Esophageal Motility Disorders: Diagnosis and Treatment Strategies

The esophagus transports a bolus from the pharynx into the stomach. The upper/lower esophageal sphincter (UES/LES) and esophageal contractions play a crucial role in its transportation [1]. Swallowing triggers the relaxation of the UES/LES and deglutitive inhibition followed by peristaltic contractions. Excitatory and inhibitory neurons both regulate these sequential movements via the vagus nerve and intrinsic enteric nervous system. Dysfunctions of these neurons cause esophageal motility disorders, leading to esophageal symptoms, including dysphagia and noncardiac chest pain.

Esophageal motility disorders are categorized as primary and secondary disorders. The infiltration of carcinoma around the LES, for example, may cause secondary esophageal motility disorders. Since secondary disorders generally require specific diagnostic tests and treatment rather than a manometric diagnosis and treatment for esophageal motility, we mainly focused on primary disorders in this review.

High-resolution manometry (HRM) is essential for diagnosing primary esophageal motility disorders. However, the recognition of these disorders and HRM by general practitioners in Japan is limited. Therefore, the present review summarizes evidence on the etiology, pathophysiology, diagnosis, and treatment of esophageal motility disorders.

The following modalities are used to diagnose esophageal motility disorders. While HRM and the functional lumen imaging probe (FLIP) are very specific to esophageal motility disorders, they are only performed at limited tertiary centers; therefore, interviews, endoscopy, and barium swallow are useful screening tools. In addition, it is important to note that patients’ symptoms and the findings of multiple modalities are both considered prior to the initiation of invasive treatment because a gold standard has not yet been established for diagnosing esophageal motility disorders other than achalasia.

No symptoms are specific to esophageal motility disorders. Although dysphagia to liquids and chest pain are empirically regarded as symptoms of esophageal motility disorders, a physical obstruction (i.e., esophageal cancer), acute coronary syndrome, and gastroesophageal reflux disease (GERD) may also cause these symptoms. Therefore, clinicians need to consider a work-up for heart disease and endoscopy before testing for esophageal motility disorders.

Previous medical histories, particularly upper gastrointestinal surgeries, and medications are relevant for patients with esophageal symptoms. Opioids may be associated with spastic esophageal contractions and impaired relaxation of the LES [2].

Endoscopy is essential for distinguishing organic diseases from esophageal motility disorders. Hiatus hernia, Schatzki’s ring, peptic stricture, eosinophilic esophagitis (EoE), and malignant disorders may cause esophageal symptoms. In EoE patients with normal endoscopy, only biopsies provide diagnostic evidence [3]. Endoscopy is sometimes helpful for the diagnosis of esophageal motility disorders. In patients with achalasia, a dilated esophagus with retained food or liquid, dysmotility, and stenosis are classical findings suggesting impaired esophagogastric junction (EGJ) outflow (shown in Fig. 1a); however, they are often not visible. “Esophageal rosette,” “Gingko leaf sign,” and “pinstripe pattern” are characteristic findings in some patients with achalasia. Esophageal rosette consists of the non-visibility of the esophageal palisade vessels and radially distributed folds toward the esophageal narrowing at the end of a deep inspiration (shown in Fig. 1b) [4]. In achalasia patients with Gingko leaf sign, the morphology of a longitudinal section of the EGJ is shaped like a Gingko leaf and the full extent of EPV or rosette-like folds is not visible (shown in Fig. 1c) [5]. Pinstripe pattern is defined as the presence of longitudinal wrinkles on the mucosa of the esophageal body (shown in Fig. 1d) [6]. A corkscrew esophagus suggests spastic esophageal contractions, including achalasia type 3 (shown in Fig. 1e). Although these findings may be highly specific, there are currently no prospective multicenter studies on patients with dysphagia. Therefore, normal endoscopy does not always indicate normal motility.

Barium swallow, which is widely available and easily performed in clinical practice, assesses bolus transport from the esophagus into the stomach by ingesting barium contrast. While few comparative analyses of barium swallow and manometric diagnosis have been conducted to date, limited evidence shows that classical findings, such as the air-fluid level, bird’s beak sign, and rosary bead/corkscrew appearance (Fig. 1f), have unsatisfactory diagnostic yields [7‒9]. Several reasons for this have been proposed. The assessment of esophageal peristalsis may be subjective due to the difficulties associated with quantifying esophageal contractions. Furthermore, the methodology of barium swallow (i.e., the amount and concentration of ingested barium and the use of solid/liquid barium) has not yet been standardized. Hata et al. [10] reported a diagnostic flowchart based on the findings of barium swallow with novel findings, which needs to be validated in a multicenter study. Moreover, a liquid barium swallowing test cannot assess luminal distensibility, which is relevant, particularly in patients with disorders of EGJ outflow. Barium swallow using “Onigiri,” a Japanese rice ball, may enable the evaluation of distensibility, thereby increasing diagnostic yield [11].

