Abstract
Background
Achalasia is characterized by failure of relaxation of the lower oesophageal sphincter (LOS) and abnormal peristalsis during swallowing. The study aimed to observe the effects of intervention in three sub-types of achalasia and compare the intervention outcomes among the three sub-types.
Methods
Forty-one patients underwent Eckardt scoring for severity of achalasia, followed by high-resolution manometry (HRM). After three and six months of intervention (pneumatic dilatation or 'Heller's Cardiomyotomy), Eckardt scoring and HRM were repeated and compared with the initial results.
Results
Out of the 41 patients, 13 were diagnosed with type I achalasia (31.71%), 18 with type II (43.90%), and 10 with type III (24.39%). Significant differences between the pre- and post-intervention values of median integrated relaxation pressure (IRP) and Eckardt score were found in all three sub-types. Although the beneficial effect of intervention lasted up to six months postintervention, it was less than three months postintervention values. The intervention success rates were highest for both laparoscopic Heller's myotomy (LHM) and pneumatic dilatation (PD) in Type II Achalasia at three and six months postintervention, respectively.
Conclusion
One-time intervention is effective in all three sub-types. This benefit tends to taper over time but remains significant after six months of intervention. Type II Achalasia shows the best intervention outcomes compared to the other two sub-types at three months and six months post-intervention. Type III Achalasia shows the least response compared to other sub-types and is the poorest responder to intervention. The benefit of one-time intervention also deteriorates most in type III achalasia at the end of six months.
Keywords: Achalasia, High resolution manometry, Lower oesophageal sphincter
Introduction
Achalasia is a motility disorder involving the oesophagus where there is a problem with relaxation of the lower oesophageal sphincter (LOS) during swallowing along with abnormal peristalsis. This results in various symptoms that are common to patients with achalasia e.g., regurgitation, chest pain, dysphagia, etc. The pathophysiology of achalasia is only partially understood, and it has been hypothesized that there is an imbalance between excitatory and inhibitory neurons in the myenteric plexus, with the latter being predominantly affected.1, 2, 3, 4
High-resolution manometry (HRM) is the gold standard for the diagnosis of achalasia.5,6 The Chicago Classification v3.0 divides achalasia into three subtypes, and gastric outlet obstruction.7
The treatment protocol for achalasia, however, is similar for all three subtypes.8 There are various modalities of treatment available for achalasia patients, e.g. drug therapy, pneumatic dilatation (PD), Heller's myotomy, botulinum injection etc.1,9The three subtypes are distinct in terms of their responsiveness to medical or surgical therapies. Subjective assessment of the severity of dysphagia has been described and can be used to assess the symptomatic benefits obtained after therapy.10 However, a clear-cut consensus on the choice of therapy for the various subtypes based on the treatment outcomes has not been reached. A higher percentage of patients with type II achalasia (based on manometric tracings) are treated successfully with PD or laparoscopic Heller's myotomy (LHM) than patients with types I and III achalasia.1,7,9,11
This pilot study was designed to study the effect of intervention in the three subtypes as well as compare the effects between the three subtypes.
Materials and methods
The study was carried out at the gastrointestinal (GI) motility lab of the Dept. of Physiology in collaboration with the Dept. of Gastroenterology, Armed Forces Medical College. A total of 41 patients were included in this prospective cohort study who were diagnosed as one of the achalasia subtypes as per the Chicago Classification of Esophageal Motility Disorders v 3.0,7 over a duration of 3 years. Patients suffering from concurrent GI disorders that affect oesophageal motility and previously diagnosed and managed cases of achalasia were excluded from the study. The study protocol was approved by the institutional ethical committee. Informed consent from all patients was obtained prior to the study. All guidelines as per the Declaration of Helsinki and good clinical practice guidelines were followed.
