Association between serum gastrin levels, gastric acid secretion and age in early gastric cancer

This study evaluated the effect of gastric acid secretion and serum gastrin response on tumor differentiation for early gastric cancer according to patients' age. We investigated the association between serum gastrin levels, gastric acid secretion and the histologic types of 335 early gastric carcinomas limited to the mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal ulcers. The preoperatively examined basal acid output, maximal acid output and peak acid output after administration of tetragastrin and serum gastrin levels before and after ingestion of a test meal were determined. Patients with differentiated cancer and duodenal ulcer showed a significant negative correlation between gastric acid secretion and age, while the former group also had a significant positive correlation between serum gastrin levels and age. On the other hand, patients with undifferentiated cancer did not show any such correlation between gastric acid and age, but showed a significant positive correlation between serum gastrin, integrated gastrin response and age. Patients with gastric ulcer did not show any such correlations. These data suggest that both low acid secretion and endogenous hypergastrinemia, especially in the elderly, may play an important role in differentiated and undifferentiated gastric carcinomas.     

Zollinger-Ellison syndrome and antral G-cell hyperfunction in patients with resistant duodenal ulcer disease

We measured basal and pentagastrin-stimulated acid secretion, as well as basal and meal-stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin-related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger-Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti-Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger-Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal-stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16% vs duodenal ulcer 2% P = 0.0144). In the presence of duodenal ulcer disease resistant to H2-blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin-related syndromes, Zollinger-Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.     

Gastric ulcer: effect of healing on gastric acid secretion and fasting serum gastrin levels

In 15 patients with uncomplicated gastric ulcers, basal and peak gastric acid outputs and fasting serum gastrin levels were studied before and after healing. The mean basal acid output [4.0 +/- 1.3 (SEM) mEq H+/hr], the mean peak acid output (29.5 +/- 5.1 mEq H+/hr), and the mean fasting serum gastrin level (80.3 +/- 16.7 pg/ml) in these patients did not change significantly with healing. Failure of gastric secretory function to change with healing suggests that mucosal resistance factors are more important than gastric acid secretion in the pathogenesis of a gastric ulcer.     

Gastritis duodenitis, and circulating levels of gastrin in duodenal ulcer before and after vagotomy

Biopsy specimens have been taken from five standard sites in the stomach and from the duodenal bulb in order to investigate the association of gastritis and duodenitis with duodenal ulcer. Twenty patients with chronic duodenal ulcer were investigated in this manner and in addition had gastric secretion tests and a radio-immune assay of serum gastrin under differing conditions. The patients were then treated either by a truncal vagotomy and pyloroplasty (TVP) or by a highly selective vagotomy without a drainage procedure (HSV). All the investigations were repeated three months postoperatively. Duodenal ulcer was usually associated with gastriitis, although this varied in extent and severity from patient to patient. In nearly all the patients, gastritis was present at the pyloric end of the stomach and along the lesser curve. In more than half of the patients, gastritis was also present in the body of the stomach but the fundus was usually spared. Chronic duodenitis was found in the duodenal bulb in all these patients. After vagotomy there was a marked increase in both the extent and severity of the proximal gastritis in both treatment groups but the distal gastritis remain almost unchanged. There was little change in the incidence of duodenitis after vagotomy but its severity was lessened. No correlation was found between the peak acid output (PAO) in response to Histalog and the severity of the gastritis or the duodenitis either before or after operation, with one exception. The postoperative PAO was significantly less in those patients who developed a severe proximal gastritis after vagotomy. No relationship was found between the severity of the distal gastritis and the levels of serum gastrin. No correlation was found between either the basal or peak acid output and the corresponding serum gastrin levels before or after vagotomy.     

Differences in antral response to meat extract in duodenal ulcer patients

Although acid secretion is important in the pathogenesis of duodenal ulcer formation, the antral phase of gastric secretion has not been adequately studied. In 60 duodenal ulcer and 12 normal patients, basal, antral and peak acid secretion was investigated. Antral function was assessed by instilling meat extract sodium and measuring acid and serum gastrin output. Two groups of patients were thus identified: 1. Antral responders in whom meat extract caused a significant increase in serum gastrin and acid output. 2. Antral nonresponders in whom meat extract did not significantly lead to an elevation in gastrin and acid output.     

