Normal Functional Luminal Imaging Probe Panometry Findings Associate With Lack of Major Esophageal Motility Disorder on High-Resolution Manometry

Abstract

Background & Aims:

A normal esophageal response to distension on functional luminal imaging probe (FLIP) panometry during endoscopy might indicate normal esophageal motor function. We aimed to investigate the correlation of normal FLIP panometry findings with esophageal high-resolution manometry (HRM) and outcomes of discrepant patients.

Methods:

We performed a retrospective study using data from a registry of patients who completed FLIP during sedated endoscopy. We identified 111 patients with normal FLIP panometry findings (mean age 42, 69% female) and corresponding HRM data. A normal FLIP panometry was defined as esophagogastric junction (EGJ) distensibility index greater than 3.0 mm²/mmHg, an absence of repetitive retrograde contractions, and a repetitive antegrade contraction pattern that met the Rule-of-6s. HRM findings were classified by Chicago classification system v3.0.

Results:

HRM results were classified as normal motility in 78 patients (70%), ineffective esophageal motility in 10 patients (9%), EGJ outflow obstruction in 20 patients (18%), and 3% as other. In patients with EGJ outflow obstruction based on HRM, the integrated relaxation pressure normalized on adjunctive swallows in 16/20 patients (80%), and in 8/9 patients (88%) who completed barium esophagram had normal barium clearance. Thus, although 23/111 patients (21%) with normal FLIP panometry had abnormal HRM findings, these HRMs were often considered to be false positive or equivocal results. All patients with an abnormal result from HRM were treated conservatively.

Conclusions:

In a retrospective cohort study, we found that patients with normal FLIP panometry results did not have a clinical impression of a major esophageal motor disorder. Normal FLIP panometry results can exclude esophageal motility disorders at the time of endoscopy, possibly negating the need for HRM in select patients.

Introduction

The functional luminal imaging probe (FLIP) utilizes high-resolution impedance panometry to measure esophageal luminal parameters and their relationship to distension pressure (distensibility) during sustained volumetric distension. In addition to evaluating esophagogastric junction (EGJ) opening and distensibility, esophageal contractility in response to distension can be observed via the comprehensive esophageal functional evaluation provided with FLIP panometry. Thus, FLIP panometry carries the potential to evaluate esophageal motility at the time of sedated endoscopy.^{1, 2}

While esophageal high-resolution manometry (HRM) is thought to be a gold standard for defining esophageal motility, HRM carries several notable limitations. HRM and its clinical classification scheme are susceptible to both false positive and false negative clinical classifications making it an imperfect gold standard. The EGJ outflow obstruction (EGJOO) classification within Chicago Classification v3.0 in particular is problematic as the integrated relaxation pressure (IRP) is susceptible to pressure artifacts often leading to a falsely positive diagnosis of a major esophageal motility disorder.^3–5 Additionally, even patients with clinical achalasia may have normal lower-esophageal sphincter (LES) relaxation pressure on HRM.⁶ Last, because HRM is placed trans-nasally and performed awake over an extended time period it is often poorly tolerated and generally disliked by patients.

FLIP panometry, on the other hand, can evaluate esophageal motility during sedated endoscopy. FLIP panometry has demonstrated promise in identifying major esophageal motility disorders, achalasia in particular.¹ Thus, we hypothesized that a normal FLIP panometry would be associated with a normal esophageal motility evaluation and predictive of a favorable clinical course with conservative management. In this study, we aimed to investigate the correlation of normal FLIP panometry with HRM in patients undergoing an esophageal motility evaluation and the resulting clinical course for any patients with discrepant FLIP panometry and HRM.

Methods

Subjects

Adult patients presenting to the Esophageal Center of Northwestern for evaluation of esophageal symptoms between November 2012 and September 2019 who completed HRM and FLIP during upper endoscopy were prospectively evaluated and data maintained in an esophageal motility registry. Additional clinical evaluation (i.e. barium esophagram) was obtained and management decisions made at the discretion of the primary treating gastroenterologist. This prospective database was retrospectively reviewed to identify patients with a normal FLIP panometry study (defined below) that also had a corresponding HRM study. Patients with previous upper gastrointestinal surgery, previous pneumatic dilation, previous botulinum toxin injection, eosinophilic esophagitis, severe reflux esophagitis (LA-classification C or D), hiatal hernia > 3cm, or evidence of mechanical obstruction on endoscopy (i.e. esophageal stricture) were excluded. There is overlap in this study cohort with previous reports.¹

Clinical data, including demographics, patient symptoms,^18,19 prescribed treatments, timed barium esophagram (TBE) and endoscopy results were attained from patient electronic medical records. The study protocol was approved by the Northwestern University Institutional Review Board.

