Achalasia

Chapter 14

Achalasia Miguel A. Valdovinos-Díaza, Alejandra Altamirano-Barrerab a

Department of Gastroenterology of the National Institute of Medical Sciences and Nutrition Salvador Zubiran (INCMNSZ), Mexico City, Mexico, Gastrointestinal Motility Lab, INCMNSZ, Mexico City, Mexico

b

Key Points ●

Achalasia is an uncommon major esophageal motility disorder characterized by abnormal LES relaxation and aperistalsis. Genetic predisposition, viral infections, immune-mediated inflammation and neurodegenerative factors are the proposed mechanisms for the pathophysiology of achalasia.

●

Pneumatic dilation, surgical and endoscopic myotomy are the most efficacious therapeutic modalities.

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Introduction Achalasia is an uncommon major esophageal motility disorder with a mean prevalence of 10 per 100,000 adults per year and an incidence of 1 per 100,000 adults per year. Achalasia affects equally men and women and white and non-white people. Loss of peristalsis and incomplete relaxation of the lower esophageal sphincter (LES) are the two manometric findings that characterize achalasia. These motor abnormalities result from the loss of myenteric neurons of the esophagus. Dysphagia to solids and liquids, chest pain, regurgitation of esophageal content, weight loss, cough, aspiration and heartburn are the principal clinical manifestations. Diagnostic tests for achalasia include esophageal motility testing endoscopy and barium swallow. HRM identifies three subtypes of achalasia, with therapeutic and prognostic implications. The more effective therapeutic modalities for achalasia are pneumatic dilation, surgical or endoscopic esophageal myotomy. Botulinum toxin injection into the lower esophageal sphincter is a temporary therapy that should be reserved for those patients with a high surgical risk. Achalasia patients require a close follow-up for early identification of symptomatic recurrence after treatment and for the potential esophageal neoplasia development.

Definition Achalasia is an esophageal motility disorder characterized by failure of relaxation of the LES and aperistalsis of the esophagus. Achalasia is derived from the Greek khalasis, translated as “not loosening or relaxing.” In 1674, Sir Thomas Willis was the first who describe and termed this disease. Until 1929, Sir Arthur Hurst coined the term “achalasia” suggesting that it may be due to the “loss of normal inhibition” in the distal esophagus [1].

Epidemiology Achalasia has an equal distribution across gender and race, but with an increasing incidence with age and variable prevalence in different countries that ranges up to 10 per 100,000 adults per year [2]. The peak incidence is between 30 and 60 years of age. A study in a Zimbabwean population, the reported incidence was 0.03 per 100,000 people, in Chicago 1.07 per 100,000 people and in Canada 1.63 per 100,000 people [3]. In a recent study in England, a prevalence of 27.1 per 100,000 people was reported. In the United States, rates of hospitalization for achalasia range from 0.25 per 100,000 to 37 per 100,000. Although the incidence is low, the chronic and progressive course of this condition significantly affects quality of life, work productivity, and functional status of achalasia patients [4].

Clinical and Basic Neurogastroenterology and Motility. https://doi.org/10.1016/B978-0-12-813037-7.00014-5 © 2020 Elsevier Inc. All rights reserved.

