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.     

Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux

Experimental studies have shown that the severity of esophageal mucosal injury in gastroesophageal reflux disease is related to the reflux of both gastric and duodenal juice. The purpose of this study was to determine whether duodenal juice potentiates esophageal injury in patients with reflux disease or, inf act, causes no harm allowing acid and pepsin to do the damage. A total of 148 consecutive patients who had no previous gastric or esophageal surgery underwent endoscopy and biopsy, manometry, and 24-hour esophageal pH and bilirubin monitoring. Esophageal injury was defined by the presence of erosive esophagitis, stricture, or biopsy-proved Barrett's esophagus. Exposure to duodenal juice, identified by the absorbance of bilirubin, was defined as an exposure time exceeding the ninety-fifth percentile measured in 35 volunteers. To separate the effects of gastric and duodenal juice, patients were stratified according to their acid exposure time. One hundred patients had documented acid reflux on pH monitoring, and in 63 of them it was combined with reflux of duodenal juice. Patients with combined reflux (50 of 63) were more likely to have injury than patients without combined reflux (22 of 37; P < 0.05). When the acid exposure time was greater than 10%, patients with injury (n = 40) had a greater exposure to duodenal juice (median exposure time 17.2% vs. 1.1%, P = 0.006) than patients without injury (n = 5), but there was no difference in their acid exposure (16.9% vs. 13.4%). Patients with dysplasia of Barrett's epithelium (n = 9) had a greater exposure to duodenal juice (median exposure time 30.2% vs. 7.2%, P = 0.04) compared to patients without complications (n = 25), whereas acid exposure was the same (16.4% vs. 15%). Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa.     

Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized.

OBJECTIVE: The author's goal was to determine the role of duodenal components in the development of complications of gastroesophageal reflux disease. SUMMARY AND BACKGROUND DATA: There is a disturbing increase in the prevalence of complications, specifically the development of Barrett's esophagus among patients with gastroesophageal reflux disease. Earlier studies using pH monitoring and aspiration techniques have shown that increased esophageal exposure to fluid with a pH above 7, that is, of potential duodenal origin, may be an important factor in this phenomenon. METHODS: The presence of duodenal content in the esophagus was studied in 53 patients with gastroesophageal reflux disease confirmed by 24-hour pH monitoring. A portable spectrophotometer (Bilitec 2000, Synectics, Inc.) with a fiberoptic probe was used to measure intraluminal bilirubin as a marker for duodenal juice in the esophagus. Normal values for bilirubin monitoring were established for 25 healthy subjects. In a subgroup of 22 patients, a custom-made program was used to correlate simultaneous pH and bilirubin absorbance readings. RESULTS: Fifty-eight percent of patients were found to have increased esophageal exposure to gastric and duodenal juices. The degree of mucosal damage increased when duodenal juice was refluxed into the esophagus, in that patients with Barrett's metaplasia (n = 27) had a significantly higher prevalence of abnormal esophageal bilirubin exposure than did those with erosive esophagitis (n = 10) or with no injury (n = 16). They also had a greater esophageal bilirubin exposure compared with patients without Barrett's changes, with or without esophagitis. The correlation of pH and bilirubin monitoring showed that the majority (87%) of esophageal bilirubin exposure occurred when the pH of the esophagus was between 4 and 7. CONCLUSIONS: Reflux of duodenal juice in gastroesophageal reflux disease is more common than pH studies alone would suggest. The combined reflux of gastric and duodenal juices causes severe esophageal mucosal damage. The vast majority of duodenal reflux occurs at a pH range of 4 to 7, at which bile acids, the major component of duodenal juice, are capable of damaging the esophageal mucosa.     

