Lower esophageal sphincter pressure and serum gastrin levels after mapped antrectomy

We investigated the effect of mapped antrectomy with gastroduodenostomy on serum gastrin levels in fasting patients and resting lower esophageal sphincter (LES) pressure. Serum gastrin levels in fasting patients were lower in those who had an antrectomy without vagotomy (P less than .05) as compared to control subjects or patients with antrectomy and vagotomy. Resting LES pressure was similar in patients and controls and was not affected by the presence or absence of vagotomy. These findings suggest that (1) mapped antrectomy and gastroduodenostomy without vagotomy are followed by a decrease in serum gastrin and (2) resting LES pressure is not affected by mapped antrectomy and a decrease in serum gastrin level.     

Studies of the release of gastrin from the human duodenum induced by gastrin-releasing peptide

In the present study the influence of duodenal exclusion and vagotomy on basal release of gastrin from extra-antral stores has been investigated in addition to the consequences of these procedures on the gastrin response to gastrin-releasing peptide (GRP) infusion. Basal gastrin concentrations and the response to GRP were measured in seven patients after a Whipple operation, in seven patients after antrectomy combined with selective gastric vagotomy and B I reconstruction, in seven patients operated on with antrectomy, selective gastric vagotomy, and Roux-en-Y reconstruction, and finally in seven patients after antrectomy, truncal vagotomy, and Roux-en-Y reconstruction. Gastrin was measured by a highly specific radioimmunoassay. Very low concentrations were obtained after a Whipple operation, and no increase followed GRP infusion. The basal gastrin concentrations were slightly higher in antrectomized patients, irrespective of whether a selective gastric vagotomy had been added. However, in these patients a significant gastrin response followed GRP infusion. Duodenal exclusion seemed not to influence the response to GRP. On the other hand, extragastric vagotomy was followed by low gastrin concentrations in the basal state and only a marginal response to GRP administration. These results strongly suggest that GRP releases gastrin from the human duodenal mucosa and that duodenal exclusion does not alter the response of the duodenal gastrin cells to GRP stimulation. Vagal denervation of the duodenal mucosa seems to suppress the gastrin response to GRP, indicating an excitatory influence of the vagus nerve.     

Extragastric gastrin

Gastrin release in the basal state and following a standard protein meal has been estimated in patients after partial gastrectomy, partial gastrectomy with truncal vagotomy, and total gastrectomy.Following partial gastrectomy, gastrin rose from 8 +/- 0.8 to 20 +/- 3.8 pg/ml with a protein meal. The rise in the partial gastrectomy with truncal vagotomy group was 27 +/- 0.8 to 92 +/- 1.5 pg/ml and after total gastrectomy was 13 +/- 1.5 to 58 +/- 4.6 pg/ml.These results provide evidence for the release of gastrin from extragastric sites.     

Effect of Antrectomy and Vagiscretion on Gastric Acid Output and Gastrin Secretion

In three dogs with denervated Heidenhain pouches, ingestion of cooked beef liver caused increased acid output and gastrin secretion. After antrectomy and gastrojejunal anastomosis, ingestion of the liver did not increase sernm gastrin levels throughout the experiment. Acid output, however, although markedly reduced, was elevated over basal levels during the last three hours of the four-hour experiment. Total abdominal vagotomy did not alter gastrin secretion but further inhibited acid output in response to the test meal. These results indicate that in the dog intestinal gastrin is not released in response to a beef liver meal. Acid output postantrectomy, although reduced, does respond to the meal and is further decreased after vagotomy. A hormonal mechanism other thati tlie re-lease of intestinal gastrin is responsible for the intestinal phase of gastric acid secretion.     