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Pathophysiology Achalasia is an idiopathic disease. The primary cause of achalasia is thought to be a selective loss of inhibitory postganglionic neurons in the myenteric plexus of the distal esophagus and LES, resulting in an imbalance of excitatory and inhibitory neuronal activity. The excitatory neurons release acetylcholine (Ach) while the inhibitory neurons release nitric oxide (NO) and vasoactive intestinal polypeptide (VIP). The loss of the inhibitory neuronal activity of VIP and NO with an unopposed excitatory action of Ach results in failure of LES relaxation and loss of esophageal peristalsis [5]. Esophageal myenteric immune-mediated response and inflammatory state accompanied by T cell infiltration, triggered by a yet unknown etiologic factor may be a pathogenic mechanism in the early stage of achalasia. This pathologic condition may cause neuritis and ganglionitis, with no initial ganglion cell loss or with only mild to severe fibrosis in the smooth muscle layer. Later on, the progressive destruction of myenteric ganglion cells and the occurrence of neural fibrosis would lead to the classic subtype I of achalasia [6]. In a recent cross-sectional study our group compared immunohistochemical stains of LES muscle specimens from patients with achalasia to those of controls. We found capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%) as the relevant histopathological findings in achalasia patients [7]. Multiple studies have suggested that chronic latent or active neurotropic viral, bacterial or parasitic infections are associated with achalasia. The proposed virus candidates include herpes simplex virus (HSV), a neurotropic virus with predilection for squamous epithelium, John Cunningham virus, bornavirus, varicella zoster, measles, and human papilloma virus [8]. New findings in molecular pathology in patients with achalasia have suggested the hypothesis that achalasia is an autoimmune disorder. The proposed autoimmune etiology of achalasia is supported by the presence of anti-myenteric antibodies in the circulation and inflammatory T cell infiltrates in the myenteric plexus, as well as demonstrated statistical correlations between the disease and particular HLA class II antigens namely those carrying the DQA1*0103 and DQB1*0603 alleles [9, 10]. In addition, patients with achalasia are 3.6 times more likely to have other autoimmune diseases, including uveitis, type I diabetes, rheumatoid arthritis, systemic lupus erythematous, Sjögren syndrome, scleroderma, ankylosing spondylitis, myasthenia gravis, Guillain-Barre syndrome, autoimmune acquired hemophilia A, polyglandular autoimmune syndrome type II, psoriasis and asthma [11]. Genetic factors may play an important role in the development and progression of achalasia. The existence of familial cases suggests that achalasia may be inherited and thus have a genetic component. Furthermore, there is statistical association of achalasia with well-defined genetic disorders such as Allgrove syndrome (achalasia, alacrima, and adrenocorticotrophic hormone-resistant adrenal insufficiency), multiple endocrine neoplasia type 2 (MEN 2), Riley-Day syndrome (familial dysautonomia) and Smith-Lemli-Optiz syndrome (mutations in the DHCR7 gene that reduce or eliminate the activity of 7-dehydrocholesterol reductase) [12]. In summary, the initial event for achalasia development may be a viral infection that induces a persistent inflammation in the myenteric plexus in a subject with a genetic predisposition to develop a chronic auto-inflammatory response that has the potential to progress to the disease.

Clinical presentation Dysphagia for liquids and solids is the cardinal symptom of achalasia being present in approximately 95% of patients. Regurgitation of esophageal content occurs in about 70% of cases [13]. Regurgitation is more frequent in the supine position during the night and can cause aspiration with cough, hoarseness, wheezing and episodes of pneumonia [14]. Chest pain is experienced by 40–50% of cases and it is more frequent in women and subtype III of achalasia. Heartburn is due to stasis and fermentation of retained food in the esophagus. This symptom may be confounded with gastroesophageal reflux and patients are treated with proton pump inhibitors resulting in a delayed diagnosis. Weight loss is reported by 35–91% of patients, with and average weight loss of 10 ± 8kg [15] (Table 1). There are different scores to quantify the severity and frequency of symptoms. The Eckardt symptom score is the grading system most frequently used for the evaluation of symptoms and efficacy of therapeutic modalities. It gives points (0–3 points) for four symptoms (dysphagia, regurgitation, chest pain and weight loss), ranging from 0 to 12. Eckardt scores ≤3 obtained after any therapeutic intervention is usually considered a successful treatment [16] (Table 2). Patients with a previous fundoplication or bariatric procedures may also have signs and symptoms that mimic achalasia manifestations. In this context, it is very important to rule out mechanical causes of obstruction, such as anastomotic stricture, tight lap-band and tight fundoplication [17]. Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is found mainly in endemic areas of 21 Latin American countries, particularly in the Amazon basin of Brazil, Argentina, Colombia and Bolivia. However, in the past decades it has been increasingly detected in the United States of America, Canada, European and some Western Pacific countries. This is due mainly to the mobility of the population between Latin America and the rest of the world.

