gastrins and Bile-Reflux

The decline in duodenal ulcer disease and the established relation of peptic ulcer to Helicobacter pylori have virtually abolished the need for elective ulcer surgery. However, a substantial proportion of the population around retirement age has previously been subjected to partial gastric resection due to peptic ulcer, and the long-term outcome of these patients is of continuing relevance. Patients subjected to elective surgery could represent a selected group of healthy subjects with a lower overall morbidity, but reports indicate that patients operated on for peptic ulcer have more advanced disease associated with excess smoking and a different pattern of social behavior. The surgical procedure induces enterogastric reflux, leading to profound changes in the remnant mucosa and the formation of carcinogens in the gastric juice. In addition, metabolic abnormalities are common, especially fat malabsorption. Evaluation of the impact of these factors on morbidity and mortality is difficult. Increased mortality in gastrointestinal tumors (especially gastric stump carcinoma), respiratory diseases and other smoking-related malignancies, and suicide are found in the long-term follow-up after partial gastric resection due to peptic ulcer. However, these hazards to life are offset by a decreased mortality in cardiovascular disease. Preventive measures against suicide and especially tobacco smoking are recommended to improve th outcome for this cohort.

Topics: Bile Reflux; Cardiovascular Diseases; Female; Gastrectomy; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Nutrition Disorders; Peptic Ulcer; Prognosis; Risk Factors; Sex Factors; Smoking; Stomach Neoplasms; Suicide; Time Factors

To determine the results of a new surgical procedure for patients with Barrett's esophagus.. In addition to pathologic acid reflux into the esophagus in patients with severe gastroesophageal reflux and Barrett's esophagus, increased duodenoesophegeal reflux has been implicated. The purpose of this study was to establish the effect of a new bile diversion procedure in these patients.. Sixty-five patients with Barrett's esophagus were included in this study. A complete clinical, radiologic, endoscopic, and bioptic evaluation was performed before and after surgery. Besides esophageal manometry, 24-hour pH studies and a Bilitec test were performed. After surgery, gastric emptying of solids, gastric acid secretion, and serum gastrin were determined. All patients underwent highly selective vagotomy, antireflux procedure (posterior gastropexy with cardial calibration or fundoplication), and duodenal switch procedure, with a Roux-en-Y anastomosis 60 cm in length.. No deaths occurred. Morbidity occurred in 14% of the patients. A significant improvement in symptoms, endoscopic findings, and radiologic evaluation was achieved. Lower esophageal sphincter pressure increased significantly (p < 0.0001), as did abdominal length and total length of the sphincter (p < 0.0001). The presence of an incompetent sphincter decreased from 87.3% to 20.9% (p < 0.0001). Three of seven patients with dysplasia showed disappearance of this dysplasia. Serum gastrin and gastric emptying of solids after surgery remained normal. Basal and peak acid output values were low. Twenty-four hour pH studies showed a mean value of 24.8% before surgery, which decreased to 4.8% after surgery (p < 0.0001). The determination of the percentage time with bilirubin in the esophagus was 23% before surgery; this decreased to 0.7% after surgery (p < 0.0001). Late results showed Visick I and II gradation in 90% of the patients and grade III and IV in 10% of the patients.. This physiologic approach to the surgical treatment of patients with Barrett's esophagus produces a permanent decrease of acid secretion (and avoids anastomotic ulcer), decreases significantly acid reflux into the esophagus, and abolishes duodenoesophageal reflux permanently. Significant clinical improvement occurs, and dysplastic changes at Barrett's epithelium disappear in almost 50% of the patients.

Topics: Adult; Aged; Barrett Esophagus; Bile Reflux; Duodenum; Female; Follow-Up Studies; Fundoplication; Gastric Acid; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Postoperative Complications; Prospective Studies; Vagotomy

In order to delineate the role of enterogastric reflux in changes of postoperative gastric secretory functions, 22 patients with peptic ulcers, who were randomly assigned to partial gastrectomy without vagotomy with either Billroth II or Roux-en-Y anastomosis, were prospectively studied before and 6 months after surgery. Preoperatively, there were no significant differences in gastric secretory functions between the two groups of 11 patients. Postoperatively, median fasting bile acids in the stomach increased in the Billroth II patients from 0.35 to 16.10 mumol/hr (p less than 0.01), but significantly decreased in the Roux-en-Y patients from 0.30 to 0.10 mumol/hr (p less than 0.05), which indicated adequate prevention of enterogastric reflux after the Roux-en-Y procedure. Gastrectomy resulted in significant reductions of median values of basal acid output (4.6 vs 0.6 mmol/hr, p less than 0.01, and 4.2 vs 0.4 mmol/hr, p = 0.02), peak acid output (31.6 vs 4.2 mmol/hr, p less than 0.01, and 38.7 vs 4.5 mmol/hr, p less than 0.01), serum pepsinogen A (121 vs 86 micrograms/L, p less than 0.01, and 92 vs 45 micrograms/L, p less than 0.01), meal-stimulated serum gastrin secretion (1472 vs 199 pM.60 min, p less than 0.0001, and 1017 vs 199 pM.60 min, p less than 0.0001) in the patients with Billroth II and Roux-en-Y anastomosis, respectively. There were, however, no significant differences in gastric secretory parameters between the two groups when studied 6 months after surgery. Therefore it is concluded that after gastrectomy, enterogastric reflux does not affect the secretory function of the gastric remnant within the first 6 months after surgery.

