Achalasia and esophago-gastric junction outflow obstruction: focus on the subtypes

Authors

  • G. Boeckxstaens,

    1. Department of Gastroenterology, Translational Research Centre for Gastrointestinal Disorders, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium
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  • G. Zaninotto

    1. Department of Surgical and Gastroenterological Sciences, UOC General Surgery, Sts Giovanni e Paolo Hospital, University of Padova, Padova, Venice
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Address for Correspondence
Guy Boeckxstaens, Department of Gastroenterology, Translational Research Centre for Gastrointestinal Disorders, University Hospital Leuven, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
Tel: +32 16 330671; fax: +32 16 330723; e-mail: guy.boeckxstaens@med.kuleuven.be

Abstract

Background  The choice between pneumatic dilation and surgical myotomy is mainly determined by the preference and expertise of the treating physician. Ideally, however, treatment should be personalized to provide the optimal clinical outcome. The introduction of high resolution manometry has not only improved the specificity to diagnose achalasia, but also identified three different manometric subclasses.

Purpose  To review, the data suggesting differences in clinical response to treatment depending on the manometric profile.

Introduction

Achalasia is a relatively rare esophageal motility disorder characterized by an impaired lower esophageal sphincter (LES) relaxation and the absence of esophageal peristalsis, resulting in a functional outflow obstruction at the esophago-gastric junction (EGJ)1. Although the pathogenesis of achalasia remains unknown (and no definitive therapy is therefore available), the medical community learnt nearly hundred years ago how to palliate dysphagia in achalasia patients by lowering the LES pressure by cutting the cardia muscular coat2 (myotomy) or disrupting its fibers with forceful endoscopic dilations3, or, more recently, by paralyzing them with botulinum toxin4. This last solution has been shown to have only a temporary effect and is now considered only for high-risk patients or as a bridge to more definitive therapies.

Pneumodilation or Laparoscopic Heller Myotomy?

The choice between pneumatic dilations and surgery has been swinging like a pendulum for many years: at the very beginning, dilations were burdened by an excessive risk of perforations and myotomy was generally preferred. With the advent of low-compliance, non-expandable balloons of increasing diameters in the 1980s, the risk of perforation was substantially reduced and pneumatic dilation (PD) became the primary form of therapy for achalasia, whereas surgery was relegated to an ancillary role for treating PD failures. Thanks to the introduction of minimally invasive surgery in the early 1990s, the last 20 years have witnessed a gradual shift in the treatment algorithm for this disease and nowadays, laparoscopic Heller myotomy (LHM) has been recommended as the first choice for achalasia treatment5. In the ‘real world’, however, the physician’s expertise, the patient’s personal preference and the local availability of an experienced surgeon or endoscopist have been the main determinants orienting the choice of therapy6. A large randomized trial recently demonstrated that LHM and a series of PDs achieve the same results in treating dysphagia in achalasia patients: both therapies were effective in nearly 90% of patients with a medium follow-up of 3 years7. This remarkable result raises the question of why both treatments sometimes fail.

Prognostic Factors

In general, failures – especially early after treatment – have been interpreted as the outcome of faulty technique in performing the LHM (short or incomplete myotomy, mainly in the distal part of the LES)8 or PD (inadequate dilation due to insufficient pressure or small balloon diameter, or short dilation time, or dislocation of the balloon). It is certainly peculiar, however, that after a careful standardization of both treatments (PD and LHM), and even in the hands of experienced surgeons and endoscopists, the failure rate is much the same, giving the impression that this 10% of patients represent a ‘minority’ of achalasia patients in whom whatever therapy is attempted is likely to fail.

Few predictors of the outcome of therapy for achalasia have been described: the presence of a large, decompensated sigmoid-shaped mega-esophagus is generally accepted to be a negative prognostic factor for both PD and LHM. Young age (<40 years), a high posttreatment LES pressure (>10 mmHg) and incomplete obliteration of the balloon’s waist during PD are negative prognostic factors for PD9,10. Daily chest pain, an esophagus <4 cm wide before treatment, and stasis on the barium esophagogram after treatment were recently identified as other negative prognostic factors for both treatments7. An LES resting pressure >35 mm Hg is reportedly a positive prognostic factor for LHM10. Be that as it may, the reasons for any treatment failures remain obscure in most cases.

