Importance of duodenogastric reflux in gastro-oesophageal reflux disease

BACKGROUND: Bile in the oesophagus occurs frequently in patients with gastro-oesophageal reflux disease (GORD) and has been linked to Barrett's metaplasia and cancer. Although duodenogastric reflux is a prerequisite for bile in the oesophagus, little is known about its importance in GORD. METHODS: Some 341 patients with GORD were assessed by simultaneous 24-h gastric and oesophageal bilirubin monitoring. Definitions of increased bilirubin exposure were based on the 95th percentiles in healthy volunteers. The relationship between gastric and oesophageal bilirubin exposure and the correlation with disease severity were analysed. RESULTS: Of the 341 patients with GORD, 130 (38.1 per cent) had increased gastric and 173 (50.7 per cent) had increased oesophageal bilirubin exposure. Of the 173 patients with bile in the oesophagus, 89 (51.4 per cent) had normal and 84 (48.6 per cent) had increased gastric bilirubin exposure. Of these 84 patients, 75 (89 per cent) had oesophagitis or Barrett's oesophagus (P = 0.003). These effects were mainly related to differences in supine reflux. CONCLUSION: Bile in the oesophagus originates from either normal or increased gastric bilirubin exposure. Patients with increased duodenogastric reflux are more likely to have oesophagitis or Barrett's oesophagus. These findings highlight the role of duodenogastric reflux as an additional factor in the pathogenesis of GORD.     

胆囊切除后十二指肠胃反流的临床研究

本研究通过检测１４例胆囊结石病人胆囊切除术前后胃内胆酸含量，发现其十二指肠胃反流（ＤＧＲ）发生率分别为８５７１％和１００％，正常对照组为２１４３％，差异显著（Ｐ＜０．０１）；同时检测手术前后血清胃泌素分别为１６２９５±５６２８ｐｇ／ｍｌ、１４７．８７±３７．６１ｐｇ／ｍｌ，均显著高于对照组１０５０５±２６．８５ｐｇ／ｍｌ，而基础胃酸排量、最高胃酸排量与对照组比较无明显差异。作者分析，此种病人胃肠道激素改变是影响Ｏｄｄｉ括约肌运动状态和胃－幽门－十二指肠协调运动的主要因素，亦即是引起ＤＧＲ的基本原因，也是胆囊切除术后综合征的原因之一，其治疗可选用促胃肠动力药物。     

Roux-en-Y reconstruction for severe postoperative duodenogastric reflux disease

Thirty-two patients underwent Roux-en-Y diversion because of symptomatic postoperative duodenogastric reflux. Operative mortality was nil, but eight patients had transiently delayed gastric emptying postoperatively. At follow-up 45 months (range 9-89 months) after the Roux-en-Y operation 28 (88%) patients were in good clinical state; four patients were classified as poor. The main cause for a poor clinical outcome was a stomal ulcer in three patients. Atrophic gastritis was seen in the operative specimens of 22 patients. Severity of gastritis evaluated by gastroscopic biopsies at follow-up was less marked in 16 patients as compared to the histology of the samples from the original operation (P less than 0.001). Intestinal metaplasia had regressed in nine cases and proceeded in three cases (NS). Severe postoperative duodenogastric reflux can be treated by the Roux-en-Y reconstruction with good subjective relief of symptoms and beneficial histologic changes in the gastric stump mucosa.     

Cholecystectomy and duodenogastric reflux]

With the aim of evaluating whether cholecystectomy causes an increase in duodenogastric reflux (DGR) 34 patient (12 males and 22 females, mean age 50 years) were examined before and 6 months after cholecystectomy. DGR was evaluated by assaying total and individual biliary acids in gastric juice and was expressed as fasting bile reflux (FBR) in mumol/h. The histology of gastric mucosa in endoscopic biopsies taken from the antrum and body was also analysed. FBR of total biliary acids rose from 2.4 mumol/h before surgery to 41.33 mumol/h after cholecystectomy (p = 0.000). A significant increase was observed for all the individual biliary acids. Histological tests of gastric mucosa revealed an increased percentage of chronic atrophic gastritis of the antrum following cholecystectomy. Histological conditions in the body were unaltered. The results of this study show that there is a significant increase in DGR (months after cholecystectomy together with increased histological damage to the mucosa of the antrum. Further studies are necessary in order to evaluate whether the two phenomena are related.     

