Endoscopic appearance of GERD: Putative role of cell proliferation

BACKGROUND: Erosive esophagitis is a frequent endoscopic feature in patients with gastro-oesophageal reflux disease. However, most of patients with heartburn/regurgitation have a non-erosive reflux disease. The reason for this heterogeneous impact of gastro-oesophageal reflux disease on oesophageal mucosa is unknown to date. AIM: To evaluate the cell proliferation status of oesophageal epithelium in both healthy normal subjects and patients with gastro-oesophageal reflux disease with or without erosions. MATERIALS AND METHODS: All the subjects underwent endoscopy and biopsies were taken at 5 cm from the squamo-columnar junction. Specimens were analysed both at histology and at transmission electron microscopy. Cell proliferation was evaluated by MIB1 immunostaining. Of the 85 subjects were studied, 10 were healthy controls with normal pH-testing and macroscopical, histological and ultrastructural patterns; 37 were patients with erosive esophagitis, and 38 patients with non-erosive reflux disease. RESULTS: At histology, of the 37 patients affected by erosive esophagitis, 30 had normal mucosa and 7 showed mild oesophagitis. One patient with non-erosive reflux disease showed signs of oesophagitis at histology. At TEM, all patients with gastro-oesophageal reflux disease had ultrastructural patterns of damage i.e. dilations of intercellular spaces (DIS), and all controls had a normal ultrastructural pattern. The mean (+/-SD) MIB1-LI values of normal subjects and non-erosive reflux disease and erosive oesophagitis patients were 62.2% (+/-9.1), 29.7% (+/-7.2) and 16.2% (+/-5.2), respectively; there were significant differences among the three groups (p<0.001). CONCLUSIONS: Oesophageal mucosa of patients with reflux symptoms presents a decrease in MIB1 immunostaining of 50% and 25% in non-erosive reflux disease and erosive esophagitis patients with respect to normal subjects.     

Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease: Spectrum disease or distinct phenotypic presentations?

BACKGROUND: The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed. AIM: To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations. METHODS: Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period. RESULTS: Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls. CONCLUSIONS: In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.     

Reflux rising! An essay on witnessing a disease in evolution

BACKGROUND AND AIM: The prevalence of gastro-oesophageal reflux disease is thought to be rising but supporting evidence is sparse. We assessed trends from data prospectively collected over 25 years at our centre which serves Rotherham's 250000 population. PATIENTS AND METHODS: Detailed computerised records have been kept of all patients investigated for upper gastrointestinal symptoms. Definition: Erosive oesophagitis=endoscopy-verified erosive changes. Non-erosive reflux=heartburn+/-regurgitation but normal endoscopy. Gastro-oesophageal reflux disease=erosive oesophagitis+non-erosive reflux, i.e. total. RESULTS: The data, presented in 5-year time periods spanning 1977-2001, showed four major changing trends. (1) The numbers with newly diagnosed gastro-oesophageal reflux disease rose markedly, affecting both erosive oesophagitis and non-erosive reflux. Gastro-oesophageal reflux disease: n=714; 1587; 2381; 3812; 3880. (2) The proportion of women affected rose from 0.36 to 0.82. (3) Gastro-oesophageal reflux disease patients were older than the general population; the mean age at presentation rose from 48.0 to 53.5 years. (4) Presentation with haemorrhage (percentage of erosive oesophagitis) rose from 5.2% to 10.9% but, as with stricture (around 4%), remained uncommon. Throughout, few (4.4%) changed from non-erosive reflux to erosive oesophagitis. CONCLUSION: The marked increase in gastro-oesophageal reflux disease cannot be accounted for by greater awareness alone for the demographic profile has changed, or by misclassification as erosive oesophagitis was diagnosed on endoscopic appearances. The dramatic five-fold increase in gastro-oesophageal reflux disease is a new phenomenon, perhaps an example of a disease in evolution.     

