Duodenogastric Reflux before and after Surgical or Medical Therapy for Duodenal Ulcer

Duodenogastric reflux was studied in 48 duodenal ulcer patients before and after medical (n = 8) or surgical therapy with either combined truncal vagotomy and gastrojejunostomy (n = 13) or pyloroplasty (n = 12), Polya partial gastrectomy (n = 8), or highly selective vagotomy (n = 7). Seven healthy subjects served as controls. The reflux was assessed both by using 99mTc diethyliminodiacetic acid (HIDA) scintigraphy and by measuring intragastric bile acid levels following endoscopic gastric juice aspiration. Before therapy, duodenal ulcer patients had significantly higher intragastric bile acid concentrations than did normal subjects (p less than 0.001). After truncal vagotomy and drainage, or partial gastrectomy, bile acid levels increased significantly, whereas they remained unchanged after medical therapy. Conversely, they were found to be significantly decreased after highly selective vagotomy. The results of HIDA scan measurements were compatible with those of gastric juice bile acids. We conclude that surgical treatment for duodenal ulcer by highly selective vagotomy is the only form of therapy, among the types considered, that leads to a reduction in duodenogastric reflux. It is of interest that medical therapy of the duodenal ulcer does not improve abnormal duodenogastric reflux, possibly contributing to both the failure of the medical treatment and recurrence of the ulcer.     

Suppression of somatostatin release by duodenogastric reflux in dogs.

The effect of duodenogastric reflux on systemic and portal venous blood concentrations of somatostatin has been studied in the dog. Duodenogastric reflux suppressed somatostatin concentrations in both systemic and portal venous blood, but this did not occur when bile alone was diverted into the stomach. The suppression was also much less marked when truncal vagotomy accompanied the reflux. These findings suggest that altered somatostatin activity may play a part in the production of the pathophysiological changes occurring in clinical conditions such as peptic ulceration, in which there is an increase in duodenogastric reflux.     

The aetiology of gastric stump carcinoma in the rat

This study investigated the aetiology of gastric stump carcinoma in the rat. These carcinomas were induced by duodenogastric reflux without the need to administer carcinogens. Carcinoma was only detected when pancreatic exocrine secretions were present in the reflux. Malignant change was associated with dysplasia but not intestinal metaplasia or adenocystic proliferation of glands. The extent of resection increased tumour yield, but a truncal vagotomy did not. No difference was detected in intragastric pH, bacterial flora, or bile acid concentration between animals with and without carcinoma.     

Nonsteroidal antiinflammatory drugs: Effect on pyloric sphincter and duodenogastric reflux

We have investigated the effect of nonsteroidal antiinflammatory drugs on canine pyloric sphincter pressure, mucosal potential difference (PD), and duodenogastric reflux in 5 dogs. Only intragastric aspirin at doses of 30 and 100 mg/kg caused a significant (P<0.05) decrease in pyloric sphincter pressure, an increase of duodenogastric reflux, and changed the mucosal PD. Neither intravenous aspirin, intragastric phenylbutazone, or intrarectal indomethacin produced these changes. The mechanism for the aspirin effect may be mediated by local pathways related to changes in mucosal PD. We postulate that increased duodenogastric reflux may be an aggravating factor for the gastric mucosal damage caused by intragastric aspirin.     

Characteristics of Distal Partial Gastrectomy Patients with Esophageal Symptoms of Duodenogastric Reflux

Objectives : Partial gastrectomy patients with anatomic alterations to the pylorus and acid secretion are excellent models for studying the controversial role of duodenogastric reflux in producing esophageal symptoms and esophagitis. Methods : We studied 13 partial gastrectomy patients who had recent upper gastrointestinal endoscopies and chronic duodenogastric reflux symptoms. Simultaneously, acid and duodenogastric reflux were assessed by ambulatory 24-h esophageal pH and bilirubin monitoring. Abnormal values for both acid and bilirubin reflux were defined by previous studies of healthy volunteers from our laboratory. Symptoms were recorded and correlated with acid and duodenogastric reflux episodes. Results : Mean percent time bilirubin reflux for the entire group was 26.8 ± 7.2% (range 0.4–91.2%), whereas mean percent total acid reflux was 4.6 ± 2.4% (range 0.0–26.1%). Ten (77%) patients had abnormal duodenogastric reflux, but three patients (23%) also had associated abnormal acid reflux. Only these three patients had esophagitis, two ulcerative and one Barrett's esophagus. A total of 75 symptoms (36 heartburn, 33 epigastric pains, three regurgitation, two nausea/vomiting, one abdominal distension) were reported; 65% were acid related. Of patients with heartburn and regurgitation, 97% were associated with acid reflux episodes. Conclusions : Although excessive amounts of duodenogastric reflux are common in partial gastrectomy patients, esophagitis and Barrett's esophagus are seen only in patients with concomitant acid reflux, and most esophageal symptoms are acid related. Therefore, acid rather than duodenogastric reflux is the main culprit in this syndrome and should be aggressively treated.     