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TABLE 1  Frequency of symptoms in patients with achalasia [50–52] Symptoms

Frequency (%)

Dysphagia

90

Heartburn

75

Regurgitation or vomiting

45

Chest pain

15

Epigastric pain

15

Odynophagia

5

Cough or asthma

20–40

Chronic aspiration

20–30

Hoarseness or sore throat

33

Unintentional weight loss

10

TABLE 2  Eckardt score for symptomatic evaluation in achalasia [16] Score

Weight loss (kg)

Dysphagia

Retrosternal pain

Regurgitation

0

None

None

None

None

1

<5

Occasional

Occasional

Occasional

2

5–10

Daily

Daily

Daily

3

>10

Each meal

Each meal

Each meal

Therefore, Chagas disease should be rule out in patients with clinical symptoms and diagnostic tests suggestive of achalasia in patients coming from endemic countries [18].

Diagnosis Endoscopy Upper endoscopy has a low diagnostic yield in achalasia; its main role is in ruling out mechanical obstruction, esophageal cancer, or pre-malignant lesions secondary to chronic stasis. 2–4% of patients with clinical suspicion of achalasia have pseudoachalasia from an infiltrating tumor or stenosis. Age older than 55 years, short duration of dysphagia (<1 year) and significant weight loss (>6.8kg) on presentation are risk factors for pseudoachalasia secondary to a malignant neoplasm. Mucosal biopsy is essential for the diagnosis of esophageal carcinoma [19, 20]. The presence of a dilated esophagus with retained saliva and a puckered gastroesophageal junction are the classical endoscopic findings in idiopathic achalasia [21]. However there are cases with normal appearing esophagus or with sequel of chronic stasis such as retained food, superficial ulcers, esophagitis and candidiasis. A very tight esophagogastric junction or a failure to introduce the endoscope into the stomach may indicate infiltration and further evaluation with biopsy, endoscopic ultrasound and CT scan is mandatory.

Barium esophagram Barium esophagram is a complementary test in the diagnosis of achalasia. Barium swallow is useful to define the morphology of the esophagus (diameter and tortuosity) and other abnormalities such as epiphrenic diverticula. A narrow esophagogastric junction (EGJ) with “bird beak” appearance and poor emptying of barium are the common findings. (Fig. 1) Severe proximal dilatation with stasis of food, tortuosity, angulation and megaesophagus are signs of a late or end stage achalasia. However, dilation of the esophagus and a narrow EGJ may be absent during the early stages of the disease [22] (Fig. 2).

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FIG. 1  Barium esophagram: Narrow esophagogastric junction (EGJ) with “bird beak” appearance, esophageal dilation with poor emptying of barium.

FIG. 2  Barium esophagram in early stage of achalasia.

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Timed barium esophagram (TBE) is an additional technique useful in the assessment of esophageal emptying particularly after treatment. TBE is estimated by measuring barium column height 1, 2 and 5min after ingestion of a large barium bolus. The rate of barium emptying is a predictor of long-term response to therapy [23].

Esophageal manometry The presence of aperistalsis and incomplete LES relaxation are the characteristic manometric findings of achalasia. HRM is the gold standard test for the diagnosis and classification of achalasia. Clinical phenotypes of achalasia have been identified with HRM and categorized in the Chicago classification v3.0 (CC) [24]. CC emphasizes that the fundamental assessment of deglutitive contractility is of whether or not an EGJ outflow obstruction is present as defined by an integrated residual pressure (IRP) >15 mmHg. Disorders of EGJ outflow obstruction are further divided into three achalasia subtypes and EGJ outflow obstruction based on the contractile and pressurization patterns in the body of the esophagus [24]. ●

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Type I is characterized by absent peristalsis with no compartmentalization of intrabolus pressure. This phenotype represents late stage achalasia with loss of muscle tone and dilation of esophageal body (Fig. 3A). Type II: Panesophageal pressurization is present in at least 20% of swallows in a 30 mmHg isobaric contour. This phenotype likely represents early stage achalasia. The smooth muscle retains its tone and swallows generate an increased panesophageal isobaric pressure (Fig. 3B).

