Esophageal Motility Disorders

The esophagus functions solely to deliver food from the mouth to the stomach where the process of digestion can begin. Efficient transport by the esophagus requires a coordinated, sequential motility pattern that propels food from above and clears acid and bile reflux from below. Disruption of this highly integrated muscular motion limits delivery of food and fluid, as well as causes a bothersome sense of dysphagia and chest pain. Disorders of esophageal motility are referred to as primary or secondary esophageal motility disorders and categorized according to their abnormal manometric patterns. See the images below.

The typical picture of achalasia. Note the "bird-beak" appearance of the lower esophageal sphincter (LES), with a dilated, barium-filled esophagus proximal to it. Image courtesy of Andrew Taylor, MD, Professor, Abdominal Imaging, Department of Radiology, University of Wisconsin Medical School, Madison.

The response to amyl nitrate (a smooth muscle relaxant), with partial relaxation of the lower esophageal sphincter (LES), allows some barium to pass through it into the stomach. Image courtesy of Andrew Taylor, MD, Professor, Abdominal Imaging, Department of Radiology, University of Wisconsin Medical School, Madison.

Esophagram of a 65-year-old man with rapid-onset dysphagia over 1 year. Although esophagram shows a typical picture of achalasia, this patient had adenocarcinoma of the gastroesophageal junction. This is an example of pseudoachalasia, which reinforces the absolute need for esophagogastroduodenoscopy (EGD) in patients with radiologic diagnosis of achalasia. Image courtesy of Andrew Taylor, MD, Professor, Abdominal Imaging, Department of Radiology, University of Wisconsin Medical School, Madison.

An esophagram demonstrating the corkscrew esophagus picture observed in a patient with manometry confirmed findings of diffuse esophageal spasm (DES). Image courtesy of Andrew Taylor, MD, Professor, Abdominal Imaging, Department of Radiology, University of Wisconsin Medical School, Madison.

Response to amyl nitrate, with disappearance of the spasm on esophagram. Image courtesy of Andrew Taylor, MD, Professor, Abdominal Imaging, Department of Radiology, University of Wisconsin Medical School, Madison.

Anatomy

The tubular esophagus is a muscular organ, approximately 25 cm in length, and has specialized sphincters at proximal and distal ends. The upper esophageal sphincter (UES) is comprised of several striated muscles, creating a tonically closed valve and preventing air from entering into the gastrointestinal tract. The lower esophageal sphincter (LES) is composed entirely of smooth muscle and maintains a steady baseline tone to prevent gastric reflux into the esophagus.

The body of the esophagus is similarly composed of 2 muscle types. The proximal esophagus is predominantly striated muscle, while the distal esophagus and the remainder of the GI tract contain smooth muscle. The mid esophagus contains a graded transition of striated and smooth muscle types. The muscle is oriented in 2 perpendicular opposing layers: an inner circular layer and an outer longitudinal layer, known collectively as the muscularis propria. The longitudinal muscle is responsible for shortening the esophagus, while the circular muscle forms lumen-occluding ring contractions.

Esophageal peristalsis

The coordination of these simultaneously contracting muscle layers produces the motility pattern known as peristalsis. Peristalsis is a sequential, coordinated contraction wave that travels the entire length of the esophagus, propelling intraluminal contents distally to the stomach. The LES relaxes during swallows and stays opened until the peristaltic wave travels through the LES, then contracts and redevelops resting basal tone. Low peristaltic amplitudes normally occur at the transition zone between the striated and smooth muscle portions; however, the peristalsis is uninterrupted.

Primary peristalsis is the peristaltic wave triggered by the swallowing center. The peristaltic contraction wave travels at a speed of 2 cm/s and correlates with manometry-recorded contractions. The relationship of contraction and food bolus is more complex because of intrabolus pressures from above (contraction from above) and the resistance from below (outflow resistance).

The secondary peristaltic wave is induced by esophageal distension from the retained bolus, refluxed material, or swallowed air. The primary role is to clear the esophagus of retained food or any gastroesophageal refluxate.

Tertiary contractions are simultaneous, isolated, dysfunctional contractions. These contractions are nonperistaltic, have no known physiologic role, and are observed with increased frequency in elderly people. Radiographic description of this phenomenon has been called presbyesophagus.

Esophageal motility disorders

Esophageal motility disorders are not uncommon in gastroenterology. The spectrum of these disorders ranges from the well-defined primary esophageal motility disorders (PEMDs) to very nonspecific disorders that may play a more indirect role in reflux disease and otherwise be asymptomatic. Esophageal motility disorders may occur as manifestations of systemic diseases, referred to as secondary motility disorders.

