Int J Gastrointest Interv 2020; 9(2): 53-61
Published online April 30, 2020 https://doi.org/10.18528/ijgii200012
Copyright © International Journal of Gastrointestinal Intervention.
Department of Medical Gastroenterology, AIG Hospitals, Hyderabad, India
Correspondence to:* Department of Medical Gastroenterology, AIG Hospitals, Plot No 2/3/4/5, Survey No 136, 1 Mindspace Rd., Gachibowli, Hyderabad, Telangana 500032, India.
E-mail address: email@example.com (M. Ramchandani).
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Achalasia cardia is a rare esophageal motility disorder. Although a primary neurological disorder, the treatment modalities of achalasia are primarily endoscopic or surgical. Pneumatic dilatation (PD) or laparoscopic Heller’s myotomy (LHM) have been the mainstay of achalasia management for several decades. With the introduction of third space endoscopy, the endoscopic management of achalasia has revolutionized. Randomized studies have concluded the superiority of per-oral endoscopic myotomy (POEM) over PD. In addition, the short-term outcomes of POEM are similar to LHM. POEM is a relatively new technique and long-term data is eagerly awaited. The main concern after POEM is a high incidence of gastroesophageal reflux disease (GERD) which is found in about half of the patients undergoing this procedure. GERD is higher after POEM when compared to PD and LHM with fundoplication. The management of achalasia should be individualized and based on factors like patient characteristics (age, sex, comorbidities), subtyping on high resolution manometry, patient/doctor preference, and surgical risk of the patient.
Keywords: Dilatation, Esophgeal achalasia, Heller myotomy, Per-oral endoscopic myotomy procedure
Achalasia cardia is a primary esophageal motility disorder of unknown etiology. It is characterized by esophageal aperistalsis and insufficient relaxation of the lower esophageal sphincter (LES) in response to deglutition.1 The most widely accepted pathophysiological basis of achalasia is selective loss of inhibitory innervation from the myenteric plexus of the esophagus and LES due to genetics, infection, and autoimmune etiologies.1
The goal of achalasia treatment is to reduce the LES pressures, alleviate symptoms of dysphagia and regurgitation, improve esophageal emptying, and prevent the development of end stage achalasia.
Treatment modalities for achalasia include pharmacological therapy, endoscopic (botulinum toxin [BT] injection, pneumatic dilatation [PD], and per-oral endoscopic myotomy [POEM]), and surgical (laparoscopic Heller’s myotomy [LHM] and esophagectomy) (Table 1).2,3 Of these, pharmacotherapy and BT injection are primarily utilized in high risk patients who are not candidates for more durable treatment options like PD, LHM, and POEM.4,5
In this review, we shall limit our discussion to the major modalities used for achalasia i.e., PD, POEM, and LHM.
PD works by circumferential stretching and in some cases tearing of LES circular muscle fibres. PD is an effective and widely utilized endoscopic treatment for achalasia. The most widely used balloon dilator is the non-compliant, polyethylene balloon i.e., RIGIFLEX (Boston Scientific, Natick, MA, USA). Pneumatic balloons are available in three diameters (3.0, 3.5, and 4.0 cm) for graded dilatation (Fig. 1).6
Initial response rates with PD is around 71% to 90%. However, relapse rates after initial remission are found in 30%–50% patients on follow-up.7–9 Graded and on demand dilatation is the accepted standard of care with respect to PD. With this approach, a long-term remission rate of up to 90% has been reported in recent trials.10,11 The median time to relapse after PD in long-term follow-up studies (> 10 years) is between 5–11 years.7,9,12,13
In ‘graded approach’ the smallest balloon (30 mm) is used for dilatation initially (35 kPa for 1 minute followed by 55 kPa for 1 minute). Subsequent dilatations are performed using incrementally larger balloons in those with persistent or recurrent symptoms (35 mm after 1–3 weeks, and 40 mm if Eckardt’s score > 3). In cases with late relapse (> 1 year) after completion of graded regimen, repeated dilatations have been shown to be effective in ameliorating the symptoms. In a large, retrospective study, long-term (10 years) response rates were superior with on demand dilatations as compared to single dilatation (90% vs 50%).8 However, in patients with persistent symptoms or early relapse (< 1 year) after graded PD alternative options like LHM or POEM should be considered. Some experts perform incremental dilatations on the same or consecutive days until pre-specified manometric (LES pressure < 15 mmHg) or radiographic goals are met.14 It is important to note that the technique of PD is not standardized making it difficult to compare the outcomes between different studies.
