Bile Reflux Gastritis Research Articles

Clinical and radionuclide evaluation of bile diversion by Braun enteroenterostomy: prevention and treatment of alkaline reflux gastritis. An alternative to Roux-en-Y diversion.

OBJECTIVE AND SUMMARY BACKGROUND: Symptomatic, medically resistant postgastrectomy patients with alkaline reflux gastritis (ARG) have increased enterogastric reflux (EGR) documented by quantitative radionuclide biliary scanning. Even asymptomatic patients after gastrectomy have increased EGR compared with nonoperated control patients. Roux-en-Y biliary diversion, although successfully treats the clinical syndrome of ARG, has a high incidence of early and late postoperative severe gastroparesis, Roux limb retention (the Roux syndrome), or both, which often requires further remedial surgery. As an alternative to Roux-en-Y diversion, this review evaluates the efficacy of the Braun enteroenterostomy (BEE) in diverting bile away from the stomach in patients having gastric operations. Based on previous pilot studies, the BEE is positioned 30 cm from the gastroenterostomy. Thirty patients had the following operations and were evaluated: standard pancreatoduodenectomy (8), vagotomy and Billroth II (BII) gastrectomy (6), BII gastrectomy only (10), and palliative gastroenterostomy to an intact stomach (6). All anastomoses were antecolic BII with a long afferent limb and a 30-cm BEE. Four symptomatic patients with medically intractable ARG and chronic gastroparesis had subtotal BII gastric resection with BEE rather than Roux-en-Y diversion. Eight control symptomatic patients and six asymptomatic patients with previous BII gastrectomy and no BEE were evaluated. Radionuclide biliary scanning was performed within 30 days in all patients and at 4 to 6 months in 14 patients. Bile reflux was expressed as an EGR index (%). After operation, 18 of 34 patients (53%) had no demonstrable EGR while in the fasting state for as long as 90 minutes. The range of demonstrable bile reflux (EGR) in the remaining 16 patients was from 2% to 17% (mean, 4.5%). Enterogastric reflux in the 14 control patients (with no BEE) ranged from 5% to 82% (mean, 42%). The four patients with ARG and chronic gastroparesis treated by subtotal gastrectomy and BEE had postoperative EGR of 0%, 2%, 2%, and 4%, respectively. They are asymptomatic with no evidence of bile reflux gastritis. In the 14 patients who had late evaluation, EGR ranged from 0% to 16% (mean, 5.5%). No patient had signs or symptoms of ARG after operation. Braun enteroenterostomy successfully diverts a substantial amount of bile from the stomach. The ARG syndrome might be prevented by performing BEE during gastric resection or bypass in a variety of operations. Conversion to a BII with BEE may be an alternative to Roux-en-Y diversion in treating medically resistant ARG and subsequent may avoid the Roux syndrome.

The effect of bile acids on the growth and adherence of Helicobacter pylori

Bile reflux gastritis occurs in the absence of Helicobacter pylori (H. pylori). The aim of this study was to see if the bile acids cheno or ursodeoxycholic acid affected the growth or adherence of H. pylori in vitro. Twenty-seven strains growth were inhibited by 0.1% chenodeoxycholic acid whereas only 11 out of the 27 were inhibited by 0.1% ursodeoxycholic acid. Growth was totally inhibited by a combination of 0.05% chenodeoxycholic acid +0.05% ursodeoxycholic acid. Chenodeoxycholic acid was a more effective inhibitor of adherence in that the number inhibited and percentage inhibition were greater than with ursodeoxycholic acid. Bile salts might be useful in the treatment of H. pylori infection.

Complications associated with surgical treatment of congenital intrinsic duodenal obstruction

Although survival rates for infants undergoing surgical treatment for congenital intrinsic duodenal obstruction are high, long-term follow-up suggests a high complication rate related to surgical therapy. We reviewed 33 neonates who underwent surgery for congenital intrinsic duodenal obstruction during the past 10 years. There were 20 girls and 13 boys; the mean gestational age was 36 weeks, and mean birthweight was 2,485 g. Bilious vomiting and intestinal obstruction were the most frequent presenting symptoms. Hydramnios was present in 75% of cases and 21% had associated Down's syndrome. Findings at laparotomy included duodenal atresia (14), annular pancreas (11), and duodenal diaphragm (8). The most frequent surgical procedure was side-to-side duodenoduodenostomy (DD), followed by duodenojejunostomy and resection of web with Heineke-Mikulicz type duodenoplasty. Bowel transit was reestablished at a mean of 13.1 days (range, 6 to 45 days). Seventy-percent of patients developed postoperative complications, the most frequent being megaduodenum with blind loop syndrome or bile reflux gastritis (22%), cholestatic jaundice (17%), gastroesophageal reflux (17%), delayed transit (8%), and bowel obstruction (8%). Six patients (18%) required secondary surgical procedures for postoperative complications (ie, megaduodenum, nonfunctioning anastomosis, missed intrinsic stenosis). Two patients died (6%). Stagnation and functional obstruction in the proximal duodenum is the main factor influencing the morbidity rate among these patients. Consideration should be given to the tapering duodenoplasty and diamond-shaped anastomosis in order to help reduce problems associated with megaduodenum and help restore earlier bowel transit.

