Fasting Plasma Gastrin Levels Research Articles

Efficacy of Vonoprazan, a Novel Potassium-Competitive Acid Blocker, in Patients with Proton Pump Inhibitor-Refractory Acid Reflux

Background/Aim: We evaluated the efficacy of vonoprazan (VPZ), a novel potassium-competitive acid blocker, in patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD), exhibiting continued pathological esophageal acid exposure (EAE). Methods: Despite ≥8 weeks of appropriate PPI therapy, patients with ­persistent reflux symptoms and pathological EAE times (EAETs ≥4%) were invited to switch to VPZ treatment. After an 8-week-course of once-daily VPZ (20 mg), multichannel intraluminal impedance-pH (MII-pH) monitoring was repeated to compare gastric acid exposure times (GAETs), EAETs, and other reflux parameters relative to the baseline values. Before each MII-pH study, reflux symptom severities were scored using the Gastrointestinal Symptom Rating Scale; erosive esophagitis and fasting plasma gastrin levels were also assessed. Results: From among the 124 patients undergoing MII-pH monitoring, 13 patients (median age, 69 years; females, 64%) were monitored at baseline (while on PPI therapy) and after VPZ therapy. The median GAET associated with VPZ treatment (23.8%) was less than that for PPI treatment (41.1%; p = 0.01), including both daytime and nighttime measurements. VPZ therapy resulted in better median EAET values (4.5%) than did PPI therapy (10.6%) during the 24-h monitoring period (p = 0.055). EAE normalization was achieved in 46% of VPZ-treated patients and was associated with complete gastric acid suppression (p = 0.005). After switching to VPZ, reflux symptoms (p < 0.01) and erosive esophagitis (p = 0.01) improved. Conclusion: In patients with PPI-refractory GERD, VPZ provides more potent gastric acid suppression, more effective EAE control, enhanced symptom improvement, and better esophagitis healing than PPIs.

Diagnostic and Treatment Approaches for Refractory Peptic Ulcers.

Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use. NSAID use should be discontinued when possible. Platelet cyclooxygenase activity tests can confirm surreptitious use of NSAIDs or aspirin. Cigarette smoking can delay ulcer healing. Therefore, patients who smoke should be encouraged to quit. Zollinger-Ellison syndrome (ZES) is a rare but important cause of refractory gastroduodenal ulcers. Fasting plasma gastrin levels should be checked if ZES is suspected. If an ulcer is refractory despite a full course of standard PPI treatment, the dose should be doubled and administration of another type of PPI considered.

Effects of Dexlansoprazole MR, a Novel Dual Delayed Release Formulation of a Proton Pump Inhibitor, on Plasma Gastrin Levels in Healthy Subjects

Dexlansoprazole MR is a modified release formulation of a proton pump inhibitor being developed for the treatment of acid-related disorders. The purpose of this study is to characterize the plasma gastrin (PG) profile associated with administration of dexlansoprazole MR. Forty-two healthy subjects receive dexlansoprazole MR 90 mg, dexlansoprazole MR 120 mg, and lansoprazole 30 mg once daily for 5 days in a randomized, open-label, 3-period crossover study with at least 14-day washout intervals. Twenty-four-hour PG profiles are obtained at baseline (day -1 of period 1) and on days 1 and 5 in each period. Fasting PG levels are determined on days 8 and 12 in periods 1 and 2. On day 1, 24-hour PG levels increase from baseline to a similar extent with all regimens. On day 5, 24-hour PG levels with both dexlansoprazole MR regimens increase further and to a similar extent and are slightly higher than PG levels with lansoprazole. For all regimens, fasting PG levels on days 5 and 6 are higher than baseline levels (P<.05) and start to decrease by day 8, returning to near baseline at day 12. In this study, dexlansoprazole MR administration results in moderate increases in PG, similar to lansoprazole, which return to baseline levels within 7 days post dosing.

Gastric corpus atrophy following eradication of Helicobacter pylori

Atrophic gastritis can develop in patients with Helicobacter pylori infection leading to a reduction in basal acid output. Whether the atrophy that develops is reversible is controversial. To investigate the effect of H. pylori eradication in infected subjects who had developed atrophy of the corpus mucosa. Ten H. pylori positive patients with corpus atrophy were identified at oesophagogastroduodenoscopy (OGD). They received eradication therapy with amoxicillin, clarithromycin and omeprazole. Repeat OGD with biopsy was performed at least 3 months later. Fasting plasma gastrin was measured at baseline and at re-endoscopy. H. pylori eradication was confirmed by 13C urea breath testing. Median time to re-endoscopy was 5 months. There was improvement in corpus atrophy in 50% of patients after H. pylori eradication, and a significant reduction in plasma gastrin (P = 0.03). The index patients had a significant diminution of basal acid output compared to controls. Corpus atrophy as defined by the Sydney System is reversible in some patients after H. pylori eradication. Improvement in atrophy is associated with a fall in fasting plasma gastrin levels. This may have implications in the prevention of gastric carcinoma.

