Discussion

In this study, we describe the clinical and manometric characteristics of our cohort of patients with EGJOO with and without other coexisting CC diagnoses. We hypothesised that patients with EGJOO may have concomitant oesophageal body dysmotility, possibly contributing—at least in part—to their oesophageal symptoms, and that a new subclassification—a modification of the CC—would be more useful clinically. In our proposed scheme, we start with the recognition of EGJOO using median IRP >15 mm Hg as an essential HRM criterion. We then proceed to independently assess the oesophageal body contractility using CC V.3 criteria and classify it as normal or abnormal, such as achalasia, IEM, DES (including JE) or combined IEM+DES (figure 6). In this fashion, we recognise several subtypes of EGJOO, each with variable symptoms of oesophageal dysfunction and each potentially with their own therapeutic implications. This results to two key differences: (1) we incorporate achalasia (all three types) into the five subgroups of EGJOO; (2) in contrast to the hierarchical CC classification, we allow for dual diagnoses, one pertaining to EGJ malfunction, the other to oesophageal dysmotility.

We do not propose to term achalasia as EGJOO. We are using EGJOO as a starting point in defining EGJ physiology and, in its full version, we get achalasia (all three types). We are simply suggesting that the HRM interpretation starts with EGJ assessment that may or may not turn out to be achalasia. We (and others) also acknowledge the possible evolution of EGJOO to achalasia; hence our proposal is not entirely without substance. As for the subcategories and their value, we already have three types of achalasia that are well accepted without knowing for certain if such subcategorisation helps us manage the condition better and much more outcomes research will be needed in this regard. It is because of such clinical and manometric heterogeneity of EGJOO that we propose this new scheme. Specifically, if the EGJOO is associated with DES, treatment with botulinum toxin in the distal oesophagus and the EGJ could improve clinical outcomes. If in contrast, EGJOO is associated with IEM, injection of the EGJ with Botox may precipitate or aggravate acid reflux. Since achalasia may be preceded by the EGJOO diagnosis in some cases and since many authors in the field recommend an f/u HRM to look for achalasia, why not simplify things and start out with EGJ assessment. If present, one can look at the body motility and classify it as achalasia or not and classify it, again using elements of the CC, as the other types of EGJOO that we propose.

EGJOO, a relatively new diagnosis, established by the CC and based on HRM parameters, such as median IRP >15 mm Hg, and is considered relatively rare, ranging from 1.6% to 11%, with few reports in the literature, is mostly retrospective in nature.2 10–12 The condition is characterised by high prevalence of dysphagia (80%), regurgitation (90%) or chest pain (65%), as already reported. In our series of 478 HRM studies performed in symptomatic patients, the prevalence of EGJOO was 24% with more than 50% being associated with other motility disorders, such as DES, JE, or IEM. In addition to the well-described structural abnormalities reported in other series (such as hernia, fundoplication), we encountered many patients suffering from functional (idiopathic) EGJOO associated with Parkinson’s disease, GERD and EoE, which ranged from 16% to 79% and possibly explains the intermittent nature of this condition.

In our cohort and like other studies, symptoms in patients with EGJOO did not always require treatment and treatment response was variable, suggestive of a considerable degree of heterogeneity.2 4 Because of inherent biases in the assessment of therapeutic response to intervention in a retrospective study without the use of specific endpoint assessment, we were not able to decipher any differences among the five subtypes. Nevertheless, surgery (primary or reparative), endoscopic injection or botulinum neurotoxin to the EGJ, distal oesophagus or both, and endoscopic balloon dilation of the EGJ were used. In our cohort and despite observation of longer than 2 years, we only observed evolution of EGJOO to achalasia in one patient, unlike prior studies.4 11 However, this possibility needs to be considered and repeat evaluation because of the efficacy and availability of established treatment options for any of the subtypes of achalasia.13 Our study was also enriched by several patients who, despite the discomfort of HRM, underwent repeat (second and third) HRM over the course of 2 years (table 2). These data suggested a fluidity of the manometric diagnosis over time, questioning our ability to firmly establish the diagnosis and emphatically decide on therapy. For these reasons, longitudinal follow-up and repeat HRM should be suggested to recognise evolution towards achalasia, and towards regression or recharacterisation to another diagnosis. We believe that our proposed classification, matched by a repeat assessment 3–6 months later, may allow a better characterisation and hopefully lead to better therapeutic outcomes.

