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Clinical Gastroenterology and Hepatology 2017;15:325–334

AGA CLINICAL PRACTICE UPDATE:


EXPERT REVIEW
Functional Lumen Imaging Probe for the Management of
Esophageal Disorders: Expert Review From the Clinical Practice
Updates Committee of the AGA Institute
Ikuo Hirano,* John E. Pandolfino,* and Guy E. Boeckxstaens‡

*Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine,
Chicago, Illinois; and ‡Department of Gastroenterology, Translational Research Center for Gastrointestinal Disorders,
University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium

The functional luminal imaging probe is a Food and Drug he evolution of esophageal function testing has
Administration–approved measurement tool used to
measure simultaneous pressure and diameter to guide
T moved rapidly over the last 10 years along the
continuum of manometric technique and bolus transit
management of various upper gastrointestinal disorders. assessment. This has involved major improvements in
Additionally, this tool is also approved to guide therapy dur- manometry where the current state of the art is high-
ing bariatric procedures and specialized esophageal surgery.
resolution manometry with esophageal pressure topog-
Although it has been commercially available since 2009 as the
raphy.1 Along similar lines, the evaluation of bolus transit
endolumenal functional lumen imaging probe (EndoFLIP),
the functional luminal imaging probe has had limited pene- has also evolved from a singular assessment of bolus
trance into clinical settings outside of specialized centers. transit during videofluoroscopy to a more comprehen-
This is primarily because of a paucity of data supporting its sive approach where intraluminal impedance monitoring
utility in general practice and a lack of standardized pro- can describe bolus transit in the context of a simulta-
tocols and data analysis methodology. However, data are neous pressure analysis to combine the strengths of
accumulating that are providing guidance regarding both techniques.2 However, these advances primarily
emerging applications in the evaluation and management of represent modifications and improvements on existing
foregut disorders. This clinical practice update describes the technology and the assessment of esophageal function
technique and reviews potential indications in achalasia, has not moved far beyond an assessment of contractile
eosinophilic esophagitis, and gastroesophgeal reflux disease.
patterns and bolus movement.
Best Practice Advice 1: Clinicians should not make a diag-
Recently, a new technology has become available, the
nosis or treatment decision based on functional lumen
imaging probe (FLIP) assessment alone. functional lumen imaging probe (FLIP), which focuses on
Best Practice Advice 2: FLIP assessment is a complementary measuring mechanical properties of the esophagus as
tool to assess esophagogastric junction opening dynamics opposed to contractile patterns and bolus transit.3 The
and the stiffness of the esophageal wall. development of this techniques was based on previous
Best Practice Advice 3: Utilization should follow distinct concepts and techniques developed by Hans Gregerson
protocols and analysis paradigms based on the disease and Satish Rao.4 FLIP uses high-resolution impedance
state of interest. planimetry during volume-controlled distention to
Best Practice Advice 4: Clinicians should not utilize FLIP in measure luminal cross-sectional area (CSA) along an
routine diagnostic assessments of gastroesophageal reflux axial plane. This is synchronized to a singular pressure
disease.
measure within a fluid-filled bag (Figure 1) and thus,
Best Practice Advice 5: FLIP should not be used to diagnose
allows for an assessment of luminal geometry and
eosinophilic esophagitis but may have a role in severity
assessment and therapeutic monitoring. pressure akin to compliance measurement. This
technique has been used to assess the mechanical
Keywords: Functional Lumen Imaging Probe; Impedance properties of the esophageal wall and opening dynamics
Planimetry; Achalasia; Gastroesophageal Reflux Disease; of the esophagogastric junction (EGJ) in various esoph-
Eosinophilic Esophagitis. ageal diseases. Whether this new information can lead to
improvements in clinical outcome is just being explored

Abbreviations used in this paper: CSA, cross-sectional area; DI, Most current article
distensibility index; EGJ, esophagogastric junction; EoE, eosinophilic
esophagitis; FLIP, functional lumen imaging probe; GERD, © 2017 by the AGA Institute
gastroesophageal reflux disease; LES, lower esophageal sphincter; 1542-3565/$36.00
POEM, per-oral endoscopic myotomy. http://dx.doi.org/10.1016/j.cgh.2016.10.022
326 Hirano et al Clinical Gastroenterology and Hepatology Vol. 15, No. 3