Evaluation of duodenogastric reflux in gallstone disease before and after simple cholecystectomy

Duodenogastric reflux (DGR) has been suggested as an etiopathogenic factor in gastric disease in patients with gallstones. We evaluated the DGR levels in 15 patients before and after simple cholecystectomy for gallstones and compared the results with those of 15 healthy subjects. Gastric juice was obtained by continuous nasogastric suction for 24 hours. The bile acids (BA) present in the samples were quantified by thin-layer chromatography and in situ spectrofluorometry. The mean BA concentration for the control subjects was 2.25 mumol reflux/hour, whereas the mean value for the 15 patients with cholelithiasis was 8.86 mumol reflux/hour before cholecystectomy and 24.55 mumol reflux/hour after cholecystectomy. Five patients did not have detectable BA in the gastric juice in both analyses; the remaining 10 patients showed a significant increase in the BA after surgery. From these data, we conclude that gallstone disease is not always accompanied by an increased DGR. However, in patients in whom DGR is present, its level is higher than in control subjects and increases significantly after cholecystectomy. This is probably due to the greater amount of bile in the duodenum that may reflux through an incompetent pyloric channel.     

Variability in the composition of physiologic duodenogastric reflux

Duodenogastric reflux has long been associated with various diseases of the foregut. Even though bile is often used as a marker, duodenogastric reflux consists of other components such as pancreatic juice and duodenal secretions. The aim of this study was to investigate the occurrence of duodenogastric reflux, its components, and the variability of its composition in normal subjects. Twenty healthy volunteers (7 men and 13 women) whose median age was 24 years underwent combined 24-hour bilirubin and gastric pH monitoring and intraluminal gastric aspiration. All probes were placed at 5 cm below the lower border of the lower esophageal sphincter. Aspiration was performed hourly and at any time when bilirubin and/or pH monitoring showed signs of duodenogastric reflux. Elastase and amylase were measured in the aspirate. All volunteers had episodes of physiologic duodenogastric reflux. A total of 70 episodes of duodenogastric reflux were registered with a median of three episodes (range 1 to 8) per subject. Most bile reflux occurred separately from pancreatic enzyme reflux. Pancreatic enzyme aspirate was significantly more often associated with a rise in pH in comparison to bile reflux (P <0.01). Duodenogastric reflux is a physiologic event with varying composition. Both bile and pancreatic enzyme reflux frequently occur separately. These findings could explain the disagreement regarding assessment and interpretation of duodenogastric reflux in the past. Thus monitoring of duodenogastric reflux requires more than the detection of just one component. Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20,1998.     

Complications of gastroesophageal reflux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux.

The factors contributing to the development of esophageal mucosal injury in gastroesophageal reflux disease (GERD) are unclear. The lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and the presence of excessive duodenogastric reflux (DGR) was evaluated in 205 consecutive patients with GERD and various degrees of mucosal injury (no mucosal injury, n = 92; esophagitis, n = 66; stricture, n = 19; Barrett's esophagus, n = 28). Manometry and 24-hour esophageal pH monitoring showed that the prevalence and severity of esophageal mucosal injury was higher in patients with a mechanically defective lower esophageal sphincter (p less than 0.01) or increased esophageal acid/alkaline exposure (p less than 0.01) as compared with those with a normal sphincter or only increased esophageal acid exposure. Complications of GERD were particularly frequent and severe in patients who had a combination of a defective sphincter and increased esophageal acid/alkaline exposure (p less than 0.01). Combined esophageal and gastric pH monitoring showed that esophageal alkaline exposure was increased only in GERD patients with DGR (p less than 0.05) and that DGR was more frequent in GERD patients with a stricture or Barrett's esophagus. A mechanically defective lower esophageal sphincter and reflux of acid gastric juice contaminated with duodenal contents therefore appear to be the most important determinants for the development of mucosal injury in GERD. This explains why some patients fail medical therapy and supports the surgical reconstruction of the defective sphincter as the most effective therapy.     

Gastric symptoms and duodenogastric reflux in patients referred for gastroesophageal reflux symptoms and endoscopic esophagitis.

