Keywords
achalasia cardia - motor dysphagia - Chicago classification - hypercontractile esophagus
- distal esophageal spasm - esophagogastric junction obstruction
Introduction
The busy endoscopy practice of clinicians at academic centers and private setups alike,
which had dipped to around less than 10% of their usual caseload during the coronavirus
disease-2019 (COVID-19) pandemic, is now beginning to pick up.[1] Esophageal motility disorders (EMDs) contribute a major caseload fraction to the
busy endoscopist's practice. Endoscopy has always been an important part of diagnostic
work-up and therapeutic armamentarium of EMDs. The role of endoscopy includes, but
is no limited to, ruling out alternate etiologies of dysphagia, contributing to the
confirmation of the diagnosis and therapy of EMDs. Moreover, some of the EMDs diagnosed
with high resolution manometry (HRM), such as distal esophageal spasm (DES) and ineffective
esophageal motility (IEM) arise secondary to reflux disease and esophagogastric junction
(EGJ) outflow obstruction (EGJOO) may be mimicked by other disorders on HRM, such
as opioid-related esophageal pathology; hence, documentation of gastroesophageal junction
anatomy and evidence of gastroesophageal reflux on endoscopy is equally important.[2]
[3] Most of the endoscopy continuing medical education webinars and conferences for
the busy endoscopy practitioner focus on the in-vogue topics of therapeutic endoscopy
largely restricted but not limited to per-oral endoscopic myotomy (POEM) and third
space endoscopy, but we must not forget the all-encompassing role of endoscopy in
the management of EMDs.
As we pull back ourselves to resume our busy endoscopy practice from the inevitable
pause due to COVID-19 pandemic, there is time to reflect—are we missing in our busy
endoscopy practice the EMDs?
Spectrum and Current Classification of Esophageal Motility Disorders
Spectrum and Current Classification of Esophageal Motility Disorders
The spectrum of EMDs in India has been explored previously. A decade earlier, a study
at our center on 250 patients with dysphagia evaluated with conventional manometry
showed that achalasia cardia (AC) was the commonest EMD in nearly three-quarters of
the patients evaluated over a period of 5 years for dysphagia.[4] However, with the advent of HRM and emergence of the Chicago classification as the
quintessential classification system to classify and interpret EMDs, other EMDs that
were earlier not appreciated using conventional manometry are being diagnosed more
frequently. A more recent study using HRM has now shown that IEM is the commonest
motility disorder accounting for nearly 40% of patients with dysphagia or retrosternal
discomfort and AC is a distant second (26%).[5]
The most recent iteration of the Chicago classification (version 4.0) was developed
with consensus of 52 experts in neurogastroenterology and motility and recommends
testing in both supine and upright positions and the use of provocative maneuvers
such as multiple rapid swallows in supine position and rapid drink challenge in upright
position.[6] It classifies EMDs into disorders of EGJ outflow (EGJO) and disorders of peristalsis.
The disorders of EGJO are characterized by a raised median integrated relaxation pressure
(IRP) and are further identified as AC if they are accompanied by absent peristalsis.
AC is further subclassified as type I (characterized by 100% absent peristalsis),
type II (>20% swallows showing evidence of panesophageal pressurization in the simultaneous
contraction), and type III (>20% swallows showing spasm), with a distal latency (DL) < 4.5 seconds
indicating simultaneous contractile activity with distal contractile integral (DCI) > 450 mm
Hg s cm ([Fig. 1]). The diagnosis of EGJOO needs to be made only when there is manometric evidence
of raised IRP in supine and upright positions and >20% of the swallows showing intrabolus
pressurization along with symptoms of dysphagia and noncardiac chest pain and evidence
of obstructive physiology on timed barium swallow (TBE) or functional lumen imaging
probe (FLIP).[6]
Fig. 1 The high-resolution manometry findings of achalasia cardia with raised integrated
relaxation pressure. (A) Type I achalasia with 100% absent peristalsis. (B) Type II achalasia with more than 20% swallows showing panesophageal pressurization
along with absent peristalsis. (C) Type III achalasia with more than 20% swallows with spasticity and distal latency
less than 4.5 seconds.
