33: Overview of Esophageal Motility Disorders

Primary esophageal motility disorders are characterized by abnormalities of esophageal peristalsis or contractions that interfere with swallowing and transit of food through the esophagus, producing symptoms of dysphagia and chest pain. The disorder is considered primary (idiopathic) when the cause of the patient's symptoms and altered motility cannot be attributed to other systemic diseases (e.g., diabetes mellitus, scleroderma, amyloidosis, or neuromuscular disorders that affect striated muscle). The classic presentation is achalasia, a disorder characterized by failure of the lower esophageal sphincter (LES) to relax. There are several nonspecific esophageal motility disorders, including diffuse esophageal spasm (DES), nutcracker esophagus, ineffective esophageal motility (IEM), and other abnormalities of the LES. Whether these represent true disorders, a continuum of disease or merely abnormal motility patterns that are associated with but not the physiologic causes of symptoms remains a controversy (Table 33-1). Lack of a meaningful classification system adds to this confusion. Current systems classify the disorder based on aberrant esophageal motility patterns documented on manometric studies in the context of dysphagia and pain that cannot be explained by other thoracic or cardiac disease. These systems fall short because the cause of most motility abnormalities is unknown. Patients can have abnormal manometric tracings and be perfectly healthy. Conversely, therapies may correct the abnormal tracing, but symptoms do not improve. Strategies for managing esophageal dysmotility disorders include conservative management, treatment with drugs and other agents, and surgery. In the sections that follow we review current knowledge about the pathophysiology of the primary esophageal motility disorders and recent advances in diagnosis and treatment.

Normal Esophagus

The normal human esophagus uses two sphincters to control the passage of food and prevent the reflux of stomach contents: the upper esophageal sphincter (UES) and the LES. The LES is often adversely affected in primary esophageal motility disorders. The normal LES is located in the most distal portion of the esophagus and acts as the barrier between the esophagus and the stomach. It has a resting pressure of 15 to 25 mm Hg, which is usually sufficient to prevent gastroesophageal reflux. The body of the esophagus is composed of layers of motor, mixed, and smooth muscle that contract and relax in a coordinated fashion during peristalsis. A normal swallow begins with the relaxation of the LES and initiation of a peristaltic wave that moves the food bolus through the entire esophagus, terminating at the gastroesophageal junction (GEJ), where the relaxed LES permits the food bolus to progress into the stomach. Immediately after the bolus passes, the sphincter resumes its contracted state, forming a barrier between the highly caustic stomach contents and the esophageal lumen.

Neuronal control of normal peristalsis of the human esophagus involves both central (CNS) and enteric (ENS) components of the nervous system. The proximal esophagus, composed of striated muscle, depends on direct motor neuron sequencing by the CNS. In contrast, the distal esophagus is composed of smooth muscle. Propulsive motility in this region is controlled by a combination of central and myenteric neural circuitry. Peristalsis in the smooth muscle segment of the healthy esophagus can be described as a progressive aboral wave of contraction, preceded by inhibition of distal segments, including the LES. The occurrence, amplitude, and duration of the contraction and the velocity of propagation depend critically on the coordination of excitatory and inhibitory neuronal influences.¹ The excitatory innervation is mediated predominantly by acetylcholine, which acts on the muscarinic receptors, whereas inhibitory innervation involves mostly nitric oxide (NO) synthesis.²

The inhibitory function of NO is ubiquitous in the gastrointestinal tract.³ Its synthesis from l-arginine results from the activation of neuronal nitric oxide synthase (nNOS). NO mediates smooth muscle relaxation via an enzymatic cascade involving activation of soluble guanylate cyclase, production of guanosine 3,5-monophosphate (cGMP), and stimulation of cGMP-dependent protein kinase. Nerves and fibers immunoreactive for nNOS in the esophagus are localized to circular muscle in the distal segment.² The normal peristaltic contraction likely depends on a balance between a cholinergic excitatory tone and an inhibition that is progressively more profound in distal segments.² NO also plays a critical role in relaxation of the LES,⁴ although inhibitory neuropeptides, particularly vasoactive intestinal peptide, also have been implicated in LES relaxation.⁵

