Basal acid output and gastric acid hypersecretion in gastroesophageal reflux disease

The purpose of this study was to evaluate possible differences in basal gastric acid secretion with regard to severity of gastroesophageal reflux disease. Basal acid output was determined by nasogastric suction in 228 patients with gastroesophageal reflux disease who received upper gastrointestinal endoscopy and were diagnosed with either pyrosis alone (N = 98), erosive esophagitis with or without pyrosis (N = 87), or Barrett's esophagus (N = 43). Mean basal acid output for the 228 patients with gastroesophageal reflux disease was 6.5 ± 5.6 meq/hr, which was significantly different from 65 normal subjects with a mean basal acid output of 3.0 ± 2.7 meq/hr (P < 0.0001). Compared to normal subjects, mean basal acid outputs significantly differed for patients with pyrosis (P < 0.05), esophagitis (P < 0.01), and Barrett's esophagus (P < 0.01). There was also a significant difference in mean basal acid output between the patients with pyrosis and Barrett's esophagus (P < 0.01). Nineteen of the 98 patients with pyrosis (19%), 24 of the 87 patients with esophagitis (28%), and 15 of the 43 patients with Barrett's esophagus (35%) had gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr). One hundred forty-six patients with gastroesophageal reflux disease were treated with ranitidine in doses that resulted in complete healing of esophagitis and disappearance of pyrosis. Ninety-three patients responded to ranitidine 300 mg/day; however, 53 patients required increased dose of ranitidine (mean 1205 mg/day, range 600–3000 mg/day). There was a significant correlation between basal acid output and daily ranitidine dose required for therapy for the 146 patients with gastroesophageal reflux disease (r = 0.53,P = 0.0001). Furthermore, a significant association was also found between the presence of gastric acid hypersecretion and the requirement for increased doses of ranitidine (greater than 300 mg/day) (P = 0.00001). These results indicate that there is a subset of patients with gastroesophageal reflux disease who do have idiopathic gastric acid hypersecretion. Moreover, these patients have an apparently higher requirement for medication dosage in order to achieve therapeutic efficacy.     

Correlation between basal acid output and daily ranitidine dose required for therapy in Barrett's esophagus

We prospectively evaluated basal gastric acid secretion in 42 consecutive patients with Barrett's esophagus to determine the optimal dose requirement for an H₂-receptor antagonist in relation to the gastric acid secretory status of each patient. All patients with Barrett's esophagus had pyrosis and 31 of the 42 patients had erosive esophagitis. Mean extension of Barrett's epithelium was 6.9 cm (range 2–17 cm). Mean basal acid output for the patients with Barrett's esophagus was 8.0±5.2 meq/hr, which was significantly different compared to a group of 65 normal subjects with mean basal acid output of 3.0 ±2.7 meq/hr (P<0.001). There was no correlation between basal acid output and extension of Barrett's epithelium. All patients with Barrett's esophagus were treated with ranitidine, with 24 requiring standard-dose (300 mg/day) and 18 requiring increased doses (mean 1170 mg/day, range 600–2400 mg/day) for complete healing of esophagitis and disappearance of pyrosis. There was a significant correlation between basal acid output and daily ranitidine dose required for therapy (r=0.52,P<0.001). Fifteen of the 42 patients with Barrett's esophagus (36%) had gastric acid hypersecretion. There was a significant association between gastric acid hypersecretion defined as a basal acid output of greater than 10.0 meq/hr and a requirement for increased daily ranitidine doses (greater than 300 mg/day) (P<0.0002). No side effects occurred with any of these high doses of ranitidine. We conclude that as a group, patients with Barrett's esophagus have significantly higher basal acid outputs than normal subjects and many require increased therapeutic doses of ranitidine. Furthermore, there is a significant correlation between basal acid output and therapeutic daily ranitidine dose and a significant association between gastric acid hypersecretion and the requirement for increased daily ranitidine doses.     