Manometric evaluation of the interdigestive antroduodenal motility in subjects with fasting bile reflux, with and without antral gastritis.

The interdigestive antroduodenal motor activity was studied in 15 patients with bile reflux without gastritis (group A), 17 with bile reflux and chronic antral superficial gastritis (group B) and in nine healthy controls (group C), by manometric recording of phases of the interdigestive motility complex (IDMC) over 240 minutes, or until two consecutive migrating motor complexes (MMCs) had been recorded, whichever the shorter. In the patients with bile reflux the occurrence of MMCs was decreased and median duration of the IDMC was significantly prolonged (group A = 162.5 min; group B = 185.0 min), compared with controls (group C = 92.0 min; p less than 0.01 v groups A and B). There were no differences in motility pattern between patients with and without gastritis, suggesting that motor abnormalities are not caused by gastritis, but may precede its occurrence. Delayed occurrence of motor activity fronts increases duodenogastric reflux, but correlation with gastric mucosal lesions was not shown, suggesting that other mechanisms are involved.

HPLC assay of conjugated bile acids in gastric juice during ursodeoxycholic acid (Deursil®) therapy of bile reflux gastritis

A rapid high-performance liquid chromatographic method for the direct assay of the taurine and glycine conjugated bile acids in human gastric juice is described. After extraction with Sep-Pak C 18 cartridges, compounds are baseline resolved on a reversed-phase column and detected by UV absorption. The procedure is linear from 10 μmol l −1 to 1200 μmol l −1, with recovery rates ranging from 87 to 100%. The present method is applicable to the quantification of bile acid conjugates in human gastric bile with satisfactory sensitivity, selectivity and precision. Intragastric bile acid compositions in 10 patients with bile reflux gastritis during Deursil® or placebo treatment are presented.

Simultaneous determination of free and conjugated bile acids in human gastric juice by high-performance liquid chromatography

A high-performance liquid chromatographic procedure has been developed for the simultaneous assay of the major free bile acids and the corresponding glycine and taurine conjugates in man. No preliminary fractionation into the free, glyco- and tauro-conjugated forms was required. An Ultrasphere ODS column with UV detection at 210 nm and methanol-acetate buffer gradient elution were used. The retention volume of the conjugates was dependent on the sodium acetate concentration in the mobile phase. The method is applicable to the quantification of intragastric bile acids with satisfactory sensitivity, selectivity and precision. Unconjugated and conjugated bile acids present in the gastric juice of patients with bile reflux gastritis were determined directly after Sep-Pak C 18 cartridge purification.

Esophagitis and gastroduodenal disorders associated with diabetic gastroparesis

• The prevalence of associated gastrointestinal disorders with diabetic gastroparesis was studied retrospectively by reviewing all data on patients with diabetic gastroparesis who were admitted to the Hospital of the University of Pennsylvania, Philadelphia, over a four-year period. Twenty diabetic patients with intractable nausea and vomiting, thought to be secondary to diabetic gastroparesis, underwent upper gastrointestinal tract endoscopy after failure to respond to conventional therapy for gastroparesis within several days. Nine (45%) patients had normal upper endoscopic examination results. Eleven (55%) patients were discovered to have other gastrointestinal tract disorders that could explain their persistent symptoms of nausea and vomiting. Specifically, three patients had<i>Candida</i>esophagitis, four had erosive esophagitis, two had gastric ulcers, one had duodenal erosions, and one had bile reflux gastritis. These 11 patients improved when therapy was altered to treat their additional disorder. Management of diabetic gastroparesis is discussed with emphasis on early upper gastrointestinal tract endoscopy for patients who fail to respond to therapy initially. (<i>Arch Intern Med</i>1987;147:1477-1480)

