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Bile reflux gastritis.

Bile reflux gastritis is a disabling postgastrectomy condition characterized by abdominal pain, bilious vomiting, and weight loss. The syndrome appears to be caused by free enterogastric reflux of bile and other proximal small bowel constituents. Endoscopic confirmation of bile reflux and documentation of gastritis support the diagnosis but are not specific for it. Results of medical therapy with chelating agents or drugs that promote gastric motility have been disappointing. Diet and antacids frequently aggravate symptoms. The only effective treatment is surgical diversion of bile away from the gastric mucosa. During a recent seven-year period, 15 patients had diversionary operation for bile reflux gastritis diagnosed by history and endoscopic findings. Before operation, medical management had failed to yield improvement in any case. After operation, all patients showed improvement, and pain was relieved in 85%. Based on our experience, we conclude that current medical therapy may alter but not cure symptoms of bile reflux gastritis; Roux-en-Y diversion is the treatment of choice in patients with persistent symptoms; and delayed gastric emptying is a common complication after the Roux-en-Y procedure, but in our series, the incidence was reduced by using the Tanner 19 modification. New cytoprotective agents that may offer an alternative to operation are currently being studied.

Adult

The clinical significance of bile reflux.

Although bile reflux into the stomach has been a subject of major interest during the last 15 years, its role in gastric pathology is not fully understood. The simple technique of sampling gastric contents and measuring bile acids is probably the most useful and reliable method available. Whether the reflux always precedes ulceration or is caused in some way by the gastritis remains unresolved, for bile reflux is common in many clinical situations where gastritis is present. After gastric surgery bile has been blamed for the gastritis which occurs as well as symptoms of post prandial epigastric discomfort, heartburn and bile vomiting. This is probably the only clinical situation where further procedures have been examined which specifically divert bile away from the stomach with good results. Bile reflux is also very common in patients with heartburn suggesting that bile and acid are both necessary to produce oesophagitis and heartburn. This is borne out by clinical observations and experimental work in animals. With the exception of those patients who have had gastric surgery, we have little or no evidence of the consequences of bile exclusion from the stomach in other pathological situations.

Bile Acids and Salts

Gallbladder function and fasting enterogastric bile reflux.

The relationship between gallbladder function and duodenogastric reflux of bile has been investigated in the fasting phase by 99Tcm-EHIDA biliary scintigraphy in 370 patients with abdominal pain. This isotope is cleared from the blood-pool by hepatocellular function and is excreted into the biliary tract. Obstruction of the common bile duct was found in 79 patients, leaving 291 who were evaluable for duodenogastric bile reflux. Gallblader function was present in 169 and absent in 122 patients. Duodenogastric reflux of bile was observed in 82 patients, 10 of whom had had previous gastric surgery. Only 298 of 169 (17%) patients with a functioning gallbladder showed evidence of enterogastric bile reflux compared to 43 of 122 (35%) with absent gallbladder function (p less than 0.005 by Chi Square). These results suggest that continuous bile flow into the duodenum in the absence of a functioning gallbladder facilitates duodenogastric reflux.

Adult

[Clinical characteristics of bile reflux gastritis].

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.

Adult

[An experimental study on the effect of vagotomy on stress ulcer and the influence of bile reflux].

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.

Animals

Spontaneous bile reflux in the elderly.

Duodenogastric bile reflux is common in postoperative stomach but has been reported in intact stomachs. Spontaneous bile reflux in the elderly has not been studied before. This has been assessed in dyspeptic elderly and young patients. Total bile acid (TBA) levels and pH were measured in the samples of fasting gastric juice. Antral biopsies were taken for histological examination including Helicobacter pylori identification. TBA levels were significantly higher in elderly patients with gastritis in comparison to elderly and young normal groups. Only 10% of elderly patients with gastritis and 7% with gastric ulcer has abnormal TBA (> 1 mmol/l). There was some correlation between the pH and TBA but a significant proportion of elderly patients has pH > 4 with a normal TBA. TBA levels were not significantly different in H. pylori +ve and H. pylori -ve patients. Nineteen elderly patients had evidence of reactive gastritis. Five of these patients had raised TBA levels with severe H. pylori infection. The remaining 15 patients had normal TBA. These patients were on NSAIDs and 4 of them had H. pylori infection. We conclude that spontaneous bile reflux in the elderly is uncommon. Hypochlorhydria which is observed in the elderly is not caused by alkaline bile reflux. The main cause of reactive gastritis in the elderly is NSAIDs ingestion.

