Esophageal motility disorders in highresolution Dustin Carlson MD MSCI Assistant Professor of Medicine Gastroenterology Northwestern University Director Mario Tonelli Esophageal Function Lab ID: 723621
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Slide1
Esophageal function testing:Esophageal motility disorders in high-resolution
Dustin
Carlson, MD, MSCI
Assistant Professor of Medicine - Gastroenterology
Northwestern
University
Director, Mario Tonelli Esophageal Function Lab
Esophageal Center of NorthwesternSlide2
DisclosuresConsulting (Medtronic, Inc)
Speaker (Medtronic,
Inc
)
License
agreement surrounding FLIP
panometry
systems, methods, and apparatus granting rights to U.S. Patent Application Number 15/546,986 and Canadian Patent Application Number
2,975,603 (Medtronic
,
Inc
)Slide3
Esophageal Motility Evaluation1. Understand indications and standard methods for evaluating esophageal motility and function
2
. Understand the diagnostic approach and basic therapeutic strategies in
achalasia
3
. Appreciate the clinical implications of esophageal motility diagnosis beyond achalasia
OBJECTIVESSlide4
EGD
yes
Approach to patient with
esophageal complaints:
-Heartburn, Dysphagia, Regurgitation, Chest pain, Food impactions
-
Diff
Dx
: GERD, EoE, EMD/Achalasia- difficult to distinguish on history
Esophagitis LA B or higher
Hiatus hernia > 3 cm
Eosinophilic esophagitis
Normal or suspect EMD
Escalate antireflux therapy
-may need pH-impedance on meds if fails therapy
no
no
no
yes
Biopsies- target EoE treatments
yes
May cause reflux and dysphagia
May require surgery- will need
preop
w/u
motility and potentially reflux testing
yes
Stricture
Dilation therapy based on morphology and etiology
no
Follow up in clinic
Assessed during
endoscopy
visit
Esophageal
Function testing
Initial Encounter: potentially prescribe
a
4-8
week course of
PPI and schedule endoscopy
Visit 5: Debrief
Schedule endoscopy or Surgery
Esophageal Center at NorthwesternSlide5
Esophageal function testingEsophageal reflux (pH) monitoringEvaluation of non-erosive gastroesophageal reflux:
objective
GERD diagnosis
Wireless (Bravo™)
48-96 hours
Catheter based (with or without impedance)24 hoursEsophageal
manometry
High resolution
manometry
(HRM)Evaluation of esophageal motility
Indications:Non-obstructive dysphagia
Prior to anti-reflux surgeryEsophageal Center at NorthwesternSlide6
The manometry studyTransnasal
catheter placement
After application of topical anesthetic to
nare
(lidocaine)
Catheter positioned spanning from oropharynx to a few cm into the stomachBaseline recording/basal EGJ pressure10 supine, 5-ml liquid
swallows
Basis
for Chicago Classification of esophageal motility diagnosesRequires
awake patient+/-Supplementary maneuvers
Esophageal Center at NorthwesternSlide7
Esophageal manometry
Time
100
50
0
150
mmHg
Time
Conventional manometry
Line tracings
High-resolution manometry
Esophageal pressure topography
Swallow
SwallowSlide8
High-resolution manometry: esophageal pressure topography
UES
EGJ
100
50
0
150
mmHg
30
Pressure
TimeSlide9
Integrated relaxation pressure (IRP)
Deglutitive
LES
relaxation
Mean of the 4 seconds (contiguous or non-contiguous) of maximal deglutitive relaxation in the 10s following UES relaxation; referenced to gastric pressure
HRM/EPT metrics
Length along the esophagus
100
50
0
150
mmHg
10 seconds
Gastric
EGJ
IRP 9 mmHgSlide10
Distal latency
LES
UES
Length along the esophagus
100
50
0
150
mmHg
Deglutitive inhibition of esophageal contraction
Time from swallow onset (UES relaxation) to
contractile deceleration point (CDP)
HRM/EPT metrics
3
0
Distal latency 7 secondsSlide11
Distal contractile integral (DCI)
LES
UES
Length along the esophagus
100
50
0
150
mmHg
Contractile vigor
Pressure amplitude x duration x length of distal esophageal contraction, i.e. transition zone to proximal margin of EGJ
HRM/EPT metrics
2
0Slide12
HRM/EPT metricsSummary
HRM metric
HRM abnormal threshold
Associated disorder
Integrated relaxation pressure (IRP)
>15 mmHg
(median)
Achalasia
EGJ outflow obstruction
Distal latency
< 4.5 seconds
Spasm
Distal contractile integral (DCI)
>8000 mmHg-cm-s
<450 mmHg-s-cmHypercontractileHypocontractile
values
reflect Sierra-vintage HRM assemblies Slide13
HRM/EPT interpretation caveatsAffect manometric pressure:
Patient position
Bolus size
Bolus consistency
HRM assembly
Application of normal/abnormal values based on testing with similar brand assemblies Herregods
, TV, et al. Normative values in esophageal high-resolution manometry.