In the case of normal IRP, disorders of peristalsis are considered. A diagnosis of
absent contractility can be made in the presence of 100% failed peristalsis. The diagnosis
of DES requires >20% premature swallows with DL < 4.5 seconds along with presence
of dysphagia and/or noncardiac chest pain. DES differs from achalasia by having some
peristalsis (DL > 4.5 seconds), whereas in achalasia all the contractions are simultaneous
(DL < 4.5 seconds). Similarly, the diagnosis of hypercontractile esophagus requires
>20% swallows with DCI > 8,000 mm Hg s cm along with symptoms of dysphagia and/or
noncardiac chest pain. The diagnosis of IEM has been made more stringent requiring
>70% ineffective swallows (failed and weak) or >50% failed swallows ([Fig. 2]).
Fig. 2 The high-resolution manometry tracings of (A) normal liquid swallow, (B) ineffective esophageal motility, and (C) hypercontractile esophagus.
Since the manometric diagnosis of EMDs can be mimicked by several etiologies such
as EGJOO by opioid use and IEM and DES by gastroesophageal reflux disease (GERD),
primary EMDs are by themselves thought to be rare. The new iteration emphasizes the
fact that a manometric pattern does not equate with a diagnosis of primary EMDs such
as EGJOO, DES, and hypercontractile esophagus, and additional symptoms and physiologic
tests such as TBE and/or FLIP are required for a conclusive diagnosis. This might
increase precision in diagnosis and prevent overtreatment. However, prospective evaluation
in the real-world setting remains to be seen.
Identification of Alternate Etiologies Mimicking Esophageal Motility Disorders on
Endoscopy
Identification of Alternate Etiologies Mimicking Esophageal Motility Disorders on
Endoscopy
Pseudoachalasia, by definition, is characterized by an identifiable cause mimicking
the clinical and manometric findings of AC. The prevalence of pseudoachalasia varies
between 1 and 5% of all diagnosed cases of AC.[7] The most common cause of pseudoachalasia is an underlying malignancy, most commonly
a gastroesophageal junction malignancy (40%).[7] However, several benign causes such as amyloidosis and postsurgical alterations
can lead to similar clinical and manometric findings. The hypothesis explaining the
mechanism of such findings in pseudoachalasia is direct infiltration of the submucosal
and muscular plexus by malignancy or paraneoplastic neuropathy arising as a result
of distant malignancy.[7] Clinical clues to a diagnosis of pseudoachalasia include an older age (>55 years),
short duration of symptoms (<12 months), and weight loss of > 10 kg.[8] However, these clinical clues are not specific for pseudoachalasia.
Needless to say, endoscopic evaluation is the first-line test in the evaluation of
any dysphagia, but endoscopic evaluation of mucosa is largely normal in pseudoachalasia
by definition. Hence, subtle clues that point toward the diagnosis of pseudoachalasia
on endoscopy are significant resistance at the EGJ and inability to pass the scope
into the stomach.[8] Also, retroversion of the scope and evaluation of the EGJ in detail to rule out
any malignancy is mandatory by the endoscopist. At times, a cross-sectional imaging
and endoscopic ultrasound are contributory.
The occurrence of EMDs in association with eosinophilic esophagitis (EoE) is well
known.[9]
[10]
[11] The prevalence of EMDs, including AC, in EoE ranges from 4 to 87%.[9] Apart from obvious mechanical strictures and narrowing arising due to mucosal and
muscular edema and fibrosis, dysphagia in EoE may arise as a result of underlying
motility disturbances in the face of normal endoscopic picture. The release of eosinophilic
products that have direct myoirritant and neuroirritant properties is well known.[10] Hence, it is prudent to have a high clinical suspicion for EoE so that appropriate
endoscopic mucosal biopsies may be taken to rule out underlying EoE mimicking these
disorders. Recently, we reported a patient with eosinophilic gastroenteritis presenting
with AC.[12]
Identification of Specific Esophageal Motility Disorders on Endoscopy
Identification of Specific Esophageal Motility Disorders on Endoscopy
Most of the EMDs apart from AC do not present with specific endoscopic findings. The
spectrum of endoscopic findings in AC ranges from normal to a grossly dilated sigmoid
esophagus.[13] The mucosa can range from a spectrum of being normal to stained with whitish food
and liquid residue or can be entirely not visible due to presence of liquid or solid
food residue within the lumen ([Fig. 3]).[13] The mucosa may show changes of stasis esophagitis or secondary candidiasis related
to food stagnation.[14] There may be presence of pulsion diverticula along the length of the esophagus due
to the outflow obstruction. The EGJ is characteristically tight but “pops” open on
slight pressure.[15] The nonrelaxing lower esophageal sphincter gives characteristic appearance to the
EGJ endoscopically so that the full extent of the palisade vessels is not visible
and the mucosa folds in a “rosette”-like pattern.[16] Similarly, in the absence of the characteristic rosette-like pattern, a “gingko
leaf”–like pattern of palisade vessels is seen, which is specific for AC.[17] Other characteristic findings include the pinstripe pattern and the champagne glass
appearance on endoscopy.[18]
[19] The presence of endoscopically visible but nonspecific spastic and nonoccluding
contractions can also provide diagnostic clue toward AC.[14] Rarely, one may see a simultaneous contraction in patient with achalasia or DES.[20] However, endoscopy may be entirely normal in patients with EMD, particularly in
the early stages.
