Keywords

Introduction

Achalasia is a primary esophageal motility disorder that results from loss of intrinsic inhibitory innervation of the lower esophageal sphincter (LES) and the smooth muscle segment of the esophageal body. Classic symptoms include dysphagia to solids and liquids associated with regurgitation of undigested food. The etiology of achalasia is unclear with several proposed theories including immune-mediated response of neuronal degeneration. Histologically, there has been evidence of inflammation of the myenteric inhibitory ganglion cells with some studies showing loss of inhibitory neurons via inflammation with subsequent neuronal destruction and fibrosis [1, 2]. Improvement in diagnostic modalities with esophageal pressure topography (EPT) has identified subgroups of achalasia patients based on carefully validated metrics to quantify LES relaxation and esophageal peristaltic function. Currently, the Chicago Classification is used to determine the subtype of achalasia (type I, II, or III) based on high-resolution manometry (HRM) . Along with the improvement in diagnostic tools, treatment options including endoscopic and surgical options have advanced management for achalasia. As the etiology of achalasia is still undefined, our treatment options are aimed at mechanical disruption of the LES, but a cure for achalasia is still not available.

Epidemiology

Incidence and Prevalence

The incidence of achalasia is 1/100,000, and due to the chronicity of symptoms, the prevalence is around 10/100,000 [3,4,5,6]. Achalasia has no age nor gender preference, and its chronicity affects patient’s health-related quality of life, work productivity, and functional status [7]. In Iceland, 62 cases of achalasia were diagnosed over a 51-year surveillance (overall incidence 0.6/100,000 per year) [4]. In the United States, hospitalization for achalasia ranged from 0.25/100,000 (<18 years old) to 37/100,000 (>85 years old) [8, 9].

Age

The peak incidence is between 30 and 60 years old [10, 11].

Gender and Race

Achalasia occurs equally among women and men and is without racial predilection.

Genetics

Utilizing research from twin and sibling studies, genetic underpinnings of achalasia show an association with other diseases, such as Parkinson’s, Allgrove syndrome, and Down syndrome [12,13,14]. The most well-known genetic syndrome is Allgrove syndrome , also known as “triple A” syndrome , which included achalasia, alacrima, and adrenal insufficiency due to a defect in the AAAS gene (chromosome 12q13) with defective tryptophan-aspartic acid repeat protein [15,16,17]. Familial cases of achalasia combined with abnormal polymorphisms of nitric oxide or interleukin expression (IL-23 and IL-10) have added support for a genetic etiology [18,19,20].

Case-control studies and a genetic association study have shown the contribution of human leukocyte antigen (HLA) class II genes in to susceptibility to achalasia [21,22,23]. A genetic association study in achalasia and controls mapped a strong major histocompatibility complex association signal by imputing classical HLA haplotypes and amino acid polymorphism. To date, the only known achalasia risk factor is an eight-residue insertion located in the cytoplasmic tail of HLA-DQβ1 receptor [24]. Data are otherwise sparse on genetic and/or phenomic association in achalasia. Studies of molecular pathology have also suggested the consideration of achalasia as an autoimmune inflammatory disorder [25, 26]. This is supported by the presence of anti-myenteric antibodies in the circulation and inflammatory T-cell infiltrates in the myenteric plexus in achalasia. Patients with achalasia are 3.6× more likely to have other autoimmune diseases including uveitis, Type I diabetes, rheumatoid arthritis, systemic lupus erythematous, and Sjögren’s syndrome [27]. However, at this time, there is no role for genetic testing in routine clinical practice.

Pathogenesis

Esophageal peristalsis is a result of complicated contractile and relaxation forces. One of the keys to understanding the pathogenesis of achalasia is to better characterize the role of autonomic ganglia in controlling distal esophageal and LES contractility. Esophageal contraction is predominately orchestrated by the postganglionic neurons which are the neurons targeted in achalasia (Fig. 7.1) [28].

Fig. 7.1
figure 1

Neuronal injury that secretes VIP and NO leads to unopposed excitatory activity and failure of LES relaxation. (Adapted from: Patel et al. [28])

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Precise balance of the contractions and inhibitions is responsible for the manometric observation of a normal esophageal peristalsis post deglutition [29,30,31,32]. In achalasia, the selective destruction of the neuroinhibitory fibers lead to loss of peristalsis and inability of the LES to relax leading to the classic manometry findings of achalasia (Fig. 7.2). The causes of an initial reduction of inhibitory neurons is unknown with theories including a possible autoimmune etiology (herpes, measles) which may trigger neuronal degeneration in a genetically predisposed host [33]. Achalasia patients are more likely to have concomitant autoimmune diseases and higher prevalence of serum neural antibodies [27, 34]. However, infectious etiologies should also be kept in the differential as seen in Chagas disease by the parasite Trypanosoma cruzi, which can cause achalasia [35].

