[Current surveillance policy for Barrett's oesophagus in the Netherlands]. / Huidig beleid bij de surveillance van de barrettslokdarm in Nederland.

OBJECTIVE: To gain more insight into current surveillance and treatment of patients with Barrett's oesophagus with the aim of developing new guidelines. DESIGN: Questionnaire. METHOD: In 2004, a questionnaire was sent to 337 physician-endoscopists who were all registered with the Netherlands Society of Gastroenterology. The questionnaire inventoried various aspects of surveillance and treatment of patients with Barrett's oesophagus. RESULTS: Of the 289 respondents (86%), 96% carried out surveillance or had it carried out, on at least a proportion of their patients with Barrett's oesophagus. A total of 258 respondents (89%) carried out the surveillance themselves. An endoscopic indication of the presence of Barrett's oesophagus was, for 31% of the respondents, enough reason to carry out surveillance of this condition irrespective of the results of pathological investigations. 75% applied an age limit for surveillance for Barrett's. The median age limit is 75 years (interquartile distance: 70-75) and 46% of the treating professionals limited themselves to patients who, on the basis of age and co-morbidity, may undergo oesophageal resection. The choice of treatment in early neoplasia, surgical or endoscopic, depends not only on the histological diagnosis, but also on the age and the co-morbidities of the patient. CONCLUSION: Surveillance of Barrett's oesophagus is widespread in the Netherlands, and in general is carried out in accordance with international guidelines. The possibilities of treating patients with high-grade dysplasia or intramucosal carcinoma of the oesophagus endoscopically, and of consulting external advisory bodies are still insufficiently utilized.

[Guideline "Dyspepsia"]. / Richtlijn 'Maagklachten'.

For the management of patients with dyspepsia a multidisciplinary working party has made recommendations, i.e. about indications for prompt endoscopy, the management of dyspeptic complaints of recent onset, the application of diagnostic tests and treatment of recurrent dyspepsia and the indications for long term use of acid suppressants. Endoscopy is indicated in every patient with alarm symptoms, i.e. blood loss, dysphagia, weight loss or anemia in combination with dyspepsia. Age alone is not a decisive factor in this. Given the good prognosis of recent onset dyspepsia, the application of diagnostic tests is generally not required. Treatment should be restricted to antacids or H2 receptor antagonists. Only in case of persistent or recurring complaints, diagnostic tests or another treatment (Helitobacter pylori diagnostic tests, empirical treatment or endoscopy) should be considered. Testing for H. pylori is especially effective in patients at risk for peptic ulcer disease: those with recurrent complaints, and those with a history of peptic ulcer, without typical reflux symptoms or those with a history ofpeptic ulcer. Short term empirical treatment with a proton pump inhibitor is especially effective in patients with typical reflux symptoms. Endoscopy is the only way to rule out malignancy, and should be used to solve serious diagnostic uncertainty in patient or physician. The only indication for continuous proton pump inhibitor treatment is severe oesophagitis. All other patients with less severe reflux disease should preferably be treated on either on demand or intermittent basis. Long term proton pump inhibitor treatment is not indicated for patients with peptic ulcer disease or functional dyspepsia.

Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial.

BACKGROUND: Helicobacter pylori gastritis may progress to glandular atrophy and intestinal metaplasia, conditions that predispose to gastric cancer. Profound suppression of gastric acid is associated with increased severity of H pylori gastritis. This prospective randomised study aimed to investigate whether H pylori eradication can influence gastritis and its sequelae during long term omeprazole therapy for gastro-oesophageal reflux disease (GORD). METHODS: A total of 231 H pylori positive GORD patients who had been treated for > or =12 months with omeprazole maintenance therapy (OM) were randomised to either continuation of OM (OM only; n = 120) or OM plus a one week course of omeprazole, amoxycillin, and clarithromycin (OM triple; n = 111). Endoscopy with standardised biopsy sampling as well as symptom evaluation were performed at baseline and after one and two years. Gastritis was assessed according to the Sydney classification system for activity, inflammation, atrophy, intestinal metaplasia, and H pylori density. RESULTS: Corpus gastritis activity at entry was moderate or severe in 50% and 55% of the OM only and OM triple groups, respectively. In the OM triple group, H pylori was eradicated in 90 (88%) patients, and activity and inflammation decreased substantially in both the antrum and corpus (p<0.001, baseline v two years). Atrophic gastritis also improved in the corpus (p<0.001) but not in the antrum. In the 83 OM only patients with continuing infection, there was no change in antral and corpus gastritis activity or atrophy, but inflammation increased (p<0.01). H pylori eradication did not alter the dose of omeprazole required, or reflux symptoms. CONCLUSIONS: Most H pylori positive GORD patients have a corpus predominant pangastritis during omeprazole maintenance therapy. Eradication of H pylori eliminates gastric mucosal inflammation and induces regression of corpus glandular atrophy. H pylori eradication did not worsen reflux disease or lead to a need for increased omeprazole maintenance dose. We therefore recommend eradication of H pylori in GORD patients receiving long term acid suppression.