DNA damage in the stomach after vagotomy measured by 32P-postlabelling.

This study analysed gastric mucosal DNA by 32P-postlabelling in a series of patients who have had previous vagotomy for benign peptic ulcer disease. DNA adduct levels were found to be significantly higher in patients who had had previous truncal vagotomy than in those who had had previous highly selective vagotomy (p < 0.001). Intragastric bile concentrations were also considerably higher in patients after truncal vagotomy but there was no correlation between intragastric bile concentrations and DNA adduct levels. These results suggest that, although duodenogastric reflux may be a cause of gastric mucosal DNA damage in the stomach after vagotomy, measurement of total intragastric bile does not accurately reflect genotoxic insult.     

Gallstones, cholecystectomy, and duodenogastric reflux of bile acid

It has earlier been suggested that cholecystectomy, by eliminating the reservoir function of the gallbladder, will induce reflux of bile to the stomach. In the present study 23 patients were studied for duodenogastric reflux of bile acid before and 3 months after cholecystectomy. At the test the gastric contents were continuously aspirated via a nasogastric tube, collected at 15-min intervals for 2 h in the fasting patient, and analyzed for volume and bile acid concentration. The results were compared with those in 14 control subjects. Significant duodenogastric reflux of bile acid (greater than 100 mumol/h) was seen more frequently in gallstone patients than in controls. This is explained by a high prevalence of bile acid reflux in patients with a reduced or absent opacification of the gallbladder at cholecystography. Cholecystectomy increased the prevalence of bile acid reflux in the patients with well-opacified gallbladders at cholecystography. The duodenogastric reflux of bile acid in patients with a poor filling of the gallbladder at cholecystography was not further enhanced by cholecystectomy. It is concluded that gallstone patients have an increased tendency to duodenogastric reflux of bile acid. This tendency is further enhanced by removal of a functioning gallbladder. The findings may explain some of the symptoms in patients with gallstones. The reflux may also be responsible for symptoms in the so-called postcholecystectomy syndrome.     

Duodenogastric reflux causes growth stimulation of foregut mucosa potentiated by gastric acid blockade

We investigated whether duodenogastric reflux (DGR) together with gastroesophageal reflux causes growth stimulation of the foregut mucosa and if additional gastric acid suppression enhances the effect of DGR. DGR was induced in rats using a split gastroenterostomy. A cardiomyotomy was performed across the gastroeophageal junction in order to enhance reflux into the esophagus. DGR rats were divided into six subgroups: DGR, DGR + truncal vagotomy, DGR + omeprazole, DGR + gastrin receptor blockade, DGR + omeprazole + gastrin receptor blockade, and DGR + gastrin. Two sham groups, one with and one without omeprazole treatment, served as controls. DGR significantly increased the weight and DNA content of the esophageal and gastric mucosa, which was further enhanced by vagotomy or omeprazole. Histology revealed foveolar hyperplasia in the stomach and esophageal mucosal hyperplasia in these groups. In addition, severe esophagitis was found in the DGR group receiving omeprazole. Omeprazole without DGR had no growth-stimulating effect on the foregut mucosa. DGR-induced growth stimulation was accompanied by hypergastrinemia. Increased growth in the stomach but not the esophagus was inhibited by gastrin receptor blockade. Gastrin administration did not result in enhancement of DGR-induced growth stimulation of the foregut mucosa. It is concluded that DGR, often present in severe reflux esophagitis, causes mucosal growth of the foregut of rats. This trophic response may explain why severe reflux esophagitis is associated with an increased risk of esophageal adenocarcinoma. DGR-induced growth stimulation of the foregut is potentiated by gastric acid suppression, suggesting that chronic antisecretory medication in gastroesophageal reflux may not always be advisable. Omeprazole + DGR caused severe esophageal damage, which may explain why antisecretory medication may fail to heal severe reflux esophagitis.     