Fig. 7.2
figure 2

High-resolution manometry showing the three subtypes of achalasia. Type I is characterized by absent contractility; type II shows pan-esophageal pressurization; and type III shows simultaneous contractions. (Adapted from: Patel et al. [28])

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The exact cause of the alterations in the myenteric plexus, including progressive degeneration and destruction of myenteric neurons, in patients with achalasia remains to be determined. However, studies have suggested a significant decrease or absent NO innervation in the myenteric plexus of patients with achalasia [29, 36]. The current hypothesis is that an initiating event, probably an environmental insult such as a viral infection, creates a cascade of inflammatory changes and damage to the myenteric plexus [33, 37, 38]. This inflammation triggers an autoimmune response, leading to chronic inflammation with subsequent complete destruction of the inhibitory neurons in the myenteric plexus (Fig. 7.3) [1]. A recent study evaluated 26 specimens in patients with achalasia and found inflammatory changes including capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%) [26].

Fig. 7.3
figure 3

Possible mechanisms for the development of achalasia ranging from viral triggers, genotype susceptibility, and genetic changes interacting with immune changes which can lead to esophageal neuronal changes. (Adapted from: Patel et al. [28])

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Opioids

Detrimental effects of opioids on esophageal motility has been known since the 1980s where repeated dosing of morphine in healthy individuals led to an increase in LES pressure and decreased sphincter relaxation [39]. However, recently multiple studies have shown increased rate of esophagogastric junction outflow obstruction (EGJOO) , type III achalasia, and esophageal spasm in patients on chronic opiates suggesting possible opioid-induced esophageal dysfunction [40,41,42,43]. The largest retrospective cohort included 2342 patients (224 on chronic daily opioids) and found that patients on opioids were more likely to report dysphagia (62% vs. 43%, P < 0.01) and were more likely to have type III achalasia (13% vs 1%, P < 0.01), EGJOO (13% vs. 3%, P < 0.01), and esophageal spasm (3% vs. 0.5%, P < 0.01) [44].

Management of patients with narcotics is difficult, but in the case of achalasia-like symptoms, reduction of narcotics to the lowest dose tolerated or transitioning to non-opioid analgesia is preferred. Manometric abnormalities in patients with opioid-induced esophageal dysfunction can normalize when patients are studied off opiates [45]. In one small case series, three out of five patients using pneumatic dilation for opioid-mediated esophageal dysfunction had little improvement in symptoms [43]. If the opioid cannot be stopped, injection with botulinum toxin can be considered. More invasive procedures, such as pneumatic dilation, surgical myotomy, and peroral endoscopic myotomy (POEM), should be approached with significant caution and reserved for refractory cases after discussion about the risks, benefits, and potential failure given the lower than average response rate in patients on chronic opioids [46, 47].

Diagnosis

Clinical Manifestations

The diagnosis of achalasia starts with symptom presentation of dysphagia, typically to solid and liquids. Patients can also present with associated regurgitation of undigested food or chest pain. Occasionally, patients report having reflux symptoms and are nonresponsive to acid suppression. A high index of suspicion for achalasia should be present for patients with reflux symptoms and regurgitation without symptom improvement despite acid suppression. Younger patients are more likely to report heartburn and chest pain compared to older patients [48]. Obese patients (body mass index >30) present frequently with choking and vomiting [49]. Despite their symptoms of dysphagia, the degree of weight loss varies with a recent study showing the correlation of achalasia with phenotype, where type II achalasia patients were most likely and type III achalasia least likely to have weight loss compared to type I achalasia [50].

Respiratory symptoms are also common due to the increased risk of aspiration secondary to retained food and saliva in the esophagus. Of 110 patients with achalasia, 40% of patients reported at least 1 respiratory symptom daily, which improved after therapy directed at the LES [51, 52]. In a retrospective study, the symptoms of dysphagia preceded respiratory symptoms by an average of 24 months, supporting the retention hypothesis as the etiology for aspiration and respiratory complaints [53]. However, there are several other etiologies of respiratory causes and dysphagia, including oropharyngeal dysphagia, connective tissues diseases (i.e., scleroderma), or extraesophageal gastroesophageal reflux disease (GERD) which should be on the differential.

