Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management

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.     

Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study

OBJECTIVES: In Barrett's esophagus, early adenocarcinomas are often missed on endoscopic biopsy. We therefore examined the distribution and extent of dysplasia and carcinoma in the resected esophagus for comparison with the preoperative biopsy findings. METHODS: Patients whose endoscopy showed Barrett's esophagus but no visible cancer had four-quadrant esophageal biopsies taken every 2 cm. After resection for high-grade dysplasia or early adenocarcinoma, the esophagus was mapped histologically. RESULTS: Nineteen patients had surgery for high-grade dysplasia; two of them (10.5%) had adenocarcinoma in the resected esophagus. Eleven patients had resection after a biopsy diagnosis of adenocarcinoma or suspicion of adenocarcinoma. Esophagectomy mapping confirmed carcinoma in only five of them. Median surface areas were: total Barrett's esophagus 32 sq cm, low-grade dysplasia 13 sq cm, high-grade dysplasia 1.3 sq cm, adenocarcinoma (seven cases) 1.1 sq cm. CONCLUSIONS: Areas of high-grade dysplasia and microscopic carcinoma in Barrett's esophagus are often small. Biopsy differentiation between these lesions is difficult. A systematic endoscopic biopsy protocol will reduce the chance of missing early malignancy in Barrett's esophagus.     

Is prophylactic treatment after myocardial infarction evidence-based?

In Barrett's esophagus, the squamous lining of the lower esophagus is replaced by columnar epithelium. Barrett's esophagus is associated with gastroesophageal reflux and an increased risk of the development of esophageal cancer. Endoscopy shows red columnar epithelium in the lower esophagus. Biopsy is needed to confirm intestinal metaplasia. Some cases progress from dysplasia to invasive adenocarcinoma. Medical or surgical antireflux treatment controls symptoms and esophagitis, but Barrett's esophagus remains. Patients are usually followed up by endoscopy for detection of dysplasia or early cancer. For patients with low-grade dysplasia, follow-up is adequate; however, for those with high-grade dysplasia, esophagectomy or experimental endoscopic mucosal ablation is advised.     

Detection of donor-derived Langerhans cells in MHC class II immunodeficient patients after allogeneic bone marrow transplantation

Barrett's esophagus can progress to dysplasia and adenocarcinoma. Although the incidence of adenocarcinoma of the gastroesophageal junction has increased suddenly in the United States and Europe, we do not know how much of this increase is related to Barrett's esophagus. Interest in mucosal cell abnormalities at the gastroesophageal junction has led researchers to re-examine short-segment Barrett's esophagus. In this recently described condition, specialized columnar epithelium is found in the distal 2 to 3 cm of the esophagus, yet it is not clear how it relates to conventional long-segment Barrett's esophagus, in which the metaplastic epithelium extends higher than 2 to 3 cm above the squamocolumnar junction. The reported prevalence of short-segment Barrett's esophagus found on diagnostic endoscopy varies from 8% to 32%. This wide variation would be lessened by standardized location of biopsy specimens and of endoscopic and histologic staining techniques. Based on the information available, it is apparent that the age range and sex ratios are similar. Although reflux symptoms may be more common in short-segment Barrett's esophagus, disturbances in esophageal motility are less severe and there is less reflux as measured by continuous pH monitoring. Furthermore, recognized complications of Barrett's esophagus, such as ulceration, stricture, high-grade dysplasia, and adenocarcinoma, appear to be uncommon in short-segment Barrett's esophagus.     

Midtrimester maternal serum screening after multifetal pregnancy reduction in pregnancies conceived by in vitro fertilization

