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.     

Definition for idiopathic gastric acid hypersecretion

Zollinger-Ellison syndrome and other gastric acid hypersecretory states in which a specific etiology is identified are defined as a basal acid output of greater than 15.0 meq/hr. To determine the level of basal acid output that defines idiopathic gastric hypersecretion, basal acid outputs were investigated in normal subjects and patients with duodenal ulcers, and functional and statistical definitions for idiopathic gastric acid hypersecretion were developed. Sixty-five normal subjects were evaluated to define idiopathic gastric acid hypersecretion on a statistical basis, and 22 patients with refractory duodenal ulcers were evaluated to define idiopathic gastric acid hypersecretion on a functional basis. Mean basal acid output for the 65 normal subjects was 3.0±2.7 meq/hr. Even though the mean basal acid output for the group of 28 normal male subjects was slightly higher than for the group of 37 normal female subjects, the groups were not significantly different. The 95% confidence interval around the mean basal acid output for all normal subjects was 2.4–3.7 meq/hr, with little difference between the male and female groups. The mean basal acid output plus two standard deviations and the mean basal acid output plus three standard deviations for the 65 normal subjects were 8.4 meq/hr and 11.1 meq/hr, respectively. Of 109 patients with active duodenal ulcers treated for eight weeks with standard doses of antisecretory medication, 22 showed no healing as documented by endoscopy. The mean basal acid output for these 22 patients with nonhealed duodenal ulcers was 18.7 meq/hr (range 10.1–49.1 meq/hr) while mean basal acid output for the 87 patients with healed duodenal ulcers was 7.5 meq/hr (range 0.0–27.9 meq/hr). The difference in mean basal acid output between these two groups was statistically different (P<0.001). All patients with refractory duodenal ulcers had basal acid outputs of greater than 10.0 meq/hr. Our results indicate that the definition for idiopathic gastric acid hypersecretion should be a basal acid output of greater than 10.0 meq/hr, since, based on refractory duodenal ulcer disease, the functional definition for idiopathic gastric acid hypersecretion is a basal acid output of greater than 10.0 meq/hr, which in our data also corresponds well to the statistically defined range of basal acid output in normal subjects.     

Helicobacter pylori and gastric acid output in peptic ulcer disease

Helicobacter pylori is associated with peptic ulcer, and a causal relationship has been postulated. We investigated the association betweenHelicobacter pylori and gastric acid output. Two hundred forty-one patients were studied: 173 with duodenal ulcer, 51 with gastric ulcer (41 corpus, 10 prepyloric), and 17 with combined gastric and duodenal ulcer. In 194 patients (80%),Helicobacter pylori could be demonstrated histologically from gastric antral biopsies. The presence or absence ofHelicobacter pylori was not influenced by age, sex, or use of tobacco or analgesics. Patients with duodenal ulcer or combined gastric and duodenal ulcer had similar gastric acid outputs irrespective of the presence or absence ofHelicobacter pylori. However, gastric ulcer patients withHelicobacter had higher basal and maximal acid outputs when compared to patients withoutHelicobacter (mean basal output: 4.1 mmol/hr vs 2.4,P<0.05; mean maximal output 19.5 mmol/hr vs 14.4,P<0.05). AlthoughHelicobacter pylori is associated with both gastric ulcer and duodenal ulcer, its significance may be different in the two diseases.     