Natural history of gastro-oesophageal reflux disease without oesophagitis (NERD) – a reappraisal 10 years on

BACKGROUND AND AIM: Ten years ago we published a study describing the 6-month outcome of 33 outpatients with typical gastro-oesophageal reflux disease symptoms and pH-metry proven excess gastro-oesophageal reflux but without endoscopical evidence of oesophagitis, currently referred to as patients with gastro-oesophageal reflux disease without oesophagitis. We now present an update of that report concerning morbidity, drug consumption and quality of life of the original patients 10 years after the initial diagnosis. METHODS: The study consisted of the retrieval and revision of all clinical and instrumental records concerning the cohort of 33 above-mentioned patients. Data are available regarding annual intervals within the first 5 years from original diagnosis and, subsequently, with a follow-up ranging from 7 to 14 years (median 10 years). The records of these 33 patients were reviewed, including the results of clinical visits at the outpatients department, of oesophagogastroduodenoscopies and pH- metries. Finally, a telephonic interview was conducted by means of a structured questionnaire, aiming at evaluating present symptoms, actual therapy if any, health-related quality of life and other information regarding any gastro-oesophageal reflux disease symptoms. RESULTS: Of the original 33 patients, 31 are still alive and 2 were lost to follow-up. Of the 29 remaining, only 1 is definitively not complaining of any gastro-oesophageal reflux disease-related symptoms. Within 5 years of the first diagnosis, oesophagitis was found in all but one of the 18 subjects who underwent repeated endoscopy. At the latest follow-up check, after a median of 10 years, out of the 28 still complaining of gastro-oesophageal reflux disease symptoms, 21 (75%) were presently taking antisecretory drugs (proton pump inhibitors and H-2 receptor antagonists) because of gastro-oesophageal reflux disease symptoms/lesions, 12 of whom intermittently or on demand and the remaining 9 continuously. Two patients (2/28) underwent antireflux surgery, but despite this were still taking antisecretory drugs (in one case H2-RA; in the other proton pump inhibitor). The health-related quality of life, self-evaluated by the patient by means of a VAS scoring from 0 (worst possible) to 10 (best possible) increased significantly from 3.2 to 6.5 from baseline (before therapy) to present time, possibly due to the positive effect of present therapy. CONCLUSIONS: Our study conducted on a cohort of endoscopy-negative patients with pH-metry-confirmed reflux disease has shown that after a median time of 10 years following the original diagnosis, the majority of patients have, in fact, developed reflux oesophagitis and are on prolonged antisecretory therapy because of recurrent gastro-oesophageal reflux disease symptoms/lesions. The study confirms that gastro-oesophageal reflux disease without oesophagitis, as well as gastro-oesophageal reflux disease at large, is a chronic disease characterised by increasing severity with time, which requires protracted medical therapy in a vast proportion of patients. Absence of endoscopic oesophagitis at presentation does not represent a positive prognostic factor.     

Manometric and pH-metric features in gastro-oesophageal reflux disease patients with and without Helicobacter pylori infection

BACKGROUND: The role of Helicobacter pylori in the pathogenesis and evolution of gastro-oesophageal reflux disease is still debated. AIM: To investigate the impact of Helicobacter pylori infection on the oesophageal function and on intra-gastric and intra-oesophageal pH in patients with gastro-oesophageal reflux. METHODS: Fifty patients with non-complicated-gastro-oesophageal reflux disease classified according to Savary-Miller in: grade O, n=24; grade 1, n=19; grade 2, n=6; grade 3, n=1. Of these patients, 24 were Helicobacter pylori positive and 26 negative. Patients underwent, on two different days, stationary oesophageal manometry and 24-hour gastro-oesophageal pH-metry. RESULTS: No difference was observed between Helicobacter pylori infected and non-infected individuals with regard to lower oesophageal sphincter function, oesophageal peristalsis and gastrooesophageal reflux. These parameters were more impaired in individuals with erosive gastro-oesophageal reflux disease but this result was not dependent on the Helicobacter pylori status. Helicobacter pylori did not influence the pattern of gastric pH; however, considering only individuals with non-erosive gastro-oesophageal reflux disease, gastric pH was significantly higher in infected individuals, who, histologically, also showed a corpus predominant gastritis. CONCLUSIONS: In patients with gastro-oesophageal reflux disease, Helicobacter pylori does not affect the oesophageal motility or the gastro-oesophageal reflux. These parameters are strictly related to the severity of gastro-oesophageal reflux disease as assessed at endoscopy. In patients with non-erosive gastro-oesophageal reflux disease, a corpus predominant Helicobacter pylori gastritis could be responsible for the less severe gastro-oesophageal reflux.     

Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity

BACKGROUND: Bile acid toxicity has been shown in the gastric, colonic, and hepatic tissues; the effect on oesophageal mucosa is less well known. AIMS: To determine the spectrum of bile acids refluxing in patients with gastro-oesophageal reflux disease and its relation to oesophageal pH using a new technique of combined oesophageal aspiration and pH monitoring. METHODS: Ten asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary-Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid assay of the oesophageal samples was performed using modified high performance liquid chromatography. RESULTS: The peak bile acid concentration and DeMeester acid scores were significantly higher in the patients with oesophagitis (median bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile acids detected were cholic, taurocholic, and glycocholic acids but there was a significantly greater proportion of secondary bile acids, deoxycholic and taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH, a temporal relation existed between reflux of taurine conjugates and oesophageal acid exposure (r=0.58, p=0.009). CONCLUSION: Toxic secondary bile acid fractions have been detected in patients with extensive mucosal damage. Mixed reflux is more harmful than acid reflux alone with possible toxic synergism existing between the taurine conjugates and acid.     

High prevalence of reflux symptoms in duodenal ulcer patients who develop gastro-oesophageal reflux disease after curing Helicobacter pylori infection

BACKGROUND: Gastro-oesophageal reflux disease may develop following eradication of Helicobacter pylori. However gastro-oesophageal reflux disease could be preexistent and misdiagnosed since patients often misinterpret gastro-oesophageal reflux disease symptoms or focus their attention on abdominal symptoms. A questionnaire for analysis of gastro-oesophageal reflux disease symptoms has not been used until now. METHODS: A total of 70 patients with duodenal ulcer and Helicobacter pylori gastritis, without oesophagitis and/or typical gastro-oesophageal reflux disease symptoms were studied. All patients received a questionnaire with 5 items focused on abdominal symptoms and 5 on gastro-oesophageal reflux disease symptoms. The two symptom scores were calculated separately. After Helicobacter pylori treatment, follow-up consisted of clinical controls every 3 months for 1 year. Patients were asked to describe their complaints and to answer the questionnaire. If gastro-oesophageal reflux disease symptoms recurred endoscopy was performed. RESULTS: At interview, all patients reported a significant improvement in their abdominal symptoms after eradication; however 23 patients (32.8%: group A) reported the occurrence of gastro-oesophageal reflux disease symptoms, and 5 of them developed oesophagitis; gastrooesophageal reflux disease symptoms did not appear in the remaining 47 patients (group B). Basal gastro-oesophageal reflux disease score was significantly higher in group A than in group B (1.9+/-1.5 vs 0.9+/-0.9, p<0.005), while the abdominal symptoms score was not different. Following eradication, the score for abdominal symptoms decreased significantly (4.2+/-1.5 vs 1+/-0.8, p<0.0001) in the two groups; conversely, the total gastro-oesophageal reflux disease score remained unchanged, improving in 2 patients in group A and 11 in B, and worsening in 5 in group A and in 1 in B. Presence of hiatus hernia and male sex significantly correlated with the development of reflux symptoms. CONCLUSIONS: Patients who present with gastro-oesophageal reflux disease after Helicobacter pylori eradication are likely to already be affected by gastro-oesophageal reflux disease.     

The role of cagA Helicobacter pylori strains in gastro-oesophageal reflux disease

BACKGROUND AND AIMS: The role of Helicobacter pylori infection in gastro-oesophageal reflux disease is controversial. The aim of this study was to evaluate the prevalence of colonization by cagA-positive and cagA-negative H. pylori strains in the spectrum of gastro-oesophageal reflux disease. METHODS: A total of 108 patients (50 male/58 female; mean age, 50.3 years) with dyspepsia and peptic ulcer or erosive gastritis/duodenitis were categorized into patients without reflux and patients with reflux oesophagitis graded from I to IV. All patients underwent upper endoscopy with biopsies of the antrum. H. pylori was detected by histology, urease test and polymerase chain reaction. The cagA status was diagnosed in the gastric biopsy by polymerase chain reaction. RESULTS: The overall prevalence of H. pylori colonization in patients with reflux was 68.6% and was 70.2% in those without oesophageal disease (P = 0.862). Colonization by cagA-positive strains was also not statistically different between the two groups (31.4% versus 40.4%, P = 0.332). However, patients with grades II-IV reflux oesophagitis were less colonized by the bacterium (36.4%) than patients with grade I oesophagitis (77.5%) (P = 0.009). H. pylori cagA-positive strains were also less likely to colonize the stomach of patients with grades II-IV oesophagitis (0%), than grade I reflux oesophagitis (40%) patients and controls (40.4%). CONCLUSIONS: Infection of the stomach by H. pylori and especially by H. pylori cagA strains may play a protective role against the development of the most severe forms of gastro-oesophageal reflux disease.     