Helicobacter pylori-specific IgG in chronic haemodialysis patients: relationship of hypergastrinaemia to positive serology

Chronic haemodialysis (HD) patients frequently suffer from dyspeptic symptoms and hypergastrinaemia is a common finding in these patients. Helicobacter pylori (H. pylori) infection is associated with dyspepsia and hypergastrinaemia. The aim of this study was to determine whether H. pylori is frequently found in HD patients and to explore the relationship of H. pylori with dyspeptic symptoms and/or hypergastrinaemia in these patients. Serum H. pylori specific IgG were measured by an in-house enzyme-linked immunosorbent assay (sensitivity and specificity is 97% and 91% respectively) in 103 chronic HD patients. The patients (53 M, 50 F, mean age f60 +/- 13 years) completed a questionnaire exploring the type, frequency and intensity of dyspeptic symptoms. Fasting plasma gastrin levels were also measured. Serum and plasma samples from 103 hospital patients matched for age, sex and dyspepsia were use as controls. There was no significant difference in terms of serum H. pylori IgG between HD patients and controls (0.977 +/- 0.295 vs 1.046 +/- 0.306 OD respectively). The prevalence of subjects with positive serology was relatively high in both groups, but did not differ between HD patients (73%) and controls (78%). Dyspepsia was reported in 72 (70%) cases. There was no relationship between presence (and grading) of dyspepsia or type of dyspeptic symptoms and H. pylori serology. In the HD group, patients seropositive for H pylori had a significantly higher gastrinaemia than those who were seronegative: 598 +/- 413 ng/ml vs 309 +/- 252 ng/ml (P < 0.0001). The relationship between seropositivity for H. pylori and hypergastrinaemia was significant (P = 0.00038), after adjustment by multiple regression analysis for sex, age, smoking, alcohol, months on dialysis, renal function, drugs, and dyspepsia. Data of this study suggest that H. pylori may play a role in contributing to hypergastrinaemia of HD patients.

Plasma gastrin concentrations are normal in patients with colorectal neoplasia and unaltered following tumor resection

Background/Aims: Previous studies have found that colorectal cancer patients have hypergastrinemia, but most have been inadequately controlled. Preoperative fasting and meal-stimulated gastrin levels were measured in patients with colorectal tumors (n = 42) and in carefully matched controls (n = 34). Helicobacter pylori status was assessed because it causes significant hypergastrinemia. Methods: Plasma gastrin levels were measured by radioimmunoassay. Helicobacter status was assessed using the [14C]urea breath test and serology (immunoglobulin G). Results: Preoperatively, fasting plasma gastrin levels were similar in patients with tumors (median, 55 ng/L; interquartile range, 45–82.5) and controls (77.5 ng/L; 53.7–137.5; P = 0.10). Similarly, peak gastrin levels were not significantly different in tumor patients (200 ng/L; 137.5–312.5) and controls (247.5 ng/L; 147.5–375; P = 0.21). The prevalence of H. pylori infection in patients with tumors (60%) and controls (53%) was similar in both groups. Five (20%) tumor patients who were H. pylori-positive preoperatively were negative postoperatively, and their median peak plasma gastrin level decreased from 200 ng/L to 140 ng/L. After these patients were excluded, fasting and peak plasma gastrin concentrations were similar preoperatively and postoperatively. Conclusions: When confounding factors are controlled for, plasma gastrin levels are not increased in colorectal cancer and do not decrease after curative resection. Previously noted decreases in gastrin levels after tumor resection may be attributable to loss of H. pylori infection in some patients, as noted here.

Gastrin and colorectal cancer. Evidence against an association.