FLIP Study Protocol and Analysis

Evaluation was completed after a minimum 6-hour fast. Subjects underwent upper endoscopy in the left lateral decubitus position. Conscious sedation with 3–14 mg midazolam and 50–300 mcg fentanyl was administered during the procedure. Other sedative medications, e.g. propofol, (in addition to midazolam and fentanyl) were used with anesthesiologist assistance at the discretion of the performing endoscopist in some cases.

The 16-cm FLIP (EndoFLIP® EF-322N; Medtronic, Inc, Shoreview, MN) was calibrated to atmospheric pressure prior to trans-oral probe placement. With the endoscope withdrawn, the FLIP was positioned within the esophagus such that 1–3 impedance sensors were observed beyond the EGJ with this positioning maintained throughout the FLIP study. Stepwise 5-ml or 10-ml balloon distensions beginning with 20 ml and increasing to target volume of 60 or 70 ml were then performed; each stepwise distension volume was maintained for 30–60 seconds (variations in FLIP study protocol evolved during the study period).

FLIP data were exported and analyzed as previously described using a customized program developed at Northwestern, which is available for download at http://www.wklytics.com/nmgi.^1,7,8,9 Analysis of a single FLIP study using the program takes approximately 5 minutes. The EGJ-distensibility index (DI) was calculated by dividing the median EGJ-midline cross-sectional area (CSA) by the median intraballoon pressure over the duration of the 60-ml distension volume: median CSA/median pressure = EGJ-DI in mm²/mmHg. Esophageal body contractions were identified by a transient decrease of ≥ 5 mm in the luminal diameter in ≥ 3 adjacent impedance planimetry channels. The axial length of contractions was determined by the number of consecutive impedance planimetry channels (1-cm spacing) with a decrease in luminal diameter. The direction of contractions (antegrade or retrograde) was categorized based on a tangent line placed at the onset of contraction. Specific patterns of the contractile response to distension were further categorized as repetitive if contractions of similar directionality occurred consecutively at a consistent time interval and then by contraction direction: repetitive antegrade contractions (RACs) or repetitive retrograde contractions (RRCs). The rate of repetitive contractions was derived by dividing the number of repetitive contractions by duration (time) of repetitive contraction pattern and then normalized to reflect the rate of contractions as the number of contractions per minute.

A normal FLIP panometry was defined as a) EGJ-DI >3.0mm²/mmHg,¹⁰ b) absence of RRCs, and c) presence of a RAC pattern that met the Rule-of-6s: duration of at least 6 consecutive antegrade contractions that spanned at least 6 cm in axial length occurring with a rate of 6 ± 3 contractions per minute.¹¹ FLIP panometry studies were reviewed by three physicians (AJB, JEP, DAC) with consensus achieved for all included studies.

HRM protocol and analysis

After a minimum 6-hour fast, HRM studies were completed using a 4.2-mm outer diameter solid-state assembly with 36 circumferential pressure sensors at 1-cm intervals (Medtronic Inc, Shoreview, MN). The HRM assembly was placed trans-nasally and positioned to record from the hypopharynx to the stomach with approximately three intragastric pressure sensors. After a 2-minute baseline recording, the HRM protocol was performed with ten, 5-ml liquid swallows in a supine position.^3,12 This was followed by 5 upright swallows and one or more provocative maneuvers in the upright position, including solid swallows, multiple rapid swallows (MRS) and a rapid drink challenge (RDC) (variations in HRM study protocol evolved during the study). Five boluses of 2-mL of water were swallowed less than 4 seconds apart during MRS,^13,14 and 200 mL of water was swallowed over 30 seconds during RDC.^15,16

