Water load test before and after PPI therapy in patients with gastro-oesophageal reflux disease

BACKGROUND: Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting. AIMS: To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls. METHODS: Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40 mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers. RESULTS: Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores. CONCLUSIONS: In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients.     

Natural history of gastro-oesophageal reflux disease without oesophagitis.

This retrospective study was undertaken to characterise the clinical course and reflux pattern of patients with gastro-oesophageal reflux without evidence of oesophagitis. We investigated 33 patients (12 women, 21 men; mean age 36 years) with typical symptoms, a negative oesophagoscopy, and a 24 hour oesophageal pH-metry indicative of pathological gastro-oesophageal reflux. All patients received antacids or prokinetic drugs or both for three to six months. Nineteen of 33 patients still had symptoms at the end of treatment, of whom five had developed erosive changes of the oesophageal mucosa. The other 14 discontinued treatment and remained asymptomatic during a six month follow up period. Comparison of the pretreatment pH-metry data of the 19 symptomatic patients and the 14 asymptomatic patients showed no differences in the pattern of gastro-oesophageal reflux in the two groups. We conclude that in a substantial proportion of patients with pathological reflux without oesophagitis symptoms may persist and mucosal lesions may develop during conventional treatment without any apparent change in the reflux. Patients who developed endoscopic oesophagitis did not have a more severe pretreatment pattern of gastro-oesophageal reflux when compared with those who did not develop oesophageal mucosal damage.     

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet

BACKGROUND: Coeliac disease patients show a number of gastrointestinal motor abnormalities, including a decrease in lower oesophageal sphincter pressure. The prevalence of endoscopic oesophagitis in these subjects however is unknown. Aim: To evaluate whether untreated adult coeliac patients had an increased prevalence of reflux oesophagitis and, if so, to assess whether a gluten free diet exerted any beneficial effect on gastro-oesophageal reflux disease (GORD) symptoms. PATIENTS AND METHODS: We retrospectively studied 205 coeliac patients (females/males 153/52, median age 32 years) who underwent endoscopy for duodenal biopsy and 400 non-coeliac subjects (females/males 244/156, median age 37 years) referred for endoscopy for upper gastrointestinal symptoms. Each patient was given a questionnaire for evaluation of GORD symptoms prior to and 4-12 months after endoscopy. Coeliac patients were given a gluten free diet. Oesophagitis patients of both groups, following an eight week course of omeprazole, were re-evaluated for GORD symptoms at four month intervals up to one year. Significance of differences was assessed by Fisher's exact test. RESULTS: Oesophagitis was present in 39/205 (19%, 95% confidence interval (CI) 13.8-25.0%) coeliac patients and in 32/400 (8%, 95% CI 5.5-11.1%) dyspeptic subjects. At the one year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% CI 13-42.1%) coeliacs with oesophagitis and in 23/32 (71.8%, 95% CI 53.2-86.2%) non-coeliac subjects with oesophagitis. CONCLUSION: Coeliac patients have a high prevalence of reflux oesophagitis. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that coeliac disease may represent a risk factor for development of reflux oesophagitis.     

Surgical experience improves the long-term results of Nissen fundoplication

BACKGROUND: Nissen fundoplication relieves symptoms of gastro-oesophageal reflux and effectively heals oesophagitis. During long-term follow-up some cases of recurrent reflux are seen. We investigated the possibility that long-term cure of gastro-oesophageal reflux after fundoplication is influenced by the surgeon's experience and focused interest, in line with results of surgery for rectal, gastric, and breast cancer. METHODS: One hundred and five consecutive patients were evaluated a median of 77 months after open Nissen-Rossetti fundoplication for erosive oesophagitis. Follow-up included personal interviews and upper gastrointestinal endoscopy by an investigator not previously involved in the patients' treatment. The surgeons were classified as experienced (>10 of the operations in the series), less experienced (<10 operations), or trainees. RESULTS: Of the most experienced surgeons' patients, 97% had no or at most mild reflux symptoms at follow-up, compared with 88% of the of less experienced surgeons' patients (P = 0.04). Healing of erosive oesophagitis was commoner when the operations were performed by experienced specialist surgeons (88% versus 72%; P = 0.04). The reoperation rate fell as the surgeons' experience increased, from 12% to 4%. CONCLUSIONS: Surgery for gastro-oesophageal reflux should be centralized to units specializing in the techniques and with sufficient annual numbers of operations to optimize results. This policy becomes especially advisable as laparoscopic surgery increases the numbers of treated patients.     

