Bile reflux is a factor in the appearance of severe esophagitis and Barrett's esophagus, which have been reported after sleeve gastrectomy (SG). Incompetent lower esophageal sphincter and increased gastroesophageal acid reflux have been demonstrated after this operation. Some reports have shown bile content in the antrum during endoscopic control, but no investigations objectively confirm the presence of duodenogastric bile reflux in these patients.

To evaluate the presence of duodenogastric bile reflux (DGR) after SG in patients presenting reflux symptoms.

University hospital.

Prospective study of 22 patients presenting reflux symptoms who underwent SG for morbid obesity and who received endoscopic evaluation and scintigraphic study to confirm esophagitis and duodenogastric bile reflux.

Erosive esophagitis was observed in 11 patients and Barrett's esophagus in 2 patients. Seven patients (31.8%) presented positive DGR. Among them, 3 had type B and C esophagitis. The other 4 patients did not present esophagitis in spite of reflux symptoms.

DGR may be present in patients with gastroesophageal reflux after SG. This line of investigation requires further studies to confirm this hypothesis.

This study reviews current data regarding duodenogastric and gastroesophageal bile reflux-pathophysiology, clinical presentation, methods of diagnosis (namely, 24-hour intraluminal bile monitoring) and therapeutic management. Duodenogastric reflux (DGR) consists of retrograde passage of alkaline duodenal contents into the stomach; it may occur due to antroduodenal motility disorder (primary DGR) or may arise following surgical alteration of gastoduodenal anatomy or because of biliary pathology (secondary DGR). Pathologic DGR may generate symptoms of epigastric pain, nausea, and bilious vomiting. In patients with concomitant gastroesophageal reflux, the backwash of duodenal content into the lower esophagus can cause mixed (alkaline and acid) reflux esophagitis, and lead, in turn, to esophageal mucosal damage such as Barrett's metaplasia and adenocarcinoma. The treatment of DGR is difficult, non-specific, and relatively ineffective in controlling symptoms. Proton pump inhibitors decrease the upstream effects of DGR on the esophagus by decreasing the volume of secretions; promotility agents diminish gastric exposure to duodenal secretions by improving gastric emptying. In patients with severe reflux resistant to medical therapy, a duodenal diversion operation such as the duodenal switch procedure may be indicated.

GERD is ubiquitous throughout the adult population in the United States. It commonly adversely affects quality of life and occasionally causes life-threatening complications. The new and emerging medical and endoscopic therapies for GERD and the new management strategies for BE should dramatically reduce the clinical toll of this disease on society.

Gastroesophageal reflux disease (GERD) is one of the most prevalent diseases in the industrialized countries. Approximately 15-25% of adults suffer from reflux symptoms, characterized mainly by heartburn and/or regurgitation. Currently, antisecretory medication with proton pump inhibitors (PPI) or antireflux surgery are the established options for GERD-treatment. PPI are the therapeutic gold standard in acute, long-term or on-demand therapy of GERD. Since PPI do not restore the antireflux barrier but merely suppress acid secretion a life-long tablet adherence is required in most cases. In view of limitations of PPI and the potential risks of laparoscopic surgery, several endoscopic antireflux techniques were developed and may evolve as a valuable third option. However, so far objective long-term data are lacking for choosing the appropriate patient who will benefit most from endoluminal antireflux therapy.

Primary duodenogastric reflux is a rare disorder in adults which has not yet been documented in children. Six young patients, aged 4.5 to 16.5 years (median 13.5 years) presented with atypical reflux symptoms persisting from 1 to 84 months (median 8 months) and unresponsive to classical antacid therapy. In all six patients, 24 h gastric bilimetry showed excessive bile exposures for absorbances ranging from 0.25 to 0.60. The fraction of time (supine period) above the 0.25 absorbance threshold ranged from 30% to 75% while the 95th percentile value for healthy adults is 31%. In all patients tested, hepato-iminodiacetic acid scintigraphy revealed the occurrence of a massive duodenogastric reflux and four out of five patients had an alkaline shift (fraction of time pH >8 on 24 h lower oesophageal pH monitoring) ranging from 4.2% to 20% (control values 0.0% to 2.9%). Endoscopic findings included abundant bilious gastric leak (6/6) and chronic prepyloric Helicobacter pylorinegative gastritis (2/6). Daily administration of cisapride, sucralfate with or without omeprazole resulted in an improvement of symptoms in five patients within 15 days. This treatment was ineffective in one patient who became symptom-free only after a surgical duodenal switch with fundoplication was performed.

primary duodenogastric reflux is a rare foregut disorder of unknown origin occurring in late childhood. If suspected, 24 h intragastric bilimetry appears to be a useful investigation to confirm the diagnosis.

