Achalasia is a primary motility disorder of the esophagus characterized by impaired deglutitive relaxation of the lower esophageal sphincter (LES) and disturbed peristalsis of the esophageal body. The ultimate cause of the motility disturbances is the loss of the inhibitory neurons of the myenteric plexus but the exact etiopathogenesis is unknown. Therefore, causal (and curative) treatment is not available. All of the current treatment modalities are symptomatic and targeted to alleviate the esophagogastric junction (EGJ) obstruction. Peroral endoscopic myotomy (POEM) is the most recent but already widely accepted treatment method for achalasia developed as a less invasive and fully endoscopic alternative to the traditional laparoscopic Heller’s myotomy (LHM).1 Several studies assessing the impact of POEM on esophageal physiology showed an improved esophageal emptying (demonstrated on timed barium esophagogram [TBE]) and decreased integrated relaxation pressure (IRP), which is the main diagnostic high-resolution manometry (HRM) parameter.2-4 Similar outcomes were reported for other treatment modalities such as LHM or pneumatic dilation (PD).2,5,6
Nowadays, the HRM Chicago classification (CC) can recognize 3 clinically relevant subtypes of achalasia (I-III) that can be distinguished based on the pattern of esophageal contractility and pressurization in the esophageal pressure topography. Besides elevated IRP, which is the hallmark of achalasia, patients with type I have neither esophageal peristalsis nor pressurization, type II achalasia is characterized by the so-called pan-esophageal pressurizations, and type III presents with premature (spastic) contractions.7,8 Absent or impaired peristalsis of the esophageal body in achalasia patients had mostly been believed to be irreversible even though some early studies challenged this paradigm.9-11 Speculations are ongoing whether the absent (or impaired) peristalsis is a primary (consequence of loss of neurons) or secondary (consequence of outflow obstruction) phenomenon. Recently, partial peristaltic recovery after myotomy (either laparoscopic or endoscopic) in a considerable number of patients with achalasia has been described suggesting that EGJOO plays a role in occurrence of failed peristalsis in at least some patients with achalasia.11-18 Whether there are any predictors of peristaltic recovery and whether this phenomenon is clinically relevant is unknown.
The aim of our single-center study is to thoroughly assess the post-POEM esophageal motility patterns with regard to potential peristaltic recovery and its possible clinical relevance.
This was a retrospective analysis of prospectively collected data of patients who underwent POEM at our institution between December 2012 and December 2018. The POEM protocol has been approved by the Czech Health Ministry and by the local Ethical Committee (Docket No. 1251/16 [NM 12-01]). All patients signed an informed consent prior to the procedure.
All consecutive patients with confirmed achalasia referred to our tertiary center who underwent POEM, completed at least a 3-6 month follow-up and underwent HRM prior to and after POEM were included into the analysis. Patients with other spastic motility disorders such as EGJOO, jackhammer esophagus, and distal esophageal spasms were excluded, as well as the patients where any of the HRM data were missing.
Achalasia was diagnosed in all patients by upper gastrointestinal endoscopy, HRM, and TBE performed no longer than 6 months before the procedure. Symptom severity was assessed by the Eckardt score (0-12; Supplementary Table).19 Demographic data were also recorded. All patients were followed up according to a standardized protocol. The 3-month follow-up visit included upper endoscopy, HRM, TBE, and 24-hour pH monitoring. The Eckardt score assessed at 3-6 months was used for this analysis. Treatment success was defined as an Eckardt score < 3.
POEM was performed under general anesthesia in a standard endoscopy room according to the original Inoue´s technique.1 The procedures were performed by 3 endoscopists.