Antroduodenal resistance to flow in the control of duodenogastric bile reflux during fasting

Our objectives in this study were (a) to determine the role of antroduodenal resistance in the control of fasting duodenogastric bile reflux in the dog and (b) to elucidate the contribution of the pylorus both to resistance and to reflux. Thus, we measured simultaneously throughout the interdigestive motor cycle (a) antroduodenal pressure activity by manometry, (b) antroduodenal resistance by a pneumatic resistometer, and (c) bile acid concentrations in duodenal and gastric juices. Experiments were performed in 15 conscious dogs (9 with pylorus intact and 6 with extramucosal pyloric myotomy). We found that antroduodenal resistance was lowest during phase I, increased gradually during phase II, and peaked during phase III (linear trend, p less than 0.001). Duodenogastric bile reflux was low during phase I, peaked during late phase II, and decreased again during phase III (quadratic trend, p less than 0.05). Therefore, variations in net resistance and reflux were differently related to the phases of the interdigestive motor complex. Pyloric myotomy significantly decreased antroduodenal resistance (linear trend different from control, p less than 0.001), but had no significant effect on duodenogastric bile reflux. We conclude (a) that changes in net antroduodenal resistance do not regulate duodenogastric bile reflux and (b) that the pylorus is an important determinant of antroduodenal resistance, but has no major role in the control of fasting duodenogastric bile reflux.     

Duodenogastric reflux in patients with Barrett's esophagus

The role of duodenogastric reflux in the pathogenesis of gastroesophageal reflux disease is not clear. Using hepatobiliary scanning techniques, we found evidence of duodenogastric reflux in six of 13 patients with Barrett's esophagus. This compares with only two positive studies in 19 control subjects. This difference is statistically significant P=0.038, two-tailed Fisher's exact test). Three of nine patients who had gastroesophageal reflux without Barrett's esophagus had evidence of duodenogastric reflux, a frequency not significantly different from either of the other groups. Gastroesophageal reflux of bile and pancreatic enzymes, in addition to gastric acid may contribute to the greater esophageal damage often seen in Barrett's esophagus. The presence of duodenogastric reflux in these patients may have important pathophysiologic and therapeutic implications.     

Relationship between antropyloric and intestinal motility and duodenogastric reflux in fasting dogs

Duodenogastric reflux was studied in fasting dogs with gastric and duodenal cannulae, by means of recovery from the gastric cannula of phenol red infused into the duodenum and bile acids recovered from the gastric cannula. Simultaneously, antropyloric and intestinal motility was studied in order to establish a relationship between motility and duodenogastric reflux. A different pattern of duodenogastric reflux was observed, depending on the method utilized. While a significantly higher reflux was observed during phase II in bile acid studies, an irregular pattern not related to the different phases of the interdigestive motor complex was observed in experiments with phenol red. Antral motility estimated by an antral motility index showed a statistically significant correlation with DGR estimated by both methods. Pyloric pressure and intestinal motility did not show a correlation with DGR. We concluded that the results obtained in studying duodenogastric reflux depend on the method used. The main factor related to increased duodenogastric reflux was the decreased antral motility.     

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.     

Bile reflux and oesophagitis

Duodenal contents, and especially bile acids and trypsin, are noxious to the oesophageal mucosa, their damaging potential depending on pH. Various methodologies have been used to measure duodenogastric or duodenogastro-oesophageal reflux, all of them having technical limitations. Controversy exists as to the extent of duodenogastric reflux in GORD. Reflux of both acid and duodenal contents into the oesophagus increases with worsening of oesophagitis. Experimental data suggest that bile acids and trypsin are noxious to the oesophageal mucosa and that their damaging potential depends on pH. The injurious concentrations are, however, higher than those usually observed in the human oesophagus. Direct measurement of bile acids and trypsin is difficult and various methodologies have been used to measure duodenogastric or duodenogastro-oesophageal reflux, all of them having technical limitations. Whereas available data as to the extent of duodenogastric reflux in gastro-oesophageal reflux disease (GORD) are controversial, most observations show that reflux of both acid and duodenal contents into the oesophagus increases with worsening of oesophagitis. Furthermore, acid and duodenal contents occur simultaneously in most reflux episodes. In this issue of the journal, Marshall et al. report that exposure of the gastric fundus to duodenal contents as assessed by bilirubin monitoring is similar in GORD patients with varying degrees of oesophageal mucosal injury and in healthy controls.     