The usual surgical treatment for patients with Barrett's esophagus (BE) is a classic Nissen fundoplication or posterior gastropexy with cardial calibration. However, some surgical reports as well as our experience suggest that the rate of failure of the Nissen fundoplication or Hill's posterior gastropexy in patients with BE is significantly higher than in those with reflux esophagitis without BE, probably due in part to the persistence of duodenal reflux into the esophagus. Our aim was to determine the late subjective and objective results of an operation consisting in "acid suppression" (vagotomy-partial gastrectomy) and "duodenal diversion" (Roux-en-Y anastomosis) as a primary surgical procedure for patients with BE. Altogether, 210 patients were subjected to this technique. It consisted in a primary operation in 142 patients and revision surgery in 68. They underwent complete clinical, radiologic, endoscopic, histologic, and manometric studies. In some cases 24-hour pH studies, Bilitec studies, gastric emptying, and gastric acid secretion evaluations were performed. There were two deaths (0.95%), and postoperative morbidity was low (5.3%). The late mean follow-up (58 months) for 146 patients who completed a follow-up longer than 24 months showed Visick I and II grades in 91.1% of the cases. In 14.9% of the cases 24-hour pH monitoring showed excessive acid reflux 1 year after surgery. No dysplasia or adenocarcinoma has appeared up to now. Functional studies showed significant alleviation of lower esophageal sphincter (LES) incompetence, with abolition of duodenal reflux into the esophagus. Gastric emptying of solids was normal, and basal and peak gastric acid output remained at a low level 8 to 10 years after surgery. In patients with BE, with severe damage of the LES and esophageal peristalsis, the "suppression diversion" operation completely abolishes the reflux of injurious components of the refluxate and improves sphincter competence. This effect is permanent and avoids the appearance of dysplasia or adenocarcinoma.

In summary, vagotomy plus antrectomy and the Roux-en-Y procedure is based on the following points: (a) patients who have BE show several foregut abnormalities, including incompetent lower esophageal sphincter, impairment in the esophageal clearance, severe gastroesophageal acid reflux, and frequent duodenoesophageal reflux; (b) late results of classic antireflux procedure in BE are poor with a high recurrence rate owing to a progressive loosening of the wrap; (c) the esophageal damage is produced by the injurious component of the refluxate; and (d) among patients who underwent classic antireflux surgery, a certain proportion developed dysplasia or even adenocarcinoma in the follow-up. The authors have observed that the simple correction of the valve is not enough in many cases, because it does not abolish the gastroesophageal reflux but only diminishes it. In patients who have BE and therefore have impaired esophageal clearance, few reflux episodes can maintain or even induce more damage. With the reduction diversion antireflux procedure, the quality of the corrected valve is secondary, and the main goal is to avoid the reflux of injurious components of the refluxate instead of the refluxate itself, which is almost always impossible. Late results support this hypothesis, and the authors propose this surgical procedure as an alternative treatment in patients who have complicated BE or in patients who have long-segment BE. Among patients who have gastroesophageal reflux and intestinal metaplasia of the cardia or with a noncomplicated short-segment BE, laparoscopic antireflux surgery is the authors' first choice, and only the late objective evaluation of surgical treatment demonstrates which surgical technique is the more adequate to a particular patient who has BE.

The role of duodenogastroesophageal reflux (DGER), once erroneously termed "bile reflux," in causing esophageal mucosal damage has been an area of interest in both animal and human studies. However, because of the lack of appropriate techniques to accurately measure DGER, extrapolation of findings from animal studies to humans has been difficult to make. The recent advent of the Bilitec system (Metronics Instruments, Minneapolis, MN), an ambulatory bilirubin monitoring device, is increasing our knowledge of the specific role of DGER in esophageal diseases. Studies suggest that DGER without acid reflux may result in symptoms, but unless acid reflux is present simultaneously, it does not cause esophagitis. Therefore, therapies should aim at reducing both DGER and acid reflux. Studies show that this may be accomplished by antireflux surgery or the use of proton pump inhibitors, which by reducing gastric volume, decrease the damaging potential of both acid and DGER.