It has been proposed that nutcracker esophagus, DES, and achalasia may represent a continuum of disease resulting from a progressive neuropathy primarily involving inhibitory innervation in the distal esophagus and LES.⁶ The nature of the pathology underlying the loss of inhibitory innervation is not clear, although an autoimmune interpretation is supported by the finding that sera obtained from a subset of achalasia patients bind to myenteric neuronal elements, including apparently nNOS-containing neurons.⁷ This model offers an appealingly cogent interpretation of these esophageal disorders. At early stages, such a pathologic process would be expected to alter the balance in favor of excitation, leading to the high amplitude but still peristaltic contractions characteristic of nutcracker esophagus. Further compromise of inhibitory influence would lead to loss of coordinated propagation, as observed in diffuse spasm, and finally, aperistalsis, loss of LES relaxation, and the sequelae of obstruction that is characteristic of achalasia (Fig. 33-1).

This interpretation is supported by case reports of apparent clinical transition from nutcracker esophagus to diffuse spasm^8,9 and from diffuse spasm to achalasia.^6,10 It is also in agreement with a variety of clinical and pathologic experimental evidence. In patients with diffuse spasm, achalasia, or intermediate disease, the degree of swallow-induced receptive inhibition measured manometrically correlates inversely with peristaltic velocity.¹¹ IV glyceryl trinitrate, an NO donor, produces dose-dependent increases in latency and propagation velocity, decreases the duration of swallow-induced contractions, and alleviates the symptoms in patients with DES.¹² In achalasia patients, distal relaxation in response to esophageal distention is impaired, but proximal contractile responses are preserved.¹³ In vitro circular smooth muscle strips from the LES of normal control individuals exhibit spontaneous tone and relaxation during electrical field stimulation, whereas similar strips from patients with achalasia exhibit a contraction mediated by muscarinic receptors.¹⁴

Histologic quantitation of NADPH-diaphorase–positive (nNOS containing) neurons in LES and gastric fundus muscles of achalasia patients indicates a significant reduction of such neurons relative to cancer control individuals.¹⁵ Similarly, immunohistochemical staining demonstrates an absence of nNOS in the LES of achalasia patients.¹⁶ Normal esophageal smooth muscle is innervated by fibers immunoreactive for vasoactive intestinal peptide and neuropeptide Y, whereas few such fibers are evident in smooth muscles obtained from patients with achalasia.¹⁷

Knowledge of this pathophysiology has suggested several strategies for medical treatment. Sildenafil blocks enzymatic degradation of cGMP and thus enhances relaxation of smooth muscle. In normal volunteers, sildenafil reduces contraction amplitude in the esophageal body and LES tone, and this drug shows apparent benefit for a subset of patients with nutcracker esophagus.¹⁸ Botulinum toxin acts by inhibiting autonomic acetylcholine release and has been shown to be an effective treatment for achalasia by reducing LES pressure.¹⁹ Though less effective, it provides a less risky alternative to more invasive treatments such as dilation or myotomy.

Etiology

The term achalasia originates from Greek, meaning “does not relax.” The etiology of achalasia is unknown. It is a rather uncommon disorder with an annual incidence of 1 per 100,000.²⁰ In achalasia, the LES remains in its tonically contracted state after a swallow and fails to completely relax. This may be associated with the loss of peristalsis in the body of the esophagus, predominantly in the smooth muscle segment, or lower two-thirds of the esophagus. The loss of inhibitory neuronal drive is believed to be the cause of these effects.

Clinical Spectrum

The disease affects men and women equally. The diagnosis is usually made between the ages of 25 and 60 years, with peak diagnosis at ages 30 to 40 years. The disease can present in children (see Chapter 51) as well as in patients over the age of 65 years. The hallmark features at presentation include dysphagia for liquids and solids. Patients typically have had symptoms for at least 2 to 3 years preceding the diagnosis. Dysphagia for solids occurs in about 90% of patients, and dysphagia for liquids occurs in approximately 85%. Other common features include difficulty belching, regurgitation (often undigested food is noted on one's pillow on awakening from a recumbent position), chest pain, heartburn, and weight loss (average 5–10 kg). These symptoms occur either singly or in various combinations in approximately 50% of patients.²¹ Patients very often have a sensation of retrosternal fullness radiating to the throat that is relieved by vomiting before bedtime. There may be chest pain, especially in younger patients, but attempts to differentiate these symptoms by manometric characteristics have not been forthcoming.²² Heartburn is usually associated with decreased LES pressures and resultant reflux. In patients with achalasia, heartburn may occur due to inflammatory changes in the esophageal mucosa secondary to candidiasis or irritation from pills, various ingested foods, and exposure to lactate from the bacterial formation of carbohydrates. Additional symptoms reported by patients include hiccups, possibly secondary to obstruction of the distal esophagus, and a globus sensation from esophageal distention caused by retained food. Children with achalasia may present with deficient tear production or alacrima and adrenal glucocorticoid deficiency (Allgrove syndrome). In one published report from the adult literature, 4 of 20 patients (20%) with achalasia had alacrima.

