Introduction

Oesophageal achalasia is a foregut condition characterised by defective oesophageal peristalsis and an unrelaxing lower oesophageal sphincter (LOS)1; the word ‘Achalasia’ originates from the Greek a-khalasis, meaning absence of relaxation. Although relatively rare, with a reported annual prevalence of 27/100 000, achalasia is the most extensively studied motility disorder.1 The pathophysiology of achalasia is still incompletely understood. It is characterised by the loss of inhibitory neurons responsible for releasing nitric oxide and vasoactive intestinal polypeptide, thus leading to defective oesophageal peristalsis and loss of LOS relaxation. This inhibitory innervation loss might be related to a destructive immune pathway provoked by a viral infection.2 The hallmark symptoms of achalasia include any combinations of dysphagia to solids and liquids, regurgitation of undigested food, chest pain, heartburn, vomiting and weight loss.3 Prolonged food stasis in the oesophagus causes fermentation and acidification that can lead to symptoms on par with acidic reflux. Less typical presentations of achalasia include chronic cough, aspiration pneumonia, malnutrition and refractory reflux.3 The Eckardt symptom score (ESS), developed in 1992, is commonly used in clinical practice for judging the severity of achalasia symptoms.4 The ESS is a simple, practical tool composed of the four most common symptoms; weight loss, chest pain, regurgitation and dysphagia, each scaled from 0 to 3.5 Although not originally intended to be used as a measure of therapeutic response, in view of its simplicity, ESS is widely utilised for that purpose; an ESS greater than 3 is commonly considered requiring for intervention, while a drop to 3 and below is considered to be associated with therapeutic success. However, clear limitations to the ESS cannot be ignored. For example, ESS measures frequency of symptoms not severity, regurgitation and chest pain can be the consequence of gastro-oesophageal reflux following adequate therapy rather than persistent obstruction, and incremental measurements of weight loss or gain are time dependent while the other symptoms can vary rapidly. Other measurement tools have been developed to evaluate oesophageal dysphagia. These include the Mayo Dysphagia Questionnaire–30,6 7 the Oesophageal Symptoms Questionnaire8 and the Dysphagia Symptom Questionnaire (DSQ),9 the Brief Esophageal Dysphagia Questionairre,10 and others,11 12. However, due to their length and sometimes complexity, it is not always possible to implement these in daily clinical practice or at the bedside.

The last two decades have witnessed significant progress in achalasia diagnosis and management through the introduction of high-resolution manometry (HRM), the development of the Chicago classification (CC) of motility disorders, improved techniques of barium fluoroscopy and the functional luminal imaging probe (EndoFLIP). Further, there has been an improvment have been advances in the therapeutic algorithms for pneumatic dilatation protocols, the development of peroral endoscopic myotomy (POEM) and robotic Heller myotomy. The aim of this current review is to provide an update on recent advancement in achalasia diagnosis, new technologies implemented in clinical practice and management approaches.

We performed a MEDLINE/PubMed search for achalasia. Randomised controlled trials, comparative and cohort studies on diagnosis, technology, medical, endoscopic and surgical therapy were extracted. A comprehensive narrative review was then generated by summarising the most up to date publications focusing particularly on studies published in over the last 10 years.

Diagnosis: clinical approach to oesophageal achalasia

Oesophageal dysphagia is considered an ‘alarm symptom’ that necessitates urgent endoscopic evaluation. Oesophago-gastro-duodenoscopy is always required to assess for mucosal or structural pathologies.5 Classic endoscopic findings of achalasia present in only one-third of cases and are more clearly appreciated in those with the advanced, longstanding disease. These can vary and can include any combination of presentations; dilated, food and fluid filled oesophagus, oesophageal candidiasis, oedema, signs of obstruction at the oesophago-gastric junction (OGJ), resistance to passage of the endoscope, inflammation, ulceration, even early or late squamous dysplasia and carcinoma.5

