Health Questions and Answers

Achalasia

Define achalasia.
The term achalasia (Greek = lack of relaxation) describes the pathophysiologic hallmark of the disease: failure of the lower esophageal sphincter (LES) to relax. This term has replaced the previous designation cardiospasm, which implies an exaggerated state of contraction. The second cardinal feature is aperistalsis of the body of the esophagus. However, LES dysfunction is more important because gravity appears to be able to compensate for the lack of pumping ability in the body of the esophagus, in most cases.  

How common is achalasia?
Achalasia is a relatively uncommon disorder, with prevalence estimated at about 8 cases per 10,000 and an incidence rate approximately 0.5 new cases per year per 100,000. The incidence is increased with age, particularly after the seventh decade but equal between men and women.

Define vigorous achalasia.
The term vigorous is applied to cases of achalasia in which prominent contractions can be noticed in the body of the esophagus, either on radiography or by manometry. These contractions are simultaneous and therefore fulfill the manometric definition of aperistalsis required for the diagnosis of achalasia. They should be distinguished from isobaric waves, which can be seen in patients with achalasia and represent bolus-induced passive fluctuations in pressure within the common cavity of the dilated esophagus. Vigorous achalasia may represent an early stage of the disease.

What is the relationship between diffuse esophageal spasm (DES) and achalasia?
DES may be regarded as a “cousin” of achalasia. The primary manometric distinction between DES and vigorous achalasia is the presence of at least some normal peristalsis in the former. LES dysfunction is seen often in DES but to a lesser degree than in achalasia. Some evidence suggests that in a small subset (about 5% or less) of patients, DES may evolve into classic achalasia.

What is the major pathologic lesion in achalasia? How does it produce the disease?
Although other lesions have been described, including degeneration of the vagus nerve and changes in its dorsal motor nucleus, the myenteric plexus appears to be the major site of the disease. The characteristic finding is loss of ganglion cells, which appears to be selective for inhibitory neurons (those producing nitric oxide and/or vasoactive intestinal peptide [VIP]) with relative sparing of the cholinergic (stimulatory) nerves. Thus, the normal balance of excitatory and inhibitory neural input to smooth muscle is upset. The loss of inhibition, coupled with a relative preservation of the excitatory stimulus, may be responsible for the LES abnormalities. An inflammatory infiltrate, characteristically mononuclear, is also seen commonly in the myenteric plexus. It is speculated that unchecked inflammation at this site leads to neuronal destruction and, eventually, to the clinical manifestations of achalasia.

What is the suspected cause of achalasia?
Earlier studies raised the possibility of a virus, particularly one belonging to the herpes family (because of the predilection of herpes viruses for squamous mucosa) and measles virus. A study with DNA hybridization techniques found evidence of the herpes virus in some myotomy specimens from achalasia patients. However, subsequent investigations, using the polymerase chain reaction to detect different markers, found no evidence for any known viral cause. More recently, attention has focused on a possible autoimmune basis, with reports of circulating antineural antibodies. These suspicions are given further credence by the finding that achalasia may be particularly associated with certain class II human leukocyte antigens (HLAs), such as DQB1, DQA1, and DQw1. Neurodegeneration is also a possible cause. It has been speculated that the possible site of primary involvement in achalasia is in the dorsal motor nucleus and the vagus nerve and that the myenteric abnormalities are secondary. Nevertheless, the cause of achalasia remains a mystery.

Is achalasia an acquired or congenital disease?

Most cases of achalasia are acquired. Achalasia is uncommon before age 25, with a clear-cut age-related increase thereafter. Most commonly the disease occurs in middle adult life (ages 30-60) and affects both sexes and all races nearly equally. Rare cases of familial achalasia have been described. Occasionally, achalasia may be found as part of a congenital syndrome, such as triple-A syndrome (achalasia, alacrima, and resistance to adrenocorticotropic hormone), also called Allgrove’s syndrome. The gene mutated in triple A syndrome has now been identified and encodes a protein called ALADIN (also called Adracalin or AAAS). Although the function of this protein is not known, it localizes to nuclear pore complexes (NPCs), large multiprotein assemblies that are the sole sites of nucleocytoplasmic transport, and may play a role in the differentiation and maintenance of the involved issues.

Describe the dysphagia associated with achalasia.
In general, the dysphagia due to motor disorder of the esophagus occurs with solids as well as liquids. However, many patients with achalasia complain predominately, if not exclusively, of solid food dysphagia. The converse, dysphagia for liquids only, is almost never seen. Patients often localize the dysphagia to the region of the LES. Regurgitation kf food, either active or induced by the recumbent position or bending, should raise the suspicion of achalasia, particularly if it occurs early in the course of symptoms. Patients often complain of waking up in the mornings with remnants of the previous night’s supper in their mouth.