Basal gastric acid secretion in nonulcer dyspepsia with or without duodenitis

Nonulcer dyspepsia with or without duodenitis and duodenal ulcer disease are often considered to be a spectrum of the same acid-peptic process. Some reports evaluating basal gastric acid secretion in nonulcer dyspepsia and duodenal ulcer disease have supported that impression; however, results from different studies have been mixed. In order to compare basal gastric secretory profiles in nonulcer dyspepsia and duodenal ulcer disease, we determined basal acid outputs in 66 consecutive patients with the diagnosis of nonulcer dyspepsia. All patients with nonulcer dyspepsia had at least a three-month history of epigastric abdominal pain, and all had negative upper gastrointestinal endoscopies except for 14 with duodenitis. The 66 patients with nonulcer dyspepsia were compared to 40 asymptomatic normal subjects and 114 patients with endoscopically documented duodenal ulcer disease. There was no significant difference in mean basal acid output among all 66 patients with nonulcer dyspepsia (2.9±2.7 meq/hr),the group of normal subjects (3.2±2.7 meq/hr),the 14 patients with nonulcer dyspepsia with duodenitis (3.0±2.1 meq/hr),and the 52 patients with nonulcer dyspepsia without duodenitis (2.9±2.9 meq/hr).However, mean basal acid output of the patients with duodenal ulcer disease (9.1±7.6 meq/hr)was significantly higher than all the other groups (P <0.001).The gastric acid secretory profiles determined in this study do not appear to support the view that nonulcer dyspepsia with or without duodenitis and duodenal ulcer disease are a spectrum of the same acidpeptide process.     

Hypersecretory duodenal ulcer and Helicobacter pylori infection: for-year follow-up study

Background. About 10% of duodenal ulcer patients are characterized by gastric acid hypersecretion with normal gastrin values. Relapsing duodenal ulcer after Helicobacter pylori cure has been related to high acid output and maintenance antisecretory therapy has been suggested in hypersecretory duodenal ulcer patients. The role of Helicobacter pylori infection and the effects of Helicobacter pylori cure in hypersecretory duodenal ulcer patients still remain to be fully studied.Aim. To study: a) whether gastric acid hypersecretion “per se” is a risk factor for duodenal ulcer recurrence; b) whether maintenance antisecretory therapy is necessary after eradication in hypersecretory duodenal ulcer patients.Patients. The study population comprised 8 hypersecretory duodenal ulcer patients, selected from a population of 79 Helicobacter pylori-positive duodenal ulcer patients.Methods. Hypersecretory duodenal ulcer patients were followed-up for at least 4 years after eradication. Gastric acid secretion was measured again 12 months after Helicobacter pylori eradication. Gastroscopy with histology was performed 3, 6, 12 and 36 months after treatment, ¹³C-urea breath test after 42 months; clinical questionnaires were completed every 6 months.Results. After eradication, despite a not significantly reduced high acid output (median value of basal acid output and pentagastrin-stimulated acid output, respectively, 23.1 mEg/h and 64. 1 mEg/h before treatment vs 16 mEg/h and 49.7 mEq/h 12 months after treatment), all patients were free from symptoms, none of them had duodenal ulcer relapse or complications (7/8 before treatment), or needed antisecretory maintenance therapy, except for one patient taking non-steroidal anti-inflammatory drugs.Conclusions. These findings, obtained in a selected population of hypersecretory duodenal ulcer patients with long-term follow-up, suggest that after successful Helicobacter pylori eradication gastric acid hypersecretion “per se” is not able to determine the recurrence of duodenal ulcer.     

Zollinger-Ellison syndrome

SinceHelicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that ifH. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency ofH. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18;P<0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P<0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative forH. pylori (median 32 meq/30 min;P<0.02) but serum gastrin was correspondingly lower in patients positive forH. pylori (P<0.05).H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome.H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion.Supported in part by grant DK34988 from the National Institutes of Health, U.S. Public Health Service.This work was presented in part at the American College of Gastroenterology Annual Meeting, New Orleans, October 1989, and published in abstract form in theAmerican Journal of Gastroenterology (84:1159, 1989).     