Oesophageal body and/or EGJ dysmotility may be primary or secondary to other conditions that structurally or functionally involve the oesophagus. As shown in table 1, a significant number of our patients had GERD and Parkinson’s disease. To what degree these conditions coexist or are causally related to the EGJOO and the exact mechanism(s) by which such relationship exists or evolves is unclear, but both have the potential to alter muscle function intermittently and variably over time, thereby potentially explaining the variability of the HRM diagnosis seen or repeat testing (table 2).14 15 For example, it is possible that episodic EGJOO with or without associated oesophageal body alterations, such as DES, IEM or both, could explain the well-known phenomenon of chest pain or non-obstructive dysphagia that have been well described in GERD.8 9

Our findings and our proposed new approach are in complete agreement with the study of Zheng et al who sought to determine the frequency of abnormal body motility and/or abnormal bolus movement in patients with EGJOO.16 In their series of patients, 56 (40%) were diagnosed with an abnormal motility pattern to liquids (IEM=28, DES=19, JE=6), of which 44 (76%) had abnormal bolus transit to liquids, viscous or both. Among patients with abnormal bolus transit, dysphagia and heartburn were common, like in our cohort. They concluded that a significant percentage of patients with EGJOO have abnormal oesophageal body motility and/or abnormal bolus transit and suggested that current criteria do not allow for the description of other abnormalities in oesophageal motility and bolus transit among patients who are given the diagnosis of EGJOO.

There are several strengths and limitations in our study. First, although cohort and observational in nature, our study involved many patients presenting with various oesophageal symptoms who were studied in detail and highlights the possibility of a link between oesophageal body and EGJ motor dysfunction heretofore unexplored. Second, the study population—the largest series to date—was community based, who mostly suffered by frequent but mild to moderate symptoms of oesophageal dysfunction. Therefore, our findings are generalisable and not limited to those patients with severe or protracted disease referred to tertiary centres. Third, this is the only study where repeat manometric evaluation was performed in a cohort of patients with EGJOO, highlighting the fleeting nature of this diagnosis. Some limitations need to be kept in mind. First, oesophageal impedance/pH-metry was not used in all subjects; therefore, the presence of pathologic acid/non-acid reflux could not always be ascertained or quantified. Second, our population was not assessed using elaborate and well-validated GP questionnaires but instead, through our simpler, general and practical tool previously validated and used in many previous studies in our practice setting.5 14 Third, given the retrospective nature of our study, we could not quantify the impact of selected therapy, if any. Fourth, we did not use EUS or barium radiography in the vast majority of our cohort since we were able to clarify structure based on endoscopy and, at times, CT imaging. Fifth, it is possible that the patients who underwent HRM testing represented a select group of patients with EGJOO with higher prevalence and severity of oesophageal symptoms that justified the performance of HRM, resulting in overestimation of our results. This may be particularly true of the patients with Parkinson’s disease (n=28), who comprised a significant subset of this study population (table 1). Given the uncertain evolution of EGJOO, it has been our practice to encourage patients to undergo f/u HRM; a fraction of them comply mostly because they remain symptomatic and not responding to any effort at therapy. Those with mild symptoms or those who improve are not (understandably) interested in repeat studies. A prospective study would be important to clarify this issue and eliminate selection bias. Finally, we have scattered information of variable therapies applied but in order to validate their impact one needs standardisation of outcome assessments. This was a retrospective first effort to subclassify the patients with EGJOO into groups in a way similar to achalasia subgrouping and then look at therapeutic outcomes. Therapies to be explored would be EGJ balloon dilation (variable sizes), Botox injection of the EGJ ± the lower oesophagus, prokinetics, and so on.

In summary, we believe that EGJOO is an intermittent manometric finding within a heterogeneous group of patients and is associated with other—overlapping—HRM diagnoses which, in this study, we tried to subcategorise. Symptoms may or may not reflect this additional diagnosis and management may vary, including medications, endoscopic interventions or avoidance of treatment. EGJOO was not persistent in the majority of patients retested. This temporal variability and prominent coexistence with other motility diagnoses raise questions as to the clinical significance of EGJOO. Going forward, we suggest that EGJOO not be characterised as a major motility disorder and future classification schemes should specify whether EGJOO is in isolation or linked with another motility diagnosis. A lot more work can be done looking at correlations between timed barium studies, impedance/pH, EndoFLIP, EUS, and so on, and the point of this work was to highlight some useful features to clinicians and to further research. Prospective studies will be needed to validate such subgrouping of EGJOO or further modifying it into clinically relevant clinical entities.