The management of esophageal achalasia: from diagnosis to surgical treatment
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- Dobrowolsky, A. & Fisichella, P.M. Updates Surg (2014) 66: 23. doi:10.1007/s13304-013-0224-1
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The goal of this review is to illustrate our approach to patients with achalasia in terms of preoperative evaluation and surgical technique. Indications, patient selection and management are herein discussed. Specifically, we illustrate the pathogenetic theories and diagnostic algorithm with current up-to-date techniques to diagnose achalasia and its manometric variants. Finally, we focus on the therapeutic approaches available today: medical and surgical. A special emphasis is given on the surgical treatment of achalasia and we provide the reader with a detailed description of our pre and postoperative management.
KeywordsAchalasiaPneumatic dilatationHeller myotomyEsophageal function testingLaparoscopic repair
Achalasia was first described more than 300 years ago by Sir Thomas Willis who characterized the disorder as cardiospasm, an obstruction of the esophagus at the cardia. His treatment for the disorder was to pass a piece of carved whalebone with a sponge at its end through the esophagus . In 1924, Dr. Hurst disputed the notion that achalasia was due to cardiospasm. Instead, he postulated that the disorder was a result of absence of normal relaxation of the cardia as evidenced by his inability to find a hypertrophied sphincter upon operation, thus leading to the term achalasia by Sir Cooper Perry .
Research is ongoing to determine the specific neurohormonal dysfunction implicated in the disease. Despite the smooth muscled nature of the lower esophageal sphincter (LES), it receives both cholinergic and noncholinergic signals. Acetylcholine, usually reserved as the primary neurotransmitter in skeletal muscle, has been shown to play a role in peristaltic function of the LES . Many studies also suggest that an absence of nitric oxide (NO), whose role it is to aide in relaxation of the LES, plays an important role [4–6]. In fact, reduction of NO synthase activity in the esophageal myenteric plexus has appeared in those with sporadic achalasia and Allgrove syndrome (mentioned later) [4, 7, 8]. In addition, vasoactive intestinal peptide has been implicated in the relaxation of the LES and esophageal peristalsis [9, 10]. While still other hormones and neurotransmitters have been shown to play a role, other factors such as infectious, autoimmune, and genetic factors have also been extensively studied.
Studies have tried to demonstrate an association between viral infections and achalasia, but the data have not been conclusive . Widely accepted is that Chagas disease, caused by Trypanosoma cruzi, may lead to achalasia with resultant megaesophagus .
The attribution of autoimmune factors to the pathogenesis of achalasia, while early in its discovery, shows much promise. Goldblum et al.  note in their study of 42 histopathologic esophageal specimens, that myenteric inflammation by lymphocytes is apparent with the loss of ganglion cells, and fibrosis in severe cases. Based on immunohistochemical staining, it has been found that T lymphocytes are the predominant cells responsible for myenteric nerve degeneration . In as high as 64 % of subjects, anti-myenteric autoantibodies were detected and the alleles responsible for these changes have been reported to reside on the MHC class II allele HLA-DQ [15–19].
A genetic study of 1,012 first-degree relatives of 159 adult patients failed to identify any cases of familial inheritance of the disease . However, 75 % of patients with Allgrove (triple-A) syndrome, characterized by achalasia, alacrima, and ACTH resistant adrenal insufficiency, have achalasia. In this disorder, mutations of the AAAS gene result in dysfunction of the ALADIN protein .
Symptoms of achalasia
In a study conducted by one of the authors, dysphagia was present in 94 %, regurgitation in 76 %, and chest pain in 41 % of patients. In 43 %, the LES was hypertensive, in 25 % it was hypotensive, and incomplete or absent LES relaxation was noted in 87 % with all patients experiencing aperistalsis of the esophageal body . In addition, patients with achalasia may present with symptoms of heartburn and are prescribed acid-reducing medications. However, the underlying mechanism for their heartburn is different. The symptoms of heartburn are thought to be due to stasis and fermentation of food in the esophagus after impaired emptying causing irritation rather than by reflux of acidic gastric contents [26–28]. Long-term effects of food retention include progressive esophageal dilation, nocturnal regurgitation, aspiration in 12 %, and weight loss in 35 % [25, 29].