Circadian esophageal motor function in patients with gastroesophageal reflux disease

Effective esophageal peristalsis is a major determinant of esophageal clearance function and may contribute to the development of complications in gastroesophageal reflux disease. Using 24-hour ambulatory esophageal manometry, we compared the circadian esophageal motor activity of normal volunteers to that of patients with increased esophageal exposure to gastric juice and various grades of mucosal injury (no mucosal injury, esophagitis, stricture, or Barrett's esophagus). The prevalence of a mechanically defective lower esophageal sphincter, esophageal acid exposure time, and the frequency of nonperistaltic esophageal contractions during the supine, upright, and meal periods increased with increasing severity of mucosal injury. The median amplitude of esophageal contractions was compromised only in patients with a mechanically defective sphincter. This was particularly so in patients with stricture or Barrett's esophagus and was associated with an increased frequency of ineffective contractions (less than 30 mm Hg). These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be caused by persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. The need for surgical correction of a mechanically defective sphincter before the loss of esophageal body function is implicated.     

Gastric juice protects against the development of esophageal adenocarcinoma in the rat.

OBJECTIVE: The authors investigate the effects of gastric juice on tumorigenesis in a rat model of esophageal adenocarcinoma. SUMMARY BACKGROUND DATA: In rats treated with the carcinogen methyl-n-amyl nitrosamine, squamous cancer of the esophagus develops in a time- and dose-dependent manner. When methyl-n-amyl nitrosamine treatment is preceded by an operation to induce reflux of duodenal and gastric juice into the esophagus, there is an increased yield of esophageal tumors, many of which are adenocarcinomas. When only gastric juice refluxes into the esophagus, the tumor yield is less and adenocarcinomas are not found. METHODS: Two hundred seventy 8-week old Sprague-Dawley rats were studied. Twenty unoperated rats served as controls. The remaining rats underwent the following operations: esophagoduodenostomy with gastric and vagal preservation to induce duodenogastroesophageal reflux (n = 48); esophagoduodenostomy with antrectomy and Billroth 1 reconstruction to produce reflux of duodenogastric juice with the exclusion of the antrum (n = 53); esophagoduodenostomy with proximal gastrectomy to induce hypergastrinemia and reflux of duodenogastric juice with exclusion of the body and forestomach (n = 51); esophagoduodenostomy plus total gastrectomy to produce reflux of duodenal juice alone (n = 50); and esophagoduodenostomy with vagal and gastric preservation but with division of the duodenum just beyond the pylorus and reimplantation into the jejunum, 13 cm distal to the esophagoduodenostomy. This produced reflux of duodenal juice with gastric juice diverted downstream, (n = 48). At 10 weeks of age, all rats were given 4 weekly doses of carcinogen (methyl-n-amyl nitrosamine, 25 mg/kg intraperitoneally), and survivors were killed at 36 weeks of age. RESULTS: The prevalence rate of esophageal adenocarcinoma was 30% in rats with duodenogastroesophageal reflux and 87% in rats with reflux of duodenal juice alone. Fifty-six percent of rats with reflux of duodenogastric juice with exclusion of the antrum and 72% of rats with reflux of duodenogastric juice with the exclusion of the body and forestomach developed adenocarcinoma, showing a progression increase in the prevalence of adenocarcinoma as less gastric juice was permitted to reflux with duodenal juice into the esophagus. CONCLUSION: In this rat model, the presence of gastric juice in refluxed duodenal juice against the development of esophageal adenocarcinoma. The protective effect appears to be due to acid secretion from the stomach. Continuous profound acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in patients with duodenogastroesophageal reflux.     

Usefulness of combined gastric and esophageal pH monitoring in detecting gastroesophageal alkaline and mixed reflux

96 patients with 'typical' symptoms of gastroesophageal reflux were studied by means of combined gastric and esophageal pH monitoring. The aim was to assess the incidence of 'alkaline' and 'mixed' gastroesophageal reflux episodes as well as 'acid' reflux and their reciprocal relationship with esophagitis. 'Alkaline' gastroesophageal reflux was defined whenever the pH in the esophagus rose above 7, but only when there was a simultaneous or immediately previous rise of gastric pH to similar alkaline values resulting from duodenogastric reflux. 'Mixed' gastroesophageal reflux was defined whenever the pH in the esophagus dropped to 5.5-4.5, but only when there was a simultaneous or immediately previous rise of gastric pH above 4 related to duodenogastric reflux. Our data suggest that 'alkaline' gastroesophageal reflux is a rare phenomenon while 'mixed' gastroesophageal reflux episodes are present in 21% of these patients. 87% of patients with mixed reflux had esophagitis. Until analytical studies of refluxed material are available to clarify its composition, combined gastric and esophageal pH monitoring seems a useful test to correctly interpret the 'alkaline' and 'mixed' gastroesophageal reflux.     

