Alkaline gastroesophageal reflux: implications in the development of complications in Barrett's columnar-lined lower esophagus

Barrett's esophagus is a common finding in patients with gastroesophageal reflux and is associated with a high incidence of serious complications (stricture, ulceration, and carcinoma). The reason that only a portion of patients with reflux develop Barrett's esophagus and why some are prone to develop complications is unknown. Twenty-three patients with Barrett's esophagus underwent endoscopy, 24-hour esophageal pH monitoring, and manometry. Nine of these patients with gastritis underwent 24-hour gastric pH monitoring, and three with symptoms of duodenogastric reflux underwent 99mTc-labeled hepato-iminodiacetic acid scanning. Patients with complicated (n = 12) and uncomplicated (n = 11) Barrett's esophagus were compared with each other and with patients with reflux esophagitis (n = 53) and normal volunteers (n = 50). Patients with Barrett's esophagus showed an increased exposure to acid and alkaline gastric juice compared with patients with esophagitis and normal volunteers. In the patients with Barrett's esophagus with and without complications, there was no significant difference in age, incidence of defective lower esophageal sphincter, incidence of defective peristalsis, extent of the Barrett's epithelium, or percent time the esophageal pH was less than 4. In contrast, the percent time the esophageal pH was greater than 7 was significantly greater in patients with complications. This alkaline exposure is likely to be related to duodenogastric reflux. This was supported by positive gastric pH scores for duodenogastric reflux and 99mTc-labeled hepato-iminodiacetic acid scans in patients with Barrett's complications. These findings suggest that the development of complications in Barrett's esophagus is the result of the damaging effect of refluxed duodenal juice.     

Immunosuppression in patients with Barrett's esophagus.

BACKGROUND. Patients with Barrett's esophagus have a higher incidence of esophageal cancer than has the general population. Local tissue injury and exposure to carcinogens presumably play a role in malignant transformation, but the possibility of altered host immune surveillance must also be considered. METHODS. The level of immunoreactivity was investigated in six healthy control subjects; 14 patients with gastroesophageal reflux, seven with and seven without esophagitis; and nine patients with Barrett's esophagus. Parameters studied were (1) T-cell and B-cell function with mitogen-stimulated lymphocyte blastogenesis, (2) immunosuppressive properties of autologous serum, and (3) interleukin-2 production by peripheral blood mononuclear cells. Nutritional status as a possible cause for immunosuppression was assessed by measurement of serum albumin, transferrin, and prealbumin. RESULTS. Patients with Barrett's esophagus had a significant suppression of all T-cell (p less than 0.01) and B-cell function (p less than 0.01) and interleukin-2 production (p less than 0.001) when they were compared to the controls. Interleukin-2 production was also reduced significantly compared to that in patients with gastroesophageal reflux with and without esophagitis (p less than 0.05). No differences were observed in serum immunosuppression or nutritional factors. CONCLUSIONS. Although the immunosuppression observed in the patients with Barrett's esophagus was milder than that found in other immunocompromised states, it may be sufficient to encourage the malignant transformation of Barrett's mucosa.     

Laryngopharyngeal reflux symptoms better predict the presence of esophageal adenocarcinoma than typical gastroesophageal reflux symptoms