The predictors of good response after achalasia include type II achalasia and age > 40 years. The risk factors for non-response to PD include non-graded dilatation, age < 40 years, pre-existing daily chest pain, and pre-treatment width of the esophagus of < 4 cm.11,15 In addition, spastic esophageal motility disorders including type III achalasia, Jackhammer oesophagus, and distal esophageal spasm do not respond well to PD. Of the different symptoms of achalasia, chest pain responds in only about 50% of the patients.7,9,15,16
The data on the outcomes of PD in pediatric achalasia are limited. In few studies, good response (success 87%) has been found especially in older children.17 Of note, the currently available pneumatic balloons have not been specifically designed for use in small children (< 8 years).
The resonse rate to PD is lower (~50%) in patients with symptom relapse after Heller’s myotomy. Nevertheless, PD has been shown to be a safe procedure in patients with failed myotomy.18 Similarly, the response to PD is poor (0%–20%) in cases with recurrent symptoms after POEM.19
PD dilatation is a safe procedure and major complications are uncommon. The most feared complication associated with PD is perforation which has been reported in 1%–5% of patients. Lower rates of perforation have been reported in studies from high volume centres.22 The risk factors for perforation after PD include use of larger (> 35 mm) balloon for initial dilatation, old age, and unstable balloon position during PD.11,22–24
Tachycardia and chest pain persisting > 4 hours should alert the endoscopist about the possibility of perforation.25 Majority of the perforations after PD can be managed conservatively. However, larger perforations with free flow of barium into mediastinum require surgical repair.26 For the same reason, PD should be preferably avoided in high surgical risk patients. Other management options include endoscopic closure (over the scope clips, endoscopic suturing, and esophageal stents) and video-thoracoscopic repair.27–29
LHM is a widely performed surgical procedure for achalasia cardia. The main advantage of LHM over PD is durable response and reduced requirement of repeated interventions. The technique of Heller’s myotomy has undergone several critical modifications since its initial description by Heller in 1913.2,32 These modifications include the development of minimally invasive approach, addition of fundoplication procedure to reduce the incidence of GERD and performing an extended myotomy on gastric side to prevent future recurrences.33,34
Minimally invasive approaches are associated with shorter postoperative pain, and hospital stay as compared to open surgical myotomy.35 With the availability of minimally invasive surgical options, open surgical myotomy is performed only in exceptional circumstances like in cases with multiple prior surgeries or in those who cannot tolerate a pneumoperitoneum due to severe cardiopulmonary disease.35 Currently, a laparoscopic approach is preferred as it is associated with a shorter operating time, lower rate of conversion to an open myotomy and shorter hospital stay as compared with thoracoscopic approach.36,37
Partial fundoplication is an essential component of LHM and can be performed anteriorly (Dor fundoplication, 180 degree) or posteriorly (Toupet fundoplication, 270 degree). Both the approaches are equivalent in terms of post-operative dysphagia and reduction in the incidence of GERD. In a randomized controlled trial (RCT), the incidence of GERD was lower in posterior fundoplication group. However, the difference was not statistically significant (21% vs 42%) (Table 2).38 Therefore, the choice of anterior or posterior fundoplication is largely operator dependent.
LHM has been extensively evaluated for the management of achalasia. In the European achalasia trial, the response rates to LHM at 1, 2, and 5-years are 93%, 90%, and 82%, respectively.10,11 In a more recent randomized trial, the clinical success at 2-years was 81.7%.39 Extended gastric myotomy (3 cm vs 1.5 cm) has been shown to improve success rates and reduce recurrences after LHM.33 In contrast to non-sigmoid achalasia, the outcomes of LHM in sigmoid achalasia are sub-optimal. The decision to add fundoplication in these cases should be carefully made.40
The most common complication following LHM is perforation (1%–7%) due to unrecognized mucosal injury during surgery.41 Some surgeons prefer an anterior fundoplication in these cases as it usually buttresses the repair.
GERD has been reported in 2%–26% of cases after LHM with fundoplication. In a meta-analysis, the pooled rate of post-procedure reflux symptoms, abnormal oesophageal acid exposure, and esophagitis were 8.8%, 16.8%, and 7.6%, respectively after LHM. The addition of fundoplication procedure to LHM reduces rate of pathological GERD from 47.6% to 9%. Similar reduction in esophageal acid exposure time has been reported after fundoplication (4.9% to 0.4%).34
Other adverse events are rare after LHM and include inadvertent division of vagus nerve (diarrhoea, bloating, early satiety or dumping syndrome) and splenic injury (1%–5%).42
POEM is a novel endoscopic procedure for achalasia based on the principles of submucosal endoscopy with mucosal flap safety valve technique. Since its introduction nearly a decade ago by Inoue et al,43 POEM is among the most widely performed procedures for achalasia.