What other symptoms may be associated with achalasia?
Weight loss is common but not invariable. Pulmonary symptoms (e.g., pneumonia, lung abscesses from aspiration) are much less common than in the past because of earlier diagnosis and treatment. Two surprisingly common symptoms may lead to the wrong diagnosis: chest pain and heartburn (seen in up to 50% and 25% of patients, respectively). At least two different types of chest pain are experienced by patients with achalasia. The obstructive type is associated with swallowing a food bolus and resolves with passage of food into the stomach. The second type is unrelated to eating and is more often seen in patients with vigorous achalasia. However, it is not necessarily related to esophageal contractions and may reflect abnormalities in the sensory pathway, similar to those in patients with plastic motility disorders. Heartburn is indistinguishable from that in patients with gastroesophageal reflux disease (GERD), including response to antacids. In fact, some patients with achalasia have been mistakenly diagnosed with GERD for several years. Whether heartburn results from lactic acid production due to bacterial breakdown of retained food or true acid reflux is not clear.

Does achalasia involve any other parts of the gastrointestinal tract?
Yes. The involvement of stomach and pyloric sphincter has been reported. Some studies also showed that a considerable number of patients with achalasia had dysfunction of the sphincter of Oddi.

What is the best way to diagnose achalasia?
Achalasia should be considered in all patients with a history of dysphagia for both solids and liquids. A definitive diagnosis requires two steps:

  1. confirmation of the underlying pathophysiology (best done by manometry)
  2. exclusion of cancer at the gastroesophageal (GE) junction, which can produce a similar picture (pseudo-achalasia); this requires endoscopy with particular emphasis on the retroflexed view.

What are the characteristic radiologic features of achalasia?
An atonic and dilated body of the esophagus is often seen; however, occasional early cases present with a normal-sized esophagus and prominent (nonperistaltic) contractions. The “sigmoid esophagus” is an elongated, dilated organ seen in patients with long-standing disease. Epiphrenic diverticula may accompany this picture. In most cases of achalasia, the GE junction is narrowed smoothly, giving rise to the classic “bird’s beak” and allowing only very small amounts of contrast to pass through to the stomach. Previous dilatation or surgery may alter this typical appearance. In early achalasia, these classic features may also be absent in about a third of patients.

What is required for the manometric diagnosis of achalasia?
Two manometric features:

  1. Lack of peristalsis in the body (the smooth muscle portion) of the esophagus
  2. Abnormal or absent LES relaxation in response to swallowing (with normal relaxation being more than 90%)

What is the most important potential pitfall in the manometric diagnosis of achalasia?
An occasional patient with otherwise typical features of achalasia may demonstrate complete or near-complete relaxation of the LES, but this appearance may be artifactual due to relative movement between the side-hole/point sensor in the manometry catheter and the LES. This problem can be avoided by the use of a Dent sleeve catheter, which incorporates a 6-cm long sensor device for measurement of LES pressures.

Describe the typical endoscopic features of achalasia.
Endoscopy may be reported as normal in a surprising number of patients in whom achalasia is not suspected before the procedure. In more obvious cases, esophageal dilation, varying amounts of food material or secretions, and either a lack of contractions or multiple simultaneous contractions are seen. The esophageal mucosa may demonstrate various changes, from mild erythema to frank erosions or even ulceration. Candidiasis and retained medications may cause some of these lesions; in other cases, stasis of retained material may give rise to an edematous and nodular mucosa.
A tight but relatively elastic feel as the endoscope passes (or “pops”) through the GE junction is characteristic of achalasia but may be easily overlooked if the diagnosis is not specifically entertained. The inability to pass the scope, despite moderate amounts of pressure, is highly suggestive of an inflammatory or neoplastic structure. Of interest, resistance may also be encountered at the pyloric outlet in patients with achalasia, giving rise to the “difficult pylorus” sign.

What is the difference between secondary achalasia and pseudo-achalasia?
Although achalasia is most often idiopathic, it has been described in association with various diseases, such as cancer, Chagas’ disease, amyloidosis and other infiltrative disorders, mixed connective tissue disorders, endocrine disorders, and intestinal pseudo-obstruction. Such cases are called secondary achalasia. Pseudo-achalasia refers to an achalasia-like syndrome that is produced by infiltrating cancer of the GE junction. Finally, in rare patients (typically those with small-cell lung cancer), a paraneoplastic noninfiltrative syndrome can cause the typical symptoms of achalasia.

