Pandolfino Deck LS...Definitive Therapy: • Pneumatic Dilation [30/35/40 mm]] • May start with 35 mm in young males • Routine gastrograffin is not needed • Repeat in 2-4 weeks

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Disclosures: Moderator:

Baharak Moshiree, MD, FACGMedtronic: Grant Funding

Speaker:

John E. Pandolfino, MD, MSCI, FACGMedtronic: Consultant/Speaker/Licensing Agreement: FLIP PanometryDiversatek: Consultant/GrantCrospon: Stock Options

“High‐Resolution Manometry: Thinking beyond the Chicago Classification”

John E. Pandolfino, MD, MSCI, FACGHans Popper Professor of Medicine

Feinberg School of Medicine,

Northwestern University

Chief, Division of Gastroenterology and Hepatology

Northwestern Medicine

Northwestern Memorial Hospital

High‐Resolution Manometry

Content Outline:1. Discuss the protocol beyond the 10 supine swallows required for

high‐level manometry diagnosis.

2. Discuss pitfalls with the current classification diagnoses.

3. Introduce provocative maneuvers.

Objectives:1. To learn how to perform and analyze esophageal motor function

using high resolution manometry.

2. To understand how to use manometry to alter management of patients with esophageal complaints.

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The Chicago Classification

The core of the Chicago Classification is the recognition of EPT patterns and new metrics based on EPT landmarks to better define clinically relevant phenotypes.

• Improved and more accurate metrics• IRP• Integrity • Distal Contractile Integral• Distal Latency• Pressurization

• Provided a universal language and was associated with higher intra‐ and inter‐observer agreement.

Bridging conventional manometry and high‐resolution manometry

0 30 60 90 120 150 180Color Pressure scale (mmHg)

HRM: Chicago Classification Patterns

DES

Absent Contractility

Distal Esophageal Spasm

EGJOONormal

Type I Achalasia

Type IIIAchalasia

Type IIAchalasia

Normal

EGJ Outflow Obstruction• Incompletely expressed achalasia• Mechanical obstruction

Ineffective Motility (IEM)• >50% ineffective swallows Fragmented peristalsis • >50% fragmented swallows and not

meeting criteria for IEM (mean DCI >450 mmHg-s-cm)

Distal esophageal spasm (DES)• ≥ 20% premature contractions

(DL<4.5s)Jackhammer esophagus• ≥ 20% of swallows with DCI >8,000

mmHg-s-cm and normal DL

IRP ≥ upper limit of normal ANDsufficient evidence of peristalsis such that criteria

for type III achalasia are not met

IRP is normal ANDreduced distal latency (DL)

OR DCI > 8,000 mmHg-cm-s

Yes

Yes

Yes

No

No

No

IRP is normal AND> 50% of swallows are ineffective based on DCI

values or large breaks

Achalasia Type I: 100% failed peristalsis [no PEP]Type II: 100% failed peristalsis [+ PEP]Type III: >20% premature contractions

IRP ≥ upper limit of normal AND 100% failed peristalsis or spasm

Yes

No

Chicago Classification 3.0

Disorders of EGJOutflow Obstruction

Major Disorders of Peristalsis• Entities not seen in normal

controls

Minor Disorders of Peristalsis• Impaired bolus clearance

Normal Esophageal Motor Function

Rapid contraction and Hypertensive peristalsis are not considered distinct clinical-pathological entities in CC v3.0

IRP is normal AND> 50% of swallows are effective without criteria

for spasm or jackhammer

IRP is normal AND100% failed peristalsis

Absent Contractility• No scoreable contraction by DCI and DL

criteria (should consider achalasia with borderline IRP and/or bolus pressurization)

Yes

Yes

No

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0

40

mmHg

0

100

50

0

150

mmHg

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UES

EGJ

10 s

EGJ relaxation

CDP

Distal trough

Middle trough

Proximal trough

5 10

0

10

15

20

25

30

5

Line Plots (pressure vs time) of Conventional and High Resolution

Manometry

HRM Plotted in Esophageal Pressure Topography

Time (seconds)