Is duodeno-gastro-esophageal reflux just a bystander of acid reflux?

BACKGROUND & AIM: Duodeno-gastro-esophageal reflux (DGER) as measured with bilirubin monitoring is observed in many patients with reflux disease especially in Barrett's esophagus. As acid suppression is an effective therapy of reflux disease, DGER is frequently just considered as a bystander of acid reflux. To define the importance of DGER, reflux of duodenal contents was evaluated by bilirubin monitoring in the stomach. METHODS: 100 patients with reflux disease were evaluated (62 m, 38 f, 50 (12) years). 26 patients had Barrett's esophagus, 57 had esophagitis and 17 non- erosive reflux disease (pH pos.). All patients were evaluated with simultaneous 24-hour bilirubin monitoring in the esophagus and stomach. Results were compared to 35 measurements of healthy volunteers in the esophagus and 41 measurements in the stomach. RESULTS: Normal values: DGER - Exposure time esophagus > 11.8 % using an absorbance value > 0.14, duodenogastric reflux (DGR) - Exposure time stomach >24.8 % using an absorbance value > 0.25. 56 % of the patients had DGER, 41 % had DGR. 29 of the 41 patients with DGR had DGER (71 %), while 27 of the 56 patients with DGER had physiologic duodenogastric reflux (48 %). DISCUSSION: About 30 % of the patients with reflux disease show DGER combined with excessive DGR. Therefore, DGER is not just a bystander of acid reflux. The excessive DGR in some patients adds additional potentially dangerous substances to the esophageal reflux.     

Concentration of refluxed acid and esophageal mucosal injury.

The hallmark of gastroesophageal reflux disease (GERD) is an increase in esophageal exposure to gastric juice. This exposure can result in complications such as esophagitis, stricture, and Barrett's esophagus. The aim of this study is to determine if there are specific pH exposure patterns that are associated with the development of these complications. The 24-hour esophageal pH data for 50 normal subjects and 154 patients with proven GERD were analyzed for time spent at different pH intervals. Increased esophageal acid exposure at a given interval occurred when the cumulative time of exposure exceeded the 95th percentile of that measured in the 50 normal subjects for that interval. The greatest prevalence of mucosal damage was found in the those patients with increased esophageal exposure to pH 0 to 2, corresponding to the known pKa of pepsin. This exposure was not related to a hypersecretory state. In addition, mucosal injury was associated with an increased esophageal exposure to pH 7 to 8. We conclude that mucosal injury in patients with GERD is related to the exposure time to gastric juice with a pH of less than 2 or greater than 7.     

Etiology and importance of alkaline esophageal reflux.

While an alkaline component to esophageal reflux disease is known to be present, little is known about its etiology and harmful effects. Simultaneous gastric and esophageal 24-hour pH monitoring was performed in 81 patients with foregut symptoms. The presence of a mechanically defective lower esophageal sphincter was determined by manometry and duodenogastric reflux by computer-assisted discriminant analysis of the gastric pH record. Heartburn, dysphagia, and regurgitation occurred more frequently in those with a mechanically defective sphincter (p < 0.05) and epigastric pain in those with duodenogastric reflux (p < 0.05). Esophagitis was more common and severe in those with a mechanically defective sphincter (p < 0.05). In these patients, the percentage of time over 24 hours that the esophageal pH was less than 4 was 40.5% in patients without duodenogastric reflux but only 10.2% in those with duodenogastric reflux (p < 0.005), suggesting acid damage in the former and alkaline damage in the latter. To establish the origin of the esophageal alkaline exposure, episodes of elevated fasting gastric pH greater than 4 lasting longer than 1 minute were searched for and identified in 45 patients. Esophageal pH tracings were compared for 30 minutes before and after these events. The esophageal pH was higher following these episodes in duodenogastric reflux patients (p < 0.05), suggesting a gastroduodenal origin of the esophageal alkalinization. This study shows that esophageal damage may be due to acid or alkaline reflux. The alkaline component of gastroesophageal reflux is important and should be considered in the evaluation of patients with foregut symptoms so that appropriate medical or surgical therapy can be instituted.     