Neurogastroenterology and Motility
. 2015; 27(2): 175-87
Mechanical obstruction
History of previous foregut surgeryReflux esophagitisSlide14
HRM/EPT interpretationChicago classification of esophageal motility disorders
Evaluation for
primary
motor disorders
Patients evaluated for dysphagia or esophageal chest pain
Patients without previous foregut surgery or mechanical obstructionBased on supine, 5-ml, liquid swallows
Kahrilas, et al.
Neurogastroenterology and Motility.
2015; 27(2)
Pandolfino et al, Amer J Gastroenterology. 2008 103(1): 627-35Slide15
HRM study protocolBaseline recording/basal EGJ pressure10 supine, 5-ml liquid swallows
Basis for Chicago Classification of esophageal motility diagnoses
Supplementary maneuvers
Upright swallows
Multiple rapid swallows (2ml liquid x 5 q2-3 seconds)
Viscous swallows
Solid swallows
200 ml free drink
Test meal +/- post-prandial monitoringSlide16
Kahrilas, et al. Neurogastroenterology and Motility, 2015
Disorders with EGJ outflow obstruction
Major disorders of peristalsis
Entities not seen in normal subjects
Yes
Yes
No
Achalasia
Type I: Absent contractility
Type II:
Pan-esophageal pressurization
Type
III:
Spastic
EGJ outflow obstruction
Heterogeneous classification
No
Yes
No
Minor disorders of peristalsis
Ineffective esophageal
motility Fragmented peristalsis
Normal motility
Yes
No
Abnormal IRP?
100% failed or
≥ 20% premature?
≥50% ineffective swallows
≥ 20% premature
,
≥ 20%
hypercontractile
, or 100% failed?
Distal esophageal
spasm Jackhammer
esophagus
Absent contractility
LES relaxation
Contractility pattern
Motility diagnosis
HRM Interpretation
Chicago Classification v3.0
Esophageal Center at NorthwesternSlide17
Kahrilas, et al. Neurogastroenterology and Motility, 2015
Disorders with EGJ outflow obstruction
Major disorders of peristalsis
Entities not seen in normal subjects
Yes
Yes
No
Achalasia
Type I: Absent contractility
Type II:
Pan-esophageal pressurization
Type
III:
Spastic
EGJ outflow obstruction
Heterogeneous classification
No
Yes
No
Minor disorders of peristalsis
Ineffective esophageal
motility Fragmented peristalsis
Normal motility
Yes
No
Abnormal IRP?
100% failed or
≥ 20% premature?
≥50% ineffective swallows
≥ 20% premature
,
≥ 20%
hypercontractile
, or 100% failed?
