Esophageal Motility Disorders - American College of...

Peter J. Kahrilas, MD, FACG

Esophageal Motility DisordersCurrent classification and treatment

Peter J. Kahrilas, M.D.Peter J. Kahrilas, M.D.,,Northwestern Northwestern UniversityUniversityChicago, USAChicago, USA

Bredenoord AJ et al, Neurogastroenterol Motil 2012;24(suppl 1):57-65EMD #68 v5/15/13 PJK

ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology

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Normal Esophageal MotilityPressure topography plot with key metrics

Swallow

P

DCDPLatency

DL>4 5s

Distal contractile IntegralDCI<8,000 mmHg-s-cm

EPT #35 v7/10/13 PJK

DDL>4.5s

IRP windowIRP<15 mmHg

Interpreting Clinical EPT StudiesThe tools of analysis

• IRP (Integrated Relaxation Pressure)– The best validated metric of deglutitive relaxationThe best validated metric of deglutitive relaxation– Advantages of a sleeve-type recording– Accounts for both nadir and persistence of relaxation

CCL #10a v4-18-10 PJK


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hagu

s (c

m)

0

5

10

EGJ relaxation (IRP calculation)

Leng

th a

long

the

esop

h

15

20

25

30

2 s

EGJ

eSleevedomain

0

30

015

eSleevePressureIntra-gastricPressure

35

1.6 mmHg

CCL #13 v4-30-12 PJK

IRP = mean of red fill

Deglutitive EGJ Relaxation MeasuresSensitivity in detecting achalasia

False -Achalasia sensitivity ( 2)EGJ relaxation measure False (n=62)EGJ relaxation measure

3%97%4s Integrated Relaxation Pressure (<15 mmHg )

31%69%High resolution nadir

(<10 mmHg)

48%52%Single sensor nadir

(<7 mmHg )

EPT #8 v1/29/11 PJK

Pressure (<15 mmHg )

Ghosh SK et al. Am J Physiol 2007;293:G878


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Fitting Chicago Classification to EPT StudiesHierarchical analysis

Probably AchalasiaIRP ≥15 mmHg & absent peristalsis

Yes Achalasiao Type I: classic o Type II: with esophageal compression 1o Type III: spastic

CCL #11 v1-25-11 PJK

Achalasia Subtypes

100

150

mmHg

Type I (classic)

h l

0

5

10

15

20

cm

30 mmHgPanesophageal pressurization Type II

(achalasia i h

50

0

30

achalasia

IRP= 22.3 mmHg

5 s

30 mmHg IBC25

30

35

IRP= 28.9 mmHg5 s

with compression)

30 mmHg IBC

SPV plot

300 mmHg0

5

1030 mmHg

SPV plot

150 mmHg

Kahrilas PJ et al, Gastroenterology 2013;In PressEMD #69 v7/9/13 PJK

Type III (spastic) achalasia

IRP= 52.3 mmHg5 s

Distal latency =

2.5 s

15

20

25

30

35

IRP= 28 mmHg5 s

Compartmentalized pressurization

30 mmHg IBC ‘type IV’

EGJ outflow

obstruction


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Achalasia treatment outcome by EPT subtypeType I (classic), Type II (pressurization), Type III (spastic)

Publication N, (Rx type) Type I Type II Type IIIPercent with ‘good’ outcome

Publication N, (Rx type) Type I Type II Type IIIPandolfino 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 86% (PD) 100% (PD) 40% (PD)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)

EMD #61 v3/19/13 PJK

[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; epub ahead of print

150

mmHg0

5

Pre-myotomy

UES

Pre and Post-treatment esophageal pressure topography in achalasia

Post-myotomy

100

50

30

5

10

15

20

25

30

Length along the

esophagus (cm)

UES

EGJ

Pan-esophageal pressurization

Peristaltic remnant

Proximal break

Distal break

035

5 s

EMD #57 v3/31/13 PJK Roman S, et al. JAMA Surg 2013;148(2):157-64

Type II achalasia

5 s

Weak peristalsis


5


UES 150

mmHg0

5

Pre-myotomy


Post-myotomy

UES

100

50

30

5

10

15

20

25

30

Length along the

esophagus (cm)

