Three months of octreotide treatment decreases gastric acid secretion and argyrophil cell density in patients with Zollinger-Ellison syndrome and antral G-cell hyperfunction

Methods: The effects of three months of treatment with octreotide on gastric acid hypersecretion induced by hypergastrinaemia were investigated in patients with Zollinger-Ellison syndrome (n= 5) or antral G-cell hyperfunction (n= 4). Gastric acid secretion, fasting plasma gastrin concentrations and clinical findings were examined, and a morphometrical analysis of oxyntic endocrine cells was performed. Results: Administration of octreotide 100 meg b.d. subcutaneously significantly decreased the volume density of argyrophil cells (P < 0.05) as well as basal and pentagastrin-stimulated acid secretion (P < 0.05). Although partial or complete loss of inhibition was found in most patients after 3 months, gastrin levels were decreased during the first 2 months of treatment (P < 0.05). Fundic D-cells were not affected by treatment. Positive correlations were observed between volume density of argyrophil cells and basal acid output (r= 0.65); plasma gastrin and basal acid output (r= 0.74); plasma gastrin concentrations and volume density of argyrophil cells (r= 0.80). Conclusion: These results support the important role of the enterochromamn-like cell in maintaining acid secretion, and indicate a specific role for octreotide in the therapy of gastric acid hypersecretion associated with hypergastrinaemic diseases.     

Efficacy of long-term therapy with low doses of omeprazole in the control of gastric acid secretion in Zollinger-Ellison syndrome patients

Thirteen patients with Zollinger-Ellison syndrome were investigated: 8 without, and 5 with, previous gastric surgery. After 7–34 months of treatment with famotidine, 8 out of 13 patients were resistant to this drug. Omeprazole 60 mg/day was administered to these 8 patients; after one month, the dose was reduced to 40 mg/day, and after another month to 20 mg/day. Basal acid secretion was inhibited by every dose of omeprazole. The patients were then treated with a low dose (20 mg/day) of omeprazole for a longer period. Periodic clinical and endoscopic assessments, and measurement of basal acid secretion showed the efficacy of this low dose of omeprazole in our Zollinger-Ellison syndrome patients. The drug was discontinued after 12–32 months of omeprazole treatment, and gastric acid recovery was evaluated. Four patients recovered 50% of their ‘initial basal acid secretion’ after 5 days, while two patients who had been treated with omeprazole for a longer time (30–32 months) recovered only 38 and 40%, respectively, of their ‘initial basal acid secretion’ at the tenth day. Our results indicate that the omeprazole dosage to be used in the treatment of Zollinger-Ellison syndrome must be chosen principally on the basis of basal acid secretion determination. A low daily dose of omeprazole is able to control acid secretion in Zollinger-Ellison syndrome for a long period (10–30 months). The slow recovery of gastric secretory function demonstrates the prolonged inhibitory effects of omeprazole.     

Focal oxyntic gland atrophy with endocrine cell hyperplasia in Zollinger–Ellison syndrome during omeprazole treatment

Development of focal gland atrophy of the oxyntic mucosa was found in two patients with the Zollinger-Ellison syndrome undergoing long-term treatment with omeprazole. The atrophic areas revealed florid proliferation of endocrine cells in the form of both intraglandular crescents and micronodular hyperplasia. This proliferation was significantly more pronounced than in the remaining non-atrophic mucosa. The possible relationship of these changes to long-standing pharmacological therapy for gastric acid suppression is discussed.     

Risk factors for progression to gastric neoplastic lesions in patients with atrophic gastritis

Aliment Pharmacol Ther 31 , 1042–1050

Summary

Background Atrophic gastritis, involving the gastric body mucosa, predisposes to gastric neoplastic lesions (GNL). However, regular gastroscopic‐histological follow‐up for GNL is not recommended for patients with atrophic gastritis. Aim To evaluate risk factors for the progression to GNL in a cohort of patients with atrophic gastritis. Methods A total of 300 patients with atrophic gastritis [205 women, aged 54 (18–78) years] underwent gastroscopy with six gastric antrum and body biopsies. All patients had at least one follow‐up gastroscopy/histology at an interval of at least 1 year after the atrophic gastritis diagnosis. Baseline clinical and histological features were analysed as risk factors for the development of GNL by Cox‐regression. Results During a median follow‐up of 4.3 (1–16.5) years, 15 GNL were detected in 14 of the 300 patients with atrophic gastritis: three were gastric cancer, whereas 12 were non‐invasive neoplasia. The annual incidence for GNL was 1%. Cox‐regression analysis identified the following risk factors: age over 50 years (HR 8.8, 95%CI 1.2–68.4), atrophic pangastritis (HR 4.5, 95% CI 1.5–14.1) and severe intestinal metaplasia in the gastric body (HR 4.0, 95% CI 1.3–11.8). Conclusions Atrophic pangastritis, severe body intestinal metaplasia and/or age over 50 years increase the risk for developing GNL in patients with atrophic gastritis. In this subset of patients, an endoscopic‐histological follow‐up for GNL surveillance may be worthwhile.     