Influence of intraduodenal chenodeoxycholic acid on secretory and pressure activity of the stomach and duodenum

The influence of duodenal infusion of bile acid at a concentration similar to that in the common bile-duct (50 mmol/1) on antroduodenal motility, duodenogastric reflux, gastric and duodenal secretion was studied in 10 healthy volunteers. Intraluminal pressures were recorded in the antrum and the first and second parts of the duodenum. Gastric and distal duodenal contents were collected by continuous low pressure sump aspiration during infusion of either saline or chenodeoxycholic acid (CDC) into the second part of the duodenum. Values for duodenogastric reflux and gastric and duodenal secretion were calculated with reference to the recovery of two non-absorbable markers infused into the stomach and second part of the duodenum. Each volunteer received at least 3 h of saline infusion and 2 h of CDC infusion. During saline infusion, duodenogastric reflux varied with the migrating motor complex (MMC), being statistically greater at the end of duodenal phase III activity than at other times (P<0.05). Infusion of CDC abolished the MMC and inhibited antral contractions but the amount of reflux was not increased compared with the saline period. Infusion of CDC also produced marked increases in measured bicarbonate (P<0.001), trypsin (P<0.001), phospholipase A₂ (P<0.05) and endogenous total bile acid (P<0.05) in the duodenum, although gastric acid secretion was unaffected. These findings suggest that bile acid may regulate gastroduodenal motor activity and pancreaticobiliary secretion.     

Barrett's esophagus, gastroesophageal acid reflux and duodenogastric reflux during the digestive and postprandial period]

Pathologic gastroesophageal acid reflux appears to be involved in the pathogenicity of Barrett's esophagus. The possible pathogenic role of duodenogastric reflux, however, has been suggested by several studies. The aim of this prospective study was to assess the prevalence of acid or duodenogastric reflux in patients with Barrett's esophagus. Nine patients with histologically proven Barrett's esophagus (mean length: 7.7cm; range: 2-13 cm) were studied by esophageal manometry and 24 hour pHmetry. Duodenogastric reflux was measured in the interdigestive period by aspiration and during the postprandial period using an isotopic method. The results of these different investigations were compared with healthy volunteers (n = 20 to 27). Three patients had complicated Barrett's esophagus (Barrett's ulcer: n = 2, high-grade dysplasia: n = 1). The results of the different investigations showed that a) all patients had abnormal acid exposure and an esophageal motor dysfunction (decrease in lower esophageal sphincter pressure, amplitude and duration of contractions and increase in percentage of peristaltic dysfunction); b) none of the patients had any pathologic duodenogastric reflux neither in the interdigestive nor in the postprandial period. These results a) confirm the high prevalence of acid reflux in patients with Barrett's esophagus, b) show that bile or pancreatic secretions are not involved in the pathogenicity of Barrett's esophagus.     

Ambulatory 24-hr pH monitoring of esophagus,fundus, and antrum

A method for outpatient 24-hr simultaneous recording of pH in the distal esophagus, fundus, and antrum was developed in order to detect acid, alkaline, alkalacid gastroesophageal reflux, and duodenogastric reflux and to study these phenomena in patients complaining of gastroesophageal reflux and dyspepsia related symptoms. Two hundred ninety-four studies were performed in 42 healthy volunteers and 237 patients. Three-probe ambulatory 24-hr esophagogastric pH monitoring applicability, tolerability, and capability to determine a relationship between symptoms which occurred during the tests, gastroesophageal reflux, and duodenogastric reflux episodes were assessed. Eighty-nine percent of the three-probe esophagogastric pH studies were easily performed. The examination was tolerated well by 86.1% of the patients and poorly by 13.9%. A temporal correlation between symptoms and pH activities was recognized in 61.3% when the esophageal tracing was considered (acid gastroesophageal reflux recording) and in 95.6% when the three pH traces were simultaneously interpreted. Alkalacid gastroesophageal reflux and duodenogastric reflux total percentage times were significantly higher in patients complaining of dyspeptic symptoms than in patients only affected by typical gastroesophageal symptoms. Three-probe 24-hr ambulatory esophagogastric pH monitoring is a simple, well-tolerated test that should be routinely adopted for the study of patients complaining of unclear upper gastrointestinal tract symptomatology.     

