Advances in Management of Esophageal Motility Disorders

Peter J. Kahrilas; Albert J. Bredenoord; Dustin A. Carlson; John E. Pandolfino


Clin Gastroenterol Hepatol. 2018;16(11):1692-1700. 

In This Article

Clarifying the Gray Zones: Provocative Stimuli and Ancillary Tests

Among potential findings in HRM studies, the detection of obstructive physiology at the EGJ is the most fundamental because it is ultimately the best therapeutic target. In the CC this is based on detection of an elevated IRP. However, no metric or technology has perfect sensitivity and specificity for detecting relevant sphincter dysfunction, and in marginal or atypical cases one has to consider all available evidence, including other studies and other metrics. There are clearly cases of achalasia with an IRP <15 mmHg, particularly in type I or advanced disease,[14] and there are clearly instances in which the IRP is >15 that are not achalasia.[15] Some have proposed addressing this by lowering the threshold IRP cutoff for defining type I achalasia,[16] but ultimately that only challenges the specificity of the metric because there are published cases of achalasia with IRP values as low as 3–5 mmHg.[14] Hence, in equivocal cases or when there are conflicting findings, the International Working Group on High-Resolution Manometry instead proposed to leave open the uncertainty of an achalasia diagnosis and look for supporting evidence of functionally significant esophageal outflow obstruction.[1] This can be by demonstrating compartmentalized pressurization above the EGJ during test swallows, or it can be the demonstration of esophageal pressurization during multiple rapid swallows or rapid drink challenge, 2 provocative tests of the integrity of deglutitive inhibition. With multiple rapid swallows, five 2-mL swallows are taken less than 4 seconds apart,[17,18] and with the rapid drink challenge, 200 mL water is swallowed within 30 seconds.[19,20] By providing a prolonged inhibitory stimulus, multiple rapid swallows are helpful in demonstrating the integrity of deglutitive inhibition in the distal esophagus, LES relaxation, and peristaltic reserve after the termination of the sequence.[21] The rapid drink challenge is most helpful by eliciting panesophageal pressurization, indicative of obstructive physiology at the EGJ.

Another approach to clarifying inconclusive HRM findings is to invoke ancillary tests to elicit abnormal function. The simplest of these is the timed barium esophagram wherein the patient drinks 200 mL low-density barium over 1 minute in an upright posture, followed by frontal x-rays 1, 2, and 5 minutes afterward. The degree of esophageal emptying is then estimated by measuring the height of the residual barium column in the esophagus. The most robust outcome measure of the timed barium esophagram is the height of the barium column at 5 minutes, with the proposed critical threshold ranging from 2 to 5 cm.[22,23] When a 12-mm barium tablet is used in conjunction with the timed barium esophagram, a secondary criterion of abnormality is for the tablet to become lodged at the EGJ. A positive timed barium esophagram is strong supportive evidence of functionally significant EGJ outflow obstruction, and a completely normal study makes an achalasia diagnosis highly unlikely.[23] Analogous data can be obtained by using high-resolution impedance manometry in an upright posture and using the impedance electrodes to ascertain the height of retained fluid in the esophagus at a 5-minute interval.[24] However, these tests are not very useful in clarifying the significance of EGJ outflow obstruction with preserved peristalsis because bolus clearance is often uncompromised in that condition.

An alternative investigation for clarifying the significance of EGJ outflow obstruction is with the FLIP device (Medtronic, Shoreview MN). The concept of the FLIP is to measure the distensibility of the EGJ during volumetric distention. This is achieved with a transorally positioned FLIP probe incorporating 16 closely spaced impedance electrodes within a compliant bag. With measured volumes of conductive saline distending the bag (and distal esophagus), an electrical current runs between adjacent impedance electrodes proportionate in amperage to the cross-sectional area of the esophageal lumen separating the electrodes (impedance planimetry). The result is an 8- to 16-cm high-resolution measurement of luminal cross-sectional area, represented on screen as a cylinder of varying diameter surrounding the FLIP probe. When combined with measurement of the intra-bag pressure, an EGJ distensibility index (mm2/mmHg) can be calculated.[25] The conceptual advantage of the FLIP device over HRM lies in the distinction between sphincter relaxation and sphincter opening. HRM measures relaxation; the FLIP quantifies opening. Although these are usually related, it is sphincter opening that determines the volume of bolus flow through the EGJ. The EGJ distensibility index has been reported to be low in untreated achalasia patients and in patients with poor symptomatic outcomes after achalasia treatment by using a cutoff value of 2.8 mm2/mmHg.[26]

The FLIP can also assess esophageal motility during endoscopy by using an emerging technology, Panometry.[3,27] Panometry involves the secondary processing of FLIP data into topographic plots of esophageal regional diameter changes versus time. As such, esophageal contractions can be detected with Panometry, even when they are not lumen occluding and, hence, undetectable by HRM.[3] The Panometry pattern commonly observed among controls and patients with normal peristalsis is of repetitive antegrade contractions, likely indicative of secondary peristalsis in response to sustained esophageal distention. In addition, a unique distention-induced contractile pattern, repetitive retrograde contractions, is commonly observed among patients with distal esophageal obstructive physiology and only rarely, if ever, seen among asymptomatic controls (Figure 2). First described in patients with type III (spastic) achalasia, repetitive retrograde contractions have subsequently been reported among patients with non-spastic achalasia, jackhammer esophagus, eosinophilic esophagitis, reflux, and secondary hypercontractility in post-fundoplication dysphagia.[27,28] The emerging concept is that repetitive retrograde contractions are indicative of ganglionic neural imbalance and spastic-type motility in the distal esophagus, a manifestation of either impaired nitrergic input and premature contractions (eg, type III achalasia) or augmented cholinergic input with hypercontractility and/or impaired deglutitive inhibition (eg, jackhammer esophagus).[28]

Figure 2.

Two images of FLIP Panometry showing repetitive antegrade cotractions (left) and repetitive retrograde contractions (right). Plots on top indicate the volume within the FLIP balloon (blue) and the corresponding pressure (red). On the topography plots time is on the x-axis, position along the 16-cm balloon on the y-axis, and spectral color indicates luminal diameter at each coordinate as per the scale. With the exception of the small blackened area on the first contraction in the left panel and the EGJ in the right panel, these are all non–lumen-occluding contractions. Repetitive antegrade contractions are a normal finding, and the patient on the left had normal motility on HRM. However, repetitive retrograde contractions are rarely found in normal patients and are usually indicative of obstructive physiology; the patient on the right had type III achalasia. The esophagogastric junction distensibility index (EGJ-DI) is measured at 60-mL distention, with 2.8 mm2/mmHg as the lower limit of normal.

In summary, despite being the best available single test for demonstrating abnormal esophageal physiology, HRM findings can be equivocal or negative despite strong clinical suspicion to the contrary. In such instances, the clinician needs to investigate further with provocative maneuvers or ancillary tests. The ultimate objective is to identify and localize clinically relevant obstructive physiology, recognizing that this can be limited to the EGJ or involve both the EGJ and the distal esophagus. Making this distinction has important management implications. Table 1 summarizes the HRM maneuvers and ancillary tests that have been reported to help with this decision-making.