HRM was performed at 3 tertiary centers (Institute for Clinical and Experimental Medicine, Prague, University Hospital Plzen, and Hospital Kolin). A solid-state catheter with an outer diameter of 4.2 mm and 36 circumferential sensors spaced at 1 cm intervals (ManoScan 360 High-Resolution Manometry device, Given Imaging, Los Angeles, CA, USA) was used for all measurements. The sensors were calibrated at 0-300 mmHg prior to the measurement. The catheter was inserted transnasally with the distal sensors positioned in the stomach. The recordings were performed in the supine position using the standard protocol of 30 seconds resting period without swallowing and 10 wet swallows with 5 mL of water. HRM studies were analyzed using ManoView analysis software (Given Imaging).
All HRM studies were retrospectively reviewed and manually analyzed by a single physician (Z.V.). The mean LES resting pressure (LESP), mean IRP, and esophageal body motility patterns were assessed. Both pre-POEM and post-POEM motility was then classified according to the CC version 3.0.20 Although the CC was developed and validated for patients without previous intervention on the esophagus, the descriptive character of assessment of esophageal motility based on automatically measured physical parameters enables application of this classification for categorizing the postinterventional motility findings as well, especially when the initial diagnosis is known. Achalasia was defined by manometric features of IRP > 15 mmHg and impaired esophageal peristalsis. In patients with type I achalasia and those who had previously undergone treatment, the IRP threshold was lower if otherwise the clinical diagnosis including upper endoscopy and TBE corresponded with the diagnosis of achalasia. Type II achalasia was defined by panesophageal pressurization in at least 20% of the swallows and type III by presence of ≥ 20% spastic contractions (as defined in the latest CC).20 Peristaltic contractile activity after POEM was defined as the presence of at least 3 cm isobaric contour integrity of 20 mmHg distal to the transition zone. Failed peristalsis (no peristaltic contractile activity) was defined as either < 3 cm or absent 20 mmHg isobaric contour integrity.
The main outcome was the rate of post-POEM motility patterns with partial peristaltic activity.
Secondary outcomes were clinical significance of peristaltic recovery assessed by the Eckardt score and TBE parameters and identification of possible predictive factors.
Data are presented as counts and percentages or as means with standard deviations unless specified otherwise. The non-parametric Mann–Whitney
From a total of 305 patients who underwent POEM from December 2012 until December 2018, 237 patients were included into the analysis (60 patients were excluded for incomplete examinations or missing data and 8 patients for other diagnosis than achalasia). Fifty patients (50/237, 21.1%) had received a previous treatment (LHM, PD, and botulinum toxin injection) before POEM. A total of 183 patients (77.2%) underwent POEM performed on the anterior wall, the remaining 54 patients (22.8%) received POEM on the posterior wall. A statistically significant difference in the length of myotomy was between type I vs II (10.4 ± 2.2 cm vs 11.9 ± 2.1 cm,
The mean IRP before POEM was 28.9 (± 13.3) mmHg. Twenty-three patients had IRP < 15 mmHg, in 13 patients the data were missing. The mean LESP was 42.3 (± 17.9) mmHg. Both the initial IRP and LESP were significantly lower in patients who had already undergone previous treatment (IRP 20.3 ± 9.2 mmHg vs 31.3 ± 13.1 mmHg, LES 30.0 ± 10.6 mmHg vs 45.5 ± 18.0 mmHg;
The initial HRM diagnoses before POEM were as follows: type II achalasia in 173 patients (73.0%), type I achalasia in 42 patients (17.7%), and type III achalasia in 22 patients (9.3%). Some esophageal peristaltic contractility was observed before POEM in 23 patients (9.7%), almost exclusively in achalasia type III (22 patients), and in 1 patient with achalasia type II in whom swallows with clear contractions were alternating with swallows with panesophageal pressurization.