EGJ

Peristaltic remnant

Proximal break

Distal break

Pan-esophageal pressurization

Early latency (spastic)

contraction

DL= 2.1 s

035

5 s


Type III (spastic) achalasia

5 s

Distal esophageal spasm


Post-treatment pattern

EGJ outflow obstruction

Type I achalasia

4

6

8

10

12

14

16

82

5

2

1

1

1

2

2

Number of

patients

Type I achalasia

Premature contraction

Frequent failed peristalsis

Weak peristalsis

Absent peristalsis

0

2

Type 1 Type 2 Type 3

3111

Pre-treatment achalasia subtype



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Evolution of achalasia over a 2-year period, Myenteric plexus inflammation at LES

2006 2007 2008

EMD #60 v12/10/12 PJK

Finally treated with laparoscopic Heller myotomy

Evolution of achalasia over a 2-year period, Myenteric plexus inflammation at LES

2006 2007 2008

Intact Peristalsis

Weak Peristalsis

Type II Achalasia

EMD #60 v12/10/12 PJK

Finally treated with laparoscopic Heller myotomy


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Achalasia TreatmentsGeneral principles

• Early treatment is desirable– Prevents disease progression and complications

• Dysphagia responds to Rx better than chest painDysphagia responds to Rx better than chest pain• Botox can be a useful temporizing measure

– Doubt in diagnosis– Elderly, frail patient

• Pneumatic dilation and LHM are both highly effective and highly operator dependent procedures– Leverage regional expertise

EMD #12 v4/4/11 PJK

– Comparative data from the literature are not necessarily locally or even regionally applicable

• Peroral Endoscopic Myotomy (POEM) is a promising new technique

Botox®Know when to say, “when”

EMD #29 v7/5/10 PJK


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Pneumatic Dilators used for Treating Achalasia

Microvasive® Rigiflex Dilator (3.0, 3.5, or 4.0 cm)

EMD #8 v12/10/12 PJK

g ( , , )Passed over guidewire, imaged with fluoroscopy

Microvasive™ Pneumatic Dilation35 mm dilator

EMD #9a v2/20/10 PJK


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“W i ” l i“Waist” locating the LES

EMD #9b v2/20/10 PJK


Eff t fEffacement of “Waist”

EMD #9c v2/20/10 PJK


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Achalasia TreatmentsPneumatic dilation

• 1% perforation risk

DisadvantagesAdvantages

• Outpatient procedurerequiring surgical repair

• Less efficacious than myotomy

• Less predictable than myotomyM d 2 3

p p• Can repeat• Can be long-term

solution• Halts disease

progression

EMD #11c v12/10/12 PJK

• May need 2 or even 3 successive dilations

progression• Rare post-Rx reflux

Mucosa throughMucosa throughmyotomymyotomy

Laparoscopic Heller Myotomy with DorFundoplication

EsophagusEsophagus

EMD #10 v2/20/10 PJKPeters & DeMeester

Minimally Invasive Surgery of the Foregut 1994

Right crus ofRight crus ofdiaphragmdiaphragm


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Achalasia TreatmentsLaparoscopic Heller myotomy

• Usually requires


• The most effective hospitalization

• 1% perforation risk requiring intervention

• Operative morbidity and mortality

• Expensive

treatment• The most definitive

treatment• Halts disease

progression

EMD #11d v12/10/12 PJK

p• Post-Rx reflux in > 50%

p g

Success rates of pneumatic dilation and laparoscopic Heller myotomy

The European Achalasia Trial, 2 year results

Heller myotomy (n=97)

Pneumatic dilation (n=78)

Successful treatment (%) 97% 78%

Eckardt score 1.1 ± 0.1 1.3 ± 0.1

LES pressure (mmHg) 14 ± 1 12 ± 1

Timed barium swallow (cm) 3.4 ± 0.6 4.8 ± 0.7

Boeckxstaens GE, et al. NEJM 2011:364:1807-1816EMD #43 v1/25/11 PJK


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Complication rates of pneumatic dilation and laparoscopic Heller myotomy for achalasia

Northwestern experience 2000-2011 (n=463 patients)

Lynch KL et al. Am J Gastroenterol 2012;107:1817-25EMD #42 v9/18/12 PJK

Relationship between series size and perforation rate for (modern) pneumatic dilation in achalasia

