Adult Chest Surgery

Chapter 24. Overview 

 

The primary esophageal motility disorders are characterized by abnormalities that interfere with swallowing and the transit of food through the esophagus, producing symptoms of dysphagia and chest pain. The disorder is considered primary 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). One classic disorder is achalasia, which is characterized by failure of the lower esophageal sphincter to relax. There are several other nonspecific esophageal motility disorders, including diffuse esophageal spasm (DES), nutcracker esophagus, hypercontracting esophagus, and other abnormalities of the lower esophageal sphincter. Whether these represent true disorders, a continuum of disease, or merely abnormal motility patterns that are associated with but are not the physiologic causes of symptoms remains a controversy (Table 24-1).

Table 24-1. Classification of Primary Esophageal Motility Abnormalities

Diagnosis

Motility Findings

Achalasia

Decreased and simultaneous contractions in distal esophagus

 

Incomplete LES relaxation (residual pressure >8 mm Hg)

 

Elevated resting LES pressure (>45 mm Hg)

 

Increased baseline esophageal pressure

Abnormal motility patterns (nonspecific esophageal dysmotility)

 

  Diffuse esophageal spasm

Simultaneous contractions (>20% wet swallows)

 

Intermittent peristalsis

 

Repetitive contractions (>3 peaks)

 

Prolonged duration contractions (6 s)

  Hypercontracting esophagus

Increased distal peristaltic amplitude (mean value >180 mm Hg)

     Hypertensive peristalsis (nutcracker esophagus)

Increased distal peristaltic duration (mean value >6 s)

     Hypertensive LES

Resting LES pressure >45 mm Hg

 

Associated with incomplete relaxation (residual pressure >8 mm Hg)

     Hypocontracting esophagus

Increased nontransmitted peristalsis (mean value  30%)

        Ineffective motility

Low distal peristaltic amplitude (<30 mm Hg)

        Hypotensive LES

Resting LES pressure < 10 mm Hg

     Miscellaneous

Retrograde contractions

 

Triple peaked contractions

 

Isolated incomplete LES relaxation (8 mm Hg)

 

LES = lower esophageal sphincter.

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 causes of most motility abnormalities are 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.

PATHOPHYSIOLOGY

Normal Esophagus

The normal human esophagus has two sphincters that control the passage of food and prevent gastric acid reflux from the stomach. These are the upper esophageal sphincter (UES) and the lower esophageal sphincter (LES). The LES is adversely affected in many of the primary esophageal motility disorders. The normal LES is located in the distal esophagus just above the gastroesophageal (GE) junction. It has a resting pressure of 15–25 mm Hg, which is sufficient to prevent gastroesophageal reflux. The interior lumen of the esophagus is composed of layers of motor, mixed, and smooth muscle that are innervated and become active during peristalsis. A normal swallow induces a peristaltic wave that moves the food through the entire esophagus, terminating at the GEJ. Just before peristalsis occurs, the LES undergoes a brief period of relaxation that 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.

Neuromuscular Physiology

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.The excitatory innervation is mediated predominantly by acetylcholine, which acts at the muscarinic receptors, whereas inhibition involves nitric oxide (NO) synthesis.2

The inhibitory role of NO is ubiquitous in the gastrointestinal tract.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.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.NO also plays a critical role in relaxation of the LES,although inhibitory neuropeptides, particularly vasoactive intestinal peptide, also have been implicated in LES relaxation.5

Neuropathic Primary Motor Disorders

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.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. 24-1).

Figure 24-1.

 

Normal: After swallow, food bolus is transmitted through the esophagus by waves of peristaltic contractions; the LES undergoes a brief period of relaxation just after the swallow to allow the bolus to pass into stomach before returning to normal resting pressure (15–25 mm Hg). Nutcracker esophagus: Increased distal peristaltic amplitude (mean value >180 mm Hg), increased distal peristaltic duration (mean value >6 s), normal LES. Diffuse esophageal spasm: Simultaneous contractions, repetitive contractions (>3 peaks), prolonged duration of contractions (6 s), intermittent peristalsis, and prolonged LES relaxation. Achalasia: Loss of peristaltic activity in the distal esophagus with decreased simultaneous contractions, incomplete LES relaxation (residual pressure >8 mm Hg), elevated resting LES pressure (>45 mm Hg), increased baseline esophageal pressure.