Figure 1. (A) EndoFLIP system (EF-100) with real-time 3-dimensional imaging of the EGJ. The blue color on the screen rep-
resents the narrowest portion at the EGJ. (B) A 10-cm balloon with 0.5-cm channel spacing housed within an 8-cm length FLIP
segment (EF-325). (C) Positioning of the 16-cm (EF 322) catheter with the distal portion through the EGJ and 10 recording
segments in the body of the esophagus. The paired impedance planimetry rings (black) provide the measure of diameter and
cross-sectional area. The pressure sensor (blue dot) is located in the distal aspect of the catheter and the infusion port (red dot)
in the proximal aspect of the catheter within the balloon.

and there seems to be promising results focused in compliant balloon of varying diameters based on the
achalasia and eosinophilic esophagitis (EoE). assessment required is filled with a conductive fluid from
This clinical practice update on FLIP reviews the an 80-mL syringe housed and controlled from the Endo-
methodology of the technique and the data supporting its FLIP system (Crospon, Galway, Ireland). Excitation elec-
clinical utility in specific esophageal disorders. The re- trodes at either end of the balloon emit a continuous low
view is a summary of expert opinion in the field without electric current and the voltage is measured across the
a formal systematic review of evidence. paired impedance planimetry electrodes by leveraging
Summary of the AGA Institute Best Practice Advice on Ohm’s law to provide a measurement of CSA and volume at
Utilization of the Functional Lumen Imaging Probe (FLIP) intervals based on excitation electrode spacing. A solid-
state pressure transducer is located at the distal end of
Best Practice 1. Clinicians should not make a diagnosis the bag and thus, a simultaneous measure of pressure is
Advice Statements or treatment decision based on func-
tional lumen imaging probe (FLIP)
made and an assessment of distensibility of the esopha-
assessment alone. geal body and/or EGJ can be performed. Multiple device
2. FLIP assessment is a complementary sizes are commercially available with FLIP measurement
tool to assess esophagogastric junc- segments of 6.0–16 cm (Table 1).5–8
tion opening dynamics and the stiff- The FLIP is placed into the esophagus either trans-
ness of the esophageal wall.
3. Utilization should follow distinct pro-
orally or transnasally in a sedated or awake patient. Most
tocols and analysis paradigms based protocols are performed with the catheter placed orally
on the disease state of interest. during conscious sedation or while the patient is under
4. Clinicians should not utilize FLIP in general anesthesia in the operating room. The FLIP
routine diagnostic assessments of is positioned within the esophagus by identifying the
gastroesophageal reflux disease.
5. FLIP should not be used to diagnose
waist-like constriction of the EGJ on the real-time,
eosinophilic esophagitis but may have 3-dimensional geometric display at a low fill volume
a role in severity assessment and (typically 20–30 mL) (Figure 1). Alternatively, direct
therapeutic monitoring. visualization can be used by passing the endoscope
alongside of the FLIP catheter. Variations in FLIP study
methods and protocols exist based on the disease state
and the measurement of interest (Table 2). These differ-
Methodology and Technical Aspects ences are covered in the subsequent sections focused on
specific esophageal disorders.
The FLIP consists of a 240-mm long, 3-mm outer
diameter catheter with a balloon mounted on the distal Data Analysis
end. The catheter contains 16 paired impedance planim-
etry electrodes within the balloon spaced at various in- The FLIP is indicated (and Food and Drug Admin-
tervals ranging from 4 mm to 1 cm based on the bag istration–approved for use in the United States) for clin-
configuration and length (Figure 1). An infinitely ical use as a pressure and dimension measurement device,
March 2017 Functional Lumen Imaging Probe 327

Table 1. Current FDA Approved Devices and Intended Use

Primary location
Description Model number FDA intended use (as of June 2016) of use CPT codes