CatheterConfiguration

1st

2nd

3rd

4th LES

Clouse Plots

Standard 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

The Chicago Classification

Not part of 3.0 Classificationbut should be

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Attempt to repositionCan use endoscopic placement if needed

Place catheter and document placement with at least 3 deep breaths

Yes

No

Chicago Classification 3.0 Protocol

No PIP‐ Never entered abdomen

No PIP‐Coiled

Good placement

Attempt to repositionCan use endoscopic placement if needed

Place catheter and document placement with at least 3 deep

breaths

No

Chicago Classification 3.0 Protocol‐ ? 4.0

10 supine swallows

5 upright swallows

2-3 MRS

2 solid swallows

Generates the classic CC 3.0 Diagnosis

Can help with False (+) IRPVascular/contact artifact

Rapid Drink Challenge

May unmask subtle obstruction

Will help refine peristaltic contractile reserve and deglutitive inhibition

Post-prandial mealPrimary regurgitation and belching- achalasia ruled out

Integrated relaxation pressure (IRP)The biggest problem with the Chicago Classification• Measures IBP driving the EGJ open [when it is open] or the LESP [when it is closed].

• Mean of the 4 seconds (contiguous or non‐contiguous) of maximal deglutitive relaxation in the 10s following UES relaxation; referenced to gastric pressure

Length along the esophagus

100

50

0

150

mmHg

10 seconds Gastric

EGJ

IRP 9 mmHgNormal

AchalasiaEGJOO

15 mmHg

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Integrated relaxation pressure (IRP)The biggest problem with the Chicago Classification• Measures IBP driving the EGJ open [when it is open] or the LESP [when it is closed].

• Mean of the 4 seconds (contiguous or non‐contiguous) of maximal deglutitive relaxation in the 10s following UES relaxation; referenced to gastric pressure

Normal

Achalasia

EGJOO

15 mmHg

50%

30 mmHg10 mmHg

A:EGJ Outflow Obstruction C:Type I Achalasia D:Type III achalasiaB:Type II Achalasia


Achalasia Subtypes:Contractile and Pressure Profiles

Achalasia Type I‐ normal IRP

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Achalasia Type I ‐ normal IRP

Achalasia Type II ? III

Achalasia Type II‐

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Achalasia Type III

Achalasia Type III

Symptoms of dysphagia ± chest pain and bland regurgitationGERD symptoms- not responding to PPI therapy

Upper Endoscopy

Mechanical Obstruction/EsophagitisTreat appropriately Normal

Esophageal dilatation, EGJ resistanceRetained food, Diverticulum

High Resolution ManometryTBE and FLIP may be helpful in patients

unable to tolerate HRM

Inconclusive DiagnosisEGJOO or absent contractility

Achalasia I or II Achalasia III

Confirmatory Testing with

TBE and/or FLIP to confirm

diagnosis before offering

definitive therapy

Definitive Therapy• Tailored myotomy

via POEM or tailored Heller myotomy

Definitive Therapy: • Pneumatic Dilation [30/35/40 mm]]

• May start with 35 mm in young males• Routine gastrograffin is not needed• Repeat in 2-4 weeks if no response

• Lap Heller Myotomy • Recommend Dor or Toupet fundoplication]

• POEM• Standard myotomy length• All patients discharged with PPI therapy

Patients unfit for definitive therapy:• BoTox• Smooth muscle

relaxants

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Intact Peristalsis Weaker Peristalsis Type II Achalasia

EGJOO: Epidemiology and Natural History

EGJOO: Relevance• EGJOO‐ natural history

• Many patients may improve and the factors that predict symptom persistence was predicted by maximum distal contractile integral (DCI) and IRP in both EGJOO and HE (P<.05).