Bleeding duodenal ulcer

Basal gastric acid output was analyzed prospectively in 110 patients with endoscopically documented duodenal ulcer disease to determine the frequency of gastric acid hypersecretion in patients with bleeding versus nonbleeding ulcers. Thirty-eight patients with stigmata of an actively or recently bleeding duodenal ulcer had a mean basal output of 12.6±8.9 meq/hr. In comparison, 72 patients with nonbleeding duodenal ulcers (and no history of prior bleeding) had a significantly lower mean basal acid output of 8.7±7.5 meq/hr (P<0.05). Twenty-four of the 38 patients (63%) with bleeding and 28 of the 72 (39%) with nonbleeding duodenal ulcers had gastric acid hypersecretion, defined as a basal acid output of greater than 10.0 meq/hr. There was a statistically significant association between bleeding duodenal ulcer and acid hypersecretion (P=0.01). All 110 patients were treated with standard doses of H₂-receptor antagonists for eight weeks. In that time, 87 patients healed and 23 patients (14 with prior bleeding and nine with nonbleeding duodenal ulcers) remained unhealed. Significantly more patients who had bled had nonhealing duodenal ulcers (P=0.004). Irrespective of bleeding history, all 23 patients with nonhealing duodenal ulcers at eight weeks had basal acid outputs of greater than 10.0 meq/hr (range 10.1–49.1 meq/hr). These 23 patients with nonhealing duodenal ulcers were treated with increased doses of ranitidine (mean 690 mg/day, range 600–1200 mg/day) for up to eight additional weeks. All were observed to have complete endoscopic healing documented within that period. These results suggest that bleeding duodenal ulcers are often associated with gastric acid hypersecretion and that these ulcers are less likely to heal after eight weeks of standard dose H₂-receptor antagonist therapy. Similarly, nonbleeding duodenal ulcers associated with gastric acid hypersecretion are also less likely to heal after standard doses of antisecretory therapy.     

Bile acid reflux and possible inhibition of Helicobacter pylori infection in subjects without gastric surgery

Bile acids are generally known to inhibit growth of Helicobacter pylori in vitro, but whether they do so in humans with no gastric surgery has been uncertain. The present study addresses this issue. Among healthy control subjects with preserved acid secretion, H. pylori-positive subjects were older and had lower gastric bile acid concentrations than H. pylori-negative subjects (P < 0.05). Among gastric ulcer patients with preserved acid secretion, H. pylori-positive patients had a higher basal acid output than H. pylori-negative patients (P < 0.05). Among H. pylori-positive subjects with preserved acid secretion, duodenal ulcer patients had a higher basal and maximum acid output than healthy control subjects (P < 0.01). In conclusion, gastric bile acids may suppress initial stages of H. pylori infection in subjects without gastric surgery. However gastric bile acids may have little effect on peptic ulcer disease, once H. pylori infection is established.     

DNA-DNA hybridization demonstrates apparent genetic differences betweenHelicobacter pylori from patients with duodenal ulcer and asymptomatic gastritis

We asked whether different clinical outcomes ofHelicobacter pylori infection might be a reflection of genetic differences in infecting organisms. Using DNA-DNA hybridization we examined whether hybridization levels groupedH. pylori isolates corresponding to the type of disease (gastric ulcer, duodenal ulcer, asymptomatic gastritis) from which they were recovered. Target DNAs were prepared fromH. pylori strains cultured from gastric biopsy specimens of 25 patients; 5 with gastric ulcers, 9 with duodenal ulcers, and 11 from asymptomatic volunteers endoscopically proven not to have peptic ulcer disease. DNA-DNA hybridization was performed with whole genomic probes made from an isolate from each of the three disease categories. Using a DNA probe from an isolate from a duodenal ulcer patient, we found that isolates from patients with duodenal ulcer and nonulcer gastritis yielded significant differences in levels of hybridization. The levels of hybridization of DNA fromH. pylori isolates from duodenal ulcer patients, gastric ulcer patients and nonulcer gastritis controls were 85.5%±7%, 83%±3%, and 78.3%±5%, respectively (mean±sd), and the difference between the hybridization levels obtained with duodenal ulcer and nonulcer control target DNAs was statistically significant (P=0.025). These data suggest that the outcome of infection (eg, ulcer or no ulcer) may be due to virulence factors encoded by genomic DNA. If such differences exist, it should be possible to produce probes that would identify the ulcer virulence gene(s) and clearly distinguish between ulcerogenic and nonulcerogenic strains ofH. pylori.This work was supported by Veterans Affairs; by grant DK 39919 from the National Institute of Diabetes and Digestive and Kidney Diseases and by the generous support of Hilda Schwartz.     