FIG.  3  HRM subtypes of achalasia. (A) Achalasia subtype I: Absent peristalsis (red arrows), incomplete LES relaxation (circle). (B) Achalasia subtype II: Pan-esophageal pressurization (red arrows), incomplete LES relaxation (circle). (C) Achalasia subtype III: Premature contractions with shortened distal latency (arrow) and incomplete LES relaxation (circle). (D) EGJ outflow obstruction: Intact esophageal body peristalsis (red arrows), elevated IRP (circle).

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●

Type III: is characterized by premature contractions with shortened distal latency in at least 20% of swallows. This phenotype is also known as spastic achalasia. In these cases, timing of esophageal body peristalsis is abnormal and contractions arrive in the distal esophagus earlier than expected and are not peristaltic [25] (Fig. 3C). Esophagogastric junction outflow obstruction is an esophageal motor disorder defined by an elevated median IRP with an intact esophageal body peristalsis (Fig. 3D). This major motor disorder has been considered as a very early stage achalasia or an achalasia variant, but it has also been recognized in mechanical structural processes at the EGJ such as hiatal hernia, fundoplication, gastric band and eosinophilic esophagitis [24].

This achalasia classification in three different phenotypes has therapeutic and prognostic implications. Different studies have demonstrated that achalasia type II has the better treatment outcomes to either pneumatic dilation or laparoscopic Heller myotomy, followed by type I and type III [26].

Functional lumen imaging probe (FLIP) FLIP is a device used for the assessment of esophageal distensibility. Multiple, closely spaced impedance planimetry channels and a pressure sensor located within a distensible bag are used to simultaneously measure luminal diameters and intrabag pressure during controlled volumetric distension of the esophagus. Recently, FLIP topography is used to measure esophageal body contractility with concurrent assessment of EGJ distensibility. With this technology, the Chicago group has shown that FLIP topography provides a well-tolerated method for esophageal motility assessment at the time of upper endoscopy, especially in patients with achalasia. They also demonstrated the FLIP topography is a complementary technique to HRM particularly in patients with non-obstructive dysphagia with a previous normal HRM [27]. More studies to define the diagnostic usefulness of FLIP topography in the evaluation of achalasia patients are needed.

Treatment There is not definite cure for achalasia. Current treatments options are aimed to reduce the functional obstruction at the EGJ and facilitate esophageal emptying. Current therapies include pharmacological agents, endoscopic and surgical therapeutic modalities. Nevertheless, there is no intervention that improves esophageal peristalsis. The objectives of therapeutic procedures are relief of symptoms, improvement of esophageal clearance and prevention of esophageal dilation.

Pharmacological agents Pharmacological agents have a very limited efficacy in the management of achalasia. Clinical response to drugs is poor and their incidence of side effects is considerable. Calcium channel blockers (CCBs) and nitrates are the two most commonly used medications. CCBs such as nifedipine, in sublingual doses of 10–30mg given 30min before meals, inhibits LES muscle contraction, reduces the LES resting pressure by 30–60% and improves symptoms in approximately 75% of cases [28]. However, side effects such as headaches, orthostatic hypotension and ankle edema occurs in up to 30% of patients. Nitrates inhibit LES contraction by dephosphorylation of the myosin light chain. Short or long acting nitrates have been employed in the management of achalasia. Wen et al. in a Cochrane review found only two randomized controlled trials involving achalasia patients treated with any type of nitrates [29]. They concluded that no recommendations could be given due to poorly designed studies. 5′-Phosphodiesterase inhibitors, like sildenafil, have also been used to treat achalasia and spastic disorders of the esophagus. These compounds reduce LES pressure and attenuate distal esophageal contractions by blocking the enzyme that degrades cyclic guanosine monophosphate induced by nitric oxide. Side effects of sildenafil include chest pain, headache, hypotension and dizziness [30]. The 2018 International Society for Esophageal Diseases (ISDE) Guidelines do not recommend the use of CCBs, nitrates or 5′-Phosphodiesterase inhibitors due to a lack of convincing evidence of efficacy of these drugs in the symptomatic relief in patients with achalasia [20].