Subtypes

EPT is a major advancement in the field of esophageal physiology [54]. With the innovative advent of EPT and HRM, achalasia is now recognized to present with three distinct manometric subtypes (Fig. 7.2) [55].All three phenotypes have impaired EGJ relaxation and absent esophageal peristalsis, but the distinguishing features are in the pattern of esophageal pressurization. Type I achalasia is characterized by absence of esophageal pressurization to more than 30 mmHg and has 100% failed peristalsis (aperistalsis), type II is associated with panesophageal pressurization to greater than 30 mm Hg, and type III has spastic contractions due to abnormal lumen obliterating contractions with or without periods of panesophageal pressurization [56].

Manometric subtypes have been shown to have prognostic and treatment implications. Success rates for both pneumatic dilation (PD) and Heller myotomy (HM) are significantly higher in subtypes I and II than type III. The latter subtype (type III) responds the least to reducing the LES pressure, as the segment affected by the spastic motility extends well above the LES [57]. This subtype of achalasia is characterized by chest pain due to lumen obliterating spastic contractions in the distal esophagus. It is proposed that type III achalasia may represent early disease with progression to type II followed by type I over time. However, pathophysiologic basis of this proposed progression is lacking. Recent studies also suggest that type I achalasia may represent decompensated esophagus to outflow obstructions caused by a dysfunctional LES accompanied with a complete aganglionosis [58].

Esophagogastric Junction Outflow Obstruction (EGJOO)

When the IRP is greater than 15 mmHg but there is peristalsis that does not meet criteria for type I, II, or III achalasia, the Chicago Classification labels this as EGJOO. This potential phenotype of achalasia is an important but heterogenous group [59]. There are multiple etiologies of EGJOO including incompletely expressed or early achalasia, esophageal wall stiffness, infiltrative cancer, hiatal hernia, obesity, or opiate-induced [45]. Further evaluation with endoscopic ultrasound, CT, or functional luminal imaging probe (FLIP) can be done to better elucidate the etiology of EGJOO. In some studies, patients with EGJOO were monitored conservatively, and their “disorder” resolved spontaneously [60, 61]. To increase the yield of EGJOO, provocative maneuvers during HRM can help, including rapid drink challenge or solid meal challenge [62, 63]. The mechanism of these maneuvers is that increasing the volume or viscosity of the bolus increases esophageal pressurization and thus IRP increases [47].

Esophagogastroduodenoscopy

Symptoms of dysphagia should prompt an esophagogastroduodenoscopy (EGD) with mucosal biopsies. These findings can help rule out GERD, eosinophilic esophagitis (EoE), or structural causes, such as rings or webs. On EGD, a “puckered” gastroesophageal (GE) junction with retention of solid or liquid material proximal to GE junction is commonly seen (Fig. 7.4). In more advanced cases, the esophagus can be dilated or tortuous due to chronic stasis. There can be resistance with passage of the endoscope through the GE junction due to failure of the LES to relax. When achalasia is suspected, a thorough retroflexion should be completed to fully evaluate the GE junction and cardia to rule out malignancy, which can cause pseudo-achalasia. Due to the stasis from the failure of the LES to relax, there can be esophageal candidiasis, which in the context of an intact immune function should prompt concern for esophageal dysmotility. Endoscopy can be helpful for its ability to rule out other causes of dysphagia and help support a diagnosis of achalasia, but other testing is often needed to confirm the diagnosis of achalasia.

Fig. 7.4
figure 4

Endoscopic evaluation of achalasia showing (a) puckered GE junction and (b) retained saliva. (Adapted from: Patel et al. [28])

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Histological Features

Though biopsies are more helpful to rule out other causes of dysphagia, such as EoE, histopathological analysis has been performed on achalasia patients. Prior studies have shown predominantly capillaritis with varying amounts of plexitis, nerve hypertrophy, venulitis, and fibrosis with identified presence of HSV-1 antibodies supporting a possible neurotropic viral infection leading to an autoimmune inflammatory cascade [25]. In a concentrated histopathological examination, subtypes of achalasia showed greater degree of myenteric ganglion cell loss in type I achalasia compared to type II proposing that type I achalasia may represent disease progression from type II achalasia [58]. In all types of achalasia, there was a spectrum from complete neuronal loss to lymphocytic inflammation to apparently normal tissue suggesting a pathogenically heterogeneous patient group with a common esophagogastric junction outflow obstruction.

