Barrett's esophagus: chemoprevention

The clinical applicability of the experimental data discussed previously remains questionable, and results of clinical studies on chemoprevention in Barrett's esophagus are needed. The utility of selectively targeting acid exposure, ODC, and COX-2 is not clear, and elucidation of that role will be facilitated by a better understanding of the contribution of these factors in the development of Barrett's cancers. The insights already gained into the basic mechanisms of acid exposure, ODC, and COX-2 in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma hold promise for the development of future therapies aimed at these molecular targets and their signaling pathways. In preclinical studies, the ability of COX-2 selective NSAIDs and DFMO to inhibit carcinogenesis is encouraging. Results of well-designed, prospective clinical studies, however, are still needed to establish the efficacy of potent acid suppression, COX-2 inhibitors, and DFMO in the prevention of this malignancy.     

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.     

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.     

Barrett's esophagus

Esophageal cancer staging is a widely accepted indication for endoscopic ultrasonography (EUS). The evaluation of Barrett's esophagus (BE) with EUS is indicated only when there is high-grade dysplasia or a concern for malignancy in an endoscopic lesion. Because the options for the management of BE and early adenocarcinoma are diverse, proper selection of patients by accurate staging with EUS is critical, particularly when nonoperative management is considered. For example, patients with BE with high-grade dysplasia may be offered esophagectomy in some medical centers, but nonoperative therapies such as endoscopic ablative therapy or mucosal resection may be the preferred treatment options in other gastroenterology practices. This article discusses the scientific evidence for the use of EUS in BE or early esophageal adenocarcinoma.     

Barrett's esophagus: endoscopic resection

In experienced hands, ER is a safe method of resecting dysplastic lesions and early carcinomas of the GI tract, and it has decisive advantages compared with other local endoscopic treatment procedures (such as thermal destruction and PDT). The opportunity for histological processing of the resected specimen provides information regarding the depth of invasion of the individual layers of the GI tract wall. Additionally, it has advantages regarding excision with healthy margins. This means that even when there is infiltration of the submucosa that has not been detected before treatment--in which case local endoscopic therapy is no longer appropriate--a patient with early Barrett's cancer still is able to undergo surgical resection. As was shown recently, the morbidity and mortality of ER are significantly dependent on the frequency with which esophagectomy is performed in each center. When there were more than 20 procedures of this type per year, the surgical mortality was 8%, whereas in centers conducting fewer than 10 procedures per year the rate was 21%. In view of the consequent claim that ER should only be performed at high-volume centers, curative endoscopic treatment of early esophageal carcinomas also should be performed only in centers with a similar frequency to that of the surgical high-volume centers. It is only in these conditions that the conclusion is defensible that patients with HGIN or mucosal Barrett's carcinoma should undergo ER with curative intent instead of radical ER. Randomized and controlled studies comparing radical esophagectomy with endoscopic therapy are desirable, but they are difficult to conduct, not least because valid 5-year survival data show no significant difference between patients who have undergone endoscopic treatment for early Barrett's cancers and the average German population of the same age and sex.     

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.     

Barrett's esophagus. A continuing conundrum

Barrett's esophagus, a condition in which the distal esophagus is lined by columnar epithelium, is almost always caused by gastroesophageal reflux and often occurs in conjunction with a sliding hiatal hernia. Patients are typically white men in their 50s who smoke and drink, and they present with complaints of regurgitation, heartburn, and/or dysphagia. Endoscopic biopsies are required to confirm the diagnosis. Complications, such as stricture, ulcer, dysplasia, and malignant degeneration, occur in many cases. Adenocarcinoma is the most serious complication. Medical treatment, including life-style changes as well as pharmacologic therapy, usually relieves symptoms and heals esophagitis, but when it fails, antireflux surgery is indicated. Patients without evidence of dysplasia should undergo endoscopy yearly; those with mild dysplasia require more frequent surveillance. If biopsies disclose severe dysplasia, esophagogastrectomy should be performed.     

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.     

Barrett's esophagus: screening and prognosis

The diagnostic criteria for Barrett's disease have changed very considerably during the last 10 years. Classically, the definition asked for columnar epithelium in the lower esophagus extending for at least 3 cm proximally. Now, the diagnosis rests on the finding of specialised intestinal metaplasia, i.e. columnar epithelium with goblet cells, in the esophagus, regardless of the extension. This is important because it is this type of metaplasia that is associated with an increased risk for the development of esophageal adenocarcinoma and esophageal adenocarcinoma is the tumor with the fastest rising incidence in the western world in recent years. The criteria of the current definition of Barrett's esophagus are described in detail and the implications this change in definition carries for screening and surveillance of patients is discussed.     