Distal esophageal
spasm Jackhammer
esophagus
Absent contractility
LES relaxation
Contractility pattern
Motility diagnosis
HRM Interpretation
Chicago Classification v3.0
1. Insufficient LES relation
2
. Lack of peristalsis
Esophageal Center at NorthwesternSlide18
AchalasiaMost well defined esophageal motility disorder
Diagnosis:
Abnormal LES relaxation pressure
IRP > upper limit of normal (e.g. 15 mmHg)
Absent (type I and II) or spastic (type III) contractility
Esophageal Center at NorthwesternSlide19
Time
100
50
0
150
mmHg
Time
Swallow
Swallow
Esophageal manometry –
achalasia
Achalasia
Insufficient LES Relaxation
Loss of Esophageal
peristalsis
Normal motility
LES Relaxation
Esophageal
peristalsisSlide20
Achalasia
Most well defined esophageal motility disorder
Diagnosis:
Abnormal LES relaxation pressure
IRP > upper limit of normal (e.g. 15 mmHg)
Absent (type I and II) or spastic (type III) contractilityEffective
interventions
Pneumatic dilation
Laparoscopic Heller’s
myotomy
POEM (Per-Oral Endoscopic Myotomy)
Botulinum toxin injection
Esophageal Center at NorthwesternSlide21
Achalasia treatment
Pneumatic dilation
Heller’s myotomy
With partial fundoplasty
Per-oral endoscopic myotomy (POEM)
-------
Botulinum toxin injection
Target: Lower Esophageal Sphincter (LES)
Aim: Relieve esophageal outflow obstruction
Improve esophageal emptying Improve symptomsSlide22
Achalasia treatmentBotulinum toxin
injection
Endoscopic
Pre-synaptic inhibition of acetylcholine release
~50% reduction in LES pressure
6-24 month duration of effect Typically reserved for non-surgical (or pneumatic dilation) candidates
Vaezi, M, et al. ACG clinical guidelines. Amer J of Gastroenterol. 2013; 108.Slide23
Achalasia treatmentPneumatic dilationEndoscopic
Typically fluoroscopy-guided
Staged dilations 30mm, 35mm, +/- 40mm
Complication:
Perforation rate ~2% (1-4%)
Microvasive® Dilator
(3.0, 3.5, or 4.0 cm)
Passed over guidewire, imaged with
fluoroscopySlide24
Achalasia treatmentLaparoscopic Heller’s Myotomy
With Dor Fundoplication (anterior, 180
0
) or
Toupet fundoplasty (posterior, 270
0)Peters & DeMeesterMinimally Invasive Surgery of the Foregut 1994Slide25
Achalasia treatmentPer-oral endoscopic myotomy (POEM)
Enter
into the submucosa in the mid esophagus
Creation of submucosal tunnel ≈ half esophageal circumference
Myotomy begun ≈ 3 cm distal to entry, ≈ 7 cm above EGJ
Myotomy completionClipping
Phalanusitthepha, C. et al. Annals of Translational Medicine. 2014; 2(3)
1
2
3
4
5Slide26
Length along the esophagus (cm)
Absent peristalsis
No pressurization
Abnormal LES relaxation
Median IRP > 15 mmHg
0
5
10
15
20
25
30
35
Achalasia -
subclassification
Abnormal LES relaxation pressure
IRP > upper limit of normal (15 mmHg)
Absent (type I and II) or spastic (type III) contractility
Time
Absent peristalsis
Pan-esophageal pressurization
Spastic contraction
Time
Time
Type 3
Type 2
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
<4.5s
100
50
0
150
mmHg
30
Type 1Slide27
100
50
0
150
mmHg
Length along the esophagus (cm)
Absent peristalsis
No pressurization
Abnormal LES relaxation
Median IRP > 15 mmHg
0
5
10
15
20
25
30
35
Achalasia - subtype implications
Absent peristalsis
Pan-esophageal pressurization
Spastic contraction
Type 3
Type 2
Type 1
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
<4.5s
Most common
Best response to therapy
Least common
Worst response to therapySlide28
Achalasia subtypes - prognosis
Publication
N, (Rx type)
Type I
Type II
Type III
Pandolfino 2008 [1]
99
(PD, LHM, Botox)
56%
(n=21)
96%
(n=49)
29%
(n=29)
Salvador 2010 [2]
246
(LHM)
85%
(n=96)
95%
(n=127)
69%
(n=23)
Pratap 2011 [3]
51
(PD)
63%
(n=24)
90%
(n=24)
33%
(n=3)
Rohof 2013 [4]
176
(RCT: PD, LHM)
86% (PD)
81% (LHM)
(n=44)
100% (PD)
95% (LHM)
(n=114)
40% (PD)
86% (LHM)
(n=18)
Percent with ‘good’ outcome
[1] Pandolfino
JE, et al Gastroenterology 2008;135:
1526
[2] Salvador R, et al J Gastrointest Surg 2010;14:1635
[
3] Pratap N, et al Neurogastroenterol Mot 2011;17:205
[
4] Rohof W, et al Gastroenterology;
2013; 144(4)
Slide courtesy of Dr. Peter KahrilasSlide29
100
50
0
150
mmHg
Length along the esophagus (cm)
Absent peristalsis
No pressurization
Abnormal LES relaxation
Median IRP > 15 mmHg
0
5
10
15
20
25
30
35
Achalasia – subtype implications
Absent peristalsis
Pan-esophageal pressurization
Spastic contraction
Type 3
Type 2
Type 1
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
<4.5s
Most common
Best response to therapy
Least common
Worst response to therapy
Myotomy preferred treatmentSlide30
Achalasia treatment: European Achalasia Trial
Years since start of study
Moonen, et al.
