Barrett's esophagus represents replacement of normal distal esophageal squamous epithelium with specialized columnar epithelium containing goblet cells. Typically arising in the setting of chronic gastroesophageal reflux disease, the presence of Barrett's esophagus carries a 50- to 100-fold increased risk of developing esophageal cancer. Risk factors include male sex, smoking history, obesity, Caucasian ethnicity, age > 50 and > 5-year history of reflux symptoms. Aggressive medical or surgical antireflux therapy may ameliorate symptoms, but have not yet been proven to affect the risk of developing esophageal adenocarcinoma in randomized trials. Although dysplasia is an imperfect biomarker for the development of subsequent malignancy, random sampling of esophageal tissue for dysplasia remains the clinical standard. There have been no studies to establish that endoscopic screening/surveillance programs decrease the rates of death from cancer. Fit patients with Barrett's esophagus and high-grade dysplasia should undergo esophagectomy to prevent the risk of developing esophageal adenocarcinoma. For non–operative candidates, endoscopic ablative approaches may represent a reasonable therapeutic alternative.
This article by Drs. Schuchert and Luketich describes in sharp detail what we know about Barrett's esophagus. More importantly, these authors are very clear about how much we don't know about this enigmatic intermediary. Barrett's metaplasia is the link between the most common disease of the upper gastrointestinal tract, gastroesophageal reflux, and the most rapidly increasing cancer of the GI tract, esophageal adenocarcinoma. While it is likely that esophageal adenocarcinoma may develop in the absence of Barrett's esophagus, the evidence suggests that the vast majority of individuals with esophageal adenocarcinoma have Barrett's esophagus first. If we are to make any inroads in improving the outcome of patients with esophageal cancer, it will be by developing methods of early detection and effective treatment of Barrett's esophagus.
Barrett's esophagus is a very prevalent disorder in high-risk populations, (white males > 50 years old). Cost-effectiveness of endoscopic screening can be demonstrated in high-risk groups with reflux symptoms. The tough nut to crack is detecting those with minimal reflux symptoms and extraesophageal reflux symptoms before their first symptom becomes dysphagia. By the time dysphagia develops, most patients are incurable. Increasing data suggest that superesophageal symptoms such as cough-not otherwise explained-may be as worrisome as chronic heartburn for the presence of esophageal adenocarcinoma.
Once Barrett's esophagus is detected, the treatment is indeed controversial. While fundoplication confers the best protection of the esophagus from acid, bile, and any refluxate, prospective trials do not yet provide sufficient power to prove that antireflux surgery protects against cancer. Nonetheless, these same trials demonstrate a greater chance of Barrett's regression in patients treated with laparoscopic fundoplication.
Surveillance of patients with dysplasia is indeed a tricky matter. Low-grade dysplasia suffers from the greatest interobserver variability and is the dysplastic form most sensitive to regression. High-grade dysplasia rarely regresses, and usually progresses-over a 5- to 8-year period-to adenocarcinoma. While it is tempting to perform surveillance endoscopy (per the Seattle protocol) until invasive cancer is detected, there is a risk to this. In most studies, one or two patients in the surveillance arm will have lymph node–positive esophageal cancer at the time they come to the operating room. The presence of lymph node invasion in esophageal cancer drops the prognosis from 90% survival to < 40% 5-year survival. It is for these reasons that a good-risk patient with high-grade dysplasia should be referred for definitive therapy, removing all involved Barrett's epithelium. Currently, only esophagectomy provides definitive protection.
Nodules in a field of Barrett's esophagus frequently contain early invasive adenocarcinoma and should all be biopsied. Endoscopic mucosal resection is an appealing option for treating early and localized esophageal cancer, especially that found in a nodule. If the resection margins are positive or if the tumor invades the submucosa (by traversing the muscularis mucosa), the risk for lymph node metastasis increases significantly. Invasive cancer that is not confined to the mucosa should be treated with esophagectomy, unless the patient has a poor chance of surviving the operation.
For high-risk patients, ablative therapy has come a long way, offering promises of complete control of Barrett's esophagus. Photodynamic therapy (PDT) is effective in reducing the incidence of adenocarcinoma, but the frequency with which individuals develop cancer despite PDT is quite alarming. Radiofrequency ablation with balloon-based electrodes is one of the more promising technologies for eliminating Barrett's epithelium, avoiding the problem of "buried glands" that may hide invasive cancer.
The techniques of minimally invasive esophagectomy have made this major operation much more patient-friendly. In addition to the techniques of Dr. Luketich, patients with high-grade dysplasia are very amenable to a transhiatal, laparoscopic inversion esophagectomy. As this technique has evolved, the outcomes and the length of stay continue to improve such that few patients need to be hospitalized beyond a week, and the complications are few.
It should be clear from this review and commentary that Barrett's esophagus management is in flux, with medical and surgical treatment options evolving rapidly. Improvement in the early detection of cancer will require new cost-effective methods for screening large numbers of patients at risk.
-John G. Hunter, MD
Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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