Do non-steroidal anti-inflammatory drugs cause duodenal ulcer? Evaluation of basal acid output and ulcer complications

Non-steroidal anti-inflammatory drug (NSAID) use and basal acid outputs determined by nasogastric suction were evaluated prospectively in 184 patients with endoscopically documented duodenal ulcer. The mean basal acid output and percentage of gastric acid hypersecretion for duodenal ulcer patients who used NSAID were compared with duodenal ulcer patients who did not use NSAID to determine whether patients using NSAID who develop duodenal ulcer have basal acid outputs in the normal range or in the duodenal ulcer range. Results were compared with 65 normal subjects and 105 patients with nonulcer dyspepsia. There were no significant differences with regard to the percentage of male gender, mean age, mean basal acid output, percentage of gastric acid hypersecretion and percentage of cigarette smoking history between duodenal ulcer patients who used NSAID and duodenal ulcer patients who did not. However, significant differences were observed between duodenal ulcer patients who used NSAID and duodenal ulcer patients who did not use NSAID with regard to the percentage of bleeding duodenal ulcer (59 compared with 23%; p= 0.0008) and the percentage of patients with giant duodenal ulcer (41 compared with 5%; P= 0.00001). These results suggest that NSAID use does not cause duodenal ulcer but does make pre-existing duodenal ulcer worse by causing duodenal ulcer complications.     

Age Does Not Affect Basal Gastric Acid Secretion in Normal Subjects or in Patients with Acid-Peptic Disease

Objective: To determine whether basal acid output was affected by patient age. Methods: Basal acid output determined by nasogastric suction was prospectively evaluated in normal suhjects (n = 65) and patients with gastroesophageal reflux disease (n = 228), gastric ulcer (n = 81), duodenal ulcer (n = 184), and nonulcer dyspepsia (n = 105). Resutts: There was no correlation between hasal acid output and age for the normal subjects and the patients with gastroesophageal reflux disease, gastric ulcer, duodenal ulcer, and nonulcer dyspepsia. However, there was a significant inverse correlation hetween age and basal acid output for the 33 male patients with gastric ulcer ( r =−0.41, p ≤ 0.05) and the 130 male patients with duodenal ulcer ( r = −0.18, p = 0.05). Furthermore, mean basal acid outputs were signiflcantly higher for male patients than for female patients with gastroesophageal reflux disease ( p ≤ 0.001), gastric ulcer ( p ≤ 0.05), and duodenal ulcer ( p ≤ 0.001). Mean basal acid output for the 184 patients with duodenal ulcer was significantly higher than the mean basal acid output for the 228 patients with gastroesophageal reflux disease ( P ≤ 0.001), and both were signiflcantly higher than mean hasal acid outputs for the normal suhjects and the patients with gastric ulcer and nonulcer dyspepsia ( p ≤ 0.0005). Conclusions: Basal acid output can vary with gender and acid-peptic disease process; however, basal acid output does not vary with regard to age of subject.     

Gastric acid secretion and gastric emptying of liquids in 99 male duodenal ulcer patients

Gastric acid hypersecretion and accelerated gastric emptying are commonly considered as possible determinants of duodenal ulcer, but the relative frequencies of these gastric dysfunctions have never been evaluated in a homogeneous group of patients. We studied basal and pentagastrin-stimulated gastric acid secretion and gastric emptying of a radiolabeled caloric liquid meal in 99 consecutive male patients with endoscopically proven, active, uncomplicated duodenal ulcers. Compared to matched healthy subjects, ulcer patients presented increased basal and stimulated acid secretion (P<0.001).Sixty-nine patients had peak acid output values above the 95% confidence limits of the control population (14.2–30.6 meq/hr).Cigarette smoking was correlated with gastric acid hypersecretion. No significant difference was found between duodenal ulcer patients and controls in mean gastric emptying times. Ulcer patients showed a greater variance of gastric acid secretion and emptying values than healthy subjects. This reflects varied gastrointestinal function among ulcer patients. No significant correlation was found between gastric acid output and gastric emptying times. These findings suggest that gastric acid hypersecretion, but not accelerated gastric emptying of liquids, play a relevant role in the pathogenesis of duodenal ulcer.     