On-demand proton pump inhibitor therapy in patients with gastro-oesophageal reflux disease

On-demand therapy is an established modality in long-term therapy with histamine-2-receptor antagonists, in cases of mild non-erosive gastro-oesophageal reflux disease. In the literature, only a few studies have specifically addressed the problem of proton pump inhibitors on-demand treatment. The evidence, so far, available suggests that this might be an effective modality of long-term treatment in the majority of patients with non-erosive gastro-oesophageal reflux disease. This treatment modality appears to be the most cost-effective and the best tolerated medical regimen for gastro-oesophageal reflux disease. It also seems to be able to restore the impairment of health-related quality of life due to gastro-oesophageal reflux disease symptoms. Although the current standard of care for patients with non-erosive gastro-oesophageal reflux disease is maintenance therapy with daily administration of a proton pump inhibitor agent, on-demand therapy, with the same drug, may be a reasonable long-term choice. The ideal proton pump inhibitors for such treatment will be those with a more rapid onset of action, more profound acid inhibition, more predictable therapeutic effect and less drug-drug interactions. Newer proton pump inhibitors, like esomeprazole, the S-chiral isomer of omeprazole, are promising drugs for on-demand treatment of gastro-oesophageal reflux disease.     

Should we screen reflux oesophagitis patients for coeliac disease?

OBJECTIVES: Oesophagitis and gastro-oesophageal reflux have been implicated recently in the manifestations of coeliac disease. The aim was to investigate this association in a primary-care setting. METHODS: First, the prevalence of coeliac disease was calculated in 1198 adults with oesophagitis, in 2541 adults with reflux symptoms and in 200 adults suffering from dysphagia; 5459 patients with a history consistent with dyspepsia and 709 patients with a suspicion of coeliac disease served as controls. Second, the prevalence of oesophagitis was estimated in 382 untreated and 232 treated coeliac patients; controls here comprised 5404 patients with dyspeptic symptoms and 2525 patients with reflux symptoms. Third, oesophagitis and oesophageal reflux symptoms were investigated before and after a gluten-free diet was followed in 67 adults with coeliac disease. The diagnosis of coeliac disease was based on small-bowel histology; histological exclusion of the disease was unambiguous in all controls. Oesophagitis was identified by endoscopic inspection. RESULTS: Altogether, 0.9% of patients with oesophagitis and 0.6% of those with oesophageal reflux symptoms had coeliac disease. The corresponding percentages were 1.0% in patients with dyspepsia and 12% with suspicion of coeliac disease. The prevalence of oesophagitis was 5.2% in untreated coeliac disease, 5.6% in treated coeliac disease, 7.0% in patients with dyspepsia, and 27% in symptomatic reflux disease. In coeliac patients, the reflux symptoms were mild but nevertheless were alleviated on a gluten-free diet. CONCLUSIONS: This study does not support the conception that patients with reflux oesophagitis should be screened vigorously for coeliac disease. The association between these two conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for reflux symptoms in coeliac disease.     

Effect of acute and chronic administration of the GABA B agonist baclofen on 24 hour pH metry and symptoms in control subjects and in patients with gastro-oesophageal reflux disease

BACKGROUND AND AIMS: The gamma-aminobutyric acid (GABA(B)) agonist baclofen has been shown to reduce reflux episodes during the first three postprandial hours in patients with gastro-oesophageal reflux disease (GORD) and in normal controls. The aim of the study was to assess the effect of acute (one day) and chronic (four weeks) administration of baclofen on 24 hour pH metry and symptoms in GORD patients and normal controls. PATIENTS AND METHODS: Acute study: 28 patients with GORD with none or mild oesophagitis at endoscopy and 15 controls underwent oesophageal and gastric 48 hour pH metry in which baclofen or placebo was given for 24 hours in a double blinded manner. Chronic study: 16 GORD patients received baclofen (10 mg four times daily) or placebo for four weeks. Twenty four hour oesophageal pH metry and reflux symptom scores were evaluated before and at the end of treatment. RESULTS: Acute study: the number of reflux episodes and per cent time with pH <4 was significantly lower after baclofen in GORD patients and controls (p<0.003; p<0.0007). Gastric pH increased significantly in GORD patients and controls (p<0.001; p<0.05). Chronic study: four weeks after initial administration of baclofen, the number of reflux episodes and percentage of time with pH <4 significantly decreased in all GORD patients (p<0.003; p<0.02). Symptom scores significantly improved after treatment with baclofen (p<0.0007). CONCLUSIONS: The GABA(B) agonist baclofen reduces 24 hour gastro-oesophageal reflux and increases gastric pH in GORD patients and controls. When given for one month to GORD patients, baclofen reduces oesophageal acid refluxes and significantly improves symptoms. Baclofen may be useful in the therapy of GORD.     