Manometry studies were analyzed using ManoView version 3.0 analysis software (Medtronic) to measure the integrated relaxation pressure (IRP), distal contractile integral (DCI), and distal latency (DL) according to the Chicago Classification v3.0.^3,12 Esophageal motility disorders were generated from ten supine swallows according to the Chicago Classification v3.0. A median IRP >15 mmHg was applied as the criterion for the diagnosis of EGJOO. Failed (DCI <100 mmHg*s*cm) or weak (DCI 100–450 mmHg*s*cm) swallows were applied as a criterion for classification of ineffective esophageal motility (IEM). Distal latency <4.5 seconds was applied to classify distal esophageal spasm (DES). On MRS, contractile augmentation was considered if the DCI of the post-MRS peristaltic wave was greater than the median value of the 10 supine swallow DCI values.¹³

When available, impedance tracings with channels placed at 5, 10, 15, and 20-cm proximal to the EGJ were analyzed based on previous methods.¹⁷ Complete bolus clearance was defined as bolus entry at the 20-cm channel and bolus exit at the 15-cm, 10-cm, and 5-cm channels. Normal bolus transit was defined as complete bolus clearance in > 70% of swallows.

Esophagram

A TBE was obtained in patients at the discretion of the patients’ treating physicians. In patients who had a TBE, the barium column height above the EGJ was measured from images obtained at 1, 2 and 5 minutes after ingestion of 200 mL barium. If there was no contrast retention, a 12.5 mm barium tablet was also administered, and images obtained at timed intervals until passed into the stomach.

Statistical Analysis

Descriptive statistics were applied. Results were reported as percentage, mean ± standard deviation (SD), range, or median and interquartile range (IQR) depending on data distribution.

Results

Subjects

During the study period between November 2012 and September 2019, 111 (16%) of 718 consecutive patients with esophageal symptoms, non-obstructive endoscopy and corresponding HRM had normal FLIP panometries (Supplementary Figure 1). Demographic and baseline assessment data are listed in Table 1. HRM was performed on the same day as or day after FLIP in 86% of patients. The longest interval between FLIP and HRM was 7 months. There were no interval treatments between FLIP and HRM beyond acid suppressive therapy. The 111 patients with normal FLIPs had a median [IQR] EGJ-DI at 60 mL fill volume of 5.5 [4.6–7.3] mm²/mmHg.

Table 1: Normal functional luminal imaging probe (FLIP) panometry patient characteristics based on high-resolution manometry (HRM) diagnosis.

^aThe majority of patients received midazolam and fentanyl with conscious sedation; monitored anesthesia care (MAC) typically involved utilization of propofol. ^bWidely patent rings were considered clinically insignificant. ^cOne patient had both LA grade B esophagitis and a widely patent ring and was included in both totals/percentages. ^dIndividual values listed given small sample size. BEDQ, brief esophageal dysphagia questionnaire; DES, distal esophageal spasm; EGJ, esophagogastric junction; EGJ-DI, esophagogastric junction distensibility index; EGJOO, esophagogastric junction outflow obstruction; GERD, gastroesophageal reflux disease; GERDQ, gastroesophageal reflux disease questionnaire; IEM, ineffective esophageal motility; IQR, interquartile range; IRP, integrated relaxation pressure.

