Endoscopy-negative Gastro-oesophageal Reflux Disease Research Articles

On‐demand requirements of patients with endoscopy‐negative gastro‐oesophageal reflux disease: H2‐blocker vs. proton pump inhibitor

It is questionable whether a symptomatic condition with few serious medical consequences requires proton pump inhibitor (PPI) treatment. If effective, a less-potent treatment may be preferable. To compare an H2-blocker in an effervescent formulation with a PPI in on-demand treatment of endoscopy-negative gastro-oesophageal reflux disease (GERD). Included were patients with heartburn and/or acid regurgitation for at least 3 months duration, a negative endoscopy and a positive response to 7 days of lansoprazole 60 mg daily. Following pH-metry, the patients were randomized to receive either ranitidine effervescent tablets 75 mg or lansoprazole capsules 15 mg to a maximum of four per day on-demand. The numbers taken were registered monthly for 6 months. If treatment was unsuccessful (lack of efficacy or side effects), patients were registered as failures. One hundred and three patients were included and 63 were considered for statistical analysis; 32 on lansoprazole and 31 on ranitidine. Seventeen (55%) on ranitidine and four (13%) on lansoprazole failed. The average number of tablets per day was 1.2 in the lansoprazole group and 3.1 in the ranitidine group. On-demand treatment in patients with endoscopy-negative GERD gives a high success rate with a fairly low dose of PPI. The H2-blocker had significantly less success; nevertheless, almost half were satisfied with the treatment.

International Validation of ReQuest™ in Patients with Endoscopy-Negative Gastro-Oesophageal Reflux Disease

Background: Reflux Questionnaire (ReQuest™), a newly developed gastro-oesophageal reflux disease-sensitive scale, can be used to reliably evaluate the effect of treatment on gastro-oesophageal reflux disease symptoms. Aim: International validation of this scale, in patients suffering from endoscopy-negative gastro-oesophageal reflux disease. Methods: In this open, multicentre and multinational clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest™ were completed both in the pre-treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test–retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well-being questionnaire by means of correlation coefficients. Results: Factor analyses confirmed the content validity of both long and short version of ReQuest™. Psychometric calculations proved high internal consistency (Cronbach’s alpha: 0.9), test–retest reliability [Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale 0.6; Psychological General Well-being –0.4). Conclusion: ReQuest™ proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy-negative gastro-oesophageal reflux disease patients.

Programme of stepping down from twice daily proton pump inhibitor therapy for symptomatic gastro‐oesophageal reflux disease associated with a formulary change at a VA medical center

In July 2001, our Veterans' Affairs hospital changed its formulary proton pump inhibitor (PPI) from lansoprazole to rabeprazole. All patients previously receiving lansoprazole 30 mg twice daily were switched to rabeprazole 20 mg once daily. To determine if patients with gastro-oesophageal reflux disease (GERD), who were previously managed on lansoprazole 30 mg twice daily, could be maintained on rabeprazole 20 mg once daily. Four hundred and thirty-five patients had received lansoprazole 30 mg twice daily for at least 12 months before the formulary change. Medical records were reviewed for 12 months before and after the formulary change. There were 432 men and three women with a mean age of 66.7 years (range: 38-91). Two hundred and twelve patients were excluded. Of the remaining 223, 111 (50%) were maintained successfully on rabeprazole 20 mg once daily. Twenty-three (10%) stayed off all acid suppression during follow-up. The number of endoscopies and clinic visits did not significantly change during the follow-up. Fifty-six percent who had erosive oesophagitis failed a dose taper compared with 31% of those with endoscopy-negative GERD (P<0.025). Most patients receiving twice daily PPI therapy for GERD could be maintained on once daily PPI or no acid suppression for 12 months of follow-up. Dose reduction was more successful in those without erosive oesophagitis.

