Achalasia is a rare motility disorder of the esophagus characterized by the absence of peristalsis and defective relaxation of the lower esophageal sphincter. Patients present at all ages with dysphagia and regurgitation as main symptoms. The diagnosis is suggested by barium swallow and endoscopy and confirmed by manometry. Because there is no curative treatment for achalasia, treatment is confined to disruption of the lower esophageal sphincter to improve bolus passage. The most successful therapies are pneumodilation and laparoscopic Heller myotomy, with comparable short-term clinical rates of success. The prognosis of achalasia patients is good, but re-treatment is often necessary.
Key points
- •
Achalasia is a motor disorder of the esophagus with dysphagia, regurgitation, and weight loss as the main symptoms.
- •
Manometry is the “gold standard” for diagnosing achalasia.
- •
Pneumatic dilation and laparoscopic Heller myotomy are the most commonly used treatment modalities and have comparable rates of success.
- •
Peroral endoscopic myotomy is an interesting new treatment with high short-term rates of success.
- •
Patients with achalasia should be monitored on a regular basis to prevent possible complications, such as sigmoidlike esophagus and esophageal carcinoma.
Introduction
Achalasia is a rare chronic motility disorder of the esophagus with an estimated annual incidence of 1 per 100,000 persons. It is characterized by the absence of peristalsis and defective relaxation of the lower esophageal sphincter (LES). These motor abnormalities result in impaired bolus propulsion and stasis of food in the esophagus, with dysphagia, retrosternal pain, and regurgitation of undigested food as the main symptoms. Since the first description of achalasia by Sir Thomas Willis in 1974, several theories on pathophysiology have been reported. To date, it is widely accepted that the lack of relaxation in achalasia is due to a loss of inhibitory innervation of the LES. Nevertheless, the exact mechanism causing this loss of inhibitory neurons is far from elucidated and treatment is still confined to mechanical disruption of the LES. Treatment modalities available for this purpose include pneumatic dilation, laparoscopic Heller myotomy (LHM), and, recently, peroral endoscopic myotomy (POEM). In this review, the current management and treatment options of achalasia are discussed.
Introduction
Achalasia is a rare chronic motility disorder of the esophagus with an estimated annual incidence of 1 per 100,000 persons. It is characterized by the absence of peristalsis and defective relaxation of the lower esophageal sphincter (LES). These motor abnormalities result in impaired bolus propulsion and stasis of food in the esophagus, with dysphagia, retrosternal pain, and regurgitation of undigested food as the main symptoms. Since the first description of achalasia by Sir Thomas Willis in 1974, several theories on pathophysiology have been reported. To date, it is widely accepted that the lack of relaxation in achalasia is due to a loss of inhibitory innervation of the LES. Nevertheless, the exact mechanism causing this loss of inhibitory neurons is far from elucidated and treatment is still confined to mechanical disruption of the LES. Treatment modalities available for this purpose include pneumatic dilation, laparoscopic Heller myotomy (LHM), and, recently, peroral endoscopic myotomy (POEM). In this review, the current management and treatment options of achalasia are discussed.
Diagnosis
The diagnosis of achalasia is suspected in patients with dysphagia (94% of the patients), regurgitation (76%), heartburn (52%), and weight loss (35%). The first diagnostic step is to rule out anatomic lesions and pseudoachalasia using endoscopy and barium swallow. Pseudoachalasia is a syndrome that may lead to a similar clinical picture as achalasia. Approximately 2% to 4% of patients suspected of achalasia suffer from pseudoachalasia. The most common cause of pseudoachalasia is malignancy infiltrating the gastroesophageal junction. In general, patients with pseudoachalasia are older and have a shorter history of symptoms, and weight loss is more prominent. When pseudoachalasia is suspected, endoscopy, endoscopic ultrasound, or computed tomographic scanning of the chest can exclude an infiltrating malignancy.
In the early stages of idiopathic achalasia, both barium swallow and endoscopy can be normal. In more advanced cases, endoscopy may show a dilated esophagus with retained food and some resistance at the gastroesophageal junction. Barium swallow typically reveals a “bird-beak” image at the junction, with a dilated esophageal body and an air-fluid level in absence of an intragastric air bubble ( Fig. 1 ). Barium swallow is of key importance in defining the morphology of the esophagus (diameter and axis) and associated conditions, such as epiphrenic diverticulae. Endoscopy is diagnostic in one-third of the patients; barium swallow is diagnostic in in two-thirds of the patients. Diagnostic certainty is provided by manometry in 90% of the patients and requires 2 pathognomonic abnormalities: aperistalsis of the esophageal body and an incomplete relaxation of the LES after deglutition. However, despite the absence of peristalsis, there can still be substantial pressurization within the esophagus. Pandolfino and colleagues proposed classification into 3 different subtypes: type I, classic achalasia with no evidence of pressurization; type II, panesophageal pressurization; and type III, vigorous achalasia or 2 or more spastic contractions of the distal esophageal segment ( Fig. 2 ). Interestingly, the therapeutic response differs between the manometric subtypes: panesophageal pressurization is found to be a predictor of a positive treatment response, whereas spastic achalasia is associated with a negative treatment response. Adopting this classification will be useful in predicting outcomes in future prospective studies.