Fig. 3 The characteristic endoscopic findings of achalasia cardia include a dilated esophagus
with food residue and secondary mucosal changes related to stasis esophagitis.
Although HRM is the gold standard test to diagnose EMDs, the use of endoscopic evaluation
as a diagnostic modality has been tested. Cameron et al video-recorded the endoscopic
evaluation of patients with motility disorders as well as healthy controls.[21] On evaluation of the recordings by blinded clinicians, the presence of lumen-occluding
contractions and no difficulty in opening EGJ was significantly different between
healthy controls and those with AC.[21] However, the small sample size and the low specificity of the findings prevent widespread
use of endoscopy as a diagnostic modality.[21]
In another study by Matsubara et al evaluating endoscopic among 380 patients with
dysphagia, an abnormal endoscopy was seen in nearly two-thirds of those with an EMD.[14] They specifically looked for luminal food residue, resistance at EGJ, dilation of
the esophageal lumen, and the presence of spastic and non–lumen-occluding contractions
by endoscopy. Endoscopy findings were abnormal in 116/127 (91.3%) of patients with
AC, 20/30 (66.6%) patients with DES, and 6/10 (60%) patients with hypercontractile
esophagus but only in 14/60 (23.3%) patients with IEM and 1/6 (16.7%) patients with
fragmented peristalsis.[14] The utility of these findings as a diagnostic criterion is limited by their low
specificity and the effect of drugs used in endoscopy such as benzodiazepines and
anticholinergics on the contractility of the esophagus.
Endosonography for Esophageal Motility Disorders
Endosonography for Esophageal Motility Disorders
The role of endoscopic ultrasonography (EUS) has traditionally been limited to rule
out pseudoachalasia in patients with a high degree of suspicion. The role of EUS in
EMDs has been evaluated by Krishnan et al, who in their retrospective case series
of 62 patients with EMD showed that EUS was able to contribute to an alternative diagnosis
and change the management in 9/62 (15%) of the patients.[22] The patients with a changed diagnosis were predominantly those who has been initially
diagnosed as having AC or EGJOO; there was no change in diagnosis or management of
those who has been diagnosed with jackhammer esophagus or DES.[22]
Oumrani et al have also evaluated EUS in 69 patients with EMD and showed that esophageal
wall thickening was present in 43 (62%) of the patients.[23] Ultimately, 3/69 (4.3%) patients were diagnosed as pseudoachalasia but EUS did not
contribute to the diagnosis in these cases.[23] Moreover, they showed that there was no correlation of esophageal thickness with
symptoms as assessed by the Eckardt score or with response to treatment.[23] The esophageal wall thickness was not significantly different among the various
types of EMD.[23] The significance of esophageal muscular wall thickness in AC remains unresolved
with contradictory evidence.[24]
[25]
Emerging Role of Functional Lumen Imaging Probe and Panometry
Emerging Role of Functional Lumen Imaging Probe and Panometry
Although HRM is still the gold standard to diagnose EMDs, there are certain cases
that cannot be adequately characterized using HRM. The FLIP is a high-resolution impedance
planimetry–based device used to assess the distensibility and geometry of the EGJ.