Recent large population studies suggest an overall 2.2–3.4 % total risk of developing esophageal carcinoma with the majority (1.3–2.7 % of cases) as squamous cell carcinoma; a 16–28 fold increased risk over the general population [30, 31]. The analysis of esophageal resection specimens in patients with end-stage achalasia has shown that diffuse squamous hyperplasia associated with papillomatosis and basal cell hyperplasia, and lymphocytic esophagitis were present and may be related to the increased risk of squamous cell carcinoma . In fact, a proposed etiology of squamous cell carcinoma in patients with achalasia includes fermentation of retained food with subsequent nitrosamine production by bacterial overgrowth . Therefore, a common implication of these findings is that duration of symptoms may be directly related to cancer risk induced by long standing chronic inflammation. A study from Meijssen et al.  has shown an interval of 17 years between the onset of dysphagia and the diagnosis of squamous cell carcinoma in patients followed longitudinally. In addition, adenocarcinoma in Barrett’s metaplasia has been reported in patients secondary to the development of gastroesophageal reflux after treatment for achalasia. In fact, Csendes et al.  have shown that the risk of Barrett’s esophagus after Heller myotomy and Dor fundoplication for achalasia is 13.4 %, which predisposes the patient to a small risk of progression to adenocarcinoma.
In summary, treatment for achalasia does not diminish the risk of developing squamous cell carcinoma and increases the risk of adenocarcinoma in Barrett’s metaplasia. These findings should be discussed with the patient once treatment is planned, as well as the need for periodical endoscopic and histologic follow-up.
Endoscopy is likely the first test to be performed in patients with any esophageal disorder to rule out mechanical obstructions, peptic ulcer strictures, esophagitis, or even cancer. Although, others would turn to barium swallow first in the evaluation of dysphagia [36, 37]. However, manometry is the most sensitive diagnostic tool and is considered the gold standard for the diagnosis of achalasia [38, 39]. Fluoroscopic barium swallow provides additional information; a bird’s beak appearance of the esophagus, esophageal dilation, delayed esophageal emptying, and tertiary contractions are all characteristics of achalasia [29, 40]. Important criteria for diagnosis of achalasia are lack of peristalsis, absent or incomplete relaxation of the LES in response to swallowing on manometry, and diagnostic findings on barium swallow [25, 39]. A variant of achalasia has also been described. Vigorous achalasia, while typical of younger patients, is thought to be an earlier stage of the disease and it is characterized by high amplitude, simultaneous nonperistaltic contractions >37 mmHg, and a high incidence of chest pain [41, 42].
High resolution manometry (HRM) and the Chicago classification
In 2008, the Chicago Classification was developed and researchers using HRM subdivided achalasia into three types. Type I, classic, is defined as achalasia with minimal esophageal pressurization, type II is defined as achalasia with panesophageal pressurization, and type III is defined as achalasia with spasm and premature contractions [43, 44]. Pandolfino et al.  showed that type II patients had the best response to intervention, up to 96 %, while type I had up to a 56 % response and type III had a dismal 29 % response. Using the same classification system, Salvador et al.  find that failure rates were the following: type I 14.6 %, type II 4.7 %, type III 30.4 %.
Medical management of achalasia
Calcium channel blockers and nitrates are the two most common medications used for treating achalasia. They work by relaxing smooth muscle and lower LES resting pressure for a limited amount of time. Of the available calcium channel blockers, sublingual nifedipine is the usual agent and its effect on the LES include a 28–48 % decrease in resting LES pressure with a 20–45 min lag to time of maximal effect and a greater than 60 min duration . Alternatively, sublingual isosorbide dinitrate decreases the LES pressure by 64–66 % with approximately 15 min before maximal onset and lasts 60–90 min [47–49]. Despite the efficacy of these pharmacologic agents, at least in the short term, their side effects, such as headaches, hypotension, and pedal edema can be very limiting . Even with the improvement in dysphagia, symptoms tend to persist and authors suggest that medical therapy should be reserved for those who are unable to undergo more definitive treatment [46, 50].