Adult

The relationship between acid and bile reflux and symptoms in gastro-oesophageal reflux disease.

BACKGROUND: The role of bile in the genesis of oesophageal symptoms and disease is incompletely understood. A new method of ambulatory bile monitoring may help to define this role. AIMS: To establish the relationship between symptom events and acid and bile reflux episodes. PATIENTS: 59 consecutive patients presenting for further investigation of gastro-oesophageal reflux disease. METHODS: All patients underwent combined ambulatory pH and bile monitoring. For each patient, a symptom index (SI) was calculated in relation to both acid reflux and bile reflux episodes. RESULTS: Patients were divided into those without (group 1, n = 21) and those with (group 2, n = 38) acid reflux. A total of 394 symptoms were identified in 59 patients. In group 1, there were fewer symptom events per patient (mean 4.1) than group 2 (mean 8.1). Twenty three per cent of symptom events were associated with acid reflux in group 1 and 41% in group 2. Only 6% of symptom events in both groups were related to bile reflux. In group 1 both the acid and bile related SI score were low. In group 2 the bile related SI score was low, but the acid related SI score was high. CONCLUSIONS: Symptoms are much more often related to acid reflux than bile reflux. Bile reflux does not seem to be a major factor in producing oesophageal symptoms.

Adult

Gastric pathology in cholecystectomy patients: role of Helicobacter pylori and bile reflux.

The data regarding the role of Helicobacter pylori infection in patients with bile reflux are conflicting. Bile reflux is often observed after cholecystectomy. This study focuses on the role of H. pylori in gastric pathology of patients who had undergone cholecystectomy. Eighty-seven consecutive patients were included in the study. An upper gastrointestinal endoscopy was performed, and biopsy specimens were taken in the antrum, incisura angularis, and in the gastric body. The presence of bile reflux in gastric fluid at endoscopic examination was recorded. The overall H. pylori infection rate was 62%, with no difference between patients with (59.7%) and without (64%) endoscopic bile reflux (p = 0.67). The intestinal metaplasia rate in gastric mucosa was significantly higher in patients with both H. pylori and bile reflux than in patients without infection and bile reflux (36.4% vs. 5.6%, p = 0.02). Moreover, the mean number of years after cholecystectomy in patients with intestinal metaplasia was significantly higher than in those without metaplasia (21.1 +/- 7 vs. 11.5 +/- 8 years, p < 0.0001), whereas mean age did not differ significantly between groups (60.3 +/- 12 vs. 55.8 +/- 11 years, p = 0.14). Furthermore, we found four cases of gastric cancer, three with H. pylori infection. The mean number of years after cholecystectomy was significantly higher in patients with gastric cancer than in other patients (21.8 +/- 4 vs. 12.2 +/- 8 years, p = 0.009). This study found that H. pylori infection is frequent in cholecystectomized patients, also in the presence of endoscopic bile reflux. Bile reflux seems to act synergistically with H. pylori infection on gastric pathology.

Adult

Healthy controls have as much bile reflux as gastric ulcer patients.

Data on duodenogastric reflux of bile in gastric ulcer are conflicting. We therefore measured intragastric bile acid concentration and its composition from individual bile acids, duodenogastric bile acid reflux rate, gastric emptying rate, and secretion rates of volume and acid in 30 patients with gastric ulcer and in 66 healthy controls, both in the fasting state and after feeding a liquid meal. Patients had higher gastric bile acid concentrations (p less than 0.05) than controls in the fasting state, but the overlap between the groups was considerable. In fasting patients with corpus ulcer, gastric secretion rates were significantly decreased when compared with controls. There was no difference between patients and controls with respect to gastric emptying rate, bile acid reflux rate, intragastric amount of bile acids, and bile acid composition in the fasting state. Postprandially, all parameters tested were similar in patients and controls. Controls showed high reflux rates with similar frequency as did ulcer patients. We conclude that increased gastric bile acid concentrations in the fasting stomach of patients with gastric ulcer are the result of gastric hyposecretion and not of increased reflux. They probably are pathogenetically irrelevant.