[Decreasing prevalence of Helicobacter pylori: a consequence of treatment of gastroduodenal ulcers]. / Dalende prevalentie van Helicobacter pylori: consequenties voor de behandeling van gastroduodenale ulcera.

Four patients with gastroduodenal ulcers in the absence of Helicobacter pylori illustrate the decreasing prevalence of this microorganism. One was a 19-year-old boy with nausea, diarrhoea and weight loss caused by multiple gastroduodenal ulcers due to the Zollinger-Ellison syndrome. Another was a 36-year-old man with abdominal discomfort caused by an ulcer due to Crohn's disease. The other two cases concerned a 29-year-old man and a 68-year-old woman with relapsing ulcer disease and active bleeding, in whom no causal factors could be determined. Recent studies suggest a decreasing prevalence of H. pylori leading to both a relative and an absolute decrease of gastroduodenal ulcers attributed to H. pylori. Future treatment strategies will have to take these altered prevalence rates into consideration.

Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy.

BACKGROUND: We have previously observed that profound acid suppressive therapy in Helicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis. AIM: To investigate if H pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes. PATIENTS/METHODS: In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months. RESULTS: In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in the H pylori positive group that became H pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p

Atrophic gastritis during long-term omeprazole therapy affects serum vitamin B12 levels.

BACKGROUND: Omeprazole maintenance therapy for gastro-oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori-infected patients and with a decreased absorption of protein-bound, but not of unbound cobalamin. AIM: : To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy. METHODS: Forty-nine H. pylori-positive GERD patients were treated with omeprazole for a mean (+/- s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow-up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow-up for histopathological scoring according to the updated Sydney classification. RESULTS: At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow-up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow-up. During follow-up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136-716) vs. (T1) 341 (136-839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156-716) at latest follow-up (P < 0.01). CONCLUSIONS: The development of atrophic gastritis during omeprazole treatment in H. pylori-positive GERD patients is associated with a decrease of serum vitamin B12 levels.

Omeprazole versus high-dose ranitidine in mild gastroesophageal reflux disease: short- and long-term treatment. The Dutch Reflux Study Group.

OBJECTIVE: Patients with reflux esophagitis suffer from a chronic condition that may cause considerable discomfort because of recurrent symptoms and diminished quality of life. This study was designed to evaluate acute and long-term treatment comparing standard doses of omeprazole and high-dose ranitidine. METHODS: Patients with endoscopically verified symptomatic esophagitis grade I or II were initially treated with omeprazole 20 mg daily or ranitidine 300 mg twice daily for 4-8 wk. Patients who were symptom free were randomized to maintenance treatment with omeprazole 10 mg daily or ranitidine 150 mg twice daily. Patients were seen every 3 months or at symptomatic relapse. RESULTS: The percentage of asymptomatic patients after 4 and 8 wk treatment were 61% and 74%, respectively, for omeprazole and 31% and 50%, respectively, for ranitidine. Of 446 patients treated initially, 277 were asymptomatic, of whom 263 entered the maintenance study. The estimated proportion of patients in remission after 12 months of maintenance treatment with omeprazole 10 mg daily (n = 134) and ranitidine 150 mg twice daily (n = 129) were 68% and 39%, respectively (p < 0.0001). CONCLUSIONS: Omeprazole 20 mg daily is superior to high-dose ranitidine in the symptomatic treatment of reflux esophagitis grade I and II. Furthermore, omeprazole at half the standard dose is more effective than ranitidine in a standard dose in keeping patients in remission for a period of 12 months.

Hypergastrinaemia during long-term omeprazole therapy: influences of vagal nerve function, gastric emptying and Helicobacter pylori infection.