OBJECTIVE: To determine whether the presence of laryngopharyngeal reflux symptoms is associated with the presence of esophageal adenocarcinoma (EAC). BACKGROUND: Most patients diagnosed with EAC have incurable disease at the time of detection. The majority of these patients are unaware of the presence of Barrett's esophagus prior to cancer diagnosis and many do not report typical symptoms of gastroesophageal reflux disease (GERD). This suggests that the current GERD symptom-based screening paradigm may be inadequate. Data support a causal relation between complicated GERD and laryngopharyngeal reflux symptoms. We theorize that laryngopharyngeal reflux symptoms are not recognized expeditiously, resulting in chronic esophageal injury and an unrecognized progression of Barrett's esophagus to EAC. METHODS: This is a case-comparison (control) study. Cases were patients diagnosed with EAC (n = 63) between 1997 and 2002. Three comparison groups were selected: 1) Barrett's esophagus patients without dysplasia (n = 50), 2) GERD patients without Barrett's esophagus (n = 50), and 3) patients with no history of GERD symptoms or antisecretory medication use (n = 56). The risk factors evaluated included demographics, medical history, lifestyle variables, and laryngopharyngeal reflux symptoms. Typical GERD symptoms and antisecretory medication use were recorded. Multivariate analysis of demographics, comorbid risk factors, and symptoms was performed with logistic regression to provide odds ratios for the probability of EAC diagnosis. RESULTS: The prevalence of patients with laryngopharyngeal reflux symptoms was significantly greater in the cases than comparison groups (P = 0.0005). The prevalence of laryngopharyngeal reflux symptoms increased as disease severity progressed from the non-GERD comparison group (19.6%) to GERD (26%), Barrett's esophagus (40%), and EAC patients (54%). Symptoms of GERD were less prevalent in cases (43%) when compared with Barrett's esophagus (66%) and GERD (86%) control groups (P < 0.001). Twenty-seven percent (17 of 63) of EAC patients never had GERD or laryngopharyngeal reflux symptoms. Fifty-seven percent of EAC patients presented without ever having typical GERD symptoms. Chronic cough, diabetes, and age emerged as independent risk factors for the development of EAC. CONCLUSIONS: Symptoms of laryngopharyngeal reflux are more prevalent in patients with EAC than typical GERD symptoms and may represent the only sign of disease. Chronic cough is an independent risk factor associated with the presence of EAC. Addition of laryngopharyngeal reflux symptoms to the current Barrett's screening guidelines is warranted.     

Symptoms, acid exposure and motility in patients with Barrett's esophagus.

INTRODUCTION: Barrett's esophagus, a syndrome in which the squamous mucosa that normally lines the distal esophagus is replaced with columnar epithelium, is found in a small percentage of patients presenting with gastroesophageal reflux disease (GERD). The columnar epithelium may be protective, guarding people afflicted with Barrett's esophagus from experiencing symptoms related to acid reflux. The purpose of this study was to investigate whether people with Barrett's esophagus subjectively experience fewer symptoms or symptoms of decreased severity, despite sustaining greater acid exposure, than those with GERD but without Barrett's syndrome. METHODS: We conducted a chart review of patients with GERD. Criteria for inclusion in the study were esophagogastroscopy, motility testing and a 24-hour pH study. Fifty-eight patients (29 men, 29 women) fulfilled these criteria. The diagnosis of GERD was based on an abnormal 24-hour pH study (DeMeester score). Of these 58 patients, 21 (14 men, 7 women) were found to have histologically confirmed Barrett's esophagus. A questionnaire to assess the key symptoms of GERD was administered, with a severity score ranging from 0 to 3 (3 being the most severe) for each symptom. RESULTS: Patients with Barrett's esophagus experienced symptoms significantly less severe (p < 0.01) than those with GERD. Patients with Barrett's esophagus also had a greater degree of acid exposure as identified by higher DeMeester scores (p = 0.056), longer episodes of acid exposure, a greater number of long episodes (> 5 min) of acid exposure (p = 0.033) and an increased percentage of time when their pH was less than 4. Patients with Barrett's esophagus had decreased resting lower esophageal sphincter tone, and number and amplitude of peristaltic contractions. CONCLUSIONS: For patients with Barrett's esophagus, the columnar epithelium may serve a protective function in guarding against symptoms of acid reflux. This has implications for the diagnosis and management of this condition.     

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.     

