The history and clinical manifestations of Acid Reflux Disease are the most important diagnostic aids; objective testing can quantify the extent and severity of the process. In the vast majority of sufferers, typical symptoms of Acid Reflux Disease and the response to initial gastric acid suppressive therapy make the diagnosis relatively easy. Diagnostic evaluation becomes important when symptoms are atypical and/or do not respond to therapy.
DOCUMENTING REFLUX.
Reflux during a barium swallow in adults is uncommon unless vigorous provocative maneuvers are employed. When spontaneous reflux of barium is seen, it usually denotes free reflux. The absence of reflux seen radiographically does not, however, imply that the sufferer does not have Acid Reflux Disease.
The 24-hour monitoring of esophageal pH can be performed with a portable unit, which allows the sufferer to follow an almost normal lifestyle. During the prolonged monitoring period, the relationship between symptoms (heartburn, chest pain, wheezing) and episodes of acid reflux can be ascertained, and calculations can be made of the number of episodes of reflux and the amount of time the esophagus is acidified (pH - 4). A small amount of reflux, especially in the postprandial period, can be seen normally. Repeated and prolonged bursts of acid exposure suggest that abnormal gastroesophageal reflux is present.
In children and infants, reflux can be measured noninvasively by scanning the esophageal area with a gamma-camera after placing a solution of 99m Tc sulfur colloid in the stomach. An abdominal binder is used to increase intra-abdominal pressure and to stress the gastroesophageal junction if free reflux is not seen.
LINKING REFLUX TO SYMPTOMS.
If pain is the predominant symptom, rather than heartburn, a Bernstein test may be performed using the same catheter as is used for esophageal manometry. After a 5-minute period of dripping normal saline in the mid-esophagus, the infusion is changed to 0.1 N hydrochloric acid. Reproduction of the symptoms during acid infusion (usually 4 to 5 minutes into the infusion), followed by rapid symptom disappearance after returning to a saline infusion, suggests an esophageal cause of the discomfort.
As another approach, the sufferer is asked to signal the time of discomfort during prolonged pH monitoring of the esophagus. If the sufferer signals discomfort at the same time that acid reflux is demonstrated by the pH probe, then a causal relationship is more likely.
ASSESSING THE EFFECT OF REFLUX ON THE ESOPHAGEAL MUCOSA.
A barium swallow detects gross changes, such as stricture formation or a deep esophageal ulcer, but misses the much more common shallow ulcerations and erosions, which are detected by endoscopy. Only discrete lesions such as erosions and ulcerations should be taken as proof of esophageal damage, because endoscopic findings, such as erythema, edema, or friability, are subject to wide interobserver variation. In approximately one-half of sufferers with moderate to severe symptoms of Acid Reflux Disease, the mucosa appears absolutely normal, but a biopsy may demonstrate the histologic changes of reflux.
APPROACH
Endoscopy is generally indicated if symptoms are prolonged and do not respond to empiric treatment, or if systemic manifestations, such as weight loss, anemia, and occult blood-positive stool are present. If the appearance of the esophageal mucosa is normal during endoscopy, biopsies can also be obtained to search for objective evidence of microscopic esophagitis. If dysphagia is present, a barium swallow is appropriate. Uncommonly, reflux is demonstrated, a stricture found, or a deep ulcer seen, which leads to immediate endoscopy for more complete evaluation. After first evaluation, it may be appropriate to begin empiric therapy (see Treatment, below). If the response to therapy is poor, esophageal pH monitoring can confirm the diagnosis. At the same time, esophageal manometry may be performed to estimate LES pressure and to determine the presence or absence of peristaltic waves.
Prevention of retrograde flow of gastrointestinal contents is a major function of the lower esophageal sphincter (LES) . Retrograde flow is prevented by the lower esophageal sphincters, which remain closed between swallows.