Studies on the Mechanism of the Lower Esophageal Sphincter Pressure Response to Alkali Ingestion in Humans

To clarify the lower esophageal sphincter (LES) pressure response to alkali ingestion, normal subjects and postantrectomy patients with either a gastroduodenostomy or gastrojejunostomy were studied in a double-blind controlled fashion. LES pressure and serum gastrin concentrations were measured after ingestion of a 100 ml bolus of either 0.4 M NaHCO3 or 0.4 M NaCl. In addition, the effect of a therapeutic dose (30 ml) of a commercial antacid preparation was studied in a double-blind fashion in 14 patients with gastroesophageal reflux disease. Peak increases in LES pressure above basal were significantly higher (p less than 0.05) after NaHCO3 than after NaCl in normal subjects and in patients with vagotomy and Billroth I antrectomy, but not in patients with vagotomy and Billroth II antrectomy. Serum gastrin concentrations were unaffected by alkali. Thirty milliliters of liquid antacid containing aluminum and magnesium hydroxide resulted in a small sustained rise in LES pressure over the first 50 min after ingestion, but this was not statistically different than the placebo response. It is suggested that: 1) neither the antrum nor intact vagi nor gastrin were required for NaHCO3 ingestion to increase LES pressure; 2) the increase in LES pressure with NaHCO3 ingestion appears to rely upon an intact duodenum and may relate to volume and osmolarity of the alkali load; and 3) therapeutic doses of a liquid commercial antacid does not significantly increase LES pressure in the presence of an intact stomach.     

Role of antrum and duodenum in the control of postprandial gastric acid secretion and plasma gastrin concentration in dogs.

Three dogs were provided with Pavlov pouches. In two subsequent operations the antrum and the duodenal bulb were removed and the gastrointestinal continuity was restored by gastroduodenostomy. Gastric acid and gastrin secretion were stimulated by a test meal. The feeding experiments were repeated after each operation. The gastrin response to a test meal was markedly reduced but not eliminated by antral resection. Additional removal of the duodenal bulb significantly lowered the basal plasma gastrin concentration and abolished the gastrin response to feeding. The acid response to test meals was significantly increased by antrectomy. Extirpation of the duodenal bulb reduced the postprandial acid output to or below preantrectomy levels. The findings indicate that the antrobulbar region exerts a complex influence on gastric acid secretion which may result in stimulation or inhibition of the HCl glands. Removal of the pyloric antrum and the duodenal bulb does not effectively reduce postprandial acid secretion.     

Serum gastrin in duodenal ulcer: Part IV Effect of selective gastric vagotomy

Serum gastrin has been measured in 30 patients following selective gastric vagotomy. Basal serum gastrin was 52+/-5.7 pg/ml which was significantly lower than the corresponding level in 50 patients following truncal vagotomy (84+/-7.9 pg/ml). After a standard protein meal serum gastrin rose to 136+/-8.3 pg/ml at 60 minutes after the meal. The peak rise above basal levels was significantly lower than that achieved in patients who had undergone truncal vagotomy.These results complement our previous hypothesis that section of extragastric vagal fibres permits the release of additional gastrin above that expected with the diminution of acid secretion, and hence the decrease in inhibition of gastrin release from the antrum.     

Gastric and extragastric gastrin release in normal subjects in duodenal ulcer patients, and in patients with partial gastrectomy (Billroth I).

In 10 normal subjects, in 32 patients with duodenal ulcer (DU), and in 11 patients with partial gastrectomy (Billroth I), serum gastrin rose significantly after an oral and intraduodenal test meal. The highest increases were observed in DU patients after the oral as well as after the intraduodenal test meal. After the intraduodenal test meal in 4 normal subjects and in 17 DU patients an increase of gastric acid secretion and serum gastrin was measured. In basal state, after an intraduodenal or an oral test meal, DU patients with normal gastric acid secretory capacity had higher serum gastrin concentrations than DU patients with gastric hypersecretion. There was a good correlation between peak serum gastrin levels after the oral and after the intraduodenal test meal. From these data it is concluded: (1) Intraduodenal application of a test meal results in release of gastrin from extragastric sites. (2) Extragastric gastrin is biologically active. (3) DU patients are able to release more antral and more extragastric gastrin in response to a test meal. Further studies, however, are necessary to show the significance of these findings in the pathogenesis of peptic ulcer disease.     

