Development Of Gastro-oesophageal Reflux Disease Research Articles

Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study

BackgroundShorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD)...

Lifestyle measures in the management of gastro-oesophageal reflux disease: clinical and pathophysiological considerations.

Several lifestyle and dietary factors are commonly cited as risk factors for gastro-oesophageal reflux disease (GORD) and modification of these factors has been advocated as first-line measures for the management of GORD. We performed a systematic review of the literature from 2005 to the present relating to the effect of these factors and their modification on GORD symptoms, physiological parameters of reflux as well as endoscopic appearances. Conflicting results existed for the association between smoking, alcohol and various dietary factors in the development of GORD. These equivocal findings are partly due to methodology problems. There is recent good evidence that weight reduction and smoking cessation are beneficial in reducing GORD symptoms. Clinical and physiological studies also suggest that some physical measures as well as modification of meal size and timing can also be beneficial. However, there is limited evidence for the role of avoiding alcohol and certain dietary ingredients including carbonated drinks, caffeine, fat, spicy foods, chocolate and mint.

Dysmotility and reflux disease

In the last decade, with the advent of new oesophageal testing [i.e. 24-h impedance-pH monitoring, combined impedance-manometry, high-resolution manometry (HRM)], relevant progress in understanding the mechanisms contributing to the development of gastro-oesophageal reflux disease (GORD) has been made, allowing a better management of patients with this disorder. The aim of our review is to report the state-of-the-art about oesophageal motor disorders in patients with reflux disease and to stimulate new research in this field. Hypotensive lower oesophageal sphincter (LOS), transient LOS relaxations, impairment of oesophagogastric junction including hiatal hernia, oesophageal bolus transit abnormalities and presence of ineffective oesophageal motility have been strongly implicated in GORD development. In particular, the majority of recent studies carried out with HRM and impedance-pH testing reported that these motor abnormalities are increasingly prevalent with increasing severity of GORD, from nonerosive reflux disease and erosive oesophagitis to Barrett's oesophagus. Defining and characterizing oesophageal dysmotility in patients with reflux disease is of maximum importance in order to properly diagnose these patients and to treat them with the best management of care. New studies are needed in order to better understand the physiomechanic basis of oesophageal dysmotility in GORD patients.

Reflux symptoms and obesity.

In the paper titled “Assessment of the relationship between reflux and body mass index with different regression models” Pourhoseingholi et al (1), report the results of a population based cross sectional case controlled study (1). The study investigates the relationship between body mass index (BMI) and reflux symptoms. The authors report that they found no correlation between BMI and reflux symptoms using 3 different statistical tools. On initial reflection this study appears to be contradicting the widely accepted belief that reflux is more prevalent in people with high BMI (2). Western population are aging and facing a relentless increase in the prevalence of obesity. Population studies from the United States suggest 15% of adults aged between 20 and 75 years are obese. Furthermore the incidence of obesity increased at an amazing 5 % per year between the early 1992 and 2005. It is anticipated that by 2020, as a result of increased food intake and reduced physical activity, approximately 40% of adults will be obese. Coinciding with this temporal increase in obesity there has been an increase in the prevalence of gastro-oesophageal reflux disease (GORD) and oesophageal cancer (3). It is only natural that investigators would wonder if the increasing prevalence of obesity is contributing to the increasing prevalence of these two conditions. The pathophysiology of GORD has been extensively studies. Any condition that compromises integrity of the lower oesophageal sphincter will predispose to the reflux of gastric contents into the oesophagus and the development of GORD. GORD is associated with the presence of a hiatus hernia, increased frequency of transient lower oesophageal sphincter relaxation and a weak lower oesophageal sphincter basal tone. GORD can be diagnosed by questionnaires, endoscopy and oesophageal manometry and pH studies. Oesophageal manometry and pH studies have shown that obesity is associated with increased exposure of the oesophagus to gastric acid reflux (4). Studies have also shown that obese patients have an increased frequency of transient lower oesophageal relaxations and a weaker lower oesophageal sphincter compared to non-obese individuals. It thus seems very plausible that obesity predisposes to GORD. These clinical studies have been supported by epidemiological studies. These have confirmed an association between obesity and GORD in a white population, with a progressive increase in the proportion of subjects reporting GORD symptoms as BMI increased (5). GORD symptoms are associated with the presence of Barrett’s oesophagus (BO) and the development of oesophageal adenocarcinoma (OA). The incidence of oesophageal adenocarcinoma has been progressively increasing in Western populations. Studies have investigated obesity as a risk factor for both BO and OA. Studies have suggested that obesity predisposes to both BO and OA in North American populations but the results of similar studies investigating adenocarcinoma of the gastric cardia have been conflicting (3). Before we consider the conclusions from this study, we must first look at the differences between this study and many of the studies that have previously been reported from Western populations. The study used a survey in the general population - subjects were not recruited from hospital clinics. The population surveyed was also young. Lastly we know that obesity is less prevalent in Iranian populations than in many Western populations. We may conclude that in a young population, with a low prevalence of obesity, as reported in this study, obesity is not a major risk factor for reflux symptoms. Had the authors surveyed an older population, with reflux symptoms and predisposing factors, such as a hiatus hernia, there findings may well have been different. The reader can conclude that there are many risk factors for GORD and that as populations become ‘Westernised’ that the aetiology of GORD in their aging society will change. In 10 years time we may predict that the Iranian population will be older and, perhaps, suffering from the Western obesity epidemic. It will then be interesting to compare the results of this study, current studies in Western populations and Iranian studies performed in an older society.