Schupack et al. NGM, Volume: 29, Issue: 10, Pages: 1-9.

•EGJOO‐ not always achalasia in evolution• Can be an artifact‐ Fake

• Too reliant on IRP • Can be mechanical obstruction or an anatomical issue

• Missed on EGD

Need supportive evidence• HRIM

• elevated upright IRP and IBP, abnormal motility, paradoxical response to CCK

• FLIP• EGJ‐DI < 2.0, absent contractility or RRCs

• TBE• Barium tablet/retention

EGJOO: Relevance

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Upright Integrated Relaxation Pressure Facilitates

Characterization of EGJOO: Triggs et al 2019

RAD‐EGJOO No RAD‐EGJOO

Upright IRP > 12

46 91

Upright IRP <12

1 17

Metrics• RDC‐IRP: > 12 mmHg with achalasia, > 8 mmHg for EGJOO• 6/199 [IEM/NL]‐ positive with > 8mmHg• 3/34 [aperistalsis]‐ positive with > 12mmHg• 22/23 [EGJOO‐upright > 15 mmHg]‐ positive with > 8mmHg

• 10/209 [IEM/Nls]– failure of deglutitive inhibition• 11/17 [Jackhammer/Spasm] – failure of deglutitive inhibition

Validation of RDC with normative ranges: Ang et al 2017

Validation of Standard test meal in Healthy Controls with Dysphagia Patients: Ang et al 2017

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EGD‐ No FLIP access

yesEsophagitis LA B or higher, stricture, EoE or other mechanical obstruction

Hiatus hernia > 3 cm

HRIM using stepwise assessment and provocative testing to assess

EGJOO

• Treat appropriately using antisecretory therapy and dilation therapy as needed.

• Perform biopsies to assess EoE if suggestive and ? tumor

yes • May require surgery• will need preop w/u motility and potentially reflux testing

no

10 Supine swallows/10 Upright swallows

yesTBE with tablet

• Likely artefact‐ treat conservatively

Abnormal MRS [IRP > 8 mmHg], RDC [IRP > 12 mmHg] and

Test Meal‐200 gms Rice [IRP > 25mmHg]

Type I, II and III Achalasia• Treat appropriately based on subtype

IRP elevated + Normal or Borderline Peristalsis

no

no Negative Retention of barium and Tablet

Positive Retention of barium and Tablet

Positive Retention of Tablet/no barium

Achalasia TXBoTox/ PD

Repeat EGD with stepwise Dilation

Approach to Dysphagia, Chest Pain, Food Impaction

CC 3.0 Diagnosis of EGJOO in a Patient with Dysphagia, Chest Pain, Food Impaction

IRP ≥ upper limit of normal AND sufficient evidence of peristalsis such that criteria for type III achalasia are not met

Presumed – NEGATIVE EGD- NO previous surgery or hernia

ArtifactNL IBP and evidence of

poor emptying is typically related to IEM and not elevated IBP

Evolving AchalasiaSub-threshold PEP,

compartmentalized IBP and evidence of poor emptying

Mechanical ObstructionSub-threshold PEP,

compartmentalized IBP and evidence of poor emptying

• Resolves with position change• MRS,RDC and STM –Negative

Confirmatory Testing not needed.

Definitive Therapy: • Pneumatic Dilation [30/35/40 mm]

• May attempt TTS before• POEM• ? BoTox if unfit for surgery and/or there are

contraindications

• Usually will not resolve with position change.

• MRS, RDC and STM –typically positive

Confirmatory Testing• TBE – negative for barium and positive

for tablet retention.• EGJ-DI on FLIP < 3.0 and fixed

obstruction may suggest mechanical obstruction.

• Usually will not resolve with position change.• MRS, RDC and STM –typically positive

Confirmatory Testing• TBE – Positive for barium and positive for

tablet retention.• EGJ-DI on FLIP < 3.0, no fixed obstruction +/-

abnormal response to volumetric contraction.