Esophagitis and Gastroduodenal Disorders Associated With Diabetic Gastroparesis

The prevalence of associated gastrointestinal disorders with diabetic gastroparesis was studied retrospectively by reviewing all data on patients with diabetic gastroparesis who were admitted to the Hospital of the University of Pennsylvania, Philadelphia, over a four-year period. Twenty diabetic patients with intractable nausea and vomiting, thought to be secondary to diabetic gastroparesis, underwent upper gastrointestinal tract endoscopy after failure to respond to conventional therapy for gastroparesis within several days. Nine (45%) patients had normal upper endoscopic examination results. Eleven (55%) patients were discovered to have other gastrointestinal tract disorders that could explain their persistent symptoms of nausea and vomiting. Specifically, three patients had Candida esophagitis, four had erosive esophagitis, two had gastric ulcers, one had duodenal erosions, and one had bile reflux gastritis. These 11 patients improved when therapy was altered to treat their additional disorder. Management of diabetic gastroparesis is discussed with emphasis on early upper gastrointestinal tract endoscopy for patients who fail to respond to therapy initially.

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.

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.

Effect of sodium taurocholate on the human gastric mucosa at acid and neutral pH's

This study was conducted to determine whether taurocholate alters human gastric function and structure at a neutral pH, when ionized, and to contrast this with its effect at an acid intraluminal pH, when pronated. Five fasted healthy subjects were studied on 4 days in random order. Net ion fluxes, mucosal damage (as quantitated endoscopically), and potential difference were measured. The control solution instilled into the stomach in the first, third, and fourth 15-min periods contained 200 ml of 100 mM HCl, 54 mM mannitol, and [14C]polyethylene glycol. Taurocholate (10 mM) was added to the control solution (pH 1.1) or citrate buffer (pH 7.0) during the second 15-min period. The effect of citrate buffer alone or control solution alone was also tested. Because hydrogen and sodium fluxes could not be quantitated at pH 7 in the presence of citrate buffer, the net ion fluxes during the 15 min immediately after exposure to the test agent were measured. At both pH 1.1 and 7.0 taurocholate produced similar and significant increases in net hydrogen ion flux (−1.7 ± 0.4 and −1.8 ± 0.3 mmol/15 min, respectively), net sodium ion flux (1.8 ± 0.4 and 1.7 ± 0.2 mmol/15 min, respectively), decreases in potential difference, and mucosal erosions. The net hydrogen ion fluxes were significantly greater than occurred after citrate buffer alone or the HCl control. The net sodium fluxes after taurocholate in citrate were significantly greater than the pH 1.1 acid control, but not citrate buffer alone. These findings indicate that pronated (pH 1.1) or ionized (pH 7.0) taurocholate significantly damaged the in vivo human gastric mucosa. Taurocholate at pH 7 could in part be responsible for the gastric mucosal injury that occurs in patients with bile reflux gastritis.

Searching for the best weight reduction operation.

At the University of Minnesota under the supervision of one staff surgeon both jejunoileal bypass (JIB) and gastric bypass (GIB) operations have been performed for weight reduction in morbidly obese individuals. During the last 14 years 727 patients underwent end-to-end (40 to 4 cm) JIB and more than 570 patients underwent GIB. This report is based on a comparison of 205 JIBs performed between July 1975 and July 1979, 106 Alden-loop type GIBs (GIB-loop) performed between July 1975 and July 1979, 53 loop GIBs with enteroenterostomies between the limbs of the loop (GIB-EE) performed between May 1980 and May 1981, and 57 Roux-en-Y GIBs (GIB-Roux) performed between May 1981 and May 1982. Adequate weight loss occurred in 80% of the patients who returned for follow-up in all groups. The percentage of excess body weight loss was similar for the first year (65% for JIB, 62% for GIB-loop, 69% for GIB-EE, and 71% for GIB-Roux). The operative mortality and the immediate morbidity rates were uniformly low. The long-term complications for JIB were 37.7% arthralgia, 7.1% oxalate urolithiasis, 5.6% incisional hernia, and 1.4% liver failure. The complications for GIB-loop were 10.2% nausea/vomiting, 1.9% bile reflux gastritis, and 2.8% anastomotic problems; for GIB-EE 23% nausea/vomiting, 7% bile gastritis, 4.6% incisional hernia, and 3.7% anastomotic problems; and for GIB-Roux 16% nausea/vomiting and 1.7% anastomotic problems. The anastomotic problems consisted of afferent loop obstructions and stomal stenosis; there were no leaks. At 1 year plasma cholesterol reduction for JIB averaged 42% (p less than 0.001), GIB-loop 14% (p less than 0.001), GIB-EE 7% (NS), and GIB-Roux 17% (p less than 0.001). One year after operation 49% of 88 JIB patients showed progression of liver disease on sequential biopsy specimens and 20% improvement. In the 78 GIB patients with sequential biopsies, liver disease progressed in 8% and improved in 65%. In summary, comparable therapeutic weight reduction occurred with all the assessed procedures; however, the GIB-Roux was associated with far fewer serious long-term complications. At this time the GIB-Roux procedure is the weight reduction operation we recommend.