EndoFLIP System EF-100 For use in a clinical setting to measure 91040 (esophageal
EndoFLIP 8-cm EF-325N pressure and dimensions in the UES,LES, measurements)
measurement catheter esophagus, pylorus, and anal sphincters. pylorus, anal
It is intended to be used as an adjunct sphincters
EndoFLIP 16-cm EF-322N to other diagnostic methods as part of a Esophagus
measurement catheter comprehensive evaluation of patients
with symptoms consistent with
gastrointestinal motility disorders.
EsoFLIP 6- to 20-mm ES-320 To dilate esophageal strictures caused Esophagus 43220,43229
Dilation Catheter by esophageal surgery, primary (both TTS)
gastroesophageal reflux, radiation therapy.
EsoFLIP 8- to 30-mm ES-330 For use in a clinical setting for dilating LES 43214,43233
Dilation Catheter the gastroesophageal junction of a (both wire guided)
patient with achalasia.

FDA, Food and Drug Administration; TTS, through the scope; UES, upper esophageal sphincter.

as an adjunctive test in patients with symptoms consistent akin to the data presentation used in high-resolution
with esophageal hypersensitivity and to estimate the size manometry and represents a novel method to visualize
of a stoma produced by a gastric band. Thus, clinical ap- diameter changes over time with simultaneous pressure
plications for FLIP are varied and data analysis can be during controlled volume distention. The benefits of FLIP
tailored to target the specific disease of interest. topography are the ability to define EGJ distensibility and
During FLIP assessment, measurements of 16 CSA function while simultaneously obtaining information
and pressure are simultaneously taken using a 10-Hz regarding the contractile activity and distensibility of the
sampling rate. The 16 CSA measures are recorded at esophageal body. This approach has been used to better
various intervals based on electrode spacing to assess characterize the motor activity in the body of the
the relationship between luminal CSA and distending esophagus in achalasia subtypes where patients were
(intrabag) pressure. In its most simple form, FLIP can be categorized based on 3 distinct body patterns that con-
used real-time to assess the narrowest area along the 16 sisted of repetitive antegrade contractions, repetitive
recording sites positioned within the anatomic zone of retrograde contractions, or absence of activity
interest while measuring simultaneous pressure. This (Figure 2).12,13
can be assessed visually using the 3-dimensional display Data analysis techniques have also been modified and
that provides a color-spatial reference and a concomitant refined in the assessment of disease activity in EoE
number measurement of the diameter (Figure 1). The (Figure 3). The distensibility plateau is the metric of pri-
distensibility index (DI) is the typical measure of mary interest in EoE and represents the point of nar-
sphincter distensibility and is calculated by dividing the rowest diameter (or CSA) along the esophagus that
median narrowest CSA (within the anatomic zone of demonstrates resistance to further distention during an
interest) by the median intrabag pressure over a set escalation in balloon pressure.14 This is derived by plot-
timeframe (or distention volume).5 The DI and narrow- ting the narrowest CSA across the esophageal body as a
est diameter during distention can be derived from this function of pressure and has been shown to be substan-
real-time analysis; however, FLIP measurements are tially different between asymptomatic control subjects
dynamic with CSA and pressure fluctuation occurring and EoE patients both with and without stricture. This
during a stable distention volume because of respiratory analysis may also be hampered by catheter movement and
and vascular artifacts and the effect of both spontaneous esophageal contractility being misinterpreted as a fixed
and balloon distention-induced esophageal contraction. luminal narrowing and thus, various analysis approaches
Thus, various methods using the FLIP Analytics software have been used, such as wavelet decomposition, maximal
(Crospon) or other external software methods (eg, diameter, and FLIP Analytics software filtering. A recent
MatLAB, The Math Works, Natick, MA) have been study comparing these 3 approaches suggests that the
developed to counteract these effects using various maximal diameter approach using the maximal diameter
filtering techniques and analysis paradigms.9–11 attained at each axial location may be the most accurate.11
Given that impedance planimetry data are acquired in Additionally, FLIP topography can also be used to assess
high resolution over a space-time domain, the diameter areas of narrowing along the body over the entire study to
data at each axial location along the catheter can be assess the distensibility plateau.
expressed as a topography plot using interpolation and a There are limitations in the current analysis tech-
color scale to depict diameter size (Figure 2).9,10 This is niques because most require postacquisition processing
328
Hirano et al
Table 2. Summary of FLIP Methods and Results of Studies Evaluating EGJ Distensibility in Asymptomatic Control Subjects
a b c
FLIP length, IP channel Test setting, Pressure Fill volume, EGJ-DI, Comparator
Author, y N cm spacing, mm sedation Placement zero mL mm2/mm Hg group

