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The American College of Gastroenterology (ACG) has updated its guidelines for the diagnosis and treatment of gastroesophageal reflux disease (GERD) to reflect the continuing advances in this area. The updated guidelines appear in the January 2005 issue of the American Journal of Gastroenterology and are available online at http://www.acg.gi.org/phy-sicians/guidelines/GERDTreatment.pdf. The original guidelines were published in 1995 with the support of the ACG and its Practice Parameters Committee and were updated once before, in 1999. For all versions, the collaborators reviewed the scientific literature using the National Library of Medicine's MEDLINE database. Where studies were lacking, expert consensus was derived from a combination of the literature and personal experience. Abstracts presented at meetings were included only if they incorporated unique data from ongoing trials. The committee evaluated each guideline and gave the evidence a score from I to IV, with I being the strongest.

The ACG guidelines define GERD as "symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus." The authors emphasize that the guidelines apply to adult patients and represent the preferred, but not the only, approach; treatment should be individualized according to the patient and circumstances. Many aspects of treatment for GERD may change as understanding of the condition improves; areas for additional study include impedance and "tubeless" pH monitoring, small caliber unsedated endoscopy, and more cost-effective screening for Barrett's esophagus.

Diagnosis

Typical symptoms of GERD include heart-burn (pyrosis) and regurgitation that often follow large or high-fat meals, may be aggravated by bending over or lying down, and usually are relieved by antacids. The presence of typical symptoms combined with endoscopic changes is 97 percent specific for GERD (Table 1).

"Alarm symptoms" suggestive of complicated disease include dysphagia, odynophagia, bleeding, weight loss, and anemia. Patients with these symptoms are more likely to have peptic strictures or esophagitis. Barrett's esophagus is three to six times more likely in patients who have had symptoms of GERD for more than one year. However, these symptoms cannot be relied on for predicting complications.

The ACG guidelines also address the role of empiric therapy, endoscopy, ambulatory reflux monitoring, and esophageal manometry in the diagnosis of patients with GERD (Table 1).

EMPIRIC THERAPY

Evidence Level IV. In patients who have a history typical of uncomplicated GERD, an initial trial of empiric medication and lifestyle changes is appropriate. Most patients with GERD experience symptom relief through medical therapy, so empiric therapy is a simple and cost-effective (although not optimally sensitive or specific) diagnostic test. A diagnosis of GERD can be assumed in patients who respond to therapy; however, unresponsive symptoms do not rule out GERD. In patients with symptoms of GERD that are refractory to therapy, additional testing should be considered to exclude complications, and the diagnosis may need to be changed.

ENDOSCOPY

Evidence Level III. Endoscopy is the preferred technique for diagnosing complications of GERD because it allows for evaluation of the esophageal mucosa. Endoscopy at presentation and additional testing should be considered in patients with symptoms suggestive of complicated disease, and in those at risk for Barrett's esophagus (Table 1); endoscopic biopsy is the only reliable method for the diagnosis of Barrett's esophagus and evaluation for dysplasia. Endoscopy may be more reliable when performed after initial therapy, because inflammatory changes that could be mistaken for dysplasia would be less prevalent; however, this has not been proven. Barium radiography is 80 percent accurate for severe esophagitis, but is neither sensitive nor specific for diagnosing GERD, and is not recommended.

The presence of Barrett's esophagus or esophagitis is diagnostic for GERD, but normal endoscopy results are found in the majority of symptomatic patients and neither rule out GERD nor indicate a lower severity of symptoms. Patients with so-called "endoscopic negative" disease have similar requirements for therapy and should receive the same treatment considerations as patients who have erosive esophagitis, including, in some patients, long-term proton pump inhibitor (PPI) therapy.

AMBULATORY REFLUX MONITORING

Evidence Level III. Ambulatory reflux monitoring of the esophagus with pH testing is the best tool for studying actual amounts of reflux in a given patient. It can help confirm reflux in patients with normal endoscopic findings, and in those whose symptoms continue despite an acid-suppression trial or therapy. Ambulatory pH reflux monitoring is highly sensitive and specific (96 percent) in patients with erosive esophagitis, although some inaccuracies have been reported. It enables the identification of excess esophageal acid exposure and esophageal-acid-related symptoms.

