1. 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 Northwestern
Objective 1. Understand indications and standard methods for evaluating esophageal motility and function     Learning points:     ​A. An esophageal motility evaluation is primarily indicated for the evaluation of non-obstructive dysphagia and prior to anti-reflux surgery.     B. High-resolution esophageal manometry is the traditional method to evaluate esophageal motility and diagnose esophageal motility disorders, such as achalasia     C. Esophageal pH testing is utilized to objectively diagnosis GERD for suspected non-erosive reflux disease.
Objective 2. Understand the diagnostic approach and basic therapeutic strategies in achalasia.     A. Achalasia is the classic esophageal motility disorder characterized by i) impaired swallow-associated lower esophageal sphincter relaxation and ii) absent or uncoordinated (spastic) contractility
Achalasia is associated with reduced distensibility at the esophagogastric junction.     B. Achalasia therapies (pneumatic dilation, laparoscopic Heller's myotomy, POEM, and botulinum toxin injection) target the lower esophageal sphincter to improve esophageal outflow obstruction.     C. Manometric achalasia subtypes carry prognostic information (best prognosis with type II - panesophageal pressurization) and may direct management decisions (myotomy preferred for type III - spastic)
Objective 3. Appreciate the clinical implications of esophageal motility diagnosis beyond achalasia.  Learning points:     A. EGJ outflow obstruction is a clinically heterogeneous manometric classification. 
    B. Distal esophageal spasm and jackhammer esophagus are rare esophageal motility disorders that can be primary or secondary in nature     C. Functional dysphagia or GERD is considered in patients with dysphagia, but without a major esophageal motility disorder on HRM

2. Disclosures Consulting (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)

3. Esophageal Motility Evaluation
OBJECTIVES
1. 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

4. Approach to patient with esophageal complaints:
Approach to patient with esophageal complaints: -Heartburn, Dysphagia, Regurgitation, Chest pain, Food impactions -Diff Dx: GERD, EoE, EMD/Achalasia- difficult to distinguish on history
Initial Encounter: potentially prescribe a 4-8 week course of PPI and schedule endoscopy
EGD
yes
Escalate antireflux therapy
-may need pH-impedance on meds if fails therapy
Esophagitis LA B or higher no
yes
Dilation therapy based on morphology and etiology
Assessed during
endoscopy visit
Stricture no
yes
Eosinophilic esophagitis
Biopsies- target EoE treatments no
May cause reflux and dysphagia
May require surgery- will need preop w/u motility and potentially reflux testing
yes
Hiatus hernia > 3 cm no
Normal or suspect EMD
Esophageal Function testing
Visit 5: Debrief
Schedule endoscopy or Surgery
Follow up in clinic
Esophageal Center at Northwestern

5. Esophageal function testing
Esophageal reflux (pH) monitoring
Evaluation of non-erosive gastroesophageal reflux: objective GERD diagnosis
Wireless (Bravo™)
48-96 hours
Catheter based (with or without impedance)
24 hours
Esophageal manometry
High resolution manometry (HRM)
Evaluation of esophageal motility
Indications:
Non-obstructive dysphagia
Prior to anti-reflux surgery
Esophageal Center at Northwestern

6. The manometry study Transnasal catheter placement
After application of topical anesthetic to nare (lidocaine)
Catheter positioned spanning from oropharynx to a few cm into the stomach
Baseline recording/basal EGJ pressure
10 supine, 5-ml liquid swallows
Basis for Chicago Classification of esophageal motility diagnoses
Requires awake patient
+/-Supplementary maneuvers
Esophageal Center at Northwestern

7. Esophageal manometry Conventional manometry Line tracings
High-resolution manometry
Esophageal pressure topography
Swallow
Swallow
100 50
150
mmHg
Time
Time

8. High-resolution manometry: esophageal pressure topography
100 50
150
mmHg 30
UES
EGJ
Time

9. Integrated relaxation pressure (IRP)
HRM/EPT metrics
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
100 50
150
mmHg
Length along the esophagus
IRP 9 mmHg
EGJ
10 seconds
Gastric