Erythropoietin adjuvant therapy and sustained virological response in HCV-infected patients

1. Martin-Merino E, Ruigomez A, Garcia Rodriguez LA, Wallander MA, Johansson S. Depression and treatment with antidepressants are associated with the development of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2010; 31: 1132–40. 2. Lewis JD, Schinnar R, Bilker WB, Wang X, Strom BL. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf 2007; 16: 393–401. 3. Ruigomez A, Garcia Rodriguez LA, Wallander MA, Johansson S, Graffner H, Dent J. Natural history of gastro-oesophageal reflux disease diagnosed in general practice. Aliment Pharmacol Ther 2004; 20: 751–60. 4. Egede LE. Major depression in individuals with chronic medical disorders: prevalence, correlates and association with health resource utilization, lost productivity and functional disability. Gen Hosp Psychiatry 2007; 29: 409–16. 5. Peytremann-Bridevaux I, Voellinger R, Santos-Eggimann B. Healthcare and preventive services utilization of elderly Europeans with depressive symptoms. J Affect Disord 2008; 105: 247–52.

Laparoscopic Anti-Reflux Surgery is Effective in Obese Patients with Gastro-Oesophageal Reflux Disease

Obesity has long been regarded as a risk factor for the development of gastro-oesophageal reflux disease (GORD). It has been claimed that surgical efficacy of laparoscopic anti-reflux operations is decreased in obese patients. The aim of this study was to assess whether laparoscopic anti-reflux surgery is effective in obese patients with GORD compared to non-obese patients. A total of 366 patients (mean age 44 years; range, 12-86 years) underwent laparoscopic anti-reflux surgery between 1997-2003. Of these, 74 patients were considered obese; 58 patients had a body mass index (BMI) of 30-34 kg/m(2) and 16 were classified as morbidly obese with a BMI >or= 35 kg/m(2). Pre-operative symptomatic scoring, indications for surgery, pH studies, operative times and complications were compared between obese and non-obese patients. Symptomatic outcome and Visick score between the two groups were assessed at 6 weeks, 6 months and 1 year following surgery. Failure of medical treatment was the main reason for surgery in all groups. Operative time was longer in obese patients (mean time 93 min compared to 81 min; P = 0.0007), the main difficulty being gaining access because of their body habitus. All groups found the procedure to be effective in symptomatic outcome, 91% of obese patients compared to 92% of non-obese patients scored Visick I or II at 6 weeks' postoperatively. Similar Visick scoring was shown between the two groups at 6 months and 1 year, and in the morbidly obese group. The outcome of laparoscopic anti-reflux surgery is similar between obese and non-obese patients with no trend towards a worse outcome in the obese or morbidly obese. Obesity should not be seen as a contra-indication, although it may be more technically challenging in this group of patients. Good results can be achieved in obese patients.

Does body mass index differ between patients with Barrett’s oesophagus and patients with chronic gastro‐oesophageal reflux disease?