After POEM the esophageal motility patterns were reclassified according to the CC categories to 112 absent contractility, 42 type I achalasia, 15 type II achalasia, 11 type III achalasia, 26 ineffective esophageal motility (IEM), 18 EGJOO, 10 fragmented peristalsis, and 3 distal esophageal spasm (DES). The changes in the HRM findings and CC diagnosis before and after POEM are summarized in Table 3, examples of HRM studies in Figure 1. Panesophageal pressurization observed in 180 patients prior to POEM (all patients with type II achalasia and 7 patients with type III) disappeared after myotomy in 160 patients (88.9%), (154/173 [89.0%] in type II, 6/7 [85.7%] in type III). Compartmentalized pressurization observed in 14 patients with type III achalasia prior to POEM disappeared in all but 2 patients (both had IRP > 15 mmHg). In the group of patients with some peristaltic contractile activity observed prior to POEM (n = 23) this also persisted after POEM in all but 2 patients. Majority of the patients with post-POEM IRP > 15 mmHg had type II achalasia before the myotomy (60/81, 74.1%) while the HRM post-POEM diagnoses were: 37 achalasia type I, 18 EGJOO, 11 achalasia type II, 10 achalasia type III, and 5 absent contractility (examples of HRM studies in Fig. 2).
From 214 patients without any signs of peristaltic contractions before POEM (achalasia type I and all but one type II cases) some signs of esophageal peristalsis after POEM were encountered in 47 patients (22.0%). The CC categories of these were 4 fragmented peristalsis, 7 achalasia type III, 2 DES, 14 EGJOO, and 20 IEM. Examples of HRM studies of different post-POEM HRM findings are shown in Figure 1.
Further, we compared the manometric parameters of the groups with (n = 47) and without (n = 167) partial peristaltic recovery. The pre-POEM IRP, LESP, and post-POEM IRP were significantly higher in those patients in which the esophageal contractions newly appeared after POEM, but none of those or other measured parameters has proven to be a significant predictor of peristaltic recovery in the logistic regression model (Table 4). Between the achalasia subtypes, peristaltic recovery occurred more often in type II (24.4%; 95% CI, 18.0-30.8%) vs type I (11.9%; 95% CI, 2.4-23.8%). However, the trend for more frequent peristaltic recovery in type II was not statistically significant (
The mean Eckardt score before POEM was 6.9 ± 2.1. Treatment success at 3-6 months was achieved in 224 patients (224/231, 97.0%). The mean post-POEM Eckardt score was 0.4 ± 0.8. Interestingly, the Eckardt score was 0 also in the majority of the patients in which the post-POEM IRP did not normalize (< 15 mmHg; 60/80, 75.0%). On the TBE the mean height of the column at 5 minutes significantly decreased from 7.9 ± 4.2 cm prior to POEM to 1.4 ± 2.5 cm after POEM (
To our knowledge we present the largest series of patients with achalasia evaluated for post-POEM esophageal motility by HRM. Our main finding is that in 22.0% of patients after POEM the peristaltic or rather contractile activity in the esophageal body recovered after the obstruction of the EGJ was relieved, and it happened predominantly in type II achalasia (statistical trend). We did not find any association of this phenomenon with a symptomatic outcome.
Examining whether the esophageal peristalsis, generally not present or disturbed in patients with achalasia, may recover after relieving EGJ obstruction has 2 principal reasons. Firstly, it may provide deeper insight into the esophageal pathophysiology and help to elucidate whether the absent or abnormal peristalsis is a primary or secondary phenomenon. Secondly, if the peristaltic recovery occurs, it is still unclear whether it is clinically significant.
