Mack C. Mitchell Jr.
Physiology of Swallowing
Normal swallowing requires the coordination of the skeletal muscles of the pharynx, the cricopharyngeus muscle (the upper esophageal sphincter), and the proximal third of the esophagus, with the smooth muscle of the distal body of the esophagus and the lower esophageal sphincter (LES). Whereas the initiation of swallowing is voluntary, involuntary processes subsequently propel the swallowed bolus through the esophagus into the stomach. The following sequence of events occurs during normal swallowing: relaxation of the upper esophageal sphincter to permit entry of the bolus into the esophagus, closure of the sphincter to prevent esophageal or pharyngeal regurgitation and aspiration, propulsion of the bolus distally by esophageal peristalsis, relaxation of the LES to allow easy entrance of the bolus into the stomach, and prompt closure of the LES to prevent reflux of gastric contents.
Dysphagia
Dysphagia, difficulty in swallowing, may result from abnormalities in any of the anatomic structures or disturbances in the physiologic events involved in normal swallowing. It is an extremely specific symptom and should never be dismissed as an emotional problem or symptom of globus hystericus (discussed later in this chapter). Occasionally, dysphagia may be accompanied by pain on swallowing,odynophagia, but the two symptoms are distinct and may occur independently. Two types of dysphagia exist: oropharyngeal dysphagia (the inability to initiate the act of swallowing) and esophageal dysphagia (difficulty in transporting material down the esophagus).
Clinical Evaluation
History
Because of the complexity of the swallowing mechanism, many disorders can cause dysphagia. Information from the history can be helpful in elucidating the underlying disorder. Difficulty in swallowing solids strongly suggests an anatomic obstruction such as carcinoma, stricture, or esophageal ring, whereas difficulty in swallowing solids and liquids suggests a motility disturbance such as achalasia, scleroderma, or diffuse esophageal spasm (DES).
The history may also be useful in identifying the region of abnormal function as either oropharyngeal or esophageal. Symptoms suggestive of oropharyngeal dysphagia include difficulty in initiating a swallow, regurgitation of liquid through the nose, aspiration with swallowing, and an inability to propel a bolus of food into the esophagus. Patients with esophageal dysphagia complain of retrosternal fullness after swallowing and of the feeling
P.646
that food is stuck at a certain point in the esophagus, often relieved by regurgitation. Esophageal dysphagia is most commonly caused by structural abnormalities (ring, stricture, or tumor) but may be caused by reflux esophagitis or by a primary motility disorder. Table 42.1lists several common causes of dysphagia.
|
TABLE 42.1 Types of Dysphagia |
||||||||||||||||||
|
||||||||||||||||||
Mild weight loss may be described by patients with any type of chronic dysphagia, the result of a voluntary decrease in intake of food that often accompanies their symptoms. More severe weight loss with anorexia suggests carcinoma or achalasia.
Special Studies
To determine the cause of dysphagia, one or more of the following procedures should be used: radiologic studies, esophagoscopy, or esophageal motility studies. The evaluation can establish a diagnosis in 95% of cases. Consultation with a gastroenterologist is helpful for most patients with dysphagia, both for evaluation of the clinical problem and for esophagoscopy and motility studies.
Radiology
The initial study in most patients with dysphagia is usually a barium swallow, a procedure that can identify motility disturbances and anatomic abnormalities. A barium swallow is the easiest procedure for the patient to tolerate (it takes only 15 to 20 minutes and is associated with little discomfort). As with all radiologic studies, the radiologist should be told which disorders are most likely, based on the initial assessment. Without this communication, the radiologist may perform a routine barium swallow looking only for carcinoma, stricture, or reflux and potentially miss esophageal rings or diverticula that may require special techniques to visualize. Careful fluoroscopic control is required to evaluate motility. If oropharyngeal dysphagia is suspected, the barium swallow should be recorded on videotape or cine film to observe the rapid activity of pharyngeal contractions and to detect abnormal esophageal contractions. A marshmallow should be added to localize the site of the obstruction if esophageal dysphagia is suspected. A double-contrast study (carbon dioxide pellets are added to the barium meal to distend the esophagus) should be performed to identify mucosal abnormalities associated with gastroesophageal reflux. Barium studies often can detect both structural and functional abnormalities that cause dysphagia. However barium studies may miss certain anatomic lesions such as reflux esophagitis, small ulcers, or early cancers well as motor disorders of the esophagus. Since a positive study seldom yields a specific diagnosis, endoscopy or esophageal manometry is usually necessary. For this reason, there is no consensus regarding the need for a barium swallow in all patients with dysphagia; many clinicians are comfortable in doing endoscopy initially, unless a pharyngeal obstruction is suspected.
Endoscopy
Esophagoscopy is an essential part of the evaluation of dysphagia. Because the barium swallow may miss some lesions, endoscopy should be performed in all patients with persistent dysphagia, particularly for solid foods. The procedure is well tolerated and can be performed on an ambulatory basis even in the elderly. When a lesion is detected by radiography, endoscopy provides the most direct approach to determine if it is inflammatory or neoplastic. Biopsies and brushings for cytologic examination can be obtained under visual guidance. Furthermore, the endoscope may disrupt esophageal webs or rings that are causing the dysphagia. Inability to pass the endoscope through the esophagus into the stomach confirms an anatomic cause of the dysphagia and rules out a primary motor disturbance (e.g., achalasia).