Esophageal motility disorders are less common than mechanical and inflammatory diseases affecting the esophagus, such as reflux esophagitis, peptic strictures, and mucosal rings. The clinical presentation of a motility disorder is varied, but, classically, dysphagia and chest pain are reported. In 80% of patients, the cause of a patient's dysphagia can be suggested from the history, including dysmotility of the esophagus. Before entertaining a diagnosis of a motility disorder, first and foremost, the physician must evaluate for a mechanical obstructing lesion.

Esophageal motility disorders discussed in this article include the following:

• Achalasia

• Spastic esophageal motility disorders, including diffuse esophageal spasm (DES), nutcracker esophagus, and hypertensive LES

• Nonspecific esophageal motility disorder (inefficient esophageal motility disorder)

• Secondary esophageal motility disorders related to scleroderma, diabetes mellitus, alcohol consumption, psychiatric disorders, and presbyesophagus

Primary esophageal motility disorders are idiopathic in nature, but postviral, infectious, environmental, and genetic factors have been hypothesized.

The pathophysiology of the primary esophageal motility disorders is poorly defined, with the exception of achalasia. The underlying cause of all the primary motility disorders remains elusive. The secondary motility disorders, such as scleroderma esophagus or esophageal motility disorder of diabetes, are better understood from the standpoint of the preexisting underlying disorders.

Achalasia

Achalasia is the best defined primary motility disorder and the only one with an established pathology. The predominant neuropathologic process of achalasia involves the loss of ganglion cells from the wall of the esophagus, starting at the LES and developing proximally. The degree of ganglion cell loss parallels the disease duration such that, at 10 years, ganglion cells are likely completely absent. At the LES, the loss of inhibitory nerves is demonstrated by loss of nitric oxide synthase and vasoactive intestinal peptide (VIP) immunohistochemistry staining. Variable amounts of inflammatory cells have been described within the myenteric plexus along with the disappearing nerves. In the peristaltic esophageal body, achalasia is characterized by a loss of intrinsic acetylcholine-containing nerves.

Extrinsic nerves may also be affected, characterized by Wallerian degeneration of the axoplasm and myelin sheaths within the vagus nerve and dorsal motor nucleus. Anatomically, the circular muscle layer at the LES is thickened, but, microscopically, individual muscle cells are grossly normal.

The physiologic process of achalasia is correlated most directly to the loss of the inhibitory nerves at the sphincter, resulting in failure of the LES to completely relax and causing relative obstruction. Manometry may reveal elevated LES pressure greater than 40 mm Hg in more than 60% of patients; however, hypertensive LES is not universal or required for the manometric diagnosis. The loss of nerves along the esophageal body causes aperistalsis, leading to stasis of ingested food and subsequent dilation of the esophagus. Nonperistaltic isolated contractions or low-amplitude simultaneous contractions of the esophageal body may be observed. If high-amplitude (>60 mm Hg) simultaneous contractions occur, the entity is categorized as vigorous achalasia, which may represent an early stage of classic achalasia. Physiologic characteristics of achalasia are additionally useful in assisting with establishing the diagnosis through chemical challenge testing.

With the partial ganglion cell loss in patients with achalasia, edrophonium (acetylcholine esterase inhibitor) increases LES pressure while atropine (muscarinic antagonist) decreases LES pressure. This characteristic likely explains why the botulinum toxin (acetylcholine release inhibitor) may have therapeutic benefit in patients with achalasia.

Spastic motility disorders of the esophageal body

No documented abnormalities exist regarding the distribution of myenteric neurons in patients diagnosed with spastic motility disorders of the esophageal body, but diffuse fragmentation of vagal filaments, increased endoneural collagen, and mitochondrial fragmentation are described. There appears to be a functional imbalance between excitatory and inhibitory postganglionic pathways, disrupting the coordinated components of peristalsis. In DES, muscular hypertrophy or hyperplasia has been described in the distal two thirds of the esophagus. Muscle wall thickening has been described in patients who are asymptomatic and, conversely, has been absent in some patients with typical symptoms and manometric findings. This controversial finding causes difficulty in attributing symptoms or manometric abnormalities to muscle structure changes. In addition, anxiety states may also play a role in some patients.

Scleroderma esophagus

In scleroderma, the primary defect in this systemic process is related to smooth muscle atrophy and fibrosis. Esophageal dysmotility develops as the smooth muscle of the esophagus is replaced by scar tissue, gradually leading to progressive loss of peristalsis and a weakening of LES. Motility is preserved at the proximal striated muscle portion of the esophagus.