Cell proliferation of squamous epithelium in gastro‐oesophageal reflux disease: correlations with clinical, endoscopic and morphological data

The microscopic assessment of squamous epithelium lesions in gastro-oesophageal reflux disease (GERD) is subjective. The Ki67 nuclear antigen expressed by proliferating cells provides an objective measure of regeneration in the squamous epithelium. To evaluate Ki67 expression in GERD patients and controls, in comparison with histological lesions, pH-metry and endoscopic data. Eighty-seven patients with GERD symptoms and 20 symptom-free controls underwent endoscopy and 24-h pH monitoring. Oesophageal biopsies (4 cm, 2 cm and Z-line) were stained with Ki67/MIB-1 antibodies; the Ki67-positive nuclear area was assessed with an image analysis system and expressed as percentage of the whole epithelial area (Ki67-%). Ki67-% was significantly higher in 32 patients with erosive oesophagitis, 44 endoscopy-negative GERD and 11 patients with functional heartburn than in controls (P = 0.0001). Both controls and patients showed a progressive increase in Ki67-% from 4 cm to the Z-line (P < 0.0001). Ki67-% showed a significant correlation with other conventional histological lesions (P ranged between 0.0151 and <0.0001). Ki67 evaluation provides quantitative and objective data on squamous epithelium proliferative activity. This marker can be applied in the distinction of endoscopy-negative GERD from healthy controls.

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

Objective. A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. Material and methods. Twelve patients (7 M, age range 24–65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25–54 years). Results. In the patients’ group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)±6 (SEM) versus 86±6 and 232 min±16 versus 160±7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): −22 min (mean); −10 to −34 (95% CI) and −48 min; −10 to −85, respectively, decreased both percentage of time at pH < 4 (p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R2<0.005). Conclusion. The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.

Review article: oesophageal pH monitoring – technologies, interpretation and correlation with clinical outcomes

Using a simple 'test' to diagnose gastro-oesophageal reflux disease is difficult because accurately measuring gastric refluxate and correlating reflux events with symptom episodes is complex. This paper reviews the safety, tolerability and diagnostic accuracy of Bravo (Medtronic, Shoreview, MN, USA), ambulatory oesophageal pH monitoring technology. Catheter-based pH electrodes inhibit patients' normal activity, and can yield erroneous results because of placement or subsequent migration of the probe or errors in the thermal compensation algorithm that is requisite for antimony pH electrodes. Bravo pH studies reliably discriminated oesophagitis patients from controls, but are less discriminatory in endoscopy-negative gastro-oesophageal reflux disease patients. The Bravo system can be accurately placed using endoscopic landmarks and pH studies demonstrated more accurate in vivo pH recording than with a catheter-based system. The Bravo system detected fewer reflux events of short duration compared with a catheter-based system. Studies examining the correlation between reflux events and symptoms have not yet been conducted using the Bravo system. In conclusion, the Bravo system offers a more user-friendly ambulatory pH monitoring technique that more accurately records pH compared with a catheter-based system. More research is needed to determine whether the detection of reflux events with Bravo will provide a good correlation with symptom episodes.

International validation of ReQuest in patients with endoscopy-negative gastro-oesophageal reflux disease.

Reflux Questionnaire (ReQuest), a newly developed gastro-oesophageal reflux disease-sensitive scale, can be used to reliably evaluate the effect of treatment on gastro-oesophageal reflux disease symptoms. International validation of this scale, in patients suffering from endoscopy-negative gastro-oesophageal reflux disease. In this open, multicentre and multinational clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest were completed both in the pre-treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test-retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well-being questionnaire by means of correlation coefficients. Factor analyses confirmed the content validity of both long and short version of ReQuest. Psychometric calculations proved high internal consistency (Cronbach's alpha: 0.9), test-retest reliability [Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale -0.6; Psychological General Well-being -0.4). ReQuest proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy-negative gastro-oesophageal reflux disease patients.

Review article: acid suppression in the management of gastro-oesophageal reflux disease--an appraisal of treatment options in primary care.