In addition to clinical symptoms, patients with achalasia carry a significant risk of developing squamous cell carcinoma of the esophagus. In a Scandinavian study, the calculated risk of developing esophageal cancer over several years was 16 times higher in achalasia patients compared to controls. In one study of over 200 patients in the United States, a similar risk was noted. Despite these findings, the cost-effectiveness of routine endoscopic screening for cancer among achalasia patients has not been established.

Diagnosis

The diagnosis of achalasia is based initially on clinical symptoms and confirmed by radiographic, endoscopic, and manometric evaluation and criteria. Many patients are treated initially for gastroesophageal reflux disease or misdiagnosed as a result of the very often slow progression of clinical symptoms. In one study, the average duration of symptoms before diagnosis was 4 to 5 years.²² Therefore, patients occasionally don't get diagnosed until later stages of the disease. In these cases, signs of achalasia can sometimes even be seen on plain chest films that demonstrate a widened mediastinum secondary to a dilated esophagus. In addition, a gastric air bubble is often absent because of incomplete relaxation of the LES.

Barium swallow is the initial radiographic examination of choice for patients with suspected achalasia. The classic finding is a dilated esophagus with a beak-like narrowing at the GEJ. This finding is over 90% accurate for the diagnosis of achalasia²³ (Fig. 33-2). The beak-like narrowing is caused by the persistent contraction of the LES, which fails to relax completely, thus decreasing the passage of contrast through the area. With primary achalasia, the narrowing at the GEJ is symmetric. One must suspect a secondary cause of achalasia (e.g., invasion of the GEJ by a tumor) if the narrowing is asymmetric. On fluoroscopy, loss of peristalsis can be noted in the smooth muscle, or lower two-thirds, segment of the esophagus. Occasionally, high-amplitude nonperistaltic contractions termed vigorous achalasia are noted.

Esophageal manometry performed with nonperfused catheter systems can confirm the initial presumptive diagnosis of achalasia made from clinical symptoms and radiographic findings.²⁴ The classic features of achalasia on conventional esophageal manometry include: (1) aperistalsis in the smooth muscle segment of the esophagus, usually accompanied by low-amplitude contractions secondary to a dilated esophagus, (2) elevation of the LES resting pressure, and (3) incomplete relaxation of the sphincter after a wet swallow (Fig. 33-3). Often, the esophageal body resting pressure may be higher than the gastric pressure, as the elevated LES pressure prevents the intraluminal pressure from relaxing to the gastric baseline. Achalasia is classified as vigorous when the amplitude of the simultaneous contractions in the esophageal body is greater than the lower limit of normal (>30 mm Hg). The vigorous form may represent an earlier presentation of achalasia when some of the intramural ganglion cells are still present, and some prior studies suggested that the response to therapy may be better in this subgroup.²⁵

High-resolution manometry (HRM) utilizes a larger number of pressure sensors spaced throughout the catheter than conventional manometry, providing enhanced details in the characterization of each swallow. Data from high-resolution esophageal manometry can be interpreted and displayed in color-coded plots called esophageal pressure tomography or Clouse Plot.²⁶ With HRM, esophageal motility disorders can be categorized according to the Chicago Classification using several calculated parameters. Under this system, achalasia is defined by impaired GEJ deglutitive relaxation (normal: eSleeve 3-second nadir <15 mm Hg) and aperistalsis. It can be further classified into three subtypes (I, II, and III), distinguished by the esophageal body intraluminal pressure response with each swallow. Type I achalasia shows no change in esophageal body pressurization with swallowing, whereas type II achalasia results in panesophageal simultaneous pressurization (>30 mm Hg). Type III (spastic) achalasia is characterized by simultaneous, abnormal, lumen-obliterating contractions or spasm.²⁷ Among the three subtypes, type II has been shown to be most responsive to therapy regardless of modality, and is an independent predictor of treatment success. On the other hand, type III achalasia has been associated with the lowest treatment response rate and is a negative predictor of treatment response.²⁷