Technical complications of Roux-en-Y gastrojejunostomy.

The Roux-en-Y gastrojejunostomy has become an increasingly popular technique for gastrointestinal tract reconstruction since it is purported to obviate many of the classic complications of the Billroth II gastrojejunostomy. In a review of over 900 Roux-en-Y gastrojejunostomies, seven patients with complications mimicking those seen with Billroth II reconstruction were identified. These complications included duodenal stump blowout, proximal blind loop or afferent loop syndrome, and bile-reflux gastritis. These complications resulted from technical problems in construction of the Roux-en-Y. Once the complications were diagnosed, they were amenable to operative correction. Recognition of the potential for these complications following Roux-en-Y gastrojejunostomy should aid in early diagnosis and treatment.

Postvagotomy and cholecystectomy syndrome.

Seventy-five patients with unsatisfactory results following vagotomy, drainage and cholecystectomy have been reviewed. The operations were performed together in 45 patients, vagotomy preceded cholecystectomy in 16 patients and cholecystectomy was performed before vagotomy in 14 patients. The interval between the two operations when cholecystectomy was performed first was 7.1 +/- 1.66 SE years, whereas when vagotomy was performed first this was 3.1 +/- 1.03 SE years (p less than 0.05). Forty-three patients had symptomatic bile reflux gastritis and 59 had postvagotomy diarrhea. Dumping, bilious vomiting and recurrent peptic ulceration occurred in 11 patients, nine and five patients, respectively, and were no more frequently encountered than would have been expected after vagotomy and drainage alone. In the light of the information derived from the addition of cholecystectomy to vagotomy and drainage a pathophysiology of postvagotomy diarrhea without dumping, and bile reflux gastritis without bilious vomiting or recurrent chronic peptic ulceration is postulated.

Intragastric alkali infusion: a simple, accurate provocative test for diagnosis of symptomatic alkaline reflux gastritis.

Alkaline reflex gastritis is a disabling clinical syndrome, occurring most often after gastric surgery. It is characterized by abdominal pain and bilious vomiting, and, presumably, is due to gastric irritation by regurgitated duodenal contents. The only known effective treatment is by surgical diversion to prevent the duodenal reflux. Unfortunately, the clinical diagnosis is difficult to prove, and the results of surgery are too often disappointing because of inaccurate patient selection. This is a report of a new test for distinguishing patients with symptomatic bile reflux gastritis. The test consists of blind sequential infusion into the stomach, via nasogastric tube, of 20 ml of 0.1 N HCl, normal saline, 0.1 N NaOH, and the patient's own gastric contents. Each solution is given twice. A positive test is defined as reproduction of the patient's usual pain by NaOH, and/or gastric contents, but not by acid or saline. Fifteen of 21 patients with clinical symptoms and endoscopic findings suggesting bile gastritis had a positive alkali infusion test, while only one of 18 normal controls and none of 17 controls with other causes of abdominal pain had a positive test (p less than 0.001). Of the 21 patients with clinical-endoscopic bile gastritis, 15 have had surgical treatment by Roux-en-Y gastrojejunostomy. Nine of ten patients with positive test had excellent symptomatic relief after surgery. Zero of five patients with a negative test were relieved of pain after the operation. Tis simple test appears to be a sensitive, specific, and accurate means for selecting patients for surgical treatment of alkaline reflux gastritis.

Biologic gastric emptying time using Tc-99m TETA polystyrene resin in various clinical conditions.