Adenocarcinoma of the esophagus has been reported to be increasing in incidence in a number of regions throughout the world, while the incidence of squamous cell carcinoma (SCCA) of the esophagus is mostly stable or decreasing. To evaluate the increasing tendency of adenocarcinoma of the esophagus.

We studied retrospectively the records of patients with histologically proven esophageal cancer between 1970 and 1999 at the Yonsei Medical Center.

Total cases of esophageal cancer were 969 patients of which the cases of adenocarcinoma and SCCA were 27 patients and 918 patients, respectively. The ratio of esophageal adenocarcinoma to SCCA was 0.0375 in the 1970s, 0.0241 in the 1980s and 0.0292 in the 1990s. There was no statistical difference (p = 0.811) in the ratios of adenocarcinoma of the esophagus between the three consecutive 10-year groups.

In conclusion, unlike the US and other western countries, it seems that the ratio of esophageal adenocarcinoma compared to SCCA has not increased among patients with esophageal carcinoma at the Yonsei Medical Center.

The contribution of duodeno-gastroesophageal reflux to the development of Barrett's esophagus has remained an interesting but controversial topic. The present study assessed the risk for Barrett's esophagus after partial gastrectomy.

The data of outpatients from a medicine and gastroenterology clinic who underwent upper gastrointestinal endoscopy for any reason were analyzed in a case-control study. A case population of 650 patients with short- segment and 366 patients with long-segment Barrett's esophagus was compared in a multivariate logistic regression to a control population of 3047 subjects without Barrett's esophagus or other types of gastroesophageal reflux disease.

In the case population, 25 (4%) patients with short-segment and 15 (4%) patients with long-segment Barrett's esophagus presented with a history of gastric surgery compared with 162 (5%) patients in the control population, yielding an adjusted odds ratio of 0.89 with a 95% confidence interval of 0.54-1.46 for short-segment and an adjusted odds ratio of 0.71 (0.30-1.72) for long-segment Barrett's esophagus. Similar results were obtained in separate analyses of 64 patients with Billroth-1 gastrectomy, 105 patients with Billroth-2 gastrectomy, and 33 patients with vagotomy and pyloroplasty for both short- and long-segment Barrett's esophagus. Caucasian ethnicity, the presence of hiatus hernia, and alcohol consumption were all associated with elevated risks for Barrett's esophagus.

Gastric surgery for benign peptic ulcer disease is not a risk factor for either short- or long-segment Barrett's esophagus. This lack of association between gastric surgery and Barrett's esophagus suggests that reflux of bile without acid is not sufficient to damage the esophageal mucosa.

It is known that duodenogastro-oesophageal reflux (DGOR) increases with worsening gastro-oesophageal reflux disease (GORD). It is unclear whether this is accompanied by increasing duodenogastric reflux (DGR).

To investigate the extent of DGR in a control group and 66 patients with GORD, using the technique of ambulatory gastric bilirubin monitoring.

Sixty-six patients with reflux symptoms (30 grade 0 or 1 oesophagitis (group 1), 16 grade 2 or 3 oesophagitis (group 2), 20 Barrett's oesophagus (group 3)) and 17 healthy controls were studied. All underwent oesophageal manometry followed by 24-h ambulatory oesophageal and gastric pH monitoring and gastric bilirubin monitoring.

Median per cent total oesophageal acid exposure (pH < 4) was significantly less in the control group (0.6%) than in group 1 (2.8%, P< 0.05) and groups 2 and 3 (7.5% and 7.8% respectively, P< 0.001). There was no significant difference between any group in median per cent total time gastric pH was greater than 4. There was no significant difference in median per cent total gastric bilirubin exposure (absorbance > 0.14) between any group. However, in each group gastric bilirubin exposure was greater in the supine position than the upright position, being significantly greater in the control group (P< 0.05) and group 1 (P < 0.001).

Gastric bilirubin exposure is similar across the spectrum of GORD severity. It is greater in the supine than in the upright position.

