Advances in the Diagnosis and Management of Achalasia and Achalasia-Like Syndromes: Insights From HRM and FLIP

Abstract

High-resolution manometry, Chicago Classification v4.0, the functional lumen imaging probe, Panometry, and peroral endoscopic myotomy (POEM) are all now integral parts of the landscape for managing achalasia or, more precisely, achalasia-like syndromes. This narrative review examines the impact of these innovations on the management of achalasia-like syndromes. High-resolution manometry was the disruptive technology that prompted the paradigm shift to thinking of motility disorders as patterns of obstructive physiology involving the esophagogastric junction and/or the distal esophagus rather than as siloed entities. An early observation was that the cardinal feature of achalasia-impaired lower esophageal sphincter relaxation-can occur in several subtypes: without peristalsis, with pan-esophageal pressurization, with premature (spastic) distal esophageal contractions, or even with preserved peristalsis (esophagogastric junction outlet obstruction). Furthermore, there being no biomarker for achalasia, no manometric pattern is perfectly sensitive or specific for 'achalasia' and there is also no 'gold standard' for the diagnosis. Consequently, complimentary physiological testing with a timed barium esophagram or functional lumen imaging probe are employed both to improve the detection of patients likely to respond to treatments for 'achalasia' and to characterize other syndromes also likely to benefit from achalasia therapies. These findings have become particularly relevant with the development of a minimally invasive technique for performing a tailored esophageal myotomy, POEM. Now and in the future, optimal achalasia management is to render treatment in a phenotype-specific manner, that is, POEM calibrated in a patient-specific manner for obstructive physiology including the distal esophagus and more conservative strategies such as a short POEM or pneumatic dilation for obstructive physiology limited to the lower esophageal sphincter.

Keywords: Achalasia; Dysphagia; Esophagus; Functional lumen imaging probe; Manometry.

Figure 1

Achalasia subtypes and achalasia-type esophagogastric (EGJ) outflow obstruction. A. Type I achalasia: integrated relaxation pressure (IRP) is elevated (> 15 mmHg) with 100% failed peristalsis (distal contractile index [DCI] < 100 mmHg•s•cm), and without panesophageal pressurization. B. Type II achalasia: IRP is elevated with 100% failed peristalsis and panesophageal pressurization to > 30 mmHg observed in ≥ 20% of test swallows. Note that this recording was obtained with an impedance-manometry catheter with the impedance signal (evident by the purple shading) showing retained fluid in the distal half of the esophagus. On timed barium esophagram, the level of barium retention would correspond to the level of purple shading. C. Type III achalasia: IRP is elevated with a normal DCI (> 450 mmHg•s•cm), and premature contractions (distal latency < 4.5s). D. EGJ outflow obstruction: IRP is elevated with preserved peristalsis and compartmentalized pressurization between the peristaltic contraction and the EGJ. Note the differences between the spatial pressure variation (SPV) plots to the right of the type III achalasia and EGJ outflow obstruction panels. The SPV plots illustrate the top-to-bottom pressure profile within the Clouse plot at the time indicated by the black dashed line. In type III achalasia this has multiple peaks indicating multiple points of luminal closure, often reported as a ‘corkscrew’ or ‘rosary bead’ on an esophagram and interpreted as distal esophageal spasm, while with compartmentalized pressurization, the zone of pressurization is a flat plateau, indicating pressurization within a chamber sealed at both ends. This would also be the case with type II achalasia except the plateau extends from the upper sphincter to the lower sphincter making it panesophageal pressurization.

Figure 2

Contractile response (CR) patterns observed in FLIP Panometry. The topographic images are of time (x axis), position along the probe (y axis) and luminal diameter (color). Hence, contractions appear much as they do in HRM with the distinction being that it is luminal diameter rather than pressure that is being portrayed. The normal CR (A) is of repetitive antegrade contractions (RACs) observed at some time during the 50, 60, or 70 mL distention volumes, each of which is maintained for at least 60 seconds. With a borderline CR (B), antegrade contractions are observed but not meeting RAC criteria. With an impaired/disordered CR (C), contractions are observed but without any distinct antegrade contractions. No contractility is observed with absent CR (D) usually seen with non-spastic achalasia or an HRM pattern of absent contractility. With the spastic/reactive CR (E) sustained occluding contractions (SOC), sustained LES contraction (sLESC), or repetitive retrograde contractions (RRCs) are seen, any one of which constitutes a spastic reactive CR.

Figure 3

Results of further evaluation of EGJ outflow obstruction (EGJOO) obstruction patients using provocative maneuvers, FLIP panometry, and timed barium esophagram (TBE) as proposed in Chicago Classification v4.0. Initially, all EGJOO diagnosed are considered inconclusive but with the addition of FLIP panometry 49% became conclusive and 22% were deemed normal, leaving 29% still inconclusive. Note that while all of the patients had both HRM and FLIP panometry only a portion of them had TBE and the rapid drink challenge (RDC) as indicated in the Figure. The associated finding from RDC and TBE are shown to emphasize the value of complimentary testing and the potential for inconsistency in diagnosis among testing modalities. PEP, panesophageal pressurization.

Figure 4

Meta-analysis of studies reporting clinical outcomes of achalasia patients that were classified by manometric subtype after treatment with botulinum toxin injection, pneumatic dilation (PD), laparoscopic Heller myotomy (LHM), or per-oral endoscopic myotomy (POEM). The major conclusions from the meta-analysis were that: (1) POEM was more successful than LHM for both type I (OR 2.97, P = .03) and type III achalasia (OR 3.50, P = .007), (2) POEM was the most efficacious treatment across the entire achalasia spectrum with pooled response rates of 95% 97% and 93% for type I, II, and III achalasia, respectively, (3) PD had a lower but not significantly different success rate compared with POEM or LHM in type II achalasia, and (4) botulinum toxin injection was inferior in all subtypes.