Gastro-oesophageal reflux disease (GERD) is one of the most common conditions presenting to the primary care physician. Despite progress in understanding and treatment of the disease, strategies for capitalizing on these advances are less well developed. In many practices, H2-receptor antagonists still remain the most widely prescribed treatment for GERD, despite the availability of the more effective acid-suppressant proton pump inhibitors. This review examines the relative efficacies of acid-suppressant drugs in minimizing oesophageal acid exposure and outlines the evidence for the superiority of proton pump inhibitors over standard-dose H(2)-antagonists in symptom relief, erosion healing and prevention of relapse in GERD. Current prescribing patterns and considerations for the general practitioner are also examined. The availability and impact of over-the-counter H(2)-antagonists on the treatment of GERD and their relative cost-effectiveness vs. proton pump inhibitors are also addressed. A hierarchy of drug efficacy (full-dose proton pump inhibitor > half-dose proton pump inhibitor > high-dose H(2)-antagonist > standard-dose H(2)-antagonist or prokinetic) applies in principle to all GERD patients, (with or without oesophagitis). The most effective initial therapy for GERD is also likely to be the most cost-effective one, if treatment failure leads to higher utilization of medical resources. The application of these recommendations to the management of non-endoscoped GERD, endoscopy-negative GERD and low-grade oesophagitis as well as higher grade oesophagitis is also reviewed.

Helicobacter pylori infection is associated with milder gastro-oesophageal reflux disease.

We have previously demonstrated a negative relationship between the prevalence of Helicobacter pylori and gastro-oesophageal reflux disease (GERD). To study the effects of H. pylori infection on the severity of GERD. Ethnic Chinese patients with frequent heartburn and/or endoscopic oesophagitis were studied. Endoscopic examination was performed to assess the severity of oesophagitis (modified Savary-Miller grading) and the presence of hiatus hernia. Biopsies were taken for rapid urease testing and confirmation of Barrett's oesophagus. Risk factors which may affect the severity of oesophagitis (age, sex, smoking, drinking, diabetes mellitus, hiatus hernia, H. pylori status and body mass index) were evaluated by a multiple regression model. The cagA status of H. pylori infected GERD and age-and-sex matched controls were determined by Western blot. Age-and-sex matched non-reflux patients were recruited as controls for comparison. Two hundred and twenty-five patients with GERD were studied, of whom 77 (34%) were infected with H. pylori. Oesophagitis and Barrett's oesophagus were found in 140 patients (62%) and six patients (3%), respectively. H. pylori infected patients had significantly less severe oesophagitis compared to the uninfected group (P=0.022). All patients with Barrett's oesophagus were uninfected. Factors that predicted severe oesophagitis included age over 60 years (P < 0.001) and hiatus hernia (P < 0.001). H. pylori infection was the only factor that showed a negative correlation with severe oesophagitis (P=0.011). The prevalence of the cagA positive strain in endoscopy-negative GERD, erosive oesophagitis and control subjects was 70, 76 and 78%, respectively (P=0.75). H. pylori infection is associated with milder GERD.

The Efficacy of a Pectin-Based Raft-Forming Anti-Reflux Agent in Endoscopy-Negative Reflux Disease

Background.- Patients with heartburn as their main complaint but normal oesophageal mucosa at endoscopy are classified as having endoscopy-negative gastro-oesophageal reflux disease (GORD). They have mainly postprandial reflux and low total acid exposure and could possibly be managed with a non-systemic drug. In such patients we examined the effect of a pectin-based raft-forming anti-reflux agent (Aflurax (Idoflux)) on the severity of heartburn. Methods: Patients with heartburn but with normal/ erythematous oesophageal mucosa (n = 65) were randomized to double-blind treatment with two 1200-mg tablets of Aflurax or two placebo tablets four times daily for 4 weeks. The main outcome measure was heartburn severity on day 15 and day 29. Results: The number of patients scoring heartburn severity on day 15 as none, mild, moderate, and severe were 6, 14, 8, and 3, respectively, with Aflurax versus 2, 6, 13, and 11 with placebo (p < 0.05). No further treatment effect was found on day 29. Conclusion: Aflurax reduces heartburn in patients with endoscopy-negative GORD.