Therapy: • Behavioral Therapy or

neuromodulator• Consider w/u for GERD

Definitive Therapy: • TTS Balloon or Savary Dilation• ? BoTox if no response to dilation

Distal latency and Distal Contractile Integral

LES

UES

Length along the esophagus

100

50

0

150

mmHg

• Deglutitive inhibition of esophageal contraction

• Contractile Vigor

Distal latency 7 seconds

IRP → Normal (9.3)DCI → Elevated (14500)CFV → Normal (4.5)IBP → Normal (14.6)IBC → Intact

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Distal Esophageal SpasmDefining Relevant Phenotypes

Pandolfino JE, et al. Gastroenterology 2011

Leng

th a

long

the

eso

phag

us (

cm)

100

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mmHg

30

10

Le

ng

th a

lon

g th

e e

sop

ha

gu

s (c

m)

30

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15

1

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Rapid Premature Contraction

DL = 4.4 s

CFV = 6 cm/s

2 s

Time (s)

3.0 cm

Bolus Escape

30 cm/s

DL = 3.0 s

CFV = 45 cm/s

2 s

Time (s)

15 cm/s

3 cm/s

1 cm/s

2 cm/sDL = 7.0 s

CFV = 15 cm/s

5.5 cm

Premature Contraction Rapid Contraction

2 s

Time (s)


A: Jackhammerstandard swallow‐ no pain

B: Jackhammer‐ Normalprotocol swallow + sildenafil

C: Jackhammer‐Spasmduring chest pain event

D: Jackhammer‐Absent ContractilityAfter POEM

Jackhammer EsophagusEvolution and Treatment

A)Nutcracker: A single-peak jackhammer swallow with normalized POSP-CI (composite DCI=15237 mmHg-cm-s), the POSP-CI/PREP-CI ratio was 1.56.

B)Jackhammer: A multiple-peak jackhammer swallow with prolonged POSP-CI (composite DCI=16502 mmHg-cm-s), the POSP-CI/PREP-CI ratio was 2.93 .

Hypercontractile Esophagus: Heterogeneous Patterns

Xiao et al. Neurogastroenterol Motil. 2018 May;30(5):e13262

Nutcracker JackhammerNormal

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Step 1: Assess the severity of the motility disturbance

Approach to patient with: Jackhammer or Spasm

• Number of abnormal swallows• Pattern‐ repetitive peaks/ abnormal morphology• High DCI• Evidence of EGJOO• Abnormal MRS

Step 2: Assess context in terms of presentation and anatomy

• GERD versus Dysphagia• Hiatus hernia• Endoscopic evidence of obstruction• Opioid use

Step 3: Consider further diagnostics

• GERD dominant‐ BID PPI trial‐ Reflux testing• Dysphagia

• [IRP‐ NL]‐ Esophagram with barium Tablet• [IRP‐ Inc]‐ FLIP‐ 322

• Dilation • EUS with deep muscle biopsy

Step 4: Medical Management

Approach to patient with: Jackhammer or Spasm

• Levsin• CCB/ Nitrates

•Viagra• BoTox• TCA‐ if considering functional overlap

Step 5: POEM • LAST RESORT‐ NEED TO HAVE OBSTRUCTION

Khasab et al. Endosc Int. Open. 2018 Aug;6(8):E1031-E1036. doi: 10.1055/a-0625-6288.

