Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care--the ProGERD study.

BACKGROUND: The evolution of gastro-oesophageal reflux disease (GERD) under current management options remains uncertain. AIM: To examine whether, depending on the initial presentation, non-erosive (NERD) and erosive reflux disease (ERD) without Barrett's oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition. METHODS: Patients with the primary symptom of heartburn were included at baseline, and stratified into non-erosive (NERD) and erosive reflux disease (ERD), LA grades A-D (Los Angeles classification). After a 2- to 8-week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett's oesophagus after 5 years. RESULTS: A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5-year follow-up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett's oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett's oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett's oesophagus at 5 years. CONCLUSION: Most GERD patients remain stable or improve over a 5-year observation period under current routine clinical care.

[New epidemiology of acute gastrointestinal hemorrhage]. / Neue Epidemiologie der akuten gastrointestinalen Blutung.

Due to progress in general medicine and especially in gastroenterology, the incidence of acute gastrointestinal hemorrhage could be expected to have decreased during the last 25 years. However, published epidemiological data cannot, in general, fulfill this hope. The interpretation of potential trends is, however, often limited by low study quality. For example, questionable bleeding sources such as erosions in the upper gastrointestinal tract or colon diverticula are often rather uncritically named the definitive causes of bleeding. However, there is clear evidence of changes in grouping of patients. After the almost complete disappearance of Helicobacter pylori in younger indigenous populations of most industrialized countries, it is mostly elderly comorbid people with additional risk factors (NSAID use, low-dose aspirin, anticoagulation) who are affected. Not unexpectedly, this group has generally experienced no change in incidence and in fact shows a deterioration of prognosis in case of acute bleeding.

A summary of Food and Drug Administration-reported adverse events and drug interactions occurring during therapy with omeprazole, lansoprazole and pantoprazole.

BACKGROUND: Pantoprazole is claimed to have a lower potential for drug interaction than other proton pump inhibitors. AIM: To estimate the frequency of adverse events and drug interactions reported to the Food and Drug Administration in patients receiving omeprazole, lansoprazole or pantoprazole. METHODS: The study involved a search of the Food and Drug Administration's database for adverse events and drug interactions with omeprazole, lansoprazole or pantoprazole as primary or secondary suspect drug. An estimate of the amount of drug dispensed during the adverse event collection period (from US drug launch) was obtained from the International Medical Statistics health database. RESULTS: Of the suspected drug interactions recorded, vitamin K antagonist interactions, although rare, were the most common. The frequency of vitamin K antagonist interactions was 0.09 per million packages for omeprazole and 0.11 per million packages for lansoprazole and pantoprazole. Interactions with benzodiazepines or phenytoin were even rarer, being reported in less than 10 patients on each proton pump inhibitor. CONCLUSION: The frequency of reported drug interactions was low for omeprazole, lansoprazole and pantoprazole and vitamin K antagonist interactions were by far the most common. These potentially important drug interactions, although rare, were no less frequent on pantoprazole than on omeprazole or lansoprazole, suggesting a class effect.

Treatment of Helicobacter pylori in functional dyspepsia resistant to conventional management: a double blind randomised trial with a six month follow up.

BACKGROUND: Previous studies on the treatment of Helicobacter pylori infection in functional dyspepsia have shown little, if any, effect on dyspeptic symptoms. However, whether such treatment might be of benefit in patients resistant to acid inhibitors has not been formally tested. AIM: The present study investigated the effect of H pylori treatment in patients with functional dyspepsia resistant to conventional treatment. PATIENTS: A total of 181 H pylori positive patients with chronic functional dyspepsia who had not responded to a one week antacid run-in and two week double blind antisecretory or placebo treatment were included. METHODS: Patients were randomised to two weeks of treatment with omeprazole 40 mg twice daily combined with amoxicillin 1 g twice daily or omeprazole 20 mg once daily alone. The primary outcome variable ("response") was defined as no need for further therapy or investigations for dyspeptic symptoms 4-6 months after treatment. RESULTS: H pylori infection was healed in 10% of patients after omeprazole and in 52% after omeprazole plus amoxicillin. The respective "response" rates were 66% and 62% (NS). H pylori treatment and cure of H pylori infection had no effect on complete resolution of all dyspeptic symptoms, individual symptoms, or various aspects of quality of life. CONCLUSION: In functional dyspepsia, H pylori treatment and cure of H pylori are no more effective for symptoms over six months than short term acid inhibition. These results do not support treatment of H pylori in functional dyspepsia.

Primary prevention of diclofenac associated ulcers and dyspepsia by omeprazole or triple therapy in Helicobacter pylori positive patients: a randomised, double blind, placebo controlled, clinical trial.