Surgical management of peptic esophageal stricture. Twenty-year experience

The consensus in the conflict about surgical management of peptic esophageal stricture presently favors conservative antireflux procedures with dilatation rather than resection. However, emphasis is now shifting to the controversy of conservative surgical treatment versus medical management with dilatation alone. We analyzed the influence of seven variables on the postoperative result in 160 patients undergoing antireflux operations with dilatation for peptic esophageal stricture. The mean follow-up is 47 months (range 6 to 240) and the mean age is 57 years (range 13 to 83). One hundred seven patients operated on early in the course of the disease have better results (90% good, 9% fair, 1% poor) than 31 patients having a previous failed operation (52% good, 23% fair, 26% poor) and 22 patients having multiple dilatations (45% good, 23% fair, 32% poor) (p less than 0.05). Intraoperative manometry improves results (p less than 0.05), and postoperative reflux has a negative influence on results (p less than 0.05). The postoperative lower esophageal sphincter pressure in patients without reflux (17.7 +/- 1.3 mm Hg) is higher than in those with reflux (8.9 +/- 0.8 mm Hg, p less than 0.05) and is an accurate predictor of the risk of reflux (p less than 0.001). Intraoperative and postoperative sphincter pressures are objective indicators of outcome but because of variability are not predictive (p less than 0.05). The presence of Barrett's esophagus and the age and sex of patients do not alter outcome. Adenocarcinoma did not develop in patients with Barrett's esophagus once reflux was eliminated. This information indicates that conservative antireflux operation with dilatation is the treatment of choice in patients with peptic esophageal stricture.     

Does Barrett's esophagus impact outcome after laparoscopic Nissen fundoplication?

BACKGROUND: This study was undertaken to compare patients with gastroesophageal reflux disease (GERD) with or without Barrett's esophagus for severity and frequency of symptoms and their response to antireflux surgery. METHODS: Eighty patients with GERD and Barrett's esophagus and 93 concurrent patients with GERD alone, all of whom underwent laparoscopic Nissen fundoplication, were compared by using symptom scores graded by a Likert scale. RESULTS: Before fundoplication, patients with Barrett's esophagus had higher DeMeester scores. Symptom scores were not different for patients with versus without Barrett's esophagus before or after laparoscopic Nissen fundoplication. CONCLUSIONS: Before and after fundoplication, patients with Barrett's esophagus, despite more severe reflux, have symptoms nearly identical in frequency and severity when compared with patients with GERD alone. Regardless of presence of Barrett's, all improve dramatically with laparoscopic Nissen fundoplication. Barrett's esophagus does not impact presentation before or outcome after laparoscopic Nissen fundoplication.     

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.     

Outcome of esophageal adenocarcinoma detected during endoscopic biopsy surveillance for Barrett's esophagus

BACKGROUND: In an attempt to reduce mortality from esophageal adenocarcinoma, it has been recommended to enroll patients with Barrett's esophagus in endoscopic surveillance programs in order to detect malignant degeneration at an early and possibly curable stage. The aim of this study was to assess the impact of endoscopic biopsy surveillance on outcome of Barrett's adenocarcinoma. METHODS: Between November 1992 and June 2000, 312 patients with histologically proven esophageal adenocarcinoma were referred to our department. Ninety-seven of these patients had Barrett's adenocarcinoma. In 12 (12.2%) patients, cancer was discovered during endoscopic surveillance for Barrett's metaplasia. RESULTS: The prevalence of gastroesophageal reflux disease in the Barrett's group was 38.8% versus 8% (p < 0.01) in non-Barrett's patients. In the surveyed group, there were 9 (75%) early stage tumors (Tis-1/N0) versus 9 (10.6%, p < 0.01) in the nonsurveyed patients. Three of 5 surveyed patients operated on for high-grade dysplasia proved to have invasive carcinoma in the esophagectomy specimen. All surveyed patients were alive at a median follow-up of 48 months; the median survival in the nonsurveyed group was 24 +/- 3 months (p < 0.01). CONCLUSION: Endoscopic surveillance of Barrett's esophagus provides early detection of malignant degeneration and a better long-term survival than in nonsurveyed patients.     

