Colonic mucosal biopsies obtained during confocal endomicroscopy are pre-stained with fluorescein in vivo and are suitable for histologic evaluation.

BACKGROUND AND STUDY AIMS: Confocal laser endomicroscopy (CLE) with intravenous infusion of fluorescein allows noninvasive, real-time in vivo visualization of gastrointestinal mucosa at ~ × 1000 magnification ("virtual biopsy"). Conventional biopsies obtained during these procedures serve as the reference and established diagnostic standard. The aim of the present study was to assess whether the standard histologic biopsies that are obtained during CLE retain fluorescein in the tissues and allow the visualization of mucosal structures without any additional staining. PATIENTS AND METHODS: CLE optical imaging of the mucosa was performed in 16 patients who were undergoing CLE colonoscopy. Standard conventional biopsies were also obtained from both normal colonic mucosa and colonic polyps. De-paraffinized mucosal sections were examined under a fluorescence microscope for the presence and distribution of fluorescein, and then underwent immunostaining for expression of vascular endothelial growth factor (VEGF). RESULTS: Standard mucosal biopsy sections from patients undergoing CLE displayed a strong fluorescence and showed well-delineated mucosal structures. In colonic adenomas, there was a 4.6-fold increased vascular permeability compared with normal mucosa (P<0.001), indicated by fluorescein leakage to the extravascular space. Immunostaining demonstrated an aberrantly increased expression of VEGF in the epithelium of colonic adenomas but not in the epithelium of normal mucosa or hyperplastic polyps. CONCLUSIONS: This study shows for the first time that standard colonic biopsies obtained during CLE retain fluorescein, show excellent delineation of mucosal structures without additional staining, allow the evaluation of mucosal microvasculature and vascular permeability, and are suitable for immunostaining.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

In vivo real-time imaging of human duodenal mucosal structures in celiac disease using endocytoscopy.

BACKGROUND AND AIMS: Celiac disease is a gluten-induced enteropathy whose diagnosis is based on histological evidence of villous atrophy. The diagnosis may be difficult if the orientation of histological sections is other than optimal. During upper gastrointestinal endoscopy we studied in vivo duodenal mucosa in patients with celiac disease using endocytoscopy, a novel diagnostic technique allowing in vivo real-time visualization of mucosa under x 450 magnification. METHODS: Sixteen patients with documented celiac disease and seven controls without celiac disease were studied. Endocytoscopic images obtained from several fields were compared in a blinded fashion to standard histology. RESULTS: Endocytoscopy showed three different patterns of in vivo histology: (1) the presence of normal-appearing, long, thin villi, lined with clearly distinguishable surface epithelial cells, considered to be normal duodenal mucosa (n = 15, all controls and eight celiac disease patients); (2) the presence of thick, shortened villi, reflecting partial villous atrophy (n = 4); and (3) the total absence of villi and the presence of enlarged crypt orifices, reflecting total villous atrophy (n = 4). Good concordance between endocytoscopy and standard histology was found in all 16 patients with celiac disease. CONCLUSIONS: Endocytoscopy allows in vivo, real-time, noninvasive visualization and characterization of villous architecture and may be a promising method for in vivo evaluation of duodenal mucosa in celiac disease.

Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators.

BACKGROUND: Growing evidence suggests that patients with irritable bowel syndrome (IBS) have increased intestinal permeability. In addition, mucosal soluble mediators are involved in the pathophysiology of pain in IBS. We aimed to investigate (1) paracellular permeability in colonic biopsies of patients with IBS; and (2) the ability of soluble factors from colonic biopsies to reproduce these alterations in vitro. METHODS: Paracellular permeability in colonic biopsies of healthy subjects and patients with IBS was measured by mounting the biopsies in Ussing chambers. Cleared supernatant (SUP) of the culture from colonic biopsies was collected and applied to Caco-2 cells for 48 h. Paracellular permeability and transepithelial resistance (TER) were evaluated. mRNA expression of the tight junction proteins, zonula occludens (ZO)-1 and occludin, was assessed in colonic biopsies. Abdominal pain was assessed using a validated questionnaire. RESULTS: Permeability of colonic biopsies was significantly higher in patients with IBS compared to healthy subjects. These changes were associated with significantly lower expression of ZO-1 mRNA in biopsies of IBS as compared to healthy subjects. Compared to healthy subjects, SUP of IBS markedly reduced TER and significantly increased permeability in Caco-2 cells. SUP of IBS patients induced a significant decrease of ZO-1 mRNA in Caco-2 as compared to healthy subjects. SUP-induced increased paracellular permeability correlated with the severity of abdominal pain. CONCLUSIONS: Our study shows that colonic soluble mediators are able to reproduce functional (permeability) and molecular (ZO-1 mRNA expression) alterations observed in IBS patients. These findings might pave the way both to identify novel biomarkers as well as new therapeutic targets in IBS.