Funnel plot

U d ll 35 dil ti

Number of patients in series (n)

100

200

300

400

Northwestern experience

Used all 35 mm dilations

European Achalasia trial

With the first

Procedural esophageal perforations (%)

0

EMD #55 v1/25/13 PJK Lynch KL et al. Am J Gastroenterol 2012;107:1817-25

0 1 2 3 4 5 6

With the first 13 cases (7.2%)


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Per-Oral Esophagomyotomy (POEM）Novel alternative to LHM or PD for achalasia

……laparoscopic Heller-Dor myotomy still requires 5 abdominal skin incisions for trocar placement. Pasricha initially reported a method of submucosal endoscopic myotomy with no skin incision in an experimental model [1]. Subsequently, Inoue modified the technique and applied it clinically…[2].

１. Pasricha, et al. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy 2007;39(9):761-4.

2. Inoue H, et al. First clinical experience of submucosal endoscopic myotomy foresophageal achalasia with no skin incision. Gastrointest Endosc 2009;69:A122

EMD #34 v7/21/10 PJK

POEM (1) Enter into the submucosa in the mid esophagus

mucosal layer

View through transparent distal cap on endoscope

Triangle tip knife

EMD #35a v7/21/10 PJK Courtesy of H. Inoue

endoscope


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POEM (2) Creation of submucosaltunnel ≈ half esophageal circumference

palisade vessels

mucosal layer

EMD #35b v7/21/10 PJK Courtesy of H. Inoue

POEM (3) Myotomy begun ≈ 3 cm distal to entry, ≈ 7 cm above EGJ

EMD #35c v7/21/10 PJK Courtesy of H. Inoue


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POEM (3) Myotomy completion

EMD #35d v7/21/10 PJK Courtesy of H. Inoue

POEM (4) Clipping

EMD #35e v7/21/10 PJK Courtesy of H. Inoue


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Achalasia TreatmentsPer-Oral Endoscopic Myotomy (POEM)

• New


• Incisionless (NOTES)• Learning curve situation • Limited data on

morbidity, mortality, post-op reflux

• Long term?

( )• Surgical efficacy

without surgical morbidity

• (Should) halt disease progression

EMD #11d v12/10/12 PJK

Long term?p g• Potential to ‘customize’



Yes1

o Type I achalasia: classic o Type II achalasia: with esophageal

compression o Type III achalasia: (includes spastic)

Major motor disorderIRP ≥15 mmHg OR absent peristalsis OR reduced latency OR DCI >8,000

mmHg-s-cm

No, but…

2

CCL #11 v11-14-11 PJK


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Yes1




mmHg-s-cm

No, but…

2

Absent peristalsisDistal esophageal spasmo Pseudorelaxation?o Spastic achalasia with low LESP?EGJ outflow obstructiono may be an achalasia variant Hypercontractile (Jackhammer)

esophagus

Yes

CCL #11 v11-14-11 PJK

esophagus

Latency vs contraction velocity as criterion for DESLatency is a much more specific abnormality

mmHg

0

0.2

Normalized length

along the esophagus

CDP

2

0.4

0.6

0.8 CDP

Distal contraction latency

50th and 95th percentile of normal

for latency

CDP

Propagation velocity = 15 cm/sDistal contraction latency (DL) = 7.0 s

EPT #30 4/4/11 PJK Roman S, et al. Am J Gastroenterol 2011;106:443

8

10 5 10 15 20

Time (s)


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Phenotypes of rapid propagationRefining the diagnosis of DES

Rapid Contraction Weak Contraction

0150

100

5015 cm/s

3 cm/s 1

cm/s

27.0 s

15 cm/s

5.9 s

0

5

10

15

20

25

5.5 cm5.5 cm

-25 cm/s

EPT #32 v1/30/12 PJK

mmHg

02 cm/s 0.5

cm/s

7.0 s

2 s

Time (s)

0.5 cm/s 2 s

Time (s)