Recording of Esophageal Motility
Esophageal manometry is the most effective procedure for the evaluation of esophageal motor function (Table 42.2). This study measures the strength, function, and coordination of the upper esophageal sphincter and LES and the body of the esophagus in response to a swallow. The procedure is well tolerated, takes only about 30 minutes, and involves the passage of a narrow catheter through the nose or the mouth into the stomach. Recordings of the amplitude and coordination of contractions within the pharynx and esophagus can identify motility abnormalities like achalasia or DES. Esophageal manometry should
P.647
be considered when no structural cause of dyphagia is identified.
|
TABLE 42.2 Esophageal Motility Disorders |
||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||
Specific Causes of Dysphagia
Carcinoma of the Esophagus
Cancer of the esophagus should always be suspected as the cause of dysphagia in patients older than the age of 40. Overall, esophageal cancer is still relatively rare—approximately 14,000 new cases per year are diagnosed in the United States. Whereas the incidence of squamous cell carcinoma (SCC) is falling in the United States, the incidence of esophageal adenocarcinoma (AC) is rising dramatically (1). The incidence of SCC is higher in urban areas compared to rural areas of the United States, particularly among African American men (1). In this country cigarette smoking, caustic strictures, achalasia, and alcohol consumption are the major risk factors for SCC. AC is predominantly a disorder of Caucasians and men are six times more likely than women to be affected. Most AC of the esophagus develops in areas of Barrett metaplasia, a replacement of the normal squamous cells of the gastroesophageal junction by columnar cells. Cigarette smoking and obesity, but not alcohol, are also linked to esophageal AC.
Squamous cell cancer is most common in the middle to distal third of the esophagus, while adenocarcinoma occurs primarily in the distal third of the esophagus. Carcinoma of the cardia of the stomach may extend into the lower esophagus and obstruct the esophageal lumen.
Diagnosis
The diagnosis of esophageal cancer is generally made only after symptoms have developed, and the tumor has spread to regional lymph nodes. In patients with predisposing conditions, such as Barrett mucosa, earlier detection of the cancer may be achieved by regular endoscopic surveillance every 2 to 3 years with biopsy and cytologic brushings of the entire esophagus. Most patients with esophageal cancer have dysphagia for solid food for several months that progresses to dysphagia for solids and liquids, usually with progressive weight loss. Odynophagia (pain on swallowing) may accompany the dysphagia. Occult blood loss is common but hematemesis is unusual.
The diagnostic evaluation of patients suspected of having esophageal carcinoma should include a barium swallow followed by upper endoscopy. If the radiograph is negative, the endoscopic examination may still reveal mucosal lesions. Even when the tumor is already defined by radiograph, endoscopy is necessary to establish a histologic diagnosis that can guide subsequent therapy. Endoscopies and/or cytology provide a specific diagnosis in more than 95% of cases of esophageal cancer. The radiographic appearance of the tumor also provides useful information about the degree of esophageal obstruction, the length
P.648
of the tumor, and the appearance of the fundus of the stomach. With these two techniques, cancer of the esophagus can be differentiated from other esophageal lesions, such as peptic stricture of the esophagus, achalasia, severe esophagitis, and esophageal varices.
After the diagnosis is confirmed, computed tomography of the chest and abdomen should be obtained to evaluate the possibility of local extension, and to identify hepatic metastases. Endoscopic ultrasound is the most sensitive and specific method for staging this disease and should be considered in all preoperative evaluations (2). When patients present with dysphagia from esophageal cancer, half will have incurable disease at surgery even when staging procedures show disease confined to the esophagus (3).
Therapy
Esophageal cancer is highly lethal with 5-year survival rates of 40% to 60% for those with localized disease and 18% to 25% in those with regional nodal involvement. Surgery is the preferred treatment for clinically resectable esophageal tumors. Preoperative chemoradiotherapy appears to provide a survival benefit compared to surgery alone in patients with clinically resectable disease. Although the optimal combination, dose, and schedule of medications has not been established, multiagent chemotherapy appears to be better than single agent, cisplatin (3). Patients with adenocarcinoma detected during regular screening of Barrett mucosa have a better prognosis than other patients with esophageal cancer.
Palliation (maintenance of an open esophagus so that the patient can swallow food and saliva) should be the major aim of therapy if the tumor is not resectable. Dilation of the lumen with mercury-weighted rubber dilators, guidewire-assisted polyvinyl dilators, or various balloon dilators may all provide palliation. Treatment with thermal coagulating dilators or laser therapy occasionally may be helpful. Esophageal prostheses have been used in palliation, particularly in patients with tracheoesophageal fistulas. Chemotherapy or surgical palliation should also be considered in selected cases. Unfortunately, no well-designed clinical trials that compare different modalities have been done, so the choice of palliation must be individualized after consultation with a surgeon, an oncologist, and a gastroenterologist.
Achalasia
Achalasia is characterized by the complete absence of esophageal peristalsis and failure of LES relaxation. The condition occurs in all age groups, with a peak incidence in the fourth and fifth decades. The incidence of this disorder is approximately 1 in 100,000 population per year. Men and women are equally affected by the disease. The most common complaint is progressive dysphagia for both solids and liquids, often with regurgitation of ingested material. Nocturnal coughing and even aspiration pneumonia may be the presenting symptoms. Occasionally, substernal chest pain is associated with the dysphagia.
Pathogenesis
The pathogenesis of achalasia is unknown. Several studies have described abnormalities in the myenteric ganglion cells in the distal esophagus (LES zone), in the body of the esophagus, and in the vagal nucleus and its peripheral fibers. Although these findings have not been consistent, pharmacologic studies have further supported the concept of denervation of the esophagus. There is an exaggerated response of the LES and the body of the esophagus to cholinergic stimulation and to gastrin, consistent with the concept of denervation hypersensitivity. The etiology of the neuropathic changes is unknown.