Treatment
As the pathophysiology of achalasia remains poorly understood, treatment is still confined to mechanical disruption of the LES. Treatment modalities available for this purpose include pharmacotherapy, pneumatic dilation, LHM, and, recently, POEM.
Pharmacologic Treatment
Reduction of the LES pressure can be achieved by smooth muscle relaxants. Nitrates or nitric oxide––related molecules increase the nitric oxide concentration in smooth muscle cells, which subsequently increases cyclic guanosine monophosphate levels, resulting in smooth muscle relaxation. Calcium channels blockers ensure smooth muscle relaxation by reducing the intracellular calcium, required for esophageal muscle contraction. Both nitrates and calcium channel blockers decrease LES pressure in a dose-dependent manner and thereby improve esophageal emptying. The results published are rather scarce and show only variable results with initial improvement ranging between 50% and 90%. The effect, however, is transient due to tolerance, and side effects, such as hypotension, headache, and peripheral edema, are common. As a result, there is infrequently a place for these drugs in the clinical management of achalasia.
Endoscopic Injection of Botuline Toxine
As Botulinum toxin (Botox) is a potent inhibitor of acetylcholine release from nerve endings, it counteracts the unopposed LES contraction mediated by cholinergic nerves, thereby lowering LES pressure. In general, a total dose of 100 IU is endoscopically injected in the LES using a sclerotherapy needle, in 4 gifts, one in each quadrant. LES pressure decreases on average by 50% and esophageal emptying improves. Increasing the dose to 200 IU does not improve rate of success, whereas repeating a 100 IU injection after 1 month may improve its efficacy. Unfortunately, these effects are short lasting and decline in time: rates of success drop from 80% to 90% after 1 month to 60% to 70% after 6 months, and to only 53% to 54% after 1 year. As a consequence, therapy has to be repeated, but the response decreases with further injections, probably from antibody production to the foreign protein. Predictors of good clinical response are older age (>50) and vigorous achalasia. When compared with pneumatic dilation, its long-term efficacy is inferior and costs are higher. Botox should be preferentially reserved for patients with significant comorbidity, excluding conventional treatment with laparoscopic myotomy or pneumatic dilation, or for patients on a waiting list for surgery.
Pneumatic Dilation
Pneumatic dilation aims at disrupting the LES by forceful inflation of an air-filled balloon. To date, the most commonly used balloon is the Rigiflex balloon (Boston Scientific Corp, Natick, MA, USA), which is commercially available in 3 diameters (3.0, 3.5, 4.0 cm). Briefly, this noncompliant polyethylene balloon is inserted over an endoscopically placed guidewire and positioned across the LES. After confirmation of the correct position, by either fluoroscopy or endoscopy, the balloon is inflated until the waist, caused by the impression of the esophagogastric junction, is completely flattened. The pressure required is usually 7 to 15 psi of air, held for 15 to 60 seconds. Although this technique has been introduced many years ago and is currently widely accepted, there is no real consensus on the distension protocol. Some investigators only perform 1 dilation, but most use a graded dilation protocol with increasing balloon sizes starting with a 3.0-cm balloon, followed by a 3.5-cm balloon, and then a 4.0-cm balloon in subsequent sessions. Graded dilation is more effective than single dilation with a 3.0-cm balloon. The 3-year rate of success for a single dilation with a 3.0-cm balloon is 37% in comparison to 86% for the graded dilation protocol. Irrespective of the protocol used, a large portion of patients will relapse, mainly during the first year after treatment. Risk factors for relapse are mainly young age, male sex, single dilation with a 3.0-cm balloon, posttreatment LES pressure greater than 10 to 15 mm Hg, and poor esophageal emptying on a timed barium swallow. Long-term remission can be achieved in most of the patients with repeated pneumatic dilation. However, selecting these patients remains a challenge because symptoms do not correlate with functional data (LES pressure measurements, stasis on barium swallow).
Pneumatic dilation can be safely performed after LHM, although larger diameter balloons are often required. Rate of response is lower (50%) with no increased risk of complications.