United States data

Esophageal motility disorders, excluding achalasia, lack population-based studies. The 2 best-characterized motility disorders, achalasia and DES, represent only a small percentage of diagnosed motility disorders. The incidence of achalasia is 1-3 case per 100,000 population per year.[1] As with any other chronic illness, prevalence exceeds incidence significantly. Familial clustering is observed, but a genetic relationship is not established. Nutcracker esophagus is the most common motility disorder (>40% of all motility disorders diagnosed), but it is the most controversial in significance.

The incidence of esophageal dysmotility appears to increased in patients with spinal cord injury (SCI).[2] In a study of 12 patients with paraplegia (level of injury between T4-T12), 13 patients with tetraplegia (level of injury between C5-C7), and 14 able-bodied individuals, Radulovic et al found 21 of the 25 patients (84%) with SCI had at least one esophageal motility anomaly compared to 1 of 14 able-bodied subjects (7%). Among the anomalies seen in SCI patients were type II achalasia (12%), type III achalasia (4%), esophagogastric junction outflow obstruction (20%), hypercontractile esophagus (4%), and peristaltic abnormalities (weak peristalsis with small or large defects or frequent failed peristalsis) (48%).[2]

Altered esophageal motility is sometimes seen in patients with anorexia nervosa.[3]  It is also seen in patients following eradication of esophageal varices by endoscopic sclerotherapy, in association with an increased number of endoscopic sessions but not with manometric parameters.[4] Features of esophageal motility after endoscopic sclerotherapy are a defective lower sphincter and defective and hypotensive peristalsis.

International data

In Europe, the incidence of achalasia is similar to that of the United States.

Race-, sex-, and age-related demographics

Racial and environmental differences in the incidence of achalasia and other esophageal motility disorders might be present; however, because of the low incidence of disease and underdiagnosis in developing countries, these differences have not been demonstrated. Racial differences in the incidence of achalasia and other esophageal motility disorders have not been established.

Achalasia affects both sexes in equal numbers. No reliable information for other motility disorders exists.

Achalasia commonly presents in the fifth decade but rarely may develop in children as well as in elderly persons.

Achalasia

Achalasia is a progressive disease that requires chronic therapy. Depending on the rate and extent of disease progression, therapy might include endoscopic and surgical interventions. Advanced achalasia can lead to malnutrition, dehydration, and aspiration.

Even after therapy, patients continue to have mild symptoms related to aperistaltic esophagus and, thus, will want to still follow careful eating habits.

Scleroderma esophagus

Scleroderma is a systemic disease with a progressive nature. Systemic complications are the major cause of mortality.

Significant acid reflux might lead to disabling symptoms, caused by reflux or its complications.

Spastic esophageal motility disorders

Whether or not symptomatic relief is achieved, the prognosis in patients with spastic esophageal motility disorders is favorable. Life expectancy is not affected, and weight loss is rare.

If symptoms progress, then the workup should be repeated because DES can progress to achalasia.

Mortality/morbidity

Achalasia is associated with significant and progressive symptomatic discomfort. When advanced, this condition can lead to such severe dysphagia that malnutrition, weight loss, and dehydration can develop. Increased incidence of both esophageal squamous cell and adenocarcinoma is observed in patients with long-standing achalasia. Therapeutic procedures and operations are associated with a small but significant risk of mortality and morbidity.

Spastic esophageal motility disorders are associated with symptomatic discomfort but do not lead to the severity of dysphagia observed in patients with achalasia. Chest pain is, in fact, a more common complaint that may precipitate emergency room visits and cardiologic evaluations.

Scleroderma esophagus is associated with severe and progressive acid reflux symptoms and complications. Associated complications, including strictures, Barrett esophagus, and adenocarcinoma of the esophagus, are the concern.

Complications

Achalasia and squamous cell carcinoma

With achalasia, the risk of squamous cell carcinoma of the esophagus is higher than that of the general population. However, no studies to date have shown convincing evidence that surveillance is worthwhile.

The pathogenesis is not well documented, but chronic mucosal irritation is incriminated.

Squamous cell carcinoma usually develops several years after the diagnosis of achalasia. The risk typically starts increasing after approximately 10 years of having the disease process. At the time of diagnosis, the esophagus usually is dilated, and the tumor is advanced.

Patients should be counseled about their disease. They should be well informed about its lifelong nature. Possible complications, therapeutic options, expected outcomes, and dietary modifications should be explained.

Reassurance is important in patients with spastic motility disorders, especially in the setting of noncardiac chest pain. 

For patient education resources, see Heartburn and GERD Center and Digestive Disorders Center, as well as Acid Reflux (GERD) and Heartburn.

Achalasia

Note the following:

• Progressive dysphagia for both solids and liquids is the hallmark of achalasia. Dysphagia for solids is more common than for liquids.