[Future prospects in digestive endoscopy: wireless capsule endoscopy]. / Nouvelles perspectives en endoscopie diagnostique: la vidéocapsule.

Since the beginning of the millennium, the development of wireless capsule endoscopy has represented a major technological advance. The capsule is ingested by the patient and images are transmitted via several sensors positioned on the skin of the patient and downloaded in a computer system. The first applications were focused on the exploration of the small bowel which was previously considered as an obscure area for conventional endoscopy. Wireless capsule endoscopy of the small bowel is now an established technique with many acknowledged indications for the diagnosis of obscure bleeding, anemia of presumed digestive origin, Crohn's disease and small bowel tumors. Recently, thanks to technological progresses, novel capsules have been developed for specific segments of the gut namely the oesophagus and the colon. Recent data suggest that these new capsules could have potential applications for the diagnosis of oesophageal varices, Barrett's oesophagus and for the screening and/or surveillance of polyps of the colon. However, further studies are required before such strategies could be approved for clinical use or even replace conventional endoscopic modalities. In the long-term, progresses in signal processing as well as in the miniaturisation of sensors or markers may lead to a new generation of endoscopic robots. This technological breakthrough may ultimately result in new concepts and change current practice of digestive endoscopy.

Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: a 3-year interim analysis of the LOTUS trial.

BACKGROUND: With the introduction of laparoscopic antireflux surgery (LARS) for gastro-oesophageal reflux disease (GORD) along with the increasing efficacy of modern medical treatment, a direct comparison is warranted. The 3-year interim results of a randomised study comparing both the efficacy and safety of LARS and esomeprazole (ESO) are reported. METHODS: LOTUS is an open, parallel-group multicentre, randomised and controlled trial conducted in dedicated centres in 11 European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg once daily, which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan-Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol. RESULTS: 554 patients were randomised, of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the intention to treat population, p = 0.25 (90% vs 95% per protocol). No major unexpected postoperative complications were experienced and ESO was well tolerated. However, postfundoplication complaints remain a problem after LARS. CONCLUSIONS: Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD.

The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.

BACKGROUND: Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. METHODS: In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. RESULTS: A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. CONCLUSIONS: Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.

Antireflux surgery for non-erosive and erosive reflux disease in community practice.

BACKGROUND: Antireflux surgery has been mainly evaluated in tertiary referral centres. Data regarding post-operative outcome in non-erosive reflux disease are lacking. AIM: To assess long-term outcome after antireflux surgery performed in a community practice setting. METHODS: We selected consecutively 60 non-erosive reflux disease patients and 61 erosive oesophagitis patients with symptomatic gastro-oesophageal reflux disease. After surgery, each subject answered a validated disease-specific health-related quality of life questionnaire and another questionnaire focusing on symptoms, late morbidity and drug use. RESULTS: After a 43-month median follow-up, an excellent outcome was reported by less than two-thirds of patients. Quality of life scores were lower in the non-erosive reflux disease group, especially in female patients. Non-erosive reflux disease patients reported more daily symptoms and more reflux-related symptoms (P = 0.04). Proton-pump inhibitor use was higher in non-erosive reflux disease patients (P < 0.005). Multivariate analysis identified four independent predictive factors associated with better outcome, namely male gender, abnormal preoperative acid exposure, a long duration of symptoms and surgical expertise. CONCLUSIONS: In community practice, the results of antireflux surgery are inferior to those reported by tertiary centres. Outcome seems poorer in non-erosive reflux disease especially in female patients. Nearly one-third of the non-erosive reflux disease patients continue to take proton-pump inhibitors. These results highlight the need for careful selection of patients before antireflux surgery.

Ambulatory 24-h oesophageal impedance-pH recordings: reliability of automatic analysis for gastro-oesophageal reflux assessment.

