Outcomes of Treatment for Achalasia Depend on Manometric Subtype

Wout O. Rohof; Renato Salvador; Vito Annese; Stanislas Bruley Des Varannes; Stanislas Chaussade; Mario Costantini; J. Ignasi Elizalde; Marianne Gaudric; André J. Smout; Jan Tack; Olivier R. Busch; Giovanni Zaninotto; Guy E. Boeckxstaens

Disclosures

Gastroenterology. 2013;144(4):718-725. 

In This Article

Discussion

Different success rates have been reported for the 3 manometric subtypes of achalasia, suggesting that classification by manometry may be useful to determine the treatment of choice.[9–11] In the present study we confirmed that the manometric subtype is indeed an important determinant of clinical success, with type I and especially type III achalasia having an increased odds rate for treatment failure compared with type II. The main symptoms for treatment failure are dysphagia in type I, and dysphagia, chest pain, and regurgitation in type III. Of note, type I and II patients, representing the majority (90%) of achalasia patients, had an excellent response to both LHM and PD during a mean follow-up period of 43 months, with only a small difference in success rate between PD and LHM in type II patients (100% vs 93%, respectively). Mainly patients with type III have an impaired response rate to PD, but because of the small patient number, there was no significant difference compared with LHM. Based on our current data, we conclude that achalasia subtyping is clinically helpful to estimate the success rate irrespective of the treatment (LHM or PD) used, but may prove relevant only to determine the most optimal treatment option in type III patients.

In achalasia, substantial variability in residual esophageal pressure patterns and dynamics is observed using high-resolution manometry. Based on the residual dominant distal esophageal pressurization pattern, Pandolfino et al[9] classified achalasia into 3 types (type I, no pressurization; type II, panesophageal pressurization; and type III, rapidly propagating contractions). Interestingly, after a follow-up period of at least 1 year, the treatment success rate of type II patients (96%) was significantly higher compared with type I (56%) and type III (29%) patients. Moreover, the number of interventions (PD, LHM, and Botox combined) was twice as high in type III compared with type II patients, suggesting that patients with type II respond better to treatment. Because of the low number, no comparison could be made between the different treatments used. In the same line, Salvador et al[10] reported better clinical response to LHM (n = 246) for type II patients (success rates of type I: 85%, 82 of 96; type II: 95%, 121 of 127; and type III: 70%, 16 of 23; P = .0007). Although the follow-up period in our study was longer (median, 43 mo) compared with the previous 2 studies (range, 6–31 mo), our results are largely comparable, confirming that the highest success rate was observed in type II achalasia (96% after 2 years) compared with type I (81%; P < .01) and type III (66%; P < .001). Also, in a Cox regression analysis model, type I and type III were identified as risk factors for treatment failure with a hazard ratio of 4.0 and 6.8, respectively. Taken together, we confirmed that type I and in particular type III achalasia are important predictors of treatment failure.

In this study we provide more insight into the functional differences and the symptoms underlying treatment failure in the different subtypes. Chest pain scores before as well as after treatment are higher in patients with type III achalasia compared with types I and II. Although chest pain has been shown repeatedly to be an independent predictor of therapeutic failure, the mechanisms leading to this symptom are incompletely understood.[3,12] It is hypothesized that chest pain is evoked mainly by high-amplitude esophageal contractions rather than esophageal widening.[9] Our data are in line with this hypothesis because type III patients have the narrowest esophagus and the highest contraction amplitude, associated with the highest chest pain score. It also should be noted, however, that patients with type III achalasia reported more symptoms of dysphagia and regurgitation than patients with types I and II. Patients with type I achalasia had a higher dysphagia score after treatment compared with patients with type II achalasia. The higher dysphagia score was associated with impaired esophageal emptying on timed barium esophagogram in type I patients. Moreover, type I patients had a significantly wider esophagus. Esophageal stasis and a wide esophagus have been identified as risk factors for treatment failure in multiple earlier studies.[3,16,17] For instance, Vaezi et al[16] showed that 90% of patients with persistent stasis but without symptoms failed therapy within 1 year after initial treatment. Furthermore, Zaninotto et al showed that a wider esophagus is an important risk factor for treatment failure in a large study with patients treated by LHM.[18] Combined high-resolution manometry (HRM) and impedance measurements have shown that esophageal emptying in achalasia mainly occurs during panesophageal pressurizations.[15] The absence of esophageal pressurization in type I achalasia therefore might explain differences in esophageal stasis levels and thereby contribute to higher dysphagia scores and impaired success rates.