Beaumont et al, 200936 10 6.4 4 Awake Oral Gastric 10–60 3.7  0.9 Barrett’s, postablation
Kwiatek et al, 20105 20 6.4 4 Endoscopy, conscious Oral Gastric 10 3.2 (2.3–6.7) GERD
20 2.2 (1.2–6.5)
30 4.2 (1.7–10.4)
40 7.3 (3.8–11.4)
Kwiatek et al, 201114 15 8 5 Endoscopy, conscious Oral NR 20 0.9 (0.3–1.4) EoE
30 0.8 (0.4–2.8)
Rohof et al, 20126 15 6.4 4 Awake Nasal Atm 50 6.3  0.7 Achalasia
Nathanson et al, 201237 50 8 5 Intraoperative, general Oral Gastric 30 1.1 (0.7–1.6) —
anesthesia 40 1.2 (0.83–2.2)
Tucker et al, 20138 22 6.4 4 Endoscopy, conscious Oral NR 20 4.0 (2.4–7.5) GERD
30 6.1 (4.3–8.0)
Rieder et al, 201316 4 8 5 Awake Oral NR 30 2.5 (2.0–6.3) Achalasia
40 2.7 (2.4–8.3)
Fukazawa et al, 201438 9 8 5 Awake Nasal Atm 20 2.9  (0.6) Intrasubject following mosapride
40 7.1  (0.9)
50 8.2  (0.8)
Lottrup et al, 201539 10 8 5 Awake Oral Atm 20 1.9  0.5 GERD, hiatal
30 2.8  0.6 hernia

Clinical Gastroenterology and Hepatology Vol. 15, No. 3


40 3.8  0.9
50 3.9  0.7
Carlson et al, 201512 10 16 10 Endoscopy, conscious Oral Atm 50 7.1 (3.8–8.9) Achalasia
60 6.2 (4.6–8.1)
Mikami et al, 201640 9 6.4 4 Awake Nasal Atm 20 1.8  (0.2) Intrasubject following
30 3.5  (0.6) metoclopramide
40 4.5  (0.5)

NOTE. Courtesy of Dustin Carlson.


Atm, atmospheric; IP, impedance planimetry; NR, not reported.
a
Length of the cylindrical, measurement segment.
b
Conscious sedation with midazolam and fentanyl or pethidine.
c
Results extrapolated from figures if not directly reported and represented as median (interquartile range) or mean  standard deviation (standard error).
March 2017 Functional Lumen Imaging Probe 329