Plasma gastrin has been reported to be elevated among patients with colorectal cancer. The objectives of the present study were to confirm this observation and, if confirmed, to shed light on the reason for the elevation. Presurgical and postsurgical fasting plasma gastrin levels were compared between 24 patients hospitalized for colorectal adenocarcinoma resection and 25 control patients hospitalized for other surgery. Elevated presurgical gastrin levels in the case group that fell after surgery would be consistent with production of gastrin by the tumor. High presurgical gastrin levels in the case group that did not change following surgery would be consistent with excess gastrin production by G cells. The mean presurgical gastrin levels were 21.9 +/- 3.7 pM (cases) and 45.1 +/- 18.0 pM (controls). The mean postsurgical gastrin levels were 20.5 +/- 3.9 pM (cases) and 43.4 +/- 14.6 pM (controls). These results do not provide support for the hypotheses that gastrin is elevated in colorectal cancer patients or that gastrin is secreted by colorectal tumors in sufficient quantities to be measurable in the plasma.

Histology of gastric biopsies from peptic ulcer patients before and after short-term treatment with omeprazole or H2-receptor antagonists

Sixty patients with duodenal or prepyloric ulcers were given omeprazole (30 or 40 mg o.m.; average period of treatment: 2.9 weeks) or histamine H2-receptor antagonists (cimetidine 400 mg b.i.d. or ranitidine 150 mg b.i.d.; average period of treatment; 3.5 weeks) for a single period ranging between 2 and 6 weeks. At the end of the treatment period fasting plasma gastrin levels were moderately increased in both groups in comparison with the pretreatment values. Endoscopic biopsies were taken from the oxyntic mucosa at the beginning and at the end of the treatment period. Light microscopy of the biopsies was aimed particularly at determining the number of endocrine cells. In addition, the mucosal thickness and the volume densities of the parietal cells, the lamina propria and the gland lumina were measured. There were no significant differences in the endocrine or parietal cell populations, between biopsies taken from the patients before and after treatment with omeprazole or histamine H2-receptor antagonists. The mucosal thickness and the densities of the lamina propria and of the gland lumina remained unaffected by the treatment.

Elevated gastrin levels in patients with colon cancer or adenomatous polyps

Gastrin has been shown to stimulate the growth of carcinogenic-induced colon cancer in animals, and some human colon cancers grown in vitro or as xenografts in nude mice. We determined fasting plasma gastrin levels in control subjects and patients with adenomatous polyps or adenocarcinoma of the colon to determine whether abnormal levels occurred in either patient group. Blood samples were obtained from 73 patients undergoing colonoscopy, primarily for evaluation of Hemoccult-positive stools. Fasting plasma gastrin was significantly greater in patients with adenomatous polyps (24.2 +/- 5.7 pM, N = 25) or colon cancer (84.5 +/- 28.5 pM, N = 20) than in controls (9.9 +/- 0.9 pM, N = 28). Elevations were due to gastrin values greater than control mean + 2 SD in nine patients with polyps (19.5-150.2 pM) and eight with cancer (20.7-403.2 pM). None of the patients had identifiable causes (drugs, prior surgery) for elevated gastrin levels. Our results indicate that elevated plasma gastrin occurs in subgroups of patients with adenomatous polyps or adenocarcinoma of the colon. The cause and potential role of elevated gastrin for polyp and tumor growth in these patients is not known.

An evaluation of the safety of ranitidine during seven years daily oral administration to beagle dogs.

1. Ranitidine hydrochloride was administered orally to Beagles at doses equivalent to 50 mg once daily, or 5 mg twice daily, of ranitidine base/kg for more than 7 years. 2. Apart from looseness of faeces, seen mainly after doses of 50 mg/kg and only rarely after the first year of such treatment, there were no adverse clinical effects. There were no deaths related to treatment. 3. Periodic gastroscopy revealed nothing abnormal. 4. Peak plasma levels of ranitidine occurred within 2 h of dosing; levels were proportional to the doses administered. 5. There were no major differences in fasting plasma gastrin levels between treated and untreated dogs; the expected increase occurred in response to the provision of food and, predictably, this was greater following a dose of ranitidine. 6. A normal histamine-induced gastric secretory response was demonstrated. 7. Necropsy revealed no lesions of toxicological significance. Macroscopically the stomachs appeared normal but microscopic examination showed some gastritis in both treated and control dogs. No changes in enterochromaffin-like (ECL) cells were detected. Electron microscopy showed unimpaired secretory activity of parietal cells. 8. Thus, after more than 7 years administration to beagle dogs of doses in excess of the normal daily therapeutic dose, the stomachs showed no changes attributable to treatment and their secretory capacity was unimpaired.

Effect of short- and long-term feeding of omeprazole on rat gastric endocrine cells.