Gastric acid hypersecretion in refractory gastroesophageal reflux disease

We prospectively evaluated gastric acid output (mEq/h), gastric volume output (ml/h), ambulatory 24-h esophageal pH monitoring, and the endoscopic appearance of the esophagus in 23 patients undergoing treatment of chronic long-standing pyrosis. Twelve of these 23 individuals (52%) remained symptomatic after 3 mo of standard antisecretory treatment with ranitidine, 150 mg twice daily. When compared with initial responders, those patients who did not experience complete symptomatic relief on therapy had significantly higher basal acid output (p less than 0.001), basal volume output (p less than 0.02), and basal upright (but not supine) reflux time (p less than 0.05). Nine of the 12 patients who did not respond to initial treatment had gastric acid hypersecretion (basal acid output greater than 10 mEq/h), and 10 of the 12 had Barrett's epithelium compared with only 1 patient in the initial-responder group (p less than 0.001). All 12 nonresponders were treated for an additional 3 mo with increased doses of ranitidine (mean, 1280 mg/day; range, 600-1800 mg/day), and complete disappearance of pyrosis occurred in 10 of the 12, although no significant endoscopic regression was observed in the extent of the underlying columnar mucosa in those with Barrett's esophagus over the 6-mo duration of the study. A significant correlation was shown between the daily ranitidine dose required to eliminate symptoms and the pretreatment basal acid output (r = 0.81, p less than 0.001); gastric acid output had to be almost totally suppressed (i.e., less than 1 mEq/h) for pyrosis to disappear completely. No side effects occurred with any of these high doses of ranitidine. We conclude that a subgroup of patients with long-standing symptomatic gastroesophageal reflux disease who do not respond to standard ulcer-healing doses of histamine2-receptor antagonists are hypersecretors of basal gastric acid and require increased acid-suppressive therapy. Many of these individuals also have underlying Barrett's epithelium.     

24-Hour Intragastric Acidity and Plasma Gastrin during Long-Term Treatment with Omeprazole or Ranitidine in Patients with Reflux Esophagitis

The reduction in intragastric acidity and the subsequent increase in plasma gastrin were compared during long-term treatment with either omeprazole or ranitidine in 19 patients with erosive reflux esophagitis. The patients received 40 mg omeprazole in the morning or 300 mg ranitidine twice daily. After healing, half the dose was given as maintenance treatment for 1 year. Intragastric acidity and plasma gastrin were measured 24 h before entry and monthly with the high dose and after 1, 6, and 12 months with the low dose. Omeprazole reduced intragastric acidity more effectively than ranitidine (p < 0.001). This difference in efficacy was more pronounced during the daytime. Plasma gastrin increased more after omeprazole than after ranitidine (p < 0.01), and both drugs showed a normal postprandial response and approached fasting levels before the next dose. During long-term treatment with 20 mg omeprazole in the morning no progressive alterations were observed in 24-h intragastric acidity or plasma gastrin.     

Gastroesophageal Reflux Disease in the Elderly: More Severe Disease That Requires Aggressive Therapy

Objective: To evaluate gastroesophageal reflux disease in the elderly (people ≥ 60 yr). Methods: Basal gastric-acid secretion was prospectively determined in 228 consecutive patients with symptomatic gastroesophageal reflux disease who had upper gastrointestinal endoscopy and were diagnosed with either pyrosis alone (n = 98), erosive esophagitis (n = 87), or Barrett's esophagus (n = 43). Results: Patients ≥ 60 yr (n = 66) had significantly more esophageal mucosal disease (erosive esophagitis, Barrett's esophagus) than patients < 60 yr (n = 162)- 81% versus 47% ( p = 0.000002, Fisher's exact test). Furthermore, 87% of patients ≥ 70 yr had esophageal mucosal disease. For each decade from < 30 yr to ≥ 70 yr, there was a significant increase in esophageal mucosal disease ( p = 0.002; X ² test, 23.96); however, there were no significant differences in severity of pyrosis symptoms or in mean basal acid output for each decade. When 146 of the 228 patients with gastroesophageal reflux disease were given enough ranitidine (mean, 630 mg/d; range, 300–3000 mg/d) for the relief of all pyrosis symptoms and healing of all esophageal mucosal disease, there were no significant differences in ranitidine therapy between each decade. Conclusions: Elderly patients with pyrosis symptoms severe enough to require upper gastrointestinal endoscopy have gastroesophageal reflux disease with more esophageal mucosal disease (erosive esophagitis, Barrett's esophagus) than patients < 60 yr, and like younger patients, may require markedly increased doses of ranitidine as large as 2400 mg/d for effective therapy.     