A High-resolution 16-channel water perfusion assembly with Electronic Pressure Transducers manufactured by the Royal Melbourne Hospital, Australia, was used for esophageal manometry. Patients came after an overnight fast of 12 h. Any drug interfering with GI motility was stopped for five half-lives prior to the test. A total of 10 wet swallows with 5 ml of potable water were performed at intervals of 30 s, in both sitting and lying positions. Eckardt scoring for the severity of achalasia was obtained. The analysis of HRM data were done using Trace 1.2 V software (Royal Melbourne Hospital, Victoria, Australia). Thereafter, intervention (either PD or LHC) was performed at the gastroenterology department. The patients were offered all available treatment modalities. Based on age and barium imaging, patients with sigmoid oesophagus were specifically referred for surgery. PD was done by either of the two available endoscopists. The end point of dilatation was done under endoscopic guidance with a non-compliant balloon with a wide enough diameter, starting at 30-mm diameter (up to 35 mm). The balloon was inflated up to 12 psi (Maximum) and maintained for 60 s/till obliteration of the waist as seen under fluoroscopy. LHC was done by the same surgical team. End points in surgery were “longitudinal muscles split, the gastroesophageal (GE) junction extending 4 cm above and 2 cm below, including the oblique muscle fibers of the stomach. It was continued until the mucosa popped out. It was ensured that the mucosa wasnot breached”. Standard procedures were followed. Anterior fundoplication was added in all cases. Patients with Eckardt symptom score ≥2 were considered for intervention.1 After three and six months of intervention, the patients were called for follow-up, HRM and Eckardt Scoring were repeated, and the results were compared with the initial results. An Eckardt symptom score of ≥2 was considered a failure to respond to treatment. Since treatment was considered in patients with Eckardt score ≥2, we also considered this the cut-off mark for failure instead of the more accepted score of >3.1,10
The results were put to statistical analysis using “IBM SPSS Statistics 20 software”. The data were presented as mean ± standard deviation (SD). All values were rounded off to the second decimal place. A one-way Analysis of Variance (ANOVA) test was performed to compare continuous variables between achalasia subtypes. Pearson's chi-square test was performed to compare the distribution of categorical variables between achalasia subtypes and to compare intervention response between 3 achalasia subtypes at three and six months. Repeated measures ANOVA was performed to compare the outcome of intervention over ‘median integrated relaxation pressure (IRP)’ and ‘Eckardt symptoms score’, at three and six months within a group. A post-hoc Bonferroni test was performed to find out which groups were significantly different from each other.
Results
Out of the 41 patients, 13 were of ‘Type I achalasia’ (31.71%), 18 patients were of ‘Type II achalasia’ (43.90%) and 10 patients were of ‘Type III achalasia’ (24.39%). There was no significant difference between characteristics of the study population, as shown in Table 1.
Table 1.
Baseline characteristics of 41 patients according to 3 achalasia subtypes.
| Type I (n = 13; 31.71%) | Type II (n = 18; 43.90%) | Type III (n = 10; 24.39%) | p-value | |
|---|---|---|---|---|
| Age | 37.69 ± 3.07 | 36.72 ± 2.93 | 38.4 ± 2.59 | 0.327a |
| Gender | 0.96b | |||
| Male (n = 19) | 6 (46.15%) | 8 (44.44%) | 5 (50%) | |
| Female (n = 22) | 7 (53.85%) | 10 (55.56%) | 5 (50%) | |
| Median IRP | 26.63 ± 5.78 | 25.50 ± 3.85 | 25.83 ± 5.62 | 0.820a |
| Total Eckardt Score | 4.92 ± 1.71 | 4.11 ± 1.08 | 4.40 ± 1.65 | 0.312a |
IRP, integrated relaxation pressure.
One way ANOVA test.
Pearson's Chi-square test.
On looking at the effect of intervention (13 Type I achalasia-7 PD and 6 LHM, 18 Type II achalasia-8 PD and 10 LHM, 10 Type II achalasia- 4 PD and 6 LHM) over median IRP and Eckardt score at intervals of three months and six months, we found a significant difference between the pre- and post-intervention values of ‘median IRP’ and ‘Eckardt Score’, in all the three subtypes of achalasia (Table 2). The success rate of treatment after three months was higher and statistically significant for both LHM and PD (91% vs. 71.4%, p < 0.05) in Type II achalasia. The success rate of treatment after six months was also higher and statistically significant for both LHM and PD (72.72% vs. 42.85%, p < 0.05) in Type II achalasia. The success rate of LHM intervention was better than PD intervention but was not statistically significant in Type III Achalasia patients (50% vs. 0%) because of a smaller number of patients. The success rate of LHM and PD was similar but not statistically significant at three and six months (50% vs. 42.85% and 72.77% vs 42.85%, respectively).
Table 2.