Acid and gastrin levels after bombesin and calcium infusion in patients with incomplete antrectomy

In 17 patients with postoperative recurrent peptic ulcer, incomplete antrectomy (I.A.) was found by endoscopic biopsies in 5. No evidence of I.A. was found in the remaining 12 patients. Gastric acid output and gastrin levels were measured in basal conditions and following a calcium I.V. infusion (4 mg/kg hr of Ca⁺⁺ over 4 hr) and a bombesin (BBS) I.V. infusion (15 ng/kg min over 90 min). Basal gastrin levels were significantly different in the two groups of patients: BBS infusion augmented significantly serum gastrin levels in all patients with I.A., while BBS infusion had no significant effect on serum gastrin levels in the group of patients wihtout I.A. Acid output following BBS infusion showed a pattern similar to the pattern seen for gastrin. Calcium infusion augmented gastric acid secretion and gastrin levels in the patients with I.A.; however, the response to calcium could not clearly separate in all instances patients with I.A. from patients without I.A. It is concluded that the BBS infusion test may be helpful in the diagnosis of I.A. in patients with postoperative peptic ulcer.Research was carried out with a grant from C.N.R. No. 72.00893.04.     

Is antral gastrin important in the resistance of duodenal ulcers to H2 receptor antagonists or in recurrent ulceration after highly selective vagotomy?

Basal serum gastrin, integrated gastrin response to a meal, and integrated gastrin response to insulin induced hypoglycaemia were measured in 60 patients with duodenal ulcer before and after elective highly selective vagotomy to determine whether antral gastrin has a role in resistance to H2 receptor antagonist treatment which the patients had received before surgery or in the development of recurrent ulceration after vagotomy. The basal gastrin, integrated gastrin response to a meal, and the integrated gastrin response to insulin were similar in patients whose ulcers healed after H2 receptor agonist treatment or were refractory to at least three months of this treatment. The same parameters measured before or after highly selective vagotomy were similar in patients who eventually developed recurrent ulceration compared with those who did not. As expected the basal and meal stimulated (but not insulin stimulated) serum gastrin values increased after highly selective vagotomy. Ulcer patients with particularly high gastrin values (whether basal or stimulated) were not more resistant to H2 receptor antagonist treatment or prone to develop ulcer recurrence after highly selective vagotomy. This study suggests that antral gastrin is not important in 'resistance' of duodenal ulceration either to H2 receptor antagonist treatment or to highly selective vagotomy.     

Effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion,release of gastrin,and pancreatic polypeptide in the anesthetized dog

The short-term effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion and release of gastrin and pancreatic polypeptide (PP) were studied in 18 anesthetized dogs. Together with an intravenous infusion of secretin (250 ng/kg/hr) bombesin (500 ng/kg/hr) was given before and after truncal vagotomy, antrectomy, and sham operation (N=6 dogs per group). Peak incremental pancreatic protein output in procedures (tachyphylaxis). Neither truncal vagotomy nor antrectomy significantly altered the pancreatic protein response to bombesin when compared with sham operation. Bombesin produced a mean 1-hr increase over basal of 196 pM for gastrin, which was abolished by antrectomy but not appreciably affected by truncal vagotomy and sham operation. The mean 1-hr increment (207 pM) for PP in response to bombesin was not changed by truncal vagotomy, antrectomy, and sham operation. This study shows in the anesthetized dog that exogenous bombesin stimulates release of PP as well as gastrin; that the release of gastrin by bombesin is not vagally dependent; that neither truncal vagotomy nor antrectomy alter the release of PP by bombesin; and that the action of bombesin on pancreatic protein secretion does not depend on release of gastrin or on intact vagal nerves.Parts of this paper have been presented at the 12th European Pancreatic Club Meeting, Copenhagen, Denmark, October 11–13, 1979, and at the 3rd International Symposium on Gastrointestinal Hormones, Cambridge, England, September 15–18, 1980.     