		HRM classification
	Total cohort (n=111)	Normal motility (n=78)	IEM (n=10)	EGJOO (n=20)	Absent contractilityd (n=2)	DESd (n=1)
Age (yrs), mean ± SD	42 ± 15	42 ± 15	35 ± 12	45 ± 18	34, 66	44
Sex (female), n (%)	77 (69.4%)	57 (73.1%)	6 (60%)	13 (65%)	1 (50%)	0 (0%)
Indication, n (%)
Dysphagia	78 (70.3%)	54 (69.2%)	7 (70%)	15 (75%)	1 (50%)	1 (100%)
Reflux symptoms	15 (13.5%)	12 (15.4%)	1 (10%)	2 (10%)
Dysphagia & Reflux symptoms	11 (9.9%)	8 (10.3%)	1 (10%)	2 (10%)
Chest pain	5 (4.5%)	4 (5.1%)		1 (5%)
Systemic sclerosis	2 (1.8%)		1 (10%)		1 (50%)
Patient-reported symptom scores
GERDQ18, n (%) completed	84 (75.7%)	56 (71.8%)	8 (80%)	17 (85%)	2 (100%)	1 (100%)
median [IQR]	9 [7–10]	9 [6–10]	8 [7–10]	9 [8–11]	9, 13	10
BEDQ19, n (%) completed	79 (71.2%)	53 (68%)	8 (80%)	16 (80%)	1 (50%)	1 (100%)
median [IQR]	10 [5–17]	8 [4–19]	11 [7–18]	11 [5–17]	---, 10	20
Sedationa
Midazolam (mg), range	3–14	3–14	8–12	4–12	6–9	10
Fentanyl (mcg), range	50–300	50–300	125–200	75–250	125–175	200
MAC, n (%)	13 (12.7%)	8 (10.3%)	2 (20%)	3 (15%)
Objective endoscopy findings, n (%)
LA grade A esophagitis	4 (3.6%)	3 (3.9%)	1 (10%)
LA grade B esophagitis	8 (7.2%)c	7 (9%)c			1 (50%)
Widely patent ringsb	4 (3.6%)	4 (5.1%)c			1 (50%)
Hiatal hernia on HRM, n (%)
No hernia	88 (79.3%)	63 (80.7%)	8 (80%)	14 (70%)	2 (100%)	1 (100%)
Small hernia (1–3 cm)	23 (20.7%)	15 (19.2%)	2 (20%)	6 (30%)
IRP (mmHg), median [IQR]	9.9 [7–13.1]	9.3 [6.9–11.9]	5.2 [2–8.3]	20.9 [17.7–25.5]	5.5, 14	9
EGJ-DI (mm2/mmHg), median [IQR]	5.5 [4.6–7.3]	5.8 [4.7–7.4]	6.2 [5–10]	4.9 [3.8–6.5]	3.1, 5	3.7
Maximum EGJ diameter (mm), median [IQR]	23.4 [21–27.5]	24 [21.6–28]	23.7 [21.2–26.8]	21 [18.4–25.3]	19.5, 19.7	20.6

High-resolution manometry findings among patients with normal FLIP panometry

Among the total 111 patient cohort, the motility classification based on Chicago classification v3.0 of HRM was normal motility in 78 (70.3%) patients, IEM in 10 (9%), EGJOO in 20 (18%), absent contractility in 2 (1.8%) and DES in 1 (0.9%), Table 1. Thus, 79.3% of patients with FLIP panometry did not have a major esophageal motor disorder on corresponding HRM (Figure 1).

Figure 1: Examples of normal functional luminal imaging probe (FLIP) panometry among patients without a major motor disorder on high-resolution manometry (HRM).

Patient examples of normal FLIP panometry (top left: topography, bottom left: intra-balloon pressure) with corresponding HRM (right). A) A single supine swallow from HRM is displayed, the median integrated relaxation pressure (IRP) on 10 supine swallows was 12.2 mmHg and the HRM diagnosis was normal motility. B) The HRM diagnosis on supine swallows was ineffective esophageal motility with 10/10 ineffective supine swallows (middle). Multiple rapid swallows (MRS; right) demonstrated contractile reserve with normal augmentation.¹³ EGJ, esophagogastric junction. DCI-distal contractile integral.

Patients with ‘abnormal’ HRM and normal FLIP panometry

Esophagogastric junction outflow obstruction on high-resolution manometry

Among the 20 patients with elevated supine IRP and thus EGJOO on HRM, 17 (85%) had normal bolus transit on the supine swallows (Table 2). Additionally, 16 (80%) had an IRP < 12mmHg on adjunctive maneuvers such as upright swallows, MRS, or RDC (Table 2). Ten of 20 patients with EGJOO on HRM underwent TBE: 8 showed normal emptying (Figure 2), one showed temporary delay of the barium tablet but no retention, and one had an incomplete study. The other 10 patients with EGJOO did not have TBE despite often being recommended. The overall clinical impression was not of an achalasia-variant in any of these 20 patients with EGJOO on HRM, and thus, none underwent botulinum toxin injection, pneumatic dilation, or LES myotomy at our center. Of those with available clinical follow-up (3 patients were lost to follow-up), 4/17 patients had empiric dilation performed with 54 French Savary (1 patient) or 20 mm through-the-scope balloon (3 patients). None who were dilated showed any sign of mucosal disruption, but one had symptomatic improvement. Three patients had strong vascular signals noted on HRM, prompting referral for endoscopic ultrasound, which was normal in one patient and showed mild extrinsic compression by the aorta in the other who completed it. Additionally, one patient was diagnosed with dysphagia lusoria by cross-sectional imaging. The remainder were treated with proton pump inhibitor (PPI) for presumed gastroesophageal reflux disease (GERD), a neuromodulator and/or behavioral medicine, pharmacologic smooth muscle relaxant, observation alone, or a combination of the above (Table 2).