AIM: elucidate the mechanisms that lead to severe hypergastrinaemia during long-term omeprazole therapy for gastro-oesophageal reflux disease (GERD). PATIENTS AND METHODS: A total of 26 GERD patients were studied during omeprazole maintenance therapy. Twelve patients with severe hypergastrinaemia (gastrin > 400 ng/L) were compared with 14 control patients (gastrin < 300 ng/L). Helicobacter pylori serology and a laboratory screen were obtained in all patients. Gastric emptying was scored by the evidence of food remnants upon endoscopy 12 h after a standardized meal. Gastric antrum and corpus biopsies were analysed for histological parameters, as well as somatostatin and gastrin concentrations. All patients underwent a meal-stimulated gastrin test and the hypergastrinaemia patients also underwent a vagal nerve integrity assessment by pancreatic polypeptide testing (PPT). RESULTS: Severe hypergastrinaemia patients had a longer duration of treatment (80 vs. 55 months; P = 0.047) and were characterized by a higher prevalence of H. pylori infection (9/12 vs. 2/14, P = 0.004), corpus mucosal inflammation and atrophic gastritis (P < 0.04). This was reflected in lower serum pepsinogen A concentrations (mean +/- S.E.M. 53.6 +/- 17.9 vs. 137 +/- 16.0 mg/L, P = 0.03), pepsinogen A/C ratio (1.8 +/- 0.3 vs. 4.1 +/- 0.6, P = 0.005) and mucosal somatostatin concentrations (2.75 +/- 0.60 vs. 4.48 +/- 1.08 mg/g protein, P = 0.038). Two patients in the hypergastrinaemia group had signs of delayed gastric emptying, but none in the normogastrinaemia group did (P = N.S.). In addition, both groups had a normal meal-stimulated gastrin response. CONCLUSION: Severe hypergastrinaemia during omeprazole maintenance therapy for GERD is associated with the duration of therapy and H. pylori infection, but not with abnormalities of gastric emptying or vagal nerve integrity.

[Reflux esophagitis; is the preventive eradication of Helicobacter pylori needed in patients on omeprazole?]. / Reflux-oesofagitis: preventieve eradicatie van Helicobacter pylori nodig bij patiënten die omeprazol krijgen?

The pattern of Helicobacter pylori gastritis depends on acid secretion. Profound acid suppressive therapy with proton pump inhibitors leads to a decrease of antral gastritis, but an increased severity of corpus gastritis. As such, maintenance therapy with these drugs for gastroesophageal reflux disease has consistently been associated with an increased incidence of atrophic gastritis in H. pylori infected patients. For this reason, the preventive effect of H. pylori eradication in these patients needs to be considered; this is being studied in prospective trials.

Omeprazole as a diagnostic tool in gastroesophageal reflux disease.

OBJECTIVE: To determine the diagnostic value of empirical treatment with omeprazole in the diagnosis of gastroesophageal reflux disease (GERD). METHODS: Patients with symptoms suggestive of GERD underwent upper gastrointestinal endoscopy and 24-h esophageal pH monitoring. Patients with reflux esophagitis grade 0 or 1 were included in the study and were randomized to double-blind treatment with either 40 mg omeprazole or placebo o.m. The effect of treatment was evaluated after 1 and 2 wk with a symptom questionnaire with a four-grade Likert scale, and symptomatic response outcome was compared with the results of 24-h pH-metry. RESULTS: Ninety-eight patients were included; however, 13 were excluded from the final analysis because of protocol violation. Of the remaining 85 patients, 54 had no signs of esophagitis at endoscopy, and 31 had esophagitis grade 1. The pH registration showed pathological gastroesophageal reflux in 47 patients (55%). Forty-one patients were randomized to treatment with omeprazole and 44 to placebo. There was a significant correlation between the pH registration result and response to omeprazole (p = 0.04, chi2), but not to placebo (p = 0.16). With pH-metry as the gold standard, the omeprazole test had positive and negative predictive values of 68% and 63%, respectively, for the diagnosis of GERD. When the omeprazole test was used as the gold standard, the positive and negative predictive values of pH monitoring were 68 % and 63 %, respectively. Similar sensitivity was found when the pH-metry was compared with presence of esophagitis. CONCLUSION: Determination of the symptomatic response to 40 mg of omeprazole for 14 days is a simple and inexpensive tool for the diagnosis of GERD, with a sensitivity and specificity comparable to 24-h pH monitoring.