BACKGROUND: The rising incidence of esophageal adenocarcinoma in western countries requires a new strategy in the management of dysplasia in Barrett's esophagus. Esophagectomy, which has high morbidity and mortality rates, has been recommended to treat patients with severe dysplasia. Strictly superficial laser coagulation with tissue ablation therefore is a desirable option for the management of dysplasia in Barrett's esophagus because the tissue to be ablated is only about 2 mm thick. Potassium-titanyl-phosphate (KTP) laser light with a wavelength of 532 nm is preferentially absorbed by hemoglobin and therefore combines excellent coagulation with limited tissue penetration. We report first clinical results with KTP laser superficial vaporization of dysplasia and early cancer in Barrett's esophagus. METHODS: Eight men and 2 women 43 to 84 years of age with short segments of Barrett's esophagus or traditional Barrett's esophagus and histologically proved low-grade (n = 4) and high-grade (n = 4) dysplasia or early adenocarcinoma (n = 2) were selected for this pilot study. For all patients thermal endoscopic destruction was conducted with a frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) KTP laser system. Laser therapy was performed by means of the free-beam method with coaxial insufflation of gas. An average of 2.4 sessions per patient were required for ablation of the Barrett's mucosa. RESULTS: Two to three days after laser treatment the response of the ablated mucosa was assessed with endoscopy and biopsy. Samples taken showed fibrinoid necrosis of the mucosal layer. A complete response was obtained for all 10 patients. Replacement by normal squamous cell epithelium was induced in combination with acid suppression therapy of up to 80 mg omeprazole daily. No complications occurred. In two patients biopsy showed specialized mucosa beneath the restored squamous cell epithelial layer. Follow-up times were as long as 15 months (mean value 10.6 months). CONCLUSIONS: KTP laser destruction of Barrett's esophagus induced mucosal regeneration with normal squamous cell epithelium in combination with acid suppression. Limitation of the depth of thermal destruction in Barrett's esophagus minimizes risk for perforation or stricture formation. KTP laser ablation of Barrett's esophagus seems to be feasible and safe in short segments of Barrett's esophagus with dysplasia or early cancer.     

Management of dysplasia in the columnar-lined esophagus

The management of patients with high-grade dysplasia in Barrett's esophagus is complex and controversial with regard to electing continued endoscopic biopsy surveillance until an early adenocarcinoma is detected or proceeding with partial esophagogastrectomy. Clinical recommendations to patients for either option should be individualized and based on several parameters reflecting patient and clinician factors. Available data on interpretational variation in the diagnosis of dysplasia; limitation of diagnostic errors with the use of a rigorous, systematic endoscopic biopsy protocol; new information on the apparent benign natural history of high-grade dysplasia in some patients; and the morbidity and mortality of esophageal resection all suggest that recommendation for continued endoscopic biopsy surveillance is an appropriate clinical practice in selected patients. Ongoing research investigations on high-grade dysplasia in Barrett's esophagus aim to reduce the potential for diagnostic errors, simplify cancer surveillance, and develop therapeutic interventions that are safer than but as effective as surgery.     

Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation

OBJECTIVE: Barrett's esophagus is associated with significantly increased risk of development of esophageal adenocarcinoma. Replacing columnar epithelium with the normal squamous lining in this condition offers the possibility of decreasing the risk of degeneration to invasive adenocarcinoma. This study aimed to establish the feasibility of argon beam plasma coagulation (ABPC), in conjunction with control of gastroesophageal reflux, to restore the squamous lining. METHODS: Thirty patients with Barrett's esophagus (four low-grade dysplasia, three high-grade) were recruited from our surveillance program, and underwent endoscopic ABPC. RESULTS: Twenty-seven patients completed treatment, with macroscopic replacement of their columnar lining by squamous epithelium, histologically confirmed in all 27, and followed up for a median of 9 months (range, 6-18 months). Two patterns of squamous replacement were identified: 70% of patients showed squamous epithelium with no persistent intestinal metaplasia, and in 30% the new squamous epithelium covered areas of underlying intestinal metaplasia. One patient has withdrawn from the study. Two esophageal perforations, with one death, occurred early in the study. CONCLUSION: ABPC, in conjunction with control of gastroesophageal reflux, allows squamous regrowth in both benign and dysplastic Barrett's esophagus. Despite the theoretical safety advantages of ABPC over techniques such as laser, esophageal perforation may occur with this technique. It is too soon to recommend ABPC for dysplastic or nondysplastic Barrett's because follow-up is too short to show a decreased incidence of and mortality from adenocarcinoma.     

Potential application of p53 as an intermediate biomarker in Barrett's esophagus

Diagnosis of the neoplastic progression in Barrett's esophagus using the histologic classification of dysplasia is frequently difficult. The tumor suppressor protein p53, when mutated, confers a promoter effect on cell growth. The purpose of this study was to evaluate the applicability of p53 as an intermediate biomarker of malignancy in Barrett's esophagus. Archival analysis of 100 biopsy specimens of Barrett's esophagus and 10 esophageal adenocarcinomas were compared with 35 chronic esophagitis biopsy specimens. Immunocytochemistry using an anti-p53 monoclonal antibody was performed and elevated immunoreactivity quantitated microscopically. Data were analyzed using a logistic regression model. Significant p53 immunoreactivity occurred as follows: chronic esophagitis (0%), Barrett's esophagus without dysplasia (10%), with low-grade dysplasia (60%), with high-grade dysplasia (100%), and adenocarcinoma (70%). All cases of Barrett's esophagus were significantly immunoreactive when compared with the chronic esophagitis cases (p = 0.001). There was an increase in p53 immunoreactivity as the histologic classification progressed toward adenocarcinoma (p = 0.001). Progression to high-grade dysplasia may be predicted based on p53 immunoreactivity. These findings suggest a role for p53 as an intermediate biomarker in Barrett's esophagus.     