Perforation is the most important and serious complication of pneumodilation with an overall rate of 1.9%. Early diagnosis is crucial, either by assessment of pain evoked by ingestion of water 1 to 2 hours after the procedure or by routinely performing a postdilation radiograph of the esophagus using water-soluble contrast. In a recent retrospective study, Vanuytsel and colleagues identified age (>60 years) as the most important risk factor for esophageal perforation (hazard ratio 3.4 compared with <60 years). In a large recent European trial, the risk for perforation was also significantly higher when the first dilation was performed with a 3.5-cm balloon compared with a 3.0-cm balloon. Small perforations and deep painful tears can be managed conservatively with antibiotics and by ingesting nothing by mouth. However, surgical repair through thoracotomy is best for large, symptomatic perforations with extensive soiling of the mediastinum.
Other minor complications of pneumodilation are gastroesophageal reflux disease in 15% to 35% of the patients, and responding to proton pump inhibitors, chest pain, aspiration pneumonia, transient fever, and bleeding, usually without a decrease in hemoglobin.
Laparoscopic Heller Myotomy
During LHM, an anterior myotomy of both muscular layers of the LES is performed extending 2 to 3 cm onto the proximal stomach, thereby decreasing the LES pressure and improving dysphagia. The LES pressure is more consistently lowered than with pneumatic dilation. Depending on the distal extent of the myotomy to the cardia, LES pressure is lowered by 55% to 75% with remaining LES pressure usually less than 10 mm Hg. To reduce postoperative gastroesophageal reflux disease, a partial fundoplication (anterior Dor or posterior Toupet) is performed. In a study comparing Dor and Nissen (360°) fundoplication, the efficacy in preventing abnormal reflux was similar, but dysphagia was more frequently observed after Nissen fundoplication (2.8 vs 15%, P <.001). Rates of success for LHM are high. A recent meta-analysis including 3086 patients reported rates of success of 89% after a mean follow-up of 35 months. Younger patients, especially men and patients with higher LES pressure, may benefit most from primary surgery. However, similar to pneumatic dilation treatment, rates of success decline over time to 60% after 6 to 10 years. In patients with recurrent symptoms after LHM, both pneumodilation and redo myotomy lead to good rates of success, ranging from 50% to 67% for pneumodilation and 58% to 87% for redo myotomy.
Pneumatic Dilation Versus Laparoscopic Heller Myotomy
Before the introduction of laparoscopic surgery, repeated endoscopic pneumodilation had been the treatment of choice. This choice was mainly because open Heller myotomy is accompanied by a significant postoperative morbidity and requires several days of hospitalization. However, the situation has changed enormously in favor of surgery because most procedures are performed via the laparoscopic approach. Comparison between these 2 techniques is rather difficult because different groups of investigators often use different outcome measures, and randomized controlled data, comparing pneumodilation and LHM, were lacking until recently. A large retrospective longitudinal study of 1461 patents with a follow-up period of 10 years stated that patients who underwent peumodilation needed re-treatment more often than those who had LHM (64% vs 38%). However, in this study, repeated pneumodilation was seen as an adverse outcome. Because “on-demand” pneumodilation is nowadays the accepted approach in achalasia treatment, this cannot be viewed as a failure of therapy. Another cross-sectional follow-up study of 179 patients (106 pneumodilation vs 73 LHM) showed similar rates of success for pneumodilation and LHM. Recently, Boeckxstaens and colleagues reported the results of a prospective, multicenter trial in which 201 patients were randomized to either graded pneumodilation (n = 95) or LHM (n = 106). In this study patients were allowed to be re-treated to a maximum of 3 series of pneumatic dilation. Both treatments had comparable rates of success at 2 years: 86% for pneumatic dilation and 90% for myotomy. Although in this study age was not a predictive factor of clinical success for either treatment, patients younger than the age of 40 treated with pneumodilation presented more often with recurrent symptoms requiring redilation. This finding seems to support the proposal to preferentially treat younger patients, especially men, with LHM. Although longer follow-up is required, the data from the European achalasia trial indicate that both treatments are equally effective.
Peroral Endoscopic Myotomy
Recently a new endoscopic technique (POEM) was developed to treat achalasia. The endoscopist creates a submucosal tunnel to reach the LES and to dissect the circular muscle fibers over a length of 7 to 10 cm in the esophagus and 2 cm in the stomach. Inoue and colleagues reported a rate of success of 100% and a significant reduction in LES pressure in 17 patients after a follow-up of 5 months. A recent European study reporting on their experience in 16 patients confirmed the high rate of success (94%). Hungness and colleagues reported results from a prospective nonrandomized trial comparing POEM versus laparoscopic Heller myotomy. Operation time was shorter in POEM, but therapeutic success (Eckard <3) after 6 months did not differ significantly between the 2 procedures (89%). It should be emphasized though that follow-up in these studies is still short and that prospective randomized trials comparing POEM to pneumodilation or LHM are needed to determine the place of POEM in the treatment of achalasia.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