Diagnosis
A chest radiograph often suggests the diagnosis. The normal gastric air bubble is absent, and an air–fluid level in the dilated esophagus is sometimes seen behind the heart. With a very dilated and tortuous esophagus, the mediastinum appears widened. The typical features on barium esophagogram (Fig. 42.1) include smooth tapered narrowing of the distal esophagus that fails to open properly, retention of barium and secretions in the more proximal esophagus, and absence of peristalsis. The distal narrowing is often described as a bird beak or pen quill deformity. The patient must be examined while upright to demonstrate the height of the retained barium-filled column.
Esophageal manometry demonstrates three distinct abnormalities in patients with achalasia: absence of peristalsis of the smooth muscle of the esophagus, failure of the LES to relax after a swallow, and elevated LES pressure. If possible, manometry should be done in every patient suspected of having achalasia. In achalasia, the basal LES pressure is usually elevated, at times to very high levels, and the degree of relaxation is incomplete. Thus, there is a constant high-pressure zone that impedes the passage of the esophageal contents. Peristalsis is also absent, further impairing the propulsion of the bolus distally. Manometry may demonstrate high-amplitude, simultaneous, repetitive contractions that are not peristaltic. Patients with this finding on manometry are classified by some as having vigorous achalasia and often have severe chest pain (6).
Patients who present early in the course of disease with mild symptoms and minimal esophageal dilation may appear to have normal LES relaxation (because of a manometric artifact) and normal sphincter pressure and yet have true achalasia. In such cases, technetium-labeled food studies with the patient in the upright position should be performed to confirm delayed emptying and the abnormal LES (7).
|
FIGURE 42.1. Barium swallow in a patient with achalasia. The esophagus is dilated and the tapered distal segment never opens normally. Under fluoroscopy, no peristalsis is seen, but simultaneous contractions are noted. |
P.649
Differential Diagnosis
Achalasia must be differentiated from other disorders that lead to obstruction of the passage of food into the stomach. Esophageal strictures, both peptic and neoplastic, and carcinomas at the esophagogastric junction may result in symptoms and in a radiographic and manometric picture similar to that of achalasia (8). Thus, all patients with a clinical or radiographic diagnosis of achalasia should be evaluated with endoscopy. Failure to pass the endoscope into the stomach indicates an anatomic obstruction. Scleroderma, with its associated esophageal motility disturbance, may result in dysphagia with diminished peristalsis seen on the radiograph. If stricture has not occurred, the patient will demonstrate a wide-open sphincter through which barium passes easily. By the time patients with esophageal scleroderma develop stricture and dilation of the esophagus that may mimic achalasia, they usually have other obvious stigmata of scleroderma (particularly tight skin of the face and hands or Raynaud phenomenon). Furthermore, on esophageal manometry the LES pressure in scleroderma is low rather than high, as it is in achalasia, but like achalasia, the disorder of motility is confined to the smooth muscle portion (distal two-thirds) of the esophagus, with a normally functioning proximal segment. In patients from South America (or individuals who have spent time there), Chagas disease, caused by infection of the ganglion cells with Trypanosoma cruzii, may cause a megaesophagus with manometric patterns identical to that of achalasia. Some patients with idiopathic intestinal pseudo-obstruction may also have a manometric pattern similar to that of achalasia.
Therapy
Two types of definitive therapy exist for achalasia: pneumatic dilation and surgery. Both forms of therapy are aimed at reducing the pressure gradient between the esophagus and the stomach, thus decreasing the severity of the dysphagia. The aperistalsis and impaired sphincter relaxation persist after therapy. Pneumatic dilation, an outpatient procedure, is performed by a trained gastroenterologist. The esophagus is aspirated completely before the dilation. After premedication with analgesics and sedatives, a balloon dilator is passed into the stomach. Under fluoroscopic guidance, the balloon portion is positioned across the LES. It is then inflated for 10 to 30 seconds, causing a forceful disruption of the LES muscle. The dilator is then removed and can be blood streaked. The patient usually experiences chest pain during the procedure. The major risk of the procedure is esophageal perforation, which occurs in up to 5% of dilations. Satisfactory results (long-term improvement in dysphagia, weight gain, and decrease in retention of barium) can be expected in approximately 85% of cases. In successful cases, there is immediate relief of symptoms. The patient is observed for 4 to 6 hours and discharged. Dilation can be repeated if symptoms of dysphagia recur or worsen, but most patients have only minimal symptoms for many years after therapy. Repeat esophageal manometry is not necessary unless symptoms recur.
Surgical therapy, the Heller myotomy, involves a transection of the circular muscle of the LES zone to the level of the mucosa. This surgical approach provides results similar to those after pneumatic dilation, with a success rate of 80% to 85%. The procedure may cause significant reflux esophagitis in 10% to 25% of patients. As a result of this complication, some advocate combining a fundoplication
P.650
with the myotomy. Until recently, the procedure required a thoracotomy, but it can now be performed by either a laparoscopic or thoracoscopic approach. These minimally invasive techniques have made myotomy a better tolerated procedure with shorter hospitalizations, but because pneumatic dilation can be performed on outpatients without general anesthesia, it is usually the procedure of choice. Surgery is reserved for failure of repeated dilations to provide symptomatic relief, esophageal perforation secondary to pneumatic dilation, inability to perform dilation because of the shape of the esophagus or the presence of a large epiphrenic diverticulum, and inability to exclude carcinoma.
|
TABLE 42.3 Therapy for Esophageal Motility Abnormalities Associated with Chest Pain |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Medical therapy with nitrates, calcium channel blockers (Table 42.3), and even mercury bougienage may offer transient improvement in some patients. Pharmacologic therapy should be reserved for patients in whom pneumatic dilation or myotomy is contraindicated or for patients with very mild disease.