Differences between peptic ulcer and control patients on the basis of the response to secretin

The secretin injection test is considered a useful adjunct to the diagnosis of gastrinoma, although it may lack specificity. This study determined whether the release of gastrin in response to secretin was different in duodenal ulcer and control patients. Tests were performed on 10 duodenal ulcer patients, 10 normal control subjects, 20 patients asymptomatic after ulcer surgery, of whom 13 had a vagotomy and drainage, 4 a highly selective vagotomy and 3 a vagotomy and antrectomy. The secretin test was also performed in 49 patients with endoscopically proven recurrent ulcers. The surgery performed in this latter had consisted of a vagotomy and drainage in 36, a highly selective vagotomy in 7 and a vagotomy and antrectomy in 6 patients. The basal plasma gastrin level was similar in normal controls, duodenal ulcer patients and patients with vagotomy and antrectomy, both with and without recurrent ulcers. The level was elevated in all the other groups of patients with vagotomy both with and without recurrent ulcer. The plasma gastrin did not change significantly after secretin injection in the normal control or asymptomatic ulcer surgery patients, but rose in the duodenal ulcer patients and all the groups of patients with recurrent ulcer. Most of these increases were validated statistically as were the differences in response between the ulcer and control patients. These results indicate that there are differences in the plasma gastrin response to intravenous secretin between active duodenal ulcer and control patients. This findings may aid our understanding of the pathophysiology of peptic ulcer disease and explains the lack of specificity of the secretin test.     

Serum gastrin in duodenal ulcer: Part III Influence of vagotomy and pylorectomy

Following truncal vagotomy and anterior pylorectomy for duodenal ulcer, fasting serum gastrin levels were higher at 84 +/- 7.9 pg per ml than in unoperated patients with duodenal ulcer (16 +/- 1.5 pg per ml). In response to a standard protein meal, the peak serum gastrin achieved in the vagotomized group was 259 +/- 37.8 pg per ml at 75 minutes after ingestion, a much higher response than that obtained with a standard meal plus prior atropinization in the unoperated duodenal ulcer patients.These results suggest that truncal vagotomy allows release of gastrin which was previously inhibited with the vagi intact and the temporal characteristics of the response indicate that some of this gastrin is derived from an extragastric source. The results also exemplify the dependence of gastrin estimations as measured by this immunoassay on the acidity of the contents bathing the gastric antrum.     

Bile acid and lysolecithin concentrations in the stomach in patients with duodenal ulcer before operation and after treatment by highly selective vagotomy, partial gastrectomy, or truncal vagotomy and drainage

Duodenogastric reflux of bile acids and lysolecithin in the course of a standard test meal was measured in normal people and in patients with duodenal ulcer before operation and more than one year after highly selective vagotomy, Polya partial gastrectomy, truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy. Before operation, duodenal ulcer patients had significantly higher fasting, post-prandial, and peak bile acid concentrations in the stomach than had normal subjects. After Polya partial gastrectomy, fasting, post-prandial, and peak concentrations of bile acids and lysolecithin were significantly higher than in preoperative duodenal ulcer patients. After highly selective vagotomy, in contrast, bile acid concentrations in the stomach were significantly lower than in preoperative duodenal ulcer patients and post-prandial and peak lysolecithin concentrations were less than half (NS) those recorded in preoperative duodenal ulcer patients. After highly selective vagotomy, bile acid concentrations were also significantly lower than bile acid concentrations after Polya partial gastrectomy, truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy; and post-prandial and peak lysolecithin concentrations were significantly lower than after Polya partial gastrectomy and truncal vagotomy and gastrojejunostomy. Thus, when used in the treatment of patients with duodenal ulcer, highly selective vagotomy keeps `bile' out of the stomach, probably through its effect on gastric smooth muscle, combined with the preservation of an intact antropyloroduodenal segment. In contrast, Polya partial gastrectomy, truncal vagotomy and gastrojejunostomy, and truncal vagotomy and pyloroplasty all lead to a significant increase in reflux of bile acids and lysolecithin into the stomach. The clinical importance of these findings is that both gastritis and, in the long term, gastric carcinoma may prove to be less common after highly selective vagotomy than after partial gastrectomy or vagotomy with a drainage procedure.     