• Retrospectively, symptoms are present on average as long as 6 years prior to presentation.

• Regurgitation of food retained in the proximal dilated esophagus is a common occurrence, especially at night, requiring patients to sleep using multiple pillows or upright in a chair. This symptom worsens as the esophagus dilates with time.

• Chest pain may be another early symptom, characterized by a squeezing retrosternal pain radiating to the neck, jaw, arms, or back. The chest pain may worsen with food and can awaken patients from sleep.

• A sensation of heartburn may be reported by 30% of patients and is assumed to be related to retained food fermentation and lactic acid.

• Emotional stress or rapid eating may worsen all of the symptoms described above.

• Weight loss is common with achalasia; however, the loss is usually slight.

Spastic esophageal motility disorders

Chest pain is the hallmark of spastic esophageal motility disorders, although patients with spastic esophageal motility disorders also may report dysphagia. Similar to the chest pain of achalasia, it may mimic angina. The mechanism is not clear but may be related to transient esophageal muscle ischemia, luminal distension, or altered visceral sensation.

Dysphagia is not necessarily related to chest pain. Dysphagia for solids and liquids is a common symptom and especially seen in DES. Dysphagia may be intermittent and nonprogressive in nature, typically not prolonging mealtime or causing weight loss.

Patients also commonly report heartburn, regurgitation, or other esophageal complaints of reflux disease due to ineffective acid clearance from the esophagus.

Weight loss is common with achalasia; however, the loss is usually slight.

Scleroderma esophagus

Scleroderma involves the esophagus in more than 75% of patients, regardless of clinical type. Two forms of this disease exist–(1) progressive systemic sclerosis (PSS), characterized by diffuse scleroderma, and a more fulminant form with early involvement of internal organs or (2) CREST syndrome, characterized by calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. The severity of esophageal involvement does not correlate necessarily with severity of involvement of other organs. In fact, dysphagia may be the presenting clinical symptom in some patients.

The esophageal symptoms of scleroderma usually reflect the severity of acid reflux disease, including heartburn, regurgitation, and dysphagia.

Erosive esophagitis is observed in as many as 60% of patients, and the incidence of Barrett esophagus and adenocarcinoma of the esophagus is increased.

Dysphagia usually is due to diminishing peristalsis, peptic strictures, or a combination of both.

In patients with primary motility disorders, results of a physical examination often are unrevealing.

Clinical signs of scleroderma in the proper clinical setting must be noted, especially skin changes.

A bedside swallowing challenge may be performed with a glass of water.

Evaluate the patient's general nutrition and hydration status if significant dysphagia is reported.

Radiography

Chest radiography is not required to establish the diagnosis.

In patients with long-standing achalasia, the esophagus dilates and exhibits a sigmoid appearance. An air-fluid level, a widened mediastinum, and the absence of a gastric air bubble often are observed.

Patients with spastic esophageal motility disorders show no abnormalities on chest radiographs.

Esophagraphy

Note the following:

• Advanced achalasia produces a dilated intrathoracic esophagus with an air-fluid level. The classic sign is a tapering of the LES, creating the characteristic "bird-beak" appearance. Early achalasia would reveal a normal anatomical esophagus with loss of peristalsis and transient stasis just above the GEJ.

• Occasionally, epiphrenic diverticula are noted immediately above the LES.

• Hiatal hernia reportedly is observed in 10-20% of patients with achalasia.

• In patients with DES, the classic esophagram findings are of a "corkscrew" or "rosary bead" esophagus. Pseudodiverticula and curling also suggest DES.

• In patients with scleroderma esophagus, the esophagram shows a slightly dilated esophagus, weak or absent peristalsis, and free reflux often is demonstrated.

Manometry

Esophageal manometry evaluates esophageal motor pattern, contraction amplitude, and LES pressure and function.[5, 6] The manometric criteria for diagnosis of the primary esophageal motility disorders are shown in the images below:

Normal manometry results show normal esophageal body peristalsis with normal lower esophageal sphincter (LES) pressure and relaxation. The LES pressure tracing is at the level of the sleeve (tracing 6).

Achalasia manometry picture Note the nonrelaxing lower esophageal sphincter (LES) and the absence of esophageal body peristalsis. The LES pressure tracing is at the level of the sleeve (tracing 6).

Manometry demonstrates diffuse esophageal spasm with simultaneous contractions of the esophagus observed throughout the tracing. The lower esophageal sphincter (LES) pressure tracing is at the level of the sleeve (tracing 6).

Achalasia

In patients with achalasia, aperistalsis of the esophageal body and incomplete relaxation of the LES are the manometric hallmark of this disease. Using these criteria, diagnosis can be achieved in more than 90% of patients. In the remaining 10%, the manometry is nondiagnostic, which probably is related to inability to position the catheter across the LES due to extensive esophageal dilation and tortuosity.