Ineffective Esophageal MotilityAssessing Integrity and Contractile Vigor

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Quantifying Bolus retention beyond IBHEsophageal Impedance Integral

Complete Emptying

Z1 Z2

11.4s

8.5s

4.2s

Before emptying

Z1

Z2

Bolus Escape

Bolus Retained

8.3s

12.3s

6.7s

K Ohms

Z1Z2

Z2

Before emptying

Emptying Bolus Retained

10.8s

7.7s

4.3s

Before emptying

During emptying

Normal swallow Retrograde escape Failed

Table. Antidepressants With the Best Evidence to SupportTheir Use in a Specific Esophageal Disorder With a Functional Component

Esophageal disorder Medication Class DoseFunctional chest pain Imipramine TCA 25–50 mga

Sertraline SSRI 50–200 mga

Venlafaxine SNRI 75 mg

Hypersensitive esophagus Citalopram SSRI 20 mg

Refractory GERD Fluoxetine SSRI 20 mg

Globus Amitriptyline TCA 25 mg

*GERD, gastroesophageal reflux disease; SNRI, serotonin‐norepinephrine reuptake inhibitors.aEscalating dose.

Editorial‐ CGH 2014: Maradey‐Romero & Fass

Neuromodulation and Behavioral InterventionMEDS- NOT FDA APPROVED

Upper Endoscopy

Obstructive process: ring, stricture, etc.

NormalEsophageal dilatation

EGJ resistanceRetained foodDiverticulumHigh Resolution Manometry

*FLIP™ panometry may be helpful when manometry

is technically difficult to perform

Absent Contractility+

IRP < 14

-Scleroderma pattern or achalasia

•EGD with FLIP™ panometry or TBE with Barium tablet to rule out obstructive process.

•Negative FLIP™ panometry /TBE

-Treat GERD-Alter Diet/meds

Hypercontractility+

IRP < 14

-Jackhammer

•EGD with FLIP™ panometry or TBE with Barium tablet to rule out obstructive process•-Try SMR-No response to meds-POEM

Absent Contractility+

IRP > 20

•Type I achalasia

•No further testing.•-PD/POEM

PEP+

IRP > 20

•Type II Achalasia

•No further testing-PD/POEM

DES+

IRP > 20

•Type III Achalasia, opioids.

•Worst treatment response

-Tailored POEM

Normal/Borderline+

IRP > 20

•EGJOO

•EGD ± FLIP™ panometry or EUS to rule out obstructive process.

•Also schedule TBE•FLIP abnl•Dilation•Botox

-FLIP™ panometrynormal-Artifact- follow conservatively.

Chicago Classification DiagnosisBased on body pattern and IRP

IRP -14- 20 mmHg + AC, PEP, JH, BL, NL –FLIP or TBE with Barium tablet may be helpful

Utilizing HRM/EPT in the Management of Dysphagia

Spasm+

IRP < 14

-Spasm

-No further testing-Try SMR-No response to meds-POEM

Normal/Borderline+

IRP < 14

-IEM/Normal

•Likely associated with underlying GERD and visceral hypersensitivity

•Tx GERD•Neuromodulators and CBT/HYP

•Alter diet/ meds

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Approach to patient with: Regurgitation

Refractory Regurgitation may be reflux:But it may also be:

1. Achalasia

• Most common presentation of achalasia is GER.

2. Rumination

• Should be at the top of your differential.

3. Belching disorder

• Patients have a hard time describing.

tLESR

LES relaxation and

crural inhibition

Liquid reflux

NU IRB

Rumination # 1 HRM only

Increased IGP pressure

Liquid reflux

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NU IRB

Supragastric Belching

No LES relaxation

Air reflux

SummaryThe Chicago Classification is not perfect.• Achalasia classification good and there are some subtle issues.

• EGJOO should never be diagnosed with manometry alone as most are normal.

• Jackhammer is a heterogeneous disorder and should be further phenotyped as most are not a primary motor abnormality.

• Weak peristalsis is a borderline motor disorder but should not be forgotten.

• There are other patterns of motility occurring between and after swallows that may be important.

Questions?Moderator:

Baharak Moshiree, MD, FACG

Speaker:

John E. Pandolfino, MD, MSCI, FACG

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Documents

Pandolfino Deck LS...Definitive Therapy: • Pneumatic Dilation [30/35/40 mm]] • May start with 35 mm in young males • Routine gastrograffin is not needed • Repeat in 2-4 weeks