The role of the antrum and the vagus nerve in the metabolism of histamine in the human gastric mucosa.

The effects of antrectomy and proximal gastric vagotomy on the metabolism of histamine in the human gastric mucosa were studied in the basal state and during pentagastrin stimulation in patients with duodenal or gastric ulcer disease. Mucosal biopsy specimens were taken from the antral and oxyntic gland areas, whereafter histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Vagotomy was followed by a decrease in the acid secretory capacity and an increase in basal serum gastrin levels. Histamine content of the oxyntic mucosa increased after vagotomy, but the ability of pentagastrin to form new amounts of the amine was impaired. Antrectomy caused a decrease in acid secretion and a fall in gastrin concentrations. Basal histamine content and rate of amine formation in the remaining oxyntic mucosa were unaffected by antrectomy. Antrectomy impaired the ability of pentagastrin to release histamine. Histamine methyltransferase was not affected by pentagastrin, vagotomy, or antrectomy. In conclusion, both antral gastrin and the vagus nerve seem to exert a regulatory influence on the metabolism of histamine in the human oxyntic mucosa. The withdrawal of these factors either causes impaired ability of pentagastrin to release histamine from its storage site or counteracts the ability of pentagastrin to accelerate histamine synthesis.     

Effect of acid secretory capacity and chronic endogenous hypergastrinemia on pancreatic secretion and intestinal morphology in the rat

To study the trophic effects of gastrin on the gastrointestinal tract, chronic endogenous hypergastrinemia was produced in rats by implantation of the gastric antrum into the colon. Rats were sham-operated (normal gastrin, normal acid) or were prepared with BII gastrojejunostomy and antral resection (low gastrin, low acid), or BII gastrojejunostomy and antral implantation into colon (high gastrin, acid present). To separate effects of hypergastrinemia from those of acid hypersecretion, two additional groups were prepared with total gastrectomy and either resection of the antrum (low gastrin, no acid) or antral implantation into colon (high gastrin, no acid). After 12 weeks, the pancreatic secretory response to secretin was measured. The animals were then sacrificed, and liver, pancreas, small intestine, and colon were weighed. In separate groups of animals villous height and width and crypt depth of small intestine and transverse colon were measured. Serum gastrin concentrations increased three- to fivefold in fasting and fed antral implant animals. Serum gastrin levels in the fed state were lower in antrectomy rats compared to controls but did not differ in the fasting rats. Pancreas and colon were heavier in all hypergastrinemic rats. Liver weights did not differ between hypergastrinemic animals and controls. Stimulated pancreatic bicarbonate secretion following secretin infusion was elevated only in hypergastrinemic, hyperacidic rats. Hypertrophy of the small bowel was seen in antral implant rats only when the gastric remnant was preserved (ie, when acid was present). Colonic mucosal thickness was increased in antral implant rats with or without gastrectomy. No significant increases in small-bowel villous height or crypt depth were found in antral implant rats. Thus, chronic endogenous hypergastrinemia caused pancreatic and colonic hypertrophy independent of acid secretion. In addition to hypergastrinemia, gastric hyperacidity was also needed for enlargement of small bowel or increase in secretin-stimulated pancreatic bicarbonate secretion.     