Gut
. 2016
Boeckxstaens GE, et al. NEJM
2011:364:1807-1816
Pneumatic dilation*
Laparoscopic Heller’s myotomy
RCT: Pneumatic dilation vs Laparoscopic Heller’s myotomy
*+/- repeat dilationSlide31
POEM outcomes115 consecutive patients (2012-2015)
After 15 patient “learning curve”
Follow-up at > 1 year
Average 2.4 years, range 12 - 52 months
Positive outcome in
92% of patientsEckardt score of ≤3
Positive outcome in 18/20 (90%) of type III achalasia
GERD 40% (of 68 patients evaluated)
Positive
pH study or LA-B-D
esophagitisNorthwestern experience
Hungness, E. et al. Annals of Surgery, 2016; 264(3): 508-17Slide32
Achalasia treatment: POEMA trialAbstract: DDW 2017 (Ponds, et al.)International, multi-centered randomized trial of patients with newly diagnosed achalasia
133 patients: 66 PD and 67 POEM
12 month follow-up
Treatment success (
Eckardt
score of ≤3) rates:PD: 52/66 (79%)
POEM: 59/64 (92%)
RCT: Pneumatic dilation vs
POEMSlide33
Kahrilas, et al. Neurogastroenterology and Motility, 2015
Disorders with EGJ outflow obstruction
Major disorders of peristalsis
Entities not seen in normal subjects
Yes
Yes
No
Achalasia
Type I: Absent contractility
Type II:
Pan-esophageal pressurization
Type
III:
Spastic
EGJ outflow obstruction
Heterogeneous classification
No
Yes
No
Minor disorders of peristalsis
Ineffective esophageal
motility Fragmented peristalsis
Normal motility
Yes
No
Abnormal IRP?
100% failed or
≥ 20% premature?
≥50% ineffective swallows
≥ 20% premature
,
≥ 20%
hypercontractile
, or 100% failed?
Distal esophageal
spasm Jackhammer
esophagus
Absent contractility
LES relaxation
Contractility pattern
Motility diagnosis
Esophageal motility disorders:
beyond achalasia
Chicago Classification v3.0
Esophageal Center at NorthwesternSlide34
EGJ outflow obstruction
Heterogeneous
May represent:
Achalasia variant
Early/“Evolving” achalasia
Subtle mechanical obstruction
Hiatal hernia
Pressure artifact
Vascular or anatomic
Normal motility
15-mmHg IRP = 95th percentile of asymptomatic controls
IRP 30 mmHg
100
50
0
150
mmHg
30
IRP 18 mmHg
IRP 32 mmHg
IRP 28 mmHg
IRP 35 mmHg
IRP 22 mmHg
Asymptomatic volunteerSlide35
EGJ outflow obstructionHeterogeneous clinically
May represent:
Achalasia variant
Early/“Evolving” achalasia
Subtle mechanical obstruction
Hiatal hernia
Pressure artifact
Vascular or anatomic
Normal motility
Variable management strategies
Dilation
Pneumatic/Heller/POEM/Botox
GERD;
Functional
GERD;
Functional
GERD;
HH repairSlide36
EGJ outflow obstruction?Supplementary HRM interpretation
Degree
of IRP elevation
Contractile/peristaltic pattern
Elevated intra-bolus pressure
Upright swallows
Normalization of IRP
Supplementary/Additional Testing
Esophagram
Timed barium
esophagram
Barium tablet
FLIPEndoscopic ultrasoundSlide37
Kahrilas, et al. Neurogastroenterology and Motility, 2015
Disorders with EGJ outflow obstruction
Major disorders of peristalsis
Entities not seen in normal subjects
Yes
Yes
No
Achalasia
Type I: Absent contractility
Type II:
Pan-esophageal pressurization
Type
III:
Spastic
EGJ outflow obstruction
Heterogeneous classification
No
Yes
No
Minor disorders of peristalsis
Ineffective esophageal
motility Fragmented peristalsis
Normal motility
Yes
No
Abnormal IRP?
