Barrett's esophagus

The Barrett's esophagus showing columnar metaplasia upward to the esophagus from the esophago-gastric junction is one of the final appearance of reflux esophagitis and important as a precancerous state of esophageal adenocarcinoma. Especially the Barrett's mucosa with intestinal metaplasia has high potential risk for adenocarcinoma. Although the clinical definition of the esophago-gastric junction is not easy, the criteria of the esophago-gastric junction and the Barrett's mucosa proposed by the Japanese Society for Esophageal Diseases is useful. The gastro-esophageal reflux is important in the development of Barrett's mucosa not only in the classical Barrett's esophagus but also in the short-segment Barrett's.     

Preface: Recent perspectives of the Barrett's esophagus

As the prevalence of reflux esophagitis is increasing in Japan, due to increased amount of energy intake and improved hygiene with the reduced H. pylori infection, the number of patients having Barrett's esophagus is also increasing. In the Western countries, adenocarcinoma of the esophagus is rapidly increasing among the white elder male, where the reflux esophagitis is more common. Terminology of Barrett's esophagus is still confusing. Recent proposal of endoscopic evaluation of Barrett's esophagus is based on the endoscopic findings, not histologic findings. In the development of adenocarcinoma of the esophagus, several steps of genetic abnormalities might be involved. We still do not know whether we may experience an increase of adenocarcinoma of the esophagus in Japan or not.     

Barrett食管的临床及病理研究

目的:探讨Barrett食管的临床及病理特点。方法:回顾性分析32例经胃镜及病理确诊的Barrett食管的临床表现、内镜及病理特点。结果:32例Barrett食管患者中临床出现反酸25例(78.1%)、胸骨后疼痛22例(68.8%)、烧心感18例(56.3%),无症状者6例(18.8%),胃镜检查伴有反流性食管炎表现者27例(84.4%),胆汁反流者10例(31.3%),病理检查结果全部病例食管下段均有柱状上皮化生。结论:Barrett食管多见于老年人,是反流性食管炎发展的结果,具有恶变为食管癌的潜在危险,其确诊须组织病理检查,内科治疗只能缓解及改善症状,发现恶变及早手术。     

Pathophysiology of Barrett's esophagus--motility disorder of esophagus

Barrett's esophagus is a premalignant condition of reflux esophagitis and the prevalence is increasing in western countries. Although pathogenesis of Barrett's esophagus is still unknown, several studies have indicated that Barrett's esophagus is related to increased acid reflux through decreased lower esophageal sphincter tone and reduced esophageal contractions. In this article recent studies of Barrett's esophagus on pathophysiology of esophageal motility is reviewed.     

In vivo endoscopic optical coherence tomography of esophagitis, Barrett's esophagus, and adenocarcinoma of the esophagus

BACKGROUND AND STUDY AIMS: We studied the feasibility of endoscopic optical coherence tomography imaging in esophageal disorders, including Barrett's esophagus and Barrett-related adenocarcinoma. Optical coherence tomography is a high-resolution cross-sectional imaging technique with a resolution of almost 10 microm. PATIENTS AND METHODS: The mucosal architecture of reflux esophagitis (n = 9) and Barrett's esophagus (n = 9) including Barrett-related esophageal cancer (n = 6) was studied by optical coherence tomography imaging. RESULTS: In different stages of reflux esophagitis edema, fibrinoid deposits, or loss of the epithelial layer were observed. Optical coherence tomography images of Barrett's esophagus substantially differed from normal esophagus, reflux esophagitis, and esophageal carcinoma. A stratified structure of the mucosa was still preserved in Barrett's esophagus. However, images of Barrett-related cancer lacked the regular structure of the esophagus. CONCLUSIONS: The high consistency of the first optical coherence tomography findings, the resolution of up to 10 microm, and the distinct pattern of normal, inflammatory, premalignant and malignant tissues make optical coherence tomography a promising method for endoscopically obtained optical biopsy.     

Barrett's esophagus complicating scleroderma

Two patients with scleroderma whose esophageal involvement was associated with longstanding reflux esophagitis were found to also have Barrett's esophagus. Since Barrett's esophagus is a premalignant condition, these patients with scleroderma should be considered at high risk for the development of adenocarcinoma of the esophagus.     