In the future, ambulatory testing may be achieved by radiotelemetry capsule monitoring, in which a capsule is attached to the esophageal mucosa, or combined impedance and acid testing to measure acid and nonacid reflux.

ESOPHAGEAL MANOMETRY

Evidence Level III. Esophageal manometry generally is used to accurately place ambulatory pH monitoring probes, although adequate placement recently has been reported with a tubeless system. This technique is useful for excluding rare motility disorders such as achalasia and scleroderma in patients being considered for antireflux surgery, and also has been used preoperatively to measure peristalsis.

Treatment

Various treatment options, including lifestyle modification, patient-directed therapy, acid suppression, use of promotility agents, maintenance therapy, and surgery, are evaluated in the ACG guidelines (Table 2).

LIFESTYLE MODIFICATION

Evidence Level IV. The results of most randomized trials show a 20 to 30 percent response to symptoms of GERD with placebo therapy, and this often is attributed to lifestyle modifications. The true efficacy of lifestyle modifications has yet to be documented reliably, but many studies have indicated that they may reduce distal esophageal acid exposure. Modifications thought to be effective include elevating the head of the bed, reducing fat intake, quitting smoking, and remaining upright for three hours after meals. Foods such as chocolate, alcohol, peppermint, coffee, onions, and garlic are reported to decrease lower esophageal sphincter pressure, but no randomized trials on their efficacy are available. Although lifestyle modifications alone are not likely to control symptoms in most patients with GERD, they may be beneficial, and educating patients about behaviors that may contribute to reflux is therefore reasonable.

PATIENT-DIRECTED THERAPY

Evidence Level IV. Over-the-counter medications such as antacids and antirefluxants (e.g., alginic acid) are viable treatment options for milder forms of GERD, and may relieve symptoms in approximately 20 percent of patients. A combination of the two therapies may be more effective than antacids alone. Histamine [H.sub.2]-receptor antagonists ([H.sub.2]RAs) have been shown to decrease gastric acid, and can be used as premedication by patients who are able to predict symptom occurrence. H2RAs are thought to remain effective for longer than antacids, although their peak potencies are similar. Over-the-counter prescription-dose omeprazole (Prilosec) is avail-able in the United States for the short-term (i.e., 14 days) treatment of heartburn.

Patients should not self-medicate for more than 14 days without further physician evaluation because of the risk of Barrett's esophagus and other complications.

ACID SUPPRESSION

Evidence Level I. Acid suppression is the basis of treatment for GERD, and can be accomplished most quickly and effectively with PPIs. In 33 randomized trials that included more than 3,000 patients with erosive esophagitis, more patients experienced symptom relief and healing of esophagitis with PPI therapy (approximately 80 percent) than with [H.sub.2]RA therapy (50 to 60 percent). Even when higher and more frequent doses of H2RAs are used, the improvement rates do not match those of PPIs. Long-term PPI therapy is extremely beneficial in patients with chronic or complicated GERD, and safety concerns are minor (e.g., possible vitamin [B.sub.12] deficiency). The five PPIs available in the United States--omeprazole, lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium)--are effective in prescription dos-ages; they should be taken before meals (generally before breakfast if taken once daily, although a recent study proposed taking PPIs before the evening meal to control nighttime acid).

Higher-than-approved dosages of PPIs may be appropriate in certain situations, such as in patients who show only a partial response to standard doses or are having breakthrough symptoms, in empiric treatment trials for supraesophageal GERD symptoms, and in cases of severe esophageal dysmotility or Barrett's esophagus. The dose should be divided and the second dose given before the evening meal, not at bedtime.

There is no proven benefit to controlling acid in patients with Barrett's esophagus, but if these patients want complete acid control, high-dose twice-daily PPI therapy is necessary. In many patients, gastric acid will still be secreted. An additional nighttime [H.sub.2]RA may be effective, but probably not in the long-term.