Symptoms of gastro-oesophageal reflux disease in elderly people.

The frequency and the possible age-related characteristics of gastro-oesophageal reflux disease (GORD) were investigated in 195 consecutive elderly subjects (mean age 74 years), referred to endoscopy for abdominal symptoms or sideropenic anaemia. In the 105 of these patients in whom there was any suspicion of GORD, 24-hour pH monitoring was carried out. All the patients were interviewed before the examinations. Erosive or complicated (grade 2-4) oesophagitis was found in 18% of patients. The main symptoms in these patients were dysphagia, respiratory symptoms and vomiting. Chronic cough, hoarseness or wheezing were present in 57% of patients with oesophagitis compared with 33% of those without oesophagitis (p less than 0.001). The occurrence of heartburn and regurgitation did not differ significantly between patients with or without oesophagitis, although the mean symptom scores were higher in those with oesophagitis. Dyspepsia and chest pain were not typical symptoms in oesophagitis. Of patients with oesophagitis 29% had no typical symptoms of GORD; only 24% of patients with regurgitation had oesophagitis. In 24-hour pH monitoring, a significant increase in the occurrence of symptoms was not seen until total reflux time pH less than 4 exceeded 10%. The occurrence of heartburn did not correlate with the extent of reflux in the pH study. In conclusion, typical symptoms of GORD in the aged were regurgitation, dysphagia, respiratory symptoms and vomiting rather than heartburn.     

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.     

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.     

The Effect of Cisapride in Maintaining Symptomatic Remission in Patients with Gastro-Oesophageal Reflux Disease

Background: Successful treatment of gastro-oesophageal reflux disease (GORD) has traditionally been assessed as healing of reflux oesophagitis, which may not be relevant in patients with moderate disease. In these patients symptom relief and patient satisfaction with therapy are of fundamental importance. Cisapride has well-documented prokinetic effects and may be well suited for long-term therapy of GORD, but its effectiveness in purely symptomatic treatment is unknown. We therefore compared two dosage regimens of cisapride with placebo over a period of 6 months in patients with evidence of gastro-oesophageal reflux, initially treated with antisecretory medication, with regard to maintaining symptom relief and satisfaction with treatment. Methods: Five hundred and thirty-five patients with reflux oesophagitis grade 1 (n = 293) or 2 (n = 124) or with no reflux oesophagitis but pathologic 24-h pH-metry (n = 118) achieved satisfactory symptom relief with an H₂-receptor antagonist or proton pump inhibitor within 4–8 weeks. In a double-blind randomized, parallel-group study, they were then treated with cisapride, 20 mg at night or 20 mg twice daily, or placebo and followed up for a maximum period of 6 months. Relapse was defined as dissatisfaction with therapy or an average consumption of more than two antacid tablets a day. Results: Median time to relapse was 63 days for cisapride, 20 mg twice daily; 59 days for cisapride, 20 mg at night; and 49 days for placebo. Time to relapse was not significantly different (P = 0.09). Presence and grade of oesophagitis at base line, type of therapy before randomization, and pattern of non-reflux symptoms at base line did not influence these findings significantly. Conclusion: The study indicates that cisapride is of limited value in maintenance therapy of GORD in patients in whom symptom relief has been accomplished with potent antisecretory medication. This ‘step-down’ approach to therapy seems disadvantageous in the long-term therapy of GORD.     

Surgical Experience Improves the Long-Term Results of Nissen Fundoplication

Background: Nissen fundoplication relieves symptoms of gastro-oesophageal reflux and effectively heals oesophagitis. During long-term follow-up some cases of recurrent reflux are seen. We investigated the possibility that long-term cure of gastro-oesophageal reflux after fundoplication is influenced by the surgeon's experience and focused interest, in line with results of surgery for rectal, gastric, and breast cancer. Methods: One hundred and five consecutive patients were evaluated a median of 77 months after open Nissen-Rossetti fundoplication for erosive oesophagitis. Follow-up included personal interviews and upper gastrointestinal endoscopy by an investigator not previously involved in the patients' treatment. The surgeons were classified as experienced (&gt;10 of the operations in the series), less experienced (&lt;10 operations), or trainees. Results: Of the most experienced surgeons' patients, 97% had no or at most mild reflux symptoms at follow-up, compared with 88% of the of less experienced surgeons' patients (P = 0.04). Healing of erosive oesophagitis was commoner when the operations were performed by experienced specialist surgeons (88% versus 72%; P = 0.04). The reoperation rate fell as the surgeons' experience increased, from 12% to 4%. Conclusions: Surgery for gastro-oesophageal reflux should be centralized to units specializing in the techniques and with sufficient annual numbers of operations to optimize results. This policy becomes especially advisable as laparoscopic surgery increases the numbers of treated patients.     