The role of acid in the pathogenesis of gastro-oesophageal reflux disease (GERD) has been extensively studied and is well accepted. The role, if any, of non-acid reflux, in particular duodenogastro-oesophageal reflux, is much debated. The availability of new technology to detect non-acid reflux has heightened interest in this question. This article reviews the following: How do we define non-acid reflux? Does duodenogastro-oesophageal reflux (alone or in combination) cause oesophageal injury, symptoms or both? What is its role in complicated GERD? What methods are available to assess non-acid reflux? Does non-acid reflux need treatment and if so what modalities are available?

The effect of long-term acid suppression therapy in Barrett oesophagus remains unknown, but the high intragastric pH generated has been shown to increase the cytotoxicity of duodenal refluxate on foregut mucosa. However, recent work suggests that duodenogastric reflux (DGR) may be reduced by omeprazole.

To investigate the effect of omeprazole on the reflux of duodenal contents into the gastric antrum in Barrett patients and healthy subjects.

Fifteen patients with Barrett oesophagus and 14 healthy subjects underwent oesophageal manometry followed by 24-h ambulatory oesophageal and gastric pH and gastric bilirubin monitoring. The bilirubin sensor (modified by the addition of a weighted tip to facilitate manoeuvrability) was sited in the gastric antrum under fluoroscopic control. Combined ambulatory pH and bilirubin monitoring was repeated after 2 weeks on omeprazole 20 mg b.d.

Changes in oesophageal acid reflux and gastric alkaline shift due to omeprazole were as expected (P < 0.001). There was no difference in total antral DGR between the Barrett and control groups (P = 0.56), and omeprazole had no significant effect on DGR in either group (P = 0.77 and 0.27, respectively).

DGR into the antrum is of a similar level in Barrett patients and healthy controls. Omeprazole does not reduce the reflux of duodenal contents across the pylorus. Further work is required on the increased cytotoxic potential of continuing DGR in those on long-term acid suppression.

The aim of this study was to review the need for regular endoscopic biopsy of Barrett's esophagus in children.

This was a retrospective case-notes review of 38 children with Barrett's esophagus treated between January 1982 and August 1997. The mean age at diagnosis was 6.3 years (range, 1 to 15 years). All had gastroesophageal reflux at diagnosis. Two patients were treated medically, and 36 underwent antireflux surgery (32 Nissen fundoplication, four Thal procedures). At follow-up, for a mean of 43 months (range, 0 to 13 years), 25 underwent repeated endoscopy and biopsies, two underwent further surgery and biopsies, and four underwent endoscopy only. Seven have had follow-up at their referring hospital.

In the 27 patients who underwent rebiopsy, there was continued evidence of Barrett's esophagus in 15. There was reversion to normal tissue in 10 patients, and mild esophagitis was present in two. There was no evidence of any dysplastic or malignant change in any patient. All cases that reverted to normal esophagus or mild esophagitis had previously undergone a Nissen fundoplication.

Dysplastic degeneration and malignant change did not occur in any of the authors' patients. In addition, 12 patients with Barrett's esophagus reverted to normal. The authors therefore question whether regular endoscopic surveillance is necessary in children under 16 years of age.

Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are decreasing in incidence. Age-standardized incidence rates for the years 1982-1993 for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non-cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age-standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance (P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non-adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non-adenocarcinoma of the oesophagus. The incidence of non-cardia stomach cancer continues to fall.

Bile acid reflux is an important component of duodenogastro-oesophageal reflux but there is no effective method of quantifying it. The contribution of bile acids to oesophageal pH is unknown.

Oesophageal aspirates were collected over 15 h using a new automated suction device and pH was monitored in ten asymptomatic volunteers (group 1) and 30 patients with reflux oesophagitis (group 2, minimal mucosal injury; group 3, erosive oesophagitis; group 4, stricture or Barrett's oesophagus). Bile acid assay was performed by high-performance liquid chromatography.

The concentration of bile acids was significantly higher in group 3 (median (interquartile range) 124 (50-301) mumol/l) and group 4 (181 (85-591) mumol/l) compared with group 1 (0 mumol/l) and group 2 (14 (0-100) mumol/l). Patients in groups 3 and 4 also had significantly greater DeMeester acid scores. Combined bile acid and oesophageal acid reflux was observed in eight of ten patients with stricture or Barrett's oesophagus. There was no correlation between total bile acid concentration and oesophageal acid or alkaline exposure.

