Recent advances in dysphagia management

Esophagogastric junction outflow obstruction

EGJOO is a heterogeneous diagnostic group composed of patients with evolving achalasia, mechanical obstruction, or an artifact related to inherent issues with the IRP measurement. An elevated IRP can be a positional artifact or related to an extreme bend in the catheter, and the IRP may normalize with positional changes. Thus, it is extremely important to measure the IRP in both the supine and upright positions to assess whether this artifact is falsely leading to a diagnosis of EGJOO⁷. There are complementary findings on HRM that increase the likelihood of a true obstruction, such as evidence of compartmentalized intrabolus pressurization, poor bolus transit, and concomitant hypercontractility. However, these findings have not been shown to be accurate enough to confirm an outflow obstruction, and other tests, such as a timed barium esophagram with a barium tablet or functional luminal imaging probe (FLIP) panometry assessment of EGJ opening, can be helpful in confirming a true obstruction. If a true obstruction is noted on these examinations, it is still difficult to determine whether this is achalasia in evolution, and further assessment may be required before achalasia treatment is considered in difficult and equivocal cases. Cross-sectional imaging or endoscopic ultrasound can be helpful but should be limited to EGJOO patients with dysphagia and overt obstruction noted on esophagram if a mechanical obstruction or pseudoachalasia presentation is suspected (older age at onset, weight loss out of proportion, and abnormalities at the EGJ during endoscopy).

Jackhammer esophagus

Similar to EGJOO, jackhammer esophagus, which is diagnosed on the basis of two swallows with a DCI value above 8000 mm Hg*s*cm, is a very heterogeneous classification. Meeting these criteria, however, is not enough evidence to refer patients for invasive treatments. As mentioned above, this pattern can be associated with obstruction at the EGJ and is also seen in the context of gastroesophageal reflux disease (GERD) and EoE. Given this heterogeneity, further workup focused on ruling out an obstruction and empiric trials with smooth muscle relaxants should precede referral for myotomy⁸. Many patients with diagnosed jackhammer esophagus will have a benign course, especially when this pattern is found incidentally during a pre-operative workup for GERD and thus observation and follow-up may also be reasonable. Currently, there are no criteria to distinguish true primary motor dysfunction in patients with jackhammer related to obstruction from features such as repetitive multipeaked contractions, caused by disrupted deglutitive inhibition, or long-duration post-peak contractions. Unfortunately, none of these patterns has sufficient predictive value to determine which patients will respond to therapy focused on reducing smooth muscle contractility. Recently, there has been substantial interest in the role of eosinophilic infiltration and inflammation of the circular muscle in primary motor disorders and this may lead to more aggressive assessment of muscle histology in the diagnostic paradigm⁹.

Eosinophilic myositis

EoE is an important etiology in dysphagia and currently is the leading cause of emergent food impaction in the US¹⁰. This disorder is associated with a chronic immune/antigen-mediated eosinophilic inflammatory response that leads to fibrosis and remodeling of the esophageal wall¹¹. Although the cause of dysphagia in this patient group is believed to be related to mechanical narrowing of the lumen, there is evidence that EoE is associated with motor dysfunction¹². In fact, case reports documenting resolution of classic achalasia patterns after corticosteroid treatment in patients with diagnosed EoE have been published¹³. There has also been emerging evidence that eosinophilia may extend beyond the mucosa and involve the smooth muscle of the esophagus in patients presenting with major motor disorders¹⁴. Studies focusing on achalasia reported high rates of eosinophilic inflammatory ganglionitis in myotomy and esophagectomy specimens. Similarly, case series have described dense eosinophilic infiltration from biopsies in patients with jackhammer esophagus undergoing peroral endoscopic myotomy (POEM)¹⁵. These studies have also reported the presence of eosinophil-derived secretory products with neurotoxic and cytotoxic effects within the circular smooth muscle, lending further credibility to the biologic plausibility of this pathogenic mechanism^16,17. It is conceivable that these effects target and destroy the enteric neurons associated with normal peristalsis or that this inflammatory response leads to release of other factors that promote hypercontractility.

Although the above data only indirectly support this interesting hypothesis, more evidence is required before we begin to treat achalasia and jackhammer esophagus with steroid therapy. Future prospective studies should be performed to assess whether these abnormalities are truly pathogenic and not related to the underlying disease state.

Opioid esophagus

The effects of opioids on gastric, small intestine, and colonic motility have been well described in the literature and most physicians understand that opioids can lead to constipation and reduce intestinal transit¹⁸. Similarly, opioids can affect esophageal motility likely through similar mechanisms and this effect has been studied by using various pharmacologic intervention studies¹⁹. In 1996, Penagini et al. reported on the effects of morphine and naloxone on esophageal motor function²⁰. Their findings suggested that the residual LES pressure during swallowing was increased and the duration of LES relaxation and percentage of relaxation were decreased by opioids. In addition, the authors found that peristaltic velocity was increased with minimal changes in contractile amplitude. These findings have been consistently found in other studies by using slightly different protocols in controls and thus it appears that opioids may alter the inhibitory component of esophageal peristalsis and LES relaxation. More recently, the Mayo team reported on the prevalence of CC diagnoses in 121 opioid users who were either on opioids at the time of manometry or off for at least 24 hours before the test²¹. The authors found that the rates of both type III achalasia and EGJOO were more common in current users of opioids compared with those patients who had discontinued opioids for at least 24 hours.