Rats were tube-fed with omeprazole (40 mumol/kg body weight twice daily) for 30 and 60 days. As a result, fasting plasma gastrin levels were significantly elevated, while plasma somatostatin levels remained normal. Gastrin concentrations in the antral mucosa were unchanged after 30 days, but significantly elevated after 60 days. The relative stomach weight and the area of the antral and oxyntic mucosa increased significantly; however, the oxyntic mucosa thickness and the volume density of the parietal cells did not increase. Highly significant changes occurred in the endocrine cells of the antrum and corpus. The volume density of the argyrophilic (Grimelius technique) cells of the oxyntic mucosa increased time-dependently, and so did the volume density of the antral G cells, while the volume density of the antral D cells decreased. This resulted in a remarkable increase in the G/D cell ratio. All functional and morphological changes are reversed 42 days after omeprazole feeding for 60 days. The findings in the endocrine cells of the antral mucosa are explained by the omeprazole-induced permanent elevation of the intragastric pH and in the endocrine cells of the oxyntic mucosa by the following hypergastrinaemia.

Fasting and food-stimulated plasma gastrin levels in chronic Chagas' disease.

Chagas' disease is known to be associated with extensive lesions of the intramural neurons of the digestive tract. In order to evaluate the contribution of the intramural plexuses to the control of plasma gastrin levels in man, we performed the following measurements: (a) fasting plasma gastrin in 18 chagasic patients and 16 control subjects; (b) integrated gastrin response to food in 9 chagasic patients and 10 controls, (c) basal acid secretion and gastric acid responses to graded doses of pentagastrin in 14 chagasic and 13 controls. Fasting plasma gastrin levels and integrated gastrin response were significantly higher in chagasics than in controls. Basal and maximal acid secretion and responsiveness of acid-secreting gastric cells were lower in chagasics. These results indicate that the intramural plexuses play a role in the control of gastrin release in man.

Vagal control of migrating motor complex-related peaks in canine plasma motilin, pancreatic polypeptide, and gastrin.

The role of the vagus nerve in the control of fasting plasma pancreatic polypeptide (PP), gastrin, and motilin levels was investigated in conscious dogs. Lowest plasma levels of motilin (81 +/- 8 pmol/L), PP (19 +/- 1 pmol/L) and gastrin (5 +/- 1 pmol/L) were observed during phase I of the migrating motor complex (MMC). Significant peaks in plasma motilin (127 +/- 11 pmol/L, P less than 0.005), PP (26 +/- 2 pmol/L, P less than 0.005), and gastrin (14 +/- 2 pmol/L, P less than 0.005) were seen, coinciding with the appearance of phase II (PP and gastrin) or phase III (motilin) of the migrating motor complex in the upper gut. Whereas bilateral vagal blockade abolished the peaks in PP and gastrin, a significant (P less than 0.025) increment in plasma motilin remained, which correlated with the late phase III equivalent of the vagally independent complex (VIC) in the duodenum. This VIC-related motilin peak (170 +/- 20 pmol/L) was significantly higher (P less than 0.025) and the time course (9 +/- 2 min) significantly shorter (P less than 0.01) than the peak (127 +/- 11 pmol/L) and duration (31 +/- 9 min) observed without vagal blockade. Thus, in fasting, the cyclical increments of PP and gastrin are both dependent on excitatory vagal innervation, whereas excitatory pathways controlling phase III associated peak motilin release are nonvagal. In addition, the pattern of fasting motilin release and the amplitude of peak motilin secretion may be affected by vagal inhibition.

The early diagnosis of gastrinoma.

Despite the increasing awareness of gastrinoma and its lethal peptic ulcer sequelae, the diagnosis is often initially missed or made as a terminal event. The authors screened all patients with peptic ulcer symptoms serious enough to warrant hospital admission or those associated with diarrhea, nephrolithiasis, hypercalcemia, or pituitary abnormality. In a one-year period (1979-1980) nine (of 14 suspected) new gastrinoma patients were identified using a sensitive and specific gastrin radioimmunoassay in combination with provocative tests including IV secretin, calcium, and food. Conventional upper GI series, CAT scan, arteriography, and endoscopy provided no additional information other than to confirm the presence of ulcer disease. Basal plasma gastrin levels were more than 200 pmol L-1 in only three of the nine (normal fasting plasma gastrin levels are less than 25 pmol L-1). Three patients presented with acute ulcer perforation, and the diagnosis of gastrinoma was suspected because of multiple ulcers and pancreatic masses. In three other patients, previous duodenal ulcer surgery had failed. One patient with dyspepsia, high basal plasma gastrin, negative secretin and calcium infusion studies, and a positive meal test was diagnosed as having G-cell hyperplasia; this was confirmed by biopsy and antral gastrin extraction. Antrectomy alone resulted in cure. In all patients tested, a positive calcium infusion or secretin bolus (greater than 100% rise over basal) strongly suggested the diagnosis of gastrinoma, which was confirmed at surgery. In the acute perforations, initial management with omental patch and cimetidine therapy allowed survival of two patients, while emergency total gastrectomy in the third resulted in death due to esophagojejunal leak. Elective patients were treated with cimetidine initially for at least two weeks before total gastrectomy. In this group there were no operative mortalities, and postoperative morbidity was minimal. This series illustrates three important points: (1) careful screening of an ulcer population using gastrin radioimmunoassay and provocative tests has enabled a high yield of gastrinomas while conventional investigations are of minimal values; (2) a high index of suspicion in appropriate cases is necessary; and (3) total gastrectomy performed under elective circumstances is safe and allows the patients to resume a normal and healthy life without the sequelae of aggressive peptic ulceration or daily drug administration.