POEM is performed with the patient in supine position under general anaesthesia. Contraindications to POEM include coagulopathy, cirrhosis with portal hypertension, severe erosive esophagitis, esophageal submucosal fibrosis (e.g., radiation, endoscopic mucosal resection, radiofrequency ablation), and severe cardiopulmonary diseases.44,45
We have previously described the technique of POEM procedure.46 In brief, the steps of POEM procedure include mucosal incision, creation of a submucosal tunnel, myotomy, and closure of mucosal incision with multiple clips (Fig. 2). The length of esophageal myotomy is decided on the type of achalasia and manometry findings. Long esophageal myotomy is required in cases with type III achalasia. On the other hand, the length of gastric myotomy should be at least 2-cm in all the achalasia sub-types to avoid future recurrences. However, a long gastric myotomy (> 4 cm) should be avoided as it may lead to higher risk of severe erosive esophagitis.47
Several variations in the POEM technique have been described in the literature. These include orientation of myotomy (anterior, posterior or greater curvature), length of myotomy (short vs long), and thickness of myotomy (full thickness vs selective circular). All the approaches have similar efficacy with no clinically relevant difference in adverse events or incidence of GERD.48–52 Muscle fibres are cut in 1–2 o’clock and 5–6 o’clock position in anterior and posterior myotomy, respectively (Fig. 3). Currently, posterior approach is being increasingly used by endoscopists due to technical ease as accessories emerge from 6 o’clock position. Also, in patients with a history of prior Heller’s myotomy posterior orientation is preferred to avoid submucosal fibrosis during POEM.53 Therefore, the technique of POEM is largely operative dependent. However, greater curvature myotomy is not performed widely as it leads to disruption of ‘angle of His’ which may predispose to GERD.
A novel cautery device (Speedboat-RS2; Creo Medical Ltd., Chepstow, Wales, UK) which uses bipolar radiofrequency energy for cutting and microwave for coagulation has been described in creation of submucosal tunnel in POEM.54 The use of the device has been described recently for endoscopic submucosal dissection.55 The advantages of the device is that there is no need to change accessories for submucosal injection (has integrated injection needle) and coagulating vessels, capability of rotation to optimize cutting and coagulation, bipolar cutting and protective hull avoiding injury to muscle and mucosa.54,55
Over last decade, multiple studies with short- and medium-term follow-up have concluded the safety and efficacy of POEM for achalasia.56,57 The technical and clinical efficacy of POEM is > 90% and 80%–90%, respectively. POEM is also effective in patients with a history of prior treatment.58 The efficacy of POEM in patients with recurrent symptoms after LHM is 81% to 95% in different studies.59–61 Majority of the published data depicts the outcome of POEM on short-term follow-up. The efficacy of POEM in studies reporting long-term outcomes is between 80%–90%, suggesting that the response is durable after POEM.62–65 The long-term efficacy of POEM remains to be seen in large, prospective studies as these studies are mostly retrospective with only a proportion of patients completing entire follow-up.
A risk score (Zhongshan POEM score) has been proposed based on history of previous treatment, mucosal injury, and clinical reflux to predict risk of failure after POEM based on data from a large cohort (
POEM is a safe procedure with relatively uncommon serious adverse events. Different severity grading systems utilized in the published literature has resulted in considerable heterogeneity in the incidence of adverse events. The incidence of major adverse events in large studies ranges from 0.5% to 3.3%.62 Insufflation related events are common during POEM but usually do not translate into clinically significant adverse events. These include subcutaneous emphysema (7.5%), pneumothorax (1.2%), pneumomediastinum (1.1%), and pneumoperitoneum (6.8%).68 The use of CO2 which has a higher diffusion capacity than air has remarkably reduced the occurrence of insufflation related adverse events.69
Mucosal injuries are the second most common adverse events during POEM. Most of them can be identified and managed intra-operatively. A history of submucosal fibrosis, previous myotomy (Heller’s or POEM), mucosal edema, long tunnel (> 13 cm) are predisposing factors for mucosal injury.70 Other adverse events are rarer and include major bleeding, aspiration pneumonia, delayed mucosal barrier failure, mediastinitis, esophageal leaks, and pulmonary like pleural effusion.68 Most of them do not require major surgical intervention and can be managed intra-operatively.