Oesophageal pH-impedance monitoring allows detection of acid and non-acid gastro-oesophageal reflux (GOR) events. Visual analysis of impedance recording requires expertise. Our aim was to evaluate the efficacy of an automated analysis for GOR assessment. Seventy-three patients with suspected GORD underwent 24-h oesophageal pH-impedance monitoring. Recordings analysis was performed visually (V) and automatically using Autoscan function (AS) of Bioview software. A symptom index (SI) > or =50% was considered for a significant association between symptoms and reflux events. AS analysis detected more reflux events, especially non-acid, liquid, pure gas and proximal events. Detection of oesophageal acid exposure and acid reflux events was similar with both analyses. Agreement between V and AS analysis was good (Kendall's coefficient W > 0.750, P < 0.01) for all parameters. During pH-impedance studies, 65 patients reported symptoms. As compared to visual analysis, the sensitivity and specificity of a positive SI determined by AS were respectively 85.7% and 80% for all reflux events, 100% and 98% for acid reflux and 33% and 87.5% for non-acid reflux. Despite good agreement with visual analysis, automatic analysis overestimates the number of non-acid reflux events. Visual analysis remains the gold standard to detect an association between symptoms and non-acid reflux events.

Review: what do we mean by GERD?--definition and diagnosis.

Gastro-oesophageal reflux disease (GERD) is a condition in which the gastro-oesophageal reflux provokes symptoms or complications. Since the majority of patients with heartburn do not have mucosal breaks, expressions such as 'endoscopy-negative reflux disease' (ENRD), 'non-erosive reflux disease' (NERD), or even 'reflux-like dyspepsia' and 'functional heartburn' are frequently employed despite the lack of consensus concerning their exact meaning. Moreover, definition of a disease does not mean that precise diagnostic criteria exist. Diagnostic approaches to GERD differ considerably between primary and secondary care. The primary care physician's role is to decide, on the basis of symptoms and clinical examination, if it is likely that the patient has some serious problem which requires urgent investigation and intervention. In practice, a symptom-based diagnosis can often be made reliably because heartburn and regurgitation are very specific for GERD. The secondary care physician has to make a full evaluation of an already highly-selected patient and, as far as possible, to make a comprehensive, accurate diagnosis, using whatever investigative tools are required. However, there is no 'gold standard' for the diagnosis of GERD and 24-hour pH monitoring lacks sensitivity in NERD. Recently, impedance-pH monitoring has been introduced and promising results have been reported. However, this new technology needs further validation and technical improvement before being employed in routine clinical investigation.

A comparative study of the early effects of tenatoprazole 40 mg and esomeprazole 40 mg on intragastric pH in healthy volunteers.

BACKGROUND: Tenatoprazole is a novel proton pump inhibitor with a seven-hour plasma half-life. AIM: To compare the effects of tenatoprazole 40 mg and esomeprazole 40 mg on intragastric acidity during the first 48 h in healthy volunteers. METHODS: This randomized two-period crossover study included 24 Helicobacter Pylori-negative subjects; tenatoprazole 40 mg or esomeprazole 40 mg daily were given before breakfast for two consecutive days, with a 2-week wash-out between the administration periods. Intragastric pH was monitored for 48 h. RESULTS: Over 48 h, tenatoprazole 40 mg exerted a more potent acid inhibition than esomeprazole 40 mg (median pH: 4.3 vs. 3.9, P < 0.08; per cent of time above pH 4: 57% vs. 49%, P < 0.03; proportion of subjects with at least half of the time above pH 4: 71% vs. 46%). These differences resulted from better night-time acid control with tenatoprazole 40 mg than esomeprazole 40 mg (first night median pH: 4.2 vs. 2.9, P < 0.0001; second night: 4.5 vs. 3.2, P < 0.0001). The duration of nocturnal acid breakthroughs was significantly reduced during both nights. In contrast, no significant difference was detected during the daytime periods between both regimens. CONCLUSION: Over the first 48 h, tenatoprazole 40 mg achieves a better overall and night-time control of gastric pH than esomeprazole 40 mg. The translation of better early control of acidity into clinical benefits deserves further studies.

Normal values and day-to-day variability of 24-h ambulatory oesophageal impedance-pH monitoring in a Belgian-French cohort of healthy subjects.