Analysis of thirty-two patients with Schatzki's ring

Schatzki's ring is a distinct anatomical entity associated with hiatal hernia; however, its significance is unclear. Thirty-two patients with a radiologically demonstrated Schatzki's ring were compared with 32 patients with hiatal hernia and no Schatzki's ring. Schatzki's ring was confirmed on endoscopy in 59 percent of patients. Seventy-five percent of patients with Schatzki's ring presented with dysphagia compared with 41 percent of control patients (p less than 0.01). Heartburn and regurgitation were less frequent than in control subjects (38 percent versus 91 percent, p less than 0.0001). Schatzki's ring patients were found to have a lower incidence of proven gastroesophageal reflux on 24-hour pH monitoring. Those with proven reflux were found to have a more efficient lower esophageal sphincter than control patients. Sixty-two percent of Schatzki's ring patients without proven reflux had a history of chronic ingestion of drugs known to be damaging to the esophageal mucosa, whereas only 26 percent of patients with reflux had this history. This was found in 16 percent of controls. Sixty-two percent of Schatzki's ring patients without reflux responded to a single dilatation compared with 37 percent of those with reflux. These findings suggest an etiologic relationship between pill lodgement and Schatzki's ring in patients without reflux and indicate that different therapy should be employed in these patients.     

Barrett's esophagus in children. Diagnosis and management.

OBJECTIVE: To determine the local prevalence and optimal therapy for children with Barrett's esophagus (BE), the authors studied children with esophageal strictures or gastroesophageal reflux (GER), or both, to diagnose BE and to follow after therapy. SUMMARY BACKGROUND DATA: Barrett's esophagus is seldom reported in children and therapeutic recommendations are unclear. Barrett's esophagus usually develops during the mucosal reparative process after acid-reflux injury to the esophageal mucosa. Risk factors for BE include conditions that are associated with GER such as mental retardation, esophageal stricture, esophageal atresia, and reversed gastric tube esophagoplasty. Barrett's syndrome increases the risk of esophageal adenocarcinoma by 30 to 40 times. METHODS: All children with the risk factors had repeated esophagoscopy and multiple mucosal biopsies before and after therapy. RESULTS: Eleven children have been documented with BE. The initial diagnoses were: GER, 5; esophageal atresia, 4; nasogastric intubation, 1; lye ingestion, 1. A gastric tube esophagoplasty had been performed in three patients with BE in the esophagus proximal to the anastomosis. Three children with mid-esophageal strictures and long segments of BE had total resection with colic interposition. An additional two patients with tight stricture were treated with colic-patch esophagoplasty without resection. The final three patients were treated with fundoplication alone. CONCLUSIONS: Barrett's esophagus can be caused by acid from gastric tubes but responds to H2 blockers and diet. Resection eliminates BE; esophagoplasty only controls the stricture and must be accompanied by fundoplication. Barrett's esophagus persists in patients with fundoplication alone if reflux control is incomplete. The authors conclude that acid reflux must be controlled to treat BE successfully or the involved segment must be resected. Esophagogastrostomy apparently predisposes to BE.     

Value of tests for evaluation of gastroesophageal reflux in children

The accuracy of five tests for the diagnosis of gastroesophageal reflux in children was performed in 93 symptomatic children with gastroesophageal reflux and 16 nonreflux patients. These tests include the barium esophagram, the Tuttle test, extended esophageal pH monitoring, esophagoscopy, and esophageal biopsy. Esophagoscopy was less sensitive in detecting reflux in patients than any other test (P = less than 0.001), and biopsy was more likely to identify reflux patients than the barium swallow (P = less than 0.02), but there was no test superior to others. The severity of esophagitis noted at endoscopy or the presence of eosinophils or neutrophils in the mucosa was not associated with a decreased possibility that one other test would be normal or that surgical repair of the reflux would be performed. Patients with extended esophageal pH test scores markedly elevated were less likely to have another negative test (P = less than 0.01) and more likely to have surgical repair of gastroesophageal reflux (P = less than 0.001). Obtaining two tests of esophageal function that agree increases the certainty of diagnosis, and use of several tests are indicated if the results of a single test do not support the clinical impression.     

Esophageal manometry and 24-hour pH monitoring in the diagnosis of pulmonary aspiration secondary to gastroesophageal reflux.