Long-term treatment with lansoprazole for patients with Zollinger-Ellison syndrome

BACKGROUND: Normalization of gastric secretion and cure of associated upper gastrointestinal lesions by resection of gastrinoma is possible in approximately 20% of patients with Zollinger-Ellison syndrome, leaving approximately 80% dependent on medical treatment with proton pump inhibitors for acid suppression. METHODS: Lansoprazole was given for 3-48 months (median 28 months) to 26 Zollinger-Ellison syndrome patients with peptic ulcer manifestations in all and oesophagitis in 13. Starting with 60 mg/day. the dose was individualized to lower basal acid output to less than 5 mmol/h for those with intact stomachs and less than 1 mmol/h in those who had prior gastrectomy or with oesophagitis. The patients were studied every 3 months for 1 year and then every 6 months with gastric analysis (basal and maximal acid and pepsin output) and endoscopy with biopsy for enterochromaffin-like (ECL) cells. RESULTS: Lansoprazole inhibited basal acid output by 95%, pepsin output by 65% and remained effective at the initial mean (66 +/- 4.3 mg/day) or smaller doses (56 +/- 12 mg/day) at 48 months. Mucosal lesions healed and symptoms (ulcer-type pain, diarrhoea, heartburn, weight loss) resolved rapidly, usually within a few weeks. Serum gastrin and ECL cell populations, which were elevated before treatment, remained statistically unchanged but one of the three multiple endocrine neoplasia I (MEN-I) patients developed a small carcinoid. Of the three patients with metastatic gastrinoma at diagnosis one has died and one has progressed, while the third has had stable liver metastases for 26 years. Ulcer-type relapses occurred in three of the five post-gastrectomy patients, one with fatal jejunal ulcer perforation despite adequate acid suppression. No biochemical or clinical adverse events due to lansoprazole were encountered. CONCLUSION: Lansoprazole effectively inhibits acid and pepsin secretion in Zollinger-Ellison syndrome patients without any demonstrated side-effects. Despite strict acid control, post-gastrectomy Zollinger-Ellison syndrome patients were more liable to ulcer relapse, while oesophagitis was not a marker for therapeutic difficulty.     

Helicobacter pylori infection after gastrectomy and vagotomy in duodenal ulcer patients

The eradication of Helicobacter pylori (Hp) is known to reduce the recurrence rate of duodenal ulcer (DU) to similar extent as gastrectomy but it is not clear what is the prevalence of Hp in DU patients after surgical interventions such as gastrectomy or vagotomy. The purpose of this study was to evaluate the influence of gastrectomy or truncal vagotomy with pyloroplasty on the prevalence of Hp in 51 DU patients just before and 6-8 months after these procedures. Using C14-urea breath test (UTB), rapid CLO-test and histology of the biopsy samples of gastric mucosa obtained during gastroscopy, the Hp was detected in all DU subjects submitted to operation. Following distal gastric resection (antrectomy) with Billroth II anastomosis (N = 32) due to an ulcer resistance to conservative therapy, peptic ulceration was not observed during 6-8 months in any of the examined subjects and the Hp was only rarely observed (only in 3 out of 32 operated patients). Histologically, in antral biopsies taken prior to surgery, all DU patients presented chronic active gastritis. After the surgery, the absence of Hp was confirmed also by histology. Histological evaluation of gastrectomy stump biopsies revealed typical chronic gastritis with concomitant foveolar hyperplasia and focal gland dilation. Following selective vagotomy and pyloroplasty (N = 19), the scarring of duodenal bulb (without active ulcer) was seen in 4 out of 19 operated patients but the Hp was detected in all (100%) cases. Gastric biopsies prior and after vagotomy revealed chronic active gastritis associated with Hp infection. Basal plasma gastrin was reduced after gastrectomy by about 30% and basal and maximal pentagastrin-induced acid secretion was decreased by about 60% and 70%, respectively. Vagotomy did not reduce activity of the mucosal inflammation and the incidence of Hp. Basal plasma gastrin level was increased by about 60%, while basal and pentagastrin induced acid secretion was decreased by 25% and 40%, respectively. Because of the high ulcer recurrence rate after vagotomy as opposed to low recurrence after gastrectomy, it is reasonable to conclude that (1) the disappearance of Hp and reduction in plasma gastrin and gastric acid secretion were probably the major factors responsible for the high efficacy of gastrectomy in prevention of ulcer recurrence, (2) in non-complicated DU, gastric surgery should be avoided and replaced by conservative anti-Hp therapy involving both antisecretory or bismuth agents and antimicrobial drugs which should provide similar therapeutic effects as surgery and (3) vagotomy should be eliminated as the method of treatment of DU because of the high recurrence of peptic ulceration and the failure of this procedure to affect the Hp status.     