BACKGROUND: Impedance-pH monitoring is the most sensitive method for detection and characterization of gastro-oesophageal reflux episodes. Normal values from European subjects are lacking. AIM: To build a database of gastro-oesophageal reflux patterns from French and Belgian healthy subjects. METHODS: Seventy-two healthy subjects (35 men, mean age 35 years, 18-72) underwent 24-h ambulatory impedance-pH studies. Gastro-oesophageal reflux episodes were detected using impedance and characterized by pH as acid, weakly acidic, or weakly alkaline. Analysis was performed visually and effects of age, gender and intra-individual reproducibility were evaluated. RESULTS: The total number of gastro-oesophageal reflux episodes was 44 (25,58,75) of which 59% were acid, 28% were weakly acidic and 10% weakly alkaline. Half of gastro-oesophageal reflux episodes were mixed (liquid/gas) and 22% reached 15 cm above the lower oesophageal sphincter. The bolus clearance time was 11 s while acid was chemically cleared in 34 s. Male gender was associated with increased number and proximal extent of total and acid gastro-oesophageal reflux. Repeated studies in 27 subjects showed good reproducibility for number, acidity and air-liquid composition of reflux (Kendall's W-values = 0.72-0.85). CONCLUSIONS: This study demonstrates good reproducibility of 24-h ambulatory impedance-pH studies and provides values of reflux patterns in healthy subjects for comparisons with European gastro-oesophageal reflux disease patients.

Human intestinal circadian clock: expression of clock genes in colonocytes lining the crypt.

Biological clock components have been detected in many epithelial tissues of the digestive tract of mammals (oral mucosa, pancreas, and liver), suggesting the existence of peripheral circadian clocks that may be entrainable by food. Our aim was to investigate the expression of main peripheral clock genes in colonocytes of healthy humans and in human colon carcinoma cell lines. The presence of clock components was investigated in single intact colonic crypts isolated by chelation from the biopsies of 25 patients (free of any sign of colonic lesions) undergoing routine colonoscopy and in cell lines of human colon carcinoma (Caco2 and HT29 clone 19A). Per-1, per-2, and clock mRNA were detected by real-time RT-PCR. The three-dimensional distributions of PER-1, PER-2, CLOCK, and BMAL1 proteins were recorded along colonic crypts by immunofluorescent confocal imaging. We demonstrate the presence of per-1, per-2, and clock mRNA in samples prepared from colonic crypts of 5 patients and in all cell lines. We also demonstrate the presence of two circadian clock proteins, PER-1 and CLOCK, in human colonocytes on crypts isolated from 20 patients (15 patients for PER-1 and 6 for CLOCK) and in colon carcinoma cells. Establishing the presence of clock proteins in human colonic crypts is the first step toward the study of the regulation of the intestinal circadian clock by nutrients and feeding rhythms.

Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies.

BACKGROUND: Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety. AIM: To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies. METHODS: Safety data were collected from patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and changes in laboratory variables were analysed. RESULTS: Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12 , folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the first year. CONCLUSION: No major safety concerns arose during 5-12 years of continuous PPI therapy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

Role of viscous guar gums in lowering the glycemic response after a solid meal.

The aim of the present study was to investigate how guar gum viscosity acts on starch digestion and glucose absorption in humans. Six healthy subjects received a mixed diet composed of 60.4% carbohydrate in the form of maize glucose or pregelatinized starch, to which was added 5.6% low- or high-viscosity guar gums. Meals were ingested or instilled in the duodenum and postprandial insulin and glucose responses were monitored for 3 h. Infusion of meals containing glucose showed that the delay in the diffusion rate to the duodenal mucosa due to bolus viscosity was not significant. Infusion of meals containing starch showed that a decrease in the digestion rate of starch in the upper small intestine accounted for part of the effect of viscosity on glycemic response, whereas the main effect of guar gum was apparently to slow gastric emptying.

Pasta cooking time: influence on starch digestion and plasma glucose and insulin responses in healthy subjects.

The influence of pasta cooking time on starch digestion and plasma glucose and insulin responses was studied in 12 healthy subjects. During 3 consecutive days, one of three pasta test meals (50 g starch) cooked for 11, 16.5, and 22 min was served to each volunteer in a random order. Hydrogen and methane breath excretion was measured after pasta ingestion; plasma responses were compared with those of an equivalent oral glucose-tolerance test. No significant differences were found between cooking times and plasma indices, orocecal transit time, or incremental hydrogen excretion (delta peak hydrogen). With one exception, pasta meals that were completely absorbed were ingested by methane producers. Postprandial delta peak hydrogen was significantly lower in methane than in nonmethane producers (p less than 0.02). These results point to a lack of influence of cooking time on nutritional characteristics of pasta and suggest that starch malabsorption determined by breath-hydrogen-test criteria may be underestimated in methane producers.