Table 2: High-resolution manometry (HRM) and timed barium esophagram (TBE) findings in patients with esophagogastric junction outflow obstruction (EGJOO) on HRM and their clinical management.

^aNo impedance on HRM. ^bNot preformed. ^cRapid drink challenge (RDC) not completed in 30 seconds. ^dShaded boxes indicate HRM or timed barium esophagram (TBE) findings considered normal; integrated relaxation pressure (IRP) <12 mmHg for upright position, RDC, and multiple rapid swallows (MRS).^4,15 EGJ, esophagogastric junction; EUS, endoscopic ultrasound; PPI, proton pump inhibitor; SMR, smooth muscle relaxant

EGJOO patient	Maximum EGJ diameter (mm)	Median supine IRP (mmHg)	Hiatal hernia size on HRM (cm)	Normal bolus transit d	IRP in upright position (mmHg)d	IRP on RDC (mmHg)d	IRP on MRS (mmHg)d	TBEd	Clinical management
1	20	20.6	0	N/Aa	9	N/Ab	6	Incomplete	Neuromodulator/ Behavioral medicine
2	19.3	24.6	0	Yes	11	7.9	7.5	Normal	Dilation/ Neuromodulator/ Behavioral medicine
3	21	19.5	1	Yes	9	1	3.1	Normal	PPI
4	21	15.8	0	Yes	11	N/Ac	5.3	N/Ab	PPI
5	21.8	17.5	0	Yes	10	N/Ab	9	N/Ab	Lost to follow-up
6	21.6	18.5	2	Yes	10	N/Ac	N/Ab	N/Ab	Lost to follow-up
7	33.8	21.1	2	Yes	17	3.7	10.8	Normal	Neuromodulator/ Behavioral medicine
8	25.3	20.4	2	Yes	15	N/Ac	8.7	Normal	EUS recommended/ not completed
9	30.2	23	0	Yes	26	N/Ac	11	Normal	Dilation alone
10	18.2	26.2	2	Yes	12	N/Ac	N/Ab	Normal	Observation
11	21.7	29.1	0	Yes	17	N/Ac	11.8	Normal	EUS: mild extrinsic compression by aorta
12	18.4	25.9	0	Yes	18	N/Ab	10.4	N/Ab	Lost to follow-up
13	26.5	18.6	0	Yes	13	N/Ac	5.5	N/Ab	SMR
14	24	17.3	0	Yes	23	N/Ac	9.3	N/Ab	Dilation/PPI
15	33.2	28	0	Yes	24	N/Ac	2.1	N/Ab	Dilation alone
16	29.4	16.5	0	Yes	13	N/Ac	9	N/Ab	PPI
17	20.7	21.4	2	Yes	18	14.1	16	N/Ab	PPI/ Neuromodulator/ Behavioral medicine
18	16.7	16	0	Yes	14	N/Ab	N/Ab	Tablet delayed	PPI
19	18.2	21.8	0	No	23	N/Ac	11	Normal	Dysphagia lusoria
20	29.5	29.1	0	No	18	N/Ac	14	N/Ab	EUS normal

Figure 2: Example of normal functional luminal imaging probe (FLIP) panometry with esophagogastric junction outlet obstruction on corresponding high-resolution manometry (HRM).

A) Normal FLIP panometry (top: topography, bottom: intra-balloon pressure). On supine swallows (such as B, single supine swallow), the median integrated relaxation pressure (IRP) was 19 mmHg. However, the median IRP in the upright position (C, single upright swallow), on multiple rapid swallows (not displayed, IRP was 3 mmHg), and D) on rapid drink challenge was normal (<12 mmHg).^4,15 E) Timed barium esophagram showed no retention at 1 minute; there was clear esophagogastric junction (EGJ) opening. DCI, distal contractile integral

Ineffective esophageal motility on high-resolution manometry

The IEM classification was derived from 50–70% ineffective swallows in 5/10 patients and ≥ 80% ineffective swallows in 5 patients. Additionally, contractile augmentation on MRS was observed in 6/6 patients that completed MRS, including 3/3 patients with ≥ 80% ineffective swallows (Figure 1). Five of 10 patients with IEM on HRM had a TBE with normal emptying. Four patients were treated with a PPI for presumed GERD. Three were treated with neuromodulators and/or behavioral medicine for a presumed functional component to their symptoms. Three were treated with a combination of PPI and neuromodulator/behavioral medicine, one of which also received a cricopharyngeal dilation with 54 French Savary for coexisting oropharyngeal dysphagia. No patients required further invasive interventions, including surgery.