Prevention of Relapse of Reflux Esophagitis after Endoscopic Healing: The Efficacy and Safety of Omeprazole Compared with Ranitidine

Ninety-eight patients with erosive and/or ulcerative esophagitis unhealed after at least 3 months' treatment with standard doses of cimetidine (≥1200mg daily) or ranitidine (≥300 mg daily) were primarily included in an acute healing phase study, and 51 were allocated to 40 mg omeprazole once daily and 47 to 300 mg ranitidine twice daily. After 12 weeks of treatment, 46 (90%) patients given omeprazole were healed, compared with 22 (47%) allocated to ranitidine. Healed patients were then given maintenance treatment with either 20 mg omeprazole once daily or 150 mg ranitidine twice daily for 12 months. Plasma gastrin was determined and gastric mucosal biopsy specimens were obtained during the entire study to assess the structure of the exocrine and endocrine cell populations of the oxyntic mucosa. Sixty-seven per cent of the total number of patients randomized to omeprazole were maintained in clinical and endoscopic remission throughout the 12-month study period as compared with only 10% among those given ranitidine (p < 0.0001). After 4 weeks of omeprazole treatment basal gastrin levels were slightly increased, with a 95% confidence interval for the change of from 8.6 to 16.9pmol/l. No further increase in basal gastrin levels was observed during the ensuing study months. No significant histopathologic lesion was found in the oxyntic gland mucosa. In conclusion, omeprazole was far superior to ranitidine in preventing recurrence, a goal achieved without adverse events and significant abnormalities in the oxyntic mucosal exocrine or endocrine cells but with a moderate increase in basal gastrin levels.     

Effect of omeprazole and high doses of ranitidine on gastric acidity and gastroesophageal reflux in patients with moderate-severe esophagitis

Thirty to fifty percent of patients with reflux esophagitis fail to heal after treatment with conventional doses of H2-receptor antagonists, whereas omeprazole administration induces more than 90% healing. To investigate the effect of omeprazole and higher-than-presently-recommended doses of H2-blockers, we evaluated gastric acidity and gastroesophageal reflux in 17 patients with severe-moderate esophagitis before and after treatment with 300 mg ranitidine twice daily or 20 mg omeprazole once daily. Three pH-metric studies were performed, in a cross-over design, before and after 8 days of treatment with omeprazole or ranitidine. Both drugs significantly reduced intragastric acidity (p less than 0.001) during both night and day hours. Median hourly 24-h intragastric pH was 1.8 in the basal study, 2.9 after ranitidine, and 3.4 after omeprazole. Intragastric acidity fell from 84.0 mmol/L in the basal study to 14.2 mmol/L (79% inhibition) with ranitidine and 9.3 mmol/L (84% inhibition) with omeprazole. Patients with esophagitis were significantly more exposed to acid than healthy subjects, in both the supine and upright position (p less than 0.01). The time with esophageal pH less than 4 dropped from 23.9% in the basal study to 8.5% with ranitidine and to 7.2% with omeprazole (p less than 0.001). Both drugs significantly reduced esophageal exposure to acid in both the supine and upright positions (p less than 0.001), whereas neither had any effect on esophageal acid clearance.     

24-hour intragastric acidity and plasma gastrin during long-term treatment with omeprazole or ranitidine in patients with reflux esophagitis

The reduction in intragastric acidity and the subsequent increase in plasma gastrin were compared during long-term treatment with either omeprazole or ranitidine in 19 patients with erosive reflux esophagitis. The patients received 40 mg omeprazole in the morning or 300 mg ranitidine twice daily. After healing, half the dose was given as maintenance treatment for 1 year. Intragastric acidity and plasma gastrin were measured 24 h before entry and monthly with the high dose and after 1, 6, and 12 months with the low dose. Omeprazole reduced intragastric acidity more effectively than ranitidine (p less than 0.001). This difference in efficacy was more pronounced during the daytime. Plasma gastrin increased more after omeprazole than after ranitidine (p less than 0.01), and both drugs showed a normal postprandial response and approached fasting levels before the next dose. During long-term treatment with 20 mg omeprazole in the morning no progressive alterations were observed in 24-h intragastric acidity or plasma gastrin.     

