A 53-year-old man, who is otherwise healthy and has a 20-year history of occasional heartburn, reports having had worsening heartburn for the past 12 months, with daily symptoms that disturb his sleep. He reports having had no dysphagia, gastrointestinal bleeding, or weight loss and in fact has recently gained 20 lb (9 kg). What would you advise regarding his evaluation and treatment?The Clinic a l Problem Gastroesophageal reflux disease is the most common gastrointestinal diagnosis recorded during visits to outpatient clinics. 1 In the United States, it is estimated that 14 to 20% of adults are affected, although such percentages are at best approximations, given that the disease has a nebulous definition and that such estimates are based on the prevalence of self-reported chronic heartburn. 2 A current definition of the disorder is "a condition which develops when the reflux of stomach contents causes troublesome symptoms (i.e., at least two heartburn episodes per week) and/or complications." 3 Several extraesophageal manifestations of the disease are well recognized, including laryngitis and cough (Table 1). With respect to the esophagus, the spectrum of injury includes esophagitis (Fig. 1A), stricture (Fig. 1B), the development of columnar metaplasia in place of the normal squamous epithelium (Barrett's esophagus) (Fig. 1C), and adenocarcinoma (Fig. 1D). Of particular concern is the rising incidence of esophageal adenocarcinoma, an epidemiologic trend strongly linked to the increasing incidence of this condition. 4-6 There were about 8000 incident cases of esophageal adenocarcinoma in the United States in 2004, 7 which represents an increase by a factor of 2 to 6 in disease burden during the past 20 years. 8,9 Esophagitis occurs when excessive reflux of acid and pepsin results in necrosis of surface layers of esophageal mucosa, causing erosions and ulcers. Impaired clearance of the refluxed gastric juice from the esophagus also contributes to damage in many patients. Whereas some gastroesophageal reflux is normal (and relates to the ability to belch), several factors may predispose patients to pathologic reflux, including hiatus hernia, 10,11 lower esophageal sphincter hypotension, loss of esophageal peristaltic function, abdominal obesity, 11,12 increased compliance of the hiatal canal, 13 gastric hypersecretory states, 14 delayed gastric emptying, and overeating. Often multiple risk factors are present.A consistent paradox in gastroesophageal reflux disease is the imperfect correspondence between symptoms attributed to the condition and endoscopic features of the disease. In a population-based endoscopy study in which 1000 northern Europeans were randomly sampled, 15 the prevalence of Barrett's esophagus was 1.6%, and that of esophagitis was 15.5%. However, only 40% of subjects who were found to have Barrett's esophagus and one third of those who were found to have esophagitis reported having reflux symptoms. Conversely, two thirds of patients reporting reflux symptoms had no esophagitis. Furthermore, altho...