Theoretical and practical implications of calcitonin therapy in gastroduodenal ulcer

Calcitonin (CT) inhibits basal and pentagastrin stimulated gastric acid and pepsin secretion by 60 to 70% when CT is infused over a short period of time. Vagal and histamine-mediated stimulations are less diminished. A long-term infusion of CT inhibits persitently basal and pentagastrin-stimulated acid and pepsin secretion over more than 24 hours in patients with duodenal ulcer, stress bleeding and Zollinger-Ellison-Syndrome. To date, the therapeutic efficiency of CT in gastroduodenal bleeding has not been evaluated in a controlled trial. CT inhibits gastric secretion also after oral application. In an endoscopically controlled double blind trial we were not able to demonstrate a significant benefit of oral CT in patients with gastric ulcer. In ulcer bleeding CT does not apear reasonable in comparison with histamine-H2-receptor antagonists which apparently is more efficient and less costly.     

Superselective vagotomy. Preliminary results

Twelve patients suffering from an intractable duodenal ulcer are included in this review. Eleven were treated by superselective vagotomy without drainage, one had a selective vagotomy with pyloroplasty. A peroperative control of the gastric acidity after pentagastrin stimulation was used in all cases and permitted section of forgotten nerve fibers. Short-term results are satisfactory: after 2-6 months the clinical state of the patients is excellent (Visick I and II), basal acidity is decreased by 58 to 66% of preoperative value, the Hollander tests are negative except two. After more than 6 months, the few available results are satisfactory except one case of recurrent ulcer. The one case with a 1 year follow-up is excellent, clinically and as to acid secretion.     

Relationships between gastric acid secretion and recurrent duodenal ulcer after selective vagotomy and pyloroplasty in men

Relations between gastric acid secretion measurements and recurrence of duodenal ulcer within 1 to 4 years after selective vagotomy and pyloroplasty were evaluated in a series of 117 men. The discriminatory ability of spontaneous, histamine- and insulin-activated acid secretion measurements was significant and similar to that after truncal vagotomy and drainage. The measurements were of no practical value for the diagnosis of recurrent duodenal ulcer after vagotomy, but they provided a rationale for selective surgery in patients with duodenal ulcer and patients with recurrent duodenal ulcer after vagotomy.     

Some thoughts on tolerance

In 4 duodenal ulcer patients the morphology of parietal cells has been studied before and one year after proximal gastric vagotomy (PGV). The average basal gastric acid secretion of the 4 patients was reduced from 9.2 m.mol/h before to 0.9 m.mol/h one year after PGV (90% reduction). The reduction in acid secretion was not accompanied by changes in the morphology of the parietal cells. Light microscopical studies indicated that the average cell size was about the same before and one year after PGV. Electron micro scopical studies showed only negligible changes in the parietal cell ultrastructure.     

Protein and RNA synthesis in larvae of the yellow mealworm beetle (Tenebrio molitor) during cooling and cold acclimatization

Adult patients with symptoms of gastric disease were randomly assigned to two treatment groups (roxatidine group, n = 115; famotidine group, n = 113) or untreated control group (placebo, n = 111). The treatment groups randomly received 75 mg of roxatidine or 20 mg of famotidine at 9 pm, and 12 - 13 h later gastric juice secretion was measured with gastric X-ray films in both groups. Mean gastric juice secretion was significantly lower in the treated groups (roxatidine, 16.1 ml/12 h; famotidine, 19.9 ml/12 h) than in the untreated controls (placebo, 49.5 ml/12 h). Gastric juice suppression by roxatidine and by famotidine, respectively, was 82% and 37% in patients with gastric ulcer; 71% and 39% in patients with duodenal ulcer; 70% and 64% in patients with gastritis; and 68% and 86% in patients with no evidence of disease. It is concluded that roxatidine was more effective than famotidine for gastric juice suppression in patients with peptic ulcer. In patients with no evidence of gastric disease, however, famotidine was more effective than roxatidine.     

NCI? What is it? What do they do?