In patients with achalasia or esophagogastric outflow obstruction (EGJOO), timed barium esophagogram (TBE), which evaluates the emptying of barium from the esophagus at 1, 2, and 5 min, may increase sensitivity and provide information on posttreatment conditions (shown in Fig. 1g–i) [12, 13].

HRM catheters have closely spaced pressure sensors and display changes in esophageal pressure using colored topographic plots. HRM and its diagnostic criteria, the Chicago Classification, have been developed to obtain a more detailed understanding of the pathophysiology of esophageal motility disorders [14‒17]. Although HRM is essential for diagnosing achalasia and selecting specific treatments, its clinical relevance to other disorders remains controversial [18‒20]. Therefore, the recently updated guidelines, the Chicago Classification version 4.0 (CCv4.0), suggest additional maneuvers for HRM (i.e., the water swallow test in the upright position and the rapid drink challenge) to minimize ambiguity [17]. The CCv4.0 criteria are shown in Figure 2. Cut-off values for key parameters in the criteria differ among HRM systems [21]. Cut-off values for the Starlet system, which has predominantly been employed in Japan, were previously reported [22‒24].

The FLIP catheter, which has a distensible balloon with impedance sensors and a pressure sensor, is transnasally intubated during sedated endoscopy. The balloon is distended with fluid from a dedicated pump. FLIP shows the real-time cross-sectional area and luminal distensibility. It also assesses secondary peristalsis. FLIP is still in the early clinical stage and is currently regarded as a supportive diagnostic tool for HRM [25].

Achalasia is an esophageal motility disorder that is characterized by the loss of the myenteric plexus, leading to impaired relaxation of the LES and no peristalsis [26]. Although the incidence and prevalence of achalasia were previously reported to be approximately 1/100,000 and 10/100,000 per year, respectively, a recent study suggested a higher incidence and prevalence, possibly due to advances in diagnostic technologies [27, 28]. Achalasia is categorized into 3 types using HRM: type 1 with failed contractions, type 2 with failed contractions accompanied by pan-esophageal pressurization, and type 3 with premature contractions [17]. The extent of the loss of ganglion cells was shown to be slightly higher in patients with achalasia type 1 [29].

Treatments for achalasia include medications, botulinum toxin injections, pneumatic dilation (PD), per-oral endoscopic myotomy (POEM), and laparoscopic Heller myotomy (LHM). Although calcium channel blockers, nitrates, and sildenafil have been reported to reduce EGJ pressure, the effects of these medications on patients’ symptoms remain controversial. In addition, adverse effects, such as hypotension and headache, make prescriptions challenging. Botulinum toxin inhibits the release of acetylcholine from nerve endings, leading to a decrease in EGJ pressure. The short-term effects of botulinum toxin injections have been established; however, they need to be repeated for symptom relapse. This treatment is only considered for patients with severe comorbidities who are rarely candidates for invasive treatments. These pharmacological treatments are not approved for patients with achalasia by the regulatory agency in Japan.

PD is generally performed using endoscopy and fluoroscopy. It is widely available, with a low risk of perforation of 1.0–3.2% [30]; however, the 2-year/5-year efficacies of PD are lower than those of POEM [31, 32]. Therefore, PD may be selected for patients with severe comorbidities or those living in an area where myotomy cannot be performed. Predictors of good outcomes of PD are an older age (>40–45 years), female sex, a non-dilated esophagus, and type 2 achalasia [26, 33].

LHM has been performed for decades. Although its efficacy and safety are well-established and similar to those of POEM, POEM has recently been recommended as the first-line treatment, particularly for patients with type 3 achalasia because the length of myotomy may be adjusted by endoscopists. The clinical success rate of POEM was previously reported to be 79–98% in 12- to 75-month follow-ups [30]. Comparative controlled studies demonstrated that POEM was preferable to PD in 2- and 5-year follow-ups [31, 32], and similar to LHM, while posttreatment reflux esophagitis developed more often in patients undergoing POEM [34]. Treatment selection depends on local expertise and shared decision-making with patients.