It consists of a 240-cm-long and 3-mm-wide catheter on the distal end of which an
infinitely compliant 10-cm-long balloon is mounted.[26] The distal end of the catheter that is within the balloon has 16 paired impedance
sensors and the distal end of the catheter has a solid-state pressure sensor. The
balloon is placed endoscopically or via image assistance across the EGJ after inflating
the balloon with a special saline solution. An electrical current is passed between
the electrode pairs housed on the catheter within the balloon and the voltage across
the impedance electrodes is measured. The impedance between the electrodes is determined
by Ohm's law. The calculated impedance is inversely related to the cross-sectional
area across the two electrodes, which can be calculated. The diameter of the lumen
can also be measured by the same principle. The metric used to assess the distensibility
is the distensibility index (DI), which is computed by dividing the lowest median
cross-sectional area with the pressure across the distal most pressure sensor. A DI
of 2.8 mm2/mm Hg has been suggested as the cut-off for AC.[27] FLIP can be used to diagnose cases of AC with similar physiology of a nonrelaxing
EGJ not meeting the HRM IRP criteria for AC.[28] Since the HRM catheter measures only lumen-occluding contractions, slight decrease
in distensibility or opening of the EGJ is often not appreciable with HRM; however,
such cases exhibit a decreased DI and can be diagnosed confidently as AC. Similarly,
FLIP has been used to assess the therapeutic response intraoperatively while performing
the myotomy during laparoscopic Heller's myotomy and POEM.[29] The DI has also been used to predict the response to pneumatic dilation, with a
>1.8 mm2/mm Hg rise in DI predictive of clinical response.[30] The Chicago classification version 4.0 recommends using FLIP to confirm the HRM
findings of EGJOO since similar manometric findings may be seen in normal individuals
and in those with GERD.
The diameters measured by FLIP can be represented on space–time axis with color coding
for the diameters in a manner similar to Clouse plots to obtain tracings of contraction
pattern throughout the length of the esophagus known as FLIP topography or panometry.
These patterns can be used to characterize peristalsis and differentiate between the
subtypes of AC. The busy endoscopist must keep abreast of these recent advances in
EMD diagnosis and management.
Role of Timed Barium Esophagogram in Diagnosis and Management of EMDs
Role of Timed Barium Esophagogram in Diagnosis and Management of EMDs
A TBE involves serial image acquisition at 1, 2, and 5 minutes in left posterior oblique
position after ingestion of 100 to 250 mL of 45% (weight by volume) of barium sulfate.[31] In addition to providing anatomical evidence of dilated esophagus and bird's beak
appearance typical of achalasia, it provides quantitative measure of esophageal emptying.
The height and width of the contrast column can be measured or, alternatively, the
area of retained contrast can be measured to give an objective parameter. Usually,
the contrast column empties completely at 5 minutes in healthy individuals. Postdilation
or myotomy decline in height of column by 50% is predictor of optimal response.[32] The advantage of TBE over HRM lies in certain cases in which the manometry catheter
cannot be placed across lower esophageal sphincter (LES) and hence IRP cannot be measured.
Also, patients with symptoms and HRM findings compatible with EGJOO must have evidence
of inadequate emptying or relaxation on physiologic tests such as TBE or FLIP to qualify
as EGJOO according to the Chicago version 4.0. FLIP has additional advantage of use
as an intraprocedural modality to tailor the length of myotomy but is limited by its
availability only at centers of expertise.
Conclusion
The role of endoscopist in the diagnosis and management of EMDs cannot be undermined.
The first-line investigation in patients with dysphagia remains endoscopy. It serves
to rule out mechanical obstruction as well as certain etiologies such as pseudoachalasia,
GERD, and EoE, which may mimic EMDs on clinical and manometric grounds. Moreover,
endoscopy provides supporting role in providing clues for diagnosis of EMDs, primarily
AC. However, HRM remains the gold standard for diagnosis of EMDs and their classification.
The use of HRM is essential and is the standard of care, as emphasized by the recent
Chicago classification version 4.0. The manometric patterns are not diagnostic of
primary EMDs such as EGJOO, DES, and hypercontractile esophagus, which require presence
of clinical symptoms and additional evidence of deranged emptying and relaxation with
TBE and FLIP. Newer technologies such as FLIP and panometry are emerging to fill in
the gap to diagnose EMDs not adequately characterized by HRM. While endoscopy holds
a firm ground in management of EMDs, with procedures ranging from pneumatic balloon
dilation, to POEM, to endoscopic botulinum toxin injection, it also holds a firm ground
in surveillance and management of postmyotomy reflux that these patients often experience.
With a hefty role to play, it is impossible for the busy endoscopist to miss EMDs
in their busy practice.