Eosinophilic oesophagitis (EoE) is a chronic oesophageal autoimmune/allergic condition with a worldwide increasing prevalence, commonly causing dysphagia and food impaction.13 EoE may exhibit obstructive features on manometry, sometimes with features of achalasia or OGJ outflow obstruction (OGJOO). EoE should always be excluded in patients found to have OGJOO on manometry or imaging. In those with achalasia who have an increased eosinophil count on histology, it is not clear if EoE can simply coexist concomitantly, if eosinophils are enhanced due to food stasis or if there is a direct pathological link.14 In a single centre retrospective review, out of 109 patients with EoE who had manometry, Ghisa et al described 14.7% patients with obstructive motor disorders, 7% of whom had manometric features of achalasia.15 In a systematic review of 48 studies that included manometry during the assessment of patients with EoE, Sykes et al found that out of a total of 802 patients, 5% had obstructive motor disorders, of whom achalasia was diagnosed in 3%14

Achalasia subtypes and the CC V.4.0

HRM is the gold-standard test for studying oesophageal peristalsis and LOS function. HRM technology constructs a colourful topographic spatiotemporal plot of oesophageal peristalsis and LOS pressure over a time axis.16 The CC is an internationally accepted algorithm for analysing and interpreting HRM studies as well as classifying oesophageal motor function. Recently this has been updated to its fourth iteration (CC V.4.0).17 CC V.4.0 is a hierarchical schematic working algorithm that divides manometric pathologies into two categories; disorders of the OGJ relaxation and disorders of oesophageal body peristalsis (figure 1). Integrated relaxation pressure (IRP) is the manometric parameter to appraise relaxation capability of the OGJ and is a measure of the pressure gradient between the distal oesophagus and upper stomach measured during the peristalsis relaxation window18; an elevated IRP represents outflow obstruction (system-specific normal values need to be used). Based on the pattern of oesophageal peristalsis, different phenotypes of obstruction are described (figure 2). Such subtyping has meaningful applications to therapeutic decision-making. All achalasia subtypes are associated with OGJ obstruction, defined as an increased IRP. Absent oesophageal body peristalsis defines achalasia type I and suggests a chronic form with a dilated oesophagus. Simultaneous pan-oesophageal pressurisation is observed in achalasia type II with a yet undilated but aperistaltic oesophagus such that all pressure sensors are activated together within the pressurised lumen. Achalasia type III is characterised by spastic, ‘premature’ contractions whereby oesophageal body contractile activity is too rapid for successful bolus transport (figure 2).17 OGJOO is characterised by increased IRP but with normal oesophageal peristalsis. OGJOO might be secondary to structural or mucosal pathologies (eg, strictures, malignant lesions, EoE, mucosal or submucosal lesions) or to an inherent reduction of muscular activity. The former is commonly uncovered through imaging and/or endoscopy.

Figure 1

Hierarchical classification for oesophageal motility disorders according to Chicago classification V.4.0. OGJOO, oesopageogastric junction outflow obstruction.

Figure 2

High resolution manometry examples of achalasia subtypes (I, II, III) and oesophagogastric junction outflow obstruction (OGJOO).

The standard study protocol for HRM testing is undertaken by swallowing a series of small volumes (5–10 mL) of water; however recently the addition of ‘provocative’ manoeuvres has entered the classification algorithm. These include swallowing larger volumes of water (free drinking of 200 mL water; the rapid drink challenge (RDC)) and solids (single bolus swallows or a test meal). The addition of such challenge swallows can uncover motility disorders that become apparent only after reproducing normal eating and drinking.19 Although inclusion of provocative swallows is now a standard part of the CC4.0 testing protocol, because achalasia has such a high sensitivity of being picked up with standard water swallows, CC4.0 suggests that provocative swallows are not required for the diagnosis achalasia; however recent studies have since underscored the importance of challenging the oesophagus even in achalasia as it can change the oesophageal subtype or uncover achalasia where standard small volume water swallows are inadequate to trigger a raised IRP.12 20–22 The latter in particular has important therapeutic implications as if aperistalsis is combined with a normal IRP during standard small volume swallows, therapy is commonly conservative; however, studies by Sanagapalli et al 22 and Dervin et al 20 have shown how a cohort of these patients can have achalasia of all subtypes uncovered when provocative testing is included. As a result, these patients can then be offered any of the achalasia therapies, with similar therapeutic responses to those with achalasia identified by standard manometry protocols with small-volume water swallows. Endoflip also can be used to uncover achalasia where diagnosis is not clear.23 (see below).