BACKGROUND: There is much controversy as to whether or not treatment of Helicobacter pylori reduces the occurrence of peptic ulcers during therapy with a non-steroidal anti-inflammatory drug (NSAID). AIM: To assess the efficacy of triple therapy or omeprazole on the occurrence of diclofenac associated ulcers in H pylori positive patients. METHODS: This was a randomised, double blind, placebo controlled, multicentre trial in H pylori positive patients requiring NSAID therapy who had no past or current peptic ulcer. They received diclofenac 50 mg twice daily for five weeks in combination with one of the four randomly assigned treatments: anti-H pylori treatment for one week (omeprazole 20 mg+clarithromycin 500 mg+amoxicillin 1 g, all twice daily) followed by placebo for four weeks (OAC-P); anti-H pylori treatment for one week followed by antisecretory treatment with omeprazole 20 mg once daily for four weeks (OAC-O); omeprazole 20 mg once daily for five weeks (O-O); or placebo for five weeks (P-P). Patients were endoscoped before and after treatment. RESULTS: Data from 660 patients were included in an intention to treat analysis. The occurrence of peptic ulcers in the four treatment groups during the study period was: 1.2% for OAC-P, 1.2% for OAC-O, 0% for O-O, and 5.8% for P-P (p<0.05 between placebo and all active treatment groups). Patients who received active treatment developed therapy requiring dyspeptic symptoms less frequently than those who received placebo (p<0.05 between placebo and all active treatment groups). CONCLUSIONS: In H pylori infected patients, all three active therapies reduced the occurrence of NSAID associated peptic ulcer and dyspeptic symptoms requiring therapy.

Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status. The Frosch Study Group.

BACKGROUND AND AIMS: Treatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence of Helicobacter pylori infection influences the response. METHODS: After a complete diagnostic workup, 792 patients with functional dyspepsia unresponsive to one week of low dose antacid treatment were randomised to two weeks of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, or omeprazole 20 mg daily. Individual dyspeptic and other abdominal symptoms were evaluated before and after treatment according to H pylori status. RESULTS: The proportions of patients considered to be in remission (intention to treat) at the end of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, and omeprazole 20 mg were, respectively, 42%, 50%, 48%, and 59% in the H pylori positive group and 66%, 73%, 64%, and 71% in the H pylori negative group. In H pylori positive patients, the therapeutic gain over placebo was significant for omeprazole 20 mg (17.6%, 95% confidence intervals (CI) 4.2-31.0; p<0.014 using the Bonferroni-adjusted p level of 0.017) but not for omeprazole 10 mg (6.8%, 95% CI -6.7-20.4) or ranitidine 150 mg (8.9%, 95% CI -4.2-21. 9). There was no significant therapeutic gain from active treatment over placebo in H pylori negative patients. Complete disappearance of symptoms and improvement in quality of life also occurred most frequently with omeprazole 20 mg and was significant in both H pylori positive and H pylori negative groups. The six month relapse rate of symptoms requiring treatment was low (<20%) in all groups. CONCLUSIONS: Omeprazole 20 mg per day had a small but significant favourable effect on outcome in H pylori positive patients. The differential response in these patients may be explained by an enhanced antisecretory response in the presence of H pylori. The effect of weaker acid inhibition was unsatisfactory.

Helicobacter pylori and functional dyspepsia: a real causal link?

This chapter reviews the evidence for a link between functional dyspepsia and Helicobacter pylori infection from three angles. In the section on pathophysiology, we evaluate how H. pylori could theoretically produce dyspeptic symptoms: many mechanisms can be proposed. In the discussion on epidemiology, we evaluate possible associations between the occurrence of symptoms and infection. Here, many studies claiming a coincidence or chronological sequence of infection and symptoms are criticized because of their poor design. In the section on the improvement of functional dyspepsia by the treatment of H. pylori infection, the conclusion is reached that if such an effect occurs at all--which is unlikely--it is very weak. The controversy on the link between H. pylori infection and functional dyspepsia is presently ongoing. Some authors are still trying to save an elegant concept that once looked so plausible but now has the facts against it.

Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.

[Gastroenterology. II: Acid research and ulcer therapy]. / Gastroenerologie. II: Säureforschung und Ulkustherapie.

Three discoveries of the last thirty years have revolutionized acid research and ulcer therapy: H2-receptors and their competitive inhibition, the acid pump and its blockade and, finally, Helicobacter pylori and its central role in ulcer disease. Today the problem of ulcer treatment is more or less solved by the correct use of antibiotics, while the cure of reflux disease is still problematic: pump blockers accelerate the healing of mucosal breaks and prevent, when given at long term, recurrences but they cannot change the natural history of reflux disease. These facts form the basis for future research.

[Reflux, lung and heart]. / Reflux, Lunge und Herz.