Endoscopic injection of botulinum toxin into the LES has been studied as a treatment of achalasia (9). A decrease in LES pressure and improved esophageal emptying are seen immediately after injection. An initial success rate of 70% to 80% has been reported after the first injection, with most patients relapsing (and requiring repeat treatment) in 6 months to 1 year. This procedure can be performed by a trained endoscopist and has no more risk than esophagoscopy alone. The therapy should be considered for patients in whom surgery has high risk and in whom the risk of perforation with pneumatic dilation is also high, but not as a long-term treatment option.
Complications
Many studies suggest that patients with achalasia are at increased risk of developing esophageal cancer. The incidence of this complication ranges from 6% to 29% in various series (8). Tumors in patients with achalasia should not be confused with cancer of the esophagogastric junction presenting with an achalasia-like picture. Cancers in patients with primary achalasia usually occur many years after the diagnosis of achalasia has been established and are usually squamous cell type, occurring in the mid-portion of the esophagus. There is no evidence that successful therapy of achalasia prevents the development of cancer.
Diffuse Esophageal Spasm
Clinical Presentation
Symptomatic diffuse esophageal spasm (DES) (10) is a disorder characterized by intermittent nonperistaltic (simultaneous) esophageal contractions that result in dysphagia and substernal chest pain. The disorder occurs with equal frequency in both sexes and at all ages (although it appears to be rare in children). The dysphagia is intermittent and is experienced for both solids and liquids. The pain is also intermittent and may be provoked by certain foods, particularly hot and cold beverages. At other times, the pain occurs spontaneously and may even awaken the patient at night. The pain is highly variable in quality and is
P.651
sometimes described as knife-like or as dull and crushing; it may radiate to the neck, back, or arms. It may be brief or last for hours. Because of its location, radiation, and crushing quality, it may be confused with the pain of ischemic heart disease. When no cardiac disease is found, many of these patients are incorrectly believed to have a psychogenic disturbance.
Diagnosis
The procedures for the diagnosis of this condition include radiographic studies and esophageal manometry. A carefully performed barium swallow, or videoesophagogram, may demonstrate nonperistaltic, spontaneous, and simultaneous contractions (tertiary waves) of the body of the esophagus. However, these abnormal contractions are often encountered during routine barium swallow and by themselves do not make a diagnosis of esophageal spasm without the appropriate clinical history. Furthermore, because DES is an intermittent condition, the barium swallow may be normal or too insensitive to detect the motility disturbance. Because the barium study is not specific, it should be done only on patients with dysphagia. Patients with suspected DES should have esophageal motility studies to confirm the diagnosis, even if they have had a barium swallow. Provocative agents (e.g., edrophonium) can be used during the motility studies to identify more clearly patients who experience chest pain of esophageal origin (described later in this chapter) (11).
Therapy
Table 42.3 lists therapy for DES and other motility disorders that cause chest pain, which are discussed in greater detail later in this chapter.
Other Primary Motility Disorders
In addition to achalasia and DES, three distinct primary motility abnormalities of the esophagus have been described that are associated rarely with dysphagia. The nutcracker esophagus and the hypertensive LES (excessively high LES pressures with normal esophageal peristalsis) are two abnormalities associated primarily with chest pain and, rarely, with dysphagia; they are discussed later in this chapter. Some patients with dysphagia referred for esophageal motility testing demonstrate contractions in the distal esophagus with amplitudes of smooth muscle contraction below 30 mm Hg in more than 30% of swallows. This is called ineffective esophageal motility because contractions of this low amplitude are incapable of effective propagation of a bolus. This abnormality is seen commonly with gastroesophageal reflux, and rarely it may be seen with dysphagia alone.
Secondary Motility Disorders
Chronic reflux esophagitis (discussed later) may cause scarring of the distal esophagus, which can result in decreased force of esophageal contractions and/or ineffective esophageal motility, either of which can lead to dysphagia. There is ample evidence that acute acid reflux does not induce esophageal spasm, but chronic reflux may cause symptoms and motility abnormalities that are radiographically similar. Treatment is aggressive antireflux therapy. Improvement in dysphagia and contraction abnormalities is variable, but the pain of chronic reflux usually diminishes with treatment.
Abnormalities of esophageal contractions associated with dysphagia may be seen in patients with hyperthyroidism or hypothyroidism, amyloidosis, and myotonic dystrophy. Diabetes mellitus has been associated with multiple radiographic and manometric abnormalities of the esophagus, but patients are seldom symptomatic. Collagen vascular disease, particularly scleroderma, may affect the esophagus as well. Chronic idiopathic intestinal pseudo-obstruction may produce manometric abnormalities indistinguishable from those of achalasia, as noted earlier in this chapter. Many authorities have used esophageal manometry to help make this diagnosis. Use of the term presbyesophagusshould be abandoned since normal aging does not produce significant alteration of esophageal motility.
Scleroderma of the Esophagus
The esophagus is affected in up to 80% of patients with scleroderma. At times esophageal symptoms may lead to the diagnosis, since the esophagus may demonstrate the characteristic abnormalities even before skin changes occur. The main symptoms of esophageal scleroderma are heartburn and dysphagia. The cause of these symptoms can be readily appreciated by examining the changes in esophageal motility. In esophageal scleroderma, the LES pressure is very low, resulting in free gastroesophageal reflux. Additionally, the peristaltic waves initially are of reduced amplitude, progressing later to complete aperistalsis in the smooth muscle portion of the esophagus, sparing the skeletal muscle portion. Because peristalsis is impaired, the refluxed acid remains in the esophagus for an abnormally long time, perhaps accounting for the development of an esophageal stricture, commonly seen in this disorder. Thus, the dysphagia may be caused by the primary motor abnormality or may signify the development of a peptic stricture.