Twenty-three consecutive patients who had persistent respiratory symptoms of unexplained etiology were evaluated to determine the presence of gastroesophageal reflux (GER) and its relationship to their respiratory complaints. Lower esophageal sphincter (LES) and upper esophageal sphincter (UES) pressures and the characteristics of the peristaltic waves in the proximal and distal esophagus were determined. Esophageal acid exposure 5 cm and 20 cm above the LES was measured using a pH probe with two antimony sensors. Aspiration was diagnosed when respiratory symptoms occurred during or within 3 minutes after a reflux episode, recorded at both levels of the esophagus. Based on these criteria, 12 patients were considered nonaspirators (group A), and 11 were categorized as aspirators (group B). Aspirators had: (1) lower LES pressure (6.1 +/- 3.1 versus 12 +/- 4.8 mm Hg, p less than 0.01); (2) decreased amplitude of peristalsis in the proximal esophagus (34 +/- 16 versus 59 +/- 21 mm Hg, p less than 0.01) and distal esophagus (46 +/- 25 versus 91 +/- 28 mm Hg, p less than 0.01), and higher incidence of simultaneous, nonperistaltic waves (30% versus 4%); and (3) lower UES pressure (44 +/- 23 versus 74 +/- 38 mm Hg). Impaired peristalsis in aspirators caused a higher acid exposure (11.4% +/- 8.0% versus 1.0% +/- 0.7% of time pH less than 4, p less than 0.01) and delayed clearance (5.5 +/- 6.5 versus 0.7 +/- 0.4 min) in the proximal esophagus. Our study shows that, in patients with respiratory symptoms of unexplained etiology, esophageal manometry and 24-hour pH monitoring will identify a subgroup of true aspirators. These patients suffer from a panesophageal motor dysfunction that affects all three barriers to aspiration: the LES, the esophageal "pump mechanism," and the UES.     

A new physiologic approach for the surgical treatment of patients with Barrett''s esophagus: technical considerations and results in 65 patients.

OBJECTIVE: To determine the results of a new surgical procedure for patients with Barrett's esophagus. SUMMARY BACKGROUND DATA: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Short-segment Barrett’s esophagus: A prevalent complication of gastroensophageal reflux disease with malignant potential

The significance of finding specialized intestinal epithelium localized to the region of the gastroesophageal junction is unclear. We tested the hypothesis that short segments of specialized intestinal epithelium are a consequence of gastroesophageal reflux disease and are premalignant. Two hundred forty-one patients with reflux symptoms underwent gastroscopy with rigorous biopsy. Barrett’s esophagus was diagnosed when specialized intestinal epithelium was present on biopsy. Patients with Barrett’s esophagus were subdivided according to the length of Barrett’s mucosa: short-segment Barrett’s (<3 cm) and extended Barrett’s (≥3 cm). Esophageal function was evaluated by manometry and 24-hour pH monitoring. In another 16 patients with small noncircumferential adenocarcinomas, the endoscopic length of Barrett’s mucosa was recorded. Thirty-three patients (14%) had short-segment Barrett’s and 37 (15%) had extended Barrett’s esophagus. Patients with short-segment Barrett’s esophagus had significantly more acid exposure than patients without specialized intestinal epithelium. Eighty-one percent of patients with short-segment Barrett’s esophagus had incresed esophageal acid exposure as did 100% of those with extended Barrett’s esophagus. All lengths of Barrett’s mucosa were associated with poor esophageal sphincter function and reduced contraction amplitudes in the distal esophagus. Twelve percent of patients with short-segment Barrett’s esophagus had dysplasia. The length of Barrett’s mucosa was ≤3 cm in 25% (4 of 16) of patients with early Barrett’s adenocarcinoma. Short-segment Barrett’s esophagus is commonly associated with gastroesophageal reflux disease. Further, short segments of specialized intestinal epithelium are premalignant in nature. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Surgery of the Alimentary Tract, San Francisco, Calif., May 19–22, 1996.     