Barium Esophagram

A noninvasive method to help with the diagnosis of achalasia is to perform a barium esophagram, which can show the classic “bird beak’s” appearance due to the narrowing of the GE junction. Other findings include aperistalsis, dilated esophagus, or a “cork appearance” of the esophagus (Fig. 7.5). However, this method is not sensitive for diagnosis of achalasia, and other modalities such as manometry are essential to confirm the diagnosis.

Fig. 7.5
figure 5

Barium esophagram showing retained contents in the proximal esophagus and “bird beak’s” appearance due to incomplete relaxation of the lower esophageal sphincter. (Adapted from: Patel et al. [28])

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Esophageal Manometry

The gold standard for diagnosis of achalasia is esophageal manometry, which involves transnasal placement of a flexible catheter into the esophagus to measure esophageal pressures and contractions along the length of the esophagus. Prior line tracings from water-perfused or strain gauge systems have now been replacement with high-resolution manometry systems that present pressure tracings in EPT plots [64, 65]. Building on the work of Clouse and plots of contractile activity, the Chicago Classification was created to define and diagnose motility disorders (Fig. 7.6) [55].

Fig. 7.6
figure 6

Manometric diagnosis of achalasia and EGJOO . The Chicago Classification v3.0, hierarchical classification. (Modified from Kahrilas et al. [55])

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By using EPT , achalasia has been further characterized into three clinically important subtypes that have shown differences in response to therapy (Fig. 7.2). The diagnosis of achalasia is made by demonstrating impaired relaxation of the lower esophageal sphincter and absent peristalsis in the absence of esophageal obstruction due to a secondary cause (i.e., pseudo-achalasia from a GE junction tumor). Manometric analysis showing an elevated integrated relaxation pressure and 100% failed peristalsis or spasm meets criteria for achalasia. The phenotype depends if there is no contractility (type I), greater than 20% pan-esophageal pressurization (type II), or greater than 20% spasm [a distal latency less than 4.5 seconds] (type III). These three subtypes of achalasia have prognostic and therapeutic implications [56].

Functional Lumen Imaging Probe (FLIP)

Per Chicago Classification version 3.0, the IRP must be greater than 15 mmHg which means the EGJ pressure is greater than 15 mmHg, which is not always the case, particularly in type I achalasia. The etiology for this may be due to in part for those with advanced disease having very low LES pressures. Prior attempts to decrease the IRP cutoff have been rejected as there are some diagnosis of achalasia with IRP values of 3 mmHg and 5 mmHg, which were seen with the use of functional luminal imaging probe (FLIP) technology and stasis on esophagram [66, 67]. FLIP has aimed to better assess this group of patients with being able to measure a distensibility index, which is a metric relating EGJ opening diameter to intraluminal distensible pressure. Using this index, a threshold of 2.8 mm2 per mmHg has been the most helpful in diagnosing abnormal EGJ function [68]. Alternatively, one can use minimal bolus flow time during HRM, a timed barium esophagram, or rapid drink challenge to also obtain this diagnosis [63, 69,70,71]. Intraoperative use of FLIP during laparoscopic HM or POEM might also offer the ability to assess the efficacy of LES myotomy in real-time and predict postoperative symptomatic outcomes [72,73,74].

Treatment Options

There is no curative option for achalasia; all treatment options are directed toward improving quality of life and attempting to preserve esophageal function and preventing esophageal stasis. Current treatment options aim to reduce the hypertonicity of the LES to improve esophageal emptying by gravity.

Therapeutic options are divided into oral pharmacological, endoscopic (pharmacological, pneumatic dilation, myotomy), and surgical (myotomy or esophagectomy) (Fig. 7.7). The choice of treatment is based on surgical candidacy, age, comorbidities, dilation of esophagus, patient preference, local expertise, and manometric subtype. The most effective therapies to help preserve esophageal function include pneumatic dilation, surgical myotomy, and POEM. Pharmacological therapy, whether oral or endoscopically injected, has decreased efficacy as compared to the three aforementioned techniques. In patients who have end-stage achalasia with severely dilated “sigmoid”-shaped esophagus and nonresponsive to other options, esophagectomy can be considered.