This study supports the theory of toxic synergism between acid and bile acids in reflux oesophagitis. Bile acids may contribute to the pathogenesis of Barrett's metaplasia.

The regeneration of intestinal metaplasia by squamous epithelium in 17 patients with Barrett's esophagus after endoscopic laser ablation in a reflux-free environment after successful antireflux surgery was prospectively examined.

All patients had antireflux surgery, and healing of reflux was verified at postoperative endoscopy and 24-hour esophageal pH monitoring. Thereafter, in 11 patients, the whole Barrett's epithelium was ablated using endoscopic Nd-YAG laser energy in 1 to 8 sessions (mean, 4). The needed energy was 965 to 11,173 joules (mean 4709), or about 1000 joules per centimeter of Barrett's esophagus. Six patients had no laser ablation but were treated by antireflux surgery and served as a control group.

In all laser-treated patients, the regenerated epithelium was histologically of squamous type in the tubular esophagus, but two patients still had intestinal metaplasia in the gastric cardia. In controls, the length of Barrett's esophagus and intestinal metaplasia remained unchanged. The length of follow-up was 26 months after the last laser session and 21 months in the control group.

The regenerated esophageal epithelium arising after laser ablation in reflux-free environment surgery is of squamous type. This treatment may have a role in preventing the development of esophageal adenocarcinoma arising in Barrett's esophagus.

Barrett's esophagus represents a metaplastic process in which the normal squamous epithelium of the lower esophagus is replaced by metaplastic columnar epithelium. Although the role of acid and pepsin in the development of Barrett's esophagus is well accepted, the importance of duodenogastroesophageal reflux in this disorder is not clear.

To determine the results of a new surgical procedure for patients with Barrett's esophagus.

In addition to pathologic acid reflux into the esophagus in patients with severe gastroesophageal reflux and Barrett's esophagus, increased duodenoesophegeal reflux has been implicated. The purpose of this study was to establish the effect of a new bile diversion procedure in these patients.

Sixty-five patients with Barrett's esophagus were included in this study. A complete clinical, radiologic, endoscopic, and bioptic evaluation was performed before and after surgery. Besides esophageal manometry, 24-hour pH studies and a Bilitec test were performed. After surgery, gastric emptying of solids, gastric acid secretion, and serum gastrin were determined. All patients underwent highly selective vagotomy, antireflux procedure (posterior gastropexy with cardial calibration or fundoplication), and duodenal switch procedure, with a Roux-en-Y anastomosis 60 cm in length.

No deaths occurred. Morbidity occurred in 14% of the patients. A significant improvement in symptoms, endoscopic findings, and radiologic evaluation was achieved. Lower esophageal sphincter pressure increased significantly (p < 0.0001), as did abdominal length and total length of the sphincter (p < 0.0001). The presence of an incompetent sphincter decreased from 87.3% to 20.9% (p < 0.0001). Three of seven patients with dysplasia showed disappearance of this dysplasia. Serum gastrin and gastric emptying of solids after surgery remained normal. Basal and peak acid output values were low. Twenty-four hour pH studies showed a mean value of 24.8% before surgery, which decreased to 4.8% after surgery (p < 0.0001). The determination of the percentage time with bilirubin in the esophagus was 23% before surgery; this decreased to 0.7% after surgery (p < 0.0001). Late results showed Visick I and II gradation in 90% of the patients and grade III and IV in 10% of the patients.

This physiologic approach to the surgical treatment of patients with Barrett's esophagus produces a permanent decrease of acid secretion (and avoids anastomotic ulcer), decreases significantly acid reflux into the esophagus, and abolishes duodenoesophageal reflux permanently. Significant clinical improvement occurs, and dysplastic changes at Barrett's epithelium disappear in almost 50% of the patients.

Experimental work in animals has implicated a role for bile in the pathogenesis of several oesophageal mucosal diseases such as oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. Recent descriptions of a high incidence of intestinal metaplasia at the gastro-oesophageal junction in patients without a classical 3-cm Barrett's columnar-lined segment, combined with a rising incidence in oesophageal and cardia adenocarcinoma, have stimulated interest in the causes of these conditions.