Another challenge is to differentiate between clinically relevant OGJOO from those that might be non-significant or be related to test artefact. Sanagapali et al described how provocative manoeuvres during HRM can discriminate between these cohorts, thus yielding implications on therapeutic appropriateness.24 The timed barium oesophagogram and functional lumen imaging probe (EndoFLIP) are also tools that can attempt to differentiate between clinically relevant and nonclinical OGJOO.25

Complementary tests in Achalasia: the old and the new

Barium radiography is an older modality for the evaluation of dysphagia that enables the assessment of the oesophageal anatomy and the degree of emptying through the oesophagus and OGJ.26 27 Barium radiography might show structural oesophageal manifestations and characteristics for advanced achalasia such as a narrow OGJ (often described as the ‘bird beak’) and the degree of oesophageal body dilatation. The main advantages of barium radiography are its wide availability, its non-invasive nature, safety and low cost. Conversely, it can miss up to one-third of achalasia cases, particularly those presenting in the early stages, type III achalasia and OGJOO.28 The use of barium radiography has been formalised such that objective measurements can be ascertained using a timed barium swallow (TBS). First introduced by de Oliveira et al,29 this test involves the ingestion of 150–200 mL of barium in the upright position to measure the maximum barium column height (and width) from images acquired at 1, 2 and 5 min; higher and wider columns of barium retained indicate poorer emptying capability.30 TBS serves as an important modality in the diagnosis of achalasia as well as to assess treatment response. A hallmark study by Blonski et al that included patients with untreated achalasia, OGJOO and non-achalasia dysphagia showed that a barium column height of 5 cm at 1 min was associated with a sensitivity of 94% and specificity of 71% for identifying achalasia.31 Vaezi et al found that barium retention is a reliable predictor for long-term treatment failure.32 Sanagapalli et al 26 revealed that the emptying capability of the oesophagus varies with different achalasia subtypes such that TBS is more reliable as a measuring tool in achalasia type I and II rather to achalasia type III and OGJOO. Furthermore, instead of isolated measurements of barium column height, Sanagapalli et al found that change in barium column height or surface area post-therapy was more accurate in correlating with treatment response.27 Penagini and colleagues have tested the correlation between RDC and TBS to assess oesophageal emptying in treated achalasia.33 Of the 175 patients, complete barium emptying occurred in 45.1% at 1 min, 64.0% at 2 min and 73.1% at 5 min. RDC-IRP (a measure of the IRP during free drinking) correlated very well with all three TBS time points (area under receiver operating curves of 0.85, 0.87 and 0.85 respectively).

EndoFLIP is an innovative complementary device that estimates the biomechanical properties of the oesophagus and OGJ. A catheter with 8 or 16 impedance sensors runs through a balloon that is gradually filled with saline.34 Filling of the balloon distends the distal oesophagus and OGJ and allows the sensors to acquire measurements as a function of the impedance and pressure transducers. Parameters measured include cross-sectional area, compliance and distensibility.35 Moreover, with the longer impedance catheters, secondary contractions at the OGJ and lower oesophagus are evoked and can be measured. Defined as panometry, these rhythmic secondary peristaltic patterns enable the classification of oesophageal motility, on par with manometry despite not measuring primary peristalsis.25 EndoFLIP can therefore be used to confirm the presence and subtypes of achalasia/OGJOO as well as uncover obstruction which may have otherwise been missed by HRM.23 36 Additionally, intraoperative EndoFLIP allows for the myotomy to be tailored in order to optimise outcome37 and can be used as an assessment of response post-therapy.38 To that end, where available, some professional guidelines recommend inclusion of the EndoFLIP device into the achalasia and OGJOO workup.39 40 The idea of using EndoFlip from the outset, at index endoscopy, even instead of manometry is attractive, but logistically it would be very difficult to determine who to target without a prior test that raises the index of suspicion to make using it at initial presentation a feasible option. EndoFlip is expensive, requires expertise, endoscopic space and sedation, so for diagnostics, it is not included for routine use within the European and Eastern guidelines. Pragmatically, where available, it should be used in specialist centres on targeted patients, commonly those in whom diagnosis is not clear and requires clarifying. Furthermore, the evidence for using EndoFlip to tailor therapy intraoperatively (during both Heller and POEM) is of growing interest.