Fig. 7.7
figure 7

Proposed mechanism of treatment for achalasia based on low and high surgical risk. (Adapted from: Patel et al. [28])

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Pharmacological Therapies

Pharmacological therapy is the least effective treatment modality for achalasia. The response to these agents is short lived, and their side-effect profile often limits compliance or dose escalation. Oral therapies are reserved for those patients who are not candidate for more definitive endoscopic or surgical options due to comorbidities. Options for therapy are varied, but the most common include calcium channel blockers (i.e., nifedipine , 10–30 mg given 30–45 minutes prior to meals) or long-acting nitrates (isosorbide dinitrate, 5–10 mg given 15 minutes prior to meals) [75,76,77,78,79,80,81]. Both calcium channel blockers and long-acting nitrates cause a rapid reduction in lower esophageal sphincter of up to 47–64%, but unfortunately this translates poorly to symptom improvement with modest dysphagia improvement [76]. An alternative option includes the use of off-label phosphodiesterase-5 inhibitors (i.e., sildenafil ) which lowers esophagogastric junction pressure, but symptom improvement is also modest, and long-term studies are lacking [80, 82]. Given the limited efficacy of oral pharmacological therapy, this option is reserved for patients who cannot undergo a more definitive therapeutic approach (Table 7.1).

Table 7.1 Nitrates and calcium channel blockers in the treatment of achalasia
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Endoscopic Options

Botulinum Toxin

For patients who cannot tolerate a more invasive approach, botulinum toxin injection (BTI), a potent inhibitor of acetylcholine release from the presynaptic terminals, is a useful treatment strategy. BTI blocks unopposed cholinergic stimulation caused by the selective loss of inhibitory interneurons. This is injected during endoscopy where under direct visualization, 100 units of toxin are injected in 25 units aliquots in 4 quadrants via a sclero-needle just proximal to the squamo-columnar junction. Issues with the use of BTI are the transitory effect of the injection which often needs repeat procedures typically every 6–12 months. Complications with the procedure include chest pain (16–25%) and rarely more serious complications of mediastinitis and allergy to an egg-based protein.

The immediate response to BTI is as high as 80–90%, but over half of patients are symptomatic at 1 year (Table 7.2) [83,84,85,86,87,88,89,90,91,92,93,94,95,96,97]. Predictive factors for response to BTI include older age (over 40 years old), type II phenotype, and decreased basal LES pressure following treatment [84]. Repeated BTI can make surgical myotomy more difficult due to the creation of fibrosis; hence BTI should not be first line for patients who are eligible for more definite endoscopic or surgical options [98]. Though more effective than oral pharmacological therapy, BTI is not as effective as PD, POEM, or surgical myotomy. As discussed previously, for patients with achalasia-like phenotype from opioids who cannot stop their opioid, BTI might be a better alternative.

Table 7.2 Botox in the treatment of achalasia
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Pneumatic Dilation (PD)

PD is performed using an noncompliant balloon that employs air pressures to disrupt or fracture the LES circular muscle fibers and is an effective nonsurgical option in the treatment of achalasia [10, 99]. Currently, the most widely used balloon dilator for PD is the Rigiflex, a nonradiopaque graded size polyethylene balloon. The Rigiflex dilators can be performed under direct visualization or under radiological guidance (fluoroscopy) [100, 101]. The dilators are available in three diameters (3.0, 3.5, and 4.0 cm), which allow a graded dilated approach. When employing this graded approach, relief of symptoms is possible in 50–93% of patients (Table 7.3) [100, 102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127].

Table 7.3 Rigiflex balloon dilatation for the treatment of achalasia
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Graded PD is performed by an initial dilation at 3.0 cm, then 3.5 cm, and finishing at 4.0 cm with 4–6 weeks in between dilations. Reassessment of symptoms and LES pressure can be performed between each session to determine the necessity of subsequent treatments. It is estimated that a third of patients treated with PD will experience symptom relapse within 4–6 years.

Predictive factors of a poor clinical response to treatment include age less than 40 years, male sex, LES pressure after dilation greater than 10–15 mmHg, and continued symptoms after one or two treatments [128,129,130,131]. Additionally, males younger than 45 years of age may not be as responsive to the serial approach possibly due to thicker LES musculature. In these patients, it is recommended to either start with PD at 3.5 cm or proceed straight to surgical myotomy as the initial step in management.