The previous Chicago Classification (CCv3) defined EGJOO as an increased integrated relaxation pressure (IRP) with the presence of esophageal peristalsis [16]. This diagnosis includes heterogeneous conditions, including achalasia variants, postsurgical interventions, cancer, luminal stricture, cardiovascular compression, opioid intake, para-esophageal hernia, and artifacts [20]. The presence of EGJOO based on CCv3.0 ranged from 5 to 24%, and 32–94% of patients did not require any treatment [20], suggesting the irrelevance of this manometric diagnosis. The criteria for the manometric diagnosis of EGJOO per CCv4 are more stringent than those per CCv3, requiring increased IRP and intrabolus pressure in both the supine and upright positions to avoid unnecessary treatment on patients with irrelevant EGJOO. Furthermore, the criteria require specific symptoms (dysphagia and chest pain) and consistent findings from other tests, such as FLIP and TBE. Although these changes are partially based on experts’ consensus, they were previously shown to be useful for detecting clinically relevant EGJOO [24, 35].

Invasive treatment for EGJOO only needs to be considered when FLIP or TBE shows objective evidence of EGJOO without spontaneous resolution. PD, botulinum toxin injections, and POEM were effective in small case series; however, a randomized trial has not yet been conducted. Acotiamide, which is clinically used to treat functional dyspepsia, was recently reported to reduce IRP in patients with EGJOO [36, 37]. Further prospective studies are warranted to confirm its effects on patients’ symptoms.

Distal esophageal spasm (DES) is characterized by premature contractions in 20% or more of water swallows with normal relaxation of the LES on HRM, accompanied by impaired deglutitive inhibition during multiple rapid swallows. Hypercontractile esophagus (HE) is characterized by hypercontractility in 20% or more of water swallows on HRM. The rosary bead/corkscrew appearance on barium swallow (or endoscopy) is supportive evidence for these diagnoses. Treatments have not yet been established for spastic disorders. Noninvasive pharmacological treatments, such as calcium channel blockers, nitrates, and phosphodiesterase-5 inhibitors, need to be considered; however, a randomized controlled study has not yet been performed and there are some side effects (i.e., hypotension and dizziness). If these noninvasive treatments are ineffective, POEM and LHM may be an option. Although POEM and LHM have been shown to attenuate symptoms in patients with DES and HE, there is currently no randomized controlled study with long-term observations after these treatments.

The etiology, diagnostic features, and treatment of patients with HE were recently reported in a nationwide cohort study in Japan [38]. Among the 4,412 HRM tests performed between January 2008 and June 2017, 89 patients (2.0%) were diagnosed with HE. The rosary bead/corkscrew appearance was observed with endoscopy in 26% of patients and with barium swallow in 34%. Thirty out of 47 patients (64%) receiving pharmacological treatments, 10 out of 13 (77%) who did not receive any treatment, 16 out of 21 (76%) receiving POEM, and 2 out of 2 (100%) undergoing LHM showed improvements.

Ineffective esophageal motility (IEM) is defined as more than 70% ineffective swallows or at least 50% failed peristalsis by CCv4.0, while it was defined as more than 50% ineffective swallows by CCv3.0. The more stringent criteria for the diagnosis of IEM per CCv4.0 are due to the clinical irrelevance of IEM in clinical practice [39, 40]. IEM per CCv4.0 is more likely to be associated with GERD [40]. The presence of IEM and/or contractile reserve after multiple rapid swallows may be of importance when considering anti-reflux surgery for patients with GERD [41]. Absent contractility is defined as 100% failed peristalsis. If a patient with absent contractility has dysphagia and/or noncardiac chest pain, achalasia type 1 needs to be ruled out with TBE or FLIP. In addition, absent contractility may sometimes be associated with scleroderma.

The treatment of hypomotility disorders is very challenging. There are currently no pharmacological treatments that improve weak contractions. Lifestyle modifications, such as cutting food into small pieces, chewing carefully, and eating in an upright position (or not lying down for a few hours after meals), and diaphragmatic breathing may be helpful but lack high-quality supportive evidence.

Although esophageal motility disorders have been intensively investigated worldwide, their clinical relevance apart from achalasia remains controversial, and effective noninvasive treatments have not yet been developed. Therefore, their diagnosis and decision-making for treatments require careful attention.

The authors have no conflicts of interest to declare.

The authors received no specific funding for this work.

Yoshimasa Hoshikawa and Katsuhiko Iwakiri contributed to the conception and design. The first draft of the manuscript was written by Yoshimasa Hoshikawa, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.