Treatment

The primary aim for all achalasia and clinically relevant OGJOO treatment is to disrupt the OGJ in order to improve oesophageal emptying, and in turn, symptoms. The main therapeutic options include pneumatic balloon dilation (PBD), laparoscopic Heller myotomy (LHM), per oral endoscopic myotomy (POEM), botulinum toxin injection (BTI), as well as cardioplasty and oesophagectomy. Treatment choice depends on the patient age, comorbidity profile, achalasia subtype, chronicity, patient preference and available expertise. Although there are several objective measurement techniques that have been used to describe a good response in the literature, the most commonly used in most studies is an Eckardt score of ≤3; however, there is considerable variability with regards to the timescale used to report response in published studies, varying from 6 weeks to several years.

Pneumatic balloon dilatation

PBD is endoscopically performed by using a non-compliant, pressurised balloon that dilates and weakens the non-relaxing LOS.41 Complications include oesophageal perforation (2.3%–3.5%) and bleeding (1%–4%).42 Although less likely when compared with the other invasive therapies, gastro-oesophageal reflux can ensue with adequate OGJ disruption (10%–31%).43 The efficacy of PBD has been demonstrated in the literature. A retrospective study of single balloon dilatation that assessed the clinical improvement of 209 patients by using the Vantrappen achalasia questionnaire before treatment, 1 month after treatment and at the time of recurrence demonstrated that initial PBD was associated with good long-term results in more than 70% and treatment satisfaction in more than 80% of patients at 70-month follow-up.44 Further, planned, graded dilatations have been shown to influence short-term and long-term response. Torresan et al showed that in the 141 patients studied, a graded PBD protocol of 30–35–40 mm was associated with a 1-month clinical remission rate (defined as ESS ≤3) of 100% and 96.2% in achalasia subtypes I and II respectively, yet without major complications.45 Vela et al also showed that compared with LHM whereby clinical response was 89% at 6 months, a single dilatation was associated with 62% clinical response while a graded dilatation was associated with a 90% response, thus equating to Heller myotomy.46 This concept was underscored by the seminal European Achalasia Trial, which randomised 201 naive patients with achalasia to LHM and planned-graded PBD. The primary outcome of clinical success (a decrease in the ESS to ≤3) at 2 years of follow-up found that there was no difference in clinical response, reflux outcome and oesophageal emptying on barium or manometry between LHM and PBD.47 The longer term results of 5 years follow-up47 reported by Moonen et al demonstrated that patients in the two treatment arms continued to exhibit comparable success rates, with a decrease in the ESS to ≤3 in 84% for LHM and 85% for PBD, along with with similar oesophageal function and radiographic barium emptying at 5 min.48 Similarly, the 10-year follow-up study recently published found that ESS remained ≤3 in 74% for both therapies.49

Starting dilatation at 30 mm is associated with a reduced perforation risk than starting at 35 mm. Chuah et al reported a perforation risk of 3% with initial 30 mm balloon dilation,50 while Boeckxstaens et al reported a perforation rate of 32% if dilation began at 35 mm.47 On the other hand, the perforation rate ranged between 2.3% and 5% with the graded PBD protocol starting with the 30 mm diameter balloon.48 51 To that end, the American College of Gastroenterology and the European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend using a graded protocol starting with the 30 mm balloon, followed routinely by a 35 mm. The 40 mm balloon can be reserved for those who remain unresponsive with an ESS >3.52–54