Progression and extending speed of Barrett's esophagus

Barrett's esophagus is one of the terminal manifestations of reflux esophagitis. Although the typical Barrett's esophagus is very rare in Japan, the prevalence rate of short-segment Barrett's esophagus is extremely higher comparing with in western countries. The discrepancy may be caused by the differences of criteria of short-segment Barrett's esophagus. Observation of Barrett's mucosa in residual esophagus after esophagectomy is a useful method of considering the extension of Barrett's esophagus. Short-segment Barrett's esophagus accompanied by gastro-esophageal reflux may show a rapid extension under some adequate conditions. Large volume prospective studies are needed to clarify the extension speed of Barrett's esophagus.     

Barrett's esophagus in scleroderma: Increased prevalence and radiographic findings

Ten of 27 patients (37%) with scleroderma who underwent endoscopy at our hospital between 1980 and 1984 for symptoms of reflux esophagitis had biopsy-proven Barrett's esophagus. Two of those 10 patients had esophageal adenocarcinomas. In a blinded review of esophagrams (all but 2 using double-contrast technique) from 16 of the 27 patients, only 1 patient was thought to be at high risk for Barrett's esophagus due to a high esophageal stricture with an adjacent reticular pattern of the mucosa. The latter patient had biopsy-proven Barrett's mucosa. Eight patients were thought to be at moderate risk for Barrett's esophagus due to reflux esophagitis and/or distal strictures in 6 and polypoid intraluminal masses in 2. Three of the 6 patients with esophagitis and/or strictures had Barrett's esophagus, and both patients with masses had adenocarcinomas arising in Barrett's mucosa. Finally, 7 patients who had no esophagitis or strictures were thought to be at low risk for Barrett's esophagus. None of those 7 had histologic evidence of Barrett's mucosa. Thus, the major value of double-contrast esophagography is its ability to classify patients into high-, moderate-, and low-risk for Barrett's esophagus to determine the relative need for endoscopy and biopsy in these patients.     

Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a condition commonly managed in the primary care setting. Patients with GERD may develop reflux esophagitis as the esophagus repeatedly is exposed to acidic gastric contents. Over time, untreated reflux esophagitis may lead to chronic complications such as esophageal stricture or the development of Barrett's esophagus. Barrett's esophagus is a premalignant metaplastic process that typically involves the distal esophagus. Its presence is suspected by endoscopic evaluation of the esophagus, but the diagnosis is confirmed by histologic analysis of endoscopically biopsied tissue. Risk factors for Barrett's esophagus include GERD, white or Hispanic race, male sex, advancing age, smoking, and obesity. Although Barrett's esophagus rarely progresses to adenocarcinoma, optimal management is a matter of debate. Current treatment guidelines include relieving GERD symptoms with medical or surgical measures (similar to the treatment of GERD that is not associated with Barrett's esophagus) and surveillance endoscopy. Guidelines for surveillance endoscopy have been published; however, no studies have verified that any specific treatment or management strategy has decreased the rate of mortality from adenocarcinoma.     

Expression of transcription factor in Barrett's esophagus

Barrett's esophagus is the result of chronic injury which is usually caused by gastroesophageal reflux. NF-kappaB is expressed in the reflux esophagitis. Specialized columnar epithelium (SCE) is characteristic of Barrett's esophagus and has a malignant predisposition. SCE expresses Cdx1 and Cdx2. Adenocarcinoma in Barrett's esophagus is believed to develop through the metaplasia-dysplasia-carcinoma sequence. P53, beta-catenin, PPARgamma, and estrogen receptor beta are closely related to the development of esophageal carcinogenesis.     

Barrett's esophagus: observations on diagnosis and management.

Barrett's esophagus is a premalignant condition that may often pass unrecognized in clinical practice. In adults, this condition is generally believed to be caused by chronic gastroesophageal reflux resulting in a metaplastic change in the epithelium of the esophagus. Diagnosis of Barrett's esophagus is established by careful biopsy of the involved esophageal mucosa. Periodic surveillance is recommended because of the risk of carcinoma. Antireflux surgery has not been shown to result consistently in the regression of the metaplastic epithelium, but potent acid suppression offers a new therapeutic approach that leads to healing of esophagitis and the potential regression of Barrett's epithelium.     