The lower esophageal sphincter is composed of smooth muscle and is innervated by parallel sets of parasympathetic excitatory and inhibitory pathways. It remains closed because of its intrinsic myogenic tone, which is modulated by the excitatory and inhibitory nerves. It opens in response to the activity of the inhibitory nerves. The neurotransmitters of the excitatory nerves are acetylcholine and substance P, and those of the inhibitory nerves are vasoactive intestinal peptide (VIP) and nitric oxide. The function of the LES is supplemented by the striated muscle of the diaphragmatic crura, which surrounds the LES and acts as an external LES. Relaxation of the LES without esophageal contraction occurs during belching and gastric distention. Gastric distention-evoked transient lower esophageal sphincter relaxation (tLESR) is a vasovagal reflex. Fatty meals, smoking, and beverages with a high xanthine content (tea, coffee, cola) also cause a reduction in sphincter pressure. Many hormones and neurotransmitters can modify LES pressure. Muscarinic M2 and M3receptor agonists, a-adrenergic agonists, gastrin, substance P, and prostaglandin F2acause contraction. Nicotine, b-adrenergic agonists, dopamine, cholecystokinin, secretin, VIP, calcitonin gene-related peptide (CGRP), adenosine, prostaglandin E, and nitric oxide donors such as nitrates reduce sphincter pressure.
Antegrade esophageal flow is achieved by the act of swallowing with the initiation of primary peristalsis. Gastroesophageal reflux is prevented by the physiologic lower esophageal sphincter (LES).
When the LES fails to function as an effective barrier to reflux, gastroesophageal reflux develops, with the associated complications of mucosal inflammation (reflux esophagitis).
Gastroesophageal reflux disease (GERD) refers to the varied clinical manifestations of reflux of stomach and duodenal contents into the esophagus and is preferable to the term "reflux esophagitis." Although GERD may be associated with a sliding hiatal hernia, the term "symptomatic hiatal hernia" tends to emphasize an anatomic entity and not the underlying pathophysiology. GERD can be characterized by any combination of symptoms and radiologic, endoscopic, or pathologic changes. In its milder manifestations, it is a common disease; its most florid state is uncommon but may be life-threatening.
HEARTBURN
Heartburn is the most common manifestation of esophageal disease and may occur in up to 20% of the population. The term "burning" rather than "pain" is usually used, although heartburn can increase in intensity until it is perceived as chest pain. Patients often illustrate heartburn with a movement of the open hand up and down the sternum, as compared with the stationary, tightly clenched fist of angina pectoris. Heartburn is usually relieved, even if only temporarily, by taking antacids. A constant burning unrelieved by antacids may well be of esophageal origin, but it does not represent heartburn. Heartburn is often worse after recumbency or lifting and may follow overeating or alcoholic indiscretion.
REGURGITATION
Regurgitation of fluid contents into the mouth often accompanies heartburn. Sometimes regurgitation is associated with eructation; often it accompanies bending over, lifting, or lying down at night. The bitter regurgitated fluid is often described as yellow-brown or green. Regurgitation at night may lead to stridor or to wheezing, a hoarse voice, and other respiratory symptoms from unrecognized reflux.
SPONTANEOUS ESOPHAGEAL CHEST PAIN
In addition to the discomfort from severe reflux, which can advance from heartburn into pain, abnormal contractile activity of the esophageal muscle can cause severe chest pain that is clinically indistinguishable from angina pectoris in terms of intensity, radiation, relationship to exercise, and even response to nitroglycerin. pain of esophageal origin can radiate directly through to the back and is often found in patients who also have dysphagia. Esophageal chest pain can last from several seconds to many hours.
REFLUX ESOPHAGITIS
Reflux of stomach contents into the lower esophagus is the first and foremost cause of esophagitis. Many causative factors are involved, less well characterized than the name implies:
Decreased efficacy of esophageal antireflux mechanisms, particularly LES tone. Central nervous system depressants, hypothyroidism, pregnancy, systemic sclerosing disorders, alcohol or tobacco exposure, or the presence of a nasogastric tube may be contributing causes. In most instances, no antecedent cause is identified.
Presence of a sliding hiatal hernia.
Inadequate or slowed esophageal clearance of refluxed material.
Delayed stomach emptying and increased stomach volume, contributing to the volume of refluxed material.
Reduction in the reparative capacity of the esophageal mucosa by protracted exposure to stomach juices.
Any one of the aforementioned influences may assume primacy in an individual case, but more than one is likely to be involved in most instances. The acid-peptic action of stomach juices is critical to the development of esophageal mucosal injury; in severe cases, refluxed bile from the duodenum also may contribute to the mucosal disruption.
MORPHOLOGY.