Animal studies concerned with defining the role of the various gastroduodenal reflux constituents in oesophageal mucosal injury are summarized and evidence for bile in the pathogenesis of Barrett's oesophagus and oesophageal adenocarcinoma is reviewed. The results of various techniques for clinical measurement of oesophageal bile reflux, such as aspiration, scintigraphy and pH monitoring, are evaluated and the significance of recent studies employing ambulatory fibreoptic bilirubin monitoring is discussed.

There seems little doubt that bile plays a significant role in oesophageal mucosal disease, in synergy with other constituents of reflux. Although ambulatory bilirubin monitoring is new, some intriguing findings have been reported and it is hoped that this technique will continue to shed light on the role of bile in the oesophagus.

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.

The role of acid and duodenogastric reflux (DGR) in the development of esophageal mucosal injury has been extensively investigated using both animal and human models. In this report, clinical and experimental data are reviewed. The mechanisms by which gastric and duodenal contents produce esophageal mucosal injury are also discussed. Acid and pepsin are unquestionably important in causing mucosal damage at low pH values in both animal and human models. Animal models suggest synergistic damaging potential for conjugated bile acids and HCI as well as that of unconjugated bile acids and trypsin in more neutral pH values. Human evidence for the involvement of bile and its constituents has been controversial; however, the advent of better technology to detect DGR is beginning to clarify the role of these constituents. The contribution of each methodology in clarifying the extent of involvement of DGR in esophageal mucosal injury is reviewed. Despite some conflicting results, preliminary human studies support the results from the animal data suggesting synergistic damaging effects for both bile and acid in esophageal mucosal injury. The implication of these studies in treating gastroesophageal reflux disease are discussed.

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.

Epidemiologic cohort studies have established that after distal gastric resection, there is a higher risk of gastric carcinoma. It is likely that a main factor of this higher risk is the excessive duodenogastric reflux induced by surgery, because the incidence of stump carcinomas is higher in Billroth II than in Billroth I, and most of the stump carcinomas are located near the stoma. In addition, several groups of investigators have suggested that duodenogastric reflux per se induces stump carcinomas in rats. There is another human duodenogastric reflux, the primary duodenogastric reflux, through the pylorus. Experiments in animals have demonstrated that this type of duodenal reflux also induces gastric carcinomas in the antrum of the stomach that has not undergone surgery. Recent clinical attention has focused on the role of duodenogastric reflux in the pathogenesis of Barrett's esophagus and subsequent esophageal adenocarcinomas. Experimentally, reflux of duodenal contents into the esophagus can cause not only Barrett's esophagus and subsequent adenocarcinomas, but also squamous cell carcinomas. These findings suggest that duodenogastric reflux may be implicated in gastric and esophageal, that is, foregut carcinogenesis.

Duodenogastric reflux has been implicated in the pathogenesis of complicated Barrett's esophagus and gastric ulceration. A group of 123 Barrett's patients were followed for a mean of 41 months; 9 (7%) developed gastric ulceration (GU). Of the Barrett's patients treated by antireflux surgery, 14% developed GU. We reviewed the gastric histology on 54 Barrett's patients (34 men, 20 women; average age 64 years) at presentation and classified the gastritis according to the Sydney system. A normal histologic pattern was present in seven patients; 15 patients had chronic pangastritis, 9 chronic antral gastritis, and 18 chronic gastritis of the corpus. Five patients had acute gastritis only, and in 74% there was reactive chronic gastritis. Of the patients with chronic gastritis, 45% (19 of 42) had histologic evidence of duodenogastric reflux, established by the bile reflux index. The presence of reactive chronic gastritis in Barrett's patients may have important pathophysiologic and therapeutic implications.

To review recent advances in the diagnosis and treatment of gastroesophageal reflux disease (GERD).

Original English language reports were obtained through a Medline search of the National Library of Medicine up to and including 1993. The reference lists of all original reports and review articles were searched to locate any further material. In the evaluation of therapeutic efficacy, randomized studies were preferentially considered; greatest priority was given to double-blind, placebo-controlled trials. Abstracts, nonrandomized trials, and non-English language publications were considered only when other data were unavailable.