Botulinum toxin Botulinum toxin A (Botox) inhibits acetylcholine release at the level of the cholinergic synapses, thus decreasing LES pressure. Endoscopic injection of Botox in the muscle of the LES has been demonstrated as a safe treatment with short-term improvement of symptoms in 85% of the patients with a single injection. The protocol consists of injection up to 100 units of toxin just proximal to the squamous–columnar junction distributed over the four quadrants. Greater doses, are shown to be no more effective [31]. Complications related to the procedure are rare and typically involve chest pain seen in 16–25%.



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However, this therapy loses efficacy with time, eventually reversed by axonal regeneration, requiring increasingly repeated injections (60% of patients starting at 6 months after the first injection, and 30% after 1 year). Predictive factors of a favorable and prolonged response to Botox are older age (>40 years old), achalasia type II, and a decreased basal LES pressure following treatment [32]. Most patients relapse and require re-treatment within 12 months. Some studies have demonstrated that repeated injections make subsequent Heller myotomy and POEM more challenging due to transmural inflammation and fibrosis occurring after botulinum toxin injection [33]. This therapy should be considered as a first line treatment only for patients who are not candidates for PD or endoscopic or surgical myotomy.

Pneumatic dilation Pneumatic dilation (PD) is the most effective nonsurgical option to treat achalasia. The objective of this procedure is to tear or disrupt the circular muscle of the LES using a forceful stretching of the EGJ with an intraluminal air-filled balloon. Rigiflex are the most common used pneumatic dilators. PD is performed under fluoroscopic guidance over a guide wire placed endoscopically. Once the correct position of the balloon at the EGJ is confirmed, the balloon is progressively inflated until the waist is flattened and a 7–15psi distention pressure is reached. The most accepted protocol is to start with 30mm balloons. Subsequent dilations can be performed with 35mm and finishing with 40mm balloons with intervals of 4–6 weeks between dilations. Reassessment of symptoms and LES pressure are evaluated between each session to determine the necessity of additional interventions [34]. PD may provide a 90% response rate at 6 months and 44% response rate at 6 years. Predictors of unfavorable clinical response include male sex, younger age <40years, height of barium column >10cm at 5min, width of the esophagus >4cm before treatment, LES pressure after dilation >10mmHg and continued symptoms after one or two treatments [35]. Achalasia type II patients have the better outcomes. Minor complications such as chest pain, transient fever, aspiration pneumonia, bleeding, tear without perforation and esophageal hematoma are reported in up to 33% of patients after PD. Esophageal perforation occurs in 0–5% of cases. Asymptomatic or small perforations can be managed with fasting, parenteral nutrition, antibiotics and esophageal stenting. Large perforations with mediastinitis require surgical repair [36]. GERD is seen in 15–35% of patients after PD and recurrence of dysphagia and GERD-related distal esophageal stricture should be excluded as a potential contributing complication. The use of PPI therapy is indicated in patients with GERD after PD. [35] PD can be done safely after a failed Heller myotomy.

