ENRD and 32 with FH. The cutoff, specificity, and sensitivity for distinguishing patients with FH were as follows: MNBI, 2,874.1 Ω, 72%, and 72%; short MNBI, 2,857.6 Ω, 74%, and 84%; and simple MBI, 2,874.1 Ω, 86%, and 78% respectively. Conclusion: Measuring the simple MBI is a quick method and is useful for distinguishing patients with FH from those in a cohort with PPI-refractory NERD.

Gastroesophageal Reflux Disease and its Association with Body Mass Index: Clinical and Endoscopic Study.

Obesity is rapidly becoming a pandemic and poses a serious health risk to the individuals. Abdominal obesity is quite common in India and is a prime risk factor for diseases like diabetes, coronary artery disease, Gastroesophageal Reflux Disease (GERD), osteoarthritis etc. A complex and multifactorial aetiopathogenesis of GERD exists in presence of obesity. The current study focuses on high Body Mass Index (BMI), a marker of obesity, as a risk factor for GERD and aims for a better understanding of their complex association. To study the association between the BMI and symptoms as well as gross endoscopic appearance of GERD. A prospective cross-sectional study was carried out at a tertiary care hospital in Maharashtra, India, between January 2016 and June 2016. A total of 176 patients referred for upper Gastrointestinal (GI) endoscopy due to dyspeptic symptoms of more than two months duration were selected. BMI (weight in kilograms/square of height in metres) was calculated for all patients and they were classified as normal weight (BMI 18.5 -24.9), overweight (BMI 25-29.9) and obese (BMI≥30). The frequency and severity of GERD symptoms was assessed by a self-administered questionnaire. Data on typical and atypical symptoms of GERD was collected. Upper GI endoscopy was done on all patients. Based on gross endoscopic appearance, the disease was divided as Endoscopy Negative Reflux Disease (ENRD) and true GERD (as per Los Angeles staging system). Association between BMI and frequency, severity and type of symptoms of GERD and also between BMI and gross endoscopic oesophagitis was studied using various statistical tests. All tests were two-tailed with a confidence level of 95%. A p-value < 0.05 was considered to be statistically significant. Typical symptoms of heartburn and acidic regurgitation were present in 71.6% subjects. The frequency and the severity of the dyspeptic symptoms increased significantly with increasing BMI (p<0.05). Based on the endoscopic gross appearance of the oesophageal mucosa, 48.3% participants had ENRD and 51.7% had erosive disease (GERD). High BMI had a statistically significant relationship with occurrence of both ENRD and GERD (p<0.05) but a statistically insignificant relationship with LA classification system for endoscopic oesophagitis. The prevalence, frequency and severity of symptoms of GERD increases with increase in the BMI. Erosive oesophagitis has significant correlation with increasing BMI, but the staging and classification of endoscopic erosive oesophagitis is independent of the BMI of the patients.

Potentiated clinoptilolite: artificially enhanced aluminosilicate reduces symptoms associated with endoscopically negative gastroesophageal reflux disease and nonsteroidal anti-inflammatory drug induced gastritis.

PurposeThe cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D), is a synthetically enhanced aluminosilicate. The aim of this study was to evaluate the possible benefits of a potentiated clinoptilolite as a gastroprotective agent in reducing the severity of clinical symptoms and signs associated with 1) endoscopically negative gastroesophageal reflux disease (ENGORD) and 2) nonsteroidal anti-inflammatory drug (NSAID) medication.Methods and patientsTwo randomized, double-blind, placebo-controlled, pilot studies, the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy, a total of 25 patients suffering from ENGORD were randomized to receive either placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent gastroscopic evaluation of their stomach linings prior to and on day 14 of the study. Gastric biopsies were obtained and evaluated via the upgraded Sydney system, whereas visible gastric events and status of the gastric mucosa were evaluated via a 0–3 rating scale. During both studies, patients recorded gastric symptoms in a daily symptom diary.ResultsIn the ENGORD study, patients who received the potentiated clinoptilolite reported a significant reduction (P≤0.05) in severity of symptoms including reduction in heartburn (44%), discomfort (54%), and pain (56%). Symptom-free days improved by 41% compared to the group who received placebo (not significant). This was over and above the benefits seen with the proton pump inhibitor. In the NSAID study, the reduction in gastric symptom severity was echoed in the group who received the potentiated clinoptilolite. Treatment with the potentiated clinoptilolite resulted in significant prevention (P≤0.05) of mucosal erosion severity as graded by the gastroenterologist.ConclusionAbsorbatox is a nonabsorbable aluminosilicate with potential gastroprotective benefits as it protected against ENGORD symptoms and NSAID-induced gastric events. The exact mechanism of action is not clear but may be due to its binding to hydrogen ions and biologically active amines and nitrates.

Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease

Approximately 25% of adults regularly experience heartburn, a symptom of gastro-oesophageal reflux disease (GORD). Most patients are treated empirically (without specific diagnostic evaluation e.g. endoscopy. Among patients who have an upper endoscopy, findings range from a normal appearance, mild erythema to severe oesophagitis with stricture formation. Patients without visible damage to the oesophagus have endoscopy negative reflux disease (ENRD). The pathogenesis of ENRD, and its response to treatment may differ from GORD with oesophagitis. Summarise, quantify and compare the efficacy of short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in adults with GORD, treated empirically and in those with endoscopy negative reflux disease (ENRD). We searched MEDLINE (January 1966 to November 2011), EMBASE (January 1988 to November 2011), and EBMR in November 2011. Randomised controlled trials reporting symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be either from an empirical treatment group (no endoscopy used in treatment allocation) or from an endoscopy negative reflux disease group (no signs of erosive oesophagitis). Two authors independently assessed trial quality and extracted data. Thirty-four trials (1314 participants) were included: fifteen in the empirical treatment group, fifteen in the ENRD group and four in both. In empirical treatment of GORD the risk ratio (RR) for heartburn remission (the primary efficacy variable) in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87).In treatment of ENRD, the RR for heartburn remission for PPI versus placebo was 0.71 (ten trials, 95% CI 0.65 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with ENRD, although the magnitude of benefit is greater for those treated empirically.

A systematic review of the treatment of gastroesophageai reflux disease with mosapride in China

Objective To evaluate the efficacy and safety of mosapride in the treatment of gastroesophageal reflux disease (GERD). Methods Papers of PubMed,EMBASE,OVID,VIP Database and WANGFANG Data were searched and reviewed according to international Cochrane Collaboration.Results A total of 21 trials (1666 patients) were included.The treatment group was with mosapride and PPI,the control group was with single PPI or PPI and placebo.The Results of Meta analysis showed:for non-erosive negative reflux disease,there was no significant difference in efficacy between two groups.As for erosive esophagitis treated with mosapride (5mg):There was no significant difference in the 4-week healing rates between treatment group and control group (P =0.06).The 4-week symptom relief rate of treatment group was better than that of control group (P＜0.01).The 6-week healing rate of treatment group was better than that of control group (P＜0.01).The 6-week symptom relief rate of treatment group was better than that of control group (P＜0.01).There was no significant difference in the 8-week healing rate of esophagitis between treatment group and control group (P =0.05).The 8-week symptom relief rate of treatment group was better than that of control group (P＜0.01).For erosive esophagitis treated with mosapride 10mg,.The 8-week symptom relief rate of treatment group was better than that of control group (P=0.02).Conclusion According to the meta-analysis of these 21 trails,mosapride was safe and effective in the treatment of GERD.However due to the quality of the literatures,the above findings should be treated with caution. Key words: Benzamides; Gastroesophageal reflux; Computer systems; Drug evaluation; Metaanalysis

Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease

Non-specific esophageal dysmotility with impaired clearance is often present in patients with gastro-esophageal reflux disease (GERD), especially those with erosive disease; however the physio-mechanic basis of esophageal dysfunction is not well defined. Retrospective assessment of patients with erosive reflux disease (ERD; n=20) and endoscopy negative reflux disease (ENRD; n=20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n=20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3cm break in 30 mmHg isocontour). Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P<0.023 vs controls, P=0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18%vs 33%, P=0.082) and ENRD (22%vs 54%, P=0.046) but not ERD (62%vs 76%, P=0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P<0.017 vs controls and P<0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r=0.52 vs 0.27). Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate.

Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease

Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux - is a common relapsing and remitting disease which often requires long-term maintenance therapy. Patients with GORD may have oesophagitis (inflammation of the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or ENRD). To assess the effects of continuous maintenance therapy in adults with GORD (both ENRD and healed oesophagitis). We searched Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982-2003), and the National Research Register (Issue 2, 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. Randomised controlled studies comparing PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo in adults with reflux oesophagitis and ENRD. One author extracted data from included trials and a second author carried out an unblinded check. Two authors independently assessed trial quality. Study authors were contacted for additional information. Maintenance of patients with healed oesophagitis: For a healing dose of PPI (generally the standard dose given by the manufacturer) versus placebo, the relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse effects were also more common and headaches were more common when comparing healing PPIs to H2RAs.For a maintenance dose of PPI (half of the standard dose) versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57) and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects were more common.H2RAs were of marginal help but beneficial for symptomatic relief. Prokinetics and sucralfate were also more effective than placebo.For ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once daily over placebo (RR 0.4; 95% CI 0.29 to 0.53). The findings in this review support the long-term treatment of oesophagitis to prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs are more effective than all other therapies, although there is an increase in overall adverse effects compared to placebo, and headache occurrence compared to H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over placebo, but the former is no longer licenced. There is only limited data for ENRD.

