The aim of this study was to characterize the clinical characteristics of patients with functional EGJ obstruction and preserved peristalsis. The major findings were that these patients experience dysphagia as a dominant symptom and that the physiology of idiopathic functional EGJ obstruction mirrors that of a known model of mechanical EGJ obstruction, post-fundoplication dysphagia. In both cases, swallowing is associated with significantly elevated distal esophageal IBP, arguing that these patients truly have EGJ outflow obstruction as opposed to a measurement artifact. Furthermore, a subset of patients with idiopathic functional EGJ obstruction with preserved peristalsis respond to treatment for achalasia, suggesting that, in some cases, this condition likely represents the incomplete expression of an achalasia syndrome. The extent of overlap between the diagnoses of functional EGJ obstruction and achalasia depends on how strictly one defines absent peristalsis. In the current study, we excluded 38 patients from the functional EGJ obstruction group because they exhibited such a high proportion of peristaltic defects that some might consider them achalasics; we did not but were not willing to rule out that possibility either. Another rationale for excluding these indeterminate patients was that the degree of their peristaltic dysfunction was so severe as to preclude the measurement of IBP.
Post-fundoplication dysphagia serves as the iatrogenic model of idiopathic functional esophageal obstruction: EGJ relaxation is impaired, flow through the EGJ is reduced, and distal esophageal IBP is increased.13
In a series of 34 post-fundoplication patients, IBP was found to be significantly increased, remaining elevated for at least 2 years after surgery.14
The development of secondary achalasia as a late consequence has also been observed following anti-reflux surgery.15
Furthermore, post-fundoplication dysphagia has been shown to resolve in parallel with the reduction of IBP following conversion to partial fundoplication.16
In the current series, we applied a systematic analysis of IBP using an algorithm devised for pressure topography plots to demonstrate that the degree of IBP developed in idiopathic functional EGJ obstruction was similar to that observed in post-fundoplication dysphagia. Among several indices of IBP tested, we found that, comparing the maximal IBP in the post-deglutitive window for the three most abnormal swallows (max-IBP) was the best discriminator between normal controls and functional obstruction patients due to the large variation in IBP observed in a ten-swallow series.
Of the 16 patients with idiopathic functional obstruction, three were noted to have hiatus hernias. In one instance, it was the CD rather than the LES that appeared to be the focus of deglutitive resistance to bolus transit, suggesting the hernia itself to be the cause of dysphagia in this individual. In the remaining 15 patients, we had no explanation for their dysphagia other than functional EGJ obstruction. Nonetheless, we expect this to be a heterogeneous group with some individuals having a variant expression of achalasia and others likely having an undetected mechanical etiology of EGJ outflow obstruction. Certainly, the treatment efficacy that we experienced is consistent with that hypothesis. In fact, the only patients who experienced a satisfactory response to treatment were the three treated with laparoscopic Heller myotomy. While these data perhaps serve to demonstrate a proof of concept, they also emphasize the need to further characterize these patients to find better predictors of treatment response and physiological markers of treatment effect. Were failed therapies a consequence of misdiagnosis or inadequate treatment? Was treatment response paralleled by decreased IBP? Were there histopathological markers of achalasia in treatment responders? Clearly, we need to address these questions in future studies.
IBP is attributable to the balance between peristaltic forces acting to move the bolus through the esophagus and downstream resistance to that movement. As evident from data in and , normal values of esophageal IBP are low, on the order of 10 mmHg, confirming that the esophagus and EGJ are normally relatively compliant. However, with functional EGJ obstruction, IBP values will often exceed 30 mmHg. This degree of IBP can be likened to balloon distention, a stimulus known to elicit symptoms of chest pain, pressure, and heartburn.17,18
The genesis of these symptoms is presumably by wall strain activating tension-sensitive afferent nerves in the esophageal submucosa and muscularis propria.19,20
Physiologically, the range of pressure thresholds stimulating vagal and spinal afferents varies from 5 to 50 mmHg,21,22
values consistent with those observed in functional EGJ obstruction patients, arguing that elevated IBP may be the primary stimulus for the perception of dysphagia. Future research into the relationship between sensory thresholds, IBP, allodynia, and hyperalgesia will likely shed further light on this.
In summary, idiopathic functional EGJ obstruction with preserved peristalsis is associated with quantifiable outflow obstruction from the esophagus comparable in severity to post-fundoplication dysphagia. This functional defect was well demonstrated by elevated maximal IBP in the worst three of ten test swallows (max-IBP). Lastly, some patients with idiopathic functional EGJ obstruction may represent an early or variant expression of achalasia. To what degree this might progress, over what length of time, and with what frequency will need to be addressed by long-term follow-up studies.