Factors predicting relapse during maintenance treatment with famotidine in patients with healed reflux esophagitis. Dutch Esophagitis Study Group.

Little is known about possible predictive factors influencing the relapse rate in patients with healed reflux esophagitis during maintenance therapy with histamine2 (H2)-receptor antagonists. Therefore, the efficacy of famotidine 20 mg twice daily was evaluated in an open-label prospective study in 317 patients who had experienced healing of erosive reflux esophagitis after treatment with famotidine; 259 patients completed the study and were assessable according to study protocol. The cumulative endoscopic relapse rates at 4, 8, and 12 months were 20%, 30%, and 36%, respectively, according to the per-protocol analysis. The most predictive determinant of relapse was the duration of acute treatment required to achieve healing: Relapse occurred significantly less often in patients who experienced healing with 6 weeks of acute treatment than in those who experienced healing with 12 and 24 weeks of treatment. The second most important determinant was the initial endoscopic severity of the disease. Patients with initial grade I esophagitis had significantly fewer relapses. Relapse rate appeared to be unrelated to initial severity and duration of symptoms, smoking habits, or strength of acute treatment. The results showed that maintenance therapy with famotidine 20 mg twice daily is effective in a large proportion of patients with healed reflux esophagitis, with few adverse effects reported.

Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin.

AIMS: To evaluate absorption of protein-bound and unbound cyanocobalamin before and during treatment with omeprazole, and cobalamin levels in patients on long-term treatment with omeprazole. METHODS: In eight former duodenal ulcer patients absorption of unbound and protein-bound cobalamin was determined by measuring 24-h urinary excretion of unbound 58Co-cyancobalamin or protein-bound 57Co-cyanocobalamin during a modified Schilling test. Tests were performed before and during treatment with 20 mg and 40 mg omeprazole daily for 9 days. Serum cobalamin levels were assessed in 25 patients with gastro-oesophageal reflux disease (GERD) before and during long-term maintenance therapy with omeprazole. Mean treatment duration was 56 months (range 36-81 months). RESULTS: Urinary excretion of unbound cobalamin was unchanged with both dosages of omeprazole. Excretion of 57Co-cyanocobalamin, however, decreased significantly during treatment with both 20 mg omeprazole (mean +/- S.E.M.: 1.31 +/- 0.20 vs. 0.54 +/- 0.17%; P < 0.02) and 40 mg omeprazole (1.25 +/- 0.26 vs. 0.29 +/- 0.06%; P < 0.02). Mean serum cobalamin levels (+/- S.E.M.) before and during therapy with omeprazole in GERD patients were 298 +/- 27 and 261 +/- 16 pg/mL (normal range 180-900 pg/mL), respectively (P = N.S.). CONCLUSIONS: Absorption of protein-bound, but not unbound, cyanocobalamin is decreased when measured by a modified Schilling test during treatment with omeprazole. However, no change in serum cobalamin levels was observed in patients with GERD after treatment with omeprazole for up to 7 years.

Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication.

BACKGROUND: Helicobacter pylori infection plays an important part in the development of atrophic gastritis and intestinal metaplasia, conditions that predispose patients gastric cancer. Profound suppression of gastric acid is associated with increased severity of gastritis caused by H. pylori, but it is not known whether acid suppression increases the risk of atrophic gastritis. METHODS: We studied patients from two separate cohorts who were being treated for reflux esophagitis: 72 patients treated with fundoplication in Sweden and 105 treated with omeprazole (20 to 40 mg once daily) in the Netherlands. In both cohorts, the patients were followed for an average of five years (range, three to eight). After fundoplication, the patients did not receive acid-suppressive therapy. The presence of H. pylori was assessed at the first visit by histologic evaluation in the fundoplication group and by histologic and serologic evaluation in the omeprazole group. The patients were not treated for H. pylori infection. Before treatment and during follow-up, the patients underwent repeated gastroscopy, with biopsy sampling for histologic evaluation. RESULTS: Among the patients treated with fundoplication, atrophic gastritis did not develop in any of the 31 who were infected with H. pylori at base line or the 41 who were not infected; 1 patient infected with H. pylori had atrophic gastritis before treatment that persisted after treatment. Among the patients treated with omeprazole, none of whom had atrophic gastritis at base line, atrophic gastritis developed in 18 of the 59 infected with H. pylori(P<0.001) and 2 of the 46 who were not infected (P=0.62). CONCLUSIONS: Patients with reflux esophagitis and H. pylori infection who are treated with omeprazole are at increased risk of atrophic gastritis.