BACKGROUND: Omeprazole, a H+/K+ ATPase inhibitor, has been shown to reduce gastric bicarbonate secretion in cats. However, there has been no study on the effect of omeprazole on bicarbonate secretion in patients with duodenal ulcer (DU). METHODS: Fifteen men with duodenal ulcer (mean age 38 years, range 22-57) were included. Baseline gastric acid output, bicarbonate secretion, and parietal and nonparietal secretions were estimated before and after omeprazole therapy (20 mg/day) for four weeks. RESULTS: Omeprazole administration did not significantly alter bicarbonate secretion (3.3 [1.2] vs 2.4 [0.4] mmol/h), though there was significant reduction in gastric acidity (44.2 [6.6] vs 20.7 [4.6] mmol/L, p < 0.01). CONCLUSION: Omeprazole reduces acid secretion but does not affect gastric bicarbonate secretion in patients with DU.     

Site of peptic ulcer. comparison of hydrochloric acid output, pepsinogen and gastrin serum levels

BACKGROUND/AIMS: Basal (BAO) and maximum (PAO) hydrochloric acid output after Histalog stimulation, basal pepsinogen (SPL-B), at 60 (SPL-60) and at 90 minutes (SPL-90), and basal gastrin (BG) levels were measured and compared in different gastric (GU) and duodenal (DU) ulcer sites. MATERIAL AND METHODS: Fifty nine patients with peptic ulcer were grouped according to Johnson's classification for gastric ulcers: type I (15), type II (16) type III (12) GU and (16) DU. Fifteen normal subjects were studied as controls. RESULTS: The BAO was greater in the DU than in the control or GU groups. No significant difference was noted in the production of hydrochloric acid after stimulation with Histalog. The SPL-B, at 60 and at 90 minutes was higher in type II GU than in the DU group and controls. The SPL-60 was higher in type II GU patients than in type III GU. Basal gastrin was higher in group DU and types II and III GU compared to the type I GU patients and controls. CONCLUSION: The topographic criteria for differentiating peptic ulcers has low discrimination capacity based on comparison of mean values of HCl acid production, pepsinogen and gastrin serum levels both basal and after stimulation with Histalog due to heterogeneity of these variables in group studies. In these studies, peptic ulcers from different sites should not be grouped as distinct entities except for type II gastric ulcers.     

Postoperative recurrent ulcer after gastric resection--results of surgical treatment]

Within a 10-year period, 50 patients with postoperative ulcer recurrence after gastric resection were treated; 31 of these had one, 8 two, 5 three and 6 four previous gastric operations. Ulcer recurrence was attributed to surgery-related causes in 78% of the cases; excessively large gastric remnant 56%, anastomotic stenosis 18%, loop problems 4%. Some 22% of the patients had causes independent of previous surgery: abuse of non-steroidal antirheumatics (NSAR) 10%, hyperacidity of normal gastric remnant 6%, Zollinger-Ellison-Syndrome 6%. The most important co-factor of ulcer genesis was chronic abuse of NSAR (38% of the total series). The interval between onset of complaints of ulcer disease and the last ulcer-dependent operation amounted on average to 13.8 (0.5-36) years. The definitive treatment of recurrent ulceration was surgery in 34 cases-indicated by ulcer complications (73.5%) or failure of medical therapy (26.5%)-and conservative treatment in 16 cases. Surgery comprised 21 re-resections, 7 thoracic truncal vagotomies 4 total gastrectomies 1 Whipple procedure and 1 enucleation of gastrinoma (hospital mortality 0%). During the follow-up period (median 7.1 years, follow-up rate 96%), the cumulative ulcer re-recurrence rate was 57% for the conservatively treated group and 17.6% for the patients treated by surgery (p < 0.05). In none of the eight patients who died during long-term follow-up was the cause of death ulcer-related.     

Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status

BACKGROUND & AIMS: There have been conflicting reports regarding acid secretion after treatment with omeprazole. This study examined acid secretion after treatment with omeprazole and its relation to Helicobacter pylori status and on-treatment gastric function. METHODS: Twelve H. pylori-negative and 9 H. pylori-positive subjects were examined before, on, and at day 15 after an 8-week course of 40 mg/day omeprazole. On each occasion, plasma gastrin, intragastric pH, and acid output were measured basally and in response to increasing doses of gastrin 17. RESULTS: In the H. pylori-negative subjects at day 15 after omeprazole treatment, basal acid output was 82% higher (P < 0.007) and maximal acid output 28% higher (P < 0.003) than before omeprazole. The degree of increase in maximal acid output was related to both on-treatment pH and on-treatment fasting gastrin levels, being 48.0% in subjects with an on-treatment pH of >4 vs. 21. 0% in those with a pH of <4 (P < 0.02) and 49.2% in subjects with an on-treatment gastrin of >25 ng. L-1 vs. 19.8% in those with a fasting gastrin of <25 ng. L-1 (P < 0.006). At day 15 after omeprazole treatment, the H. pylori-positive subjects showed a heterogeneous response with some having increased acid output and others persisting suppression. CONCLUSIONS: Rebound acid hypersecretion occurs in H. pylori-negative subjects after omeprazole treatment. Its severity is related to the degree of elevation of pH on treatment. Persisting suppression of acid secretion masks the phenomenon in H. pylori-positive subjects.     