Partial regression of Barrett's esophagus by long-term therapy with high-dose omeprazole

Background: Barrett's esophagus is mainly regarded as an acquired condition related to increased gastroesophageal reflux. Thus it is conceivable that abolition of acid reflux would lead to its regression. The aim of this study was to assess whether long-term treatment with high-dose omeprazole (60 mg/day) produces a consistent control of gastric acid production and normalizes the esophageal acid exposure, thus reducing the length of Barrett's epithelium. Methods: Fourteen patients (8 men and 6 women, mean age 52 years) with histologic diagnosis of columnar epithelium longer than 3 cm in the distal part of the esophagus were enrolled and began receiving 60 mg of omeprazole in a single daily morning dose. Before therapy and after 6 and 12 months of therapy, all patients had endoscopy with four-quadrant biopsies at 2 cm intervals. A 24-hour esophagogastric pH recording was performed at entry and after 10 days, 6 months, and 12 months of treatment in all patients. Results: The initial length of Barrett's epithelium (4.5 ± 1.9 cm) was significantly reduced after 6 months (3.1 ± 1.1; p < 0.01) and 12 months (2.1 ± 1.6; p < 0.005) of treatment. Values were significantly lower at 12 than at 6 months (p < 0.03). The 24-hour mean gastric pH after 10 days (5.89 ± 0.58), 6 months (5.71 ± 0.55), and 12 months (5.54 ± 0.76) of therapy was always higher (p < 0.001) than the basal level (1.9 ± 0.49). No significant difference in gastric pH was seen over the treatment period. The 24-hour mean percent of time in which pH in the esophagus was below 4.0 decreased significantly (p < 0.001) from a basal rate of 29.4% to 3.5%, 3.0%, and 4.9% in the various time intervals of therapy. There was a normalization of esophageal acid exposure in all patients but two. Conclusions: It can be concluded that the antisecretory effect of 60 mg/day of omeprazole is consistent and is kept constant throughout the entire 1-year treatment period. The consequent normalization of esophageal acid exposure in almost all patients in our series led to a partial, but significant, regression in the length of Barrett's epithelium. (Gastrointest Endosc 1996;44:700-5)     

Gastric secretion and emptying of liquids in reflux esophagitis

We have investigated the gastric secretory activity and the emptying half-time of a liquid meal in 17 selected patients with reflux esophagitis compared to 10 controls. The basal acid output and the basal and maximal secretory volume were higher in the patient group (P<0.05,P=0.05, andP<0.01, respectively), while the maximal acid output and the basal and maximal acid concentration were not different in the two groups. The gastric emptying half-time of a liquid meal was higher in the patient group (P<0.001). Our results show that gastric function may be altered in reflux esophagitis patients and suggest particularly that a delayed emptying of liquids may play a role in the pathogenesis of the disease in some patients.     

Prevention of relapse of reflux esophagitis after endoscopic healing: the efficacy and safety of omeprazole compared with ranitidine.

Ninety-eight patients with erosive and/or ulcerative esophagitis unhealed after at least 3 months' treatment with standard doses of cimetidine (greater than or equal to 1200 mg daily) or ranitidine (greater than or equal to 300 mg daily) were primarily included in an acute healing phase study, and 51 were allocated to 40 mg omeprazole once daily and 47 to 300 mg ranitidine twice daily. After 12 weeks of treatment, 46 (90%) patients given omeprazole were healed, compared with 22 (47%) allocated to ranitidine. Healed patients were then given maintenance treatment with either 20 mg omeprazole once daily or 150 mg ranitidine twice daily for 12 months. Plasma gastrin was determined and gastric mucosal biopsy specimens were obtained during the entire study to assess the structure of the exocrine and endocrine cell populations of the oxyntic mucosa. Sixty-seven per cent of the total number of patients randomized to omeprazole were maintained in clinical and endoscopic remission throughout the 12-month study period as compared with only 10% among those given ranitidine (p less than 0.0001). After 4 weeks of omeprazole treatment basal gastrin levels were slightly increased, with a 95% confidence interval for the change of from 8.6 to 16.9 pmol/l. No further increase in basal gastrin levels was observed during the ensuing study months. No significant histopathologic lesion was found in the oxyntic gland mucosa. In conclusion, omeprazole was far superior to ranitidine in preventing recurrence, a goal achieved without adverse events and significant abnormalities in the oxyntic mucosal exocrine or endocrine cells but with a moderate increase in basal gastrin levels.     