A gene for FG syndrome maps in the Xq12-q21.31 region

AIMS: An increased risk of adenocarcinoma of the oesophagus has been demonstrated in patients with long segments of Barrett's mucosa. The risk of cancer associated with short segments of metaplasia of the oesophagogastric junction is not known. METHODS AND RESULTS: We report a case of early adenocarcinoma of the oesophagus arising on short tongues of Barrett's mucosa associated with an oesophageal cyst. The patient was a 68-year-old man with no previous clinical history of gastro-oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead to the diagnosis of short tongues of Barrett's mucosa with high-grade dysplasia. On pathological examination of the resected specimen, an early adenocarcinoma had developed in Barrett's mucosa, localized just above the oesophageal cyst. CONCLUSIONS: As oesophageal cysts can cause symptoms suggestive of reflux, we hypothesize that this association may not be fortuitous.     

TWIST gene mutation in a patient with radial aplasia and craniosynostosis: further evidence for heterogeneity of Baller-Gerold syndrome

BACKGROUND: The optimal management of high-grade dysplasia in patients with Barrett's esophagus is controversial. The aim of this study was to assess the prevalence of unsuspected carcinoma at esophagectomy in patients with Barrett's esophagus with high-grade dysplasia after endoscopic surveillance with jumbo biopsy forceps compared with standard biopsy forceps. METHODS: Twelve patients with high-grade dysplasia in Barrett's esophagus without gross or microscopic evidence of carcinoma underwent esophagectomy after preoperative endoscopy with 4-quadrant jumbo biopsies at 2-cm intervals. The findings in this group were compared with those in a group of patients with Barrett's esophagus who underwent esophagectomy for high-grade dysplasia after biopsies obtained at 2-cm intervals with standard biopsy forceps. RESULTS: Unsuspected cancer was found in 4 of 12 (33%) patients in the jumbo biopsy group compared with 6 of 16 (38%) in the standard biopsy group (p = NS). All 6 cancers in the standard biopsy group were intramucosal, whereas 2 were intramucosal and 2 were submucosal in the jumbo biopsy group. No patients in either group had lymph node metastases. CONCLUSIONS: Unsuspected cancer is found frequently in patients with Barrett's esophagus who are undergoing esophagectomy for high-grade dysplasia despite the use of a rigorous jumbo biopsy protocol. Esophageal resection is still indicated in appropriately selected patients with high-grade dysplasia until better markers of cancer risk are available.     

Design and synthesis of small semi-mimetic peptides with immunomodulatory activity based on myelin basic protein (MBP)

Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett's esophagus, but clinical studies in patients with adenocarcinoma arising in Barrett's esophagus are lacking. Ambulatory esophageal measurement of acid and bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH probe in 20 asymptomatic volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients with GERD and erosive esophagitis, 33 patients with GERD and Barrett's esophagus, and 14 patients with early adenocarcinoma arising in Barrett's esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after laparoscopic Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients without esophagitis to those with erosive esophagitis and benign Barrett's esophagus and was highest in patients with early carcinoma in Barrett's esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients with benign Barrett's esophagus and 11 (78.6%) of 14 patients with early adenocarcinoma in Barrett's esophagus. Nissen fundoplication but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly prevalent in patients with Barrett's esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed by Nissen fundoplication but not medical acid suppression alone.     