BACKGROUND: The role of excessive duodenogastric reflux (DRG) in the genesis of gastric symptoms in patients primarily referred for both gastroesophageal reflux (GER) symptoms and esophagitis is poorly understood. METHODS: The study is based on the clinical, endoscopic, histologic, and 24-hour gastric data from the Bilitec optoelectronic device (Prodotec, Florence, Italy, licensed by Synectics Medical, Stockholm, Sweden) from 49 patients having both typical GER symptoms and gastric symptoms suggestive of excessive DGR (i.e., epigastric pain, nausea, or bilious vomiting) in the absence of previous esophageal or gastric surgery (group 1). Helicobacter pylori organisms were searched for on antral biopsy specimens with use of the Giemsa method. The percentages of total, upright, and supine time during which absorbance exceeded various thresholds through all the working range of the Bilitec device were calculated. Bilitec data from group 1 were compared with those from 16 patients with endoscopic esophagitis and GER symptoms only (group 2) and 25 healthy subjects (group 3). RESULTS: The prevalence of an abnormal Bilitec test result in group 1 increased from 27% (13/49) at the 0.25 absorbance threshold to 36% (18/49) at thresholds ranging from 0.40 to 0.60 and to 41% (20/49) when multiple thresholds ranging from 0.25 to 0.60 were considered. In group 2 one patient had an abnormal Bilitec test result at the 0.25 to 0.30 threshold, whereas the other 15 patients had a normal test result. H pylori antral infection was present in 14 group 1 patients. None of these had an abnormal Bilitec test result, whereas the test was positive in 40% of the H pylori-negative patients without endoscopic gastritis and in 70% of H pylori-negative patients with endoscopic gastritis (P = .001). CONCLUSIONS: Twenty-four-hour intragastric bile monitoring provides the clinician with unequivocal evidence of excessive DGR in 41% of patients with an intact stomach having endoscopic esophagitis, GER symptoms, and gastric symptoms suggestive of DGR. The most dependable data are obtained when absorbance thresholds higher than 0.40 are considered. H pylori antral infection and excessive DGR at 24-hour intragastric bile monitoring are mutually exclusive.     

The association of duodenogastric reflux with dumping and gastric retention.

Gastric emptying of solid and liquid meals together with duodenogastric reflux has been measured in a prospective trial of proximal gastric vagotomy and truncal vagotomy and antrectomy. Three abnormalities of motility associated with postoperative symptoms have been defined. If more than one abnormality was present in an individual there was an 80 per cent incidence of associated symptoms. Proximal gastric vagotomy produced significantly fewer abnormalities of gastro-duodenal motility than did truncal vagotomy and antrectomy.     

Relative contribution of bile and pancreatic juice duodenogastric reflux in gastric ulcer disease and cholelithiasis

Bile acid concentrations, phospholipase A2 activity and pH in the stomach were measured in the fasting state and for 2 h after a fat-containing test meal in patients with an active gastric ulcer (GU), in patients with gallstones before and after cholecystectomy and in normal subjects. Fasting and peak postprandial bile acid concentrations in the stomach were low in all normal controls. Although high concentrations were found in many patients with GU (P less than 0.01), similar concentrations were found in many patients with radiologically non-functioning gallbladders containing gallstones (NFG) (P less than 0.01) and also after cholecystectomy (AC) (P less than 0.01). Fasting intragastric phospholipase A2 activities were similar, and very high in GU and NFG patients compared with control subjects (P less than 0.01). High values were not found after cholecystectomy. There was no difference in pH profile or in postprandial phospholipase A2 between patient groups. Since patients with cholelithiasis or after cholecystectomy are not known to have an increased incidence of gastric ulceration, the significance of duodenogastric reflux in the aetiology of gastric ulcers must be questioned. If reflux does produce ulcers in GU patients then factors in addition to bile acid are probably involved. However, neither patterns of phospholipase A2 reflux nor pH profiles can explain the absence of gastric ulceration in those patients with gallstones who reflux large quantities of bile acid.     