Comparison of median IRP and Eckardt Scores before and after intervention in achalasia subtypes.
| Preintervention | Postintervention (three months) | Postintervention (six months) | p-value (Wilk's Lambda)a | |
|---|---|---|---|---|
| Type I achalasia (n = 13) | ||||
| Median IRP | 26.63 ± 5.78 | 14.68 ± 1.79 | 15.76 ± 7.54 | <0.0001 |
| Eckardt | 4.92 ± 1.71 | 1.85 ± 1.28 | 2.08 ± 1.19 | <0.0001 |
| Type II achalasia (n = 18) | ||||
| Median IRP | 25.50 ± 3.85 | 11.08 ± 4.74 | 13.43 ± 6.31 | <0.0001 |
| Eckardt | 4.11 ± 1.08 | 1.22 ± 0.81 | 1.67 ± 1.33 | <0.0001 |
| Type III achalasia (n = 10) | ||||
| Median IRP | 25.83 ± 8.62 | 17.7 ± 4.50 | 21.29 ± 4.42 | <0.0001 |
| Eckardt | 4.40 ± 1.65 | 2.40 ± 1.35 | 3.10 ± 1.52 | 0.004 |
IRP, integrated relaxation pressure.
Multivariate repeated measures ANOVA test.
At three months postintervention, both the median IRP and Eckardt score were found to have decreased significantly in all the subtypes of achalasia (p < 0.05). However, at six months postintervention, the median IRP and Eckardt scores showed significant reductions in Type I and Type II achalasia patients. While, in Type III achalasia patients, only the Eckardt score remained significantly reduced (p = 0.04) compared to preintervention values (Table 3, Figs. 1, 2 and 3).
Table 3.
Comparison between pre- and post-intervention parameters using post-hoc Bonferroni test.
| Pre- vs. post-intervention (three months) Mean differencea (p-value) |
Pre- vs. post-intervention (six months) Mean differencea (p-value) |
Post-intervention (three months) vs. post-intervention (six months) Mean differencea (p-value) |
|
|---|---|---|---|
| Type I achalasia (n = 13) | |||
| Median IRP | 11.95 (<0.0001) | 10.87 (<0.0001) | −1.09 (0.457) |
| Eckardt | 3.08 (<0.0001) | 2.85 (<0.0001) | −0.23 (0.570) |
| Type II achalasia (n = 18) | |||
| Median IRP | 14.42 (<0.0001) | 12.07 (<0.0001) | −2.35 (0.007) |
| Eckardt | 2.89 (<0.0001) | 2.44 (<0.0001) | −0.44 (0.083) |
| Type III achalasia (n = 10) | |||
| Median IRP | 8.13(0.001) | 4.54 (0.083) | −3.59 (0.001) |
| Eckardt | 2.00 (0.003) | 1.30 (0.04) | −0.70 (0.029) |
IRP; integrated relaxation pressure.
Difference between means of, preintervention – postintervention (three months), pre-intervention - post-intervention (six months) and post-intervention (three months) vs. post-intervention (six months).
Fig. 1.
Comparison of IRP and Eckardt scores at the pre-treatment, three months and six months post-treatment stage for Type I achalasia patients.
Fig. 2.
Comparison of IRP and Eckardt score at pre-treatment, three month and six month post-treatment stages for Type II achalasia patients.
Fig. 3.
Comparison of IRP and Eckardt scores at the pre-treatment, three months and six months posttreatment stage for Type III achalasia patients.
The treatment response in different subtypes of achalasia was significantly different at three months postintervention (p = 0.017) and six months postintervention (p = 0.032). We found out that the success rates at three months postintervention were 53.85% for Type I achalasia, 83.33% for Type II achalasia and 30% for Type III achalasia. At six months postintervention, the success rates were 46.15% for Type I achalasia, 61.11% for Type II achalasia, and 10% for Type III achalasia. The best treatment response after both three and six months was significantly higher among patients with Type II achalasia than Type I achalasia or Type III achalasia.
On further comparison between pairs of achalasia subtypes, intervention outcomes differed significantly only between Type II achalasia and Type III achalasia, both after three months (p = 0.005) and after six months (p = 0.009) (Table 4).
Table 4.