Prospective long-term endoscopic and histological follow-up of short segment Barrett's esophagus: comparison with traditional long segment Barrett's esophagus

OBJECTIVES: Barrett's esophagus is associated with adenocarcinoma of the cardia and esophagus, regardless of its extent. The aim of this study was to compare the prevalence and incidence of dysplasia and adenocarcinoma in short segment and traditional long segment Barrett's esophagus. METHODS: Seventy-four patients with short segment Barrett's and 78 with traditional Barrett's entered the study. RESULTS: There were no significant differences in age or gender between the two groups of patients with Barrett's esophagus. A greater percentage of patients with short segment barrett's were black (p = 0.04). The prevalence of dysplasia at diagnosis in patients with short segment Barrett's was 8.1% versus 24.4% in patients with traditional Barrett's (p < 0.007). Adenocarcinoma was noted at diagnosis only in patients with traditional Barrett's (p < 0.0005). Twenty-six patients with short segment Barrett's and 29 with traditional Barrett's were followed prospectively for 12-40 months. Dysplasia developed during follow-up in two patients with short segment Barrett's and in six patients with traditional Barrett's (p < 0.05). Neither high grade dysplasia nor cancer developed in any patients with short segment Barrett's. High grade dysplasia did develop in two patients with traditional Barrett's esophagus, and mucosal adenocarcinoma developed in one. The frequency of dysplasia on the latest surveillance examination continued to be significantly higher for patients with traditional Barrett's (p = 0.03). Follow-up surveillance biopsy specimens of Barrett's mucosa frequently demonstrated an absence of goblet cells in patients with short segment Barrett's compared with patients with traditional Barrett's (p < 0.0001). CONCLUSIONS: The prevalence of dysplasia or adenocarcinoma and the incidence of dysplasia in patients with traditional Barrett's esophagus are significantly higher than in patients with short segment Barrett's esophagus. Further prospective surveillance is required to determine whether the incidence of adenocarcinoma in patients with short segment Barrett's esophagus is significantly lower.     

Effectiveness and patient satisfaction with nurse-directed treatment of Barrett's esophagus

OBJECTIVE: Using clinical practice guidelines, a registered nurse adjusted antireflux medications, evaluated esophageal biopsy reports, determined the interval between surveillance endoscopies, and provided education for patients with Barrett's esophagus. No previous reports have assessed the effectiveness or patient satisfaction associated with registered nurse-provided primary care. Because estimates of the incidence of dysplasia and adenocarcinoma vary widely, we also prospectively followed a cohort of patients with Barrett's esophagus. METHODS: Charts were reviewed to determine the frequency of variation from guidelines, the annual incidence of dysplasia and adenocarcinoma, and frequency of reflux symptoms. Patients were mailed a questionnaire to assess satisfaction with their medical care and with the nurse. RESULTS: Variation by the nurse from the guidelines on surveillance endoscopy (1.9%) and the treatment of reflux (1.3%) was rare. Most patients were very satisfied (score of 6 on 0-6-point Likert scale) with overall medical care (88%), and patient education (76%), and most patients did not think that increased physician involvement would improve their care (93%). Ninety-seven percent of patients had control of reflux symptoms. Two patients with long segment Barrett's esophagus (n = 67) developed high grade dysplasia over 323 patient-yr of follow-up (1 of 162 patient-yr for an annual incidence of 0.6%). No patients with short segment Barrett's esophagus (n = 56) developed high grade dysplasia or adenocarcinoma over 172 patient-years of follow-up. CONCLUSION: The registered nurse in our clinical setting effectively administered clinical practice guidelines for the management of Barrett's esophagus without clinically significant morbidity or patient dissatisfaction. Before these results can be generalized to other settings, further studies will need to be performed.     

Barrett's esophagus. Clinical review of 26 cases

Barrett's esophagus was diagnosed in 26 men in a five-year period by demonstrating esophageal specialized columnar epithelium in target biopsies obtained at endoscopy or in peroral suction biopsies of the esophageal mucosa. The clinical, radiologic and manometric features of these patients were reviewed retrospectively. Esophageal lesions associated with this epithelium included distal and midesophageal strictures and ulcers, alone or in combination, or simply esophagitis. One patient had an associated adenocarcinoma. Twenty of 26 (77%) had heartburn or regurgitation, 16 (62%) had easily elicited reflux of barium while supine and 16 of 17 tested had lower esophageal sphincter pressure in the incompetent range. Ninety-six percent had one or more of these parameters positive. This series demonstrates a wide spectrum of esophageal lesions in Barrett's esophagus, and supports the concept that this lesion occurs as a consequence of gastroesophageal reflux and erosive esophagitis. The case of adenocarcinoma in this series adds to the concern that the columnar lined lower esophagus may be a premalignant lesion.     