Endoscopy

Endoscopy should be included in the evaluation of patients with a presumptive diagnosis of achalasia to examine the esophageal mucosa, GEJ, and cardia and fundus of the stomach. Inspection of the esophagus may demonstrate a dilated esophagus, whereas the esophageal mucosa may reveal signs of erythema and/or ulcerations secondary to stasis of food. Signs of esophageal candidiasis may also be present. The GEJ usually resists passage of the endoscope into the stomach. Inspection of the GEJ may reveal a tumor invading from either esophageal or gastric mucosa, indicating secondary or pseudoachalasia. The most common neoplasm is gastric adenocarcinoma. Other obstructive lesions leading to secondary achalasia should also be ruled out. Endoscopy also permits appropriate biopsy when necessary to rule out inflammatory or infectious complications or neoplasm.

Differential Diagnosis

The most important consideration in establishing the diagnosis of achalasia is differentiating primary achalasia from pseudoachalasia or secondary achalasia. The key historical points that raise suspicion for a malignant cause are short duration of symptoms (<6 months), advanced age at presentation (>60 years), and usually weight loss. Significant resistance is usually encountered when attempting to pass the endoscope through the GEJ. Esophageal manometry generally is not useful for distinguishing between primary and secondary achalasia. We recommend that patients undergo CT scan of the chest and abdomen to determine if there is an infiltrating lesion of the mediastinum or gastric cardia or fundus.

If endoscopic biopsy is unrevealing, endoscopic ultrasound with fine-needle aspiration may be helpful. Common benign conditions that mimic achalasia include (1) stricture of the distal esophagus with esophageal dilatation in scleroderma from collagen infiltration of the submucosal layers and (2) stricture of the distal esophagus from chronic gastroesophageal reflux disease resulting in dilatation of the esophagus. Fortunately, these disease entities can be differentiated from achalasia by manometry and endoscopic evaluation.

Chagas disease presents similarly to idiopathic achalasia in terms of manometric and endoscopic findings. This disease is endemic in regions of Central and South America and is caused by the parasite Trypanosoma cruzi. Evidence to raise suspicion for this diagnosis can be elicited from the history.

Treatment

The pathogenesis of achalasia involves the degeneration of ganglion cells in the myenteric plexus of the esophagus with a predilection for the abnormality to be present in the region of the LES. Treatment is targeted toward decreasing LES pressure to ease the passage of food into the stomach. There is no treatment that can restore peristalsis in the body of the esophagus. Therapy for achalasia includes medical treatment, pneumatic dilation, botulinum toxin injection, and surgery²⁸ (see Table 33-1; see also Chapters 33-35).

Medical Therapy

The goal of medical therapy is to promote relaxation of the LES through the use of appropriate pharmacologic agents. Unfortunately, none of the medications currently available provide sustained relief of symptoms. Calcium channel blockers and nitrates can relax the smooth muscles of the LES. The best results have been achieved with sublingual isosorbide dinitrate, which relaxes the LES rapidly and has sustained effects for at least 1 hour. Patients use sublingual isosorbide dinitrate just before a meal at a usual dose of 5 or 10 mg. Studies demonstrate a significant decrease in dysphagia for most patients taking this drug; however, often they cannot tolerate the headaches precipitated by the treatment. Decreasing effectiveness of the drug over time is also frequently noted.

A number of calcium channel blockers have been studied in patients with achalasia, including diltiazem, nifedipine, and verapamil. Nifedipine is the most extensively studied. A dose of 10 or 20 mg sublingually 30 minutes before eating demonstrates a decrease in both the LES pressure and symptoms of dysphagia. Oral diltiazem and verapamil have been shown to decrease LES pressure, but the symptomatic benefit is more variable. Oral verapamil can achieve adequate blood levels in achalasia despite the decrease in esophageal transit time and emptying. Unfortunately, studies have not demonstrated a consistent clinical benefit with calcium channel blockers, and their use is also limited by tachyphylaxis and other side effects, most notably headaches and hypotension.²⁹

In light of the limited benefits, medical therapy is reserved for patients who cannot or will not consider more aggressive therapy.