Prevalence of endoscopically negative and positive gastroesophageal reflux disease in the Japanese

Objective. The frequency of gastroesophageal reflux disease (GERD) has not been fully investigated in the Asian population. The aim of this study was to investigate the prevalence of GERD, endoscopy-negative GERD (NERD), and erosive GERD in Japan, and the factors influencing disease prevalence. Material and methods. A total of 2760 subjects (mean age 50.4 years, range 24–84 years) were prospectively enrolled in this multicenter study. GERD symptoms were assessed with the Japanese version of the Carlsson-Dent self-administered questionnaire (QUEST) and upper gastrointestinal endoscopy was performed on all study participants. Results. A total of 495 (17.9%) individuals were diagnosed with GERD by the presence of erosive esophagitis at endoscopy and/or by the presence of GERD symptoms. Erosive esophagitis was diagnosed endoscopically in 195 (7.1%), and symptomatic GERD was diagnosed in 351 (12.7%) based on a QUEST score of over 6. Of these 351 subjects, 300 (10.9%) were considered to have NERD. Male gender, hiatal hernia, and mild gastric mucosal atrophy were significant positive predictive factors of erosive esophagitis by multiple regression analysis. Hiatal hernia was the only significant predictor of GERD symptoms. Traditional Japanese foods, such as sweet cakes and rice cake, frequently exacerbated GERD symptoms. Conclusions. The prevalence of GERD in the Japanese was 17.9% and the prevalence rates of NERD and erosive esophagitis were 10.9% and 8.6%, respectively. The majority of symptomatic patients did not have endoscopically proven esophagitis. Hiatal hernia is the only important predictor of the presence of GERD symptoms.

Dichotomies and directions in acid‐related disorders

Presentations by international experts from old and new worlds bordering the Atlantic Ocean revealed surprising similarities with respect to the diagnosis and management of patients with upper gastrointestinal disorders. It was agreed that Helicobacter pylori infection continues to play a key role in gastroduodenal disease and has a great impact on clinical management. However, testing and treatment strategies vary in patients affected by functional dyspepsia and those receiving nonsteroidal anti-inflammatory drug (NSAID) therapy including aspirin. Among patients with gastro-oesophageal reflux disease (GERD), it was clear that we need to re-evaluate the validity of the classical concept of GERD as a progressive spectrum and instead focus on the pathophysiologic mechanisms responsible for producing the common symptom of heartburn and complications that occur in the three principle subsets of GERD patients: those with endoscopic negative reflux disease, erosive oesophagitis and Barrett's oesophagus. In addition, we need to be increasingly aware of the concept of extra-oesophageal manifestations of gastro-oesophageal reflux and the fact that GERD in adults often originates in childhood. In all these gastrointestinal disorders, proton pump inhibitor therapy has become the common thread either as a diagnostic tool or an effective short-term or long-term management strategy.

Interleukin‐8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease

Background: It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)‐8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms. Methods: Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non‐erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL‐8 mRNA was quantified by real‐time polymerase chain reaction (PCR). Localization of IL‐8 protein in the esophageal mucosa was done by immunostaining. Results: Expression of IL‐8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL‐8 mRNA was also detected in all patients with non‐erosive GERD. The level of IL‐8 expression in non‐erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL‐8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton‐pump inhibitor, decreased both IL‐8 mRNA and protein levels in the esophageal mucosa. Conclusion: These results suggest that IL‐8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non‐erosive GERD.

Dyspepsia

Dyspepsia

Review article: test and treat or treat and test in reflux disease?

The role of diagnostic testing in reflux disease is in evolution. There is little question that patients with dysphagia, bleeding or other 'alarm' symptoms, should undergo early endoscopy. A substantial proportion of patients presenting with reflux symptoms have endoscopy negative reflux disease. pH testing is both inconvenient and lacks the sensitivity and specificity required for a 'gold standard'. Empirical trials of therapy using proton pump inhibitors have shown that a trial of treatment may be the most accurate way of diagnosing gastro-oesophageal reflux disease (GERD) and may the optimal strategy from a cost-effectiveness standpoint. On the other hand, the increasing rate of oesophageal adenocarcinoma has raised questions about the possible value of screening endoscopy to determine if Barrett's oesophagus is present. The role of endoscopic testing in the average patient is therefore shifting from a diagnostic modality to one that helps manage risk by identifying Barrett's oesophagus.