This interpretation is supported by case reports of apparent clinical transition from nutcracker esophagus to diffuse spasm8,9 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 muscle of achalasia patients indicates a significant reduction of such neurons relative to cancer control individuals.15Similarly, immunohistochemical staining demonstrates an absence of nNOS in the LES.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 muscle 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, although side effects are of concern.18 Botulinum toxin acts by inhibiting autonomic acetylcholine release. Its use for the treatment of achalasia is reviewed by Brisinda and colleagues.19 Generally, botulinum toxin reduces LES pressure and associated symptoms in these patients. It is less effective than dilation but also less risky.

ACHALASIA

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 relaxes incompletely after a swallow, and there is loss of peristalsis in the body of the esophagus, predominantly in the smooth muscle segment, or lower two-thirds of the esophagus.

Clinical Spectrum

The disease affects men and women equally. The diagnosis usually is made between the ages of 25 and 60 years, with peak diagnosis at ages 30–40 years. The disease can present in children (see Chap. 38), however, as well as in patients older than age 65. The hallmark features at presentation include dysphagia for liquids and solids. Patients typically have had symptoms for 2–3 years preceding the diagnosis. Dysphagia for solids occurs in approximately 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.20 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.21 Heartburn, ironically, is associated more often with decreased LES pressures. One must be ever vigilant regarding the etiology of heartburn in patients with achalasia because inflammatory changes in the esophageal mucosa at times may be secondary to Candidaesophagitis. Furthermore, heartburn may be the result of direct irritation of the esophageal mucosa 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's syndrome). In one published report from the adult literature, 4 of 20 patients (20%) with achalasia had alacrima. Finally, patients with achalasia have a significant risk of developing squamous cell esophageal cancer.

A Scandinavian study calculated the risk of developing esophageal cancer over several years to be 16 times higher in patients with achalasia than in control individuals. In one study of over 200 patients in the United States, a similar risk was noted. However, the cost-effectiveness of routine endoscopic screening 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 4–5 years.22 Occasionally, a diagnosis of achalasia is made on the basis of plain chest films that demonstrate a widened mediastinum secondary to a dilated esophagus. Additionally, a gastric air bubble is often absent because of incomplete relaxation of the LES.

Barium enema is the initial examination for the patient with suspected achalasia. The classic finding is a dilated esophagus with a beaklike narrowing at the GEJ. This finding is over 90% accurate for the diagnosis of achalasia23 (Fig. 24-2). The beaklike narrowing is caused by the persistent state of contraction of the LES, which fails to relax completely. 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 tumor) if the narrowing is asymmetric. On fluoroscopy, loss of peristalsis is noted in the smooth muscle, or lower two-thirds segment of the esophagus. Occasionally, high-amplitude nonperistaltic contractions termed vigorous achalasia are noted.

Figure 24-2.

 

Classic findings in achalasia revealed on barium swallow. Dilatation of the esophagus and "bird's beak" at the GEJ. (Courtesy of John M. Braver, M.D.)

Esophageal Motility Study (Manometry)

Esophageal manometry performed currently with nonperfused catheter systems can confirm the initial presumptive diagnosis of achalasia made from clinical symptoms and radiographic findings.24 The classic picture of achalasia on esophageal manometry includes the following features: (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, (3) incomplete relaxation of the sphincter after a wet swallow, and finally, (4) a resting pressure in the body of the esophagus that may be higher than the gastric pressure (Fig. 24-3). (Normally, after a wet swallow, the LES will relax to or very close to the gastric pressure. However, because of loss of inhibitory neurons, the LES pressure is usually elevated and does not relax to the gastric pressure baseline.) The term vigorous achalasia is applied when the amplitude of the simultaneous contractions in the body of the esophagus are in the normal to increased range. This entity may represent an earlier presentation of achalasia, wherein some of the intramural ganglion cells are still present. However, there is little evidence that the course and response to treatment of classic versus vigorous achalasia are significantly different.

Figure 24-3.