Characteristics of reflux gastritis

The amount of postprandial duodenogastric bile reflux was correlated with detailed histologic findings in the stomachs of 107 patients with dyspepsia. The reflux was associated with infiltration of mononuclear leukocytes, neutrophilic granulocytes, and eosinophilic granulocytes and with foveolar hyperplasia in the gastric mucosa. No significant association with intestinal metaplasia emerged. Our results suggest that postprandial duodenogastric bile reflux is characterized by superficial inflammatory changes in the gastric mucosa.     

Inflammation at the cardio-oesophageal junction: relationship to acid and bile exposure

BACKGROUND: The aetiology of inflammation in cardiac mucosa at the gastro-oesophageal junction (carditis) is unclear, although gastro-oesophageal reflux has been suggested. OBJECTIVES: To correlate histological features of carditis with oesophageal acid exposure (gastro-oesophageal reflux) and proximal gastric bile exposure (duodenogastric reflux) in patients with symptoms of gastro-oesophageal reflux disease (GORD). METHODS: Sixty-six patients with reflux symptoms underwent endoscopy with biopsy, oesophageal manometry, 24-h oesophageal pH testing and 24-h proximal gastric Bilitec 2000 testing. Inflammation in glandular mucosa was assessed using the updated Sydney System. Fifteen healthy volunteers underwent pH and Bilitec 2000 testing and served as controls. RESULTS: There was no correlation between either the presence or histological grade of carditis and oesophageal acid exposure or proximal gastric bilirubin exposure. Patients with reflux symptoms had as much duodenogastric reflux into the proximal stomach as did control subjects. CONCLUSIONS: We were unable to establish either gastro-oesophageal or duodenogastric reflux as the predominant cause of inflammation in cardiac mucosa.     

Simultaneous measurement of antroduodenal motility, gastric emptying, and duodenogastric reflux in man.

In six healthy individuals, the relationship between antroduodenal motor activity, duodenogastric reflux, and gastric emptying were simultaneously examined by combined use of multiple marker perfusion and miniature strain gauge transducers. An interdigestive pattern of motor activity was observed during the fasting period;duodenogastric reflux was of variable magnitude, but reproducible in each individual. Fasting reflux was significantly reduced during phase III of the interdigestive complex. Administration of 0.15 M sodium chloride into the stomach resulted in minor and inconsistent changes in antroduodenal motility, despite the rapid and similar pattern of gastric emptying in the six subjects. This study supports the concept that motor activity in the antroduodenal region does not affect gastric emptying of inert, isotonic fluids but may be involved in the regulation of duodenogastric reflux.     

十二指肠胃反流和幽门螺杆菌感染关系研究

目的：探讨消化性溃疡患者中的十二指肠胃反流对幽门螺杆菌（Hp)感染的影响。方法：70例消化性溃疡患者，用核素^99MTC-EHIDA测定十二指肠胃反流，胃黏膜Giemsa染色后检测Hp和双抗体夹心ELISA法测定血清Hp-IgG水平。结果：在42例十二指肠胃反流阴性组中，Hp感染率为83．3％（35／42）；28例十二指肠胃反流阳性组中，Hp感染率为39．3％（11／28），两组间Hp感染率差异有显著性（P＜0．05）。而Hp阳性组46例患者中，十二指肠胃反流阳性率为30．4％（14／46）；Hp阴性组24例中，十二指肠胃反流率为58．3％（14／24），两组间十二指肠胃反流率差异也有显著性（P＜0．05）。结论：在消化性溃疡中，十二指肠胃反流对胃内Hp感染可能有抑制作用。