Dilation of the LES

Rubber bougie: Mercury-filled rubber bougies have been used to dilate the LES as a temporal measure for treating patients with achalasia, using a 50 to 60F bougie for the initial dilatation. Despite some data purporting a several-month benefit in reducing dysphagia, it is apparent that this method has limited value. Many patients report that the dysphagia is decreased, but the effect is very short-lived.

Pneumatic dilation: Pneumatic dilation of the LES is the nonsurgical treatment of choice for achalasia. Balloons of various sizes have been used, with the primary purpose of weakening the LES by tearing the muscle fibers. Older dilators were made of cloth (e.g., Brown-McHardy dilators), but these are no longer manufactured. The Rigiflex dilator is the current model. The dilator is passed over a guidewire with fluoroscopic guidance, and a Witzel balloon is passed through the endoscope and inflated under direct visualization.³⁰ Many methods have been developed for balloon dilation, with variables including balloon size (diameter range 2.5–5.0 cm), number of inflations, and amount of time the balloon remains deployed. Regardless of technique, the results are similar. A good-to-excellent result lies in the range of 60% to 85% dilation depending on the study cited. Approximately two-thirds of patients have good-to-excellent results after one or more dilations for a median follow-up of 11 years. Most prospective studies suggest that approximately 50% of patients will require a second dilation within 5 years.³¹ In direct comparison between pneumatic dilation and surgical myotomy, the success rates between the two treatment modalities appear to be similar.

Prior studies have suggested young age, postdilation LES pressure greater than 20 mm Hg, and the use of smaller balloons to be negative predictors for sustained treatment response from pneumatic dilation. On the other hand, the emptying time of barium from the esophagus after dilation appears to be the best indicator for a sustained benefit.³² If barium emptying time is prompt on examination 3 months after pneumatic dilation, most patients will experience a sustained benefit over the next several years. If pneumatic dilation is repeated for a second time and prompt emptying of barium from the esophagus is not observed, surgical correction with myotomy would be recommended (described in Chapters 34 and 35).

Although it is the current nonsurgical procedure of choice, pneumatic dilation is not performed without risk. The rate of perforation associated with this procedure ranges from 2% to 6%. Most of the perforations occur on the left side. Therefore, a modified barium swallow with Gastrografin is recommended routinely after dilation to rule out perforation. Fortunately, mortality associated with perforation is rare (<0.2%). When an obvious perforation is diagnosed, immediate surgical repair is undertaken. If Gastrografin swallow or CT scan fails to reveal an obvious perforation but the patient continues to have chest pain and fever, he or she should be kept at nothing by mouth and given a course of antibiotics, with repeat barium swallow (with or without a CT scan) to confirm resolution.

Given its success rate and less invasive nature, endoscopic pneumatic dilation has been compared to surgical myotomy for treatment outcome. The most recent prospective trial in Europe randomizing 201 achalasia patients to pneumatic dilation versus laparoscopic Hellar myotomy found no significant difference between the two groups with regard to all parameters of treatment response, including symptoms, LES pressure, esophageal emptying, quality of life, and esophageal acid exposure.³³ As patients in this study were only followed for a mean of 43 months, further studies are needed to compare the longer-term outcomes between the two therapies.

Botulinum (Botox) Injection

Botulinum toxin inhibits release of acetylcholine from neurons. It has been theorized that endoscopic injection of botulinum toxin in the anatomic area of the LES would inhibit the release of acetylcholine in neurons that play a role in LES smooth muscle tone, thereby decreasing LES pressure. Several small studies have demonstrated the benefit of endoscopic botulinum toxin injection. Unfortunately, although these initial studies demonstrated up to 90% immediate symptomatic relief, the benefit was relatively short-lived. Subsequent studies showed the median duration of benefit to be only about 6 months. Approximately two-thirds of patients were asymptomatic at 6 months, with the remission rate further decreasing to 45% at 1 year. Botulinum toxin injection has also been found to be significantly more effective in patients over age 50 (80% vs. 40%).²⁵ Even if a sustained result is not achieved, no data have demonstrated that toxin injection results in increased morbidity or worse outcomes if pneumatic dilation or surgery should follow. The drawback to using toxin injection is the high cost (approximately $300 for a vial of botulinum toxin). The advantage is its excellent safety profile. Fewer than 25% of patients receiving botulinum toxin injection experience transient mild chest pain, and fewer than 5% experience reflux symptoms.