Strategies to limit the number of patients using continuous PPI therapy have been proposed, but not well tested. The only advantage is economic, and because generic and over-the-counter PPIs are available, even this benefit is small. According to one study, out of 71 patients on PPIs, 42 percent could be treated effectively with lower cost medications and 15 percent could eliminate medication altogether. On-demand PPI therapy may make sense for patients with mild to moderate symptoms, but studies are lacking. Patients who have tried less effective medications without success should have access to long-term PPI therapy.

PROMOTILITY THERAPY

Evidence Level II. Esophagogastric motility problems such as lower esophageal sphincter incompetence and delayed gastric emptying are a root cause of GERD, and correcting these issues would make acid suppression unnecessary. Available promotility agents (e.g., tegaserod [Zelnorm], baclofen [Lio-resal]) may be useful in select patients with GERD, particularly as an adjunctive acid suppressant. However, these agents have not proved effective as monotherapy for GERD, and high side-effect profiles have decreased their use. More research is needed.

MAINTENANCE THERAPY

Evidence Level I. Because GERD is a chronic condition, and symptoms usually return once PPI therapy is stopped, continuous, even lifelong, therapy is appropriate. Maintenance therapy will vary depending on the patient; the goal is to keep symptoms under control and prevent complications. Up to 20 percent of patients may need only antacids with lifestyle changes, but up to 50 percent will relapse frequently despite therapy. Medication should be given in what-ever dosage is effective.

Full-dose PPI therapy may reduce symptom relapse, but reduced-dose PPIs (e.g., alternate-day omeprazole) have consistently proved ineffective for long-term management of GERD. Patients who experience relief with PPIs often relapse when given standard- or high-dose H2RAs with or without prokinetic therapy; once-daily dosages of H2RAs are not appropriate for patients with GERD.

Acid suppression has been proved to decrease the recurrence of peptic esophageal strictures, but Barrett's esophagus does not appear to regress. Squamous epithelium has been reported in association with long-term PPI therapy, although its significance remains unclear.

SURGERY

Evidence Level II. One option for the maintenance of GERD is antireflux surgery, or repair of the lower esophageal sphincter. The effectiveness of surgical therapy is controversial: in early trials, surgery was more effective than medication, but only low-efficacy treatments were used in comparison. Poorer outcomes and more complications are found in low-volume centers.

Candidates for surgery must be carefully selected and evaluated. Typical reflux symptoms are more likely to be relieved by surgery than are atypical and supraesophageal symptoms. According to one study that involved 100 patients, the best predictors for good surgery outcomes were age younger than 50 years and typical reflux symptoms that resolved completely with medical therapy, although lack of response to therapy often is used as a rationale. Patients with nocturnal regurgitation and those with duo-denogastroesophageal reflux may benefit from surgery; more data are needed to deter-mine which patients would benefit most. Complications of surgery may be increased with delayed gastric emptying, but there is no clear indication for routine preoperative testing. Deterioration of lower esophageal sphincter pressure and endoscopic histology after five or six years postoperative has been reported.

The availability of laparoscopic antireflux surgery has increased patient acceptance of surgical therapy. Laparoscopic techniques have been found to lower the cost of treatment and shorten the duration of hospital stay as well as reduce postoperative morbidity, although postoperative symptoms (e.g., dysphagia, belching, flatulence, diarrhea) still are common. Laparoscopic surgery may increase dysphagia compared with an open technique, may not be possible in patients who have had previous surgery, and may be less effective in very obese patients.

ENDOSCOPIC THERAPY

Evidence Level III. Endoscopic therapy is relatively new, and systematic reviews have found no definite indications for its use. However, select well-informed patients with well-documented GERD that is responsive to therapy with PPIs may benefit from the procedure. Three categories of endoscopic technique have been studied: (1) radiofrequency application to increase the lower esophageal sphincter reflux barrier; (2) endoscopic sewing devices; and (3) injection of a nonresorbable polymer into the lower esophageal sphincter area. All techniques seemed to improve reflux symp-toms, but normalization of intraesophageal acid exposure was limited and there were no significant changes in lower esophageal sphincter pressure. Possible complications of radiofrequency application include perforation, hemorrhage, and death. Data are needed on the long-term durability and safety of endoscopic techniques, their usefulness in patients with atypical GERD, and their efficacy outside the study setting.

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