Gastroesophageal reflux pattern in patients with endoscopy negative and endoscopy positive gastroesophageal reflux disease

Gastroesophageal reflux pattern in patients with endoscopy negative and endoscopy positive gastroesophageal reflux disease

Clinical analysis of endoscopy negative gastroesophageal reflux disease in the elderly

Clinical analysis of endoscopy negative gastroesophageal reflux disease in the elderly

Medical management of nocturnal symptoms of gastro-oesophageal reflux disease in the elderly.

Elderly patients with nocturnal symptoms of gastro-oesophageal reflux disease (GORD) usually experience a more aggressive and complicated disease course compared with younger patients, resulting in impaired quality of life. The severity of disease and possible complications should be evaluated with upper endoscopy once the diagnosis is suspected. Elderly patients with nocturnal symptoms of GORD and evidence of endoscopic complications (oesophagitis, Barrett's oesophagus, etc.) and those with severe endoscopically negative reflux disease (ENRD) should be treated with proton pump inhibitors. Histamine H(2) receptor antagonists are suitable for mild-to-moderate ENRD. Antacids and lifestyle modifications may be incorporated into the management as adjuncts to more potent and durable therapeutic agents. Effective treatment of nocturnal GORD symptoms in the elderly will result in relief of symptoms, healing of oesophagitis and improved quality of life, and should be maintained indefinitely to prevent relapses of the disease.

Risk Factors for the Severity of Erosive Esophagitis in Helicobacter pylori -Negative Patients with Gastroesophageal Reflux Disease

Background: The risk factors for the varying grades of erosive esophagitis (EE) severity could be better understood. For that reason, we evaluated the risk factors associated with EE in patients with gastroesophageal reflux disease. Methods: We determined the presence and severity of EE (using the Los Angeles Classification) in patients with negative serology Helicobacter pylori who underwent esophago-gastroduodenoscopy as part of screening in four prospective, multicenter, randomized, double-blind comparative trials of once-daily esomeprazole and omeprazole for the acute healing of erosive esophagitis. We also examined the baseline characteristics of enrolled patients, and identified risk factors for severe disease using a multivariable logistic regression model. Results: Erosive esophagitis was documented in 6709 patients of a total of 10,294 patients who underwent endoscopy; of these, 34% had grade A, 39% had grade B, 20% had grade C, and 7% had grade D disease. The majority of patients were male (61%) and Caucasian (93%) with a mean age of 46 years. In the regression model, the following were significant independent risk factors for severe (grades C and D) versus mild erosive esophagitis (grades A and B): severe heartburn (adjusted odds ratio 1.79); prolonged heartburn >5 years in duration (1.16); obesity (1.21); the presence of hiatus hernia (2.13); male gender (1.97); and Caucasian ethnicity (1.53). Conclusion: In this large sample of patients with predominantly H. pylori -negative gastroesophageal reflux disease, risk factors for severe erosive esophagitis were the duration and severity of heartburn, and obesity.

Pathological issues of gastric and lower esophageal cancer: helicobacter pylori infection and its eradication.

Gastric carcinoma is thought to develop via the actions of inducers and promoters of carcinogenesis. Tryptophan in charred fish or animal meat, ultraviolet rays, and irradiation, which damage genes of normal cells, have long been regarded as inducers of carcinoma, and agents such as alcohol, tobacco, aflatoxin, and nitrosoamine as promoters, with tobacco having both activities. The interaction between these environmental factors, principally diet, and Helicobacter pylori (Hp) is important in the genesis of gastric carcinoma. In this report, the histopathological feature of the Hp gastritis-carcinoma sequence is outlined, and the pathological characteristics of gastroesophageal reflux disease (GERD) and endoscopically negative reflux disease (ENRD) and the risk factors for lower esophageal carcinoma after Hp eradicated status in particular are discussed regarding aspects of cell cycle-associated factors. We conclude that (1) Infection with Hp increases the risk of gastric cancer in two histological phenotypes (i.e., diffuse undifferentiated type and intestinal differentiated type). Excessive cell replication and interrupting the mucus secretion mechanism may result in a large proportion of cells with genetic abnormalities. (2) Genetic alterations in gastric carcinogenesis may differ from those in colonic carcinogenesis. (3) The degree of GERD in Japanese patients is milder than that in patients from Western countries, although the incidence of GERD increases the status after successful eradication of Hp. It is also possible that accumulation of genetic abnormalities increases the number of cardiac and lower esophageal cancers. Investigation of cell cycle factors in GERD including ENRD can be expected to reveal the risk of carcinogenesis.