In 82 subjects 82 gastric emptying studies using Tc-99m triethylene tetramine polystyrene resin were retrospectively evaluated. All six patients with diabetic gastroenteropathy (GE) had delayed biologic gastric emptying time (BGET) that responded well to metoclopramide (MP) injection. In 11 diabetics without GE, only two had prolonged BGET with good response to MP. All 11 patients with gastric outlet obstruction also had prolonged BGET, but no significant response to MP was found in 7 studies. Five of 7 patients with active gastric ulcer had delayed BGET. Three of ten patients with previous Billroth I or II operation had accelerated BGET, and 3 of 9 patients with previous vagotomy had delayed BGET with good response to MP. Markedly prolonged BGET with significant response to MP was also observed in 3 patients with disordered gastric motility. Delayed BGET was found in one patient with bile reflux gastritis and in 2 of 6 patients with reflux esophagitis. No prolongation of BGET was observed in 6 symptomatic patients whose radiographic and endoscopic examinations were negative. BGET studies with this agent appear to be reliable and very helpful in the management of patients with gastric symptoms and for obtaining an objective measurement of the response to therapy.

The surgical treatment of bile reflux gastritis: a study of 59 patients.

Fifty-nine patients underwent duodenogastric diversion for bile reflux gastritis. Sixty per cent of 37 patients who underwent measurement of solid food gastric emptying had delayed gastric emptying. Patients were also assessed in terms of the degree of gastritis present endoscopically. Fifty-six patients were available for follow-up of from six months up to six years. The results demonstrated the following: Patients with delayed gastric emptying and reflux gastritis fared poorly after duodenogastric diversion; the greater the severity of gastritis visible by endoscopy, the better the results of diversion. Only 47% of patients achieved a satisfactory result of duodenogastric diversion.

Results of corrective surgery for alkaline reflux gastritis.

Reflux alkaline gastritis and esophagitis have been incriminated as a source of symptoms in achlorhydric patients afer operation for duodenal ulcer. Documentation of such pathologic findings has increased due to widespread use of fiberoptic endoscopy. As reported in the literature, results of remedial operations have ranged from encouraging to excellent, and evaluations have been uniformly laudatory. Correlation of the extent of symptoms and of pathologic findings has been difficult, and our results have not been as good as those reported in the literature. During a six-year period, the diagnosis of bile reflux gastritis in 13 patients was based on a characteristic symptom complex, endoscopic appearance, and histopathologic confirmation. Either a Roux-en-Y gastrojejunostomy or a Tanner-Roux 19 was the corrective procedure. There was complete relief of symptoms in five patients (38%) and partial relief in four, but no apparent relief in four others. In at least three of the patients, chronic gastritis and/or esophagitis have persisted and have not improved despite biliary diversion. Tabulation of the results of 13 remedial operations for reflux alkaline gastritis disclosed that copmlete relief of symptoms was achieved in 50% of those who had the Roux-en-Y and in 20% of those who had the Tanner 19 procedure. Based on our findings, we recommend a cautious approach to the surgical management of alkaline gastritis.

Immunofluorescence Study of Mucosal B Lymphocytes in Bile Reflux Gastritis

Intracelluar immunofluorescence staining was used to identify lymphoid cells from human gastric mucosa. Staining of serial sections for each of the five classes of immunoglobulin-containing cells revealed the presence of all classes. Their relative frequencies in the antral mucosae of 30 patients with bile reflux gastritis were 51% IgA, 16% IgM, 18.5% IgG, 2.5% IgD and 12% IgE. The mucosae of 15 control subjects showed 75% IgA, 8% IgM, 15% IgG, 1% IgD and 1% IgE and the mucosae of 30 patients with inflammatory gastritis without bile reflux revealed 67% IgA, 6.5% IgM, 22.5% IgG, 1.5% IgD and 2.5% IgE. These features suggest that allergy participates in the physiopathology of bile reflux gastritis.

SHOULD CHOLECYSTECTOMY BE COMBINED WITH VAGOTOMY AND PYLOROPLASTY?

Duodenal ulcers and gallstones, two of the commonest surgical conditions, affect respectively 10% of men and up to 20% of the population. Although many detailed studies of the treatment of these conditions have been conducted, there is no report of the results of surgery when the conditions coexist. 60 patients who had undergone vagotomy, pyloroplasty, and cholecystectomy were compared with age and sex matched controls who had undergone vagotomy and pyloroplasty alone or cholecystectomy alone. In the early postoperative period after the combined procedure there was a very high incidence of post-vagotomy diarrhœa (48·3%, p=0·00013) and bile-reflux gastritis. The findings implicate bile-acids—their excretion and handling by the small intestine—in the ætiology of post-vagotomy diarrhœa. Where the conditions coexist truncal vagotomy and pyloroplasty should be avoided in the treatment of the duodenal ulcer because of the risk of post-vagotomy diarrhœa and bile-reflux gastritis.