Idiopathic gastric acid hypersecretion

Many patients with acid-peptic disease have idiopathic gastric acid hypersecretion defined as a basal acid output >10.0 meq/hr; however, a significant proportion have basal acid outputs >15.0 meq/hr, which is within the range found in Zollinger-Ellison syndrome. Although idiopathic gastric acid hypersecretion is more common than Zollinger-Ellison syndrome, it is important that these two disorders be differentiated because of differences in treatment and natural history. In the present study, we compared 124 patients with idiopathic gastric acid hypersecretion and 137 patients with Zollinger-Ellison syndrome. There were no significant differences with regard to age at diagnosis, history of upper gastrointestinal hemorrhage, nausea, vomiting, and family history of duodenal ulcer and other acid-peptic disease. However, significant differences were observed between patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome with regard to percentage of males: 77% compared to 64% (P=0.008), mean serum gastrin: 60 pg/ml compared to 3679 pg/ml (normal <100 pg/ml) (P<0.001), mean basal acid output: 15.4 meq/hr compared to 47.0 meq/hr (P<0.001), mean age at onset of symptoms: 33 years compared to 41 years (P<0.001), mean duration of symptoms before diagnosis: 11 years compared to five years (P<0.001), percentage with abdominal pain: 67% compared to 82% (P=0.00004), percentage with diarrhea: 12% compared to 75% (P<0.000001), percentage with pyrosis: 58% compared to 40% (P=0.003), percentage with duodenal ulcer: 53% compared to 74% (P<0.000001), and percentage with esophagitis: 31% compared to 42% (P=0.0004). The differences in clinical features could be attributed to difference in mean basal acid output, and/or differences in levels of basal acid output used for diagnosis of idiopathic gastric acid hypersecretion (basal acid output >10.0 meq/hr) and Zollinger-Ellison syndrome (basal acid output >15.0 meq/hr). When 45 patients with idiopathic gastric acid hypersecretion and 39 patients with Zollinger-Ellison syndrome with basal acid outputs 15.1–30.0 meq/hr were compared, the main significant differences were with regard to mean serum gastrin: 69 pg/ml compared to 655 pg/ml (P<0.001), percentage of male gender: 82% compared to 62% (P=0.03), and percentage with diarrhea: 16% compared to 64% (P=0.000005). These results indicate that in general patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome often have similar clinical features that can be difficult to distinguish. However, the increased frequency of diarrhea and female gender should lead to a strong suspicion of Zollinger-Ellison syndrome, which can be distinguished in almost every case by measurement of serum gastrin.     

Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety.

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.     

Gastric acid and pepsin secretion in patients with Barrett's esophagus and appropriate controls

The objective of this study was to determine whether gastric secretion of acid and pepsin is different in the subset of esophagitis patients who also have Barrett's esophagus. Basal and stimulated gastric secretions were studied for 1 hr in the unstimulated state and 1 hr after pentagastrin 6 µg/kg subcutaneous injection. Because Barrett's patients are predominantly male, the 30 patients were matched with patients who had esophagitis, but not Barrett's, for sex (26 men, 4 women) and age as well as for background gastrointestinal disease (duodenal ulcer in 10, no ulcer disease in 17 and Zollinger-Ellison hypersecretors in 3). Patients with Barrett's weighed more than controls (P<0.05). Acid and pepsin output in the basal and stimulated state were no different in Barrett's and their appropriately matched controls. Overnight fasting residue—volume, pH, acid and pepsin concentrations, and bile content—were also alike. The severity of esophagitis or prevalence of esophageal ulcer or stricture was not different between those with and without Barrett's and in neither was the grade of esophagitis related to acid or pepsin output. It is concluded that Barrett's esophagus patients do not have gastric secretions different from appropriately matched controls with esophagitis alone. When present, esophagitis due to reflux in Barrett's epithelium should be treated on its merits by appropriate reduction of acid exposure.     