Effect of Cholecystokinin and Secretin on Gastric Hypersecretion in a Patient with the Zollinger-Ellison Syndrome

Summary: The intravenous injection of cholecystokinin in a patient with the Zollinger-Ellison syndrome resulted in a sharp fall in gastric acid secretion. In contrast, secretin infusion led to a further increase in the hypersecretion of acid. The latter effect is attributed to the release of extragastric gastrin for secretin infusion following total gastrectomy led to a further elevation of serum gastrin levels. Infusion of either cholecystokinin or secretin produced large volumes of bicarbonate-rich duodenal juice.     

Gut-hormone profile in totally pancreatectomised patients.

In eight totally pancreatectomised patients the release of the relevant gut hormones was determined after a standard test meal. Plasma levels of pancreatic glucagon were not significantly different from zero in our series of pancreatectomised patients. Pancreatic polypeptide was undetectable. These findings imply the absence of a significant number of normally functioning alpha cells and pancreatic polypeptide cells in extrapancreatic sites in man. Consistent with the antrectomy, duodenectomy, and resection of the upper jejunum that are performed in conjunction with a total pancreatectomy the gastrin release was significantly impaired. In contrast there was a striking post-prandial rise in enteroglucagon probably induced by the rapid intestinal transit time often seen after partial gastrectomy. In contrast plasma motilin and GIP levels were normal. Pancreatectomised man thus presents an interesting model of total deficiency of endogenous insulin, pancreatic polypeptide, and pancreatic glucagon and, in addition, greatly diminished gastrin. The considerable derangement of metabolic and intestinal function that follows total pancreatectomy may, in part, be explained by this gross disturbance of the normal physiology of gut hormone.     

Effects of proximal gastric vagotomy and antrectomy on parietal cell function in humans

Both proximal gastric vagotomy and antrectomy reduce maximal gastric acid secretion in vivo by about 60%. The combination of vagotomy and antrectomy reduces the maximal acid secretion by about 80%. This additive effect indicates that these surgical procedures differ in their mode of action. The function of isolated human oxyntic glands was studied before and after vagotomy and antrectomy, respectively, using radioactively labeled aminopyrine as a marker of parietal cell response. The basal accumulation increased after vagotomy, suggesting a vagally controlled inhibitory component. The carbachol response disappeared and the maximal response induced by histamine or dibutyryl-cyclic adenosine monophosphate was reduced by 60% (p less than 0.01) after vagotomy. This reduction could not be overcome by increasing the dose of dibutyryl-cyclic adenosine monophosphate. This indicates an intracellular effect of vagotomy peripheral to dibutyryl-cyclic adenosine monophosphate point of action. Antrectomy did not induce any statistically significant change at the glandular level, indicating that the reduced gastric acid secretion in vivo may be caused by a reduction in the number of oxyntic glands due to a removal of a trophic effect of antral gastrin.     

Antral hypergastrinemia--a report of three cases

Three patients with juxtapyloric ulcers and hypergastrinemia are presented. Fasting and food-stimulated serum gastrin concentration (SGC) were measured in 1970, 1972 and 1973 before the primary ulcer operation (selective gastric vagotomy and Jaboulay gastroduodenostomy; SGV + GD). Fasting SGC were 105, 149 and 158 pg/ml and the postprandial concentrations were 400, greater than 800 and greater than 800 pg/ml, respectively. The pentagastrin-stimulated acid secretion was within the normal range. After SGV + GD, only a slight decrease in acid secretion was observed. The hypergastrinemia persisted unchanged or decreased slightly in 1 patient. A recurrent ulcer developed and a precise antrectomy was carried out. Postoperatively, the fasting SGC was markedly reduced and the postprandial gastrin response abolished. The resected specimens were subjected to immunocytochemical gastrin cell quantitation. The number of gastrin cells was elevated in all 3 patients and the gastrin cell topography was distorted, with cells being present both in the lower and upper thirds of the antropyloric glands.