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The term reflux esophagitis was first proposed by Allison in 1946 and referred to esophageal injury caused by caustic gastric juices which would reflux back into the distal esophagus. GE reflux is now recognized as an extremely common disorder, however, accurate estimates of the incidence of this disease have proved difficult secondary to the absence of a good definition.
Diagnostic Studies in GE Reflux Disease
A number of studies are used to evaluate people who have suspected GE reflux disease. Barium esophagram is the study that was traditionally used to evaluate GE reflux disease. It is easy and inexpensive to perform and when gross reflux is demonstrated is 85% specific. The shortcoming of this study lies in its sensitivity rate of 40%. Upper endoscopy is now the most frequently used study to evaluate suspected GE reflux disease. Indeed, when erosive esophagitis is identified by the endoscopist, specificity is in the 95% range. Many patients, however, who have GE reflux disease have no evident mucosal injury so the sensitivity of the study is in the 50-60% range.
The study that is now becoming accepted as the gold standard is the 24 hour ambulatory esophageal pH monitor. This study is performed by placing a pH probe with its tip 5 cm above the lower esophageal sphincter. The device is connected to a small monitor which is carried by the patient and records the pH during the course of the study. Additionally, the patient keeps a diary as to the timing of meals, recumbency and symptoms (heartburn, chest pain, wheezing or cough). The monitor is removed after 24 hours and then analyzed by a computer.
In evaluating the results of the 24 hour pH probe a number of factors are important to consider. The two most important factors are the fraction of time the pH is less than 4 (normally less than 4.5% of the time) and the symptom index which is calculated by dividing the number of symptoms with a pH less than 4 by the total number of symptoms during the course of the study. Generally patients whose symptoms are caused by GE reflux disease will have symptom indices in the 70% plus range.
Most patients with typical symptoms of GE reflux disease without complicating features such as weight loss or dysphagia can have a clinical diagnosis of GE reflux disease made without performing numerous diagnostic studies. If the patient fails to respond to appropriate medical management, or if surgical treatment is considered, then the diagnostic testing workup becomes important.
Complications of GE Reflux Disease
Sequelae of GERD are typically broken down into the esophageal complications and the extra-esophageal manifestations.
As commonly used, Barrett's esophagus now refers to the presence of specialized intestinal metaplasia in the distal esophagus. It is only when intestinal type mucosa associated with goblet cells is seen that we use the term Barrett's esophagus. There has been an enormous surge in interest in Barrett's esophagus due to the marked increase in incidence in adenocarcinoma of the GE junction of which Barrett's esophagus is felt to be the predisposing condition. The risk of developing esophageal carcinoma in a patient with Barrett's esophagus remains a subject of great controversy. Depending on the series, the prevalence of carcinoma has ranged between 4% and 45%. Recent studies demonstrate that carcinoma will develop in patients with established Barrett's esophagus in one patient out of 80 to one patient out of 450 per year. Therefore, although the risk of esophageal adenocarcinoma is about 35 times that of the general population in patients with Barrett's, it is still a relatively low lesion.
The treatment of patients with Barrett's esophagus is as well controversial. Therapy is generally aimed at the symptoms of GE reflux disease rather than the Barrett's mucosa. A number of studies have attempted to show regression of Barrett's mucosa with proton pump inhibitors, however, it has not been shown that the overall malignant potential of the Barrett's mucosa is altered by this approach. Additionally, treatment with YAG laser, and more recently, photodynamic therapy (using argon dye laser with Photofrin pretreatment) to ablate the Barrett's mucosa in patients with dysplasia has been tried. The long-term risk and efficacy of this approach remain to be proved, and it is not yet considered generally accepted treatment.
There is consensus that patients with Barrett's esophagus require regular endoscopic surveillance. Typically, patients with Barrett's esophagus in the absence of dysplasia undergo endoscopy every one to two years with numerous surveillance biopsies. If the biopsies show no dysplasia this program is continued. If low-grade dysplasia is detected and confirmed by a second pathologist, this examination should be performed every six months until either the dysplasia is no longer documented or high-grade dysplasia is identified. Once high-grade dysplasia is identified ancompression fractured confirmed by another pathologist, surgery (total esophagectomy) is recommended. By the time high-grade dysplasia is detected on biopsy approximately one-third of patients will already have foci of invasive carcinoma found in the resected specimen. If surveillance is continued to the point where gross esophageal cancer is detected by endoscopy or biopsy, most patients will no longer have resectable lesions and therefore this approach is not advocated.