Various treatments are available for achalasia. Medical therapy with nitrate and calcium channel blockers has a short-term, limited role. The effect of botulinum toxin injection, although safe, is relatively short-lived and may be most useful for older patients (age 50 and older), in whom the risk of pneumatic dilation or surgery is escalated. Pneumatic dilation for most patients is the first-line nonsurgical therapy, capable of yielding a sustainable benefit in 70% of patients. When dilation fails, surgical myotomy is the treatment of choice.

Diffuse Esophageal Spasm

DES was first described by William Osler in 1892 in a hypochondriacal patient with chest pain. Today, DES is considered part of the spectrum of esophageal motility disorders, and it is diagnosed by esophageal manometry in patients who present with symptoms of dysphagia, chest pain, or both.

Historically, there are three requirements to make the diagnosis of DES: (1) dysphagia and/or chest pain, (2) radiographic study demonstrating tertiary or spontaneous contractions resulting in the classic radiographic finding of the “corkscrew esophagus” or “rosary bead esophagus” (Fig. 33-4), and (3) esophageal manometry study demonstrating spontaneous, repetitive, and prolonged-duration contractions (Fig. 33-5). However, more recent esophageal manometry studies in patients with DES have identified additional distinguishing criteria.³⁴ Patients who present with dysphagia as the predominant symptom tend to have lower-amplitude contractions than those who present with chest pain. Despite the increased contraction amplitude, DES patients with chest pain rarely have sustained pressure greater than 180 mm Hg. The diagnostic criteria on esophageal manometry include simultaneous contractions of at least 30 mm Hg for more than 20% of measured wet swallows. In addition, approximately 30% to 40% of patients have abnormalities of the LES that consist of either high resting pressure or incomplete relaxation after a wet swallow. Radiographic studies also may be entirely normal in patients who have dysphagia as their predominant symptom. In fact, measurement of bolus transit using electrical impedance as a part of the manometry catheter has demonstrated abnormal bolus transit even with normal radiographic examination. Patients with chest pain and higher-amplitude spontaneous contractions usually have normal bolus transit time. The pathophysiology of this disorder is still not fully elucidated, but there is evidence for a defect in the synthesis of NO (see above). On HRM, DES patients are found to have simultaneous contractions and pressurization of the distal esophagus with usually normal relaxation of the LES. They usually have a rapidly propagated pressurization of the esophagus, with a contractile front velocity >8 cm/s in at least 20% of swallows per Chicago Classification.

Nutcracker Esophagus

Nutcracker esophagus is the term ascribed to a state of high-amplitude (>180 mm Hg) peristaltic contractions in the distal esophagus associated with dysphagia and/or chest pain (Fig. 33-6). It is seen most commonly in women and carries a higher prevalence than DES in the general population. It is often part of the spectrum of irritable bowel syndrome and is associated with increased visceral sensitivity. Patterns of DES or nutcracker esophagus have been observed during periods of chest pain in patients undergoing prolonged esophageal manometric monitoring. A radiographic study obtained is frequently normal, and because contractions are peristaltic, impedance studies also demonstrate normal bolus transit. In the Chicago Classification for HRM, nutcracker esophagus or hypertensive peristalsis is defined by a contractile front velocity <8 cm/s in more than 90% of swallows and a mean distal contractile integral (a parameter integrating the length, contraction amplitude, and duration of a contraction) of >5000 mm Hg-s-cm.

Nutcracker esophagus may also be associated with a hypertensive or poorly relaxing LES. The pathophysiology is still not well clarified, but, similar to other hypercontractile disorders of the esophagus, changes in NO synthesis and degradation may be involved (see above).

Hypertensive LES

Hypertensive LES, defined as a basal LES pressure of greater than 45 mm Hg, is found often in patients who present with dysphagia. It is associated with high-amplitude peristaltic contractions in the distal esophagus in approximately 50% of the patients who present with chest pain (Fig. 33-7). Hypertensive LES also may be associated with incomplete relaxation of the LES after a wet swallow, which may be present in DES as well as in high-amplitude contraction abnormalities. As one can surmise from this discussion, there is an entire spectrum of abnormal motility patterns with various combinations that may include one, a few, or all the abnormalities described earlier in patients presenting with chest pain and or dysphagia (Table 33-2).