Digestion, excretion, and energy value of fructooligosaccharides in healthy humans.

The fate of fructooligosaccharides (FOS) in the human gastrointestinal tract was evaluated in six healthy volunteers over an 11-d period. After an equilibration phase, 20.1 g FOS/d was given in three identical postprandial doses. Distal ileal output of FOS and their constituent components were determined by intestinal aspiration after a single meal, and the amounts of FOS excreted in stools and urine were also measured. Most of ingested FOS, 89 +/- 8.3% (mean +/- SEM), was not absorbed in the small intestine, and none was excreted in stools, indicating that the portion reaching the colon was completely fermented by colonic flora. A small fraction of ingested FOS was recovered in urine. The mean estimated energy value of FOS was 9.5 kJ/g. We conclude that in healthy humans, FOS are only slightly digested in the small intestine and then fermented in the colon, resulting in reduced energy production.

Small-intestinal digestion of partially resistant cornstarch in healthy subjects.

The aims of this study were to measure the amount of starch from partially resistant starches (retrograded and complexed high-amylose cornstarches) escaping small-intestinal digestion in healthy humans by use of an intubation method and to compare these data with data obtained by indirect in vitro methods. Experiments were carried out in vivo in 6 healthy humans by using ileal intubation and stool analysis and in vitro by using 3 different methods for analyzing resistant starch. In intubated subjects, 51 +/- 2% of the retrograded and 21 +/- 2% of the complexed starch was delivered to the ileum and was fermented almost completely in the colon. In vitro estimates of the absorption of resistant starch were much lower. We conclude that technologically modified starches may substantially increase the amount of carbohydrate available for colonic fermentation in humans, but that in vitro measurements of resistant starch are inaccurate for predicting malabsorption in healthy humans.

Effects of roxatidine acetate on 24-hour gastric acidity. Early evening versus bedtime administration in healthy subjects.

The gastric antisecretory activity of roxatidine acetate was studied on 24-hour intragastric pH in 12 healthy male volunteers. The study was randomised, double-blind and double-dummy where either roxatidine acetate 150 mg as a slow release granulated formulation or placebo were administered at 7.30 pm or 10 pm. Roxatidine acetate 150 mg produced a significant decrease in the number of hours during which gastric acidity ranged between pH 1.5 and 4.0 which was consistent with the pharmacokinetic profile of the drug. There was no significant difference between the median intragastric pH values for early evening and bedtime administration of roxatidine acetate. The present data confirm that roxatidine acetate 150 mg inhibits gastric acid secretion but while a single evening dose is effective in controlling intragastric pH the results suggest there is no clear advantage in an early evening dose compared with a bedtime dose.

Treating the symptoms of gastro-oesophageal reflux disease: a double-blind comparison of omeprazole and cisapride.

BACKGROUND: Few studies have specifically addressed the management of the symptoms of gastro-oesophageal reflux disease, and there are no comparative data in this respect for acid pump inhibitors and prokinetic agents. METHODS: Following endoscopy 424 patients presenting with heartburn as the predominant symptom of gastro-oesophageal reflux disease were randomized to treatment with omeprazole 20 or 10 mg once daily, or cisapride 10 mg four times daily, in a double-blind, double-dummy, parallel group, multicentre study. Symptoms and quality of life were assessed at 4 weeks. Patients still experiencing heartburn continued therapy for a further 4 weeks and the assessments were repeated. RESULTS: At 4 weeks, heartburn was resolved in 65% (95% CI: 57-73%), 56% (48-64%) and 41% (32%-49%) of patients treated, respectively, with omeprazole 20 mg and 10 mg once daily, and cisapride. Both omeprazole doses were significantly more effective than cisapride (P < 0.01). The same order of efficacy was observed regardless of the presence of erosive oesophagitis. Regurgitation and epigastric pain also improved to a greater degree with omeprazole than with cisapride. Quality of life was improved in all treatment groups, and the improvement in the reflux dimension of the Gastrointestinal Symptom Rating Scale (GSRS) score was significantly different between groups (P = 0.002). CONCLUSIONS: Omeprazole 20 or 10 mg once daily is significantly more effective than cisapride in the resolution of heartburn, regardless of the presence of erosive oesophagitis, and this is accompanied by an improvement in patient quality of life.