The pathogenesis of scleroderma is unknown. In the esophagus, the disorder is not simply secondary to replacement of muscle fibers with collagen because the motility dysfunction can be demonstrated in the absence of histopathologic changes. It has been suggested that there is a neural defect in the esophagus rather than a primary myogenic disorder (12).
Scleroderma is a chronically progressive disease for which no specific treatment exists. Therapy of esophageal
P.652
manifestations is directed at symptomatic relief and prevention of strictures.
Patients with scleroderma who have dysphagia or heartburn should be referred to a gastroenterologist for evaluation of esophageal motility and to rule out reflux esophagitis and stricture formation. If reflux is present, the patient should be treated with intensive antireflux therapy (Table 42.4) to try to prevent stricture formation. Strictures should be dilated by bougienage, followed by long-term medical therapy with proton pump inhibitors (PPIs). In general, patients with scleroderma require a high dosage of a proton pump inhibitor (Table 42.4) for treatment of esophagitis. Antireflux surgery should be avoided because the motility disorder may cause significant dysphagia after fundoplication.
|
TABLE 42.4 Treatment of Gastroesophageal Reflux |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Esophageal Webs and Rings
Dysphagia for solid foods may be caused by esophageal webs or rings. An esophageal web is a mucosal structure that protrudes into the lumen, most commonly in the proximal esophagus. The association of iron deficiency anemia with a proximal esophageal web constitutes thePlummer-Vinson syndrome. Esophageal rings are located in the distal
P.653
esophagus and may be either mucosal or muscular; rings can be demonstrated in up to 10% of the population but rarely cause symptoms.
The ring that occurs just above the gastroesophageal junction is called a Schatzki ring. The origin of these lesions is unclear, but they are probably acquired. They are often found in asymptomatic individuals. There is some evidence that gastroesophageal reflux is associated with the development of a Schatzki ring.
Symptoms arise when the ring narrows the esophageal lumen to less than 13 mm in diameter and are rare if the lumen is more than 20 mm in diameter. A typical presenting symptom of a patient with an esophageal ring is intermittent dysphagia for solid foods. The patient may point to the area of the ring. At times a bolus of food may become impacted; the patient then regurgitates and then may be able to resume eating without further difficulty. The intermittency of the dysphagia, the chronicity of the condition, and the difficulty in making the diagnosis unless specifically suspected often result in misdiagnosis and in inappropriate therapy.
The diagnosis of esophageal ring is best made by barium swallow with a barium-coated marshmallow. The lower esophageal ring is best detected when the lower segment of the esophagus is distended, as it is during a Valsalva maneuver. Endoscopy is sometimes helpful to differentiate rings from annular strictures secondary to either reflux esophagitis or carcinoma. Cervical webs are often missed on conventional radiography but may be detected with cine studies. The webs usually are detected on the anterior surface of the esophagus, and lateral and oblique films are needed to demonstrate these lesions. Endoscopy often fails to visualize cervical webs and may disrupt the lesion during blind passage of the instrument into the esophagus. The endoscope may reveal an esophageal ring during air sufflation of the distal esophagus.
If the webs are associated with iron deficiency, treatment of the anemia causes rapid regression of the web. Otherwise, therapy involves mechanical disruption of the ring or web as well as reassurance, along with the recommendation to chew food well and slowly. Bougienage with a large-caliber dilator often disrupts the lower esophageal ring with complete relief of the dysphagia. The procedure causes transient discomfort but much less pain than does pneumatic dilation. It is ordinarily done by a gastroenterologist. Rarely, symptoms may persist after bougienage, and pneumatic dilation or even surgery may be necessary.
Globus Sensation
Globus sensation is a diagnosis often incorrectly made in patients with dysphagia who have no demonstrable organic disease. However, this condition does not produce dysphagia. Patients with globus describe the sensation of a lump in the throat, but do not have difficulty swallowing. These symptoms may be more pronounced with eating. However, when specifically questioned, patients deny dysphagia or food sticking or being held up in this region and they state that the symptom is present even when they are not eating. The pathogenesis of this condition is unknown, but hypertonicity of the upper esophageal sphincter, as a primary disorder or as a consequence of esophageal reflux, has been suggested. Gastroesophageal reflux should be ruled out (see below) before a psychologic disturbance (see Chapter 21) is diagnosed. Reassurance and an explanation of the problem form the basis for treatment. Recognizing this disorder avoids confusion in patients with true dysphagia.
Esophageal Chest Pain
Chest pain is a common and difficult diagnostic challenge. Approximately 10% to 30% of patients with chest pain have normal coronary arteries at the time of coronary angiography. Despite reassurance, many of these patients continue to take antianginal medications and are hospitalized on an average of once each year for continuing evaluation (13). Esophageal disorders may account for the symptoms in some of these individuals, but the prevalence of esophageal chest pain is unknown.
Etiology and Pathogenesis
Esophageal chest pain has been attributed to stimulation of esophageal chemoreceptors by acid reflux or of mechanoreceptors by smooth muscle spasm or esophageal distension. Cold or hot liquids may cause severe chest pain, suggesting an alteration in the sensitivity of temperature receptors in the esophagus. Transient esophageal myoischemia may be a cause of pain in patients with spastic motility disorders. Such patients have an increased frequency of psychiatric disorders and have personality profiles similar to those of patients with the irritable bowel syndrome (see Chapter 44), suggesting that chronic stress may play a role in the pathogenesis of their chest pain. Panic disorder has been diagnosed in up to one-third of patients with chest pain and normal coronary angiograms (14).