Comparison of treatment success between achalasia subtype pairs at three months and six months posttreatment.
| Type I vs. Type II achalasia (p value) | Type I vs. Type III achalasia (p value) | Type II vs. Type III achalasia (p value) | |
|---|---|---|---|
| Treatment success (three months) | 0.074 | 0.253 | 0.005 |
| Treatment success (six months) | 0.409 | 0.062 | 0.009 |
Discussion
In this study, we followed up on our patients at three and six months and again measured HRM parameters as well as Eckardt scores and compared them with preintervention values. To find out whether there was any difference in intervention outcomes among achalasia subtypes, we compared the treatm-ent success rates (as defined earlier) among the three subtypes. The success rate of LHM intervention was better than PD intervention in Type III achalasia patients, as supported by Ramchandani M. et al.12 Out of the 41 patients, 18 (43.90%) were of achalasia Type II, 13 (31.71%) were of achalasia Type I, and 10 (24.39%) were of achalasia Type III. There was no significant difference between the three subtypes vis a vis age (p = 0.327) or gender (p = 0.96) were concerned. Although several studies have suggested that Type III achalasia patients have a relatively higher incidence,1,13, 14, 15, 16 while some have found no significant difference between the incidence of three sub-types.9,11 It is possible that this variability in age distribution among the three sub-types is population specific. The three sub-types were also comparable with respect to Median IRP (p = 0.820) and total Eckardt score (p = 0.312)
A comparison of the median IRP and Eckardt score by multivariate analysis of variance (MANOVA) showed a significant difference (p < 0.05) between the means of both parameters at pretreatment, posttreatment (three months) and posttreatment (six months) for all three subtypes of achalasia. Although the statistical significance was less for Type III achalasia (p = 0.004) compared to the other two subtypes (p < 0.0001). On further comparing the posttreatment HRM findings (i.e. Median IRP) and Eckardt score with the pretreatment values, we found out that both these values decreased significantly at three months postintervention in all three subtypes of achalasia, suggesting significant improvement in clinical outcomes, although the p-values were relatively lower for Type III achalasia patients (p = 0.001 for IRP and p = 0.003, compared to p < 0.0001 for both IRP and Eckardt for the other two subtypes. Hence, clearly indicating the effectiveness of intervention in all three achalasia subtypes at the end of three months. The lower p-values for Type III achalasia could be an outcome of the small sample size, or it is likely that even though the intervention is effective in Type III achalasia, it is less so compared to the other two subtypes. On comparing the six-month posttreatment median IRP and Eckardt score with pretreatment values, we found that both these values were still significantly decreased in Type I and Type II (p < 0.0001). Whereas, for Type III achalasia patients only, the Eckardt score was significantly reduced (p = 0.04) at six months post-treatment. A significant reduction in symptom score, in the absence of a corresponding significant reduction in IRP (p = 0.083) values at six months posttreatment in Type III achalasia patients, appears more likely because of the small sample size (n = 10). All our patients have undergone intervention only once, hence suggesting that the benefit of intervention persisted even at six months posttreatment in all the achalasia subtypes.
On comparison of the median IRP and Eckardt score at six months postintervention to three-month values, we found out that both have reduced across all the achalasia subtypes. Albeit this reduction was only significant for the median IRP of Type II achalasia (p = 0.007) and both the median IRP (p = 0.001) and Eckardt score (p = 0.029) of Type III achalasia. These findings suggested that the beneficial effect of treatment, although reduced over six months, still persisted. Also, the reduction was greatest for Type III achalasia, with a mean reduction of 3.59 for the median IRP (vs. 1.09 for Type I achalasia and 2.35 for Type II achalasia) and 0.70 for the Eckardt score (vs. 0.23 for Type I achalasia and 0.44 for Type II achalasia). Yamashita et al. in their study,found a reduction in IRP in Type III achalasia patients but not in the other two subtypes.14 Rohof et al. have found reduced IRP values again in Type III achalasia, while in Type I achalasia they varied with the type of intervention.11 The difference in our outcome compared to other studies might just be a statistical phenomenon owing to the small sample size, or it could be because of differences in the ethnicity of the population invol-ved. This finding suggests that the intervention is most likely successful in causing only temporary relief, whereas the pa-thological process is ongoing and might be progressive in nature. There is evidence for the progressive nature of the disease, where symptoms worsen over time and patients need multiple interventions over time.5,17 A long-term follow-up of achalasia patients by Sawas et al. also found recurrent need for intervention because of worsening symptoms.17 Although longer duration of follow-up is required before firming up as a fact.