GERD is an important long-term adverse event of POEM procedure. Recent studies indicate a high incidence of GERD after POEM. In the published studies, the prevalence of symptoms, reflux esophagitis, and increased esophageal acid exposure after POEM ranges from 17% to 40%, 18% to 65%, and 13% to 58%, respectively.71 The predictors of post-POEM reflux include low integrated relaxation pressure after POEM, female sex, high body mass index (BMI), and the presence of hiatus hernia. However, these predictors need to be validated in large, prospective trials. On the contrary, the technical variations in POEM procedure have no significant impact on the incidence of GERD after POEM.71,72
Prevention of reflux is the one of the core concerns among the endoscopists performing POEM procedure. Several novel technical modifications have been proposed to reduce the incidence of post POEM GERD. These include avoidance of excess myotomy (> 4 cm) on the gastric side, preservation of sling or oblique fibers during posterior POEM (Fig. 4) and creating a fundoplication wrap during POEM NOTES-F (natural orifice transluminal endoscopic surgery-fundoplication) (Fig. 5).73–75 Of note, the double scope technique provides more accurate estimation of the extent of gastric myotomy and should utilized whenever feasible. Although appealing, the utility of these novel techniques remains to be seen in randomized trials.75
LHM is a more durable treatment with less requirement of re-interventions as compared to PD. On the other hand, the efficacy of single session of PD is very low (50%) and re-dilatations are required in about a quarter of patients after graded dilatation. Graded and on demand PD have been found to provide similar efficacy to LHM in the landmark European achalasia trial.11 The efficacy of PD and LHM at 1 year (90% vs 93%), 2 years (86% vs 90%), and 5 years (82% vs 91%) was comparable with no difference in the objective parameters including LES pressure, quality of life, and esophageal acid exposure.10,11 The requirement for re-dilatation was higher in a subgroup of patient less than 40 years of age.10,31
In a large retrospective study, POEM was more effective than PD in all the sub-types of achalasia. The efficacy of POEM vs PD was 92% vs 51% in type I (
The comparison between LHM and POEM is limited to one randomized trial and multiple small nonrandomized studies. A meta-analysis consisting of 74 cohort studies with more than 7,000 patients concluded that POEM results in higher rate of dysphasia relief (93.5% vs 91% at 1 year and 92.7% vs 90% at 2 years, both statistically significant) than LHM. However, the follow-up was longer in the LHM group (41.5 vs 16.2 months).78 In the only published randomized trial, POEM (112 patients) was compared to LHM plus Dor’s fundoplication (109 patients). Clinical success at the 2-year follow-up was similar in both the groups (83.0% vs 81.7%). Serious adverse events occurred in 2.7% of patients in the POEM group and 7.3% of patients in the LHM group. Reflux esophagitis was higher in the POEM group (44% vs 29%).39 POEM and LHM appear comparable in efficacy with higher reflux rates after POEM.
Achalasia cannot be cured with the currently available treatment options which are directed at reducing LES pressures. A finite proportion of cases do relapse on follow-up irrespective of the treatment modality used. Presently, there are three effective treatment options for achalasia cardia i.e., PD, POEM, and LHM. The choice between these three is based on patient characteristics like age and co-morbidities, type of achalasia, available expertise and patient’s preference (Fig. 6). The best candidates for PD are those older than 40 years and those with type II achalasia. Type I and III achalasia do not respond well as compared to type II achalasia (63% vs 33% vs 90%). The possible requirement of repeated dilatations and small risk of perforation (1%–3%) should be conveyed to the patients. Graded dilatation followed by on demand dilatation is the standard of care and anything less is likely to give sub-optimal results with PD. Both LHM and POEM are effective modalities with fewer requirement for re-interventions (Table 3).79–82 LHM and POEM should be preferred over PD in young patients (< 40 years) and those with spastic esophageal motility disorders. Since there is no difference in efficacy (type I and II achalasia), the choice between these two is largely determined by the available expertise and the treating physician or surgeon’s preference. POEM may be preferred over LHM in type III or spastic achalasia and in those with spastic esophageal motility disorders. The ability to perform long esophageal myotomy is the reason for better response rates with POEM as compared to LHM in spastic esophageal motility disorders. Similarly, POEM is more efficacious than PD in patients with prior Heller’s myotomy. In patients with relapse of symptoms after POEM, re-do POEM and LHM may be superior to PD. The major drawback of POEM is limited data on outcomes during long-term follow-up and a high incidence of GERD. LHM should be preferred to POEM in patients with high risk of post-POEM reflux like those with concomitant hiatal hernia and high BMI. On the contrary, LHM has been shown to effective in long-term and the incidence of reflux is significantly lower than POEM. The risk of GERD and possible need to stay on proton pump inhibitors for long-term should be discussed with the patient while contemplating POEM procedure. At this point, POEM may be avoided in pediatric age group as they may be exposed to acid exposure for more years of which the consequences are not well-known.
No potential conflict of interest relevant to this article was reported.
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