10. Distal latency Deglutitive inhibition of esophageal contraction
HRM/EPT metrics
Deglutitive inhibition of esophageal contraction
Time from swallow onset (UES relaxation) to contractile deceleration point (CDP)
UES
100 50
150
mmHg
Length along the esophagus 30
Distal latency 7 seconds
LES

11. Distal contractile integral (DCI)
HRM/EPT metrics
Contractile vigor
Pressure amplitude x duration x length of distal esophageal contraction, i.e. transition zone to proximal margin of EGJ
UES
100 50
150
mmHg
Length along the esophagus 20
LES

12. HRM/EPT metrics Summary >15 mmHg 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-cm
Hypercontractile
Hypocontractile
values reflect Sierra-vintage HRM assemblies

13. HRM/EPT interpretation caveats
Affect 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):
Mechanical obstruction
History of previous foregut surgery
Reflux esophagitis

14. HRM/EPT interpretation
Chicago 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 obstruction
Based on supine, 5-ml, liquid swallows
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
Pandolfino et al, Amer J Gastroenterology (1):

15. HRM study protocol Baseline recording/basal EGJ pressure
10 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 monitoring

16. Contractility pattern
HRM Interpretation
Chicago Classification v3.0
LES relaxation
Contractility pattern
Motility diagnosis
Achalasia
Type I: Absent contractility
Type II: Pan-esophageal pressurization
Type III: Spastic
Abnormal IRP?
Yes
100% failed or
≥ 20% premature?
Yes
Disorders with EGJ outflow obstruction No No
EGJ outflow obstruction
Heterogeneous classification
≥ 20% premature,
≥ 20% hypercontractile, or 100% failed?
Yes
Distal esophageal spasm Jackhammer esophagus
Absent contractility
Major disorders of peristalsis
Entities not seen in normal subjects No
≥50% ineffective swallows
Yes
Ineffective esophageal motility Fragmented peristalsis
Minor disorders of peristalsis No
Normal motility
Esophageal Center at Northwestern
Kahrilas, et al. Neurogastroenterology and Motility, 2015

17. Contractility pattern 1. Insufficient LES relation
HRM Interpretation
Chicago Classification v3.0
LES relaxation
Contractility pattern
Motility diagnosis
Yes
Achalasia
Type I: Absent contractility
Type II: Pan-esophageal pressurization
Type III: Spastic
Abnormal IRP?
100% failed or
≥ 20% premature?
Yes
Disorders with EGJ outflow obstruction
1. Insufficient LES relation No
2. Lack of peristalsis No
EGJ outflow obstruction
Heterogeneous classification
≥ 20% premature,
≥ 20% hypercontractile, or 100% failed?
Yes
Distal esophageal spasm Jackhammer esophagus
Absent contractility
Major disorders of peristalsis
Entities not seen in normal subjects No
≥50% ineffective swallows
Yes
Ineffective esophageal motility Fragmented peristalsis
Minor disorders of peristalsis No
Normal motility
Esophageal Center at Northwestern
Kahrilas, et al. Neurogastroenterology and Motility, 2015

18. 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) contractility
Esophageal Center at Northwestern

19. Esophageal manometry – achalasia
Insufficient LES Relaxation
Loss of Esophageal peristalsis
Normal motility
LES Relaxation
Esophageal peristalsis
Swallow
Swallow
100 50
150
mmHg
Time
Time

20. 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) contractility
Effective interventions
Pneumatic dilation
Laparoscopic Heller’s myotomy
POEM (Per-Oral Endoscopic Myotomy)
Botulinum toxin injection
Esophageal Center at Northwestern

21. Achalasia treatment Target: Lower Esophageal Sphincter (LES)
Aim: Relieve esophageal outflow obstruction
Improve esophageal emptying
Improve symptoms
Pneumatic dilation
Heller’s myotomy
With partial fundoplasty
Per-oral endoscopic myotomy (POEM)
Botulinum toxin injection

22. Achalasia treatment Botulinum 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.

23. Pneumatic dilation Achalasia treatment Endoscopic
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 fluoroscopy

24. Laparoscopic Heller’s Myotomy
Achalasia treatment
Laparoscopic Heller’s Myotomy
With Dor Fundoplication (anterior, 1800) or
Toupet fundoplasty (posterior, 2700)
Peters & DeMeester
Minimally Invasive Surgery of the Foregut 1994