Two major abnormalities have been associated with esophageal chest pain: esophageal motility disorders and gastroesophageal reflux disease (GERD). Studies using ambulatory pH monitoring have demonstrated clinically significant gastroesophageal reflux in approximately 45% of patients with unexplained chest pain. The typical symptom of gastroesophageal reflux—heartburn—is seen in about half of patients with GERD-related chest pain. Approximately 30% of patients with esophageal chest pain have a demonstrable motility disorder, of whichnutcracker esophagus (hypertensive esophagus, supersqueezer) is the
P.654
most common. This manometric abnormality is characterized by peristaltic contractions in the distal esophagus with contraction amplitude greater than two standard deviations above normal (less than 180 mm Hg) associated with chest pain (Table 42.2). Many of these patients have prolonged duration of contractions as well. DES (see above) is the motility disorder usually considered the principal cause of esophageal chest pain; however, studies have found it to be uncommon, representing less than 10% of esophageal motility abnormalities in patients with noncardiac chest pain (15). Other disorders, such as an isolated elevated LES pressure (hypertensive LES) and achalasia, are rarely associated with noncardiac chest pain. A large number of patients (approximately 35%) have contraction abnormalities that do not fit into one of the four categories defined here. These patients have been historically grouped under the general category of nonspecific esophageal motility disorders; however, these patients have had their motility abnormalities re-evaluated and are now classified as having ineffective esophageal motility. This abnormality is defined as low amplitude esophageal contractions (<30 mm Hg) in more than 30% of swallows (see Table 42.2) (16). Evaluation requires consultation with a gastroenterologist. Few patients have spontaneous chest pain during stationary esophageal motility testing (even if esophageal motility is abnormal), but chest pain is often reproduced when the esophagus is stimulated with intravenous edrophonium (Tensilon). This cholinergic agonist reproduces chest pain accompanied by high-amplitude esophageal contractions in 20% to 30% of patients with chest pain and normal coronary arteries (13). Edrophonium does not cause narrowing of the coronary arteries nor does it cause chest pain in normal subjects or in patients with irritable bowel syndrome. A positive test indicates that the chest pain is of esophageal origin.
Diagnosis
Unfortunately, the history is not reliable in differentiating esophageal from cardiac pain or in distinguishing among the various esophageal causes of chest pain. Location, exertional onset, and radiation do not distinguish the two entities. Heartburn, dysphagia, or odynophagia suggests an esophageal etiology, but overlap exists. Pain lasting longer than 1 hour or pain that awakens the patient from sleep is more likely to be esophageal but is occasionally seen with cardiac disease. Therapeutic trials with antacids or nitrates do not reliably distinguish between the two diseases. Intraesophageal acid perfusion can cause pain and ST-T wave changes indistinguishable from that due to coronary artery disease, so cardiac disease must be ruled out before the esophagus can be implicated. A musculoskeletal etiology should be sought by careful examination of the chest wall and the costochondral joints. Peptic ulcer disease should be excluded by history, and if biliary tract disease is suspected, it should be excluded by ultrasound. Endoscopy is normal in 80% to 90% of cases and should not be done routinely (17). If heartburn is present, consideration should be given to a short (3- to 4-week) therapeutic trial of antireflux therapy. If this trial is unsuccessful, the patient should be referred for 24-hour ambulatory esophageal pH monitoring to assess the frequency of reflux and to correlate acid reflux with episodes of pain. Esophageal pH can be monitored during exercise to determine whether there is associated acid reflux. If this study is negative, esophageal manometry with provocative testing using edrophonium should be performed. Using this systematic approach, an esophageal etiology can be established in more than 60% of patients with noncardiac chest pain.
Treatment
If gastroesophageal reflux is diagnosed, treatment should proceed as outlined later in this chapter, although most patients require higher dosages of PPIs for pain relief. Treatment of patients who have only positive provocative tests is more difficult and controversial (Table 42.3). Once cardiac disease has been ruled out, reassurance should be given to all patients, specifically indicating that the esophagus, and not the heart, is the cause of their pain. Many experience a decrease in pain with this single intervention. Patients with spastic disorders or with nutcracker esophagus may respond to a nitrate or to a calcium channel blocker. Hydralazine may be tried in patients with symptomatic esophageal spasm if nitrates or calcium blockers are not successful. Trazodone HCl (Desyrel), an antidepressant, has been used successfully to relieve chest pain in these patients and is particularly useful in patients with other symptoms suggestive of depression. Imipramine (50 mg at bedtime) also has been shown to lower the frequency of esophageal chest pain (18). This dosage, lower than that typically used to treat depression, is suspected to have a visceral analgesic effect on smooth muscle. Tranquilizers and anticholinergics have been used successfully in some patients. Patients with symptoms unresponsive to these measures may respond to biofeedback or to other psychologic interventions. Several uncontrolled studies have shown improvement in chest pain caused by esophageal motility disorders after injection with botulinum toxin (19). Rarely surgery with a long esophageal myotomy is required in patients with severe pain in whom pharmacologic therapy has failed. Many patients with esophageal chest pain, whatever the cause, continue to have intermittent symptoms despite therapeutic intervention.
Gastroesophageal Reflux
GERD is common in the United States. Approximately 10% of Americans experience daily heartburn and up to 33%
P.655
have symptoms at least monthly. Most patients complain of burning substernal pain that radiates upward, often aggravated by meals and by lying down and relieved by sitting up. Approximately 10% of people have chest pain that is similar to that of angina pectoris as the sole manifestation of reflux. The percentage of people with hoarseness, cough, or wheezing caused by GERD is unknown (20). In most cases the diagnosis and treatment of GERD can be managed successfully by the primary care provider; however, 10% to 15% of patients develop complications and require referral to a gastroenterologist.