Gastroesophageal reflux disease in patients with columnar-lined esophagus

Columnar-lined esophagus or Barrett's esophagus is closely associated with gastroesophageal reflux disease. Animal and human studies have shown not only acid but duodenogastroesophageal reflux acting in synergy with acid causes the most esophageal injury. Patients with Barrett's esophagus manifest typical and atypical symptoms of reflux. Ten percent to 25%, however, have clinically silent reflux. Early diagnosis is essential for this disease as it is a risk factor for the development of adenocarcinoma of the esophagus.     

Mutation and expression of the XPA gene in revertants and hybrids of a xeroderma pigmentosum cell line

Achalasia is characterized by failure of relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Few data are available regarding the morphologic features of achalasia, in particular its histologic progression. The esophagi of 42 patients with achalasia treated with total thoracic esophagectomy were examined histologically in order to systematically identify morphologic features of clinically unresponsive achalasia and to determine what could be learned about the disease's evolution. In all cases, myenteric ganglion cells within the esophageal body were markedly diminished, with 20 specimens having none. Twenty specimens had residual ganglion cells in the proximal esophagus, and 15 specimens had a few randomly distributed ganglion cells in the mid- and distal portions of the esophagus. Inflammation within myenteric nerves, present in all cases, generally consisted of a mixture of lymphocytes and eosinophils, occasionally with plasma and mast cells. Focal replacement of myenteric nerves by collagen occurred in all cases, and there was almost complete replacement in several cases. Actual destruction of the residual ganglion cells was not seen. The resected esophagi also shared extramyenteric morphologic features. Some features probably stemmed from physiologic obstruction, such as muscular hypertrophy, mainly of the muscularis propria (all cases), with secondary degeneration and fibrosis (29 cases), and eosinophilia of the muscularis propria (22 cases). Other changes, probably resulting from chronic stasis of ingested materials in the lumen, included diffuse squamous hyperplasia (all cases), lymphocytic mucosal esophagitis (28 cases), lymphocytic inflammation of the lamina propria and submucosa with prominent germinal centers (all cases), and submucosal periductal or glandular inflammation with complete loss of submucosal glands in half of the cases. One patient had high-grade squamous dysplasia, and another had superficially invasive squamous cell carcinoma. A third group of changes was probably due to previous esophagomyotomy, including abnormal gastroesophageal reflux, as shown by pH reflux testing (13 cases) and Barrett's mucosa (four cases). In one case of Barrett's there was low-grade dysplasia. Clinically unresponsive, surgically resected achalasia has almost total loss of ganglion cells, and widespread destruction of myenteric nerves has already occurred. The only active component is myenteric inflammation. However, it cannot be determined whether this inflammation is a manifestation of ongoing nerve destruction or whether it is a secondary phenomenon.     

Advances in the treatment of esophageal carcinoma

Recent changes in the epidemiology of esophageal carcinoma now recognize adenocarcinoma as the predominant histologic cell type. Barrett's esophagus and dysplasia in this epithelium identify patients who are at risk of developing invasive adenocarcinoma. This neoplasm is not a single entity with a consistently poor prognosis, and disease stage is important for determining therapy. These findings offer the potential for further development of therapeutic regimens. Endoscopic esophageal ultrasound is an accurate and reproducible staging tool. It allows the physician to determine clinical stage and modify treatment. T2 N0 M0 or lesser stage tumors have acceptable surgical cure rates, and patients should undergo immediate resection. Patients with more advanced T3 or N1 tumors have a potential for cure but do poorly with surgery alone. These patients should be considered for multimodality therapy. Palliative therapy should be given to patients with hematogenous metastatic disease. Treatment stratification by stage proves that esophageal carcinoma is not a uniformly fatal disease without hope for cure.     

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

OBJECTIVE: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis. METHODS: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy < or = 3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects. RESULTS: Patients with Barrett's esophagus had significantly increased acid reflux time (p < 0.01-0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (p < 0.01-0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis. CONCLUSION: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

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, in fact, 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.     

Complications of gastroesophageal reflux disease. Esophagitis, acid laryngitis, and beyond

Gastroesophageal reflux disease is a common disorder that can result in various esophageal and extraesophageal complications. Reflux of gastric contents can cause esophageal mucosal abnormalities, such as ulcers and peptic strictures, as well as pulmonary and otolaryngologic symptoms, including reflux-induced asthma and acid laryngitis. Left untreated, some complications can lead to more severe disorders, such as esophageal adenocarcinoma that develops in patients with Barrett's esophagus. Accurate recognition of these diverse manifestations allows improved identification of patients at risk for reflux-related disorders and aids in proper evaluation and treatment.