Other motility disorders on high-resolution manometry

Both patients with absent contractility on supine test swallows had weak peristalsis observed on provocative HRM maneuvers (Figure 3A). One of these patients had systemic sclerosis while the other had a history of metastatic multiple myeloma and was receiving chemotherapy and radiation; the latter had a TBE with normal emptying. The two patients with absent contractility on HRM were treated with PPI for presumed GERD and one also underwent empiric Savary dilation.

Figure 3: Examples of normal functional luminal imaging probe (FLIP) panometry among patients with absent contractility (A) and distal esophageal spasm (DES) (B) on high-resolution manometry (HRM).

Normal FLIP panometries are displayed at left, top: topography, bottom: intra-balloon pressure. A) A classification of absent contractility was derived from 10 failed supine swallows on HRM (top right). However, weak and fragmented peristalsis was elicited on provocative maneuvers, such as with a solid (graham cracker) swallow (bottom right). B) Patient example with normal FLIP panometry (left), but DES on corresponding HRM (center). While transient delay in contrast passage was observed (1-minute column, top right), the esophagus otherwise appeared normal (e.g. no corkscrew configuration) (bottom right). DCI, distal contractile integral; DL, distal latency; EGJ, esophagogastric junction; IRP, integrated contractile response

The one patient (< 1% of this normal FLIP panometry cohort) with DES on HRM completed a TBE that had normal esophageal conformation (i.e. no corkscrew appearance), no tertiary contractions, a 9 cm contrast column at 1 minute that cleared by 2 minutes, and normal passage of a barium tablet (Figure 3B). The patient was offered a smooth muscle relaxant but was lost to follow up.

Discussion

In this cohort study of 111 patients with normal FLIP panometry, as defined by EGJ-DI > 3.0 mm²/mmHg and normal contractile response (absence of RRCs and meeting the RAC Rule-of-6s), 79% did not have a major esophageal motor disorder on HRM. Among the remaining 21% with apparent disagreement with HRM, patients with normal FLIP panometry carried overall clinical impressions of not having a major esophageal motor disorder and were subsequently treated conservatively without the need for surgical interventions.

We recently described the normal esophageal response to controlled volumetric distension among asymptomatic volunteers by describing normal EGJ opening using the EGJ-DI as well as the normal contractile response to sustained distension.⁷ Compared to normal volunteers, patients with achalasia consistently demonstrated a reduced EGJ-DI.^1,11 The normal contractile response is a unique pattern of RACs, which likely represent a secondary peristalsis-like reaction that is repetitive in response to the sustained distension.⁷ Conversely, RRCs were not observed in asymptomatic volunteers, but may be observed in esophageal disorders such as spastic achalasia.⁸ We more recently refined the criteria of the normal contractile response to distension by applying the RAC Rule-of-6s, defined as a RAC pattern with at least 6 consecutive antegrade contractions spanning at least 6 cm in axial length occurring at a rate of 6 ± 3 per minute. A contractile response meeting the RAC Rule-of-6s was found in 95% of asymptomatic controls and <1% of achalasia patients.¹¹

The mild discordance between HRM and FLIP panometry interpretation is in part explained by HRM’s assessment of primary peristalsis versus FLIP panometry’s assessment of a secondary peristalsis-like response to sustained volumetric distention. For instance, FLIP panometry has revealed esophageal contractility in achalasia patients when void on HRM.⁸ Variance in FLIP panometry and HRM is also seen in asymptomatic volunteers with normal HRM in 85%, EGJOO in 10%, and IEM in 5% of the defining cohort of normal FLIP panometry parameters.⁷ In this study, a similar discordant distribution of HRM is seen in symptomatic patients with normal FLIP panometry: 70.3% normal, 18% EGJOO, 9% IEM and 2.7% other. Additionally, upon review of the HRMs of the 20 patients with EGJOO (Table 2), HRM parameters were generally normal beyond the supine IRP, such as IRP on adjunctive maneuvers or bolus transit on impedance. Additionally, 8/9 patients who completed TBE had normal emptying. These findings questioned the clinical significance of the EGJOO diagnosis on HRM, but instead suggest that elevated IRP on HRM may be related to misleading pressure artifact. Likewise, both patients with absent contractility on supine HRM had evidence of weak peristalsis on provocative HRM swallows (Figure 3A). The patient with DES on HRM had borderline distal latencies but otherwise overall normal appearance on HRM (Figure 3B). Thus, chasing isolated HRM parameters can be problematic as it does not consider the entire clinical picture.