Systematic review: impaired drug absorption related to the co-administration of antisecretory therapy

Background  Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co-administered drugs may occur.
Aim  To review evidence of impaired drug absorption related to the use of co-administered PPIs or H₂RAs.
Methods  Systematic search of MEDLINE/EMBASE/SCOPUS databases (1980–September 2008) for English articles with keywords: drug malabsorption and absorption, stomach, anti-secretory/acid inhibitory drugs, histamine H₂ antagonists, PPIs, gastric acid, pH, hypochlorhydria, gastric hypoacidity. From 2126 retrieved articles, 16 randomized crossover studies were identified investigating impaired absorption of nine different drugs in association with co-administration of PPIs or H₂RAs. Information on investigated drug, study type, features of investigated subjects, study design, type of intervention, and study results were extracted.
Results  The identified studies investigated the absorption kinetics of nine drugs. Acid suppression reduced absorption of ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin and dipyridamole (median C _max reduction by 66.5%). An increased absorption of nifedipine and digoxin (median AUC increase by 10%) and a 2-fold-increase in alendronate bioavailability were observed.
Conclusions  Gastric pH appears relevant for absorption of some cardiovascular or infectious disease agents. Antisecretory treatment may significantly modify the absorption of co-administered drugs.     

Omeprazole versus famotidine in the short-term treatment of duodenal ulcer disease

The efficacy and safety of omeprazole, in 241 patients with active recurrent duodenal ulcer from 21 Italian centres, was studied in a multicentre double-blind randomized trial comparing 20 mg omeprazole o.m. or 40 mg famotidine nocte with endoscopic examination, symptom recording, laboratory screening and gastrin assay. In a per protocol analysis, the duodenal ulcer healing rates for omeprazole and famotidine, documented by endoscopy, were 62% (68/109) and 33% (39/117) after 2 weeks of treatment (P less than 0.001), 92% (96/104) and 80% (86/108) cumulative after 4 weeks (P less than 0.05), and 99% (102/103) and 92% (96/104) after 6 weeks (P less than 0.05), respectively. The results of this trial demonstrate that 20 mg omeprazole o.m. is superior to 40 mg famotidine nocte in duodenal ulcer healing.     

Systematic review: Heliocobacter pylori infection and impaired drug absorption

Background  Impaired acid secretion may affect drug absorption and may be consequent to corporal Heliocobacter pylori- gastritis, which may affect the absorption of orally administered drugs.
Aim  To focus on the evidence of impaired drug absorption associated with H. pylori infection.
Methods  Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980–April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori , gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted.
Results  In all, five studies investigated impaired absorption of l -dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21–54% increase in l -dopa in Parkinon's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori- gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication.
Conclusions  A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori -gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.     

Antral gastrin cell hyperfunction and Helicobacter pylori infection

Background : Antral gastrin cell hyperfunction (AGCH), is a rare cause of duodenal ulcer associated with non-tumour hypergastrinaemia and acid hypersecretion.
Aim : To investigate the role of Helicobacter pylori in AGCH.
Patients : Twelve AGCH patients and eight H. pylori -positive non-hypergastrinaemic duodenal ulcer patients were compared.
Methods : Basal and peak acid outputs, gastrin-stimulation (meal and bombesin) tests, and immunohistochemistry for antral G and D cells were performed. One year after H. pylori eradication, six AGCH patients were again investigated with the same tests.
Results : Significantly more basal, and stimulated gastrin and acid secretion, were found in AGCH compared to the H. pylori -positive duodenal ulcer patients ( P <0.01). G cell counts were significantly higher in AGCH than in duodenal ulcer patients (118.8, range 58–192.4, vs. 86.1, range 49–184; P <0.05), and the resulting G/D cell ratio was also higher in AGCH patients (4.2, range 2.6–5.6, vs. 3.3, range 1.9–4.3; P <0.05). H. pylori was present in the gastric mucosa of all 12 AGCH patients. Cure of infection in six AGCH individuals resulted in marked a decrease of gastrin levels associated with a significant (23.7%; P <0.05) decrease of G cell count and an increase (12%; P <0.05) of D cell count.
Conclusions : The results indicate that AGCH may result from H. pylori overstimulation of gastrin cell function in patients with some presently undefined, familial predisposition and that an imbalance of the G/D cell ratio may have a role in the genesis of hypergastrinaemia.