Impairment of gastric secretion modulation in duodenal ulcer and in long-term PPI treatment: quantitative morphologic findings and pathophysiologic implications

Helicobacter pylori affects gastric secretion. This functional effect might have a morphometric counterpart. Therefore, the gastric cell secretory compartment was morphometrically assessed in different pathophysiologic conditions related to Helicobacter pylori infection. Nineteen Helicobacter pylori-positive nonduodenal ulcer subjects, 15 omeprazole chronically treated subjects, and 19 duodenal ulcer patients were studied against 19 controls. Somatostatin, gastrin, enterochromaffin-like, and parietal cell density was assessed in gastric biopsies. No differences in any cell type density were found between Helicobacter pylori-positive nonduodenal ulcer subjects and controls. On the contrary, differences were significant when comparing omeprazole and duodenal ulcer patients to controls (higher density of gastrin, enterochromaffin-like, and parietal cells, lower density of somatostatin cells). In duodenal ulcer a reversion to control values followed Helicobacter pylori eradication and ulcer healing. A direct linear correlation between enterochromaffin-like, gastrin, and parietal cell density was demonstrated. An almost complete map of mucosal cells involved in gastric secretion is provided by this study. The cell density pattern, identical to the omeprazole group, points to an impaired feedback control of secretion in duodenal ulcer. The reversion to control values after Helicobacter pylori eradication and ulcer healing demonstrates the pathogenetic role of Helicobacter pylori–host interaction in these changes.     

Conceivable mechanisms by which Helicobacter pylori provokes duodenal ulcer disease

A conceivable concept for the development of duodenal ulcers in Helicobacter pylori(H. pylori) infected subjects is presented in this chapter. The concept includes an explanation of the fact that only a minority of all H. pylori -infected subjects will develop a duodenal ulcer. Helicobacter pylori infection of the antrum induces a hypersecretion of gastric acid secretion, giving rise to gastric metaplasia in the duodenal bulb. This gastric metaplasia is a prerequisite for H. pylori colonization of the bulb. These events are common to all H. pylori -infected subjects. However, a much higher density of H. pylori bacteria and colonization with virulent organisms has been found in the bulb of duodenal ulcer patients, resulting in a much stronger inflammatory reaction with active duodenitis and an impaired bicarbonate secretion. These characteristics, together with acid hypersecretion, seem to be the important factors in evoking a duodenal ulcer.     

Regression of duodenal gastric metaplasia in Helicobacter pylori positive patients with duodenal ulcer disease

Background. It is unclear whether the extent of duodenal gastric metaplasia is due to Helicobacter pylori and/or acid.Aims. To investigate the role of Helicobacter pylori eradication in the regression of duodenal gastric metaplasia in patients with duodenal ulcer maintained in acid suppression conditions.Methods. Duodenal (anterior, superior, inferior walls of first part of duodenum) and gastric antrum biopsies were obtained from 44 Helicobacter pylori positive duodenal ulcer patients. Helicobacter pylori infection was diagnosed by rapid urease test, histology and ¹³C-Urea Breath Test. Patients were treated with 20 mg omeprazole tid associated with 250 mg clarithromycin and 500 mg amoxycillin four times daily for 10 days and maintained with 20 mg omeprazole daily for 18 weeks. Control endoscopies were performed at 6 and 18 weeks after beginning treatment.Results. Duodenal gastric metaplasia regression was observed in all ( ) patients in whom Helicobacter pylori was eradicated, but in only 3 out of 6 patients in whom eradication was not achieved (p<0.001).Conclusions. The present results suggest that Helicobacter pylori eradication associated with prolonged acid suppression may represent a good therapeutic strategy to achieve duodenal gastric metaplasia regression and highlight the combined role of acid and Helicobacter pylori in the pathogenesis of duodenal gastric metaplasia.     

Does Antral Distension Inhibit Gastric Acid Secretion or Stimulate Bicarbonate Secretion in ‘Healthy’ Subjects?