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.     

Long-term clinical course of extra-oesophageal manifestations in patients with gastro-oesophageal reflux disease: A prospective follow-up analysis based on the ProGERD study

BACKGROUND: Gastro-oesophageal reflux disease can be associated with extra-oesophageal reflux disease such as chronic cough or laryngeal symptoms. The aim of this study was to analyse the clinical course of extra-oesophageal reflux disease in a large population with gastro-oesophageal reflux disease and extra-oesophageal reflux disease under routine clinical care. METHODS: ProGERD is a prospective multicentre cohort study of 6215 outpatients with gastro-oesophageal reflux disease. At baseline all patients underwent endoscopies and were interviewed for extra-oesophageal reflux disease. Initial standardised treatment was esomeprazole for up to 8 weeks. After 2 years of follow-up, reflux symptoms and the prevalence of extra-oesophageal reflux disease were assessed. A multivariate analysis was performed with resolved versus persistent symptoms for chronic cough and laryngeal symptoms as dependent predictors. Independent variables were gender, age, body mass index (BMI), alcohol consumption, cigarette smoking, gastro-oesophageal reflux disease classification, history of gastro-oesophageal reflux disease in the family, duration of gastro-oesophageal reflux disease and proton pump inhibitors medication. RESULTS: Four thousand four hundred and four patients (71%) were available for analysis at 2 years, including 570 and 454 patients who had chronic cough and laryngeal disorders at baseline, respectively. In 63% and 74% of the patients, chronic cough and laryngeal disorders had resolved. Patients with persistent respiratory symptoms in year 2 had significantly more reflux symptoms. Further clinically relevant associations were smoking and non-steroidal anti-inflammatory drugs use. According to the multivariate analysis, classification of gastro-oesophageal reflux disease, proton pump inhibitors medication or duration of gastro-oesophageal reflux disease were not associated with the resolution of cough or laryngeal symptoms. CONCLUSION: In most patients with gastro-oesophageal reflux disease and extra-oesophageal reflux disease, respiratory symptoms resolve during long-term routine care. A high reflux symptom load was associated with the persistence of respiratory disorders.     

Histological findings after routine biopsy at the gastro-oesophageal junction

OBJECTIVE: Endoscopy with biopsy is an important diagnostic procedure in patients with gastro-oesophageal reflux disease. However, it is still unclear whether histological findings such as intestinal metaplasia, squamous epithelial hyperplasia, and carditis should have an impact on patient management, and whether routine biopsies at the gastro-oesophageal junction should be taken. DESIGN: Patients undergoing routine gastroscopy for various indications were biopsied twice just below, directly at, and right above the gastro-oesophageal junction. METHODS: Clinical symptoms, endoscopic oesophagitis, and histopathologies such as carditis, reflux disease, and intestinal metaplasia were determined and graded. RESULTS: Epithelial hyperplasia suggestive of reflux disease (63%), chronic carditis (94%), active carditis (40%), foveolar hyperplasia (75%), and intestinal metaplasia (14%) were frequently observed. For patients with a normal appearing Z-line, there was a weak correlation of intestinal metaplasia at the cardia with intestinal metaplasia in the stomach (Spearman's R = 0.2, P = 0.008), but no correlation with either chronic or active carditis, or with epithelial hyperplasia in the oesophagus. There was no correlation between H. pylori status or symptoms of reflux disease with epithelial hyperplasia. The severity of chronic and active carditis was closely correlated with H. pylori status (R = 0.37, P < 0.00001). The median time for gastroscopy in 30 control patients was 4.6 min, while endoscopy with additional biopsies at the gastro-oesophageal junction took a median of 8 min (U-test, P < 0.00001). CONCLUSIONS: Intestinal metaplasia at the gastro-oesophageal junction was encountered too frequently to warrant regular follow-up in a surveillance programme. Correlation of epithelial hyperplasia with symptoms of reflux disease is poor. We propose that routine biopsy at the gastro-oesophageal junction is not warranted until an impact on patient management can be demonstrated.     

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole

BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.     

The lessons learned from randomized clinical trials of GERD.