Adult

The significance of gastric bile reflux seen at endoscopy.

We evaluated the significance of bile seen in the stomach at the time of endoscopy. Twenty-three percent of 110 consecutive patients undergoing elective panendoscopy were found to have bile in their stomachs. Gastric biopsies were obtained from these patients. To assess the significance of bile reflux, the patients underwent a quantitative gastric bile analysis on two separate days. On day 1, gastric juice was aspirated by nasogastric suction, and bile acid concentrations were measured. On day 2, bile reflux into the stomach was quantitated by scintiscan measurement of gastric nucleotide after intravenous administration of 99mTc-DISIDA. Approximately half the patients with bile reflux showed histologic evidence of mucosal injury. However, fewer than half with histologic injury had significant bile reflux when measured by quantitative methods. There was no correlation among the gastric bile acid concentration, degree of histologic injury, or severity of endoscopic changes. We conclude that finding bile reflux at endoscopy is probably of no clinical significance.

Bile Reflux

Ursodeoxycholic acid treatment of bile reflux gastritis.

Intractable epigastric pain associated with nausea and bilious vomiting often follows gastric surgery and has been attributed to reflux of bile and the irritating effects of endogenous bile acids on the gastric remnant. To test the effect of changing bile acid composition of the refluxed material on the symptoms and gastric mucosal histology, 12 patients with symptomatic alkaline reflux gastritis were treated for 1 mo with placebo and for 1 mo with ursodeoxycholic acid, 1000 mg/day. Before treatment, all patients were symptomatic and manifested epigastric pain, nausea, and bilious vomiting. The gastric mucosa was erythematous, friable, and bile stained, and the histology revealed chronic inflammation. No significant change in symptoms was noted during administration of placebo. In contrast, ursodeoxycholic acid treatment resulted in a profound decrease in the intensity and frequency of pain and almost abolished nausea and vomiting. During bile acid therapy the proportion of ursodeoxycholic acid in gastric bile rose to 50% of total bile acids, whereas cholic and deoxycholic acids decreased and chenodeoxycholic acid remained unchanged. The macroscopic and microscopic appearance of the gastric mucosa, however, did not change after 1 mo of ursodeoxycholic acid treatment. These results suggest that increasing the proportion of ursodeoxycholic acid in refluxed gastric bile reduces the pain and frequency of symptoms associated with bile reflux.

Adult

The clinical pattern of duodenogastric bile reflux in the Kenyan Africans.

Forty consecutive African patients found to have duodenogastric bile reflux at endoscopy were studied. Bile reflux was found more commonly among males than females, giving a male/female ratio of 2.3:1, with a peak age at 41-60 years. ABO blood groups had no significant influence on duodenogastric bile reflux. Flatulence and borborygmi were the most consistent symptoms other than the classical dyspeptic pain pattern. Bilious vomiting was a rare finding. Duodenogastric bile reflux was more commonly associated with endoscopic gastritis (67.5%), gastric ulcer (35%) and oesophagitis (30%) than with duodenal ulcer (22.5%), deformed pyloric ring (5%) or distorted duodenal bulb (2.5%). The dysfunction in the pyloric sphincter in people with duodenogastric bile reflux appears to be more of a physiological defect than structural.

Adult

Bile reflux in benign and malignant Barrett's esophagus: effect of medical acid suppression and nissen fundoplication.

Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett's esophagus, but clinical studies in patients with adenocarcinoma arising in Barrett's esophagus are lacking. Ambulatory esophageal measurement of acid and bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH probe in 20 asymptomatic volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients with GERD and erosive esophagitis, 33 patients with GERD and Barrett's esophagus, and 14 patients with early adenocarcinoma arising in Barrett's esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after laparoscopic Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients without esophagitis to those with erosive esophagitis and benign Barrett's esophagus and was highest in patients with early carcinoma in Barrett's esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients with benign Barrett's esophagus and 11 (78.6%) of 14 patients with early adenocarcinoma in Barrett's esophagus. Nissen fundoplication but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly prevalent in patients with Barrett's esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed by Nissen fundoplication but not medical acid suppression alone.

Adenocarcinoma

The effect of healing on bile reflux in gastric ulcer.

Bile reflux has been studied by serial estimations of bile acid concentrations in the stomach before and after a liquid meal. Thirteen normal subjects and 38 patients with gastric ulcer were examined. Thirty-one in the ulcer group had the test repeated once or twice within two months of the initial test to observe any change in reflux associated with healing. Patients with gastric ulcer had significantly higher concentrations of bile acids than normal subjects, both before and after the meal, although there was an overlap between the groups. In patients with an ulcer which healed or showed some healing over two months, no consistent change in reflux was found.

Bile

[Scintigraphic image of bile reflux following gastric and intestinal surgery].

Bile reflux may occur after a variety of reconstructive procedures in the gastro-intestinal tract and biliary system. The present paper deals with reflux into the duodenum, jejunum, stomach, oesophagus and into blind loops. The demonstration of reflux by 99mTc labelled IDA acid derivatives, and a possible quantitative approach, are discussed. The advantages of an isotope method are: 1. Direct demonstration of bile reflux without any intervention in the physiological process and with little trouble to the patient, 2. The ability to use the method for various reconstructive procedures and 3. The additional information obtained which may help in the differential diagnosis of blind loops, biliary obstructions, cholecystitis or liver metastases if there has been a gastrectomy for a malignant tumour. In combination with a second administration of a radio-isotope tracer, one may be able to demonstrate abnormalities in the motility of the stomach or gut, or pyloric stenosis or gastro-oesophageal reflux.

Bile Reflux

Ambulatory oesophageal bile reflux monitoring in Barrett's oesophagus.

Bile reflux has been implicated in the pathogenesis of Barrett's oesophagus but evaluation remains difficult. Bilitec 2000 is an ambulatory system that detects bilirubin based on its spectrophotometric properties. Oesophageal bile exposure was evaluated in three groups of patients. Group 1 (n = 11) were normal controls, group 2 (n = 13) were patients with uncomplicated gastro-oesophageal reflux and group 3 (n = 12) were patients with Barrett's oesophagus. Bile reflux was greater in patients with Barrett's mucosa than in controls or those with uncomplicated reflux. This difference was seen in the supine and interdigestive periods. The percentage of time at which gastric pH was greater than 4 and oesophageal pH was above 7 did not differ between the groups. Bilitec 2000 detects greater bile reflux in patients with Barrett's oesophagus. No corresponding gastric or oesophageal alkaline shift is found. This ambulatory bile reflux monitoring system may be a useful tool in clinical practice.

Adolescent

Bile reflux and intestinal metaplasia in gastric mucosa.

AIM: To determine associations between enterogastric bile reflux and gastric mucosal pathology. METHOD: A retrospective study using fasting gastric juice bile acid measurements and antral or prestomal biopsy specimens from 350 patients, 66 of whom had previously undergone surgery that either bypassed or disrupted the pyloric sphincter. RESULTS: Bile reflux was positively associated with reactive gastritis and negatively with Helicobacter pylori density. After stratification for previous surgery, age, and H pylori status, the histological feature most strongly associated with bile reflux was intestinal metaplasia, including all its subtypes. The prevalence of intestinal metaplasia was greatest in patients with both H pylori infection and high bile acid concentrations. Bile reflux was also positively associated with the severity of glandular atrophy, chronic inflammation, lamina propria oedema and foveolar hyperplasia. CONCLUSIONS: Bile reflux is a cause of reactive gastritis. It modifies the features of H pylori associated chronic gastritis. The changes are not confined to patients who have had surgery to their stomachs. The positive associations with atrophy and intestinal metaplasia have implications for models of gastric carcinogenesis.

Adolescent