What is acid reflux?

Extraesophageal Presentations
Acid reflux–related chest pain is easily treated by H 2RAs or PPIs, with efficacy substantiated by placebo-controlled studies. The efficacy of acid suppression therapy in asthma, cough, and other pulmonary complications of GERD is more mixed. Medical antireflux therapy improves asthma symptoms and reduces the need for asthma medications in more than 60% of patients, but objective improvement of peak expiratory flow rates is observed in only 25% of patients. Best results are found with higher doses of PPIs (usually twice-daily administration) given for 2 to 3 months. Potential positive predictors of PPI response include asthma that is difficult to control, associated acid regurgitation, proximal reflux on pH testing, and healing of esophagitis with antireflux therapy. Case studies report that 60% to 96% of patients with suspected acid-related ear, nose, and throat symptoms and signs improve with acid suppression. Here again, PPIs are more effective than H 2RAs, and extended therapy for up to 3 months may be required. Predictors of response have not been identified, although patients with milder laryngeal signs show better symptom improvement. In all these possible extraesophageal presentations of GERD, failure to respond to aggressive PPI therapy, confirmed by adequate acid control by pH testing, suggests a cause of these complaints other than acid.

Esophageal Strictures
Dysphagia in patients with esophageal strictures is related to stricture diameter and severity of esophagitis. When the esophageal lumen diameter is less than 13 mm, dysphagia is a major complaint and esophageal dilation is required. Simple short strictures can be dilated by blind peroral passage of rubber Hurst (round ends) or Maloney (taper ends) mercury-filled dilators of increasing sizes (16 to 60 French, 3 French = 1 mm) to disrupt the fibrous bands producing the obstruction. Complicated longer, tighter, or more irregular strictures will require bougienage over a guidewire using hollow-centered Savary plastic-covered polyvinyl dilators or balloon (Gruentzig) dilators. Before and after dilation, medical therapy with PPI is indicated; it has been shown to be superior to H 2RAs in relieving symptoms and in reducing the frequency for repeat dilations. Maintenance PPI therapy for patients with strictures has dramatically reduced the incidence of repeat esophageal dilations and the cost of treating these patients. Recalcitrant strictures, requiring surgery, are now very uncommon and suggest another aggravating factor such as chronic pill injury.