Despite the huge number of randomized controlled clinical trials published on gastro-oesophageal reflux disease, the translation of the information gathered into clinical practice is rather limited. The aim of this article is to summarize the results of pivotal randomized controlled clinical trials and review articles on reflux disease and evaluate to what extent their results can be applied to current clinical practice. We reviewed the most relevant randomized controlled clinical trials and reviews since the publication of the first randomized controlled clinical trial on reflux oesophagitis (1978) to date. Six areas were explored, namely: (1) diagnostic "entry" criteria, (2) efficacy parameters, (3) duration of therapy, (4) degree of antisecretory effect, (5) placebo effect, (6) follow-up data. Gastro-oesophageal reflux disease is now the most frequent upper GI disorder treated by gastroenterologists in Europe and North America. There is still a dearth of information regarding the natural history of the disease. The types of information generated through randomized controlled clinical trials have had only limited applicability to routine clinical practice. In the future, large cooperative databases accumulating the clinical histories of a great variety of gastro-oesophageal reflux disease patients may help to provide us with the much needed insights into the natural history of this common disorder.     

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%.     

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.     

The role of smoking and alcohol in metaplasia and cancer risk in Barrett's columnar lined oesophagus.

Smoking and alcohol consumption predispose to oesophageal mucosal damage and exacerbates gastro-oesophageal reflux. The alcohol and smoking habits of patients with severe oesophagitis (n = 24), Barrett's columnar lined oesophagus (CLO) (n = 58), and adenocarcinoma arising in CLO (n = 23) were studied. There was no significant difference between the age (median 67, 64, and 65 years respectively) or duration of symptoms (median 10 years) in each group. Patients with benign CLO were significantly more likely to be non-smokers and non-drinkers, or both than patients with both severe oesophagitis and adenocarcinoma (p < 0.001). Of those who smoked or drank, patients with CLO had a smoking history of a median 15 pack years (range 2-60 pack years), which was less than both the severe oesophagitis (median 45.5, range 5-150 pack years) (p < 0.01), and adenocarcinoma groups (median 55.25, range 4-200 pack years) (p < 0.001). Patients with adenocarcinoma had smoked for more years in total (median 38.5, range 4-54 years) than patients with CLO (median 29.5, range 6-55 years) (p < 0.01). Patients with severe oesophagitis (median 38.5, range 27-55 years) and adenocarcinoma patients had a similar long history of smoking both of which were greater than CLO patients (p < 0.003). Half of the severe oesophagitis group drank more than 40 units/week and six more than 100 units/week (median 40, range 1-->100 units/week), whereas CLO patients who drank did so more moderately (median 10, 1-100 units/week) (p < 0.02). Adenocarcinoma patients also had a somewhat greater alcohol intake than CLO patients, median 15 (1-100 units/week) (p<0.02). Smoking and alcohol consumption do not predispose to the development od metaplastic columnar lined oesophagus in patients with severe gastro-oesophageal reflux but are strongly associated with the development of adenocarcinoma in patients with established Barrett's oesophagus.     

Routine management of gastro-oesophageal reflux disease by gastroenterologists in France: A prospective observational study

AIMS: To obtain data on routine care of gastro-oesophageal reflux disease by French gastroenterologists. PATIENTS: Five thousand and forty-five adults with gastro-oesophageal reflux disease. METHODS: Patients were recruited by a representative sample of 598 French gastroenterologists. A full disease history, with treatments given/investigations undertaken, was obtained from all patients. The patients' expectations with regard to the improvement of the symptoms' control and the corresponding assessments made by the gastroenterologists were recorded on a 4-point scale. RESULTS: The mean time since diagnosis was approximately 4 years. The most commonly presented symptom was heartburn (79% of patients). A total of 3735 patients (74%) underwent endoscopy because of gastro-oesophageal reflux disease. Erosive oesophagitis was present in 38% and Barrett's oesophagus in 8%. Medical therapy for gastro-oesophageal reflux disease was prescribed in 92% of patients, of whom 86% received proton pump inhibitors. Lifestyle advice was given to 73% of patients. Overall, 84% of patients and 72% of physicians expected 'highly' or 'moderately' improved control of gastro-oesophageal reflux disease. Gastroenterologists underrated the need for improvement of the symptoms' control as expressed by 'de novo' as well as 'previously diagnosed' patients. CONCLUSIONS: This study provides cross-sectional data on the management of gastro-oesophageal reflux disease by gastroenterologists in France. Most patients have high expectations of an improvement in their management, but gastroenterologists generally underrate these expectations.     

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.     

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.