Recently, several rather small studies addressed the issue of possible recovery of peristalsis after myotomy either laparoscopic or endoscopic, most of them predominantly focusing on the measured HRM parameters (IRP and LESP).12,14,15,21 But the phenomenon of peristaltic recovery after alleviating the obstruction of EGJ has already been observed in the past including both clinical and experimental settings.9-11,13,17,18 In our study we have shown, that the esophageal contractions were observed in 28.7% of patients after POEM including cases who had some preserved peristalsis also before POEM (achalasia type III), thus the true “recovery” with the newly appeared contractions was observed in 22.0%. This number is considerably lower compared to other studies assessing physiologic outcomes after myotomy, for example Teitelbaum et al4 reported 47.0% (8/21), and Roman et al12 even 57.0% patients with partial return of peristalsis after LHM and/or POEM. The higher percentage in the latter study may partially be explained by inclusion of patients with type III achalasia, even if in these patients “newly” appearing peristaltic recovery cannot be observed. Other studies also reported the phenomenon of peristaltic recovery after LHM.11,17,18 Parrilla et al18 observed it in 46.6% of patients. However, in another post-LHM study, the peristalsis was restored in only 25.0% patients.11 Thus, there is no doubt about the presence of the phenomenon of partial peristaltic recovery after myotomy, but the data vary largely in terms of the proportion of patients experiencing recovery. Our study reports, so far, the lowest proportion of subjects with peristaltic recovery may be attributed to the considerably higher number of analyzed patients in our study (21-45 patients in other studies vs 237 in our study) and varying methodology used to assess peristaltic recovery.
Another interesting finding is that the type II achalasia (as opposed to type I) showed some predisposition for the peristaltic recovery. Although the proportion of patients with peristaltic recovery after POEM was twice as high in type II than in type I, the difference was not statistically significant (
Although the phenomenon of partial peristaltic recovery is not rare (but also probably not as frequent as reported earlier), the clinical impact in terms of symptomatic outcome is unknown. We have not proved the partial peristaltic recovery after POEM to have impact on the symptomatic outcome neither in esophageal emptying on TBE nor in terms of the Eckardt score. Interestingly, peristaltic recovery was more frequent in patients with RE after POEM than in patients without. The explanation of this finding is challenging and several hypotheses can be speculated to address the relation between post-POEM reflux and motility disturbances. Answering this question and also other post-POEM reflux-related complications requires further long-term investigation.
Our study has several limitations. First, the CC was developed for treatment-naïve patients only, thus for its application to assess and categorize the motility findings after POEM is not validated. On the other hand, the CC classifies the motility patterns based on the measured and automatically calculated parameters which are descriptive with regard to the esophageal pathophysiology. Therefore, knowing the initial diagnosis and the intervention, we believe the measures of the main HRM parameters can be compared and the CC applied as it was used elsewhere.12 Second, for the purpose of our study we used the term “peristaltic recovery.” Obviously, it harbors inaccuracy in the term “peristaltic” because we cannot assess accurately enough whether these “recovered” contractions are truly peristaltic, ie, have the potential to propel the bolus distally. With this regard, the HRM impedance data would have been beneficial but, unfortunately, the impedance catheter was not available at our center until 2017. Third, it may be argued that for such a physiologic change, as partial peristaltic recovery is, the 3-month period is not sufficient and it would be interesting to assess the evolution of the motility patterns over time; however, it would require a dedicated study with patients willing to undergo the per se unnecessary HRM procedure again.
In summary, we demonstrated that peristaltic recovery is not an uncommon phenomenon, although it may not be as frequent as previously thought. The restoration of the contractile activity also seemed to be intertwined with the manometric subtypes of achalasia as shown in our study where the type II was more prone to show the contractile reserve (besides the obvious type III) than type I. Nevertheless, the peristaltic recovery was not associated with an improved symptomatic outcome. By extension, these findings tickle the hypothesis of possible different pathogenetic pathways in the 3 subtypes of achalasia and provide material for further research.
Zuzana Vackova designed the study, reviewed HRM studies, analyzed data, and drafted the manuscript; Jana Krajciova, Lucie Zdrhova, Pavla Loudova, Zuzana Rabekova, and Zuzana Vackova performed the HRM procedures; Jan Martinek designed the study and revised the manuscript critically; Tomas Hucl, Petr Stirand, and Jan Martinek performed POEM; Jan Mares analyzed the data and revised the manuscript critically; and Julius Spicak and Tomas Hucl revised the manuscript critically.