25. Per-oral endoscopic myotomy (POEM)
Achalasia treatment
Per-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 completion
Clipping 1 2 3 4 5
Phalanusitthepha, C. et al. Annals of Translational Medicine. 2014; 2(3)

26. Achalasia - subclassification
Abnormal LES relaxation pressure
IRP > upper limit of normal (15 mmHg)
Absent (type I and II) or spastic (type III) contractility
Type 1
Type 2
Type 3 5 10 15 20 25 30 35
Absent peristalsis
No pressurization
Absent peristalsis
Pan-esophageal pressurization
Spastic contraction
Length along the esophagus (cm)
<4.5s
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
Time
Time
Time
100 50
150
mmHg 30

27. Achalasia - subtype implications5 10 15 20 25 30 35
100 50
150
mmHg
Absent peristalsis
No pressurization
Absent peristalsis
Pan-esophageal pressurization
Spastic contraction
Length along the esophagus (cm)
<4.5s
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
Most common
Best response to therapy
Least common
Worst response to therapy

28. Achalasia subtypes - prognosis
Percent with ‘good’ outcome
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%
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)
[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 Kahrilas

29. Achalasia – subtype implications5 10 15 20 25 30 35
100 50
150
mmHg
Absent peristalsis
No pressurization
Absent peristalsis
Pan-esophageal pressurization
Spastic contraction
Length along the esophagus (cm)
<4.5s
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
Abnormal LES relaxation
Median IRP > 15 mmHg
Most common
Best response to therapy
Least common
Worst response to therapy
Myotomy preferred treatment

30. Achalasia treatment: European Achalasia Trial
RCT: Pneumatic dilation vs Laparoscopic Heller’s myotomy
Pneumatic dilation*
Laparoscopic Heller’s myotomy
25% of 96 PD patients had repeat dilation
*+/- repeat dilation
Years since start of study
Moonen, et al. Gut. 2016
Boeckxstaens GE, et al. NEJM 2011:364:

31. 115 consecutive patients (2012-2015) After 15 patient “learning curve”
POEM outcomes
Northwestern experience
115 consecutive patients ( )
After 15 patient “learning curve”
Follow-up at > 1 year
Average 2.4 years, range months
Positive outcome in 92% of patients
Eckardt 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 esophagitis
Hungness, E. et al. Annals of Surgery, 2016; 264(3):

32. Achalasia treatment: POEMA trial
RCT: Pneumatic dilation vs POEM
Abstract: 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%)

33. Esophageal motility disorders: beyond achalasia
Chicago Classification v3.0
LES relaxation
Contractility pattern
Motility diagnosis
Achalasia
Type I: Absent contractility
Type II: Pan-esophageal pressurization
Type III: Spastic
Abnormal IRP?
Yes
100% failed or
≥ 20% premature?
Yes
Disorders with EGJ outflow obstruction No No
EGJ outflow obstruction
Heterogeneous classification
≥ 20% premature,
≥ 20% hypercontractile, or 100% failed?
Yes
Distal esophageal spasm Jackhammer esophagus
Absent contractility
Major disorders of peristalsis
Entities not seen in normal subjects No
≥50% ineffective swallows
Yes
Ineffective esophageal motility Fragmented peristalsis
Minor disorders of peristalsis No
Normal motility
Esophageal Center at Northwestern
Kahrilas, et al. Neurogastroenterology and Motility, 2015

34. 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
IRP 35 mmHg
IRP 32 mmHg
IRP 18 mmHg
Asymptomatic volunteer
IRP 28 mmHg
IRP 22 mmHg
100 50
150
mmHg 30

35. EGJ outflow obstruction
Variable management strategies
Heterogeneous clinically
May represent:
Achalasia variant
Early/“Evolving” achalasia
Subtle mechanical obstruction
Hiatal hernia
Pressure artifact
Vascular or anatomic
Normal motility
Dilation
Pneumatic/Heller/POEM/Botox
GERD; Functional
GERD; HH repair