Inflammation at the cardio-oesophageal junction: relationship to acid and bile exposure

BACKGROUND: The aetiology of inflammation in cardiac mucosa at the gastro-oesophageal junction (carditis) is unclear, although gastro-oesophageal reflux has been suggested. OBJECTIVES: To correlate histological features of carditis with oesophageal acid exposure (gastro-oesophageal reflux) and proximal gastric bile exposure (duodenogastric reflux) in patients with symptoms of gastro-oesophageal reflux disease (GORD). METHODS: Sixty-six patients with reflux symptoms underwent endoscopy with biopsy, oesophageal manometry, 24-h oesophageal pH testing and 24-h proximal gastric Bilitec 2000 testing. Inflammation in glandular mucosa was assessed using the updated Sydney System. Fifteen healthy volunteers underwent pH and Bilitec 2000 testing and served as controls. RESULTS: There was no correlation between either the presence or histological grade of carditis and oesophageal acid exposure or proximal gastric bilirubin exposure. Patients with reflux symptoms had as much duodenogastric reflux into the proximal stomach as did control subjects. CONCLUSIONS: We were unable to establish either gastro-oesophageal or duodenogastric reflux as the predominant cause of inflammation in cardiac mucosa.     

Oesophagitis,Signs of Reflux,and Gastric Acid Secretion in Patients with Symptoms of Gastro-Oesophageal Reflux Disease

Johansson K-E, Ask P, Boeryd B, Fransson S-G, Tibbling L. Oesophagitis, signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal reflux disease. Scand J Gastroenterol 1986, 21, 837-847

In a study comprising 100 patients referred to a surgical clinic with symptoms suggestive of gastro-oesophageal reflux disease the value of different diagnostic procedures was investigated. Positive acid perfusion and 24-h pH tests were the commonest findings. Forty-nine per cent showed a normal oesophageal mucosa or diffuse oesophagitis at endoscopy. The severity of heartburn and regurgitation did not differ between patients with normal oesophageal mucosa and oesophagitis of various severities. The severity of macroscopic oesophagitis was significantly correlated to the total reflux time, the presence of reflux or a hiatal hernia at radiology, an open cardia or reflux at endoscopy, pressure transmission or reflux and low lower oesophageal sphincter pressure at manometry. Gastric hypersecretion was found in 66% of the patients. Gastric acid secretion was not correlated to the severity of oesophagitis or to the findings at 24-h pH test. In patients with severe oesophagitis the sensitivity for radiologic, manometric, and endoscopic signs of incompetence of the gastro-oesophageal junction was 94%.     

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

BACKGROUND: 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. AIMS: To determine the true prevalence of gastro-oesophageal reflux disease in patients with Helicobacter pylori-related duodenal ulceration. METHOD: 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. RESULTS: 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. CONCLUSION: 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.     

Reflux oesophagitis in children; the role of endoscopy: A multicentric Italian survey

BACKGROUND: The decision whether to perform endoscopy in children with suspected reflux oesophagitis is not a straightforward one. Few symptoms are specific for oesophagitis and the diagnosis is not always correlated even to visual findings on endoscopy. AIM: The aim of this study was to define the role of endoscopy and especially of histology in the diagnosis of reflux oesophagitis and to examine the correlations between symptoms, endoscopic findings and histology in children with suspected gastroesophageal reflux disease. PATIENTS AND METHODS: One hundred and thirty-six patients with a clinical diagnosis of reflux oesophagitis, aged 1-18 years (mean 8.43; standard deviation +/-4.4), were enrolled from 12 Italian Paediatrics Gastroenterology Centres; symptom score, endoscopic and histologic oesophagitis scores were observed before and after therapy with proton pump inhibitors. RESULTS: Before therapy, a high correlation between the prevailing symptom score and endoscopic score was demonstrated, but not with histologic score: there was a significant tendency for histologic grade to exceed visual findings. After therapy, endoscopic score and histologic score were significantly improved. CONCLUSIONS: Oesophageal biopsies increase the diagnostic accuracy of upper endoscopy. Histologic grading is often much more important than the endoscopic appearance, so that endoscopic oesophageal biopsies are very important aids in the diagnosis of oesophagitis. Appropriate clinical evaluation of symptoms must occur before endoscopic examination.     