Topics: Anastomosis, Roux-en-Y; Anastomosis, Surgical; Bile Acids and Salts; Bile Reflux; Biliary Tract Diseases; Eating; Fasting; Female; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pepsinogens; Peptic Ulcer; Prospective Studies

To elucidate the chemical profile and the pharmacological mechanism by which Jinlingzi powder (, JLZP) treats bile reflux gastritis (BRG).. A BRG model was established in rats by oral administration of the model solution. JLZP was orally administered for 35 d. Residual gastric rate and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and gastrin levels in the serum were measured, and stomach tissues were collected for histopathological analysis. We used ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry to identify the chemical ingredients in JLZP. Then, protein-protein interaction and herb-compound-target networks were constructed to screen potential bioactive compounds and targets. Kyoto Encyclopedia of Genes and Genomes pathway analysis was then performed to elucidate the pathway involved in the JLZP-mediated treatment of BRG. After constructing the core compound-target-pathway interaction network, molecular docking was performed to study the binding free energy of core bioactive compounds and two candidate targets [RAC-alpha serine/threonine-protein kinase (AKT1) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)].. JLZP extracts significantly promoted gastric emptying, regulating the release of cytokines (TNF-α and IL-6) and improving gastrin secretion and mucosal repair. Fifty-six compounds were tentatively characterized in JLZP. Moreover, the network pharmacology and molecular docking results showed that alkaloids and flavonoids might be the bioactive compounds in JLZP that treat BRG. JLZP might improve mucosal repair during BRG progression by modulating the phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B, hypoxia inducible factor-1, mitogen-activated protein kinase, forkhead box O, TNF, and IL-17 signaling pathways.. We elucidated the chemical constituents and the pharmacological mechanism of JLZP in treating BRG and provided a basis for clinical application.

Topics: Animals; Bile Reflux; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Gastrins; Gastritis; Molecular Docking Simulation; Network Pharmacology; Phosphatidylinositols; Powders; Rats; Tumor Necrosis Factor-alpha

To establish a rat model mimicking human bile reflux for studying the pathological effects of chronic bile reflux.. The duodenum of Sprague-Dawley rats was transected below the opening of the common bile duct, and a gastrojejunostomy was performed at the greater curvature of the forestomach. After the rats demonstrated bile reflux for 1 year, we studied the pathological features of the glandular stomach and forestomach mucosa. We also studied the effect of bile reflux on gastrin expression in the glandular stomach mucosa by using immunohistochemistry.. Chronic bile reflux caused significant hyperplasia and expansion of gastric glands in the glandular stomach. Dysplasia and cancer formation also developed, but the incidence was significantly lower than that reported in the literature. Intestinal metaplasia and ulceration in the glandular stomach were also rare. In the forestomach, the squamous epithelium showed significant hyperplasia and keratinization along with keratin pearls and keratocysts. Intestinal metaplasia was rare and no tumorigenesis was observed. Chronic bile reflux significantly increased gastrin expression in the glandular stomach mucosa.. When simulating the physiological bile reflux pathway, chronic bile reflux caused hyperplasia and expansion of gastric glands in the glandular stomach and squamous epithelial hyperplasia and keratinization in the forestomach.

Topics: Animals; Bile Reflux; Chronic Disease; Disease Models, Animal; Duodenum; Gastric Bypass; Gastric Mucosa; Gastrins; Hyperplasia; Male; Rats; Rats, Sprague-Dawley

In a follow-up study operative risk, postoperative functional disorders and incidence of anastomotic (recurrent) ulcer after partial gastrectomy with Roux-en-Y gastrojejunostomy for gastroduodenal ulcer were evaluated in 52 patients. Lethality for elective treatment was 0 and for emergency surgery (ulcer bleeding) 16.7%. 29.5% of the patients reported postoperative functional disorders. Because Roux-en-Y reconstruction prevented duodenogastric reflux, intragastric pH was low (median 2.2) and in the absence of ulcer protective, neutralizing reflux anastomotic ulcer occurred in 15.9% of the patients. With regard to the high rate of recurrent ulcer Roux-en-Y reconstruction after partial gastrectomy for primary ulcer surgery should be avoided and reconstruction procedures preferred, which guarantee duodenogastric reflux.