 

Classic features of achalasia revealed on esophageal manometry (LES = lower esophageal sphincter; S = swallow).

Endoscopy

Endoscopy should be included in the evaluation of patients with a presumptive diagnosis of achalasia. It is important to include evaluation of the esophageal mucosa, GEJ, and cardia and fundus of the stomach. Inspection of the esophagus will demonstrate a dilated esophagus, and evaluation of the esophageal mucosa may reveal esophageal erythema and/or ulcerations secondary to stasis of food, as well as secondary involvement from candidiasis. The GEJ usually resists passage of the endoscope into the stomach. Inspection of the GEJ may reveal a tumor invading either from esophageal or gastric mucosa, resulting in a secondary or pseudoachalasia presentation. The most common neoplasm is gastric adenocarcinoma. Endoscopy permits appropriate biopsy when necessary to rule out either 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 caused by malignancy. 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.

The one disorder that presents similarly to idiopathic achalasia in terms of manometric and endoscopic findings is Chagas' disease. 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 surgery25 (see Table 24-1; see also Chaps. 26, 27, 28, and 29).

MEDICAL THERAPY

The goal of medical therapy is to effect 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.26 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 first-line treatment in patients with achalasia. A 50–60F bougie is used for the initial dilatation. Despite some data purporting a several-month benefit in reducing dysphagia with bougienage, however, it is apparent that this method has limited value. Many patients report that although the dysphagia is decreased, 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.27 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 60–85% 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.28

One of the dilemmas of attempting to compare the few small prospective studies with the more numerous large retrospective studies is that no author has used an appropriate method to determine the factors that might predict long-term response. Among the variables that have been evaluated (albeit not systematically) are age, size of balloon, postdilation effect, and LES pressure. The negative predictors include young age, postdilation LES pressure more than 20 mm Hg, and possibly, the use of smaller balloons. More recently, the use of emptying time of barium from the esophagus after dilation seems to be the best indicator that the patient will experience a sustained benefit from pneumatic dilation.29

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 is the recommended procedure (described in Chaps. 26 and 27).

Although it is the current noninvasive 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, the patient 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.

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 will 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 have demonstrated the median duration of benefit to be only approximately 6 months. Approximately two-thirds of patients remained in remission at 6 months, and of this group, two-thirds remained in remission at 1 year. Therefore, only 45% of patients were asymptomatic at 1 year. It also has been noted that botulinum toxin injection is significantly more effective in patients over age 50 (80% versus 40%).30 Therefore, for young patients, we recommend pneumatic dilatation, but for patients over age 60, in whom surgery may present a significant risk, botulinum toxin injection is definitely worth attempting. 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.

NONSPECIFIC ESOPHAGEAL MOTILITY DISORDERS

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. 24-4), and (3) esophageal manometry study demonstrating spontaneous, repetitive, and prolonged-duration contractions (Fig. 24-5).

Figure 24-4.

 

On barium swallow, spontaneous and tertiary contractions yield a "corkscrew esophagus" appearance in diffuse esophageal spasm. (Courtesy of John M. Braver, M.D.)

 

Figure 24-5.

 

Esophageal manometric study demonstrating spontaneous, repetitive, and prolonged-duration contractions in diffuse esophageal spasm (LES = lower esophageal sphincter; S = swallow).

However, more recent esophageal manometry studies in patients with DES have identified additional distinguishing criteria.31 Patients who present with dysphagia as the predominant symptom have lower-amplitude contractions than those who present with chest pain, but those with chest pain rarely have sustained pressures greater than 180 mm Hg. More important, the term diffuse esophageal spasm is really a misnomer because very rarely does one see simultaneous contractions in the striated portion of the esophagus. Furthermore, the threshold for diagnosis requires simultaneous contractions of more than 30 mm Hg for 20% or more of the contractions. Additionally, approximately 30–40% 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. This observation is demonstrated quite nicely using electrical impedance as an integral part of the manometry catheter, which may demonstrate abnormal bolus transit even though the radiographic examination is normal. 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).