Botulinum toxin has been used to treat achalasia and acts by inhibiting the calcium-dependent release of acetylcholine from nerve terminals. In a literature review performed by Bassotti and Annese, a single injection of botulinum toxin has been shown to be effective in approximately 85 % of patients with achalasia but its effect diminishes over time with 50 % at 6 months, and 30 % at 1 year . In a review by Vaezi and Richter , 26 % of patients were resistant to botulinum toxin and showed no clinical response which was thought to be due to antibodies to the protein. Its effects diminish over time by terminal and nodal sprouting which lead to axons that form new synapses . In a study by Sweet et al., preoperative treatment with botulinum toxin was the only factor that was associated with poor outcome after Heller myotomy . Therefore, botulinum toxin is generally reserved for older patients as they tend toward a better response and are higher operative risks .
Pneumatic dilation (PD)
The first documented attempt at alleviating symptoms of achalasia included whalebone with a sponge affixed at its end to dilate the esophagus . Today, pneumatic esophageal dilation is performed under fluoroscopic or endoscopic guidance. The mechanism of action is to weaken the LES by tearing its muscle fibers by generating radial force by rapid inflation of the balloon . In an analysis of current literature, Katzka and Castell found that most practitioners utilized 30–40 mm balloons with variable inflation pressures and times. They noted a 2 % esophageal perforation rate with pneumatic dilation (PD) with the majority undergoing medical management of the perforation, and only 1 % requiring surgical intervention. In addition, there was a 66 % response rate at 1 year and 25 % at 10 years, respectively. Using the newer Rigiflex balloon, response rates are 88 and 29 % at 1 and 10 years, respectively. With subsequent dilation sessions, however, the perforation rate rises to 4 % . In a meta-analysis performed by Weber et al.  the 10-year remission for PD was 47.9 % while the perforation rate was 2.4 %. Tuset et al.  note in their prospective study that clinically symptomatic reflux was seen in 10 % of patients after PD.
Peroral esophageal myotomy (POEM)
POEM has emerged recently as a new technique for the treatment of achalasia. In 2010, Inoue et al.  developed the technique in which a submucosal tunnel is created and a longitudinal incision is made through the circular muscle fibers of the esophagus and onto the gastric cardia under endoscopic guidance. The total length of the incision was a mean of 8.1 cm, 6.1 cm in the distal esophagus and 2 cm in the cardia. While long-term outcomes have yet to be studied, significantly lower LES pressures, rates of dysphagia, and improved symptom scores have been reported by patients [59, 60]. However, in a prospective study performed by von Renteln et al.  9 of 16 patients experienced a full thickness dissection into the peritoneal cavity at the cardia, and 13 of 16 patients experienced full thickness dissection into the mediastinum, some requiring needle decompression, but without infectious sequelae or spillage. In a study of 119 patients by Ren et al.  25 % developed a pneumothorax, 49 % developed pleural effusions, and 44 % experienced heartburn postoperatively. Another concern is that POEM does not allow for fundoplication. As a result, Swanson et al.  note a 44 % incidence of heartburn.
Surgical treatment of achalasia
Heller first proposed a surgical repair for achalasia in 1913 by performing an anterior and a posterior myotomy through the chest . In 1924, Ziegler showed that one myotomy achieved equal results as two separate myotomies. The operation evolved as Cuschieri performed the first thoracoscopic myotomy in 1991 and showed that the procedure was effective with an average hospital stay of three days . In the 1990s, a laparoscopic approach became available. Patti et al., in reviewing both laparoscopic and thoracoscopic approaches found that the laparoscopic Heller myotomy (LHM) combined with a Dor fundoplication, a 180° wrap with the proximal extension of the myotomy 7 cm onto the esophagus and 1.5 cm onto the stomach, achieved a good or excellent relief of dysphagia in 93 %. The average length of stay was 48 h, and reflux by pH monitoring was 17 %. However, patients treated thoracoscopically had a 60 % prevalence of asymptomatic reflux by pH monitoring . Moreover, in a prospective randomized study, when an antireflux procedure was performed, only 9 % showed reflux by pH monitoring . These findings explain why today a partial antireflux procedure is always performed in conjunction with a laparoscopic Heller myotomy [66–68]. Finally, the optimal length of a myotomy is still debated. Undoubtedly, this needs to be extended to some level onto the stomach. Oelschlager et al.  have shown that when the myotomy was extended to 3 cm onto the stomach, patients experienced less dysphagia than those in whom the myotomy was only 1.5 cm long. A careful understanding on the anatomy of the LES may explain why a longer myotomy can achieve superior outcomes. The LES is an anatomical complex formed by circular muscle fibers of the esophagus, the U (or clasp) fibers, and the sling fibers of the lesser curvature of the stomach . Mattioli et al.  showed that the myotomy should be extended far into the anterior wall of the stomach near the lesser curvature, so to divide only the muscular clasps and not the gastric sling fibers, which should remain as the last component of the sphincteric function of the LES.