These results suggest that opioid use can alter esophageal motility and can be associated with higher rates of major motor disorders in patients referred for esophageal manometry. Whether these effects will resolve with discontinuation of the opioid or normalize with administration of opioid antagonists is unclear. However, an understanding of these negative effects is important when evaluating patients with dysphagia on opioids.

High-resolution impedance manometry

Although impedance assessment has been coupled to manometry for over 15 years, the impact of impedance on esophageal function testing in the context of dysphagia was minimal. It was not until impedance merged with HRM and was configured in an orientation that was similar to HRM that the impact of intraluminal impedance recordings was recognized. The early pioneers of this approach were from the lab of Taher Omari, and the initial work focused on assessing bolus passage dynamics across the pharyngo-esophageal segment as a non-radiologic assessment tool for aspiration in pediatric patients²². This group advanced this approach into the adult population and the esophagus, creating the automated impedance manometry (AIM) platform, and they developed novel metrics that focused on the impedance signal as a marker of bolus distention and simultaneous intrabolus pressurization²³. They were able to show that these metrics could predict symptoms of dysphagia and also better discriminate symptomatic functional dysphagia patients and post-fundoplication patients²⁴. Other investigators have been modifying this approach to assess the inhibitory component of peristalsis and this approach will likely evolve further to provide volume flow estimates²⁵.

In parallel, the Northwestern group began exploring new techniques that provided a more quantitative aspect to the current combined impedance manometry algorithms by developing the esophageal impedance integral (EII) and the bolus flow time (BFT)^26,27. EII was derived by developing a calculation of the cumulative impedance signal within the space–time domain of the swallow wave, focusing on the concept that drops in impedance are associated with volume-induced distention. Findings from this work suggest that EII correlates with fluoroscopy and symptom scores on the brief esophageal dysphagia questionnaire and this was superior to the standard HRM metrics used for CC²⁸. Using a similar approach and focusing on the EGJ, investigators conceptualized the BFT as a time measurement of EGJ opening by using impedance drops more than 90% of baseline as a marker of bolus presence and determining the time where a preferential flow gradient was present. Once again, this metric performed better than IRP or basal EGJ pressure in predicting bolus retention and symptoms²⁸. Newer approaches that attempt to use a more detailed assessment of the role of intraluminal impedance in predicting lumen geometry during swallowing are on the horizon.

Functional luminal imaging probe panometry

FLIP panometry is an adaptation of impedance planimetry that uses sensors that are configured in a high-resolution orientation to provide a three-dimensional image of the esophageal lumen²⁹. By combining data on lumen dimensions and adding a pressure sensor, mechanical properties of the esophagus, such as distensibility and compliance, can be measured by assessing diameter/volume pressure changes. This technique is performed while the patient is sedated during standard upper endoscopy. The approach focuses on assessing distensibility of the EGJ and has been shown to provide useful complementary information regarding EGJ function in achalasia and post-surgical obstruction^30,31. More recently, this technology was adapted to assess esophageal motor function in response to a sustained volumetric distention³². The volumetric response will elicit secondary distention-mediated contractile activity and this can be visualized by converting diameter measurements into a color topography plot that illustrates diameter changes over a space–time domain. The reductions in diameter represent contractions and these contractions can be assessed on the basis of their direction and ability to occlude the lumen. Antegrade contractions occurring in a repetitive sequence spaced about 6 to 8 seconds apart are considered to be a normal response to sustained volumetric distention and this pattern is associated with normal peristalsis on HRM (Figure 2). Contractions can occur in a retrograde direction and this pattern has been seen in the context of spastic disorders, EGJ obstruction, and chronic opioids. Failure to elicit contractions is associated with aperistalsis and weak peristalsis and may represent a myogenic dysfunction related to dilatation and atrophy or a neurogenic dysfunction related to impaired triggering. When these patterns and an already-validated methodology to assess EGJ opening are used, the patterns of response can be conceptualized into a motility classification scheme similar to the CC (Figure 2)³³. Although this device is currently being used as a complementary tool in the management of dysphagia, the unique advantages of providing both motility and biomechanical measures while the patient is sedated could make it a more mainstream diagnostic tool for the management of esophageal diseases in the future.

Figure 2. High-resolution manometric patterns (top) and the corresponding functional luminal imaging probe panometry patterns (bottom).

EGJ, esophagogastric junction; EGJ-DI, esophagogastric junction-distensibility index; RACS, repetitive antegrade contractions; RRC, repetitive retrograde contraction.

Peroral esophageal myotomy

Over the past decade, submucosal endoscopy has developed as a new tool in the armamentarium of the therapeutic endoscopist. Via these techniques, POEM has quickly been adopted as one of the three principal treatments for achalasia, along with pneumatic dilation and laparoscopic Heller myotomy^34,35. POEM was introduced in an animal model in 2007, when Pasricha et al. described creating a submucosal tunnel using a biliary dilating balloon followed by circular muscle myotomy using a needle knife³⁶. In 2008, Inoue et al. performed the first POEM in humans and published a case series of 17 patients for the treatment of achalasia³⁷. POEM was first performed for uncomplicated achalasia, but there is currently no consensus regarding formal indications, and substantial work has been carried out to study various treatment applications, including achalasia (all three clinical subtypes) and non-achalasia motility disorders (distal esophageal spasm, EGJOO, and jackhammer esophagus) and following failed prior LES targeted therapy for achalasia³⁸. This technique is continuing to mature but outcome data are promising; more than 90% of patients have reported clinical improvement^39,40.