Information obtained from histories and physical examinations suggests that GERD occurs in many patients. Evaluation of mucosal injury with use of either endoscopy or air contrast barium radiography is an important early step in the diagnosis of GERD. Endoscopy obtains tissue for histologic study, especially in Barrett's esophagus. Prolonged esophageal pH monitoring is the most useful determinant of the presence and amount of reflux of acid. Patients with GERD should be counseled on lifestyle modification and the use of antacids and antirefluxants. Histamine type 2 receptor antagonists provide symptomatic relief in 32 to 82% of patients with GERD and resolution of verified esophagitis in 0 to 82%. Responses with omeprazole therapy are higher; symptomatic responses were noted in 62 to 94% of patients, and healing of esophagitis occurred in 71 to 96%. Promotility agents and surgical therapy have a role in selected patients.

GERD is a chronic disorder that often necessitates individualized lifelong therapy. Many questions remain to be answered about the cost-effectiveness of both diagnostic tests and therapy for GERD.

A study was designed to determine whether oesophageal carcinomas can be induced through reflux of duodenal contents. Male Wistar rats weighing 230-250 g were divided into three groups according to the surgical procedure performed: (1) the duodenal contents were directed into the forestomach through a stoma (duodeno-forestomach reflux); (2) the duodenal contents were regurgitated into the forestomach through the glandular stomach (duodeno-glandular-forestomach reflux); and (3) a sham operation was performed as a control. Animals were fed standard CRF-1 solid food and tap water that was not exposed to carcinogens and were sacrificed 50 weeks post-operatively. While no neoplasia was observed in any of the 32 control rats, 4/11 (36%) with duodeno-forestomach reflux and 3/18 (17%) animals with duodeno-glandular-forestomach reflux developed carcinomas in the lower oesophagus and forestomach. The incidence in each group was significantly higher than in the controls (P < 0.01 and P < 0.05 respectively). Six of the seven lesions consisted of squamous cell carcinomas, and one was a mucinous adenocarcinoma. Oesophageal columnar epithelial metaplasia was observed in two (18%) of the animals with duodeno-forestomach reflux. Carcinomas were always surrounded by chronic inflammatory changes, including regenerative thickening, basal cell hyperplasia and dysplasia. Additional well-differentiated adenocarcinomas were observed in the prepyloric antrum of 6/18 (33%) animals with duodeno-glandular-forestomach reflux. These findings indicate that chronic reflux of duodenal contents may cause oesophageal carcinoma.

Assessment of duodenogastric bile reflux has hitherto been unsatisfactory. An ambulatory system which utilizes the optical properties of bilirubin is examined. Test readings are correlated with the laboratory values for bilirubin in each of a number of physiological solutions. For dilutions of pure bile there was a linear correlation between absorbance and bilirubin concentration (r = 0.93, p < 0.001). In the more acidic environment of gastric juice there was also a linear correlation between absorbance and bilirubin concentration (r = 0.65, p < 0.001), but absorbance values were significantly higher than those of pure bile solutions (F ratio = 130, p < 0.0001). Normal gastric secretions and saliva give low absorbance values (0.02-0.04). Common foodstuffs such as soups, tea and coffee give higher readings and may interfere with bile reflux assessment in a clinical setting. Bilitec 2000 has potential for use as an ambulatory bile reflux monitoring system but consideration should be given to a standard diet or attention must focus on the fasting period.

Acid gastro-oesophageal reflux occurs when the lower oesophageal sphincter is incompetent, but oesophagitis caused by reflux of duodenal content implies incompetence of both the pyloric and gastro-oesophageal sphincters. The term 'alkaline' reflux oesophagitis was coined long before objective analysis was made of bile in the stomach and oesophagus, and well before pH monitoring was introduced. Surgical procedures to divert bile from the stomach and oesophagus were developed on a clinical basis and gave encouraging results in the management of peptic oesophageal stricture. Alkaline oesophagitis is well recognized after gastric surgery and the entity 'primary pathological duodenogastric reflux', although contested by some, attracts growing support. Recent evidence suggests that the complications of Barrett's oesophagus may be related to duodenogastro-oesophageal reflux. Probes designed to measure gastric and oesophageal bile salts have recently been developed and may give more information in the future.