We also found out that the success rates were highest for Type II achalasia patients compared to the other two (83.33% for Type II vs. 53.85% for Type I and 30% for Type III), although the difference was significant only for the Type II vs. Type III comparison (p = 0.005) at three months posttreatment. When we compared the frequency of success rates between three achalasia subtypes at six months posttreatment, the success rates were again highest for Type II achalasia (61.11% vs. 46.15% for Type I achalasia and 10% for Type III achalasia), although the difference was only significant for the Type II vs Type III achalasia comparison (p = 0.009). Rohof et al. showed that the best treatment response was seen in Type II achalasia (95–96%) and the worst in Type III achalasia (40–66%), which support the findings of our study except differ in percentage.18 C. Andolfi et al. reported the success rates for LHM in type I, II, and III achalasia were 81%, 92%, and 71%, respectively, compared to the success rates for LHM in our study of 50%, 91%, and 50%, respectively.19 It is possible that the lack of statistical significance might have been due to a small sample size. Alternatively, this could be because almost all the patients before and after undergoing intervention were taking medications that affected LOS tone, GI motility, or smooth muscle activity in some way. Although drugs were stopped for five half-lives, their chances of affecting median IRP values were minimal, but they were still likely to affect Eckhardt symptom scores. Added to this fact, if any of these drugs are more effective in one of the achalasia subtypes, it is likely to affect the outcomes of our study. Although authors have failed to find any evidence supporting the preferential efficacy of one or more drugs in any achalasia subtype. Even with these findings, it appears clear that treatment outcomes during the follow-up period were best for Type II achalasia, while the benefits for Type III achalasia were least, with Type I achalasia lying somewhere in the middle. Various authors have also suggested higher rates of treatment failure for Type III achalasia while achieving the best outcomes for Type I achalasia in their study.1,11
Conclusion
In summary, we found that one-time intervention is effective in all three sub-types of achalasia. This benefit, although reduced over time, still remains significant even after 6 months of intervention. Type II achalasia shows the best intervention outcomes compared to the other two subtypes. The success rate of treatment after three and six months was higher and statistically significant for both LHM and PD in Type II achalasia. Type III achalasia not only shows the least response compared to other subtypes but is also the poorest responder vis-a-vis temporal aspect is being concerned i.e. the benefit of one-time intervention also deteriorates most at the end of six months.
Limitations
There were certain limitations to our study, one of which was the small sample size. Indian studies are sparse in this context. Specific treatment choices for the three subtypes of achalasia also need to be decided by further studies based on larger sample sizes. The other limitation was a follow-up period of only six months. A longer follow-up period with a higher number of patients would have given us deeper insight into the efficacy of various treatment modalities in different achalasia subtypes. Also, most of our patients, before and after treatment, were on some drugs that either affected LOS tone, GI motility, or smooth muscle activity in some way. How these drugs affect treatment outcomes in different achalasia subtypes is not known and will be investigated further.
Patients/ Guardians/ Participants consent
Patients informed consent was obtained.
Ethical clearance
Institute/hospital ethical clearance certificate was obtained.
Source of support
This paper is based on Armed Forces Medical Research Committee Project No. 4638/2015 granted by the office of the Directorate General Armed Forces Medical Services and Defence Research Development Organization, Government of India.
Disclosure of competing interest
The authors have none to declare.
Acknowledgement
None.