Long-term sequelae of Helicobacter pylori gastritis.

Chronic Helicobacter pylori gastritis has been put forward as a risk factor for development of gastric mucosal atrophy and gastric cancer. The purpose of our study was to investigate the long-term effects of H pylori gastritis on the gastric mucosa. We prospectively studied 49 subjects negative for H pylori and 58 positive subjects for a mean follow-up of 11.5 years (range 10-13 years). Serum samples were obtained at the initial and follow-up visits for determination of H pylori IgG antibodies. Gastroscopies with biopsy sampling were done in all patients at both visits. Biopsy specimens were used for assessment of H pylori infection and histology. Development of atrophic gastritis and intestinal metaplasia occurred in 2 (4%) uninfected and 16 (28%) infected subjects. Regression of atrophy was noted in 4 (7%) infected subjects. Development of atrophic gastritis and intestinal metaplasia was significantly associated with H pylori infection (p = 0.0014; odds ratio 9.0, 95% CI 1.9-41.3). The proportion of atrophic gastritis in the study population showed an annual increase of 1.15% (0.5-1.8%). We conclude that H pylori infection is a significant risk factor for development of atrophic gastritis and intestinal metaplasia. Our findings support strongly the causative role of this infection in gastric carcinogenesis.

Pharmacological management of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) ranges from episodic symptomatic reflux without oesophagitis to severe oesophageal mucosal damage, such as Barrett's metaplasia or peptic stricture. The multifactorial pathogenesis of GORD prevents medical cure of the disease. GORD is a chronic disease with a high tendency to relapse, requiring a long term treatment strategy in practically all patients. Complete healing of all mucosal lesions is not necessarily the aim of treatment in all patients. In milder forms of reflux disease, symptom relief is the most important goal. Many patients with mild GORD do well on symptomatic self-care with antacids and/or alginate. In addition, lifestyle changes should be advised to all patients: these improve symptoms and enhance the efficacy of therapy. In the acute treatment of GORD the prokinetic drug cisapride has been shown to be effective in relieving symptoms and healing grade I to II oesophagitis. Cisapride decreases symptomatic and endoscopic relapse in patients with mild GORD. Histamine H2-receptor antagonists are effective in relieving reflux symptoms in about 50% of patients, but with regard to healing, H2-antagonists appear to be mainly effective in grades I and II and not in higher grades of oesophagitis. Maintenance treatment with H2-antagonists is mainly symptomatically effective in patients with mild GORD. Proton pump inhibitors (PPIs) provide significantly higher healing rates of reflux oesophagitis than H2-antagonists, even in the more severe cases of oesophagitis and Barrett's ulcers. PPIs are also effective in patients with oesophagitis refractory to treatment with H2-antagonists. PPIs have become the drugs of first choice in healing of all patients with more severe forms of reflux oesophagitis, and increasingly also for patients with milder forms of oesophagitis, certainly those who fail to respond to other drugs. In maintenance treatment of GORD, PPIs are the most effective drugs, offering the possibility of keeping nearly all patients in remission with adjusted doses. Current patient data of up to 5 years indicate the safety of this strategy for this period, but the exact consequences of strong acid inhibition over a longer period still have to be clarified. At present, all but a few patients with GORD can be managed adequately by medical therapy.

Safety of acid-suppressing drugs.

There is an extensive literature on the adverse effects of drugs that inhibit gastric acid secretion. This study presents a critical examination of interactions between antisecretory drugs and other compounds, the frequency of serious adverse effects relating to various body systems, the safety of antisecretory drugs in pregnancy, and longer-term safety data from postmarketing surveillance studies. While interactions with some other drugs, alcohol, and certain carcinogens are of potential concern, in practice clinically significant reactions appear to be rare if they occur at all. A small number of major side-effects have been documented, but they occur rarely, and postmarketing surveillance has not detected other longer-term sequelae. Safety of these drugs in pregnancy is not established, as data are so few. It is concluded that antisecretory agents, by comparison with most other classes of drugs, are remarkably well tolerated.

The prevalence of Helicobacter pylori in peptic ulcer disease.