Etiology and Pathogenesis
The etiology of GERD is unknown. Several defects contribute to the development and progression of the disease. By far the most significant is an abnormality of the antireflux barrier: the LES. Two major abnormalities of the LES are associated with an increased frequency of reflux: a low basal LES pressure and transient LES relaxation unassociated with a swallow. The latter abnormality is the most common cause of an episode of reflux. Abnormal esophageal epithelial resistance (increased permeability to hydrogen ions), abnormalities of gastric emptying, gastric distension, and the nature of the gastric refluxate (acid, pepsin, and bile) all contribute to the development of GERD.
Diagnosis
Several diagnostic tests are available to establish the clinical diagnosis. No single test provides complete information about the cause and consequences of reflux, so careful selection among the available modalities is required. In patients with mild heartburn, a therapeutic trial of what has been termed phase I therapy, including antacids or H2 receptor antagonists in over-the-counter doses, may be an effective diagnostic approach. Studies have evaluated the utility of high dose PPIs (the equivalent of 40 to 60 mg omeprazole daily for 1 to 2 weeks) to determine if symptoms are relieved (21). If successful, no further workup may be needed. Patients with dysphagia and chest pain should be considered for further evaluation to determine the cause of their symptoms. If the diagnosis of reflux disease is established, treatment can proceed as outlined below. Patients with symptoms for more than 10 years, especially if they are 50 years or older, should have endoscopy because of the higher prevalence of Barrett esophagus (see below).
A barium swallow may be used to define macroscopic anatomic abnormalities in patients with GERD. However, since hiatal hernia or free reflux may be present in 30% to 40% of the general population, these findings, together or alone, should not be used to make a diagnosis of reflux disease. The presence of mucosal irregularities, stricture, or esophageal ulcer suggests a high likelihood (85% to 95%) that GERD is present.
Endoscopy (esophagoscopy) is the best study for the diagnosis and evaluation of reflux esophagitis or of other complications of GERD such as stricture or Barrett epithelium. If esophagitis is present at endoscopy, the diagnosis of GERD is established with 95% certainty, and no further workup is required. If a stricture is encountered, it should be biopsied to rule out carcinoma (dilation may be done at the same sitting in some patients). If Barrett mucosa is observed, biopsies can be taken to confirm the diagnosis and to rule out dysplasia or in situcarcinoma.
The diagnosis of GERD is established in most patients by the combination of history, response to therapy, and endoscopy. If the diagnosis is still in doubt or the patient presents with an atypical symptom, 24-hour ambulatory pH monitoring should be performed. Endoscopy may be normal in 40% of patients in whom reflux is subsequently verified by prolonged intraesophageal pH monitoring. The test is performed by placing a 2-mm flexible antimony probe transnasally so that the tip of the probe rests 5 cm above the LES. The probe is connected to a recording box similar to an ambulatory electrocardiographic monitor and worn about the waist. The patient can then be monitored at home eating a normal diet. Ambulatory monitoring is extremely useful in patients with noncardiac chest pain, in patients with wheezing, cough, or hoarseness due to reflux, or in patients with typical symptoms when a diagnosis is elusive. Probes may be placed at multiple levels in the esophagus to evaluate patients with atypical symptoms. All patients who are being considered for surgery should have pH monitoring to confirm the diagnosis before the operation. The study is extremely reproducible and is currently the most sensitive and specific diagnostic test for the presence of abnormal acid reflux.
Figure 42.2 outlines a suggested approach to the diagnosis of GERD.
Treatment
Treatment has traditionally been divided into phases (Table 42.4), implying that each is a distinct step to be followed in all patients. At present it is accepted that therapy should be individualized using a combination of lifestyle modifications (historically phase I therapy) and pharmacologic or surgical interventions. The overall goals of treatment are the complete relief of symptoms to improve the quality of life of the patient, the healing of erosive esophagitis if present, and the prevention of symptomatic relapse or complications.
Lifestyle modifications include elevating the head of the bed on 6- to 8-inch blocks or using a wedge designed to be placed in the bed under the shoulders and upper back. The patient should avoid sleeping on more pillows because this might actually increase abdominal pressure
P.656
and contribute to more reflux. Certain foods (e.g., coffee, citrus juice, and spices) are direct esophageal irritants and should be avoided. The patient should be instructed not to lie down after a meal because this promotes greater reflux. Avoidance of food 3 hours before going to bed has also been shown to decrease episodes of reflux. Obesity and alcohol use are both risk factors for the development of GERD, and weight loss and avoidance of alcohol may contribute to reducing the severity of reflux. Drugs that decrease LES pressure (e.g., calcium channel blockers, nitrates, sedatives, and theophylline) should be avoided. Antacids and over the counter H2 antagonists can be considered adjuncts to lifestyle modifications and should be used as needed to relieve daytime symptoms. The current practice of using PPIs as first-line therapy has relegated lifestyle modifications to a minor role in many guidelines, though the American College of Gastroenterology guidelines recommend that such modifications are part of any treatment program for GERD. Few would use behavioral modification as the only therapy for established GERD.
|
FIGURE 42.2. Approach to patients with gastroesophageal reflux. GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor. |
Pharmacologic therapy is aimed at decreasing gastric acid secretion (H2 antagonists or PPIs). Prokinetic agents that augment LES pressure and improve esophageal clearance are rarely used as primary therapy. Metoclopramide is the only prokinetic agent currently approved for heartburn; however, the high frequency of side effects precludes its widespread use except as a combination agent in patients refractory to antisecretory therapy. Proton pump inhibitors have replaced H2 antagonists as the initial choice of antisecretory therapy in GERD. If an H2receptor antagonist is used, treatment should be given with a twice-daily dose and continued for 6 to 8 weeks. Average acute
P.657
healing rates are approximately 50% with this regimen. If symptoms do not resolve, a proton pump inhibitor should be started. Although doubling the dose of H2 receptor antagonists may be mandated by some managed care algorithms, there is no evidence of improved efficacy with this strategy (22).