The anatomic changes depend on the causative agent and on the duration and severity of the exposure. Simple hyperemia ( redness) may be the only alteration. In uncomplicated reflux esophagitis, three histologic features are characteristic
1. The presence of inflammatory cells, including eosinophils, neutrophils, and excessive numbers of lymphocytes, in the epithelial layer
2. Basal zone hyperplasia exceeding 20% of the epithelial thickness
3. Elongation of lamina propria papillae with congestion, extending into the top third of the epithelial layer
Infiltrates of intraepithelial eosinophils are believed to be an early histologic abnormality, since they occur even in the absence of basal zone hyperplasia. Intraepithelial neutrophils are markers of more severe injury, such as ulceration, rather than reflux esophagitis per se.
Clinical Features.
Although largely limited to adults over age 40, reflux esophagitis is occasionally seen in infants and children. The clinical manifestations consist principally of dysphagia; heartburn; and sometimes regurgitation of a sour brash, hematemesis, or melena. The severity of symptoms is not related closely to the presence or degree of histologic esophagitis; most people experience reflux symptoms without damage to the distal esophageal mucosa, owing to the short duration of the reflux. Anatomic damage appears best correlated with prolonged exposure of the lower esophagus to refluxed material. Rarely, chronic symptoms are punctuated by attacks of severe chest pain that may be mistaken for a heart attack. The potential consequences of severe reflux esophagitis are bleeding, development of stricture, and a tendency to develop Barrett esophagus, with its attendant risks.
Several factors must work in concert to produce clinical effects of esophageal reflux. Normal subjects may have a few short-duration reflux episodes postprandially and in the upright position. Those in whom reflux has produced symptoms or pathologic changes will demonstrate more frequent and prolonged episodes of reflux, which also tend to occur at night. The factor or factors that cause this difference are not entirely known. However, important differences between persons with and without reflux might help explain these findings.
The LES is a specialized bundle of circular muscle at the lower end of the esophagus with different physical and pharmacologic characteristics when compared with the circular muscle above and below it. Although mean LES pressure is significantly lower in subjects with GERD than in normal persons, much overlap occurs between the groups; LES pressure is not very useful in predicting whether reflux is present in an individual patient unless the pressure is very low. The most common event associated with reflux appears to be a transient relaxation of the LES unassociated with either swallowing or the distention of the esophageal body by refluxed fluid. Thus, two abnormalities of LES may be associated with reflux: a sphincter with very low tone, as measured by LES pressure, or inappropriate relaxation of a normally competent sphincter.
Several factors are important in removing refluxed material from the esophagus. The upright position facilitates esophageal emptying by gravity. Peristaltic waves initiated by swallowing or by esophageal distention help remove the refluxed material. Acid placed within the esophagus is cleared less well by patients with GERD than by normal subjects, although the manometric tracings seen in both groups seem identical. Clearing of acid regurgitation occurs in two phases: the bulk of the fluid is returned to the stomach by a peristaltic contraction, and the remaining acid film clinging to the esophageal wall is neutralized by swallowed saliva.
The composition and perhaps the quantity of the refluxed material also play a role in the production of GERD. Gastric acid and pepsin seem clearly important in the pathogenesis of GERD. Bile salts, and possibly pancreatic enzymes, may be responsible in patients in whom acid is absent. The combination of bile salts plus acid is more injurious to the esophagus than either agent alone. Other less well-studied factors, such as altered or abnormal esophageal mucus, swallowed saliva of high bicarbonate content, and diminished resistance of the esophageal mucosa to digestion, may be important in determining the amount of mucosal damage in GERD.
Esophageal squamous epithelium reacts to reflux by an increase in the basal cell or germinative layer. The dermal pegs are increased in height and may become more vascular. If the process becomes more severe, the epithelial layer is destroyed, with the appearance of micro-ulcers and classic signs of inflammation in the lamina propria, such as infiltration with polymorphonuclear leukocytes and edema. Even deeper lesions cause first submucosal and then muscular inflammation and fibrosis, resulting in an esophageal stricture. Why reflux is so common, yet inflammation and stricture formation are relatively uncommon, is not known.
Reflux during pregnancy, once thought to be due to the increased abdominal pressure from the fetus, may be due mainly to diminished LES strength caused by increased estrogen and progesterone. Weight gain also tends to aggravate reflux through an unknown mechanism. Resection of the lower esophageal area for cancer or myotomy for achalasia can lead to severe postoperative reflux. Gastroesophageal reflux with stricture formation is especially severe in patients with progressive systemic sclerosis.