Surgical myotomy Laparoscopic Heller myotomy (LHM) consists of dividing the muscle bundles of the LES complex to improve the esophageal emptying. Myotomy should be extended 6cm into the esophagus and 2–3cm into the stomach as measured from the EGJ in order to obtain better symptom relief. In a systematic review and meta analysis of 39 studies with 3086 patients, the laparoscopic myotomy showed a symptom improvement in 89% of patients (range of 77–100%) [37]. The efficacy of the procedure decreases with longer follow-up periods, maintaining only a symptom relief in 57% of patients at 6 years of follow-up [36]. Achalasia type II is the phenotype with the better outcomes after LHM or PD, compared to type I and type III (symptomatic response rates of 100%, 56% and 29%, respectively) [26]. Symptoms of GERD occur in up to 48% of patients after LHM, therefore an antireflux procedure should be added to the myotomy. Nissen 360° fundoplication is associated with a high rate of postoperative dysphagia. Anterior 180° partial fundoplication (Dor) or posterior 270° partial fundoplication (Toupet) are the most recommended antireflux procedures after myotomy. The frequency of GERD symptoms or abnormal esophageal acid exposure are similar after Dor or Toupet partial fundoplications [38].

Peroral endoscopic myotomy POEM procedure include 4 main steps: (1) Submucosal injection of methylene blue and mucosal incision usually 10–12cm above the EGJ, (2) Submucosal tunnel: The endoscope with a distal cap is advanced into the submucosa and a submucosal tunnel is created. The tunnel is extended past the esophago-gastric junction for 2–3cm into the stomach. (3) Myotomy: A proximal to distal myotomy starting 2cm distal to the mucosa entry is performed; the myotomy should extend at least 2cm into the stomach. (4) Clipping: The mucosal entry is closed using endoscopic clips. The clinical success rate (Eckardt score <3) reported in two recent meta-analysis is achieved in 82–100% of patients treated with POEM [39]. Comparative studies between LHM and POEM have shown similar results in terms of efficacy. A recent study has shown that POEM is a more effective treatment than PD, particularly in patients with achalasia type III [40]. POEM is also an effective therapy in patients who have failed to previous intervention either PD or LHM. Post-procedure complications include pneumoperitoneum, pneumothorax and subcutaneous emphysema, which occur in 11–30% of patients. Major adverse events such as

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mediastinal leak and hemorrhage have been reported in less than 1.5% of cases. Mortality associated to POEM is 0.09% [41]. The occurrence of GERD is the main concern after POEM because this procedure ablates the LES without adding any type of antireflux mechanism. Symptoms of GERD post-POEM occur in 12–34% of cases, endoscopic esophagitis has been found in 20–69% of patients and abnormal pH monitoring is present in 31–50% of patients [39]. PPIs are indicated in patients who develop symptoms of GERD after POEM.

Esophagectomy The late stage of achalasia is characterized by megaesophagus or sigmoid esophagus. Esophagectomy should be reserved for patients who have failed PD and/or myotomy. A predictive factor for the need of esophagectomy is the presence of a massively dilated esophagus (>6cm). Esophagectomy is associated with a high morbidity/mortality rate, nevertheless it produces symptom improvement in 80% of patients [42]. Total or partial esophagectomy with gastric or colonic interposition and esophagogastric or esophagocolonic anastomosis are the surgical procedures that have been used. The ideal reconstruction method after esophagectomy has not been established.

Self-expanding metal stents (SEMS) The number of studies evaluating SEMS is scarce with controversial results and significant complications. Currently there is no convincing evidence to recommend the use of this device to treat patients with achalasia [20].

Endoscopic sclerotherapy Two recent studies have been published describing the use of a sclerosing agent, ethanolamine oleate, in the treatment of achalasia [43]. The rational was based on its necrotizing effect on the LES muscle. One study involving 103 patients who received endoscopic sclerotherapy every 2 weeks until dysphagia resolved, reported a symptom remission rate of 90% at 50 months follow-up [43]. Another study performed in 31 patients who received three treatments of ethanolamine oleate injections at 2-week intervals, found that the mean symptom score at 12 months was significantly reduced after the injections [44]. The long term effects and the LES fibrosis that ensues might make invasive therapies more difficult. More studies are needed to clarify the efficacy of this procedure.