Gastric acid secretion and plasma gastrin during short-term treatment with omeprazole and ranitidine in duodenal ulcer patients.

The aim of this study was to evaluate changes in peptic acid secretion, and in fasting and meal-stimulated plasma gastrin levels after a 7-day course of omeprazole 30 mg/day or ranitidine 300 mg/day, administered in accordance with a randomized, double-blind, double-dummy protocol. Ten duodenal ulcer patients were studied. Their acid and pepsin output was determined prior to and after treatment. Plasma gastrin levels were also determined under basal conditions on day 7 of treatment, and 24 hours after the last administration of the drug. With regard to acid output, omeprazole resulted in a 98% reduction in BAO and an 80% reduction in PAO, both significantly greater than those achieved with ranitidine (BAO 50%, PAO 25%). No significant changes in pepsin secretion were observed. The increase in fasting plasma gastrin observed after ranitidine and omeprazole was 86% and 242%, respectively, on day 7, and 13% and 103% twenty-four hours after final dose. Increases in meal-stimulated plasma gastrin were, respectively, 126% and 125% on day 7 and 8 after omeprazole, whereas the increase with ranitidine was 62% only on day 7 of treatment, with subsequent normalization. In addition to confirming the well-known effect of omeprazole on the physiology of gastric secretion, our data show that administration of therapeutic doses of traditional H2-antagonists is accompanied by a secondary hypergastrinemia, which is rapidly reversible after discontinuation of therapy.     

Endoscopic regression of Barrett''s oesophagus during omeprazole treatment; a randomised double blind study

BACKGROUND: Barrett's oesophagus, columnar metaplasia of the epithelium, is a premalignant condition with a 50-100-fold increased risk of cancer. The condition is caused by chronic gastro-oesophageal reflux. Regression of metaplasia may decrease the cancer risk. AIMS: To determine whether elimination of acid gastro-oesophageal reflux induces a regression of metaplastic epithelium. METHODS: Sixty eight patients with acid reflux and proven Barrett's oesophagus were included in a prospective, randomised, double blind study with parallel groups, and were treated with profound acid secretion suppression with omeprazole 40 mg twice daily, or with mild acid secretion suppression with ranitidine 150 mg twice daily, for 24 months. Endoscopy was performed at 0, 3, 9, 15, and 24 months with measurement of length and surface area of Barrett's oesophagus; pH-metry was performed at 0 and 3 months. Per protocol analysis was performed on 26 patients treated with omeprazole, and 27 patients treated with ranitidine. RESULTS: Omeprazole reduced reflux to 0.1%, ranitidine to 9.4% per 24 hours. Symptoms were ameliorated in both groups. There was a small, but statistically significant regression of Barrett's oesophagus in the omeprazole group, both in length and in area. No change was observed in the ranitidine group. The difference between the regression in the omeprazole and ranitidine group was statistically significant for the area of Barrett's oesophagus (p=0. 02), and showed a trend in the same direction for the length of Barrett's oesophagus (p=0.06). CONCLUSIONS: Profound suppression of acid secretion, leading to elimination of acid reflux, induces partial regression of Barrett's oesophagus.     