The extent of Barrett's esophagus depends on the status of the lower esophageal sphincter and the degree of esophageal acid exposure

OBJECTIVE: The purpose of this study was to assess whether the extent of intestinal metaplasia is related to the severity of the gastroesophageal reflux disease. METHODS: A total of 556 consecutive patients with symptoms suggestive of foregut disease had upper gastrointestinal endoscopy with extensive biopsies from the gastroesophageal junction and the esophagus. All patients had esophageal motility and 24-hour pH monitoring. In 411 patients, cardiac-type mucosa was identified; in 147 patients, the cardiac-type mucosa showed intestinal metaplasia. They were divided into 3 groups based on the extent of intestinal metaplasia commonly seen clinically: long segments (>3 cm), short segments (<3 cm), and limited to the gastroesophageal junction. The duration of symptoms, the status of the lower esophageal sphincter, the degree of esophageal acid exposure, and the time to clear a reflux episode were assessed in each group. RESULTS: The presence of intestinal metaplasia in cardiac-type mucosa was associated with the hallmarks of gastroesophageal reflux disease. The extent of intestinal metaplasia correlated strongly with the degree of esophageal acid exposure (r = 0.711; P <.001) and inversely with the lower esophageal sphincter pressure (r = 0.351; P <.001) and length (r = 0. 259; P =.002). Patients with a long segment of intestinal metaplasia (>3 cm) had longer duration of symptoms (16 years) than those patients with a segment of intestinal metaplasia less than 3 cm (10 years; P =.048) or those patients with intestinal metaplasia limited to the gastroesophageal junction (10 years; P =.01). CONCLUSION: The extent of intestinal metaplasia, that is, Barrett's esophagus, is related to the status of the lower esophageal sphincter and the degree of esophageal acid exposure.     

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.     

Esophagoscopy and endoscopic esophageal ultrasound in the assessment of esophageal function

Esophagoscopy is an ideal method to detect mucosal or structural abnormalities of the esophagus and proximal stomach. The exclusion of malignant dysphagia is the prime role of esophagoscopy in assessment of esophageal function. Esophagoscopy and biopsy are mandatory for mucosal assessment of patients with gastroesophageal reflux disease (GERD). Indirect and sometimes subtle evidence of abnormal esophageal motility is a valuable and underused aspect of esophagoscopy in the evaluation of swallowing disorders. Esophagoscopy has multiple roles in the appraisal and treatment of esophageal motility disorders, including the detection of secondary or pseudoachalasia, placement of manometry catheters, and dilation of peptic strictures caused by GERD associated with disorders such as scleroderma.     

Diagnosis of gastroesophageal reflux and Barrett esophagus

Gastroesophageal reflux is a very common disorder. Typical symptoms are heartburn, regurgitation and chest pain. Recently, it has been demonstrated that gastroesophageal reflux may generate or worse extraesophageal symptoms such as asthma, chronic bronchitis, posterior laryngitis, and chronic cough. The diagnosis of gastroesophageal reflux is suggested by typical symptoms which improve under a therapy with proton pump inhibitors. pH-monitoring over 24 hours is able to establish directly the diagnosis by measuring acid reflux into the esophagus. Manometry detects the two most common causes of gastroesophageal reflux: insufficiency of the lower esophageal sphincter or esophageal motility abnormalities. Gastroesophageal reflux can lead to reflux esophagitis, which is diagnosed endoscopically. An endoscopy should routinely be performed in case of dysphagia, anemia, or loss of weight. A long-term sequela of gastroesophageal reflux is the development of Barrett's-esophagus, a condition which has to be verified by endoscopy and biopsy. This premalignant lesion is defined by a metaplastic change from the normal squamous mucosa to a specialized intestinal epithelium characterized by goblet cells. Because dysplasia in these metaplastic areas can lead to esophageal adenocarcinoma, regular endoscopic surveillance with biopsies is recommended. Gastroesophageal reflux can significantly impair the quality of life and can cause complications that include the neoplastic progression from Barrett's esophagus to carcinoma. Therefore, appropriate diagnostic procedures and adequate therapy are required. This article summarizes the diagnostic approach to patients with gastroesophageal reflux, reflux esophagitis and Barrett's-esophagus. The impact of endoscopy, pH-monitoring, esophageal manometry, radiology and scintigraphy are reviewed.     

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.