A new Perspective on Management: Phenotype-directed Treatment
The ideal therapy for an esophageal motility disorder would revert swallow function to normal, render the patient symptom free, and not result in pathologic reflux. No current therapy for any of the esophageal motility disorders achieves all of these objectives, and that is unlikely to change in the foreseeable future. Furthermore, the controlled treatment data currently available lag well behind recent advances in diagnostics. Indeed, although the original description of achalasia phenotypes noted that an important distinction among phenotypes was in the differential likelihood that they would respond to achalasia treatments (best outcomes in type II and worst in type III), essentially all available controlled trials have not specified achalasia subtype. Retrospective analyses of randomized and non-randomized treatment series[30,31] have, however, confirmed the original observation of differential response rates. Furthermore, with the recognition of obstructive physiology at the EGJ or distal esophagus being important foci of treatment, several disease entities beyond classic achalasia are now being rendered treatments formerly reserved for achalasia. This is particularly relevant with the widespread adoption of the POEM procedure. Not only does POEM provide an option for surgical LES myotomy with reduced operative morbidity, but it also facilitates a calibrated myotomy, potentially extending proximally to include the entire smooth muscle segment of the esophagus. Together, these developments modified treatment aims to target obstructive physiology at the EGJ or distal esophagus as identified by physiologic testing, regardless of the specific disease entity.
The concept of phenotype-directed therapy is especially relevant with type III achalasia, characterized by obstructive contractility of the distal esophagus and noted to have less robust outcomes with therapies limited to the LES.[6,29–31] Seeking to improve on this, uncontrolled series have applied POEM to type III achalasia and gauged the length of myotomy by the length of the spastic segment seen on HRM, esophageal wall thickening on imaging studies, or intraoperative FLIP. A recent meta-analysis of these uncontrolled POEM series reported a weighted pooled response rate of 92% (confidence interval, 84%–96%) in type III achalasia, with a myotomy length ranging from 13 to 19.7 cm. Similarly, a retrospective analysis comparing treatment outcomes with laparoscopic Heller myotomy (LHM) and POEM in a 49-patient multicenter analysis found POEM to be significantly more efficacious (98.0 % vs 80.8 %; P = .01), presumably on account of the more extensive myotomy that was done (16 vs 8 cm; P < .01). Moreover, what is effective for type III achalasia should also be effective for the other esophageal motility disorders in Figure 1 characterized by obstructive physiology of the smooth muscle esophagus, DES, and jackhammer esophagus. The same POEM meta-analysis that analyzed type III achalasia outcomes reported a weighted pooled response rate to POEM of 72% (confidence interval, 55%–83%) in jackhammer and 88% in DES (confidence interval, 61%–97%). Notably, the DES response rate was only 4% less than that seen in type III achalasia, emphasizing the similarity of these entities when defined according to the CC.
At the other end of the treatment spectrum is type II achalasia, wherein there is extreme obstructive physiology at the EGJ resulting in panesophageal pressurization with test swallows, but often remnants of normal peristalsis in the distal esophagus that become evident after treatment. Hence, any treatment that relieved EGJ outflow obstruction, even if limited to the EGJ as in the case of pneumatic dilation (PD), should be effective. Consistent with that hypothesis, type II achalasia patients obtained the best treatment outcome in all of the type-specific analyses to date, regardless of the treatment. Indeed, in the European achalasia trial, which was a randomized controlled trial of PD vs LHM,[35,36] the efficacy of PD for treating type II achalasia was 100% (acknowledging acceptance of intermittent repeat PD). Considering that the cost of PD is substantially less than that of LHM and that the risk of perforation between techniques is comparable (about 1% in expert hands), this argues for PD as preferable to LHM in the initial treatment of type II achalasia.
Evident from the preceding discussion, the optimal initial achalasia treatment likely depends on the subtype, and cogent arguments can be made for POEM, LHM, and PD, all of which are relatively durable treatment options. Among these the most extensive literature, recently summarized by Pandolfino and Gawron, has compared PD with LHM and concluded that both are highly efficacious, albeit best when done in expert hands. On the other hand, uncontrolled outcome data have been very promising comparing POEM with LHM.[2,39] It is true that POEM is relatively new, but with the pioneering Japanese center recently summarizing their experience gleaned from their first 1000 POEM procedures, one can hardly classify it as experimental. However, controlled data comparing POEM with either LHM or PD are still very limited. Although some are in progress, no randomized trial has yet been reported comparing POEM with LHM, and only one, reported as an abstract (and now a manuscript in review), has compared POEM with PD (Table 2). A recent systematic review and meta-analysis of trials comparing POEM (1958 patients) with LHM (5834 patients) reported POEM to be more effective in relieving dysphagia (mean follow-up of 16 months) but also more likely to lead to post-procedure reflux (odds ratio of 9.31 for erosive esophagitis). The multicenter randomized controlled trial comparing POEM with PD in 133 treatment-naive achalasia patients reported 92% remission after 1-year follow-up in the POEM cohort compared with 70% in the PD cohort (P < .01). One perforation occurred after PD, and no severe adverse events occurred related to POEM. Endoscopy 1 year after treatment found reflux esophagitis in 48% of the POEM patients (40.0% Los Angeles A or B, 8.3% C or D) compared with 13% of the PD patients (all Los Angeles A or B, P = .02).
In summary, PD, LHM, and POEM can all be highly efficacious treatments for achalasia, but circumstances of local expertise, achalasia subtype, and patient-specific variables (comorbidities, hiatal hernia, epiphrenic diverticulum) may make one treatment preferable to another.[43,44] The reported success rates of PD are particularly variable among centers, with 2-year response rates ranging from 54% to 86% in 2 recent randomized controlled trials,[35,41] likely reflective of what constituted a "success" in each trial and balancing the aggressiveness of the dilation protocol against the associated risk of sustaining a perforation.
Clin Gastroenterol Hepatol. 2018;16(11):1692-1700. © 2018 AGA Institute