Maintenance treatment with ranitidine compared with fundoplication in gastro-oesophageal reflux disease

The study comprises 31 patients with gastro-oesophageal reflux disease who received 8 weeks' treatment with ranitidine. Sixteen of the patients received in addition maintenance treatment with ranitidine (150 mg twice daily) for another 6 months, and fundoplication was performed on 15 patients. There was a significant improvement in endoscopic and histologic findings, a decrease in gastric acid secretion, and a reduction of symptoms during short-term treatment with ranitidine. No further improvement was seen in any of the factors after half a year of ranitidine. After surgery the total reflux time during 24 h decreased to practically zero, all patients had normal endoscopic findings and negative acid perfusion tests, and reflux symptoms had disappeared completely. Anti-reflux surgery was superior to treatment with ranitidine. Reflux oesophagitis is therefore not improved any further by a half year's treatment with ranitidine beyond what is achieved with short-term therapy.     

Natural history of reflux oesophagitis: a 10 year follow up of its effect on patient symptomatology and quality of life.

BACKGROUND--Although oesophagitis is the most common diagnosis made at upper gastrointestinal endoscopy, data on the longterm outcome of affected patients are sparse. AIMS--This study assessed the level of reflux symptoms, quality of life, drug consumption, and complications in patients at least 10 years after diagnosis of oesophagitis at one centre. PATIENTS--One hundred and fifty two patients with typical reflux symptoms and a first time diagnosis by endoscopy of grade I-III oesophagitis between 1981 and 1984, were followed up using a postal questionnaire and telephone interview. RESULTS--Eighteen of 152 patients had died, 33 failed to respond, and 101 replied (mean follow up 11 years, range 121-160 months). Over 70% of patients still had heartburn at least daily (32%) or weekly (19%) or required daily acid suppression treatment (20%). Two patients (2%) had developed oesophageal strictures and one had Barrett's oesophagus. Two of eight quality of life scores (physical function and social function) measured by the Short Form-36 were significantly lower than Northern Ireland population scores. CONCLUSION--Nearly three quarters of patients previously diagnosed as having oesophagitis still had significant morbidity related to gastro-oesophageal reflux disease more than 10 years after diagnosis. Some quality of life scores were significantly lower than those of the general population.     

The role of delayed gastric emptying and impaired oesophageal body motility

Delayed gastric emptying in a variable proportion of patients with gastro-oesophageal reflux disease has been observed in most series, however a relationship between delayed gastric emptying and increased gastro-oesophageal reflux has not been convincingly demonstrated. Enhanced postprandial accommodation and delayed emptying of the proximal stomach have been described, but some controversy exists. Impaired primary peristalsis is often present especially in patients with oesophagitis and its prevalence increases with increasing severity of inflammatory mucosal lesions. Patients with gastro-oesophageal reflux disease often have defective triggering of secondary peristalsis independently of presence of oesophagitis. It is presently unclear if impaired oesophageal motility is a primary defect or an irreversible consequence of inflammation. Attempts at pharmacological improvement of impaired oesophageal motility have been so far disappointing. Patients with partially preserved neuromuscular structures need to be identified in order to select them for new prokinetic therapy.     

Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy

Esophagus - This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid...     

Eradication of Helicobacter pylori does not increase acid reflux in patients with mild to moderate reflux oesophagitis

BACKGROUND: A substantial minority of patients with gastro-oesophageal reflux disease (GERD) are infected with Helicobacter pylori, but there is controversy as to whether these patients should be treated for their infection. We hypothesized that H. pylori eradication increases gastro-oesophageal acid reflux in such patients with time. METHODS: Thirty-five consecutive H. pylori-infected patients (16 M and 19 F) with mild or moderate reflux oesophagitis were enrolled. Twenty-four-hour intra-oesophageal (n = 35) and intragastric (n = 12) pH-metry was recorded before and 15 months after H. pylori eradication. Gastric biopsy specimens from the antrum and corpus were obtained from 10 consecutive patients before and 15 months after H. pylori eradication. RESULTS: Fifteen months after eradication of H. pylori there was a significant decrease in percentage time oesophageal pH < 4 in the recumbent position only (P = 0.04). Despite a marked reduction in the severity of gastritis, there was no significant change in gastric acidity, total intra-oesophageal acid exposure or symptom score. Heartburn improved in 12, worsened in 7. and remained unchanged in 16 patients (P = 0.36) without any significant relationship to individual changes in acid exposure (P = 0.60). CONCLUSIONS: H. pylori eradication does not increase gastric acidity or gastro-oesophageal acid reflux in patients with mild to moderate reflux oesophagitis over the first 15 months.