Biomarkers in Barrett's esophagus

This article provides a framework for clinicians who are attempting the difficult task of interpreting the Barrett's biomarker literature with the goal of improving care for their patients. Although many articles. including more that 60 proposed biomarkers, have been published on this subject, only a few describe phase 3 and 4 studies that are of interest to the clinical gastroenterologist (Table 1). For year, dysplasia grade has been the sole means of risk stratification for patients with BE, and it likely will continue to be used in the foreseeable future. The current authors believe that dysplasia classification can be valuable using the team management approach and quality controls described previously. Significant problems, however, have emerged in phase 2 through 4 studies of dysplasia that make it imperative for the Barrett's field to incorporate additional biomarkers as they are validated. These problems include poor reproducibility of dysplasia interpretations, poor predictive value for negative, indefinite, and low-grade dysplasia, and inconsistent results for HGD in different centers, all of which makes it virtually impossible to develop national guidelines for surveillance. Some studies have even suggested that endoscopic biopsy surveillance using dysplasia may not be worthwhile. Currently, flow cytometric tetraploidy and aneuploidy have progressed furthest in biomarker validation (see Table 1). With proper handling, endoscopic biopsy specimens can be shipped to reference laboratories that have the instruments, computer analytic methods, and expertise to reproducibly detect tetraploidy and aneuploidy. The results of phase 4 studies indicate that flow cytometry appears to be useful in detecting a subset of patients who do not have HGD and yet have an increased risk of progression to cancer that cannot be identified by dysplasia grade. For many reasons, the authors anticipate that the number of validated biomarkers will increase substantially in the future. Biopsy repositories are now readily available for phase 3 studies that can evaluate and compare biomarkers. There are initiatives for multi-institutional Barrett's Centers of Excellence that could provide rapid progress in biomarker evaluation. In addition to new candidate biomarkers, the human genome project has provided high-throughput methodologies and methods for computer analysis of data, which can provide the volume and quality control required for clinically useful biomarkers. Currently, 17p (p53) LOH has progressed the furthest among molecular biomarkers. The authors do not recommend its routine clinical use at the present time, however. Finally, it is likely that clinicians will want to follow the results of clinical treatment-response studies and epidemiologic studies that evaluate relationship between clinical interventions or environmental risk and protective factors and surrogate endpoints, especially if the endpoints are progessing well along the phases of biomarker validation. These studies are likely to be of clinical interest because they may becoming the basis for randomized clinical trials to prevent cancer in BE.     

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.     

Carcinogenesis of Barrett's esophagus

Barrett's esophagus is a premalignant condition and remains the number one risk factor for developing adenocarcinoma. Gastro-esophageal reflux disease is a strong risk factor for both esophageal adenocarcinoma and the precancerous lesion Barrett's esophagus. Both of these conditions are related to the reflux of acid and bile into the esophagus. This results in inflammation and cell damage which initiates a sequence of events termed the metaplasia-dysplasia sequence in which the squamous epithelium is replaced by columnar epithelium exhibiting increasing degrees of dysplasia and overt malignancy. The underlying disease mechanisms remain unclear, but tumor suppression genes (p53, p16, APC) and, oncogenes (K-ras, cyclin D1, c-erb-2) seem to cause the malignant transformation of Barrett's esophagus, and the genetic or epigenetic alterations of these genes have been reported.     

Barrett's esophagus in children

Barrett's esophagus (BE) is a condition of esophageal dysplasia in which the tubular esophagus is lined with columnar instead of squamous mucosa--not with just any type of columnar mucosa, but with a specialized type with goblet cells. It is considered to be an acquired phenomenon secondary to acid exposure from gastro-esophageal reflux (GER). This report shows a review of BE of children and our data about BE from the study of 19 handicapped children with GER. 3 had intestinal dysplasia with goblet cells (BE). The % time of pH under 4 on 24-hour pH monitoring was significantly lower in the patients with esophagitis including BE than in them with normal esophagus. BE of our study seemed to be reversible after the surgery and anti-acid therapy. It is suggested that BE is not a rare condition even in children and biopsy specimens should be taken to establish the diagnosis.