Topics: Anastomosis, Roux-en-Y; Bile Reflux; Female; Follow-Up Studies; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Jejunum; Male; Peptic Ulcer; Postgastrectomy Syndromes; Postoperative Complications; Radiography; Recurrence

Thirty patients with bile reflux gastritis, proven by gastroscopy and Milk 99mTc-EHIDA Test, were studied and their clinical features were compared with those of patients with non-bile reflux gastritis. The symptoms were similar in both groups of patients, whereas histologically in bile reflux gastritis there were more hyperemia of mucosa, more obvious edema in lamina propria and more polymorphonuclear infiltration. Furthermore, in bile reflux gastritis the histological changes were more severe in the antrum and decreased in severity toward the cardia. Acid secretion was significantly lower in patients with bile reflux gastritis than in patients with non-bile reflux gastritis while the serum gastrin level was significantly higher in the former than in the latter group. The authors suggest that there may be a vicious cycle among duodenogastric reflux, low level of gastric acidity and high level of serum gastrin. When duodenogastric reflux occurs, not only the bile salts damage the gastric mucosa and subsequently cause the back diffusion of hydrogen ion but also the alkaline duodenal juice neutralizes the gastric acid, resulting in decrease of gastric acidity. The bile salts and low acidity can stimulate the release of serum gastrin which antagonizes the effects of cholecystokinin and secretin on pyloric tone and aggravates the duodenogastric reflux.

Topics: Adult; Aged; Bile Reflux; Biliary Tract Diseases; Female; Gastric Acidity Determination; Gastrins; Gastritis; Humans; Male; Middle Aged

I investigated the significance of bile reflux, when vagotomy was done to stress ulcer, by means of measuring gastric ulcer index, gastric pH and serum gastrin levels of rats. And in order to examine influence of alkali factor of bile, I measured gastric acid output and serum gastrin levels after alkali or acid solution was infused into the untreated rat's stomach. Results were summarized as follows: 1. When I infused alkali solution into the untreated stomach, there was no significant change in serum gastrin level but gastric acid output was significantly accelerated, as compared with infusing acid solution. On the other hand, when I infused alkali solution into the vagotomized stomach, serum gastrin level increased significantly and gastric acid output was significantly accelerated, as compared with infusing acid solution, so, acceleration of acid output observed when I infused alkali solution into the untreated stomach was not suppressed in spite of vagotomy operation. 2. In the vagotomized group, gastric acid output was significantly suppressed and serum gastrin level increased significantly as compared with the untreated group. But, when bile was led into the stomach in the vagotomized group, acid output was accelerated and serum gastrin level also showed a tendency to increase as compared with the group of vagotomy alone. 3. When mild stress was inflicted, stress ulcer formation was significantly prevented in the bile reflux group (vagotomy + pyloroplasty) as well as in the non-bile reflux group (vagotomy + pyloric ligation + gastroileostomy) if vagotomy was done. But, when severe stress was inflicted, stress ulcer formation was significantly prevented in the non-bile reflux group, but not prevented in the bile reflux group. As mentioned above, it was proved that stress ulcer formation was not prevented under a severe stress, if bile reflux existed, even though vagotomy was done. So, if we do vagotomy operation, we need to choose the operation method not to induce bile reflux as much as possible.

Topics: Animals; Bile Reflux; Biliary Tract Diseases; Gastric Acid; Gastrins; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological; Vagotomy

The gastric mucosa of 19 mongrel dogs was submitted to a bilio-pancreatic, isolated biliary or isolated pancreatic reflux. With an isolated biliary reflux, there is a more rapid and more severe hyperaemia and foveolar hyperplasia of the mucosa of the fundus than with an isolated pancreatic reflux. There was no significant change in the basal serum level of gastrin with any of these different types of alkaline reflux, but we observed a statistically significant increase in the level of histamine in the gastric mucosa. Hyperaemia and foveolar hyperplasia of the fundic mucosa both disappeared when the alkaline reflux was suppressed, and there was a statistically significant decrease in the basal serum level of gastrin and in the level of histamine in the gastric mucosa.

Topics: Animals; Bile Reflux; Biliary Tract Diseases; Dogs; Duodenogastric Reflux; Gastric Mucosa; Gastrins; Gastritis; Gastrostomy; Histamine; Hyperemia; Jejunum; Time Factors

The chronic antral ulcer developed spontaneously in (WB X C57BL/6)F1-W/WV mice. Natural history of the ulcer was investigated to make clear the mechanisms involved in the development of ulcer in this mutant mouse. Although no histopathologic abnormalities of the stomach were detected at the fifth day after birth, erosions developed at the tenth day and the severity of the ulcerative lesions advanced with age. Antral pH of the W/WV mice was higher than that of the congenic +/+ mice, and the content of gastrin in the glandular stomach of the former was lower than that of the latter. Therefore, hyperacidity cannot be the cause of the ulcer in the W/WV mice. Bilirubin was demonstrable in the stomach contents of the suckling W/WV mice. After subcutaneous injection of [35S]sulfobromophthalein, the 35S radio-activity in the stomach contents of the 10-day-old W/WV mice was about 40 times as great as that observed in the +/+ littermates. As the peak of the bile reflux occurred shortly before the development of obvious ulcer that penetrated beyond the muscularis mucosae, the bile reflux could be a cause rather than a result of the ulcer.

Topics: Animals; Bile Reflux; Biliary Tract Diseases; Bilirubin; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Male; Mice; Mice, Mutant Strains; Pyloric Antrum; Rats; Stomach Ulcer