The fact that patients with RACs had a high likelihood of having normal function on manometry makes physiologic sense as the secondary peristalsis-like response triggered by sustained volumetric distention would require intact neurologic function in the esophageal body. Distention can trigger extrinsic vagal-vagal reflexes that induce peristalsis, and distention can also trigger peristalsis via the intrinsic enteric nervous system without extrinsic influence. Thus, it would be logical that primary peristalsis triggered by extrinsic innervation would be associated with normal peristalsis since the neurologic and myogenic function of the esophageal body is intact during secondary peristalsis. In contrast, it is possible that patients that have normal primary peristalsis may have impaired secondary peristalsis as the esophagus may have abnormal thresholds for triggering peristalsis. Additionally, there may be paradoxical responses where the lower esophageal sphincter either contracts or does not relax during distention due to aberrant reflexes or a lack of triggering by an absent contractile response. We speculate that there may be a form of dysphagia related to an impaired contractile response to distention and subsequent reduced EGJ opening as we have previously identified a subgroup of dysphagia patients with normal motility on HRM and patterns similar to achalasia patients during FLIP panometry¹. Further research using pharmacologic interrogation may be helpful in describing these responses.

Limitations of this study is its descriptive and retrospective nature. FLIP panometry was intentionally not tested against HRM as the gold standard, because HRM abnormalities do not always equate to patient outcomes and its metrics can carry limitations. This study instead demonstrated agreement of HRM among patients selected by having a normal FLIP panometry in the majority and explored clinical outcomes in patients whose HRM and FLIP panometry did not agree. Although the patients come from a prospectively collected clinical database, management decisions were at the discretion of the gastroenterologist so certain clinical information is missing (i.e. TBE). Additionally, effects of endoscopic sedation could impact results when HRM was completed after endoscopy; however, these HRM results were utilized clinically. Finally, the patient population is that of a tertiary referral center, so it may not be applicable to the general community. However, access to our FLIP panometry analysis software is offered and thus available for use at other centers.

In conclusion, FLIP panometry offers the potential to establish normal esophageal motility and function at the time of endoscopy and provide reassurance in supporting a conservative management strategy. Thus, a normal upper endoscopy and FLIP panometry could substantially reduce the probability for presence of a major esophageal motor disorder and obviate the need for an HRM as there is good correlation with HRM and esophagram. Instead, the initial clinical management strategy could be directed toward addressing gastroesophageal reflux or a functional syndrome. Additionally, an abnormal FLIP panometry can better inform the diagnostic strategy as these patients will have a higher likelihood of having a major motor disorder. This could streamline the care of patients with esophageal symptoms and potentially avoid sending patients for unnecessary transnasal manometry. However, further longitudinal studies are needed to support this approach.

Abbreviations:

(CSA)

cross-sectional area

(BEDQ)

brief esophageal dysphagia questionnaire

(DCI)

distal contractile integral

(DES)

distal esophageal spasm

(DL)

distal latency

(EGJ)

esophagogastric junction

(EGJ-DI)

esophagogastric junction distensibility index

(EGJOO)

esophagogastric junction outlet obstruction

(FLIP)

functional luminal imaging probe

(GERD)

gastroesophageal reflux disease

(GERDQ)

gastroesophageal reflux disease questionnaire

(HRM)

high-resolution manometry

(IEM)

ineffective esophageal motility

(IRP)

integrated relaxation pressure

(IQR)

interquartile range

(LES)

lower esophageal sphincter

(MRS)

multiple rapid swallow

(PPI)

proton pump inhibitor

(RDC)

rapid drink challenge

(RACs)

repetitive antegrade contractions

(RRCs)

repetitive retrograde contractions

(SD)

standard deviation

(TBE)

timed barium esophagram