Time pattern of gastric acidity in Barrett's esophagus

Increased gastroesophageal acid reflux is frequently found in patients with Barrett's esophagus, and it has been hypothesized that gastric acid hypersecretion could be an important factor aggravating the exposure of esophageal mucosa to acid and then contributing to the development of this disorder. The aim of the present study was to assess whether the circadian pattern of gastric acidity differs between refluxer patients with and without Barrett's esophagus and normal subjects. Continuous 24-hr gastric pH monitoring was performed in 119 healthy volunteers, 20 patients with Barrett's esophagus, 37 patients with moderate and 10 patients with severe reflux esophagitis without Barrett's esophagus. In all these diseases the final diagnosis was ascertained by means of endoscopy plus biopsy. There was no difference in the 24-hr and daytime patterns of gastric pH between healthy subjects and patients with Barrett's esophagus, while nocturnal acidity was significantly lower (P<0.05) in the latter population. Gastric acidity, in contrast, was higher (P<0.05) in controls than in patients with both moderate and severe reflux esophagitis without Barrett's esophagus during the whole 24-hr period. There was no difference between refluxer patients with and without Barrett's esophagus in any of the three time intervals we analyzed. Because normal subjects had lower gastric pH than patients with Barrett's esophagus during the night and than patients with reflux esophagitis during the whole 24-hr period, gastric hyperacidity is not a relevant factor in the development of both metaplastic columnar epithelium and inflammatory changes in the distal esophagus, and other pathophysiological mechanisms are involved in these histological alterations.     

Helicobacter pylori in duodenal ulcer patients with idiopathic gastric acid hypersecretion

Thirty-three consecutive patients with idiopathic gastric acid hypersecretion (defined as a basal acid output >10.0 meq/hr with a normal fasting serum gastrin level and negative secretin stimulation test) who were being treated for duodenal ulcer disease and other acid-peptic disorders were evaluated for the presence ofHelicobacter pylori by means of a rapid urease test. Fourteen patients had duodenal ulcer and 19 had other acid-peptic disorders (gastroesophageal reflux in 14, including six with Barrett's esophagus; four with nonulcer dyspepsia; and one with erosive gastritis).Helicobacter pylori was present in 12 of the 14 ulcer patients (86%) compared to only two of the 19 nonulcer patients (11%) (P<0.0001). The distribution of basal acid output for patients with duodenal ulcer was similar to that for nonulcer patients, and no significant difference in the mean basal acid output was found amongHelicobacter pylori-positive compared toHelicobacter pylori-negative patients. Seven of the duodenal ulcer patients with a basal acid output greater than 15.0 meq/hr wereHelicobacter pylori-positive, suggesting that the organism can withstand even extreme levels of gastric acidity. In conclusion, this study demonstrates that the prevalence ofHelicobacter pylori infection in patients with duodenal ulcer disease associated with idiopathic gastric acid hypersecretion is not different from a majority of ulcer patients with normal acid secretory profiles and offers additional evidence that extreme levels of gastric acid are not bactericidal for the organism.     

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.     

OMEPRAZOLE AND COMPLICATED GASTRO-OESOPHAGEAL REFLUX DISEASE

Abstract Suppression of acid secretion with omeprazole is highly effective for the healing of oesophagitis. The aims of the present study were to determine whether recovery of gastro-oesophageal reflux disease in patients with stricture improves dysphagia and decreases the dilatation need and to compare the efficacy of omeprazole versus H₂-receptor antagonists. Thirty-eight patients with peptic stricture (grade IV oesophagitis) and erosive oesophagitis underwent endoscopic dilatation and were randomized to omeprazole (40 mg daily; n = 20) versus ranitidine (150 mg twice daily; n=18). Healing was proven endoscopically and patients were interviewed for dysphagia relief. Patients were assessed for relapse by endoscopy 6 months later. The follow-up period was a further 6 months. Patients received maintenance treatment with 40 mg omeprazole daily or ranitidine 150 mg twice daily and the total duration of treatment was 1 year. At 6 months, omeprazole produced a highly significant (P < 0.0001) greater rate of oesophagitis healing and highly significant (P < 0.0001) fewer dilatations compared with H₂-receptor antagonists (18 (90%) patients vs five (28%) patients, respectively; 3.5 vs 9.0 dilatations/patient). At 12 months, not one of the 18 successfully treated patients from the omeprazole group had relapsed. The two remaining patients required further dilatation and 40 and 60 mg omeprazole daily for healing. In comparison, all patients on ranitidine had to undergo further bougienage. In conclusion, omeprazole is a safe and effective maintenance treatment for preventing relapse of complicated reflux oesophagitis.