Immunosuppressive therapy There are only few case reports of corticosteroid use (prednisolone, methylprednisolone or beclomethasone) alone or combined with other immunosuppressive therapy (methotrexate, azathioprine or cyclophosphamide) for achalasia. A clinical improvement with recovery of peristalsis corroborated by HRM was found with these agents. This reinforces the concept of an immunemediated insult as a possible etiology. However, there is no evidence to recommend this therapeutic approach [45, 46].

Risk of esophageal carcinoma There is an increased risk of development esophageal cancer in achalasia. Older studies have shown that patients with achalasia had a 140-fold increased risk of developing cancer. In more recent studies the risk of cancer has been estimated to be only 10–50 times higher than expected in general population [47]. Squamous cell carcinoma is the most commonly malignancy associated with achalasia, although adenocarcinoma has also been diagnosed [48]. Inflammation, epithelial hyperplasia and development of dysplasia and cancer due to chronic stasis of saliva and food debris in the esophageal lumen are the hypothetical mechanisms for squamous carcinoma presentation in patients with a poor response to therapeutic interventions. Post treatment chronic gastroesophageal reflux may be another etiopathogenic mechanisms for the development of Barrett's metaplasia and adenocarcinoma. Endoscopic surveillance for early detection of esophageal carcinoma has been suggested in achalasia patients. Although there is no consensus on this topic, ASGE recommendations state that it is reasonable to initiate endoscopic surveillance 10–15 years after onset of symptoms of achalasia [49].

Treatment algorithm In general, PD, LHM or POEM should be considered as initial treatment in patients with achalasia who have no or low risk for anesthetic and surgical procedures. LHM is preferred for younger patients, particularly males with achalasia subtypes II and I [26]. PD has better outcomes in patients older than 40 years with achalasia subtypes II and I [35]. POEM studies

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Achalasia

Endoscopic botulinum toxin injection High risk patients

Pneumatic Dilation Age ³40 years Achalasia types I, II

Laparoscopic Heller myotomy Age <40 years Achalasia types I, II

POEM Any age Achalasia type III Achalasia types I, II

Treatment failure

POEM

Laparoscopic Heller myotomy

Pneumatic Dilation

Treatment failure Esophagectomy Megaesophagus Sigmoid esophagus FIG. 4  Treatment algorithm for achalasia.

suggest that patients with achalasia subtype III have a better response rate with this treatment compared with PD. Patients with achalasia types I and II have also a good response rate with POEM. Furthermore, studies comparing POEM versus LHM have reported a similar response rate in subtypes I and II of achalasia [40]. In patients with no clinical response to either PD or LHM, endoscopic myotomy is a good therapeutic alternative. This procedure should be performed in patientcentered high volume centers. PD is a safe treatment that can be used in patients who have failed to LHM. Botulinum toxin injection should be reserved for patients with a high surgical risk and uncontrolled comorbidities [32]. Esophagectomy is indicated in patients with megaesophagus and who have failed to different therapeutic interventions [42] (Fig. 4).

Conclusions Achalasia is an uncommon esophageal motility disorder characterized by abnormal LES relaxation and aperistalsis. Although the etiology of achalasia is still unknown, new findings in molecular pathology have suggested an immune-mediated hypothesis as the primary pathophysiologic mechanism. HRM and FLIP topography are the diagnostic tools used to identify the clinical phenotypes of achalasia into subtypes I, II and III. Classification of achalasia patients in these phenotypes is relevant because it has therapeutic and prognostic implications. Recent studies have demonstrated that subtype II achalasia patients have the best response rate to any therapeutic interventions. New procedures such as POEM have been developed to treat achalasia with favorable results. PD, LHM and POEM are indicated as first-line therapies in achalasia depending on the expertise of specialists who are involved in the management of these patients. More randomized controlled trials comparing PD and LHM with POEM are needed in order to define the best precision medicine approach in achalasia patients.

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Peroral endoscopic myotomy (POEM) versus pneumatic dilatation in therapy-naïve patients with achalasia: results of a randomized controlled trial. Gastroenterology 2017;152:S139.



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