2) Extra-esophageal Manifestations:
The extra-esophageal manifestations of GE reflux disease are now being more frequently recognized and treated. These manifestations include ENT manifestations including reflux laryngitis, laryngeal stenosis, laryngeal carcinoma, chronic hoarseness, chronic cough and globus sensation.
Pulmonary manifestations include asthma, chronic cough, aspiration pneumonia and pulmonary fibrosis.
The association between GE reflux disease and chronic pulmonary disease has been speculated upon for many years. The pathophysiology for this connection remains poorly understood and is complicated by the fact that many of the treatments for patients with chronic lung disease and the lung disease itself can exacerbate GE reflux disease.
The two most commonly proposed theories include a neural reflex caused by acid reflux into the distal esophagus versus micro-aspiration of tiny amounts of acid into the tracheobronchial tree with resultant bronchospasm and/or pulmonary parenchymal damage. At present, there is more evidence supporting the micro-aspiration theory. Treatment of pulmonary complications of GERD remains the same as for other forms of GERD.
3) "Cardiac" Complications:
Angina-like non-cardiac chest pain of esophageal origin was proposed by Hippocrates. For many years the concept of "esophageal spasm" has held its place in the medical literature although documenting consistent esophageal motility disorders in these patients has been difficult. Recent work by Richter et al has demonstrated that up to 50% of patients with anginal-like chest pain and negative cardiac catheterizations in fact have GE reflux disease, and certainly a trial of proton pump inhibitor therapy is warranted in patients with anginal-like pain and negative cardiac workups.
Therapy for GERD
1 ) Non-medical Therapy
The so-called lifestyle modifications to treat GERD are generally successful only in patients with minimal reflux disease and include elevation of the head of the bed by 4 to 6 inches, avoiding eating meals within 3 hours of recumbency, avoiding cigarettes and alcohol, avoiding chocolate, fatty foods and carminatives; and avoiding NSAIDS.
2) H2 Antagonists
For patients who fail lifestyle modifications, the classic drugs most commonly used to treat GE reflux disease are the H2 antagonists. In people with symptoms of mild reflux, these agents are often successful. However, in patients with erosive esophagitis healing is only seen in approximately 58%. As a general rule, therefore, patients with severely symptomatic heartburn, particularly associated with reflux disease, more potent agents are generally needed.
3) Prokinetic Agents
It is attractive to treat GE reflux disease by preventing the actual occurrence of reflux rather than neutralizing gastric contents. Prokinetic agents attempt to do this by increasing esophageal peristalsis, increasing LES pressure, and accelerating gastric emptying. The two prokinetic agents commonly used in this country include cisapride and metoclopramide. The development of
4) Proton Pump Inhibitors
The advent of proton pump inhibitors (omeprazole and lansoprazole) has been the major medical development in reflux disease in recent years. In essentially all patients with symptomatic reflux disease or erosive esophagitis, symptomatic relief and endoscopic healing of the esophageal mucosa can be achieved. Additionally, it was shown by Klinkenberg-Knoll (1994) that if the dose of the drug is increased to 40 mg daily, healing can be maintained in essentially all patients. The acceptance of this drug was delayed due to concerns about potential carcinogenic effects.
5) Anti-Reflux Surgery
With the development of new proton pump inhibitors which provide safe and effective therapy to almost all patients, the role of surgery which had previously been limited to refractory patients came into question. Enthusiasm for surgery peaked with the development of laparoscopic techniques for performing Nissen fundoplication as well as a variety of other anti-reflux operations. Most patients with GE reflux disease will decide to remain on medical therapy rather than consider surgical therapy. However, in patients with severe symptoms who are unhappy with the prospect of lifelong medical therapy, surgery should certainly be explored as an option. Before surgery is performed, the presence of adequate peristalsis in the esophageal body must be