Obesity has been demonstrated to be a risk factor for the development of gastro-oesophageal reflux disease (GERD). To perform a prospective cohort study to determine whether there was a difference in body mass index (BMI) between patients with GERD and patients with Barrett's oesophagus (BE). We prospectively enrolled patients undergoing endoscopic evaluation for GERD and collected information regarding BMI, tobacco and/or alcohol use, and family history of GERD. Patients with non-erosive reflux disease underwent confirmatory 24-h pH testing. Seven hundred and fifty one patients with GERD (mean +/- s.d. age of 55.4 +/- 14.2 years, 74% male) entered the study, and BE was present in 165 (22%, 90% male, 79% Caucasian) patients. The mean GERD symptom duration was 10.3 +/- 0.4 years (range 1-62 years) with a mean body mass index of 27.8 +/- 0.2 kg/m(2) (range 15-55) Compared with patients having GERD alone, patients with BE were more likely to be older (P = 0.001), male (P < 0.001), current or prior tobacco users (P = 0.002), and with greater duration of GERD symptoms (P < 0.001). There was no significant difference in the BMI for patients with and without BE. While obesity is a risk factor for both GERD and BMI, patients with BE did not demonstrate increased BMI compared with patients having chronic GERD.

Review article: from 1906 to 2006 – a century of major evolution of understanding of gastro‐oesophageal reflux disease

Our understanding of gastro-oesophageal reflux disease has undergone significant changes over the last century. To trace the rise in understanding of gastro-oesophageal reflux disease and highlight remaining areas of uncertainty. Literature review. In 1906, Tileston published his observations on 'peptic ulcer of the oesophagus'. Winkelstein, in 1934, first correlated symptoms of heartburn with acid regurgitation and reflux oesophagitis. In 1946, Allison described hiatus hernia as a causal factor in the development of gastro-oesophageal reflux disease. In 1958, Bernstein and Baker showed a direct relationship between oesophageal acidification and heartburn in patients with gastro-oesophageal reflux disease, irrespective of endoscopic findings, leading to the recognition of non-erosive gastro-oesophageal reflux disease. In the 1980s, continuous recordings of the lower oesophageal sphincter showed that episodes of reflux were related to transient relaxations of lower oesophageal sphincter tone. There is now increasing recognition that gastro-oesophageal reflux disease arises from the interaction of several anatomical and physiological factors. A turning point in the medical treatment of gastro-oesophageal reflux disease came with the introduction of the first proton pump inhibitor, omeprazole, in 1989. Future efforts need to identify the multifactorial interactions of gastro-oesophageal junction anatomy and physiology in patients with gastro-oesophageal reflux disease. Increased understanding of the disease will guide development of new therapies.

Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro‐oesophageal reflux disease in Western patients with non‐ulcer dyspepsia

The effect of Helicobacter pylori eradication on the development of gastro-oesophageal reflux disease is controversial. Aim To determine the incidence of symptoms of reflux disease and of erosive oesophagitis, and the relationship to changes in histological gastritis, in patients with non-ulcer dyspepsia over 12 months. Six hundred and ninety-three patients in two similar randomized placebo controlled trials of H. pylori eradication in non-ulcer dyspepsia were studied. Symptoms were assessed using the validated Gastrointestinal Symptom Rating Scale during a 1-week run-in period, at 6 months and 12 months. Endoscopy was performed at baseline to exclude patients with pathology and at 3 months and 12 months to determine if oesophagitis was present. Gastric biopsies were scored using the modified Sydney Classification. Patients without predominant heartburn, oesophagitis or ulcers at endoscopy were randomized to active (n = 297, omeprazole, amoxicillin and clarithromycin) treatment or to placebo/omeprazole (n = 306) for 1 week. The eradication rate was 82% in the active treatment group. Antrum-predominant gastritis (55%) was more frequently found than corpus-predominant gastritis (6%). In patients with antrum-predominant gastritis, heartburn and regurgitation scores improved significantly 12 months after eradication. Erosive oesophagitis developed in 15/232 patients in the eradication group (7%) compared with 2/227 (2%) in the control group, but there was no significant difference when adjusted for oesophagitis present at baseline. Antrum-predominant gastritis is the most common pattern of gastritis seen in non-ulcer dyspepsia in Western populations. Heartburn and regurgitation improve after eradication therapy or placebo in patients with non-ulcer dyspepsia; the development of oesophagitis is uncommon.