Gastric fluid bile concentrations and risk of Barrett's esophagus

Patients with Barrett's esophagus are at high risk of progression to adenocarcinoma. A growing, but conflicting body of evidence implicates bile reflux as a contributor to Barrett's esophagus. To investigate whether duodenogastric reflux was associated with an increased risk of Barrett's esophagus, a case-control study of incident Barrett's esophagus was performed. Cases (n=72) were identified by new histologically-confirmed diagnosis of specialized intestinal metaplasia (indicative of Barrett's esophagus) following upper endoscopy for refractory gastroesophageal reflux between October 1997 and September 2000. Cases were compared to gastroesophageal reflux patients without specialized intestinal metaplasia (controls; n=72). There was no difference in total bile acid concentrations between cases and controls. Risk of Barrett's esophagus did not significantly vary with increasing concentrations of total or free bile acids, respectively (OR 0.35 (95% CI 0.12, 1.02) and 0.60 (95% CI 0.22, 1.66)). Low gastric fluid pH (toxic range 3-5), was associated with a non-significant increase in the risk of Barrett's esophagus. In conclusion, no significant association between Barrett's esophagus and total or free bile acids in gastric refluxate was found. Patients with low gastric fluid pH (3-5) may represent a subset of patients at high risk of developing Barrett's esophagus.     

Helicobacter pylori is not associated with the manifestations of gastroesophageal reflux disease.

HYPOTHESIS: Helicobacter pylori is not associated with gastroesophageal reflux disease and its complications, including adenocarcinoma of the esophagus and the gastroesophageal junction (GEJ). DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Two hundred twenty-nine patients with symptoms suggestive of foregut disease underwent esophageal manometry, 24-hour pH monitoring, and upper gastrointestinal tract endoscopy, with biopsy specimens obtained from the gastric antrum, the GEJ, and the distal esophagus. In these and in an additional 114 patients with adenocarcinoma of the esophagus and the GEJ, the presence of H. pylori was determined by Giemsa stain. The presence of gastroesophageal reflux disease, defined by abnormal esophageal acid exposure, and its manifestations (carditis, erosive esophagitis, intestinal metaplasia limited to the GEJ, Barrett esophagus, and adenocarcinoma of the esophagus and GEJ) were correlated with the presence of H. pylori. RESULTS: Helicobacter pylori was found on the biopsy specimens of the gastric antrum in 14.0% (32/229) of the patients with benign disease. It was not related to the features of gastroesophageal reflux disease, including abnormal esophageal acid exposure, erosive esophagitis, or Barrett esophagus. The presence of inflamed cardiac mucosa at the GEJ or carditis was inversely related to H. pylori infection and strongly associated with increased esophageal acid exposure. There was no association between the presence of intestinal metaplasia and H. pylori infection. Helicobacter pylori was found in 22 (19.3%) of the 114 patients with esophageal adenocarcinoma, which was not different from the prevalence of H. pylori in patients with benign disease. CONCLUSION: Helicobacter pylori plays no role in the pathogenesis of gastroesophageal reflux disease or its complications.     

Duodenogastric and gastroesophageal bile reflux

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.     

Duodenogastric reflux and reflux esophagitis

Twenty-seven patients with gastroesophageal reflux were prospectively investigated to define the role of duodenogastric reflux in the development of reflux esophagitis. Duodenogastric reflux was detected and quantified by pH monitoring of the gastric environment 5 cm distal to the distal esophageal sphincter. Alkaline duodenogastric reflux was identified by the occurrence of spontaneous, intense gastric alkalinization during fasting periods. Patients with reflux with esophagitis were distinguished from those without esophagitis by having fewer of these episodes and, consequently, more acid stomachs than had patients without esophagitis. As previously shown, refluxers with esophagitis also had more frequent acid gastroesophageal reflux and prolonged gastric emptying. These findings suggest that refluxers with esophagitis have a functional gastropyloric disturbance resulting in delayed gastric emptying, decreased frequency of alkaline duodenogastric reflux episodes, and more frequent acid gastroesophageal reflux than do refluxers without esophagitis.     