The connections between gastroesophageal reflux, nonallergic asthma and angina pectoris are critically reviewed. Although there is no convincing evidence of a widespread pathophysiological link, such interaction may play a role in selected cases.

[Recurrence of reflux esophagitis can be prevented with maintenance therapy with sucralfate]. / Recidief van reflux-oesofagitis te voorkomen met onderhoudstherapie van sucralfaat.

OBJECTIVE: To determine whether the recurrence of reflux oesophagitis can be prevented with sucralfate suspension 2 g daily. DESIGN: Double-blind, placebo-controlled, multinational drug study. SETTING: Sixteen research centres in Switzerland, Germany and the Netherlands. METHOD: 184 Patients whose earlier reflux oesophagitis Savary-Miller grades I and II were cured by an antisecretory therapy before being included in the study. For 6 months, they were given 2 g of a sucralfate suspension or a placebo twice daily, with random division. The symptoms were checked monthly. Endoscopy was performed at the end of the study or when there was a clinical suspicion of recurrence. RESULTS: Eighty-eight patients of the sucralfate group and 93 of the placebo group could be evaluated. The proportion of endoscopical recurrence was significantly reduced (31 in the sucralfate group as against 55 in the placebo group; p < 0.001). This decrease was particularly clear where symptomatic recurrences were concerned (10 and 34%, respectively; p < 0.001). CONCLUSION: This is the first trial that demonstrates that sucralfate suspension can prevent recurrences of reflux oesophagitis in patients with solitary or confluent erosions previously cured with an antisecretory therapy.

Sucralfate maintenance therapy in reflux esophagitis. Sucralfate Investigational Working Team.

OBJECTIVE: to prove in a double-blind placebo-controlled multinational trial the effects of sucralfate suspension 2 g BID and placebo in the prevention of recurrent reflux esophagitis. METHODS: One hundred and eighty-four patients from 16 centers with reflux esophagitis Savary grade 1 and 2 were initially healed with antisecretory therapy before entering the study. They were randomly allocated to sucralfate suspension 2 g BID or placebo for 6 months. Symptoms were monitored monthly. Endoscopy was performed at the end of the trial or earlier in case of clinical suspension of relapse. RESULTS: The two treatment groups were well matched. We were able to analyze 88 sucralfate- and 93 placebo-treated patients. There was a significant reduction in the endoscopic relapse rate (31% in the sucralfate group vs. 65% in the placebo group, p < 0.001). This reduction was especially obvious for symptomatic relapses (10% vs. 34%, respectively, p < 0.001). CONCLUSION: This is the first study to show that sucralfate suspension is capable of preventing recurrent reflux esophagitis in patients with solitary or confluent erosions previously healed with antisecretory therapy.

[Dyspepsia: work-up or provisional treatment?]. / Dyspepsie: Abklären oder probatorisch behandeln?

Dyspepsia is defined as symptoms that are considered by a physician to originate from the upper gastrointestinal tract. The term 'functional dyspepsia' designates dyspepsia after exclusion of organic causes. Dyspepsia is a frequent problem in general practice. Mainly for economical reasons, it is impossible to perform every available diagnostic test in every patient to exclude all possible organic causes. The initial work-up is directed at identifying alarm symptoms and alarm signs from history, physical examination, and simple laboratory tests. The presence of any alarm symptoms or alarm sign requires prompt investigation. If none can be found, empirical drug treatment may be performed according to the leading symptom. Treatment failure or rapid recurrence require additional investigations, in particular by gastroscopy.

[Ulcer prevention during anti-rheumatism therapy and in intensive medicine]. / Ulkusprophylaxe unter Antirheumatikatherapie und in der Intensivmedizin.

Gastrointestinal side effects are common to all nonsteroidal anti-inflammatory drugs (NSAID). Relevant to the patient are NSAID-induced dyspepsia and ulcer complications such as hemorrhage and perforation. The most important prophylactic means is repeated verification that the NSAID cannot be replaced by other measures, e.g. physical therapy or simple analgesics. If a NSAID is needed, it should be administered at the lowest effective dose. The present drugs used in preventing NSAID-induced ulcers and their complications are far from perfect. Major problems are adverse effects, high costs and insufficient efficacy in the prevention of ulcer complications. Thus, prophylactic antiulcer treatment is recommended in high-risk patients (as a primary prophylaxis) and in patients with previous ulcers (as a secondary prophylaxis). Similar arguments apply for prevention of ulcers in intensive-care patients. Patients at risk are critically ill, those with previous ulcers and in particular those with clotting disorders. Acid-reducing drugs are recommended for nonintubated patients, whereas sucralfate is preferred in patients on artificial ventilation because it is associated with a lower risk for nosocomial pneumonias.