The crural diaphragm usually wraps around the gastroesophageal junction to augment the intrinsic LES. In a hiatal hernia, an anatomic displacement of the LES and crural diaphragm is seen. Although hiatal hernias may be associated with reflux, the presence of a hiatal hernia is now considered to be much less of a factor in GERD than previously thought, because it is present in a large percentage of normal subjects. It is not appropriate to spend time trying to define whether a hiatal hernia is present or absent in dealing with most patients with GERD; rather, the focus should be on the symptoms of reflux.
GASTROESOPHAGEAL REFLUX DISEASE
Pathophysiology: The normal antireflux mechanisms consist of the LES, the crural diaphragm, and the anatomic location of the gastroesophageal junction below the diaphragmatic hiatus. Reflux occurs only when the gradient of pressure between the LES and the stomach is lost. It can be caused by a sustained or transient decrease in LES tone. A sustained hypotension of the LES may be due to muscle weakness that is often without apparent cause. Secondary causes of LES incompetence include scleroderma-like diseases, myopathy associated with chronic intestinal pseudo-obstruction, pregnancy, smoking, anticholinergic drugs, smooth-muscle relaxants [b-adrenergic agents, aminophylline, nitrates, calcium channel blockers, phosphodiesterase inhibitors that increase cyclic AMP or cyclic GMP (including sildenofil)], surgical destruction of the LES, and esophagitis.tLESRwithout associated esophageal contraction is due to a vagal reflex in which LES relaxation is elicited by gastric distention. Increased tLESR is associated with GERD. A similar reflex operates during belching. Apart from incompetent barriers, gastric contents are most likely to reflux (1) when gastric volume is increased (after meals, in pyloric obstruction, in gastric stasis, during acid hypersecretion states), (2) when gastric contents are near the gastroesophageal junction (in recumbency, bending down, hiatus hernia), and (3) when gastric pressure is increased (obesity, pregnancy, ascites, tight clothes). Incompetence of the diaphragmatic crural muscle, which surrounds the esophageal hiatus in the diaphragm and functions as an external LES, also predisposes to GERD.
Reflux esophagitis is a complication of reflux and develops when mucosal defenses are unable to counteract the damage done by acid, pepsin, and bile. Mild esophagitis involves microscopic changes of mucosal infiltration with granulocytes or eosinophils, hyperplasia of basal cells, and elongation of dermal pegs. Endoscopic appearance may be normal. Erosive esophagitis involves endoscopically apparent mucosal damage, redness, friability, bleeding, superficial, linear ulcers, and exudates. Peptic stricture results from fibrosis that causes lumenal constriction. These strictures occur in ~10% of patients with untreated GERD. Short strictures caused by spontaneous reflux are usually 1 to 3 cm long and are present in the distal esophagus near the squamocolumnar junction. Long, tubular peptic strictures can result from persistent vomiting or prolonged nasogastric intubation. Erosive esophagitis may cause bleeding and heal by intestinal metaplasia (Barrett's esophagus) that is a risk factor for adenocarcinoma.
Clinical Features: Regurgitation of sour material in the mouth and heartburn are the characteristic symptoms of GERD. Heartburn is produced by the contact of refluxed material with the inflamed or sensitized esophageal mucosa. Angina-like or atypical chest pain occurs in some patients, while others experience no heartburn or chest pain. Persistent dysphagia suggests development of a peptic stricture. Most patients with peptic stricture have a history of several years of heartburn preceding dysphagia. However, in one-third of patients, dysphagia is the presenting symptom. Rapidly progressive dysphagia and weight loss may indicate the development of adenocarcinoma in Barrett's esophagus. Bleeding occurs due to mucosal erosions or Barrett's ulcer. Severe reflux may reach the pharynx and mouth and result in laryngitis, morning hoarseness, and pulmonary aspiration. Recurrent pulmonary aspiration can cause aspiration pneumonia, pulmonary fibrosis, or chronic asthma. By contrast, many patients with GERD remain asymptomatic or self-treated and do not seek attention until severe complications occur.
TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE (GERD)
Most mildly symptomatic patients with reflux and some moderately afflicted individuals can be helped by simple measures designed to alter the frequency or type of esophageal reflux. Elevating the head of the bed by 6 to 8 inches is a simple and effective form of therapy. Esophageal pH monitoring has shown that this simple measure decreases the frequency and length of reflux episodes. Pillows to elevate the thorax do not work well, as patients tend to roll off the pillows during the night. A foam rubber wedge can be used if the bed frame cannot be moved. Avoiding food and fluid for at least 3 hours before retiring decreases the amount of material available for reflux at night. Avoiding food that the patient finds distressing and that may decrease LES pressure, such as fatty foods, chocolate, and onions, makes sense but has never been subjected to clinical trial. Acid can be neutralized by taking 30 mL of aluminum hydroxide-magnesium hydroxide antacid 1 and 3 hours after meals and at bedtime, but most patients do not tolerate frequent antacid administration. An attempt should be made to have the patient stop smoking, drinking alcohol, and overeating.
If these simple measures are not effective, systemic medical treatment is indicated. The H2 -receptor antagonists in the usual dosage range for duodenal ulcer and titrated to the individual patient improve heartburn better than placebo. An increased frequency of administration and/or higher dosage regimens--cimetidine, 800 mg; ranitidine, 300 mg; or famotidine, 40 mg (each twice per day)--are more effective for controlling symptoms and healing peptic esophagitis, which usually requires 12 weeks.
The proton-pump inhibitors omeprazole (20 mg/day) or lansoprazole (30 mg/day) can give dramatic symptom relief and heal esophagitis in 4 to 8 weeks. Proton-pump inhibitors are usually the treatment of choice for mucosal disease, especially moderate to severe esophagitis seen endoscopically.
Prokinetic agents may also be useful in the treatment of GERD symptoms with no to mild esophagitis, occasionally in addition to gastric acid suppressants. Metoclopramide, 10 mg given three times a day, can be helpful, but CNS side effects can occur in 25% of cases and may limit its usefulness.
Summary:
Step 1. Simple measures (lifestyle changes , dietary modifications and OTC antacids)
A. Elevate head of bed
B. Avoid food and fluid intake before bedtime
C. Avoid cigarettes, coffee, alcohol
D. Avoid chocolate, peppermint
E. Avoid tight clothing around the waist
F. Take antacids 1 hour after meals, at bedtime, and as needed
G. Reduce fat in diet
H. Lose weight
Step 2a.H2 -receptor antagonists
A. Cimetidine, 300 mg q.i.d.
B. Ranitidine, 150 mg b.i.d.
C. Famotidine, 20 mg b.i.d.
D. Nizatidine, 150 mg b.i.d.
Step 2b. Prokinetic agents
Metoclopramide, 10 mg q.i.d.
Step 3. Measures for patients with GERD resistant to H2 -receptor antagonists
Proton pump inhibitor: omeprazole, 20 mg/day, or lansoprazole, 30 mg/day
Step 4. Measures for patients with GERD resistant to steps 1, 2, and 3 or patients who need long-term maintenance treatment
Surgical fundoplication
Once healing of esophagitis has been achieved with either an H2 -antagonist or a proton-pump inhibitor, recurrence rates exceed 80% if no maintenance therapy is used. Maintenance therapy for esophagitis generally requires full dosage of an H2 -receptor antagonist or a proton-pump inhibitor.
The most thoroughly evaluated classification scheme for esophagitis is the Los Angeles system, which categorizes mucosal injury as grade A, B, C, or D. However, it is important to note that the Los Angeles system does not consider strictures, hiatal hernia, or Barretts metaplasia; the endoscopist is required to describe these separately.
Los Angeles Endoscopic Grading Scheme for Esophagitis Severity
Grade A
One (or more) mucosal breaks no longer than 5 mm that do not extend between the tops of two mucosal folds.
Grade B
One (or more) mucosal breaks more than 5 mm long that do not extend between the tops of two mucosal folds.
Grade C
One (or more) mucosal breaks that are continuous between the tops of two or more mucosal folds but involve lesser than 75% of the circumference.
Grade D
One (or more) mucosal breaks that involve at least 75% of the esophageal circumference.
What is acid reflux disease? An acid reflux flash animation that simply answers frequently asked questions about GERD and Acid Reflux Surgery.
Acid Reflux Disease Complications
Hemorrhage and Perforation
Hemorrhage and esophageal perforation are rare complications of reflux esophagitis and are usually associated with deep esophageal ulcers or severe diffuse esophagitis. Clinically important hemorrhage has been reported in 7% to 18% of patients with GERD. Esophageal perforations are very rare in the PPI era, but they can result in mediastinitis and can be fatal if they are not rapidly recognized and treated.