Lesions of the upper gastrointestinal tract in patients with chronic renal failure.

Endoscopy of the upper gastrointestinal tract was performed on 84 patients with end-stage chronic renal failure undergoing hemodialysis. Gastric acid secretion and fasting plasma gastrin levels were also examined in these patients. Hemorrhagic gastritis was most frequently observed (23 cases) followed by erosive gastritis (18 cases). No patients had gastric ulcers. Duodenal ulcers were observed in only two patients. Gastrointestinal bleeding was observed in 15 cases (17.9%). Thirteen of these 15 cases had hemorrhagic gastritis, one of which had a duodenal ulcer as a complication. Fasting plasma gastrin levels (359.6 +/- 336.5 pg/ml) were significantly higher than those of normal subjects (35.2 +/- 37.1 pg/ml), but no acceleration in gastric acid secretion was observed either in the basal condition (BAO 0.8 +/- 0.7 mEq/h) or following tetragastrin stimulation (MAO 9.0 +/- 6.9 mEq/h). Our results were inconsistent with the previous reports that high frequencies of peptic ulcers and increased gastric acid secretion were observed in patients with chronic renal failure. Our data suggest that the defensive factors rather than the aggressive factors of the gastroduodenal mucosa may be involved in chronic renal failure.

Gastric secretion and basal gastrin concentration in bilharzial hepatic fibrosis.

Gastric secretion and fasting plasma gastrin levels were investigated in 26 patients with bilharzial hepatic fibrosis and 26 controls. The groups did not differ in their basal secretion. When stimulated by intravenous infusion of histamine the maximal acid output in patients with bilharzial hepatic fibrosis was significantly less than in the control group. This was unlikely to be a result of neutralisation by reflux of alkaline duodenal contents as the volumes of reflux were not different from control subjects, but was compatible with a true reduction in gastric secretion as assessed by two-component hypothesis. Neither the lowered gastric acidity nor the liver damage in patients with bilharzial hepatic fibrosis correlated with circulating gastrin. The fasting levels of plasma gastrin in these patients were not different from controls. As in other liver diseases the cause of diminished gastric secretion remains unclear.

Hypogastrinemia in hypothyroidism.

Fasting plasma gastrin levels measured by radoimmunoassay were found to be low in patients with hypothyroidism. The intravenous infection of arginine caused an increase of plasma gastrin in hypothyroid patients but was significantly lower than those in normal subjects. The decreased gastrin level in patients with hypothyroidism was significantly improved after the thyroid function was normalized by treatment.

Effect of glucocorticoids on gastrin secretion in man.

In order to investigate the effect of glucocorticoids on gastrin secretion, plasma gastrin levels were measured by radioimmunoassay in patients with Cushing's syndrome and those treated with glucocorticoids. Fasting plasma gastrin levels were significantly higher in these patients than in normal subjects, with exaggerated response to food. Conversely, short-term treatment or intravenous infusion of glucocorticoids had no significant influence on gastrin secretion in normal subjects. The possible mechanism by which glucocorticoids cause hypergastrinaemia are discussed.

Hypergastrinemia in Hyperthyroidism

Fasting plasma gastrin levels measured by radioimmunoassay were found to be elevated in patients with hyperthyroidism. The intravenous injection of arginine caused an increase of plasma gastrin in hyperthyroid patients as in normal subjects. The elevated gastrin level in patients with hyperthyroidism was significantly lowered after the thyroid function was normalized by treatment.

Successful treatment of a malignant gastrinoma with streptozotocin.

The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l.