and specialized programming using MatLAB and are thus (n ¼ 21) or laparoscopic Heller myotomy (n ¼ 11).21
not widely available. However, the manufacturer is Although additional study is needed to validate these find-
developing real-time FLIP topography and analytics of ings in a prospective manner, FLIP offers significant prom-
maximal diameter in the future software updates. ise to aid in the treatment of achalasia.
Additionally, esophageal dilatation balloons (incor-
porating a more rigid balloon material than the mea-
Achalasia surement FLIP balloons) are available (Table 1). There is
no intrabag pressure sensor included with the dilation
A hallmark of achalasia is lower esophageal sphincter balloons and thus, the diameter alone is used to target
(LES) dysfunction and achalasia treatments target the and follow dilation effect.22 A recent study demonstrated
resultant EGJ outflow obstruction; thus, FLIP seems well the feasibility and clinical effectiveness of using the
suited for evaluation of patients with achalasia. Eso-FLIP (Crospon) achalasia hydraulic dilation balloon
Studies using FLIP have consistently demonstrated an (maximal diameter of 30 mm).22 Because the EGJ can be
abnormal reduced EGJ-DI (ie, more narrowed EGJ identified with a waist on the real-time display to posi-
diameter at greater distending pressure) in treatment- tion the balloon, this device may allow for achalasia
naive patients with achalasia.6,15,16 Furthermore, dilation to be performed without the concurrent use of
studies assessing achalasia treatment response (eg, after fluoroscopy.
pneumatic dilation or LES myotomy) have reported In conclusion, FLIP seems to be useful in the evalu-
lower EGJ-DI in patients with poor symptomatic ation of achalasia and thus should be used to provide
outcomes (particularly below a threshold of 2.8–2.9 additive information beyond manometry in the man-
mm2/mm Hg) than in patients with good symptomatic agement of achalasia.
outcomes6,15; they also suggest that EGJ-DI may have a
stronger association with symptoms and esophageal
retention (per timed-barium esophagram) than mano- Gastroesophageal Reflux Disease
metric measures of LES pressures. FLIP may better
characterize EGJ function because the degree of luminal Because EGJ incompetence may contribute to GERD
opening is conceptually a more important determinant of pathophysiology in some patients, it is reasonable to
bolus flow than LES relaxation. Additionally, evaluation suspect that FLIP may help identify increased EGJ
of esophageal contractility (described in more detail distensibility (ie, greater EGJ diameters at lower dis-
later) with achalasia may also provide complementary tending pressures) in some patients with GERD. Results
clinical information to the standard achalasia assessment of studies, however, have been inconsistent. Initially, a
with esophageal manometry by further refining study demonstrated greater EGJ-DIs among 20 symp-
esophageal body contractile patterns and subtypes tomatic patients with GERD than 20 asymptomatic
(Figure 2B).12,13 volunteers.5 However, another study that compared
Intraoperative use of FLIP during laparoscopic Heller patients with typical GERD symptoms (n ¼ 18) and 48-
myotomy or per-oral endoscopic myotomy (POEM) also hour wireless esophageal pH monitoring with asymp-
offers the ability to assess the LES myotomy in real-time. tomatic control subjects (n ¼ 18) found that patients
Several studies have demonstrated an immediate increase with GERD actually had lower EGJ-DI than control
in EGJ-DI following POEM or Heller myotomy (associated subjects.8 Furthermore, EGJ-DI did not differ between
with a slight decrease following fundoplasty creation).17–20 patients with normal (n ¼ 9) or abnormal (n ¼ 9)
Furthermore, intraoperative FLIP may provide a method to esophageal acid exposure time. Recently, a study eval-
tailor the myotomy with or without fundoplasty to help uating patients with Barrett’s esophagus with hiatal
improve dysphagia (ie, avoid too low EGJ distensibility), hernia 2 cm (n ¼ 23) reported that FLIP could
while limiting gastroesophgeal reflux disease (GERD) (ie, generally identify hiatal hernia, measure both distensi-
avoid overly increasing EGJ distensibility). A recent multi- bility of LES and crural diaphragm components of the
center study assessed the association with early clinical EGJ, and that the distensibility of the LES in hiatal
outcomes (median follow-up, 122 days) and retrospectively hernia patients was greater than asymptomatic control
evaluated final intraoperative FLIP measures of 63 patients subjects.23 Although the diagnostic utility of FLIP in
with achalasia treated with POEM.19 They found a lower GERD may remain in question, further study may help
EGJ-CSA at a 30-mL fill volume of an 8-cm FLIP (but similar evaluate physiologic components related to GERD
EGJ-CSA at 40 mL) in those with a poor symptomatic pathophysiology.
outcome (n ¼ 13) than those with a good outcome (n ¼ 50). Because patients with fundoplication seem to have
EGJ-DI was numerically, but not statistically, lower among reduced EGJ distensibility compared with control
the poor outcome group at both 30- and 40-mL fill volumes. subjects,5 FLIP may be a useful tool to aid antireflux
Another recent study reported that a final intraoperative procedures (eg, fundoplication).24 Several studies
EGJ-DI (at 40-mL distention volume with an 8-cm FLIP) of demonstrated the feasibility of intraoperative FLIP
4.5–8.5 mm2/mm Hg was less likely to have dysphagia or use during fundoplication and a consistent reduction
GERD symptoms at >6 months follow-up after POEM in EGJ distensibility immediately following
330 Hirano et al Clinical Gastroenterology and Hepatology Vol. 15, No. 3

