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PubMed2005

Effects of bile reflux on gastric mucosal lesions in patients with dyspepsia or chronic gastritis.

AIM: To investigate the influences of bile reflux on profiles of gastric mucosal lesions in patients with dyspepsia or chronic gastritis. METHODS: A total of 49 patients diagnosed with dyspepsia and chronic gastritis underwent 24-h ambulatory and simultaneous monitoring of intragastric bilirubin absorbance and pH values, and then they were divided into bile reflux positive group and bile reflux negative group. Severity of pathological changes in gastric mucosa including active inflammation, chronic inflammation, intestinal metaplasia, atrophy and dysplasia as well as Helicobacter pylori (H pylori) infection at the corpus, incisura and antrum were determined respectively according to update Sydney system criteria. The profiles of gastric mucosal lesions in the two groups were compared, and correlations between time-percentage of gastric bilirubin absorbance >0.14 and severity of gastric mucosal lesions as well as time-percentage of gastric pH >4 were analyzed respectively. RESULTS: Thirty-eight patients (21 men and 17 women, mean age 44.2 years, range 25-61 years) were found existing with bile reflux (gastric bilirubin absorbance >0.14) and 11 patients (7 men and 4 women, mean age 46.2 years, range 29-54 years) were bile reflux negative. In dyspepsia patients with bile reflux, the mucosal lesions such as active inflammation, chronic inflammation, intestinal metaplasia, atrophy or H pylori infection in the whole stomach, especially in the corpus and incisura, were significantly more severe than those in dyspepsia patients without bile reflux. Moreover, the bile reflux time was well correlated with the severity of pathological changes of gastric mucosa as well as H pylori colonization in the near-end stomach, especially in the corpus region. No relevance was found between the time of bile reflux and pH >4 in gastric cavity. CONCLUSION: Bile reflux contributes a lot to mucosal lesions in the whole stomach, may facilitate H pylori colonization in the corpus region, and has no influence on acid-exposing status of gastric mucosa in patients with dyspepsia or chronic gastritis.

Adult↗
PubMedDate not supplied

Importance of bile reflux in Barrett's esophagus.

Barrett's esophagus (BE) is an acquired condition in which the squamous epithelial lining of the lower esophagus is replaced by a columnar epithelium due to chronic gastroesophageal reflux. The role of acid and bile in the development of esophageal mucosal injury and the formation of BE is controversial. Acid and pepsin are unquestionably important in causing mucosal damage and BE formation in both animal models and humans. Animal studies suggest the potential for synergistic damage from conjugated bile acids and gastric acid, as well as from unconjugated bile acids and trypsin in more neutral pH settings. Evidence of the involvement of bile and its constituents in humans has been less conclusive; however, the advent of better technology to detect bile reflux is beginning to clarify the role of these constituents. Human studies show that the reflux of bile parallels acid reflux and increases with the severity of gastroesophageal reflux disease, being most marked in BE. However, recent ex vivo studies suggest that pulses of acid reflux may be more important than bile salts in the development of dysplasia or adenocarcinoma in Barrett's epithelium. Nevertheless, antireflux surgery and aggressive acid suppression with proton pump inhibitors will decrease both acid and bile refluxes, and eliminate the synergism between these two duodenogastric constituents.

Animals↗
PubMed1989

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↗
PubMedDate not supplied

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↗
PubMed2000

Detection of bile reflux: in vivo validation of the Bilitec fibreoptic system.