Lower esophageal sphincter

LES may have a hypertensive resting pressure (>45 mm Hg), although LES pressures can also be normal but not low (60 mm Hg) are observed in patients with vigorous achalasia.

Spastic esophageal motility disorders

Each of the esophageal spastic motility disorders has certain manometric findings that are either diagnostic or associated. Note the following:

• DES is characterized by the findings of simultaneous contractions greater than 30% of water swallows, with the presence of normal peristalsis.[7] Other associated manometric findings may include repetitive contractions (>2 peaks), prolonged contractions (>6 s), high-amplitude contractions (>180 mm Hg), spontaneous contractions, incomplete LES relaxation, and increased LES pressure (>40 mm Hg).

• Nutcracker esophagus: These manometric abnormalities are the most common of the spastic motility disorders. The characteristic criterion is normal-patterned peristalsis with high-amplitude contractions greater than 180 mm Hg (2 standard deviations above the normal mean). The manometric findings associated with this condition may include repetitive contractions (>2 peaks), prolonged contractions (>6 s), and increased LES pressure (>40 mm Hg).

• Hypertensive LES: This is characterized by increased LES pressure of greater than 40 mm Hg that otherwise relaxes normally. Esophageal peristalsis is normal. Of note, elevated LES pressures may also be seen in patients with achalasia, nonspecific motility disorders, nutcracker esophagus, and DES; however, they are characterized by abnormal esophageal body motility. The significance of hypertensive LES is questionable.

• Nonspecific esophageal motor disorders: When peristaltic abnormalities are insufficient to establish one of the other motility disorders, the disorder is labeled as a nonspecific esophageal motor disorder (NEMD). Establishing a direct relation to symptoms is extremely difficult. This condition may include the following: nontransmitted waves (>20%), retrograde contractions, repetitive contractions (>2 peaks), low-amplitude contractions (< 30 mm Hg) or failed peristalsis (also referred to as inefficient esophageal motility [IEM]), isolated prolonged contractions (>6 s) or high-amplitude contractions (>180 mm Hg), spontaneous contractions, and incomplete LES relaxation. These nonspecific findings are not generally correlated to any symptoms.[8]

Ambulatory esophageal manometry

This new technique is capable of recording esophageal pressures for longer intervals and is a trial to capture motility disorders and to correlate their manometric findings with symptoms. No consensus exists regarding the interpretation or utility of this test, so it remains an investigational tool.

High-resolution manometry

In relatively recent years, high-resolution manometry has been introduced, which may provide improved identification of esophageal disease, such as motility disorders, hiatal hernia, and outflow obstruction, as well as provide ease of interpretation compared with conventional manometry.[9]  This technique may also allow for differentiating pediatric patients with dysphagia due to weak peristalsis (poor bolus clearance) from abnormal bolus flow resistance (esophageal outflow obstruction), which has potential implications for treatment planning and decision making.[10]

Salvador et al assessed high-resolution manometry (36-channel catheter, 1-cm sensor intervals) studies in 106 patients and 50 healthy controls and classified findings into abnormalities of the gastroesophageal barrier and of the esophageal body.[5] The findings were validated with endoscopic and radiographic comparisons.

The investigators demonstrated a significantly lower mean time for high-resolution manometry (8.1 mins) compared with a conventional method (24.4 mins; P< 0.0001).[5] The presence of a lower esophageal sphincter defect by high-resolution manometry was validated in 86.3% (44/51) of patients via radiography/endoscopy, and 80% (41/51) of patients had a positive pH study, endoscopic erosive esophagitis, or Barrett esophagus.[5]

Carlson et al have indicated that  esophageal pressure topography (EPT) may be the preferred assessment modality of esophageal motility over conventional line tracings (CLT).[11]  Six attending gastroenterologists and six gastroenterology fellows from 3 academic centers interpreted each of the 40 studies using both EPT and CLT formats: Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT than with EPT, and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than with EPT.

Endoscopy

Endoscopy is a crucial imaging tool used to exclude mechanical and inflammatory lesions that are causing dysmotility symptoms. When considering achalasia, endoscopic evaluation is critical in looking for a structural cause for obstruction.

Endoscopy is insensitive in determining primary motility abnormalities of the esophagus. In patients with advanced disease, the esophagus becomes atonic, dilated, and tortuous, which may be appreciated endoscopically.