Esophageal Manometry vs High Resolution Manometry

Ideally, we should aim to develop criteria enabling customized patient care, such that the most efficient therapy is recommended to each patient. Identifying positive and negative prognostic factors based on clinical features is therefore highly relevant to clinical patient management. Until recently, manometry was only used to diagnose achalasia and monitor the efficacy of treatment to reduce the LES pressure. Pull-through manometry and, later on, sleeve manometry have both proven very useful for these purposes. Two major improvements have been accomplished, however, with the introduction of high resolution manometry combined with pressure topography plotting: (i) the sensitivity of the diagnosis of achalasia has significantly improved; and (ii) manometric subtypes have been identified that are associated with different outcomes of treatment.

As discussed in detail by Bansai and Kahrilas11, a catheter containing 36 solid sensors placed 1 cm apart is easy to position, and eliminates any difficulties with interpreting tracings due to an erroneous positioning of the manometric catheter. The use of the high resolution manometry (HRM) catheter eliminated the pitfall of erroneously interpreting as a normal relaxation, the upward movement of the LES relative to the pressure or sleeve sensor and the consequent relocation in the stomach of the normal or sleeve catheters. More detailed information on the esophageal and LES pressure profiles is provided too, significantly increasing the diagnostic yield. In particular, pressurization of the esophagus can be better distinguished from non-propulsive high-amplitude contractions, whereas pseudorelaxation of the LES during swallowing due to esophageal shortening (up to 9 cm) is no longer an issue.

More detailed manometric recording and data representation in pressure topography plots have given rise to a new algorithm for classifying esophageal motility disorders, including achalasia. Although the diagnosis of achalasia focuses primarily on impaired LES relaxation and subsequent outflow obstruction, abnormalities in contractile and pressurization patterns in the esophageal body determine three different subtypes of achalasia, depending on any presence of complete failure of peristalsis or spastic contractions11. Each swallow is characterized as normal (intact isobaric contour line (pressure front velocity – PFV ≤ 8 cm s−1), failed (complete failure of contraction), hypotensive (>2 cm break in the 30 mm Hg isobaric contour line), rapidly conducted (PFV ≥ 8 cm s−1) spastic contractions, or panesophageal pressurization with simultaneous esophageal pressurization extending from the upper esophageal sphincter (UES) to the EGJ. Using these definitions, patients can be classified as: type I, achalasia with minimal or no esophageal pressurization in 8 of 10 swallows; type II, achalasia with esophageal compression (at least); or type III, achalasia with spasm (Figs 1–3). Most importantly, the authors also suggested a correlation between the manometric subtype and the final outcome of treatment.

Figure 1.

 Type I Classic achalasia (A) analogic trace and (B) color pressure topography. No distal esophageal pressurization is evident and all the contractions elicited by liquid swallows have an amplitude >30 mm Hg.

Figure 2.

 Type II achalasia (A) analogic trace and (B) color pressure topography. Simultaneous isobaric esophageal pressurization is evident at HRM and all the contractions elicited by liquid swallows have an amplitude ≤30 mmHg, with normal duration.

Figure 3.

 Type III achalasia (A) analogic trace and (B) color pressure topography. High-resolution manometric picture of rapidly propagating pressurization with spastic contractions. The high amplitude contractions of the distal esophageal body is represented by the red high-pressure area of the esophageal body contraction. (B) Conventional manometry of long-lasting, high-pressure spastic esophageal contraction.