The Bilitec ambulatory bile reflux monitor is advocated for the assessment of bile reflux. However, it has only been validated by bench top (in vitro) studies. This in vivo study used controlled 'iatrogenic' episodes of bile reflux to determine the ability of the Bilitec system to detect bile acids in the oesophageal lumen. At least 10 ml of fluid was aspirated from the stomach of each of 32 patients, and analysed quantitatively for total bile acids (TBA) and total bilirubin (TB). An in vitro assessment of this fluid with the Bilitec probe was performed initially. The Bilitec probe was then sited in the distal oesophagus, and the gastric fluid was introduced into the mid-oesophagus, through a naso-oesophageal tube, as a series of 10-ml volumes of varying dilutions (1:8, 1:4, 1:2, undiluted) to simulate gastro-oesophageal reflux events. Intraoesophageal bilirubin absorbance was compared with TBA and TB for each dilution. Both TBA and TB values correlated strongly with bilirubin absorbance in vitro (r = 0.83, p < 0.0001 and r = 0.82, p < 0.0001 respectively). However, this relationship was weaker in vivo (r = 0.64, p = 0.0001 and r = 0.68, p < 0.0001 respectively). Of the dilutions which contained potentially injurious concentrations of bile acid (>1 mmol/L), 77% were associated with absorbance >0.14 (currently accepted absorbance threshold for oesophageal bile reflux). Although in vitro sensitivity of the Bilitec probe to bile acids was excellent, in vivo sensitivity was less reliable, and 23% of significant 'bile reflux' episodes did not exceed the currently recommended Bilitec absorbance threshold for bile reflux. In contrast, false-positive results were unlikely. These findings suggest that the overall accuracy of the Bilitec system is probably sufficient for clinical use, although this method is not sufficiently reliable to be regarded as the gold standard for the evaluation of duodeno-oesophageal reflux.

Adult↗
PubMed1971

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↗
PubMed1983

[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↗
PubMed1999

Bile reflux into the esophagus. Bilitec 2000 measurements in normal subjects and in patients after Nissen fundoplication.

BACKGROUND: Bilitec 2000 is a new spectrophotometric system that can detect bilirubin within the esophagus. The aim of this study was to test this new system in vitro and in vivo with special attention to patients operated on laparoscopically for gastroesophageal reflux with Nissen fundoplication. METHODS: In vitro studies of gallbladder bile dilution curves at different pHs were performed with a combined pH and Bilitec probe and by investigation of the drift of the Bilitec system. In vivo studies were performed in 34 normal individuals and 12 patients operated on with a laparoscopic Nissen fundoplication. Intra/intervariations were evaluated in normal individuals. RESULTS: The Bilitec system was able to detect changes in absorbance value within the range 0.14-0.6. Absorbance values were about 30% lower in an acid environment. The percentage of the total time with bile reflux was a median (range) of 3.9 (0-49.6) in normal individuals, with an intravariation within the intervariation, and 8.7 (0-36.6) in patients after a Nissen fundoplication. These values did not differ significantly. Eighty-two per cent of the normal subjects had some degree of bile reflux, if an absorbance value > or = 0.14 was accepted as the threshold value for the presence of bile reflux. CONCLUSIONS: Bile reflux in normal individuals is frequent and not different from that in patients after a Nissen fundoplication. Surprisingly, the latter had bile reflux but no or minimal acid reflux. Factors other than bilirubin may interfere with the measurements.

Adult↗
PubMed1995

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↗
PubMed1993

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↗
PubMed1984

Duodenogastric bile reflux in patients with gastric ulcer.

The duodenogastric bile reflux rate in 33 patients with gastric ulcer is compared with the rates in 33 non-ulcer patients. Duodenogastric bile reflux was measured by a non-invasive isotope method using 99mTc-diethyliminodiacetic acid. Reflux occurred significantly oftener in the ulcer patients (27 of 33) than in the non-ulcer patients (14 of 33) (p less than 0.01) but did not differ significantly in quantity between these two groups. The results suggest that the magnitude of bile reflux cannot be used to distinguish between ulcer patients and non-ulcer patients.

Adult↗
PubMed2003

Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux.

BACKGROUND: The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid. AIM: To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux accompanied by erosive or non-erosive reflux disease. METHODS: Thirty-eight symptomatic patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH-metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient). RESULTS: Twenty-two patients with gastro-oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro-oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro-oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro-oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 microm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P < 0.001). No statistical differences were observed between erosive and non-erosive oesophagitis. CONCLUSIONS: The dilated intercellular space is an extremely sensitive marker of damage in gastro-oesophageal reflux disease, duodenal gastro-oesophageal reflux and non-erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non-erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 micro m provides a cut-off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.

