New Approaches in Achalasia and Gastroparesis · 2019-02-19 · New Approaches in Achalasia and...
Transcript of New Approaches in Achalasia and Gastroparesis · 2019-02-19 · New Approaches in Achalasia and...
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New Approaches in Achalasia and Gastroparesis
Robert H. Lee, MD, MASClinical Associate Professor of Medicine
Director of GI MotilityH.H. Chao Comprehensive Digestive Disease Center
University of California IrvineCDDC Symposium 2019
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Financial Disclosures
• I have nothing to disclose
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Achalasia and Gastroparesis
• Heterogeneous Disorders
• Diagnostic Pitfalls
• Treatments- Poor medical therapies- Movement toward definitive therapies
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Type I Achalasia
Aperistalsis
Non-Relaxing LES
Median 4s IRP > 10 mmHg** for 10 swallows
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No single swallow with peristaltic activity
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Type II Achalasia
Non-Relaxing LES
Pan-Esophageal Pressurization
Median 4s IRP for 10 swallows > 15 mmHg
PEP seen in ≥ 20% of swallows
No swallows with normal peristalsis
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Type III Achalasia
Incomplete LES
Relaxation
Median 4s IRP > 15 for 10 swallows
DL < 4.5 Sec Spastic contractions in ≥ 20% of swallows
No normal peristalsis
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Functional EGJ Outlet Obstruction (EGJOO)
40% resolve dysphagia spontaneously
1) Perez-Fernandez et al. Neurogastroenterol Motil 2016 2) Hoeij et al. Neurogastroenterol Motil 2015
6% evolve to achalasia over 10 months
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Achalasia Spectrum
Sodikoff et al. Neurogastroenterol Motil 2016
Type I Achalasia Type II Achalasia
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Achalasia Subtypes: Response to Therapy
Pandolfino et al. Gastroenterology 2008
AchalasiaSubtype
Type I (n=16)
Type 2 (n=46)
Type 3 (n=21)
Success with Botox
0% 86% 22%
Success with Dilation
38% 73% 0%
Success with myotomy
67% 100% 0%
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Diagnosis of Achalasia• High Resolution
Esophageal Manometry remains gold standard
• Referral for EM is delayed by mean 4.7 years
• 15% consulted ≥ 5 physicians before diagnosis
Eckardt et al. Dig Dis Sci 1997
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HRM Superior to Standard Manometry
52%
12%
5%
12%7% 7%
4%0%
28% 26%
7%3% 5%
27%
0%3%
0%
10%
20%
30%
40%
50%
60%
No MotilityDisorder
Achalasia EGJOO Non-Specific HypermotilityDisorders
Hypomotility Failure UESDisorders
Prevalence of Motility Disorders Using Standard Manometry (SM) vs High Resolution Manometry (HRM)
SM HRMRoman et al. Am J Gastroenterol 2016
*
* *
*
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Timed Barium Esophagram (TBE)
• Column Ht > 2 cm at 5 min- 85% Sens, 86% Spec for
Achalasia
- Differentiate Achalasia from EGJOO
- Also provides Objective Measurement of Emptying after intervention
1) Neyaz J Neurogastroenterol Motil 2013 2) Vaezi Am J Gastroenterol 1999 3) Blonski Am J Gastroenterol 2018
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EGJ Distensibility in Achalasia
Normal Controls Untreated Achalasia
Rohof et al. Gastroenterology 2012
EGJ Distensibility 6.3 ± 0.7 mm2/ mmHg
EGJ Distensibility 0.7 ±0.9 mm2/ mmHg
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Achalasia with Normally Relaxing EGJ?
• Eckhardt Score ≥ 7• Low or Normal 4s IRP• EGJ-DI 0.8 • Achalasia Treatments improved median
Eckardt to 2Ponds et al. Neurogastroenterol and Motil 2016
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Achalasia Treatments
Temporizing• Medical Therapies- Nitrates, Ca-Blockers,
Peppermint Oil- Ineffective
• Endoscopic- Botox Injection- Pneumatic Dilation
Definitive• Lap Heller Myotomy
• POEM
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POEM Outcomes
97.1%88.5%
82.4%
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
3 months 6 months 12months
Succ
ess
Rat
e (E
ckha
rdt<
3)
Remission Rates After POEM
71%
92%
84%
100% 100%
93%
50%
60%
70%
80%
90%
100%
DysphagiaSolids
DysphagiaLiquids
Heartburn% W
ith S
ympt
om S
core
< 2
LHM vs POEM
Heller POEM
p=0.001
1) Von Renteln et al. Gastroenterology 2013 2) Bhayani et al. Ann Surg 2013
n=70
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POEM After Failed LHM
0%
25%
50%
75%
100%
TechnicalSuccess
Adverse Events SymptomResolution
Prior HM Non-HM
p=0.49
p=0.23
p=0.02
1) Ngamruengphong et al. Clin Gastroenterol and Hepatol 2017 2) Saleh et al. Neurogastroenterol and Motil 2016
• 80% of pts improved w/ POEM• Compare to 57% rate in pts
treated with PD after LHM
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POEM Failure
• 9.8% Failure Rate
• 63% responded to repeat POEM
• 45% to LHM
• 20% to PDVan Hoeij et al. Gastrointest Endosc 2018