Medical treatment of Barrett's esophagus

In patients with Barrett's esophagus, medical treatment is necessary for the control of reflux symptom, healing of accompanying erosive esophagitis, and prevention of carcinogenesis. For this purposes, proton pump inhibitors (PPIs) and aspirin/non-steroidal anti-inflammatory drugs (NSAIDs) are increasingly used. There are enough evidences that show the usefulness of PPIs for the control of reflux symptom and esophagitis. The values of PPI and aspirin/NSAIDs for the prevention of Barrett's carcinoma are still under investigation all over the world. Since many groups are actively working to find the appropriate methods for preventing carcinogenesis on the Barrett's esophagus, we will have an evidence-based strategy for the prevention of Barrett's adenocarcinoma in near future.     

Gastroesophageal reflux disease: presentation and assessment of a common, challenging disorder

Although gastroesophageal reflux disease (GERD) is frequently referred to as a continuous spectrum, it is more useful to consider GERD as 2 discrete entities with several subsets that differ in pathophysiology, clinical presentation, natural history, and therapy. One entity is classic severe acid reflux with erosive esophagitis and its complications. Barrett's esophagus is an important subset of this group, with markedly increased acid exposure and an increased risk of adenocarcinoma. The second entity is nonerosive reflux disease (NERD) with minimal or no esophagitis. Patients with NERD do not develop local mucosa complications, like stricture or Barrett's esophagus, but their symptom severity can equal that of erosive esophagitis. Acid is involved in the symptoms of many but not all NERD patients. This acid dependence is evident either as an increase in esophageal acid reflux or a hypersensitivity to acid, and both generally respond well to proton pump inhibitor (PPI) therapy. NERD patients who are not acid-dependent have what is called functional heartburn; GERD-like symptoms are present, but there is no obvious involvement of refluxed acid. An important subset of GERD is refractory GERD, which consists of patients who fail aggressive PPI therapy. Parallel findings with other refractory syndromes can be anticipated; however, there are indications that psychosocial factors play a major role in refractory GERD, and these patients may benefit more from an integrated biopsychosocial approach. Diagnosis of GERD is usually made on clinical grounds, often supplemented by a therapeutic trial with antisecretory agents. Endoscopy is reserved for patients with alarm symptoms, such as dysphagia, anemia, or weight loss, or to detect Barrett's esophagus. Endoscopy is not useful to exclude the diagnosis of GERD because it will be negative in 70% of cases in primary care. Ambulatory 24-hour esophageal pH monitoring is necessary only when the diagnosis is in doubt, the patient fails medical management, or surgery is contemplated.     

Barrett's esophagus and esophageal adenocarcinoma: the scope of the problem

Conclusion Barrett's esophagus is probably a more common condition than previously recognized. Although the classic radiologic findings of Barrett's esophagus are present in only a small percentage of patients, this condition should be suspected whenever reflux esophagitis or peptic strictures are demonstrated on double-contrast esophagography. Recent literature also suggests that Barrett's carcinomas comprise up to 50% of all esophageal cancers. Because of the increased risk of developing adenocarcinoma in Barrett's esophagus, endoscopic surveillance has been advocated to detect dysplastic or carcinomatous changes at the earliest possible stage. When barium studies are performed on patients with known Barrett's esophagus, the radiographs should be carefully evaluated for signs of early adenocarcinoma, so these patients can be referred for appropriate management prior to the development of advanced, unresectable tumors.     

Helicobacter pylori infection and eradication

H. pylori infection is associated with various gastroduodenal diseases such as gastritis, peptic ulcer, gastric cancer, gastric MALT lymphoma. H. pylori infection is suggested that it plays a role as protective factor not promoting factor for reflux esophagitis and GERD. Epidemiological studies showed lower prevalence of H. pylori infection in reflux esophagitis and Barrett's esophagus comparing the control. Increased occurrence of reflux esophagitis after curing of H. pylori infection was reported. However, the relationship between H. pylori infection and reflux esophagitis has not been actually made clear. Also the mechanism of reflux esophagitis occurrence after H. pylori eradication is not obscure.     

