Barrett's esophagus. Reducing the risk of progression to adenocarcinoma.

A more effective approach to the surveillance and prevention of esophageal adenocarcinoma, one of the most lethal of all cancers, is urgently needed. Little progress has been made in the treatment of patients who present with symptoms of obstructive and invasive cancer. The incidence of this cancer is increasing in epidemic proportions throughout the United States and the Western world. 7,8,17,18,26,28,70,132,133 This increase is almost entirely due to carcinomas arising in an easily recognizable precancerous lesion—Barrett's metaplasia. Progression from metaplasia to invasive cancer occurs in a stepwise process that can be recognized through endoscopic biopsy. For reasons that are as yet unresolved, this cancer develops in a select population of patients. The rapid increase in the incidence of this cancer in a select group of patients over a relatively short duration of time strongly suggests that environmental factors interacting with genetically predetermined characteristics are the cause for this neoplastic epidemic. Further studies are needed to identify risk factors and cost-effective surveillance strategies that can prevent this cancer progression. Patients with Barrett's metaplasia carry an increased risk for the development of esophageal adenocarcinoma that is 30 to 125 times that of an age-matched population. It has been estimated that 700,000 to 1.5 million Americans have Barrett's metaplasia. The incidence of adenocarcinoma has been dramatically increasing over the last 3 decades. Nearly all of these develop as a result of severe gastroesophageal reflux disease (GERD)–induced esophagitis and Barrett's metaplasia. Of 1312 esophageal carcinomas diagnosed between 1946 and 1963 at the Mayo Clinic, only 3.3% were adenocarcinomas. 95 Currently, adenocarcinomas make up 60% of esophageal carcinomas at the same institution. 26 Studies indicate that there has been a 10-fold increase in the incidence of adenocarcinoma over the last 30 years. 26 Since the mid-1970s, the incidence of esophageal adenocarcinoma has risen more than 350%. 28 There has also been an increase in the incidence of gastric cardia adenocarcinoma that may be related to Barrett's-like intestinal metaplasia. Although cancer incidence is rising among women and nonwhites, the greatest risk continues to be for white men. 7,8,70 If current increasing incidence continues, esophageal adenocarcinoma will soon become a common cancer. It now affects 3.9 white men per 100,000 and fewer women or nonwhites. 70 Some have questioned whether this dramatic increase in the incidence of esophageal adenocarcinoma and Barrett's metaplasia may simply reflect increased use of endoscopy, inconsistencies in the definition of esophageal carcinoma, or changes in the way numbers are being reported. To address these issues, Kim et al 70 examined the incidence of adenocarcinoma of the esophagus in Pennsylvania in the 1980s. Working with a single tumor registry throughout Pennsylvania in which the definitions of adenocarcinoma of the esophagus did not change, there was a marked increased incidence of adenocarcinoma. The greatest incidence occurred in white men, in whom the incidence increased by an average of 8% per year (Fig. 1). Thus, Barrett's metaplasia is an extremely important clinical problem that warrants a thorough understanding of risks by gastroenterologists and other clinicians to permit the development of rational management of its epidemic increase. Adenocarcinoma of the esophagus is one of the most lethal of all cancers. Surgery offers the best hope for prolonging survival, but most patients present only after symptoms of cancer develop. 49 At that stage, widespread metastases are almost always present, and current therapies add little to the prognosis of such patients. Although studies have suggested that adjuvant therapy may offer some value in patients who are surgical candidates, the overall increase in survival is minimal. 114 Several anatomic peculiarities of the esophagus limit the values of surgery: (1) the esophagus has no serosa; (2) lymphatics drain into multiple lymph node chains in the neck, chest, and abdomen; (3) lymphatics drain from the submucosa, just millimeters below the mucosa; and (4) the esophagus is located adjacent to vital organs, including the heart and lungs. The poor prognosis of esophageal adenocarcinoma also relates to the biology of this tumor. By the time patients undergo attempted curative resection, more than 80% of patients have widespread metastases to bone marrow. 86 This metastasis occurs even in a highly select population chosen as candidates for curative resection through a thorough, systematic preoperative evaluation. Furthermore, metastatic cells retrieved from bone marrow remain extremely resistant to chemotherapy. Tumor cells cultured from bone marrow of patients who had received adjuvant chemotherapy were just as able to grow in culture as those in patients who had not received chemotherapy. 86 Furthermore, although patients who are identified as having carcinoma in situ can have a prolonged survival, survival falls to less than 50% at 5 years when the tumor has invaded 1 or 2 mm beyond the muscularis mucosa into the submucosa. 102,108 The lethal nature of this cancer and the lack of efficacy of chemotherapy and radiation therapy provide the rationale for promoting surveillance endoscopy in patients with chronic gastroesophageal reflux symptoms, particularly those with known Barrett's metaplasia. 92 No prospective, randomized study has substantiated this approach. Studies indicate, however, that patients with adenocarcinoma of the esophagus identified through endoscopic surveillance techniques have a more prolonged survival compared with patients with a similar grade and stage of tumor identified during evaluations of symptoms. 102 Further studies are clearly needed to evaluate and substantiate the value of endoscopic surveillance. Taken together, these findings suggest that health professionals should be aware of clinical risk factors that implicate the need for diagnostic endoscopy in patients at risk for Barrett's metaplasia. Most studies that have addressed this issue compared patients with adenocarcinoma with those with squamous cell carcinoma of the esophagus or with healthy controls. When such controls are used, the findings of risk factors tend to mimic risks for GERD. Studies are needed to distinguish clinical factors for patients at risk of developing Barrett's adenocarcinoma among those with benign reflux. This article discusses clinical factors that are useful in identifying patients at high risk for developing Barrett's metaplasia and esophageal adenocarcinoma. Until such data are available, it is important to use epidemiologic data to identify risk factors for developing adenocarcinoma.