Adult↗
PubMed1984

A prospective randomized study of effect of proximal gastric vagotomy and vagotomy and antrectomy on bile reflux, endoscopic mucosal abnormalities and gastritis.

71 patients participated in a double-blind trial which compared proximal gastric vagotomy (PVG) with vagotomy and antrectomy (V & A). 82 percent of the patients subsequently volunteered for endoscopy 6 to 12 months after operation and 65 percent for measurement of fasting bile reflux (FBR) and peak acid output (PAO). The results of these follow-up assessments are given in this paper. None of the 36 patients who had undergone V & A had a recurrent ulcer; in contrast ulcers or fresh scars were found in 5 of 35 patients after PGV, even in 2 who had no symptoms. Erythema of the gastric mucosa was seen more commonly after V & A than PGV. Such erythema was associated with high levels of fasting bile reflux (an objective measure of reflux of bile into the stomach) and with symptoms of bile vomiting and mild epigastric pain. High levels of fasting bile reflux were not found after PGV. Histological gastritis of the proximal stomach was equally common after both operations in patients without a recurrent ulcer. Gastritis was not related to endoscopic mucosal erythema or fasting bile reflux, but did correlate with peak acid output. These results confirm that bile reflux is associated with mucosal erythema and symptoms after V & A but that significant bile reflux does not occur after PGV. However, bile reflux is not related to gastritis, which appears to be the result of an operation (either PGV or V & A) which successfully reduces peak acid output.

Adult↗
PubMed1998

Chemical meningitis from bile reflux in a lumbar-gallbladder shunt.

OBJECTIVE AND IMPORTANCE: The gallbladder is used to divert cerebrospinal fluid (CSF) in patients with hydrocephalus when all other sites have been exhausted. This is seen in hydrocephalic patients who have reached teenage years but have undergone multiple shunt revisions, abdominal operations and repeated neck vein cannulations during childhood. One complication of the lumbar-gallbladder shunt is discussed as well as its pathophysiologic theory and management. CLINICAL PRESENTATION: A case of a patient with a lumbar-gallbladder shunt who developed chemical meningitis from reflux of bile into the CSF space is presented. The patient presented with generalized seizures. INTERVENTION: Included: ventilatory support, externalization of the shunt, correction of the metabolic abnormalities and administration of anticonvulsants and steroids. CONCLUSION: This case illustrates an unusual occurrence of reflux of bile into the CNS through a lumbar-gallbladder shunt in a patient with long-term complex communicating hydrocephalus. It also demonstrates its mode of presentation and successful management. To our knowledge, this is the first case report of its kind.

Adult↗
PubMed2004

Inflammation of the gastric remnant after gastrectomy: mucosal erythema is associated with bile reflux and inflammatory cellular infiltration is associated with Helicobacter pylori infection.

BACKGROUND: Controversy exists concerning the role of bile reflux and Helicobacter pylori ( H. pylori) infection in the development of inflammation of the gastric remnant after gastrectomy. This study was designed to investigate association of bile reflux and H. pylori infection or both with inflammatory changes in the gastric remnant. METHODS: A questionnaire on GI symptoms was returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of H. pylori infection and chronic, active inflammatory cellular infiltration in the biopsy specimens were examined microscopically with the updated Sydney system. RESULTS: No difference in the incidence of GI symptoms was observed among individual gastrectomy patients. Bile reflux was lower in patients who had undergone a gastrectomy with jejunal interposition, a pylorus-preserving gastrectomy, and a gastrectomy with Roux-Y anastomosis than those who had undergone a Billroth-II (B-II) anastomosis ( P < 0.05). Endoscopy showed positive correlation between mucosal erythema and bile reflux ( P < 0.001). No correlation was observed between the mucosal erythema and chronic and active inflammatory cellular infiltration. Infection of H. pylori correlated with chronic and active inflammatory cellular infiltration ( P < 0.001). Bile reflux did not correlate with the severity of chronic and active inflammatory cellular infiltration or H. pylori infection. CONCLUSIONS: Bile reflux into the gastric remnant was observed by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell infiltration in the gastric remnant after gastrectomy may be caused by bile reflux or H. pylori infection, respectively.