The effects of a 150-ml antral balloon distension on pentagastrin-stimulated gastric acid secretion and bicarbonate secretion were studied in nine healthy subjects and eight duodenal ulcer (DU) patients. The gastric secretions were simultaneously measured, using a luminal perfusion and pH/PCO₂ measurements. Two of the healthy subjects and six of the DU patients were positive for Helicobacter pylori. When H. pylori-positive and -negative subjects were compared, basal gastric acid and bicarbonate outputs did not differ significantly. In H. pylori-infected subjects the bicarbonate transport increased by about 70% on pentagastrin stimulation. In the H. pylori-negat'we group pentagastrin had no effect on the bicarbonate secretion. Antral distension elicited a 30-35% inhibition of pentagastrin-stimulated gastric acid secretion in the group of H. pylori-negative subjects, whereas the acid secretory level remained essentially unchanged in the positive group. Bicarbonate secretion decreased transiently by the distension in the negative subjects, whereas a slight increase was observed in the infected group. We conclude that antral distension inhibits pentagastrin-stimulated gastric acid output in healthy H. pylori-negative subjects. Our results strongly suggest that the underlying mechanism is a direct inhibition of gastric parietal cell function and not an increased gastric bicarbonate secretion. Furthermore, the results indicate that this defective distension-induced acid inhibition may be correlated to H. pylori infection rather than to duodenal ulcer disease.     

Hypersecretory duodenal ulcer and Helicobacter pylori infection: a four-year follow-up study.

BACKGROUND: About 10% of duodenal ulcer patients are characterized by gastric acid hypersecretion with normal gastrin values. Relapsing duodenal ulcer after Helicobacter pylori cure has been related to high acid output and maintenance antisecretory therapy has been suggested in hypersecretory duodenal ulcer patients. The role of Helicobacter pylori infection and the effects of Helicobacter pylori cure in hypersecretory duodenal ulcer patients still remain to be fully studied. AIM: To study: a) whether gastric acid hypersecretion "per se" is a risk factor for duodenal ulcer recurrence; b) whether maintenance antisecretory therapy is necessary after eradication in hypersecretory duodenal ulcer patients. PATIENTS: The study population comprised 8 hypersecretory duodenal ulcer patients, selected from a population of 79 Helicobacter pylori-positive duodenal ulcer patients. METHODS: Hypersecretory duodenal ulcer patients were followed-up for at least 4 years after eradication. Gastric acid secretion was measured again 12 months after Helicobacter pylori eradication. Gastroscopy with histology was performed 3, 6, 12 and 36 months after treatment, 13C-urea breath test after 42 months; clinical questionnaires were completed every 6 months. RESULTS: After eradication, despite a not significantly reduced high acid output (median value of basal acid output and pentagastrin-stimulated acid output, respectively, 23.1 mEq/h and 64.1 mEq/h before treatment vs 16 mEq/h and 49.7 mEq/h 12 months after treatment), all patients were free from symptoms, none of them had duodenal ulcer relapse or complications (7/8 before treatment), or needed antisecretory maintenance therapy, except for one patient taking non-steroidal anti-inflammatory drugs. CONCLUSIONS: These findings, obtained in a selected population of hypersecretory duodenal ulcer patients with long-term follow-up, suggest that after successful Helicobacter pylori eradication gastric acid hypersecretion "per se" is not able to determine the recurrence of duodenal ulcer.     

Giant duodenal ulcer

Patients with giant duodenal ulcer (>2 cm) have more ulcer complications (ie, bleeding) than patients with duodenal ulcer in the standard range (0.5–1.5 cm). To evaluate possible differences between patients with giant duodenal ulcer and those with duodenal ulcer in the standard range, we determined basal acid outputs by nasogastric suction, percentage of patients with daily nonsteroidal antiinflammatory drug (NSAID) use, and percentage of ulcer complications in 184 patients with endoscopically documented active duodenal ulcer. Seventeen patients had giant duodenal ulcer, and 167 patients had duodenal ulcer in the standard range. The mean basal acid outputs for the 17 patients with giant duodenal ulcer was 7.9 meq/hr (range 0.0–27.8 meq/hr) and for the 167 patients with duodenal ulcer in the standard range was 9.0 meq/hr (range 0.0–49.1 meq/hr), which were not significantly different. There was a significant difference in the percentages of ulcer complications between the 17 patients with giant duodenal ulcer and the 167 patients with duodenal ulcer in the standard range: 65% compared to 25% (P=0.001), and in the percentages of patients with regular daily NSAID use, during the one month preceding the upper gastrointestinal endoscopy: 53% compared to 8% (P=0.00001). However, a significant association between NSAID use and duodenal ulcer complication was not apparent. These results suggest that the development of giant duodenal ulcer and the significant increase in complications associated with giant duodenal ulcer are not attributable to increased basal acid output, however, they may be attributable to increased NSAID use.     