How can pseudo-achalasia be diagnosed?
A high index of suspicion should be maintained in patients presenting with what looks like achalasia but with marked weight loss and short duration of symptoms. However, these and other features, such as the age of the patient, are not highly specific. Endoscopy remains the crucial diagnostic test because the clinical history, radiographic appearance of barium study, and even manometric analysis may not distinguish pseudo-achalasia from the idiopathic form. Failure to pass the endoscope into the stomach almost invariably rules out true achalasia. A careful examination of the GE region, including a retroflexed view from the stomach, is absolutely mandatory, and biopsies should be taken of any suspicious area or lesion. Even so, the sensitivity of this method in excluding underlying cancer is reported to be around 80% or less. Endoscopic ultrasound (EUS) may provide additional value, but this has yet to be convincingly demonstrated.

Is achalasia a premalignant condition?
Yes. Esophageal cancer may arise in achalasia, thought to result from long-standing stasis and secondary changes in the epithelium. When cancer develops, it is usually of the squamous variety and arises in the dilated middle part of the esophagus, rendering it relatively silent until a late stage. The overall prevalence of esophageal cancer in achalasia is about 3%, with an incidence of about 197 per 100,000 per year. This incidence significantly increases after 15 years of achalasia. A large population-based study demonstrated a 16-fold increase in cancer risk during years 2-24 after the diagnosis of achalasia. The risk of cancer in most patients with adequate treatment remains very small.

Should patients with achalasia undergo periodic endoscopic surveillance?
Yes and no. A surveillance strategy would require 406 endoscopies to detect one cancer in men and 2220 endoscopies to detect one cancer in women. The American Society of Gastrointestinal Endoscopy recommends the following guidelines for surveillance:

  • for the rare untreated patient, periodic endoscopic surveillance after 15 years is justified
  • if effective dilation or myotomy was performed early in the course of the disease, there may be no need for endoscopic surveillance
  • patients who are treated later in the course of the disease may appear to be at increased risk for malignancy, and the role of endoscopic surveillance has not been determined.

What treatment options are available for achalasia? Describe their rationale.
All of the therapeutic options available for achalasia are palliative. Their goal is to decrease the resistance to bolus transit created by dysfunctional LES. Traditional pharmacologic therapy does so by inducing smooth muscle relaxation. Botulinum toxin injections block the excitatory neural inputs to the LES by inhibiting the release of acetylcholine from nerve endings. The theoretical rationale for balloon dilation is to achieve a partial tear of the LES muscle, but this option is somewhat speculative because the few animal studies that evaluate this method have shown no histologic evidence of damage, despite marked reductions in LES pressure. Surgical myotomy has the most straightforward rationale of all treatment options but comes at a price.

What does Viagra have to do with achalasia?
Sildenafil (Viagra) blocks phosphodiesterase type 5 (the enzyme responsible for degradation of cyclic guanosine monophosphate [cGMP]), which results in increased cGMP levels within smooth muscle and consequent relaxation. It is effective in short-term reduction of LES pressures in patients with achalasia. A recent small number, randomized, double-blind clinical trial showed that sildenafil at 50 mg significantly decreased the LES pressure tone, residual pressure in patients with primary achalasia compared to placebo group. The effect lasted less than 60 minutes. However, sildenafil had no effect of improving propagation of pressure waves in esophageal body.

What is the single most permanent treatment of achalasia?
The answer is clearly surgery, with short-term (5 years or less) efficacy around 90%. Long-term results are less positive, with only about two thirds of patients reporting good-to-excellent outcomes. This is probably due, in large part, to the sequelae of the reflux disease that invariably accompanies successful myotomy.

What is the major problem with surgery?
In the past, surgery was associated with considerable morbidity, whether done via a thoracic or abdominal approach. Recent advances in laparoscopic techniques have enabled a minimally invasive approach to myotomy, with significant reductions in perioperative pain, morbidity, and length of hospitalization. However, the major problem remains unchanged: long-term GERD, which can be particularly damaging in an atonic esophagus. Although most surgeons using an abdominal approach incorporate a “loose” antireflux procedure along with the myotomy, its effectiveness in preventing GERD remains controversial. Two long-term studies using a thoracic approach, one with and one without an antireflux procedure, were comparable in that only two thirds of patients in either study were still doing well 10 years and beyond. Although the abdominal approach may be associated with less reflux, long-term results are not yet available after laparoscopic surgery, and patients and physicians should be on guard for this complication.