Of the manometric subtypes, type II achalasia has better outcomes with PD [132]. Surgical myotomy has a greater response than a single pneumatic dilation, but a graded approach with PD is a reasonable alternative to surgery as it has similar efficacy. Given the risk of perforation, which is around 2%, all patients who undergo PD must be surgical candidates in case a perforation were to occur [133]. Depending on the length and extent of the perforation, the complication can be managed conservatively with stent placement, antibiotics, and parenteral nutrition; however, larger perforations with mediastinal contamination will need a surgical repair via thoracostomy. Post-dilation, there is an increased risk of GERD, seen in 15–35% of patients post PD due to the disruption of the LES. Hence, initiation of acid suppression is recommended for patients with pre-existing GERD or new symptoms of heartburn or reflux [134]. It is important to note that dysphagia after PD can be due to the underlying achalasia or could be due to a reflux stricture; endoscopy can help separate these two etiologies.

Peroral Endoscopic Myotomy (POEM)

Peroral endoscopic myotomy (POEM) is a minimally invasive endoscopic technique and is one of the most recent advances in the treatment of achalasia (Table 7.4). The procedure is performed endoscopically with a small mucosal incision in the mid-esophagus and creating a submucosal tunnel to the gastric cardia. This technique allows careful and selective myotomy of the circular muscle.

Table 7.4 Peroral endoscopic myotomy for the treatment of achalasia
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In 2010, Inoue and investigators published a prospective trial of 17 patients undergoing endoscopic myotomy that revealed significant reduction in the index of dysphagia symptoms (10 to 1.3, P = 0.01) as well as resting LES pressure (52.4 to 19.9 mmHg, P = 0.01) [135]. Given the safety profile of this procedure, POEM entered into clinical practice and has been studied since its inception. In 2014, Bhayani conducted a prospective observational study that compared 64 patients treated by LHM and 37 by POEM, which showed that mean operative time and length of stay were significantly higher in the LHM cohort, but complication rates were similar [136]. Moreover, patient symptoms, manometry, and postoperative esophageal acid exposure revealed similar outcomes among the two groups.

The preparation for POEM begins with a liquid diet 1–5 days prior to the procedure to minimize residual food in the esophagus [137]. The first step in the procedure involves injection of 10 mL of saline solution with contrast (methylene blue or indigo carmine) to the central esophagus 10–16 cm proximal to the squamo-columnar junction [138]. Following this, a 2 cm incision is made to gain access into the submucosal space. Then, a submucosal tunnel is dissected through the EGJ and 2–3 cm into the gastric cardia [139]. Once access is made to the circular muscle layer of the LES, the myotomy is usually extended to 6 cm into the esophagus and 2 cm below the EGJ. Since its inception, there have been multiple studies showing its efficacy in improvement of dysphagia scores and manometric or imaging modalities, with ranges of 87.5–100% efficacy [135, 136, 140,141,142,143,144,145,146,147,148,149,150,151,152,153,154]. Patients with type III achalasia have a greater than 90% response rate to POEM, possibly owing to the longer myotomy length [155].

Serious adverse events are rare with POEM. They occur at a rate of less than 0.1% with the most common serious event being perforation [156]. Another, albeit less serious, complication following POEM is GERD. Although initial studies showed significantly higher prevalence of GERD post-POEM up to 58%, recent studies in carefully selected patients have shown short-term postoperative clinical symptoms of GERD following POEM is 10.9% and might be comparable to that of LHM [157, 158]. However, given the high potential risk of reflux post-POEM, a recent clinical practice update from expert review and best practice advice from the American Gastroenterological Association recommended that this should be discussed with patients undergoing POEM including potential ramifications of indefinite need for proton pump inhibitor therapy and/or surveillance endoscopy after POEM [159].

Surgical Options

Laparoscopic Heller Myotomy

Surgical myotomy, a technique involving the division of the circular muscle fibers of the LES, was initially performed via an open thoracotomy and laparotomy approach. Studies at the time revealed good response with 60–94% of patients achieving symptomatic improvement when followed over 1–36 years, and this approach has since been replaced with laparoscopic Heller myotomy (LHM) which resulted in less morbidity and faster recovery time (Table 7.5) [75, 102, 121, 160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186]. A systematic review analyzing surgical techniques in 4871 patients reported patient symptom improvement after all surgical myotomies, which included 84.5% of those who underwent the open transabdominal approach, 83.3% of those with the open transthoracic approach, 77.6% of those with the thoracoscopic approach, and 89.3% of those who had a LHM [103]. A subset of the analysis comparing studies with LHM (3086), and the thoracoscopic approach (211) showed better symptomatic improvement with the laparoscopic approach compared to the thoracoscopic approach (89.3 vs 77.6%, P = 0.048) [103].