30

35

Pandolfino JE, et al. Gastroenterology 2011;141:469

Latency vs contraction velocity as criterion for DESLatency is a much more specific abnormality

mmHg

0

00.2

0.4

0.6

0

Normalized length

along the esophagus

50th and 95th percentile of normal

for latency

Distal contraction latency

0 5 10 15 20

0.8

1

Propagation velocity = 25 cm/sDistal contraction latency (DL) = 3.0 s

EPT #29 4/4/11 PJK Roman S, et al. Am J Gastroenterol 2011;106:443

CDP


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1070 consecutive patients with clinical EPT studies

91 Patients with rapid propagation

Premature Contractions (n=24)[Distal latency < 4.5 s]

Rapid Contractions (n=67)[CFV > 9 cm/s / normal latency]

6

18 39

27

4

14

Spastic achalasiaDES

18 4

Weak peristalsis – segmental contractionFunctional EGJ obstructionWeak peristalsisHypertensive peristalsisNormal

EPT #31 1/25/11 PJK

Jackhammer esophagus (DCI>8,000 mmHg-s-cm)Repetitive contractions not synchronized with respiration

0

5cm)

mmHg

100

50

200

20

DCI = 12,957 mmHg-s-cm

5

10

15

20

25ong

the

esop

hagu

s (c

150

0

mmHg

020

Time (s)

25

30

35

Leng

th a

lo

0 10 20 30

EPT #35 v1/30/12 PJK Roman S, et al. Am J Gastroenterol 2012;107:37


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Phosphodiesterase type 5 inhibitors for EMDBackground

• Sildenafil potentiates the activity of endogenous NO by inhibiting an enzyme (PDE type V) that catalyzesby inhibiting an enzyme (PDE-type V) that catalyzes the second messenger (cGMP) mediating NO action

• Reduces esophageal contractile amplitude for several hours

• Less consistent effect on peristaltic propagationP i ll f l f EMD i h h ili• Potentially useful for EMD with hypercontractility

EMD #37 v7/21/10 PJK

Rhee PL, et al. Am J Gastroenterol 2001;96:3251-7Bortolotti M, et al. Dig Dis Sci 2001;46:2301-6

Eherer AJ, et al. Gut 2002;50:758-64Lee JI, et al. Neurogastroenterol Motil 2003;15:617-23

Agrawal A, et al. Dig Dis Sci 2005;50:2059-62

Phosphodiesterase type 5 inhibitors for EMDCase reports with EPT

45 minutes post-sildenafil 25 mg

Fox M, et al. Neurogastroenterol Motil 2007;19:798-803

Pre-sildenafilSevere swallow-related chest pain

50 minutes post-sildenafil, solid challenge

EMD #38 v7/21/10 PJK


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Phosphodiesterase type 5 inhibitors for EMDCase reports with EPT

Fox M, et al. Neurogastroenterol Motil 2007;19:798-803

Pre-sildenafilSevere dysphagia and chest pain

Solid swallow challenge

EMD #39 v7/21/10 PJK

45 minutes post-sildenafil 25 mgReduced dysphagia, no chest pain



Yes1




mmHg-s-cm

No, but…

2


esophagus

Yes

CCL #11 v11-14-11 PJK

Not major motor disorderBut… Peristaltic abnormalities

No

3

esophagus


22




Yes1




mmHg-s-cm

No, but…

2


esophagus

Yes

CCL #11 v3-2-12 PJK

esophagus

Not major motor disorderBut… Peristaltic abnormalities

No

3

No

Weak peristalsiso with large or small 20 mmHg

isobaric contour breaksFrequent failed peristalsisHypertensive peristalsis

(nutcracker esophagus)Rapid contraction

Normal

Yes

Esophageal Motility: Impact of HRM/EPTCirca 2013

• EPT has clarified the diagnosis of achalasia and defined criteria for EGJ outflow obstruction as a distinct diagnosis

• Spasm remains difficult, but EPT may sort out subsets of reduced-latency and hypercontractileconditions amenable to specific therapies

• EPT findings should be prioritized: 1) impaired EGJ relaxation, 2) reduced latency contractions, 3) extreme hypo- or hypercontractility, 4) then….


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Esophageal Motor Disorders, What’s New?Treatment

• POEM (per-oral endoscopic myotomy) is potentially superior to existing achalasia treatmentssuperior to existing achalasia treatments

• Phosphodiesterase-type 5 inhibitors are potentially useful to treat hypercontractile EMD

EMD #40 v7/10/13 PJK


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