Achalasia Subtypes and Success of Treatment

In their series of 99 achalasia patients, Pandolfino et al.12 classified 21 patients as type I, 49 as type II, and 29 as type III; follow-up information in sufficient detail and of sufficient duration (at least a year) was available for 83 of these patients. Fourteen patients were given botox injections, 43 were treated with PD, and 26 underwent LHM. From a clinical point of view, type I patients were more likely to have esophageal dilation, whereas type II and III patients had chest pain significantly more often. The success of treatment was strongly influenced by the achalasia subtype, irrespective of the type of therapy involved. Achalasia subtype II was much more likely, and type III much less likely to respond to treatment than type I (Table 1). Patients with type II did respond excellently, with a success rate of 96%, as opposed to 56% and 29% for types I and III, respectively. In this study, success was defined as a documented improvement recorded at one or more postintervention clinical visits, such that no further intervention was recommended for at least 12 months. Although patients with type I achalasia seemed to respond best to LHM, the number of patients involved was rather small and larger studies are needed to confirm this finding. It became clear from subsequent studies, however, that the success of therapy is indeed determined by the achalasia subtype. Although largely conventional (sleeve) manometry rather than high resolution manometry was used in these studies, similar patterns can be distinguished with this technique allowing reliable sub-classification. In a large series of patients treated with LHM, Salvador et al.13 studied 249 consecutive patients (with a median follow-up of 31 months): 39% of patients were classified as having achalasia type I, 51.6% as type II and 9.4% as type III (Table 1). Patients were considered treatment failures if their postoperative symptom score was >7. At multivariate analysis, the manometric pattern was confirmed as an independent predictor of success: type II patients responded best to treatment (95.3% success rate), and patients with type III had the lowest response rate (69.6%). A smaller study reported on the short-term results (after a mean follow-up of 6 months) in 45 achalasia patients treated with PD14. As in the previous studies, patients with type II had a better clinical response (90%) than types I (63%) or III (33%) (Table 1). Finally, when the manometric tracings of the achalasia patients included in the European achalasia trial were classified according to the criteria proposed by Pandolfino et al., type I achalasia was identified in 44 patients (25%), type II in 114 (65%), and type III in 18 (10%)15. Of these 175 patients, 84 were randomized to PD and 91 to LHM. After 2 years of follow-up, the success rates were significantly higher for type II cases (96%) than for type I (81%) and type III (66%) patients, irrespective of the type of treatment15 (Table 1). The response rate was particularly low in type III patients who had PD (n = 10, 40% success rate), but otherwise largely comparable for PD and LHM in types I and II.

Table 1.   High resolution manometry achalasia subtyping and outcome of treatments
AuthorSubtypeNo. patients (%)Success rate %
  1. LHM, laparoscopic heller myotomy; PD, pneumatic dilatation.

  2. *Success after last intervention (Botulinum toxin injection, Pneumatic Dilatation or Laparoscopic Heller Myotomy were performed as first intervention; a second dilatation with larger balloon or Laparoscopic myotomy were performed as last intervention).

PandolfinoI21 (21.2)56*
II49 (49.5)96*
III29 (29.3)29*
Salvador (LHM)I96 (39)84.6
II127 (51.6)95.3
III23 (9.4)69.3
Pratap (PD)I24 (47.1)63
II24 (47.1)90
III3 (5.8)33.3
Rohof (PD & LHM)  PDLHM
I44 (25)85.781
II114 (64.7)10095
III18 (10.2)4086

Conclusions

On the basis of the information reported to date, the evidence clearly confirms that the subtype of achalasia is an independent predictor of success, with type III having the worst outcome after therapy. To what extent the subtypes represent different phenotypes or simply reflect different stages of the disease is hard to say. Recent detailed analyses of HRM tracings, combined with impedance and ultrasound images, seem to suggest that type III and type I achalasia, respectively, represent the feature of a compensated and decompensated esophagus to outflow obstructions caused by a dysfunctional LES16. The pressurization pattern typical of type II achalasia, on the other hand, stems from another, novel motor response of the esophagus involving longitudinal muscle contractions of the distal esophagus.

Be that as it may, it seems fair to conclude that type III achalasia, characterized by well-defined, lumen-obliterating spastic contractions in the distal esophagus, responds the least to therapy. In this subgroup of achalasia patients, reducing the LES pressure may not suffice to control the symptoms, especially as the segment affected by the spastic motility extends well above the LES. Chest pain, a prominent symptom in type III achalasia patients (probably associated with spastic contractions), is especially difficult to treat, explaining the lower success rates in these patients. The response to therapy in type II is rather better than that in type I, but in the European Achalasia Trial, at least there were apparently no major differences in the success rate for these subtypes between PD and LHM. Judging from the available data therefore, classifying achalasia according to its subtypes helps us inform patients with type III better about their presumably less favorable outcome, though we are not yet at a stage where the choice of treatment (LHM or PD) can be based on HRM findings.

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