References
- 1.Lee J.Y., Kim N., Kim S.E., et al. Clinical characteristics and treatment outcomes of 3 subtypes of achalasia according to the Chicago classification in a tertiary institute in Korea. J Neurogastroenterol Motil. 2013;19(4):485–494. doi: 10.5056/jnm.2013.19.4.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ghoshal U.C., Daschakraborty S.B., Singh R. Pathogenesis of achalasia cardia. World J Gastroenterol. 2012;18(24):3050–3057. doi: 10.3748/wjg.v18.i24.3050. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Poole D.P., Furness J.B. In: Physiology of the Gastrointestinal Tract. 5th ed. Johnson L.R., Ghishan F.K., Kaunitz J.D., Merchant J.L., Said H.M., Wood J.D., editors. Elsevier: Academic Press; 2012. Enteric nervous system structure and neurochemistry related to function and neuropathology; p. 571. 571. [Google Scholar]
- 4.Park W., Vaezi M.F. Etiology and pathogenesis of achalasia: the current understanding. Am J Gastroenterol. 2005;100(6):1404–1414. doi: 10.1111/j.1572-0241.2005.41775.x. [DOI] [PubMed] [Google Scholar]
- 5.Patel D.A., Lappas B.M., Vaezi M.F. An overview of Achalasia and its subtypes. Gastroenterol Hepatol. 2017;13:411–421. [PMC free article] [PubMed] [Google Scholar]
- 6.Kahrilas P.J., Bredenoord A.J., Fox M., et al. The chicago classification of esopageal motility disorders v3.0. Neuro Gastroenterol Motil. 2015;27(2):160–174. doi: 10.1111/nmo.12477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kahrilas P.J., Bredenoord A.J., Fox M., et al. The Chicago classification of esophageal motility disorders, v3.0. Neuro Gastroenterol Motil. 2015;27(2):160–174. doi: 10.1111/nmo.12477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Khashab M.A., Vela M.F., Thosani N., et al. ASGE guideline on the management of achalasia. Gastrointest Endosc. 2020;91(2):213–227.e6. doi: 10.1016/j.gie.2019.04.231. [DOI] [PubMed] [Google Scholar]
- 9.Pratap N., Kalapala R., Darisetty S., et al. Achalasia cardia subtyping by high-resolution manometry predicts the therapeutic outcome of pneumatic balloon dilatation. J Neurogastroenterol Motil. 2011;17(1):48–53. doi: 10.5056/jnm.2011.17.1.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Eckardt A.J., Eckardt V.F. Treatment and surveillance strategies in achalasia: an update. Nat Rev Gastroenterol Hepatol. 2011 Jun;8(6):311–319. doi: 10.1038/nrgastro.2011.68. [DOI] [PubMed] [Google Scholar]
- 11.Rohof W.O., Salvador R., Annese V., et al. Outcomes of treatment for achalasia depend on manometric subtype. Gastroenterology. 2013;144(4):718–725. doi: 10.1053/j.gastro.2012.12.027. [DOI] [PubMed] [Google Scholar]
- 12.Ramchandani M., Nageshwar Reddy D., Nabi Z., et al. Management of achalasia cardia: expert consensus statements. J Gastroenterol Hepatol. 2018;33 doi: 10.1111/jgh.14097. [DOI] [PubMed] [Google Scholar]
- 13.Roman S., Zerbib F., Quenehervé L., Clermidy H., des Varannes S.B., Mion F. The Chicago classification for achalasia in a French multicentric cohort. Dig Liver Dis. 2012;44(12):976–980. doi: 10.1016/j.dld.2012.07.019. [DOI] [PubMed] [Google Scholar]
- 14.Yamashita H., Ashida K., Fukuchi T., et al. Predictive factors associated with the success of pneumatic dilatation in Japanese patients with primary achalasia: a study using high-resolution manometry. Digestion. 2013;87(1):23–28. doi: 10.1159/000343902. [DOI] [PubMed] [Google Scholar]
- 15.Pandolfino J.E., Kwiatek M.A., Nealis T., Bulsiewicz W., Post J., Kahrilas P.J. Achalasia: a new clinically relevant classification by high- resolution manometry. Gastroenterology. 2008;135(5):1526–1533. doi: 10.1053/j.gastro.2008.07.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Min M., Peng L.H., Yang Y.S., et al. Characteristics of achalasia subtypes in untreated Chinese patients: a high-resolution manometry study. J Dig Dis. 2012;13(10):504–509. doi: 10.1111/j.1751-2980.2012.00622.x. [DOI] [PubMed] [Google Scholar]
- 17.Sawas T., Ravi K., Geno D.M., et al. The course of achalasia one to four decades after initial treatment. Aliment Pharmacol Ther. 2017;45(4):553–560. doi: 10.1111/apt.13888. [DOI] [PubMed] [Google Scholar]
- 18.Rohof W.O.A., Bredenoord A.J. Chicago classification of esophageal motility disorders: lessons learned. Curr Gastroenterol Rep. 2017;19(8):1–6. doi: 10.1007/s11894-017-0576-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Andolfi C., Fisichella P.M. Meta-analysis of clinical outcome after treatment for achalasia based on manometric subtypes. Br J Surg. 2019;106 doi: 10.1002/bjs.11049. [DOI] [PubMed] [Google Scholar]