Peptic ulceration arising in the lower esophagus lined by columnar epithelium was described in detail by Tileston in 1906. Although this concept was challenged in 1950 by Barrett, experimental and clinical evidence has now conclusively demonstrated that Barrett's metaplasia is an acquired condition and is a consequence of chronic reflux of gastric or duodenal contents or both. Current concepts suggest that unknown trophic factors present in these secretions stimulate proliferation of multipotential reserve cells located in the esophageal submucosal glands resulting in columnar metaplasia of the normal squamous epithelium with subsequent potential for malignant degeneration. Today, numerous patients are affected by reflux esophagitis, a lesser number by Barrett's metaplasia, and a smaller but ever-enlarging group by adenocarcinoma. Although high-grade dysplasia is considered a precursor to invasive adenocarcinoma, detection of this abnormal mucosa remains controversial and currently requires esophagoscopy with biopsy. Epithelial markers, such as increased activity of mucosal ornithine decarboxylase, sulfomucin production, nuclear DNA aneuploidy, and recently molecular analysis, have also been proposed to identify those paitents at increased risk for malignant degeneration. As more is learned about the pathogenesis of Barrett's disease, perhaps these cancers can ultimately be prevented.

Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.

Columnar-lined or Barrett's esophagus is a premalignant condition. It is almost unvariably due to chronic gastroesophageal reflux. Since there are some reports that Barrett's esophagus can be induced by chemotherapy, we investigated 20 male patients, treated with chemotherapy for testicular cancer, and 18 female patients, treated with high-dose chemotherapy for breast cancer. Only one patient in the testicular cancer group had Barrett's esophagus of the circumferential type, in addition to typical reflux esophagitis and a hiatal hernia four years after chemotherapy. In the breast cancer group one patient had an indeterminate junction. Our results do not support the hypothesis that chemotherapy poses a substantially increased risk for the development of Barrett's esophagus.

The role of reflux oesophagitis and acid in the development of oesophageal columnar epithelium was investigated in the rat. Twenty-four animals underwent total gastrectomy and oesophagojejunostomy, inducing reflux of duodenal contents into the oesophagus, and were divided into two groups: an 'acid' group, which drank syrup water with hydrochloric acid (pH 1.8), and a 'non-acid' group, which drank only syrup water (pH 6.5). Four rats were killed at 4, 8 and 12 weeks after surgery. Reflux oesophagitis was found in the lower portion of the oesophagus in all cases. Columnar epithelium was observed in the oesophagus of one rat in the non-acid group at week 8 and of three in the acid group at week 12. These results indicate that the development of columnar epithelium of the oesophagus is preceded by reflux oesophagitis and that acidic conditions may promote this change. Columnar epithelialization may result from metaplasia of squamous epithelium as well as from upward extension of columnar epithelium.

Gastroesophageal reflux disease (GERD) remains a ubiquitous problem, although therapeutic options continue to evolve. Effective therapy calls for understanding the pathogenesis. Key factors associated with GERD include incompetence of the lower esophageal sphincter, esophageal clearance, gastric contents, tissue resistance, and potency of the refluxate. Phase-type directed therapy remains the best treatment approach and histamine (H2)-receptor antagonists are now the cornerstone of therapy for patients not responsive to conservative measures. In a subset of patients with severe esophagitis who do not respond to conventional H2-receptor antagonist therapy, efficacy has been demonstrated with high-dose therapy. The acid suppressant omeprazole, highly effective in erosive esophagitis, is the drug of choice for esophagitis resistant to H2-receptor antagonists. Despite effective forms of therapy, relapse rates are high in patients with severe GERD, and maintenance therapy typically is required. With near uniformity, efficacy end points for these agents have been directed toward relief of heartburn, regurgitation, and dyspepsia. Few data exist correlating relief of GERD and improvement of chest pain. Although therapeutic strategies for treating GERD have improved, empiric treatment of suspected GERD in the patient with noncardiac chest pain does not appear to be the optimal approach and should be reserved for cases where diagnostic testing is limited or unavailable.

The tissues of the alimentary tract react to abnormal functional demands or to injury from environmental chemicals by reactions which involve change in morphology, functional characteristics and cellular proliferation. The work hyperplasia, wound repair or response to xenobiotics may become distorted by inherent, or induced, genomic abnormalities of the affected cells. It seems that some of the reactions are 'programmed' or 'planned' and depend on predetermined changes in gene expression. Although the reactions permit survival in the face of environmental hazards, the necessary alterations in gene expression may predispose to malignant change in the affected cells.