Table 7.5 Laparoscopic myotomy for the treatment of achalasia
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A complication of any myotomy is GERD, and given the surgical approach, a fundoplication at time of myotomy has helped to decrease postoperative GERD. Reflux may be less if fundoplication is added to myotomy (41.5% without fundoplication vs 14.5% with fundoplication, P = 001) [103]. A randomized controlled trial comparing myotomy with or without fundoplication reported that performing intraoperative fundoplication was associated with a lower incidence of postoperative reflux [187]. Rawlings and investigators demonstrated in a randomized control trial comparing anterior Dor with posterior Toupet fundoplication that both provide similar outcomes in terms of postoperative reflux following LHM [188].

Furthermore, LHM and POEM have been shown to have similar efficacy with a recent systematic review and meta-analysis comparing the two interventions noting improvement in dysphagia at 24 months were 92.7% for POEM and 90.0% for LHM, but patients undergoing POEM were more likely to develop GERD symptoms (OR 1.69, 95% CI 1.33–2.14) and erosive esophagitis (9.31, 95% CI 4.71–18.85) [189].

Prognosis

Despite no curative therapies for achalasia, current management allows an improved quality of life. With the advent of HRM, achalasia phenotypes have also shown prognostic implications with type II achalasia having the best prognosis after myotomy or pneumatic dilation (96% success rate) compared to type I which has 81% success rate and type III which has a 66% success rate [57]. However, success rate for type I and type III are also now >90% with the advent of POEM. Post-intervention, a timed barium esophagram by taking radiographs at 1, 2, and 5 minutes post-barium to evaluate esophageal emptying can also be considered to predict the effectiveness of treatment [190].

Achalasia is a lifelong disease and these patients need continued follow-up. These evaluations are based on determining esophageal symptoms, nutritional status, and imaging when indicated, including a timed barium esophagram [99]. For the patient who is willing to repeat a manometry, HRM can be completed to evaluate for return of esophageal contractile activity [191]. The decision for repeat treatment is based on a combination of symptoms, fitness for repeat treatment, and signs of retention on either a timed barium esophagram, EGD, or continued absence peristalsis on manometry.

Long-term complications of achalasia include an increased risk of squamous cell carcinoma (SCC) with a prevalence of 26 cases in 1000 achalasia patients [192]. The etiology of SCC is felt to be due to persistent esophageal stasis [193]. There is insufficient evidence to support routine screening for SCC; however, this decision for surveillance should be discussed with the patient and provider on a personalized approach [194]. In addition to SCC, patients with achalasia have an increased incidence of aspiration pneumonia, lower respiratory tract infections, and higher mortality [195].

Treatment Failures

Currently there is no curative treatment for achalasia. Up to 20% of patients will need additional treatment within 5 years [196,197,198,199]. Achalasia can progress to mega-esophagus or end-stage disease in around 6–20% of patients [200]. Options for these patients include botulinum toxin injection, repeat pneumatic dilation, or repeat myotomy. A recent multicenter retrospective cohort study assessing both technical and clinical efficacy of POEM in treating achalasia after a failed HM showed technical success of 98% with clinical response up to 81% in patients who had previously failed HM with median follow-up of 9 months [201]. Similarly, in an intention-to-treat analysis at 12 months, clinical success of PD after HM was also comparable to POEM at 89% [158, 202]. Lastly, redo HM also has similar clinical success rate in this group at 73–89% with median follow-up of 2–3.6 years [203, 204]. Thus, all these options can be considered in patients who have lack of response to initial therapy [205]. For patients with severe esophageal dilation with symptoms not responsive to repeat endoscopic options or myotomy, a surgical esophagectomy can be considered (Fig. 7.7).

Conclusion

Achalasia is characterized by impairment in nitrergic inhibitory neurotransmission resulting in non-relaxing LES and aperistalsis of the esophageal body. Patients often present with dysphagia to solids and/or liquid with varying degree of weight loss. Endoscopy is essential to rule out causes of pseudo-achalasia, and high-resolution manometry is the gold standard test for diagnosis. Current treatment options provide excellent palliation of symptoms in patients with achalasia (Table 7.6).

Table 7.6 Quality of evidence for GRADE system
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