Low pH induces co-ordinate regulation of gene expression in oesophageal cells

The development of gastro-oesophageal reflux disease (GORD) is known to be a causative risk factor in the evolution of adenocarcinoma of the oesophagus. The major component of this reflux is gastric acid. However, the impact of low pH on gene expression has not been extensively studied in oesophageal cells. This study utilizes a transcriptomic and bioinformatic approach to assess regulation of gene expression in response to low pH. In more detail, oesophageal adenocarcinoma cell lines were exposed to a range of pH environments. Affymetrix microarrays were used for gene-expression analysis and results were validated using cycle limitation and real-time RT-PCR analysis, as well as northern and western blotting. Comparative promoter transcription factor binding site (TFBS) analysis (MatInspector) of hierarchically clustered gene-expression data was employed to identify the elements which may co-ordinately regulate individual gene clusters. Initial experiments demonstrated maximal induction of EGR1 gene expression at pH 6.5. Subsequent array experimentation revealed significant induction of gene expression from such functional categories as DNA damage response (EGR1-4, ATF3) and cell-cycle control (GADD34, GADD45, p57). Changes in expression of EGR1, EGR3, ATF3, MKP-1, FOSB, CTGF and CYR61 were verified in separate experiments and in a variety of oesophageal cell lines. TFBS analysis of promoters identified transcription factors that may co-ordinately regulate gene-expression clusters, Cluster 1: Oct-1, AP4R; Cluster 2: NF-kB, EGRF; Cluster 3: IKRS, AP-1F. Low pH has the ability to induce genes and pathways which can provide an environment suitable for the progression of malignancy. Further functional analysis of the genes and clusters identified in this low pH study is likely to lead to new insights into the pathogenesis and therapeutics of GORD and oesophageal cancer.

Prevalence of symptomatic gastro-oesophageal reflux disease in Japanese patients with peptic ulcer disease after eradication of Helicobacter pylori infection.

The association between cure of Helicobacter pylori infection and the development of gastro-oesophageal reflux disease is controversial. To examine the prevalence of symptomatic GERD (sGERD) in Japanese patients with peptic ulcer disease after successful eradication and identify associated factors affecting sGERD development. We retrospectively examined 72 patients (40 gastric ulcer and 32 duodenal ulcer) with successful eradication. Associated factors such as age, gender, drinking and smoking habits, body mass index, presence of gastric atrophy and hiatal hernia were analysed. Seven (9.7%) of 72 peptic ulcer patients newly developed sGERD. There were no differences in mean age, gender, smoking habit, drinking habit, body mass index, or presence of gastric atrophy and hiatal hernia between the sGERD and non-sGERD groups, while the proportion of subjects aged over 70 was significantly higher in the sGERD than the non-sGERD group. Six of 40 patients with gastric ulcer newly developed sGERD while only one of 32 patients with duodenal ulcer developed it. Approximately 10% of Japanese patients with peptic ulcer disease newly developed sGERD after cure of H. pylori infection. Age > 70 years was associated with development of sGERD. Eradication in patients in this age group should be carefully determined.

Helicobacter pylori-induced duodenal ulcer frequently coincides with gastro-oesophageal reflux disease.

The relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease is complicated. Evidence does not support a causal link. There have been reports, which have implicated successful eradication of Helicobacter pylori, in patients with a duodenal ulcer, with the subsequent development of gastro-oesophageal reflux disease. However, eradication of Helicobacter pylori in these patients with improvement in their condition and a return to normal lifestyle, weight gain and discontinuation of antacids may unmask pre-existing gastro-oesophageal reflux disease. To determine the true prevalence of gastro-oesophageal reflux disease in patients with Helicobacter pylori-related duodenal ulceration. Dyspeptic patients undergoing endoscopy were prospectively screened for the presence of a duodenal ulcer. Concomitant oesophagitis, when present, was recorded. All subjects with a Helicobacter pylori-related duodenal ulcer without endoscopic evidence of gastro-oesophageal reflux disease were invited to undergo a 24-hr ambulatory oesophageal pH assessment prior to receiving treatment. A total of 97 patients with a duodenal ulcer were identified and 83.5% were Helicobacter pylori positive. Overall, 27.8% had associated endoscopic evidence of oesophagitis, 70% grade I-II and 30% grade III-IV. Of those without evidence of oesophagitis at endoscopy, 68% underwent a 24-hr pH assessment. An additional 17% were identified by this means as having gastro-oesophageal reflux disease. Overall, 44% of symptomatic subjects with Helicobacter pylori and a duodenal ulcer were found to have coexistent gastro-oesophageal reflux disease. Gastro-oesophageal reflux disease is frequently found to coexist with Helicobacter pylori-related duodenal ulcer. In addition, almost 20% of symptomatic patients without endoscopic evidence of oesophagitis will have an abnormal oesophageal pH exposure. It is plausible that the development of gastro-oesophageal reflux disease following successful eradication of Helicobacter pylori represents unmasking of existing disease rather than de novo development.

Presence of Bile in the Oesophagus Is Associated with Less Effective Oesophageal Motility

Background/Aims: Reflux of bile to the oesophagus has been shown to be of importance in the development of gastro-oesophageal reflux disease. This study aims to assess oesophageal motility patterns in relation to acid and bile reflux to the oesophagus. Methods: Forty-nine subjects with and without reflux disease underwent 24-hour ambulatory recordings of oesophageal pH, bile and 3-channel manometry. Gastroscopy was performed to assess severity of oesophagitis. The percentage of effective peristaltic contractions (oesophageal contractions with a peristaltic pattern and a pressure >30 mm Hg) were correlated to the degree of acid and bile reflux. Ten subjects were re-evaluated within 2 years post-fundoplication. Results: Acid and bile reflux were associated with fewer effective contractions (R² = 0.07, p = 0.06 and R² = 0.21, p = 0.008, respectively). However, in a multivariate model including acid, bile, age and gender dependency, only bile could show a systematic effect on the variation in percentage of effective peristaltic contractions (R² = 0.22, p = 0.001). One year after laparoscopic fundoplication, 24-hour oesophageal motility was unchanged. Conclusion: Reflux of duodenal juice to the oesophagus is associated with less effective oesophageal motility, which in turn can perpetuate the disease by less effective oesophageal clearance of bile and acid. The reduced oesophageal motility is not reversed by fundoplication.

Dysfunction of oesophageal motility in Helicobacter pylori-infected patients with reflux oesophagitis.

Helicobacter pylori infection has been suggested to be protective against gastro-oesophageal reflux disease. However, a significant proportion of patients with gastro-oesophageal reflux disease are infected by H. pylori. To study oesophageal motor function in H. pylori-infected patients with reflux oesophagitis. Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24-h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non-reflux volunteers were recruited as controls. Seventy-four patients with erosive oesophagitis (34 H. pylori-positive, 40 H. pylori-negative) and 48 non-reflux patient controls (22 H. pylori-positive, 26 H. pylori-negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori-positive and H. pylori-negative groups. Compared to H. pylori-negative patients, H. pylori-positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori-positive patients. Among patients with a similar degree of reflux oesophagitis, H. pylori-infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro-oesophageal reflux disease in patients with H. pylori infection.

Review article: is Helicobacter pylori status relevant in the management of GORD?