Gastroesophageal reflux disease and mucosal injury with emphasis on short-segment Barrett’s esophagus and duodenogastroesophageal reflux

Gastroeosphageal reflux disease has been associated with long segments of Barrett’s esophagus (≥3 cm), but little is known about its association with shorter segments. The aim of this study was to evaluate anatomic and physiologic alterations of the cardia and esophageal exposure to gastric and duodenal juice in patients with short and long segments of Barrett’s esophagus. Furthermore, these patients were compared to each other and to patients with erosive esophagitis and those with no mucosal injury. Two hundred sixty-two consecutive patients with foregut symptoms were divided into the following four groups based on endoscopic and histologic findings: group 1, no mucosal injury; group 2, erosive esophagitis; group 3, short-segment Barrett’s esophagus; and group 4, long-segment Barrett’s esophagus. Esophageal exposure time to acid and bilirubin, lower esophageal sphincter characteristics, and endoscopie anatomy of the cardia were compared between the groups. Patients with short-segment Barrett’s esophagus had elevated esophageal acid and bilirubin exposure, decreased lower esophageal sphincter pressure and length, and a high incidence of hiatal hernia. These abnormalities were similar to those in patients with esophagitis and in general less profound than those found in patients with long-segment Barrett’s esophagus. The length of intestinal metaplasia was higher in patients with a defective lower esophageal sphincter. Short-segment Barrett’s esophagus is a complication of severe gastroesophageal reflux disease and is associated with the reflux of both gastric and duodenal juice similar to that seen in patients with long-segment Barrett’s esophagus. Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14,1997.     

Specificity and sensitivity of objective diagnosis of gastroesophageal reflux disease

To evaluate the diagnostic value of different tests for gastroesophageal reflux disease, a test population was constructed from 45 patients with symptoms of heartburn and regurgitation with or without esophagitis and 45 healthy subjects, who never experienced heartburn, regurgitation, or swallowing discomfort. The test population underwent esophagoscopy, standard acid reflux test, 24-hour pH monitoring, and manometry of the lower esophageal sphincter. Sensitivity, specificity, positive predictive value, negative predictive value, and the accuracy of the tests and test combinations were calculated. Esophagoscopy had a sensitivity of 62%, that is, only 62% of patients with the disease have evidence of mucosal damage on endoscopy. Manometric measurements of the lower esophageal sphincter had a sensitivity of 84%, a specificity of 89%, and an accuracy of 87%. Twenty-four hour esophageal pH monitoring had a sensitivity, specificity, and accuracy of 96%. The results show that 24-hour pH monitoring can detect gastroesophageal reflux disease with an accuracy of 96% by measuring an increase in esophageal acid exposure. Manometry of the lower esophageal sphincter can detect a mechanically deficient sphincter as a cause of the disease with an accuracy of 87%. The test combination of 24-hour monitoring and motility studies can select patients with an accuracy of 91% who have an increase in esophageal exposure to gastric juice because of a deficient cardia. Antireflux surgery is designed to reduce esophageal exposure to gastric juice in patients with a deficient sphincter by creating a mechanical antireflux mechanism at the cardia. Therefore it is necessary to determine the mechanical status of the sphincter with manometry before surgery in such patients. Thus the indications for antireflux surgery are (1) uncontrolled symptoms of increased esophageal exposure to gastric juice; (2) a documented increase in esophageal exposure to gastric juice by 24-hour pH monitoring; and (3) a mechanically defective sphincter on motility with a pressure of 6 mm Hg or less, an overall length of 2 cm or less, and an abdominal length of 1 cm or less.     

Swedish adjustable gastric banding – an underestimated risk factor for the development of esophageal cancer?