EsoFLIP (Medtronic, Minneapolis, Minnesota) incorporates impedance planimetry with real-time objective visualisation and monitoring capable of dilating diameters between 10 mm and 30 mm via controlled volumetric distension with an external pressure sensor, thus facilitating graduated dilation during the same session.55 A recent systematic review of eight studies (222 patients) assessing the safety and efficacy of EsoFLIP dilation reported a pooled rate of clinical success (defined as ESS ≤3) of 68.7%. Four patients developed perforation or tear. EsoFLIP is evolving as a therapeutic option; however more data are needed to further validate its utility and safety.56

Laparoscopic Heller Myotomy (LHM)

Surgical myotomy involves the disruption of the LOS fibres together with a distal longitudinal incision. The preferred method has been LHM with its low morbidity and faster recovery.57 58 Moonen et al reported a durable response at 5 and 10 years with symptomatic relief (ESS ≤3) in 84% and 74% of cases, respectively.48 49 Though this method effectively relieves the obstruction, it also increases the risk of gastro-oesophageal reflux disease (GORD), so most surgeons incorporate an antireflux partial fundoplication.59 60

Adding fundoplication to the Heller myotomy reduces GORD dramatically; 24 hour pH monitoring drops from 31.5% (without a partial fundoplication) to. 8.8% (with the wrap) (OR, 6.3; 95% CI 2.0 to 19.4; p=0.003).61 Data from RCTs have shown that a partial fundoplication (either anterior 180 or posterior 270 degrees) significantly reduced the risk of GORD postlaparoscopic Heller’s myotomy.58 The 10-year outcome study of the European achalasia trial showed that of the 22 who completed endoscopy at follow-up who were randomised to Heller with Dor Fundoplication, only one exhibited Grade D oesophagitis while the rest had no or mild (grade A or B) oesophagitis. Furthermore, there was no difference in either the risk of oesophagitis or acid exposure on pH monitoring results between LHM and graded PBD.49 On the other hand, a meta-analysis that included 523 patients with achalasia who had LHM followed by an antireflux procedure showed that Dor fundoplication was associated with a significantly higher risk of clinical regurgitation and pathological acid reflux compared with the those who had other forms of fundoplication (OR=7.16, 95% CI 1.25 to 40.93, p=0.03, and OR=3.79, 95% CI 1.23 to 11.72, p=0.02, respectively). Furthermore, there was no significant difference in reflux symptoms and acid exposure between Dor fundoplication and those who had no fundoplication, thus implying that Dor fundoplication is the least optimum antireflux procedure following Heller myotomy and is no more efficacious than having no fundoplication.62 In contrast, Rebecchi et al demonstrated in their RCT that a 360° Nissen fundoplication generated more dysphagia without additional reflux protection at 5 years of follow-up.63

A network meta-analysis included nine RCTs comprising 911 participants. 372 (41%) were randomly assigned to LHM, 317 (35%) to single (not graded) pneumatic dilatation and 222 (24%) to POEM. Both POEM and LHM were superior to single pneumatic dilatation on direct and indirect comparison, but neither was significantly more effective than the other. There were no significant differences in perforation rates, need for reintervention or surgery, gastro-oesophageal reflux, erosive oesophagitis or serious adverse events.64

More recently, a systematic review and meta-analysis reported fewer surgical technical complications, reduced risk of mucosal perforation, shorter hospital stay, and a similar success rate of Robotic HM compared with the conventional LHM.65

Per-oral endoscopic myotomy (POEM)

POEM was first described in 201066 (figure 3). In the experienced hands, it has emerged as a safe and effective therapeutic option such that recent professional societal guidelines have endorsed POEM as being at least comparable to LHM.42 54 A systematic review and meta-analysis of the long-term outcome following POEM including 11 studies (2342 patients) reported a pooled clinical success rate of 87.3% (95% CI 83.6% to 91%), with a symptomatic pooled reflux rate of 22% (95% CI 14.4% to 29.5%), and a low rate of severe adverse events of 1.5% (95% CI 0.5% to 2.5%).67 Moreover, a meta-analysis by Park et al showed a better improvement of ESS when performing POEM compared with LHM.68

Figure 3

POEM procedure. (A) Submucosal tunnel. Mucosa is on the left and muscle is on the right. (B) Myotomy undertaken by selectively transecting the circular muscle. (C) Full-thickness myotomy transecting both circular and longitudinal muscle. POEM, peroral endoscopic myotomy.