Current data support PPIs as the most effective therapy for all symptoms of GERD, for both acute and long-term therapy. Healing rates for omeprazole, lansoprazole, rabeprazole, and pantoprazole are equivalent and average 85% after 8 weeks of therapy. Esomeprazole, an optical isomer of omeprazole, is the only proton pump inhibitor to demonstrate superior-healing rates when compared with omeprazole (23). Proton pump inhibitors should be considered in all patients as potential first-line agents for treatment.
Long-Term Treatment
GERD is a chronic disease. Symptomatic and endoscopic relapse of esophagitis occurs in up to 80% of patients initially treated successfully. Therefore, most patients require some form of long-term therapy (24,25), that must be individualized. H2 receptor antagonists at full dosage are approved for maintenance treatment but are effective in maintaining symptomatic and endoscopic remission in fewer than 50% of patients. The PPIs give the best symptomatic relief, and all five available agents are effective agents in maintaining symptom relief and remission of esophagitis (approximately 85% of patients, on daily therapy) (25). It is now clear that it may be as difficult to maintain remission in patients with nonerosive GERD as it is to treat patients with erosive esophagitis or Barrett esophagus, so PPIs can be considered the most effective agents for long-term therapy regardless of the presence or absence of erosions. Continuous treatment with PPIs for up to 11 years has been demonstrated to be safe without a need for special monitoring, including measurement of serum gastrin (26). It is likely that patients can be treated indefinitely with these agents.
Surgery may be considered in patients who require long-term daily medical therapy. However, there are no absolute indications for surgery, since most patients can be treated effectively with high-dose proton pump inhibitor therapy. The best predictor of a positive outcome from surgery is an initial response to medical therapy with PPIs (25). All patients, prior to surgery, should have esophageal manometry to evaluate LES pressure and esophageal peristalsis and ambulatory pH monitoring to confirm the diagnosis of abnormal acid exposure before surgery. Fundoplication around the distal esophagus provides symptomatic improvement in approximately 90% of patients. Success with the laparoscopic operation is equal to that of the open procedure (27). In experienced hands, hospitalization is reduced to 1 to 2 days, with a marked decrease in pain and an earlier return to normal activity. Simple repair of hiatus hernia, if present, has not been as effective nor have the benefits been as long-lasting. Fundoplication provides an effective barrier to reflux. Several variations of the operation are available, and local surgical expertise generally dictates the specific operation that is performed. Complications include dysphagia, which may require esophageal dilatation, and the gas-bloat syndrome from inability to belch. Studies indicate that over half of the patients treated with antireflux surgery have returned to using medication 10 years or more after the operation, a reminder that the benefit from this intervention may not be permanent (28). Care in selecting an experienced surgeon is critical. Antireflux surgery for patients with scleroderma should be avoided, because it may markedly exacerbate dysphagia. Vagotomy is not indicated in the treatment of GERD. There is no evidence that surgery reduces the risk of esophageal cancer or improves symptoms in patients with Barrett epithelium.
The Food and Drug Administration (FDA) has approved two endoscopic therapies for GERD: radiofrequency ablation of the LES region and an endoscopic sewing device. Each has been evaluated in only a small number of patients in uncontrolled single studies. Further evaluation is needed to determine the role of these procedures in GERD.
Complications
The complications of reflux include hemorrhage, ulcerations, stricture formation, and development of Barrett mucosa. Esophagitis is the cause of 5% to 10% of all cases of upper gastrointestinal hemorrhage. Peptic ulcers and strictures must be differentiated from malignancy and from ingestion of caustic substances. The presence of a midesophageal ulcer or stricture should raise the suspicion of Barrett mucosa (columnar-type mucosa that replaces the squamous mucosa of the tubular esophagus). This type of mucosa has characteristic staining features that differentiate it from normal gastric tissue. This metaplastic intestinal type of epithelium is a premalignant condition. Patients with Barrett mucosa should therefore undergo regular endoscopic surveillance (every 2 to 3 years) for the development of cancer.
Hiatus Hernia
Herniation of a part of the stomach through the normal diaphragmatic esophageal hiatus into the thorax is called a hiatus hernia. The defect is common, but the precise prevalence is observer dependent. Estimates of prevalence therefore range from 30% to 60% overall. The defect is twice as common in women as in men and is seen in 70–80% of those older than 60 years of age. Hiatus hernia
P.658
is not synonymous with reflux esophagitis, as a hernia may exist without producing symptomatic reflux and reflux may occur without hernia. If a patient has clear-cut reflux esophagitis, the treatment should not be influenced by the presence of a hiatus hernia. If a patient who does not have reflux is incidentally discovered to have a hiatus hernia, no treatment is indicated. A large hiatus hernia (>5 cm) may predispose to more serious reflux and itself cause symptoms of chest pain or dysphagia.
A paraesophageal hernia, herniation of part of the stomach through the diaphragm adjacent to the gastroesophageal junction, is potentially dangerous because of the risk of incarceration or acute obstruction, which is a surgical emergency.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.