Barrett Esophagus In general, esophagitis in the presence of Barrett esophagus can be easily healed with PPI therapy, but meaningful regression of Barrett epithelium, except for small squamous islands, is rarely reported even with high-dose PPI therapy. Recent ex vivo studies have suggested that intermittent “pulses” of acid result in enhanced Barrett epithelial cell proliferation, possibly increasing the risk of dysplasia and cancer. Some have suggested the need to eliminate all acid reflux in patients with Barrett esophagus, but this would require high and frequent doses of expensive medications and serial pH monitoring to document efficacy of therapy. Pending further clinical studies, patients with Barrett esophagus should be treated like others with chronic GERD. Esophageal resection of Barrett esophagus can prevent the progression to cancer, but this requires a total esophagectomy with high mortality, except in selected surgical centers. Therefore, ablation of Barrett epithelium in the setting of strict PPI anacidity has been proposed. Photodynamic therapy, laser, multipolar electrocoagulation, argon plasma coagulation, and endoscopic mucosal resection have been used for this purpose. In these studies, Barrett mucosa can be reversed completely in 70% to 80% of patients, but intestinal metaplasia underlying the new squamous mucosa is reported in almost all series, with the occasional residual foci of metaplasia developing adenocarcinoma. Adverse effects of ablation therapy have ranged from mild chest pain, sore throat, or odynophagia to esophageal perforation and death. The incidence of adenocarcinoma in patients with Barrett esophagus without dysplasia is probably so low that endoscopic ablation cannot be advocated outside of study protocols. Endoscopic therapy for patients with high-grade dysplasia or early cancer holds more promise, especially in the older patients with comorbid illnesses. Because there is currently no way of eliminating the malignant risk of Barrett esophagus, regular endoscopic surveillance is recommended. Biopsies should be taken from each quadrant every 2 cm axially within the metaplastic tissue. The rationale is that dysplasia within Barrett epithelium is often multifocal, and obtaining fewer tissue samples increases the risk of missing dysplastic areas. Brush cytology can compliment endoscopic biopsies. Biomarkers, such as p53, and flow cytometry may augment the yield of histological examination of biopsy specimens. Although prospective studies are not available, case series confirm that esophageal adenocarcinomas detected by endoscopic surveillance are at an earlier stage with a more favorable survival than cancers detected at the time of diagnosis of Barrett, typically when patients present with dysphagia. The appropriate surveillance interval for patients with Barrett esophagus has not been studied prospectively. However, current programs, such as proposed by the American College of Gastroenterology, are based on the grade of dysplasia. In these recommendations, the management of high-grade dysplasia remains most controversial. Some groups suggest that high-grade dysplasia may regress to lesser grades, and an intensive biopsy protocol every 3 months will differentiate high-grade dysplasia from cancer. The surgical literature contrasts with this experience. Of 126 cases with high-grade dysplasia alone by endoscopic biopsies, 41% had cancer, although usually an early stage, at the time of esophagectomy. Nevertheless, most patients with Barrett esophagus never progress to important degrees of dysplasia. Predictors of cancer progression at the initial diagnosis of Barrett esophagus are needed to define individual surveillance programs more appropriately. One study suggested that patients whose baseline biopsies are negative or show only low-grade dysplasia without increased 4N or aneuploidy on flow cytometry may have surveillance deferred for up to 5 years. Another prospective multivariate analysis revealed that progression to high-grade dysplasia or cancer was significantly and independently associated with dysplasia at diagnosis or anytime during follow-up, hiatal hernia size greater than 2 cm, and Barrett esophagus length greater than 2 cm. These patients may warrant more frequent surveillance programs.

Patients with long-segment Barrett esophagus have an estimated 30 to 125 times increased risk of developing esophageal cancer compared with the general population. Early studies suggested that the median cancer incidence was 1 per 100 patient-years of follow-up, but more recent studies with longer follow-up suggest a lower cancer rate of 1 per 200 to 250 patient-years. This is an annual incidence of approximately 0.5%, with about 500 cases of adenocarcinoma diagnosed annually. However, since the early 1980s, the incidence of squamous cell carcinoma has stayed constant, whereas the incidence of adenocarcinoma of the esophagus and esophagogastric junction has risen fivefold—a growth rate exceeding that of any other cancer. Currently, adenocarcinoma accounts for more than half of all esophageal cancers in the United States. Despite this cancer risk, most patients with Barrett esophagus die of unrelated causes. More than 90% of patients who develop cancer present with symptoms caused by the tumor itself and are unaware of their antecedent Barrett esophagus. Epidemiologic data suggest that the mean interval from developing Barrett esophagus to evolution to cancer may be 20 to 30 years.

Management of patients with Barretts metaplasia has two aspects: treating the underlying GERD and managing the risk of adenocarcinoma of the esophagus. The principles for treating peptic esophagitis and controlling symptoms in Barretts metaplasia are the same as for uncomplicated GERD with the proviso that because it is associated with extreme esophageal acid exposure, it will likely require more intensive treatment. In general, mucosal damage and symptoms can be controlled with proton pump inhibitor therapy, but surgery may be needed, or even desirable, in refractory cases.
On the basis of in vitro and in vivo cell proliferation studies reporting increased cell proliferation and decreased differentiation in tissue exposed to acid, some authorities believe that complete acid suppression is desirable in therapy for Barretts metaplasia. However, there is no clinical evidence that aggressive antisecretory therapy or antireflux surgery prevents the occurrence of adenocarcinoma or causes regression of intestinal metaplasia. Proton pump inhibitor therapy has proved to be of no avail in reversing metaplasia or preventing adenocarcinoma. Thus, the available data support titrating therapy to control symptoms and treat esophagitis, irrespective of the presence of Barretts metaplasia.