BACKGROUND: Patients with obesity are at higher risk for gastroesophageal reflux disease and also for adenocarcinoma of the distal esophagus. METHODS: Case report. RESULTS: We report on a 58-year-old male patient who developed adenocarcinoma of the distal esophagus (Barrett's cancer) 13 years after implantation of a SAGB (Swedish adjustable gastric banding). Predisposition to reflux combined with bad compliance (frequent overeating) lead to dilation of the pouch followed by impairment of the lower esophageal sphincter with a permanent exposition of the distal esophagus to refluxate. This "stasis esophagitis" over years finally ended in development of neoplasia. Consequently, the patient underwent an esophageal resection with gastric tube pull-up and intrathoracic anastomosis. CONCLUSIONS: From a functional point of view, preoperative work up before SAGB should include detailed history, endoscopy with biopsies of the z-line and esophageal manometry. In case of defective esophageal peristalsis or suspected incompliance of the patient, an implantation of a SAGB should not be performed.     

Difficulties in defining and diagnosing gastroesophageal reflux: practical implications in surgery

Today, it is difficult to set a correct definition and diagnosis of gastroesophageal reflux disease. The attempt to define it on the basis of "typical" symptoms, like heartburn and regurgitation, or "atypical" symptoms, like chronic cough, asthma, hoarseness and thoracic pain, or on the basis of endoscopic esophagitis presents notable difficulties. Moreover, the problem of a correct definition is tightly tied up to the ability to set a correct and early diagnosis. There are many diagnostics tools, but none of them is the golden standard. Today, the trend is to emphasize the role of the 24-hour pH-monitoring in diagnosing the reflux in those symptomatic patients with no visible esophagitis. However, its limit is to underline only the acid, not the duodenogastric alkaline reflux, which is also very important in the genesis of the inflammatory esophageal lesions. The esophageal manometry, however, evaluates only the mechanical state of the lower esophageal sphincter and the peristaltic function of the esophageal body but does not provide any direct information about the exposure of the esophagus to the gastric juice. The aim of this study is to analyze the problems concerning the definition and the diagnosis of the gastroesophageal reflux disease with particular attention to the practical implications on the common surgical practice, and to review some solutions reported in the literature for the difficult clinical approach to the patient with this pathology.     

Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.

OBJECTIVE: The purpose of the study was to test the hypothesis that cardiac mucosa, carditis, and specialized intestinal metaplasia at an endoscopically normal-appearing cardia are manifestations of gastroesophageal reflux disease. SUMMARY BACKGROUND DATA: In the absence of esophageal mucosal injury, the diagnosis of gastroesophageal reflux disease currently rests on 24-hour pH monitoring. Histologic examination of the esophagus is not useful. The recent identification of specialized intestinal metaplasia at the cardia, along with the observation that it occurs in inflamed cardiac mucosa, led the authors to focus on the type and condition of the mucosa at the gastroesophageal junction and its relation to gastroesophageal reflux disease. METHODS: Three hundred thirty-four consecutive patients with symptoms of foregut disease, no evidence of columnar-lined esophagus, and no history of gastric or esophageal surgery were evaluated by 1) endoscopic biopsies above, at, and below the gastroesophageal junction; 2) esophageal motility; and 3) 24-hour esophageal pH monitoring. The patients were divided into groups depending on the histologic presence of cardiac epithelium with and without inflammation or associated intestinal metaplasia. Markers of gastroesophageal reflux disease were compared between groups (i.e., lower esophageal sphincter characteristics, esophageal acid exposure, the presence of endoscopic erosive esophagitis, and hiatal hernia). RESULTS: When cardiac epithelium was found, it was inflamed in 96% of the patients. The presence of cardiac epithelium and carditis was associated with deterioration of lower esophageal sphincter characteristics and increased esophageal acid exposure. Esophagitis occurred more commonly in patients with carditis whose sphincter, on manometry, was structurally defective. Specialized intestinal metaplasia at the cardia was only seen in inflamed cardiac mucosa, and its prevalence increased both with increasing acid exposure and with the presence of esophagitis. CONCLUSION: The findings of cardiac mucosa, carditis, and intestinal metaplasia in an endoscopically normal-appearing gastroesophageal junction are histologic indicators of gastroesophageal reflux disease. These findings may be among the earliest signs of gastroesophageal reflux and contribute to the authors understanding of the pathophysiology of the disease process.     

Early and late results of the acid suppression and duodenal diversion operation in patients with barrett's esophagus: analysis of 210 cases

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.