It is proposed that LHM undertaken with a partial fundoplication should have a reduced reflux risk post-therapy than POEM which does not include an antireflux intervention.58 63 However, reflux is an umbrella term that can be defined in several ways; endoscopically defined degrees of oesophagitis, presence and intensity of symptoms, acid exposure on ambulatory pH monitoring or requirement/response to acid reducing therapy. Endoscopically, although many studies suggest an increased risk of oesophagitis in patients following POEM, on closer scrutiny, the majority are mild (grade A/B oesophagitis).69–72 Indeed grade A oesophagitis can also be seen in healthy subjects.73 74 Furthermore, most patients with reflux symptoms following POEM respond very well to standard doses of acid-reducing therapy and do not require further escalation.75 In a randomised controlled trial between POEM and LHM, Werner et al showed that at 2 years follow-up, reflux oesophagitis was present in 44% after POEM and 29% following LHM; however, in the majority this was grade A oesophagitis following both procedures, while grade C and D esophagitis was described in only 5% after POEM and 6% following LHM. On a similar note, following 24-hour ambulatory pH monitoring, an elevated acid exposure time was measured in 30% following both POEM and LHM equally.76 In a separate study undertaken by the same group, they showed that in many cases, reflux symptoms do not accurately reflect the presence of oesophagitis or pathological acid exposure.77 Rather, patients with and without symptoms of reflux following any form of achalasia therapy exhibited the same degree of acid exposure on reflux testing and oesophagitis on endoscopy; however, those with enhanced symptoms were more likely to detect perfusion of acid than those without, thus suggesting that post-achalasia therapy, a cohort of patients will develop a degree of neuromodulation and heightened oesophageal sensitivity. The authors therefore propose that the risk of postoperative reflux following achalasia therapy may be overemphasised.77

Nevertheless, active endoscopic monitoring should still be practised, monitoring possible long-term sequelae of any reflux disorder, including the development of worsening oesophagitis and Barrett’s, regardless of which achalasia therapy is performed.

POEM has been established as an effective procedure for all achalasia subtypes; however, compared with LHM, POEM is particularly suitable for those with type III achalasia. In their comparative study, Kumbhari et al showed that in those with Type III achalasia, POEM exhibited a better clinical response than LHM (98% vs 80.8%) as it permitted for a longer myotomy with a mean length of 16 cm (maximum of 26 cm) compared with LHM, which had a maximum myotomy length of 10 cm.78 The effectiveness of POEM in type III achalasia was further underscored in a recent study by Sudershan et al, with excellent ESS outcomes in the short and longer term follow-up to 1 year.79

Recently, Bourke et al have reported Eckardt scores at 6, 12 and 24 months among 16 patients with non-achalasia oesophageal motility disorders (nine patients with hypercontractile oesophagus and seven with distal oesophageal spasm) who underwent LOS preserving POEM. The median ESS decreased from 6 to 1 at 6 months after POEM and was sustained at 24 months.80 There are no comparative studies that address the treatment of spastic and hypercontractile disorders with POEM or alternative therapies, blinding is not possible and most published studies are short-term series, with subjective responses to non-validated questionnaires and considerable publication bias. To that end, the ESGE guidelines do not endorse routine implementation of POEM for non-achalasia disorders.54 Further, more studies are required with larger numbers before sphincter sparing myotomy is considered as there may be an increased risk of blown-out myotomy (BOM).