In patients with achalasia, mucosal changes due to chronic irritation and food stagnation include erythema, friable mucosa, ulceration, and candidal infection. The LES is closed tightly and does not open with air insufflation, but the endoscope can pass into the stomach with gentle mechanical pressure. Conversely, a feeling of resistance or stiffness at the gastroesophageal junction suggests another diagnosis (eg, malignancy, stricture). If resistance is felt or mucosal changes are noted, biopsies should be obtained.

Endoscopic ultrasonography

Endoscopic ultrasonography remains investigational in managing achalasia, although it has been used to work up tumors or infiltrative diseases of pseudoachalasia as well as to assist in botulinum toxin injection. Current studies are assessing the role of endoscopic ultrasonography defining motor corollaries to the various esophageal motility disorders.

Endoscopic biopsy results of the mucosa and submucosa are generally normal. The depth of a standard endoscopic biopsy is not usually deep enough to reach the myenteric nerves. Histologic findings from surgical and necropsy examinations of the smooth muscle esophagus in patients with achalasia shows fewer ganglion cells with a mononuclear inflammatory infiltrate. Circular muscle of the LES is thickened, but, microscopically, muscle cells are normal.

Gastroenterology consultation should be obtained for any patient with a suspected esophageal motility disorder for proper evaluation.

Transfer

Patients with achalasia, DES, or other motility disorders who need aggressive endoscopic or surgical interventions should be referred to centers with experienced gastrointestinal and surgical services.

Gastroenterologists dealing with such disease processes should be familiar with performance and interpretation of diagnostic and therapeutic procedures. This also is true for surgeons, who need to be familiar with the surgical intervention involved.

Outpatient monitoring

Patients require outpatient follow-up care. Changes in medical therapy often are needed, and, with progression of disease, alternative endoscopic or surgical interventions might be needed.

Good planning and awareness of complications mandate multidisciplinary follow-up care, involving primary care, gastroenterology, dietary, and surgery services as needed.

The primary underlying neuropathology process in patients with achalasia cannot be cured; therefore, the primary goal of treatment is symptomatic relief.[12] As the myenteric nerves do not regenerate, treatment goals are directed at relieving the physiologic obstruction at the level of the LES by surgical or endoscopic balloon disruption of the LES muscle or, less effectively, through medications that relax the LES smooth muscle. In the spastic motility disorders, relaxation of the esophageal body and LES smooth muscle lends some relief of dysphagia and atypical chest pain. In patients with scleroderma esophagus, treatment is more targeted, involving aggressive antireflux therapy and management of reflux complications (eg, stricture dilation).

Pharmacologic therapy

Current pharmacologic therapy can provide some symptomatic relief to patients in the early stages of achalasia when disease activity is mild or moderate. More definitive therapy is spared for patients with advanced disease. In patients with spastic esophageal motility disorders, current pharmacologic therapy provides varying degrees of symptomatic relief.

Smooth muscle relaxants, including nitrates and calcium channel blockers, were the first medications to be used in all patients with esophageal motility disorders. The greatest experience has been with isosorbide dinitrate and nifedipine. The efficacy of these agents was demonstrated in case reports and retrospective studies primarily. Other drugs used less extensively include different types of anticholinergics, amyl nitrite, nitroglycerin, theophylline, beta2-agonists, and, recently, phosphodiesterase inhibitors. The experience with these drugs is limited.

Noncardiac chest pain in the setting of spastic esophageal dysmotility often shows good response to antireflux therapy, even in the absence of typical gastroesophageal reflux symptoms. Reassurance and control of anxiety is extremely important in this setting. If antireflux therapy fails, alternatives include different classes of muscle relaxants mentioned above and pain modulators such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and trazodone. Some studies report positive results from behavior modification programs and biofeedback.

Chronic pain management with TCAs is effective in managing noncardiac chest pain that is resistant to other therapies.

Botulinum toxin injection

Botulinum toxin injections into the LES have been used in treating patients with achalasia. Botulinum toxin is a potent inhibitor of acetylcholine release from nerve terminals. A sclerotherapy needle is used to inject 80-100 units of botulinum toxin into the 4 quadrants of the LES.

This therapy may be a good alternative for poor surgical candidates, such as elderly patients or frail individuals. The major disadvantages are the high cost and the need for repeated therapeutic sessions.

Some data suggest efficacy in patients with DES and hypertensive LES dysfunction, especially focusing on symptomatic relief of pain, dysphagia, and regurgitation. More studies are needed to prove this effect.