fundoplication.24,25 Reduction in EGJ distensibility their centers; however, directly associated clinical
following transoral incisionless fundoplication has outcomes were not reported.24
also been reported.26,27 A report of pooled results of In summary, the role of FLIP for physiologic evaluation
intraoperative FLIP during laparoscopic Nissen fun- and management in GERD remains appealing; however,
doplication from 4 high-volume centers reported a the level of evidence is low and currently FLIP should not
mean final EGJ diameter of 6.1 mm (standard devia- be used in routine GERD management. Future outcome
tion, 1.4) and EGJ-DI of 1.6 mm2/mm Hg (standard studies are needed to substantiate the utility of FLIP in
deviation, 1.1), suggesting these as targets for fun- GERD and to develop metrics that predict severity and
doplication based on historically good outcomes from treatment response after antireflux procedures.
March 2017 Functional Lumen Imaging Probe 331

Figure 3. Example of data acquisition and analysis in eosinophilic esophagitis using filtering schemes and postacquisition
processing to remove the effect of contraction on the assessment of distensibility plateau and restricting diameter. The
maximal diameter technique was used to remove the contraction effect and thus, FLIP topography more accurately displays
passive lumen geometry. The narrowest diameter and pressure values are plotted in the bottom panel with simultaneous
3-dimensional images from real-time acquisition displayed at time points along the FLIP topography plot. The distensibility
plateau is approximately 11 mm (diameter) or 95 mm2 (cross-sectional area). In addition, FLIP topography also supports that
the esophagus is diffusely narrowed through the recording segment of the esophagus. Figure used with permission from the
Esophageal Center at Northwestern University, Chicago, Illinois.

Eosinophilic Esophagitis inflammation.28 Chronic inflammation is thought to


progress to fibrosis of the esophagus leading to luminal
EoE is a chronic, immune-mediated disease of the narrowing and a loss in mural compliance.29 These
esophagus characterized by esophageal symptoms (pre- remodeling consequences of EoE are the primary
dominantly dysphagia/food impaction) and eosinophilic determinant of symptoms and are typically assessed by

=
Figure 2. FLIP data analysis. Examples of data acquisition and analysis in an asymptomatic control subject (A) and a patient with
achalasia (B). The pressure (red) recordings are depicted in the upper panel. Diameter data from each impedance planimerty
channel is scaled from 5 to 30 mm and is interpolated and color coded on a hot/cold scale (small diameters are red/large di-
ameters are blue) to generate FLIP topography akin to what is visualized during high-resolution manometry. In the asymptomatic
control subject (A), real-time 3-dimensional images are depicted to show various points of interest using shape and color (small
diameters are red/large diameters are blue) to highlight narrowing. Time point 1 illustrates the baseline with minimal pressure and
balloon filling. Time points 2–4 represent propagation of a single antegrade contraction within the sequence of repetitive ante-
grade contractions where one can see the narrowing associated with contraction move distally within the 3D image and the
propagating contraction on FLIP topography noted by the red color similar to peristalsis noted on high-resolution manometry.
Time point 5 represents a period of quiescence at 60 mL with balloon diameters reaching the limits of the bag at 22 mm. In the
patient with achalasia (B), time point 1 once again represents baseline with 5-mL filling. As the volume distention occurs with filling
from 20 mL to 60 mL, the EGJ is visualized on the 3D images as a narrowing and low diameter. At time point 3, the EGJ initially
opens at an intraballoon pressure of 24 mm Hg and the distensibility index is 1.0 mm2/mm Hg. At time point 4 with a 60-mL filling
volume, the diameter is 12.5 mm and the pressure is 42 mm Hg with a distensibility index of 2.9, which is right at the cutoff value of
2.8 mm2/mm Hg for achalasia. The concomitant FLIP topography displays the narrowed zone at the EGJ that appears to remain
relatively closed through most of the study and never opens to a level greater than 12.5 mm. In addition, the contractile activity in
the body of the esophagus is erratic with both antegrade and retrograde contractions suggesting a motility disorder. Figure used
with permission from the Esophageal Center at Northwestern University, Chicago, Illinois.
332 Hirano et al Clinical Gastroenterology and Hepatology Vol. 15, No. 3