Though it is considered an effective and safe procedure, adverse events include mucosal injuries (tears and perforations) in up to 4.8% of cases and major bleeding in up to 1.4%. Mild to moderate transient postoperative pain can be seen in up to 79%. Rare adverse events reported include aspiration pneumonia (<0.1%), oesophageal leak (0.3%), pleural effusion requiring drainage (0.2%), empyema (<0.1%), cardiopulmonary complications (0.7%) and the need for conversion to surgery (0.1%).81

As CO2 is normally insufflated during the tunnelling and myotomy, gas-related events such as pneumomediastinum and pneumoperitoneum should be expected and not considered an adverse event. One study showed that a CT scan performed post-POEM will detect pneumomediastinum and/or pneumoperitoneum in up to half and subcutaneous emphysema in nearly one-third of patients.82

More recently, a complication that has been reported following LHM and POEM (but not following PBD) is BOM, defined radiologically as a wide-mouthed outpouching or pseudo-diverticulum, which leads to more than 50% increase in the oesophageal diameter. This is likely due to oesophageal wall strain in an area which is weakened by myotomy. This is more common following LHM and those with a persistently raised IRP. It is theorised, therefore, that a shorter myotomy in Type I and II achalasia should help reduce this risk, and that type III achalasia myotomy length with POEM should be tailored to the height of the spasm reflected on the manometry.83

Recently, a few technical modifications have been adopted for POEM:

Myotomy length; short versus standard

The index technique proposed by Inoue et al used a mean myotomy length of 8 cm (oesophagus 6 cm with 2cm gastric extension).66 However, recent studies have proposed a shorter myotomy with comparable clinical efficacy in type I and II achalasia.84 85 A randomised controlled trial by Nabi et al including 71 patients with achalasia type I and II demonstrated that short myotomy (2.76±0.41 cm) compared with standard myotomy (7.97±2.4 cm) was associated with a significantly shorter procedure time (44.03±13.78 min vs 72.43±27.28 min, p<0.001) yet comparable clinical success (ESS≤ 3) of 93.6% vs 96.9% at 1-year follow-up,respectively.86 Furthermore, a meta-analysis by the same group showed a similar rate of hospital stay and adverse events in the standard and short myotomies groups, but with reduced acid exposure time in the short myotomy group.87

Myotomy thickness; complete versus selective circular myotomy

Circular muscle myotomy was used in the standard techniques.70 Although limited, studies comparing complete myotomy (circular+longitudinal) with circular-only myotomy showed no difference in clinical success. On the other hand, while a complete myotomy was associated with a shorter procedure time, it seemed to be associated with a higher incidence of reflux disease88 89

Myotomy orientation; anterior (1–2 o’clock) versus posterior (5–6 o’clock) approach

The clinical outcomes of anterior versus posterior approach assessed by randomised controlled trials showed similar results at 6–12 months follow-up.90 91 In a randomised controlled trial of both approaches, Ramchandani et al showed that although overall outcomes were the same between the two, risk of mucosotomy was higher in the anterior group (20% vs 3.3%; p=0.02) while acid exposure was higher in the posterior group (13.99%±14.48 vs 2.98%±4.24; p<0.01).92 In another randomised study with longer term follow-up of 2 years, Ichkhanian et al confirmed equal efficacy and reflux burden for both anterior and posterior myotomy (85% vs 79%, respectively).93

Sling fibre preservation POEM

Recently sling fibre preservation POEM has been described, with the aiim of reducing the rate of post-POEM erosive esophagitis. A study by Shiwaku et al assessing patients who underwent posterior myotomy without preservation of the sling fibres in 68 (group 1) versus 81 with sling fibre preserving POEM (group 2) showed that the rate of severe erosive gastritis (Los Angeles grade C or more) occurred in 44.1% in group 1 versus 18.5% in group 2, with complete gastro-oesophageal flap valve preservation in group 2.94