Endoscopic therapy

Note the following:

• Esophagogastroduodenoscopy (EGD) with pneumatic dilation is the standard endoscopic therapy for patients with achalasia and can be performed on an outpatient basis. Forceful distension of the LES to 3 cm with disruption of the circular muscle layer is needed for symptomatic relief. This distension and disruption cannot be achieved with the standard bougie (to 56F), which provides temporary benefit at best. Balloon dilators specifically designed to treat patients with achalasia achieve adequate diameter for lasting effectiveness. Achalasia dilators are long, noncompliant, cylindrical balloons that are positioned fluoroscopically or endoscopically across the LES and then inflated to a certain characteristic diameter: 30 mm, 35 mm, or 40 mm.

• Technique details are variable among different practitioners.

• Response rates vary from 50-93%. If no response is seen after 2 successive balloon dilations, it is unlikely to work.

• Chest pain is felt during inflation, even under sedation. The major complication is perforation, which occurs at a rate as high as 8%. Patients should be observed for 3-6 hours before discharge, or, alternatively, a water-soluble contrast esophagram should be performed postdilation.

• If no perforation is noted, the patient's diet can be advanced slowly over a few days. Acid suppression should be used after vigorous dilation with significant mucosal tears, as they are at risk for subsequent gastroesophageal reflux. If perforation complicates a pneumatic dilation, intervention varies according to severity. Small or intramural perforations can be managed with a conservative approach, including IV antibiotics, nothing by mouth, and observation; large perforations or progression of symptoms requires surgical repair, which carries favorable prognosis if performed early. At the time of surgery, a myotomy can be coupled with a repair operation.

• After pneumatic dilation, the best outcome predictor is measuring the residual LES pressure. If the pressure is less than 10 mm Hg, the outcome usually is excellent. If the LES pressure is more than 20 mm Hg postdilation, the clinical outcome usually is poor. The dilation can be repeated, although poor initial results and rapid recurrence postdilation indicate a poor response to repeat dilation. The overall success rate with endoscopic dilation is reportedly 30-98% in different series. This therapy has no effect on future Heller myotomy if surgery ultimately is needed.

• Pneumatic dilation showed positive results in a subset of patients with DES and LES dysfunction. This is based mainly on case reports and case series. Further verification of its role in this setting is needed.

Similar to endoscopic balloon dilation for achalasia, surgical treatment targets to disrupt the LES (myotomy) and, therefore, to relieve the high pressures at the gastroesophageal junction.[13] Since the development of laparoscopic technique for LES myotomy, a trend has emerged to treat younger and older patients with myotomy who are deemed good surgical candidates. Excellent results have been reported in 80-100% of patients. In advanced cases, when the esophageal anatomy is markedly distorted or when malignancy develops, esophagectomy becomes the surgical procedure of choice. In patients with other esophageal motility disorders, surgery rarely is indicated because these disorders generally are tolerable and do not cause malnutrition or dehydration.

Heller myotomy

Heller myotomy is the operative procedure of choice in patients with achalasia.Technically, an approximate 3- to 4-cm incision is made from the distal esophagus, across the GEJ, and onto the cardia and fundus of the stomach. The incisional depth is through both layers of the muscularis propria but not through the muscularis mucosa.

Myotomy of the LES decreases the pressure across the gastroesophageal junction and eliminates dysphagia. Unfortunately, myotomy may lead to gastroesophageal reflux; therefore, fundoplication may be coupled with the myotomy at the time of the surgery.

Myotomy can be performed through either transthoracic or transabdominal approaches; however, a transabdominal technique is favored. The laparoscopy and thoracoscopy techniques decrease perioperative morbidity and hospital stay.

Efficacy is 60-100% in different series and is found to have a longer duration of efficacy compared to endoscopic balloon disruption.

The major postoperative complication of Heller myotomy is postmyotomy reflux. Reflux symptoms tend to be particularly severe due to aperistalsis in the esophageal body preventing proper acid clearance from the esophagus. Severe esophagitis, stricturing, and Barrett changes are observed in approximately 15% of patients postoperatively. Adenocarcinoma of the esophagus also is described.

Another significant complication is recurrent or persistent dysphagia, which is observed in 10-20% of patients postoperatively. Mortality is less than 0.2%.

In the European Achalasia Trial, treatment with pneumatic dilation or laparoscopic Heller myotomy was successful in a higher percentage of patients with type II achalasia than in patients with the type I or III form of the disease. Although success rates were high for both approaches in type II achalasia, the success rate was significantly higher in the group treated with pneumatic dilation.[14] However, relapse is common after pneumatic dilation; for good long-term outcomes, close follow-up and repeat dilation are required.[15]

Esophagectomy with gastric pull up or intestinal interposition

In patients with extremely advanced disease or refractory cases, 2 surgical options are esophagectomy with gastric pull up or intestinal interposition operation.

Other indications for esophagectomy are unresolved obstructive symptoms, carcinoma, or perforation during dilation. Perioperative mortality for this surgery is 4%.