Both duodenal and gastric ulcer disease are closely associated with Helicobacter pylori infection. An infected individual has an estimated lifetime risk of 10-20% for the development of peptic ulcer disease, which is at least 3-4 fold higher than in non-infected subjects. H. pylori infection can be diagnosed in 90-100% of duodenal ulcer patients and in 60-100% of gastric ulcer patients. Subjects infected with a cytotoxin-producing bacterial strain, or a strain possessing cagA, are at a higher risk of duodenal ulcer. Other factors that may influence the peptic ulcer risk in infected subjects are the amount of gastric acid production (which is increased in duodenal ulcer disease and decreased in gastric ulcer disease), the presence of gastric metaplasia in the duodenal bulb, smoking, and genetic factors (e.g. blood group O and lack of the secretor gene). After eradication of the infection, the risk of recurrence of ulcer disease is reduced to below 10% for gastric ulcer disease and to approximately 0% for duodenal ulcer disease.

Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety.

OBJECTIVE: To evaluate the long-term efficacy and safety of omeprazole in patients with gastroesophageal reflux disease resistant to treatment with histamine-2 (H2)-receptor antagonists. DESIGN: Cohort analytic study with a mean follow-up of 48 months (range, 36 to 64 months). SETTING: Patients receiving ambulatory care from referral centers. PATIENTS: 91 patients with gastroesophageal reflux disease resistant to treatment with an H2-receptor antagonist but subsequently responsive to 40 mg of omeprazole daily. INTERVENTION: Open maintenance therapy consisting of 20 mg of omeprazole daily in 86 patients and 40 mg daily in 5 patients. OUTCOME MEASURES: Endoscopy to assess healing; side effects, laboratory values, fasting serum gastrin level, and gastric corpus biopsies to assess safety. RESULTS: Esophagitis recurred in 47% of the patients receiving 20 mg of omeprazole daily, but all rehealed after the dose was doubled. Seven of 40 patients (18%) had a second relapse after a mean follow-up time of 24 months (range, 9 to 36 months) that was successfully treated with a further 20-mg dose increment for a mean period of 36 months (range, 6 to 39 months). Median gastrin levels increased initially from 60 ng/L before study entry to 162 ng/L (P < 0.01) with treatment and reached a plateau during maintenance treatment. Very high gastrin levels (> 500 ng/L) were observed in a subgroup (11%) of patients. The incidence of micronodular hyperplasia increased from 2.5% of the patients at first biopsy to 20% at the last biopsy (P = 0.001), with a corresponding progression of gastritis to subatrophic or atrophic gastritis from less than 1% to 25% (P < 0.001), which was more pronounced in patients with very high serum gastrin levels. CONCLUSIONS: Maintenance therapy with omeprazole was effective for at least 5 years in patients with gastroesophageal reflux disease resistant to treatment with H2-receptor antagonists. Treatment was accompanied by a persistent increase in serum gastrin levels and an increase of micronodular argyrophil cell hyperplasia and subatrophic or atrophic gastritis.

Prevention of duodenal ulcer relapse by long-term treatment with omeprazole.

Duodenal ulcer is a chronic disease with a high risk of relapse--if left untreated, the relapse rate is 50-80% per year (1). However, the relapse rate can be effectively reduced by inhibition of gastric acid secretion. Although many patients can be managed with episodic therapy, controlled either by the patient or doctor, continuous maintenance treatment is often necessary for patients with severe forms of the disease and those at risk of complications (2). Maintenance therapy with single night-time doses of an H2-receptor antagonist reduces relapse rates from approximately 75% to 25% per year (3). As omeprazole is more effective than the H2-receptor antagonists in the acute treatment of duodenal ulcer, healing virtually all patients within 4 weeks (4), it may also be more effective in the maintenance treatment of duodenal ulcer disease. To date, three studies have reported the effect of omeprazole on relapse rates of duodenal ulcer. A Danish multicentre study involved 195 patients, who were treated with omeprazole, either 10 mg once daily, or 20 mg once daily on Friday, Saturday and Sunday (weekend therapy), or with placebo (5). After 6 months, the remission rates were 67% and 70%, respectively, for those patients receiving omeprazole--significantly higher than in those receiving placebo (17% after 6 months). An Italian multicentre study of 81 patients found that omeprazole, both 10 mg once daily, and 20 mg once daily at weekends (Friday, Saturday and Sunday), was equally effective in preventing relapse. The proportions of patients in remission were 81% and 70%, respectively, after 6 months (6).(ABSTRACT TRUNCATED AT 250 WORDS)