Accepting that the manometric subtype is indeed an important predictor of clinical success, the main clinical question that remains is to what extent the choice of treatment (ie, PD or LHM) can be guided by the manometric subtype. For this purpose, we compared success rates for PD and LHM in the 3 subtypes. For type I achalasia, LHM and PD had similar success rates (81% vs 85%, respectively), whereas only a small difference was observed for type II achalasia (93% vs 100% for LHM and PD, respectively). Of note, our success rates for LHM were comparable with those reported previously, however, we obtained higher success rates in patients with type I undergoing PD (56%–63% vs 85%).[9,11] One explanation could be the fact that patients with mega-esophagus (esophageal diameter, >7 cm), known to be more difficult to treat and to present with type I achalasia, were excluded from our study.[9,10,18] It should be emphasized, however, that only one patient was excluded in our series based on this criterion. Alternatively, this difference may be explained by the more rigorous distension protocol we used, our protocol allowed redilation during the first years of follow-up evaluation, which was performed in 7 type I patient (23%) and 5 type II patients (13%). Based on our findings, we conclude that when a graded distension protocol allowing redilation is used, PD and LHM are both appropriate treatment options for type I and type II achalasia, at least until longer follow-up data are available.[19,20]

The largest difference was observed in type III patients, in whom the success rate after LHM was higher than after PD (86% vs 40%, respectively). Because of the small patient number (n = 18), this difference was not statistically significant (P = .12). The success rates are in line with the available literature (LHM of 70% vs PD of 33%–38%), although the number of patients with type III achalasia in previous studies is rather small as well (47 in total: 14 PD, 24 LHM, and 9 Botox).[9,10,11] It was interesting to note that dysphagia was especially high in type III patients treated with PD, a finding that was associated with impaired emptying and a wider esophagus. As shown by Pandolfino et al,[9] type III patients have a functional obstruction not only encompassing the esophagogastric junction but also the distal smooth muscle segment of the esophagus.[10] In the European Achalasia Trial, the myotomy was extended 6 cm above the esophagogastric junction, which may account for the differences in esophageal emptying, dysphagia, and regurgitation, and thereby to the higher success rates compared with PD. Therefore, in combination with the large difference in success rates both in our study and in the literature, we suggest that LHM may be the preferred treatment option in type III patients. Still, an additional study focusing on patients with type III achalasia seems indicated. Because of the very limited incidence of type III achalasia, additional studies probably need to be performed in multicenter studies to provide sufficient patient numbers.

The strength of our study is the prospective randomized trial design and the relatively large number of patients. In 12 centers in 5 European countries, patients were randomized and evaluated in a regular follow-up protocol with validated and objective outcome measures, both symptoms as well as functional outcome measures. As a result, we were able to compare the effect of the 2 standard treatments in 3 different manometric subtypes. In addition, this study provided more insight in functional differences and symptoms of treatment failure in the different subtypes. A possible limitation of our study was the use of conventional manometry instead of HRM, for which the classification was designed. However, during the initiation of the study in 2003, HRM was not available in the participating centers, and diagnosis was based on conventional manometry with a sleeve sensor. Of note, Salvador et al[10] reported 100% agreement between the classification of subtypes based on conventional pressure line tracings vs HRM plots. Although classification of subtypes based on conventional pressure line tracings might be less precise than the sophisticated HRM-based classification, our 3 patient groups were similar to those reported by Pandolfino et al,[9] in terms of both clinical features and outcome after therapy. Therefore, we are confident that our conclusions are of clinical significance.

In conclusion, achalasia types I and III are important predictors of treatment failure compared with type II, and therefore achalasia subtyping is useful to determine the risk for treatment failure. Success rates in types I and II are high for both treatment groups, whereas patients with type III have an impaired treatment response, primarily after PD. This implies that patients with type III achalasia may better be treated by LHM, or be included in a more rigorous follow-up protocol.

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