100% failed or
≥ 20% premature?
≥50% ineffective swallows
≥ 20% premature
,
≥ 20%
hypercontractile
, or 100% failed?
Distal esophageal
spasm Jackhammer
esophagus
Absent contractility
LES relaxation
Contractility pattern
Motility diagnosis
Esophageal motility disorders:
beyond achalasia
Chicago Classification v3.0
Esophageal Center at NorthwesternSlide38
Rare (<1-3% of HRM)Primary motor disorder
Spectrum: Achalasia variants
Secondary motor manifestation
Mechanical obstruction
GERD
Management?Smooth muscle relaxants
Botulinum toxin injection
POEM
Trazodone
Distal esophageal spasm
Hypercontractile
esophagus
IRP < 15 mmHg
DL < 4.5s
IRP < 15 mmHg
DCI > 8000 mmHg-cm-sSlide39
Absent contractility
Failed swallows/absent peristalsis
Normal LES relaxation
Association
with connective tissue disease (not diagnostic of CTD)
Consider achalasiaBorderline IRPSupplementary testing
Management
(if not achalasia)
Dietary modifications
Reflux therapies
IRP < 15 mmHgSlide40
Kahrilas, et al. Neurogastroenterology and Motility, 2015
Disorders with EGJ outflow obstruction
Major disorders of peristalsis
Entities not seen in normal subjects
Yes
Yes
No
Achalasia
Type I: Absent contractility
Type II:
Pan-esophageal pressurization
Type
III:
Spastic
EGJ outflow obstruction
Heterogeneous classification
No
Yes
No
Minor disorders of peristalsis
Ineffective esophageal
motility Fragmented peristalsis
Normal motility
Yes
No
Abnormal IRP?
100% failed or
≥ 20% premature?
≥50% ineffective swallows
≥ 20% premature
,
≥ 20%
hypercontractile
, or 100% failed?
Distal esophageal
spasm Jackhammer
esophagus
Absent contractility
LES relaxation
Contractility pattern
Motility diagnosis
Esophageal motility disorders:
beyond achalasia
Chicago Classification v3.0
Esophageal Center at NorthwesternSlide41
Functional dysphagiaNot meeting criteria for a major motility disorderConsider evaluation for subtle mechanical obstruction
e.g. esophagram with barium tablet
Management
Dietary modifications
Reflux
therapiesEmpiric dilation
Neuromodulator/cognitive behavioral therapy/hypnosis
Observation and re-evaluation for progressionSlide42
Esophageal Motility Evaluation: HRMHRM indicated for evaluation of:non-obstructive dysphagia and
prior to anti-reflux surgery
2
.
Achalasia:
The esophageal motility disorderEffective therapeutic options3
.
Esophageal
motility diagnosis
beyond achalasia:Achalasia-variants?Clinical, multi-modal diagnostics to direct among varied therapeutic options
ConclusionsSlide43
AcknowledgementsClinical Research Team
Sandi
Jelinek
Gwen Cassidy
Jackie Prescott
Alex Decorrevont
Francesca
Shilati
Melina
Masihi
Stephanie PetersonJoe
TriggsRyan Campagna
John
PandolfinoPeter Kahrilas
Ikuo HiranoNimi Gonsalves
Aziz AadamSri
KomanduriEric Hungness
Ezra Teitelbaum
Nat Soper
David OdellFunding sources
NIDDK:R01 DK079902 (PI:
Pandolfino)R01 DK092217
(PI: Pandolfino)P01
DK117824 (PI: Pandolfino)
Esophageal Center of NorthwesternSlide44
Thank YouQuestions?
dustin-carlson@northwestern.edu