There is growing interest in the relationship between H. pylori infection and gastro-oesophageal reflux disease (GORD). However, this relationship is complex, as yet not fully elucidated, and probably based on a multiplicity of factors. The prevalence of H. pylori infection in patients with GORD is similar, more often lower than in matched controls. There is a negative correlation between H. pylori infection and the severity of GORD. There are many hypothetical mechanisms by which H. pylori infection may protect from the development of GORD. Conversely, there are many possible mechanisms by which H. pylori infection could theoretically foster the GORD. Patients after H. pylori eradication may develop GORD, and this seems to suggest a protective role of H. pylori infection, but other possible explanations include weight gain after H. pylori eradication, changes in dietary habits and smoking, and pre-existing GORD. H. pylori infected patients treated by various acid-inhibiting therapies such as proton pump inhibitors (PPIs), H2-receptors antagonists (H2-RA) or vagotomy, have an increase of their corpus gastritis severity, both in the activity of inflammation and in the density of organisms. Long-term therapy of GORD in H. pylori infected may lead to rapid progression of atrophic gastritis intestinal metaplasia and dysplasia, and increase the risk of developing gastric cancer. More recently it has been shown that H. pylori infection may interfere with the acid suppressive therapies used for treating GORD. In our opinion the progression of gastritis depends on the threshold of acid output at which H. pylori can 'flourish'. Recently interest is growing on gastric transitional zones and Helicobacter ecology. Any decrease of acid secretion changes the behaviour of H. pylori: the activity of gastritis improves in the antrum, but it deteriorates in the body. During proton pump inhibitor treatment, H. pylori redistribution occurs within the stomach, from an antral to a corpus or fundus prevalent pattern; corpus-fundus gastritis, exacerbated by PPI therapy, may result both in a diminished acid secretion and gastro-oesophageal reflux. The interest in Barrett's oesophagus is growing due to the associated risk of adenocarcinoma. The literature seems to demonstrate that the prevalence of H. pylori infection of the stomach in Barrett's oesophagus patients is not different from that exhibited by controls, roughly one-third of the subjects. Intestinal metaplasia of the gastric cardia seems to be equally frequent in patients with and without GORD. Finally, it appears unlikely that a causal relationship exists between H. pylori infection and Barrett's-associated adenocarcinoma.

Review article: exploring the link between Helicobacter pylori and gastric cancer.

Cancer of the distal stomach, both of the intestinal and diffuse type, is strongly associated with Helicobacter pylori colonization. This bacterium causes chronic active inflammation of the gastric mucosa in the majority of colonized subjects. In a considerable number of them, this will eventually lead to a loss of gastric glands, and thus the establishment of atrophic gastritis, which is associated with the development of intestinal metaplasia and dysplasia. Development of atrophy and metaplasia of the gastric mucosa are thus strongly associated with H. pylori infection, instead of a direct and inevitable consequence of ageing. Approximately 40-50% of infected subjects develop these conditions, but they are rare in non-infected subjects. The presence of these consecutive disorders leads to a 5-90-fold increased risk for cancer of the distal stomach, in particular of the intestinal type. This sequence explains the increased risk for gastric cancer in H. pylori-infected subjects, as has been shown in various cross-sectional and longitudinal studies. In a combined analysis of three longitudinal studies, a significant trend was observed towards an increased odds ratio with longer intervals between (retrospective) serological diagnosis of H. pylori infection and observation of gastric cancer, this risk being more than eight-fold increased if the interval had been at least 15 years. This is thought to reflect development of atrophic gastritis and intestinal metaplasia with loss of H. pylori colonization in the years prior to development of cancer. Atrophic gastritis and gastric cancer thus appear closely associated with the presence of H. pylori, yet not all infected subjects will eventually develop atrophy and only a small minority develop gastric cancer. Factors that influence the risks for atrophy and cancer in the presence of infection may be related to the time that infection occurred and to characteristics of the bacterial strain and the host. Evidence for the role of these factors is now increasing. Recognition of the causal role of H. pylori in the induction of gastric cancer theoretically presents tools for cancer prevention. The efficacy of screening and bacterial eradication for prevention of distal gastric cancer is being studied in a number of large-scale intervention studies in different populations. It is hoped that these studies will also provide answers to the potential preventive role of H. pylori colonization in the development of gastro-oesophageal reflux disease and associated conditions, in particular development of cancer of the proximal stomach. Infection with H. pylori plays an important role in the aetiology of atrophic gastritis and gastric cancer. Studies suggest an eight-fold increased risk for both conditions in the presence of infection. Factors that influence the risk for both conditions in the presence of infection are the age at which infection occurred and the presence of cagA as a marker for more pathogenetic H. pylori strains. The efficacy and side-effects of intervention for the prevention of distal gastric cancer has yet to be established.

Low-Dose Pantoprazole (20mg) is Effective for Treatment of Mild Reflux Oesophagitis

Aim: Reflux of gastric acid into the oesophagus plays an important role in the development of gastro-oesophageal reflux disease (GORD). The aim of this study was to compare the efficacy and tolerability of pantoprazole 20 mg/day with ranitidine 300 mg/day in patients with mild GORD.