Intragastric bile acids and scintigraphy in the assessment of duodenogastric reflux

Following endoscopic gastric juice aspiration, intragastric bile acids were measured in 105 patients undergoing routine or review gastroscopy. Subsequently, duodenogastric reflux was assessed using 99mTc butyliminodiacetic acid (BIDA) scintigraphy and intragastric bile acid levels compared with the grades of reflux assessed scintigraphically. There was a significant correlation between both free and total intragastric bile acid levels and the degree of radiological bile reflux, especially when reflux was severe. Both endoscopic measurements of bile acids and BIDA scintigraphy appear to be useful methods for determining duodenogastric reflux, but neither may be accurate enough to quantify minor degrees of reflux.     

Implication of duodenogastric reflux in the pathogenesis of Barrett's oesophagus

Fasting and postprandial intragastric bile acid concentrations have been estimated and compared in patients with complications of Barrett's oesophagus, patients with Barrett's oesophagus without complications, patients with oesophagitis and a group of normal subjects who acted as controls. There was no significant difference in fasting intragastric bile acid concentrations between the groups. Postprandial bile acid concentrations were significantly greater in the patients with complications of Barrett's than in the remaining groups at 60, 90 and 120 min. Significant concentrations of bile acids were seen in gastric juice of unaltered pH and may be undetected on intra-oesophageal pH monitoring. Duodenogastric reflux may be implicated in the pathogenesis of complications of Barrett's oesophagus.     

Quantitative hepato-biliary scintigraphy in the diagnosis of duodenogastric reflux and dysfunction of the Oddi's sphincter in post-cholecystectomy syndrome]

Qualitative indicators of dynamic hepato-biliary scintigraphy+ were studied before and after administration of cerucal in postcholecystectomy syndrome, determined by duodenogastric reflux (24 patients), dysfunction (21 patients) and stenosis of Oddi sphincter (17 patients) and in a control group (28 volunteers) without any complaints after cholecystectomy. A conclusion was made that dynamic hepato-biliary scintigraphy+ allowed quantitative estimation of duodenal reflux to be made and the dynamics of excretion of radiopharmagent before and after administration of cerucal may be an indicator of the functional state of the Oddi sphincter.     

Clinical use of 24-hour gastric pH monitoring vs o-diisopropyl iminodiacetic acid (DISIDA) scanning in the diagnosis of pathologic duodenogastric reflux

The efficacy of o-diisopropyl iminodiacetic acid (DISIDA) scanning was compared with that of computerized analysis of 24-hour gastric pH monitoring to diagnose excessive duodenogastric reflux in 22 normal volunteers and 106 consecutive patients with foregut symptoms. DISIDA scanning had a false-positive rate of 18% in the normal volunteers. Gastric pH monitoring showed an increasing prevalence of duodenogastric reflux in patients with increasing clinical evidence of this condition, which was not seen with DISIDA scanning. Both DISIDA scanning and gastric pH monitoring identified duodenogastric reflux in most patients who had had previous pyloroplasty or antrectomy. Only gastric pH monitoring, however, showed a significantly increased prevalence of duodenogastric reflux in symptomatic patients after previous cholecystectomy compared with those who had not undergone previous surgery. These data suggest that 24-hour gastric pH monitoring is superior to DISIDA scanning in identifying duodenogastric reflux as a cause of foregut symptoms.     

胃大部切除术后十二指肠胃返流液的潜在致癌性

目的探讨长期胃大部切除术后患者十二指肠胃返流液的潜在致癌性,阐明十二指肠胃返流与残胃癌的内在关系.方法通过细胞二阶段转化实验,分别检测37例胃大部切除术后(10年以上)患者胃肠返流液的肿瘤启动性和促癌性.结果仅11.1%的患者返流液表现出明显的肿瘤启动性,而47.4%的返流液明显促进细胞恶性转化灶的形成,2者差异具有显著性意义(P＜0.05);毕Ⅱ式组患者返流液与毕Ⅰ式组相比,启动性无明显差别(P＞0.05),在促癌实验中却表现出更强的活性(P＜0.05);患者的胃肠吻合区病理类型与返流液的促癌活性亦明显正相关(rs=0.625,P＜0.01).结论通过胃大部切除术后患者的胃肠返流液证实了残胃癌的病因学假说-返流学说.胃肠吻合区的病理类型与返流液的促癌活性显著相关,与返流液的启动活性无关.