Extended Heller myotomy

Unlike achalasia, where surgical myotomy is considered early in management, in patients with refractory DES, surgical therapy is the last resort when dysphagia or pain is severe.

The operative procedure involves an extended Heller myotomy of the LES, with proximal extension to the thoracic inlet. Compared to standard myotomy, this surgery is more complex and aggressive and should be used cautiously since the symptoms are frequently not relieved.

Dietary considerations

Dietary and eating habits should to be adjusted. Smaller, more frequent meals are preferred over the larger meals of the traditional 3 meals per day pattern. Liquid foods will ultimately pass down the esophagus and through the LES with less resistance.

Patients should be instructed to take smaller bites of food, with thorough chewing and slow swallowing. Patients should follow food boluses with liquids frequently.

Instruct patients to remain in the upright posture during and for some time after mealtime (at least 2 h) to enhance esophageal emptying. Straightening of the back, raising arms above the head, and standing can increase intraesophageal pressure and enhance esophageal clearance.

Activity

Avoiding exercise and avoiding lying down during and after mealtime can enhance esophageal emptying and improve symptoms.

Drug treatment targets relaxation of the smooth muscle of the LES and esophageal body for symptomatic relief. In a subset of patients with esophageal body spastic motility disorders, relieving anxiety has been shown to improve symptoms. Commonly used medications for patients with esophageal motility disorders include calcium channel blockers, smooth muscle relaxants, anticholinergics, and antianxiety medications. No one single drug has proven efficacy in the treatment of spastic motility disorders.

Class Summary

Inhibit calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle.

Nifedipine (Adalat, Procardia)

Relaxes smooth muscles, including those of the LES and esophageal body.

Amlodipine (Norvasc)

Relaxes smooth muscles, including those of the LES and esophageal body.

Class Summary

Used for smooth muscle relaxation effects.

Isosorbide dinitrate (Isordil, Dilatrate-SR)

Relaxes smooth muscles, including those of the LES and esophageal body.

Nitroglycerin sublingual (Nitro-Bid, Deponit, Nitro-Dur)

Relaxes smooth muscle all over the body, including those of the LES and esophageal body.

Class Summary

Inhibit the cholinergic effect on the gut to induce relaxation.

Dicyclomine (Bentyl)

Treats GI motility disturbances. Blocks action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS.

Hyoscyamine (Levbid)

Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and CNS, which, in turn, has antispasmodic effects. SL tabs may be administered orally, sublingually, or chewed.

Class Summary

Relief of anxiety related to symptoms experienced by some patients with esophageal motility disorders, resulting sometimes in symptomatic relief.

Alprazolam (Xanax)

Binds receptors at several sites within the CNS, including the limbic system and reticular formation. Effects may be mediated through GABA receptor system.

Class Summary

Used in chronic pain management for noncardiac chest pain unresponsive to other treatment modalities.

Amitriptyline (Elavil)

Has analgesic effects for some forms of chronic and neuropathic pain.

Nortriptyline (Pamelor)

Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS. Pharmacodynamic effects (eg, desensitization of adenyl cyclase, down-regulation of beta-adrenergic and serotonin receptors) also appear to play a role in its mechanism of action.

Class Summary

Local anticholinergic use at the LES.

Botulinum toxin (BOTOX)

Binds to receptor sites on motor nerve terminals and inhibits release of acetylcholine, which, in turn, inhibits transmission of impulses in neuromuscular tissue.

Class Summary

For reduction in parasitemia and improvement of clinical signs and symptoms of Chagas disease.

Nifurtimox (Lampit)

5-nitrofuran derivative that is the current drug of choice in the United States for treatment of acute Chagas disease (American trypanosomiasis) due to T cruzi infection. Although the use of this drug is effective in reducing or eliminating parasitemia and clinical symptoms in acute disease, whether chronic sequelae are reliably prevented is unclear. In the chronic stage, a long-term parasitological cure may not be achieved, and the drug may not alter the course of the disease significantly.

Dose adjustments may be indicated in renal or hepatic disease. The toxicity of nifurtimox also is a limitation, and geographic variations in response to nifurtimox in patients with chronic disease have been reported.

Benznidazole (Radanil, Rochagan, Ragonil)

A 2-nitroimidazole derivative that has inhibitory effect on protein synthesis and ribonucleic acid synthesis in T cruzi cells.

Benznidazole chemotherapy has been recommended as an alternative choice for treatment of the acute and indeterminate phases of Chagas disease, but it does not appear to offer a significant efficacy or toxicity advantage over nifurtimox. Benznidazole may be preferable in some regions based on experience with local strains. The propensity of both of these agents to induce chromosomal aberrations requires further study.