Medical versus surgical treatment of achalasia
LES pressure decrease
1 year effectiveness
5 year effectiveness
10 year effectiveness
Botulinum toxin 
2.4 % risk of esophageal perforation. Up to 4 % with subsequent dilations
25 % risk pneumothorax, 49 % pleural effusion, 46–50 % reflux
4.8 % risk of esophageal perforation
Long-term surgical outcomes and end-stage achalasia
Studies suggest that patients report good outcomes 1–3 years after esophagomyotomy, but long-term outcomes show a decline in results. Chen et al. note that at 5 years 77 % of patients achieved relief of symptoms after LHM and fundoplication . At 10 years, surgical success is reported at 69–79.6 % (versus 47.9 % in the PD group) [57, 73, 75, 76]. Other studies suggest similar decline in effectiveness over time, however, the technique of 3 cm extension of the myotomy onto the cardia and Dor fundoplication were not universally utilized [76–78]. Reasons for failure of surgical therapy have been studied and are most commonly an inadequate extension of the myotomy onto the stomach or inadequate construction of the Dor fundoplication. Of these, four out of five patients had relief of dysphagia with redo myotomy and Dor fundoplication, while only one out of eight experienced relief with PD .
Despite medical and surgical advances in the treatment of the disease, 5 % of patients will progress to end-stage achalasia. It is evidenced by disabling dysphagia, recurrent aspiration and regurgitation, esophagitis, and a sigmoid, tortuous esophagus with distention >6 cm with many having failed many previous treatments requiring esophagectomy . While it is commonly thought that a sigmoid esophagus or esophageal size >6 cm require esophagectomy, studies show that LHM and Dor fundoplication achieve good results in 91 % of patients and is no more complicated with equal operative times [53, 80]. While the most experience with esophagectomy has been with thoracic or transhiatal gastric interposition, laparoscopic approaches are becoming more common . However, it is not yet known which is the optimal treatment modality.
Patient surveillance in achalasia
As previously mentioned, patients with achalasia are at an increased risk for esophageal carcinoma with a higher incidence of squamous cell carcinoma over adenocarcinoma. The most recent guidelines from the American Society for Gastrointestinal Endoscopy (ASGE) in 2006 note that “there are insufficient data to support routine endoscopic surveillance for patients with achalasia”. Reasons for this recommendations include the low incidence of carcinoma and lack of cost effectiveness. However, ASGE recommendations also state that it is reasonable to initiate surveillance 15 years after onset of symptoms of achalasia as esophageal carcinoma is usually diagnosed after this time period . Methods of assessing the esophageal mucosa for SCC include Lugol’s dye chromoendoscopy in which there is lack of absorption of the dye by abnormal squamous mucosa, or more advanced endoscopic techniques using narrow-band imaging which reveals abnormal brown colored epithelium . Unfortunately, studies have shown that despite surveillance, the majority of carcinomas are diagnosed at an advanced stage and have less than a 10 % 5-year survival [30, 82]. With an increased overall risk of carcinoma, Zaninotto et al.  recommend screening with an upper endoscopy every 3–4 years.
Conflict of interest
The authors have no conflicts of interest.