Abdominal pain in hereditary angioedema: the role of acid hypersecretion

Hereditary angioedema is a familial disorder characterized by recurrent episodes of soft tissue swelling and abdominal pain. Whereas most patients are successfully treated with androgenic steroids, some have abdominal pain unresponsive to therapy. To determine whether acid-peptic disease could account for the abdominal pain unresponsive to androgen therapy, we performed upper gastrointestinal endoscopy and determined basal acid output in 21 consecutive patients with hereditary angioedema and abdominal pain. Mean basal acid output of this group was 6.0 +/- 5.9 mEq/h, with five patients having gastric acid hypersecretion (defined as a basal acid output of greater than 10.0 mEq/h). The abdominal pain in 18 responded to stanozolol, whereas the pain in three patients did not change. Acid-peptic mucosal disease (esophagitis or duodenal ulcer) was present in these three patients with abdominal pain unresponsive to androgen therapy, all of whom had gastric acid hypersecretion (basal acid outputs of 13.7, 19.1, and 21.5 mEq/h, respectively). These three patients were treated with ranitidine but required increased doses to control their gastric acid hypersecretion, and to promote complete relief of abdominal pain and healing of their esophagitis or ulcer disease. These results indicate that there is a subset of patients with hereditary angioedema whose abdominal pain may be secondary to acid-peptic disease and gastric acid hypersecretion. Such individuals may require increased therapeutic doses of antisecretory medication to promote complete healing of esophagitis or ulcer disease. Basal acid output and upper gastrointestinal endoscopy are important determinants when evaluating abdominal pain in patients with hereditary angioedema that fails to respond to standard therapy.     

Campylobacter pylori is not associated with gastroparesis

There is a high incidence of Campylobacter pyloriin the gastric mucosa of patients with duodenal ulcer, gastric ulcer, and nonulcer dyspepsia. Factors that lead to development of this infection are unknown. We hypothesized that delayed solid-phase gastric emptying, a condition characterized by antral stasis, might predispose to Campylobacter pyloriinfection. We prospectively studied 51 patients with symptoms of gastroparesis using a solid-phase gastric emptying study and upper endoscopy. Patients were excluded if they had predominant symptoms of epigastric pain or an abnormal endoscopy. Three biopsies were obtained from the antrum and stained with H&E. When any inflammation was present, a Warthin-Starry stain was also performed. These were blindly examined for chronic inflammation, activity, and presence of Campylobacter pylori. Campylobacter pyloriwas not more common in patients with gastroparesis, documented by delayed gastric emptying, than in patients with a normal emptying study. On the contrary, there was a significantly lower incidence of Campylobacter pyloriin those with delayed emptying compared to those with normal emptying (5% vs 31%, P<0.05).Gastritis activity correlated closely with Campylobacterpresence. Inactive chronic gastritis with Campylobacterwas equally common in those with delayed or normal gastric emptying. Diabetics were no more likely to harbor Campylobacter pylorithan nondiabetics (16% vs 25%). The 5% incidence of Campylobacterin the gastroparesis group is less than, but approaches, that previously reported in asymptomatic controls. The 31% incidence of Campylobacterin the group with symptoms of gastroparesis but normal gastric emptying approaches that reported for nonulcer dyspepsia. Our data suggest that gastroparesis does not predispose to Campylobacter pyloriinfection or histologic chronic gastritis.Presented in part at the American Gastroenterological Association, New Orleans, May 1988.