Peptic Esophageal Strictures
Strictures occur in 7% to 23% of patients with untreated reflux esophagitis, especially in older men. They usually evolve over many years and may be linked to the long-term use of nonsteroidal antiinflammatory drugs. The mechanism of stricture formation is complex, starting as a reversible inflammatory process with edema, cellular infiltration, and vascular congestion, progressing to deposition of connective tissue and collagen, and ending in irreversible fibrosis. With the onset of dysphagia, there is often less heartburn, reflecting the stricture’s acting as a barrier to reflux. Dysphagia is usually limit to solids, but it may progress to liquids. Unlike malignant strictures, patients with peptic strictures have a good appetite, alter their diet, and lose little weight.
Radiographically, peptic strictures are smooth-walled, tapered, circumferential narrowings in the lower esophagus, which are usually less than 1 cm long, but occasionally they extend to 8 cm in length. In these unusual cases, the clinician should suspect a predisposing condition, such as the Zollinger-Ellison syndrome, superimposed pill esophagitis, or prolonged nasogastric intubation. A stricture in the middle to upper esophagus should raise the suspicion of Barrett esophagus or malignant disease. Although once controversial, most data today suggest that a Schatzki ring is a forme fruste of an early peptic stricture. In all cases, the nature of a peptic stricture needs to be confirmed by endoscopy with biopsies because some patients may have Barrett esophagus or unsuspected cancer.
The clinical course of reflux esophagitis depends to a great extent on whether the patient has erosive or nonerosive GERD on initial presentation. Furthermore, patients tend not to cross over from one group to another unless they are treated medically or surgically: in follow-up ranging from 6 months to more than 5 years, only 15% of patients with nonerosive disease evolved over time to having esophagitis or complications of GERD.
Nonerosive Acid Reflux Disease
Although early studies from tertiary referral centers suggested that nearly half of patients with GERD had esophagitis, studies carried out in community practices reveal that up to 70% of the patients with GERD had a normal endoscopic examination. Furthermore, another community-based study of antacid users found that 53% of patients with GERD had nonerosive disease, and two thirds of the remaining had only minimal erosive changes at endoscopy. Endoscopy-negative patients with GERD are more likely to be female, younger, thin, and without hiatal hernia. Despite their mild mucosal damage, these patients demonstrate a chronic pattern of symptoms with periods of exacerbation and remission.
Nonerosive GERD is suspected by the presence of typical reflux symptoms with a normal endoscopic examination and is confirmed by the patient’s response to antisecretory therapy. When performed, 24-hour esophageal pH monitoring identifies three distinct subset of patients with nonerosive disease. First, there are the patients with abnormal acid exposure time who are usually responsive to antisecretory therapy. Second are the patients with normal reflux parameters but a good relationship between acid reflux episodes and symptoms. This group represents 30% to 50% of patients with nonerosive GERD and has “functional heartburn.” These patients probably have heightened esophageal sensitivity to acid and are less likely to respond to antireflux therapy. The third group is characterized by normal acid exposure times and poor symptom correlation. Despite sometimes having classical reflux symptoms, other diseases such as achalasia, gastroparesis, bile reflux, or functional dyspepsia are the cause of their symptoms. Overall, patients with nonerosive GERD do not respond to antireflux treatments as well as do patients with erosive GERD, probably because these three subsets are not carefully defined before treatment.
Erosive Acid Reflux Disease
The clinical course of patients with erosive esophagitis is more predictable and is associated with complications of GERD. Controlled studies have shown that in the absence of ongoing maintenance therapy, up to 85% of patients with erosive GERD will have a relapse within 6 months, and the relapse rate is highest in those with the more severe grades of esophagitis. This observation, however, should not prevent at least one attempt to withdraw medication, because 20% of patients remain in remission for up to 1 year, especially those with milder esophagitis grades. Although the natural history of untreated erosive GERD is well studied, two European studies suggest that these patients are more prone to reflux complications. In a Finnish study, 20 patients with erosive GERD treated with lifestyle changes, antacids, and prokinetic drugs were followed up for a median of 19 years. Fourteen patients continued to have erosions, and 6 new cases of Barrett esophagus were detected. Likewise, a large retrospective European study with 6.5 years of follow-up found a high rate of complications (21%) including 13 esophageal ulcers, 15 with strictures, and 45 patients with Barrett epithelium. However, these data must be contrasted with other studies in which no patients with erosive esophagitis developed Barrett esophagus in a 2-year trial in the