The course of the reparative process in patients with gastric and duodenal peptic ulcers (a clinico-statistical study)

Clinico-statistical evaluation of reparative process in 332 gastric ulcer and 294 duodenal ulcer patients revealed factors of objective value to its course. In order of significance the factors rank as follows: area of ulcer, localization, combination with certain mucosal erosions, total fasting acidity, free fasting hydrochloric acid, basal gastric secretion, cardial function, duodenogastric reflux, sex, age, number of cigarettes smoked daily. When studying treatment effects on regeneration in ulcer patients in is necessary to take into consideration basal clinico-endoscopic parameters.     

Effect of calcium infusions of serum calcium and gastric acid secretion

37 patients were studied with calcium infusions. Of these, 20 had previously undergone truncal vagotomy and pyloroplasty for duodenal ulcer disease, and 17 were unoperated patients with duodenal ulcer disease. Calcium was given intravenously either at a dose of 5 mg/kg/h for 3 h, or 4 mg/kg/h for 4 h. Gastric juice was collected by continuous suction. Results showed the 3-hour infusion raised calcium more than the 4-hour infusion. Top serum calcium achieved, however, did not correlate with calcium-stimulated gastric acid output, either with or without vagotomy. Stimulated gastric acid secretion was markedly less with vagotomy than without. It is suggested that the level of gastric acid stimulated by infusions might discriminate complete, from incomplete, vagotomies better than insulin, and that the 4-hour infusion is safer.     

Effects of ranitidine bismuth citrate on gastric acid secretion and gastrin release in subjects with and without Helicobacter pylori infection

BACKGROUND: Ranitidine bismuth citrate is a novel antiulcerant that provides the antisecretory activity of ranitidine and the gastric mucosal protection and antibacterial properties of bismuth. METHODS: This randomized, double-blind, placebo-controlled study evaluated the effects of single doses of ranitidine bismuth citrate 200 mg, 400 mg and 800 mg and ranitidine hydrochloride 150 mg on gastrin release and suppression of gastric acid secretion, and compared acid secretory profiles and gastrin release between Helicobacter pylori-negative and -positive patients. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and in response to peptone meal stimulation. Acid secretion was measured under basal conditions and in response to peptone meal stimulation. Presence of H. pylori was determined by both 14C-urea breath test and ELISA serology. RESULTS: Inhibition of gastric acid output by ranitidine bismuth citrate was both time- and dose-dependent over the 9-h post-dose study period. Doses of ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg, which are equimolar, produced similar suppression of acid output regardless of H. pylori status. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations regardless of H. pylori status. All doses of ranitidine bismuth citrate were well tolerated. CONCLUSIONS: Ranitidine bismuth citrate caused time- and dose-dependent reductions in meal-stimulated and between-meal gastric acid output regardless of H. pylori status. The magnitude of decreased acid secretion was similar with ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations.     

Selective proximal vagotomy with duodenoplasty in the treatment of duodenal stenosis in patients with duodenal ulcer]

The results of surgical treatment of 118 patients with duodenal ulcer complicated with stenosis that have been operated on from 1981 to 1992 have been analysed. Selective proximal vagotomy (SPV) and duodenoplasty was performed in 58 (49.2%) patients (study group). SPV and gastroduodenal anastomosis by the method of Jabulay was performed in 60 (50.8%)-control group. The rate of postoperative morbidity in the study group-5.1%, in the control group-8.4%. The long-term follow up is from 1 year to 10 years (mean 5 + 0.6). The rate of recurrence of peptic ulcer is 8.6% in the study group and 10% in the control group. The modified scale (D. Johnson, 1976) was used for comparative evaluation of efficacy of two types of surgery. SPV and duodenoplasty was estimated in 175.1 points, that is 2.5 times less that SPV and gastroduodenal anastomosis (406.1 points). This demonstrates the advantages of SPV and duodenoplasty. The authors advocate SPV and duodenoplasty as a method of choice in the treatment of stenotic duodenal ulcer.