means of endoscopy.30 Unfortunately, endoscopic by FLIP can be used to define contractile activity similar
assessment of esophageal narrowing in EoE has sub- to high-resolution manometry.12 A recent study
stantial limitations in terms of accuracy when compared comparing data acquired during a FLIP assessment
with fluoroscopic imaging.31 during sedated endoscopy and standard high-resolution
FLIP assessment of the esophageal body in EoE al- manometry suggests that FLIP can accurately diagnose
lows for objective and accurate measurement of achalasia and may be complementary to manometry in
esophageal narrowing and mechanical properties of the further refining the diagnosis of functional dysphagia
esophageal body Measurement of a narrowest esopha- (normal endoscopy/normal or borderline manom-
geal body CSA and corresponding intrabag pressure etry).13 Applying this as a tool to assess hypersensitivity
during step-wise volumetric distention with the FLIP in a barostat mode application is also appealing, but
positioned in the esophageal body allows identification currently balloon distention studies are relegated to
of the distensibility plateau (Figure 3). The predictive specialized centers.
value of this assessment was reported in a study of The EndoFLIP is also being used to assess opening
patients with EoE using requirement for dilation dynamics and mechanical properties of other anatomic
therapy and risk of food impaction as endpoints. zones of interest. Data have been reported in the upper
This study supported that a distensibility plateau <225 esophageal sphincter34 and there is also great interest in
mm2 (diameter w17 mm) was the only indepen- studying the pylorus in normal rhythm gastroparetic
dent predictor (ie, not treatment type or eosinophil patients and anal-rectal function in patients with con-
count, among others) of future food impaction.32 stipation and incontinence.35 Lastly, the technique is still
Although the severity of endoscopically identified being assessed for its ability to tailor bariatric proced-
esophageal signs of remodeling (rings) is associated ures and currently it is approved by the Food and Drug
with esophageal distensibility, FLIP offers significantly Administration for this indication.
greater accuracy and precision in estimating the effects
of remodeling.33
Although FLIP seems to have significant value for the Conclusions
assessment of disease severity and clinically relevant
symptom outcomes in EoE, the identification of the The FLIP offers an innovative method that enhances
narrowest portion of the esophageal body used in the the assessment of esophageal function in various dis-
calculation of the distensibility plateau is often techni- eases. Although the strongest data seem to be focused on
cally challenging in the setting of esophageal contrac- the management of achalasia, emerging evidence sup-
tions. Thus, postprocessing the FLIP data using ports the clinical relevance of FLIP in the assessment of
software programs to filter out the contraction- disease severity and as an outcome measure in EoE
associated changes in esophageal luminal diameter is intervention trials. Ongoing studies are evaluating the
necessary.9–11 Software enhancements are being devel- applications of FLIP to GERD interventions targeting the
oped that improve the current analysis paradigms and EGJ and other foregut disorders. More work is needed,
should broaden the clinical utility of FLIP in the evalu- however, which focuses on optimizing data analysis,
ation of EoE. standardizing protocols, and defining outcome metrics
In summary, FLIP seems to be uniquely suited to before the widespread adoption into general clinical
assess the mechanical properties of the esophageal wall practice.
in EoE. Nonetheless, current recommendations are
limited by the low level of evidence and lack of gener-
alized availability of the analysis paradigms. Thus, one References
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Acknowledgments
esophageal motor activity and esophagogastric junction The authors thank Dustin Carlson and Zhiyue Lin for their help with developing
compliance in healthy volunteers. J Gastroenterol 2014; Figures 2 and 3.
49:1307–1313.
39. Lottrup C, Gregersen H, Liao D, et al. Functional lumen imaging of Conflicts of interest
This author discloses the following: John E. Pandolfino has a relationship with
the gastrointestinal tract. J Gastroenterol 2015;50:1005–1016. Medtronic Inc, and Sandhill Scientific. The remaining authors disclose no
40. Mikami H, Ishimura N, Fukazawa K, et al. Effects of metoclo- conflicts.

pramide on esophageal motor activity and esophagogastric


Funding
junction compliance in healthy volunteers. J Neurogastroenterol Supported by the National Institute of Diabetes and Digestive and Kidney
Motil 2016;22:112–117. Diseases.

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