Radiologic diagnosis of Barrett's esophagus: Critical analysis of 65 cases

A recent increase in the number of Barrett's esophagis being diagnosed is probably directly related to a proportional increase in endoscopic biopsies of the esophagus and awareness of premalignant potential of Barrett's mucosa. While the endoscopist can detect Barrett's mucosa with fair degree of accuracy, the radiologic diagnosis of Barrett's esophagus still remains a diagnostic challenge despite several well established radiologic features. We reviewed 65 patients with pathologically proven Barrett's esophagus and found a wide spectrum of radiologic features. These include hiatus hernia in 49, gastroesophageal reflux in 38, strictures in 32, esophagitis in 20, and characteristic Barrett's ulcer in 12. In addition ascending or migrating strictures were found in 10, mucosal pattern simulating areae gastricae in 5, cricopharyngeal dysfunction in 4, and fixed spiral folds in 3 patients. This constellation of radiologic features, some of which have not been previously emphasized, should further assist radiologists in suggesting the diagnosis of Barrett's esophagus.     

Pretreatment endoscopy--pro & contra: endoscopy is needed before treatment in all patients with gastroesophageal reflux disease

Most current endoscopic guidelines do not recommend the use of routine esophagoscopy in the evaluation of patients with typical symptoms of gastroesophageal reflux disease (GERD), unless alarm features are present. In patients with known reflux esophagitis, esophagoscopy is considered to have no role either in the further management or follow-up. Screening of reflux patients for Barrett's esophagus is not considered to be cost-effective. On the basis of a critical review of the available literature, and of some recent papers in particular, we disagree with these suggestions. We would argue, on the contrary, that a negative esophagoscopy can provide the GERD patient with reassurance, and that esophagoscopy allows targeted therapy to be offered if it is positive for esophagitis. When Barrett's esophagus is diagnosed, it usually leads to a surveillance program being initiated. The potential benefits of endoscopy for the patient's quality of life are probably underestimated when financial issues alone are taken into account. Even if it is true that a large percentage of GERD patients do not have endoscopic abnormalities (those with nonerosive reflux disease), surrogate tests such as the proton-pump inhibitor test or symptom questionnaires do not provide a more accurate diagnosis. We would therefore suggest that, at least in the specialist setting, all patients with suspected GERD should undergo accurate symptom analysis as well as endoscopic evaluation before treatment is started.     

Histopathological diagnosis in reflux esophagitis

We reviewed the histopathological features for the diagnosis of reflux esophagitis and gastroesophageal reflux disease(GERD) including carcinogenesis of the esophagus. Histologically, the presence of capillary dilatation, elongation of papillary, hyperplasia of basal layer, inflammatory cells-infiltration, balloon cells in the epithelium, and ulceration were evaluated in GERD cases. Although, histopathological changes were not clear in endoscopic-negative GERD cases, immunohistochemical examination with cell cycle protein(PCNA, p21, and p27) revealed the same abnormalities with GERD cases. In Japan, the majority cases of GERD are evaluated in grade according to Los Angeles system, therefore the prevalence of Barrett's esophagus and cancer is very low. We hypothesize that esophageal squamous cell carcinoma arising from GERD different from Barrett's cancer sequence, and clinicopathological long-term follow up will be required to assess the carcinogenesis including gene analysis.     

Pathogenesis of reflux esophagitis and Barrett's esophagus

An understanding of the pathogenesis of reflux esophagitis and Barrett's esophagus requires knowledge of the noxious elements in gastric juice and the three major esophageal defenses designed to protect against them. When the esophageal epithelium cannot prevent gastric acid from acidifying the intercellular spaces, the foundation is set for the development of the major symptoms, signs, and complications of reflux esophagitis. Inadequate defense by the epithelium can occur by exposure to the acidic refluxate for a prolonged period of time, because of defects in the antireflux or luminal clearance mechanisms, or by exposure to ingested products that directly impair the epithelium's intrinsic defenses, rendering it vulnerable to injury from even physiologic levels of acid reflux.     

Barrett's esophagus: Clinical issues

Barrett's esophagus has been defined conceptually as the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the distal esophagus. The condition develops as a consequence of gastroesophageal reflux disease. Barrett's metaplasia has clinical importance primarily because of its malignant predisposition, and virtually all of the contentious clinical issues in Barrett's esophagus are related in some way to its cancer risk. This article considers some key clinical issues that impact the management of patients with Barrett's esophagus.