How can postoperative GERD be avoided?
The best advice to give patients after myotomy is that they need to be followed carefully for GERD. A very low threshold should be used for initiation of antireflux medications. Proton pump inhibitors are very effective in preventing postoperative GERD symptoms.

How is balloon dilation of the lower esophageal sphincter accomplished?
Using whalebone as a dilator, Sir Thomas Willis first described dilation of LES in a patient with achalasia. Forceful dilation of the LES is achieved by stretching it to at least 30 mm or more (for adults); this obviously requires more than a simple bougie and is best accomplished by using a specially designed balloon catheter. The most commonly available device (Rigiflex by Microvasive) is passed over a guidewire and requires fluoroscopic monitoring; a typical starting balloon size for most adults is 30 mm. A less common device is the Witzel dilator, which consists of a polyethylene balloon mounted on a forward viewing endoscope that is inflated under directed visualization (with the endoscope in the retroflexed position in the stomach). It has the advantage of not requiring fluoroscopy. Otherwise, there is little science to dilation. A good stretch requires obliteration of the balloon waist; however, consideration of durations, pressure, number of inflations, presence of blood on the dilator, or induction of chest pain, are of little, if any, importance in determining efficacy.

What can be done if symptoms do not respond to the first dilation?
A larger balloon (available in 5-mm increments from 25 mm up to 40 mm) may be used to attempt further stretching of the LES, the so-called progressive method. An alternative method, championed by van Trappen and colleagues but seldom practiced in the United States, is repeated dilation (regardless of the initial symptomatic response) until certain objective parameters of esophageal emptying (usually determined radiographically) are met. Regardless of the method used, if the patient fails three dilations, most authorities recommend surgery.

What are the results of pneumatic dilation?
The overall immediate response rate to pneumatic dilation is 75-80%; long-term results show that up to one half of patients require one or more dilations over a 5-year period. Beyond this time, about 50-70% of patients continue to do well; however, up to 20% or more may eventually need surgery.

How does pneumatic dilation compare with surgery?
A classic randomized, controlled trial of surgery and dilation clearly favored surgery in terms of long-term results. However, it is not clear whether this is the most cost-effective approach, considering the long-term and cumulative costs of surgery (estimated at nearly 2.5 times more than the cost of pneumatic dilation), even in view of the perforation rate and need for retreatment associated with pneumatic dilation.

What is the major disadvantage of forceful dilation? How can it be prevented?
The major risk of dilation is perforation (estimated rate = 1-10% or even higher). Because of the empiric way in which dilation is performed, this risk appears to be inherent; there are few ways to prevent this complication. It is important to exclude stricture (malignant or benign), to ensure a near-empty esophagus, and to perform all manipulations of the balloon under fluoroscopic control. Relative contraindications cited in the literature include a tortuous sigmoid shape, previous myotomy, epiphrenic diverticula, and large hiatal hernias, but most experts do not view these as absolute. Larger balloons are expected to increase the risk for perforation. The overall perforation rate for Rigiflex dilation is about 3%, and for Witzel dilation the rate is about 6%. GERD is believed to be uncommon after forceful dilation, with an incidence of around 2%.

How is perforation treated in patients with achalasia?
Treatment is controversial. Perforations after achalasia dilation tend to be small and well contained. Thus, many authorities advocated conservative treatment (i.e., antibiotics and parental alimentation); good results are reported in the literature. However, it is difficult to predict the outcome with this form of treatment in individual cases. Surgery is definitely indicated in patients with large perforations and free flow of contrast into the mediastinum or with evidence of sepsis. When surgery is performed early, the clinical outcome and long-term course appear similar to elective myotomy.

Which patients are particularly likely to respond to dilation?
In general, older patients (over age 50) do significantly better after dilation than younger patients.

What objective parameters should be followed after dilation?
The most consistent and important parameter determining long-term response after pneumatic dilation is posttreatment LES pressure. The best results are obtained when LES pressure is <10 mmHg. It is theoretically possible that a treatment regimen based on “optimization” of esophageal emptying rather than symptomatic response alone may lead to better long-term results. A recent study showed that timed barium esophagram was an import tool to predict the long-term results. In this study, about 30% of achalasia patients reported symptoms relieved after pneumatic dilatation had an abnormal timed barium esophagram study, while 90% of these patients failed within 1 year after treatment.