Bile Reflux↗
PubMed2003

Dual-radionuclide simultaneous biliary and gastric scintigraphy to depict surgical treatment of bile reflux.

Biliary diversion procedures are performed during gastric surgery to decrease bile reflux. A 1-day dual-radionuclide examination was studied to determine its potential in the evaluation of the effectiveness of the Braun enteroenterostomy in reducing bile reflux and its effects on gastric emptying. Orally ingested gallium 67-labeled egg and intravenously administered technetium 99m diisopropyl-imino-diacetic acid were imaged simultaneously. This provided a way to depict both bile reflux and gastric emptying on the same day in patients who underwent gastric surgery. Overall, the Braun enteroenterostomy trades bile reflux, a symptomatic and premalignant disease, for gastroparesis, a less severe and often treatable disease.

Bile Ducts↗
PubMed2005

Bile reflux into the stomach and the esophagus for volunteers older than 40 years.

BACKGROUND: An increased incidence of Barrett's esophagus in cases with combined acidic and bile reflux is reported. The volunteers serving as controls in those studies were significantly younger than the patients. The aim of this study was to analyze bile reflux patterns of healthy volunteers aged comparably to patients with Barrett's esophagus. SUBJECTS AND METHODS: 19 older (8 f, 11 m; median age 51 years) (OV) and 20 younger (10 f, 10 m; median age 25 years) (YV) healthy volunteers without history of gastrointestinal disease or medication underwent simultaneous 24-hour pH and bile monitoring (Bilitec). All subjects consumed a special diet that did not interfere with bile measurements. Indicators for bile reflux in the stomach and esophagus: bilirubin probe absorption >0.25 in total measuring period (TM), upright position (excluding postprandial periods) (UP) and supine period (SP). RESULTS: There were no differences between older and younger volunteers in pH monitoring. Comparing the periods of bilirubin exposure of the stomach, the median (lower and upper quartile) percentage of time was OV = 5.7% (1.0-15.0%) and YV = 3.5% (0.1-7.8%) respectively for TM (n.s.), OV = 3.1% (0.7-9.4%) and YV = 0.4% (0.0-7.1%) for UP (n.s.), and OV = 2.1% (0.2-16.7%) and YV = 5.9% (0.0-12.2%) respectively for SP (n.s.). In 10/19 older volunteers and in 18/20 younger volunteers, no reflux of bile into the esophagus was measured. However, 4 older volunteers presented bile reflux from 4.6 to 51% of the total measuring period in contrast to the younger group with a maximum of 1.3% of TM. CONCLUSION: No significant differences in bile reflux into the stomach were distinguishable between younger and older healthy volunteers, but older volunteers more frequently exhibited bile reflux into the esophagus.

Adult↗
PubMed1996

Fiberoptic technique for 24-hour bile reflux monitoring. Standards and normal values for gastric monitoring.

Physiologic bile reflux was assessed in 27 in vivo test with healthy volunteers to define a standardized protocol and normal values for 24-hour enterogastric bile reflux monitoring (protocol with supine, upright, and meal phases and a free diet avoiding alcohol, smoking, and coffee, evaluation with different thresholds of absorbance units: 0.14, 0.25). In vitro tests with bile-sodium solutions demonstrated a linear dependence of absorbance for bilirubin up to 600 mumol/liter (range of the fiberoptic device: 0.0-1.0). Fluids and food might interfere with absorbances below 0.25 (exception: coffee). In vivo bile often remains in the stomach for more than 1 hr; these events were defined as reflux episodes. The upper limits for physiologic bile reflux are a percentage of total time of bile reflux of 28.2% and an average absorbance during a reflux episode of 0.62 (95th percentile with threshold 0.25). Comparing bile with pH monitoring (absorbance > 0.25 and/or pH > 4), an increase of bilirubin was found most frequently with constant pH (45%) or an increase of pH with constant bilirubin (36%). The hypothesis was drawn that bile and duodenal or pancreatic secretions may separately contribute to duodenogastric reflux.

Adult↗