Nutcracker Esophagus

Nutcracker esophagus is the term ascribed to a state of high-amplitude (>180 mm Hg) peristaltic contractions in the distal half of the esophagus associated with dysphagia and often chest pain (Fig. 24-6). However, not all patients with nutcracker esophagus have chest pain. It is seen most commonly in women and is more common than DES. 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 is frequently normal, and because contractions are peristaltic, impedance studies also demonstrate normal bolus transit.

Figure 24-6.

 

Nutcracker esophagus yields a state of high-amplitude (>180 mm Hg) peristaltic contractions in the distal half of the esophagus (LES = lower esophageal sphincter; S = swallow).

Nutcracker esophagus also may be associated with a hypertensive or poorly relaxing LES. The pathophysiology is still not well-clarified, but 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. Approximately 50% of the time this motility abnormality is associated with high-amplitude peristaltic contractions in the distal esophagus in patients who present with chest pain (Fig. 24-7).

Figure 24-7.

 

Hypertensive LES, defined as a basal LES pressure of more than 45 mm Hg, is found often in patients who present with dysphagia.

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 24-2).

Table 24-2. Management of Achalasia

 
 

MEDICAL MANAGEMENT OF NONSPECIFIC ESOPHAGEAL DYSMOTILITY DISORDERS

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 24-3). 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 60–90 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., Isordil 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.

Table 24-3. Possible Therapies for Diffuse Esophageal Spasm and Hypercontracting Motility Abnormalities

Limited clinical trials

  Calcium channel blockers (e.g., ditiazem)

  Antidepressants (e.g., trazodone, imipramine)

Case studies and clinical observations

  Nitrates (e.g., nitroglycerine, isosorbide dinitrate)

  Anticholinergic drugs (e.g., dicyclomine)

  Bougie dilation (17- to 20-mm diameter)

  Botulinum toxin injection

  Hot water, peppermint oil

Minimal clinical support and greater potential for adverse effects

  Pneumatic dilatation

  Esophagomyotomy

 

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 altering esophageal dysmotility. More recently, several uncontrolled trials have demonstrated a good effect with botulinum toxin injections (100 units injected circumferentially at the GEJ) in terms of reducing chest pain in patients with nonspecific esophageal motility disorders.32,33 Improvement was observed in 70% of patients, with approximately 50% of patients having complete relief of chest pain with a sustained benefit of up to 7 months.

Other treatments of 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.34 In another small series, a solution of peppermint oil improved manometric abnormalities in DES, but only two patients had improvement in chest pain with this known smooth muscle relaxant. 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%) often 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 can be identified that is substantially beneficial for the majority of patients with these motility disorders. One must individualize the specific medication or combination of medications that works best in resolving chest pain and/or dysphagia.

Hypocontracting Esophagus: Ineffective Motility

A final intriguing group of patients that presents with dysphagia without chest pain may have ineffective motility. On esophageal manometry, more than 30% of swallows are associated with nontransmitted peristalsis and low-amplitude peristaltic contractions (<30 mm Hg) in the distal esophagus (Fig. 24-8). This esophageal disorder may be a result of gastroesophageal reflux disease, but there are patients with no reflux disease who present with dysphagia and have this manometric abnormality. Radiographic studies are usually normal, but impedance determinations during esophageal manometry reveal incomplete bolus transit. Unfortunately, there are no studies that have determined adequate response to medical therapy, such as metoclopramide as a prokinetic agent.

Figure 24-8.

 

Impedance determinations during esophageal manometry reveal incomplete bolus transit in patients with hypocontracting esophagus.

SUMMARY

The pathophysiology of the primary esophageal motility disorders produces a mixed and confusing scenario. Options for treatment include conservative management, medical treatment with drugs and other agents, and surgery (see Chaps. 25, 26, 27, 28, and 29). It is quite apparent from the preceding discussion that until we develop a more profound understanding of the pathogenesis of these disorders, specific medical therapies will be expectant.

EDITOR'S COMMENT

One major take home lesson about esophageal motility disorders is the importance of distinguishing between surgical and non-surgical diseases. Achalasia is best managed surgically in the era of laparoscopic Heller myotomy (Chap. 26). This minimally invasive approach is the most effective modality for treating achalasia and is quite safe in the hands of expert practitioners, even in the older population.

–RB

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