Since the pathophysiology of the nonspecific disorders described earlier is poorly understood, there is significant treatment overlap for DES, nutcracker esophagus, and hypertensive sphincter disorders (Table 33-3). Numerous medications have been used to decrease smooth muscle contractility or modify visceral hypersensitivity, but most of the medications have not been subjected to large prospective, randomized, double-blind, controlled trials. Calcium channel blocking agents such as diltiazem have been shown to relieve chest pain compared with placebo in nutcracker esophagus. Effective doses lie in the range of 60 to 90 mg four times daily, but more recently, long-acting cardizem given in doses of 240 mg once daily is often recommended. If the individual has chest pain or dysphagia during or after eating, a 10-mg dose of a sublingual nitrate (e.g., isosorbide dinitrate or nifedipine) has been used with relief of dysphagia and, in some cases, chest pain. However, there are no controlled trials for this drug. For patients who have continued chest pain despite the use of calcium channel blocking agents or nitrates, some have benefited from tricyclic antidepressants (e.g., trazodone in a dose range of 75–150 mg/day and imipramine at 50 mg/day), which modify visceral hypersensitivity rather than alter esophageal dysmotility. More recently, several uncontrolled trials have demonstrated a good effect with botulinum toxin injections (100 units injected circumferentially at the GEJ) in reducing chest pain in patients with nonspecific esophageal motility disorders.^35,36 Improvement was observed in 70% of patients, with approximately 50% of patients having complete relief of chest pain and a sustained benefit of up to 7 months.

Other treatments with reported benefit in single studies include hot water taken with meals, which improved esophageal clearance and decreased the amplitude and duration of contractions, with symptom improvement in almost 60% of patients.³⁷ In another small series, a solution of peppermint oil, which is a known smooth muscle relaxant, improved manometric abnormalities in DES, although only two patients experienced improvement in chest pain. Sildenafil (50 mg/day) provided symptomatic relief in a small group of patients with DES and nutcracker esophagus. Although pneumatic dilation has been performed for patients with these disorders, there are no controlled trials, and the risk of perforation (up to 5%) may outweigh the benefit. The use of extended myotomy for chest pain for these nonspecific disorders is not indicated and may result in untoward complications and symptoms, such as postoperative dysphagia and reflux.

No one medical therapy has been shown to be substantially beneficial for the majority of patients with these motility disorders. Treatment strategies should, therefore, be individualized with the use of specific medication or combination of medications that may work best in resolving symptoms.

Opposite to the nonspecific motility disorders described above with hypercontractile esophageal body and/or LES is a group of hypocontracting disorders that include IEM and hypotensive LES. Patients with IEM typically present with dysphagia without chest pain. On esophageal manometry, more than 30% of swallows are associated with nontransmitted or low-amplitude peristaltic contractions (<30 mm Hg) in the distal esophagus (Fig. 33-8). This esophageal disorder may be a result of gastroesophageal reflux disease, but it is also present patients with no appreciable reflux disease. Radiographic studies are usually normal, but impedance measurements during esophageal manometry often reveal incomplete bolus transit. Treatment of underlying reflux with acid suppression therapy has resulted in improvement in symptoms and manometric findings in some IEM patients. Fundoplication in IEM patients with reflux symptoms has been shown to be safe with regard to risk of postoperative dysphagia and may lead to improvement in esophageal contractions on manometry.^38,39 A few agents such as bethanechol and buspirone have also been shown to increase esophageal body and LES contractions and decrease dysphagia symptoms in IEM patients in small studies. These effects, however, need to be further investigated and validated. Prokinetic agents, such as metoclopramide, may also be useful but adequate treatment response has not been demonstrated in a clinical study.

Primary esophageal motility disorders may result from esophageal body and LES hypocontraction, hypercontraction, or mixed response. Depending on the underlying pathophysiology and esophageal function, options for treatment may include conservative management, pharmacologic treatment, endoscopic therapy, and surgery (see Chapters 34-36). Further development of more specific medical therapies in the future will depend on a more profound understanding of the pathogenesis of these disorders.

The spectrum of esophageal motility disorders includes those that are surgically manageable and those for which there are no current surgical solutions. A comprehensive multidisciplinary approach to evaluation is required prior to surgical manipulation, despite the insistence of some patients that a surgical “cure” be attempted. Frankly, the differential diagnoses described eloquently in this chapter should prompt every surgeon to insist on manometric evaluation of every patient before undertaking any surgery for benign motility disorders or reflux.