POEM following previous therapy

Classically, the cornerstone treatment of achalasia has been LHM95; however, there is at least a 10% rate of recurrence over time.96 Historic reports suggested that repeating LHM is more effective than PBD post-failed index Heller myotomy97; reoperating in a previous surgical plane increases surgical complexity and risk of complications, which limits efficacy.97 POEM post-Heller myotomy provides an effective, safe and promising option to treat patients with failed LHM or recurrence.98 99 POEM can be carried out in either the anterior or posterior orientation, thus facilitating the ability to avoid the previously operated surgical plane. An international experience of POEM as salvation treatment following Heller myotomy in 51 patients showed a technical success rate of 100%, long-term clinical success in 94% and procedure-related adverse events rate of 13% (six patients endured intraprocedural mucosal defects, all treated endoscopically).100 Similarly, Liu et al showed that POEM undertaken after failed PBD was safe, effective and was associated with a low rate of complications.101

Botulinum Toxin Injection (BTI)

BTI can be injected into the LOS in achalasia and into the distal oesophagus in diffuse spasm and achalasia type III. Botulinum toxin inhibits the release of presynaptic acetylcholine, thus temporarily preventing muscle contractions.102 BTI is safe and is associated with limited complications, with only some reports of chest pain or allergic reactions.102 An older study by Storr et al that aimed to assess the effectiveness of BTI for the treatment of achalasia has described a significant reduction in lower oesophageal resting pressure (before 38.2±11.3 mm Hg; 1 week after 20.5±6.9 mm Hg; 1 month after 17.8±6.8 mm Hg; p<0.001). Moreover, global symptom score (dysphagia, regurgitation, chest pain) was significantly decreased after 1 week and 1 month.103 In a double-blind trial, 21 patients with achalasia received either 80 units of botulinum toxin or placebo. Response to treatment was assessed based on changes in the modified ESS (from 1 to 9) and the change in lower oesophageal pressure. One week after treatment, there was a 5.4 point mean decrease in symptoms for the patients treated with BTI compared with just 0.5 points for the placebo group (p=0.001). Furthermore, there was a 33% reduction in LOS pressure in the treatment group compared with placebo (p=0.02).104 The primary drawback however, is its short duration of action and the need for repeated therapy, generally in less than 1 year.105 Furthermore, BTI does not halt achalasia progression. To that end, societal guidelines recommend reservation of BTI for those at high risk of traditional, more invasive therapies such as the frail and elderly.

Oesophagectomy

Oesophagectomy is a major thoracic surgical intervention, rarely offered as a primary treatment for achalasia, but reserved for those with long-standing, decompensated oesophagus with anatomy that is too dilated or sigmoid in shape such that no form of OGJ disruption will help. Commonly those requiring oesophagectomy are at increased risk of malnutrition, vomiting and aspiration. Furthermore, in such cases which are commonly associated with prolonged food stasis, there may be an increased risk of squamous cell carcinoma.53 A systematic review and meta-analysis over 1307 achalasia patients treated with oesophagectomy showed a mean postoperative morbidity rate of 27% and mortality rate 2.1%.106 Decisions for such radical therapy are best taken in the context of a multidisciplinary setting, which includes a fully informed patient, with all risks and patient fitness taken into account.

Per-oral plication of the oesophagus (POPO) is an innovative endoscopic approach using the suturing Apollo Overstitch device to remodel the dilated megaoesophagus of end-stage achalasia. Hedberg et al reported five cases of POPO performed for end-stage achalasia with 100% technical success and dysphagia symptom improvement as well as subjective improvement by means of barium radiography.107 Surgical cardioplasty is an old procedure reserved for end-stage achalasia that aims to circumvent oesophagectomy and modify the LOS to facilitate oesophageal emptying.108 Several techniques have been described and modified over the years. These include opening all the cardia layers followed by gastric fundus superposition,109 cardioplasty followed by subtotal gastrectomy with Roux-en-Y anastomosis,110 laproscopic ‘hand-sewn’ cardioplasty111 and stapling the cardioplasty with side to side anastomosis between the lower oesophagus and fundus.112 Although many studies report a good outcome, these are almost all retrospective series and based on small numbers. Also, postoperative complication risk can reach 25% and there is a high rate of long-term reflux, which can sometimes be severe.