36. EGJ outflow obstruction?
Supplementary HRM interpretation
Supplementary/Additional Testing
Degree of IRP elevation
Contractile/peristaltic pattern
Elevated intra-bolus pressure
Upright swallows
Normalization of IRP
Esophagram
Timed barium esophagram
Barium tablet
FLIP
Endoscopic ultrasound VG
Vascular signal

37. Esophageal motility disorders: beyond achalasia
Chicago Classification v3.0
LES relaxation
Contractility pattern
Motility diagnosis
Achalasia
Type I: Absent contractility
Type II: Pan-esophageal pressurization
Type III: Spastic
Abnormal IRP?
Yes
100% failed or
≥ 20% premature?
Yes
Disorders with EGJ outflow obstruction No No
EGJ outflow obstruction
Heterogeneous classification
≥ 20% premature,
≥ 20% hypercontractile, or 100% failed?
Yes
Distal esophageal spasm Jackhammer esophagus
Absent contractility
Major disorders of peristalsis
Entities not seen in normal subjects No
≥50% ineffective swallows
Yes
Ineffective esophageal motility Fragmented peristalsis
Minor disorders of peristalsis No
Normal motility
Esophageal Center at Northwestern
Kahrilas, et al. Neurogastroenterology and Motility, 2015

38. Distal esophageal spasm Hypercontractile esophagus
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
DL < 4.5s
IRP < 15 mmHg
DCI > 8000 mmHg-cm-s
IRP < 15 mmHg

39. Absent contractility Consider achalasia Borderline IRP
Failed swallows/absent peristalsis
Normal LES relaxation
Association with connective tissue disease (not diagnostic of CTD)
Consider achalasia
Borderline IRP
Supplementary testing
Management
(if not achalasia)
Dietary modifications
Reflux therapies
IRP < 15 mmHg

40. Esophageal motility disorders: beyond achalasia
Chicago Classification v3.0
LES relaxation
Contractility pattern
Motility diagnosis
Achalasia
Type I: Absent contractility
Type II: Pan-esophageal pressurization
Type III: Spastic
Abnormal IRP?
Yes
100% failed or
≥ 20% premature?
Yes
Disorders with EGJ outflow obstruction No No
EGJ outflow obstruction
Heterogeneous classification
≥ 20% premature,
≥ 20% hypercontractile, or 100% failed?
Yes
Distal esophageal spasm Jackhammer esophagus
Absent contractility
Major disorders of peristalsis
Entities not seen in normal subjects No
≥50% ineffective swallows
Yes
Ineffective esophageal motility Fragmented peristalsis
Minor disorders of peristalsis No
Normal motility
Esophageal Center at Northwestern
Kahrilas, et al. Neurogastroenterology and Motility, 2015

41. Functional dysphagia
Not meeting criteria for a major motility disorder
Consider evaluation for subtle mechanical obstruction
e.g. esophagram with barium tablet
Management
Dietary modifications
Reflux therapies
Empiric dilation
Neuromodulator/cognitive behavioral therapy/hypnosis
Observation and re-evaluation for progression

42. Esophageal Motility Evaluation: HRM
Conclusions
HRM indicated for evaluation of:
non-obstructive dysphagia and
prior to anti-reflux surgery
2. Achalasia:
The esophageal motility disorder
Effective therapeutic options
3. Esophageal motility diagnosis beyond achalasia:
Achalasia-variants?
Clinical, multi-modal diagnostics to direct among varied therapeutic options

43. Acknowledgements Esophageal Center of Northwestern Sandi Jelinek
Clinical Research Team
Sandi Jelinek
Gwen Cassidy
Jackie Prescott
Alex Decorrevont
Francesca Shilati
Melina Masihi
Stephanie Peterson
Joe Triggs
Ryan Campagna
John Pandolfino
Peter Kahrilas
Ikuo Hirano
Nimi Gonsalves
Aziz Aadam
Sri Komanduri
Eric Hungness
Ezra Teitelbaum
Nat Soper
David Odell
Funding sources
NIDDK:
R01 DK (PI: Pandolfino)
R01 DK (PI: Pandolfino)
P01 DK (PI: Pandolfino)

44. Thank You Questions?