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Gastroparesis Subgroups
Diabetic (29%) Post-Surgical (13%) Idiopathic (36%)
• Women
• 86% overlap with Functional Dyspepsia
• Post-Viral
• Vagal Nerve Injury
• Fundoplication
• Roux-En-Y GastroJ
• Women
• > 5 years of Disease
• 5% and 1% incidence in DM1 and DM2
1) Camilleri et al. Am J Gastroenterol 2013 2) Parkman et al. Gastroenterology 2011
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Histology and Etiology of GP
• Diabetic GP- Fewer ganglion Cells- Less dense ganglia than Idiopathic GP
• Response to GES Therapy- Inversely related to ganglia density
Heckert et al. Neurogastroenterol and Motil 2017
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Diagnosis of Gastroparesis
• No obstruction
• Delayed GasticEmptying
- Gastric Scintigraphy- WMC- Spirulina Breath Test
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Common Mistakes with GES• Not done long
enough- 4 hr study- ↑ diagnostic yield by 25%- Correct measure is % retention
• Fails to use correct test meal
- Eggbeaters with jam and toast
1) Guo et al. Dig Dis Sci 2001 2) Abell et al. Am J Gastroenterol 2008
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Wireless Motility Capsule
pH >4 & at least 3 points above baseline by 4 hours
83% Sensitivity and 83% Specificity
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Gastroparesis TreatmentsMedical • Ineffective- TCA’s- Botox
• Problematic- Metoclopramide- Domperidone- Erythromycin
• Symptom Alleviation- Ondasetron
Definitive• Gastric Electrical
Stimulation
• Endoscopic Pyloromyotomy?
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TCA’s for Gastroparesis
Parkman et al. JAMA 2010
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Pyloric Botox Injection
• Open Label Studies
- Benefit in symptoms and GE
• (2) RCT’s- Improvement no
better than placebo1) Camilleri et al. Am J Gastroenterol 2013 2) Friedenburg et al. Am J Gastroenterol 2008 3) Ukleja et al. World J Gastrointest Endosc 2015
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The Problem Drugs• Metoclopramide- 30-50% sx improvement- Tardive Dyskinesia- Long QT- Women, non-diabetics more
likely to have SE
• Domperidone- 40-50% sx improvement- Long QT
• Erythromycin- Improves sx’s and GET- Tachyphylaxis- Long QT- IV > Oral Effectiveness
• Azithromycin- Fewer GI side effects- Long QT
1) Camilleri et al. Am J Gastroenterol 2013 2) Richard et al. Am J Gastroenterol 1993
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Ghrelin Agonists• Stimulates
hunger- ↑ proximal gastric
tone
- Stimulates Phase III MMC’s
- ↑ Gastric Emptying
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Relamorelin
Lembo et al. Gastroenterology 2016
Abdominal Pain Bloating
Nausea Early Satiety
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Gastric Electrical Stimulation (GES)
• High Frequency Low Energy
• Does not alter rate of gastric emptying
• Implanted along greater curve
• Humanitarian Use Protocol
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GES in Gastroparesis
19.5
4.753.82 4.25 4.25
0
5
10
15
20
25
Baseline 1 1/2months
ONPeriod
OFFPeriod
12months
Wee
kly
Vom
iting
Epi
sode
s
GES in Patients with DG
P < 0.001
p=.215
17.25
5.56.38
9.75
2
0
2
4
6
8
10
12
14
16
18
20
Baseline 1 1/2months
ONPeriod
OFFPeriod
12months
Wee
kly
Vom
iting
Epi
sode
s
GES in Patients with IG
p < 0.001
p=0.10
1) McCallum Clin Gastroenterol and Hepatol 2010 2) McCallum Neurogastroenterol and Motil 2013 3) Maranki Dig Dis Sci 2008
Main Predictors of Response:
1) Nausea2) Absence of Narcotic Use3) Diabetic > Idiopathic
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Pyloroplasty: A Definitive Therapy?
• Targets pylorospasm
• Same principles as POEM
Mekaroonkamol Clin Gastroenterol and Hepatol 2019
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G-POEM in Mixed Gastroparesis
0% 25% 50% 75% 100%
Nausea
Vomiting
Abd Pain
Response to G-POEM at 6 months
Resolved Improved but not resolved Unchanged Worse1) Khashab et al. Gastrointest Endosc 2017 2) Gonzalez et al. Aliment Pharmacol and Ther 2017
Predictors of Failure:1)Female Gender2)Diabetic Gastroparesis
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Conclusions: Heterogenous Disorders
• Achalasia - Types I-III and EGJOO- May represent spectrums of same disease
• Gastroparesis- IG, DG, and PSG- May represents separate disease states
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Pitfalls in Diagnosis
• Achalasia- Delays in Manometric Diagnosis- EGJOO and Achalasia with normal
manometric EGJ Relaxation
• Gastroparesis- Incorrect GE Study Protocols
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Less than Optimal Medical Therapies
• Achalasia- Ca channel blockers, nitrates
• Gastroparesis- Botox- Drugs with side effects
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Definitive Treatments
• Achalasia- POEM and LHM
• Gastroparesis- Gastric Electrical Stimulation- Relamorelin?- G-POEM?