How is botulinum toxin type A (Botox) injection administered?
Botox is available through most hospital pharmacies in vials containing 100 units of the lyophilized powder. For use in achalasia, it can be diluted in 5 mL of normal saline to yield a solution containing 20 U/mL. Flexible upper endoscopy is performed using routing sedation, and the toxin is injected via a 5-mm sclerotherapy needle into the LES region, piercing the mucosa about 1 cm above the Z-line and slanting the needle approximately 45 degrees. The injections are administered in four aliquots distributed circumferentially in four different quadrants. The original dose of 80 U/mL was chosen empirically; there is no good reason why the contents of an entire vial (100 U) cannot be administered. Precise location of the injection site may not be necessary because diffusion may take care of any minor variations. Others advocate the use of EUS to help guide injection; it is not clear whether EUS results in better outcomes than the traditional method.

What are the results of Botox treatment?
Only about two third of patients sustained improvement (beyond the first month or so). Older patients do better, and patients with vigorous achalasia may have a more favorable response than those with the classic form. Patients who respond to an initial injection remain in remission for several months (range = 4 months to >1 year). When symptoms return, patients usually respond to repeat injections of botulinum toxin. Larger doses of Botox at the time of initial injection have not been proven to improve the response rate.

What is the overall best treatment for achalasia?
Because no treatment is curative, there is no real answer. It is best for the physician to become familiar with the advantages and disadvantages of each option and to present them to the patients. The final choice depends on several factors, including patient preference and risk tolerance as well as local availability of technical expertise. Regardless of the treatment, patients need to be followed carefully and therapeutic strategies revisited on a periodic basis.

Last updated: April 20, 2010

References
WEBSITES
http://www.nlm.nih.gov/medlineplus/ency/article/000267.htm
http://www.clevelandclinicmeded.com/diseasemanagement

BIBLIOGRAPHY

  • Blam ME, Delfyett W, Levine MS, et al: Achalasia: A disease of varied and subtle symptoms that do not correlate with radiographic findings. Am J Gastroenterol 97:1916-1923, 2002.
  • Bortolotti M, Mari C, Lopilato C, et al: Effects of Sildenafil on esophageal motility of patients with idiopathic achalasia. Gastroenterology 118:253-257, 2000.
  • Brucher BL, Stein HJ, Bartels H, et al: Achalasia and esophageal cancer: Incidence, prevalence, and prognosis. World J Surg 25:745-749, 2001.
  • Cronshaw JM, Matunis MJ: The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. Proc Natl Acad Sci U S A 100:5823-5827, 2003.
  • Dunaway PM, Wong P: Risk and surveillance intervals for squamous cell carcinoma in achalasia. Gastrointest Endosc Clin N Am 11:425-434, 2001.
  • Goodgame RW, Graham DY: Manometry in classic and vigorous achalasia. Gastroenterology 103:1993, 1992.
  • Hoogerwerf WA, Pasricha PJ: Pharmacologic therapy in treating achalasia. Gastrointest Endosc Clin N Am 11:311-324, 2001.
  • Khelif K, De Laet MH, Chaouachi B, et al: Achalasia of the cardia in Allgrove’s (triple A) syndrome: histopathologic study of 10 cases. Am J Surg Pathol 27:667-672, 2003.
  • Kobara H, Uchida N, Tsutsui K, et al: Abnormal bile flow in patients with achalasia. J Gastroenterol 38:327-331, 2003.
  • Mayberry JF: Epidemiology and demographics of achalasia. Gastrointest Endosc Clin N Am 11:235-248, 2001.
  • Parkman HP, Reynolds JC, Ouyang A, et al: Pneumatic dilatation or esophagomyotomy treatment for idiopathic achalasia: Clinical outcomes and cost analysis. Dig Dis Sci 38:75-85, 1993.
  • Pasricha PJ, Rai R, Ravich WJ, et al: Botulinum toxin for achalasia: Long-term outcome and predictors of response. Gastroenterology 110:1410-1415, 1996.
  • Pasricha PJ, Ravich WJ, Hendrix TR, et al: Intrasphincteric botulinum toxin for the treatment of achalasia. N Engl J Med 332:774-778, 1995.
  • Paterson WG: Etiology and pathogenesis of achalasia. Gastrointest Endosc Clin N Am 11:249-266, 2001.
  • Rajput S, Nandwani SK, Phadke AY, et al: Predictors of response to pneumatic dilatation in achalasia cardia. Indian J Gastroenterol 19:126-129, 2000.
  • Vaezi MF, Baker ME, Achkar E, Richter JE: Timed barium oesophagram: Better predictor of long term success after pneumatic dilation in achalasia than symptom assessment. Gut 50:765-770, 2002.
  • Zhao XT, Pasricha PJ: Botulinum toxin for spastic GI disorders: A systematic review. Gastrointest Endosc 57:219-235, 2003.

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