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Updates in esophageal motility testingDiagnosis and Management of GERD, Motility and GI Functional DisordersNovember 18, 2017
Dustin Carlson, MD, MSCIAssistant Professor of Medicine - GastroenterologyNorthwestern UniversityNorthwestern Medicine
Esophageal manometry
Time
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150mmHg
Time
Conventional manometryLine tracings
High-resolution manometryEsophageal pressure topography
Swallow Swallow
High-resolution manometry: esophageal pressure topography
UES
EGJ
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 metricsLe
ngth
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e es
opha
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10 seconds Gastric
EGJ
IRP 9 mmHg
Distal latency
LES
UES
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• Deglutitive inhibition of esophageal contraction• Time from swallow onset (UES relaxation) to contractile deceleration point (CDP)
HRM/EPT metrics
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Distal latency 7 seconds
Contractile deceleration point
LES
UES
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• Inflection point along the 30mmHg isobaric contour (or pressure greater than intrabolus pressure if compartmentalized pressurization) at which propagation slows
• Within 3-cm of EGJ
30
EGJ
Contractile velocity
LES
UES
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• Rate of contractile propagation• Assessment of simultaneous contractions• Essentially replaced by distal latency
HRM/EPT metrics
Spasm: premature vs rapid contractions
Pandolfino et al, Gastroenterology. 2011 141: 469-475
Distal contractile integral (DCI)
LES
UES
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• Contractile vigor• Pressure amplitude x duration x length of distal esophageal contraction, i.e.
transition zone to proximal margin of EGJ
HRM/EPT metrics
20
HRM/EPT interpretation caveats
• Affect manometric pressure:− Patient position−Bolus size−Bolus consistency−HRM assembly
• Normal/abnormal values to follow represent Sierra-vintage assemblies (Medtronic)
• 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 surgery•Reflux esophagitis
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. 2008 103(1): 627-35
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
Baseline recording• Absence of swallows• Quiet breathing• 30-120 seconds
• Deep breaths
100
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150mmHg
20
•Accentuates pressure-inversion point•Confirm trans-hiatal catheter positioning
Basal EGJ pressure
30s
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
Stepwise HRM interpretationChicago Classification v3.0
Interpretation of esophageal manometryChicago Classification v3.0
Yes Yes
No
AchalasiaType I: Absent contractilityType II: Pan-esophageal pressurizationType III: Spastic• ≥ 20% premature swallows (low DL)
EGJ outflow obstruction• May represent evolving achalasia or mechanical obstruction
No
Yes
No
Ineffective esophageal motility (IEM)• ≥50% ineffective swallows
Normal motility
Yes
No
Abnormal IRP? 100% failed or ≥ 20% premature?
≥50% ineffective swallows
≥ 20% premature, ≥ 20% hypercontractile,
or 100% failed?
Distal esophageal spasm (DES)• ≥ 20% premature swallows (low DL)
Jackhammer esophagus• ≥ 20% swallows with hypercontractile swallows (high DCI)
Absent contractility• 100% failed swallows• Consider achalasia
EGJ outflow obstruction?
Major disorders of peristalsis?
Entities not seen in normal subjects
Minor disorders of peristalsis?
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)Pandolfino et al, Amer J Gastroenterology. 2008 103(1): 627-35
HRM/EPT metricsSummary
HRM metric HRM abnormal threshold
Associated disorder
Integrated relaxation pressure (IRP)
>15 mmHg(median)
AchalasiaEGJ outflow obstruction
Distal latency < 4.5 seconds Spasm
Distal contractile integral (DCI)
>8000 mmHg-cm-s
<450 mmHg-s-cm
HypercontractileHypocontractile
Interpretation of esophageal manometryChicago Classification v3.0
Yes Yes
No
AchalasiaType I: Absent contractilityType II: Pan-esophageal pressurizationType III: Spastic• ≥ 20% premature swallows (low DL)
EGJ outflow obstruction• May represent evolving achalasia or mechanical obstruction
No
Yes
No
Ineffective esophageal motility (IEM)• ≥50% ineffective (i.e. weak or failed) swallows
Fragmented peristalsis• ≥50% fragmented swallows
Normal motility
Yes
No
Abnormal IRP? 100% failed or ≥ 20% premature?
≥50% weak, failed, or fragmented swallows
≥ 20% premature, ≥ 20% hypercontractile,
or 100% failed?
Distal esophageal spasm (DES)• ≥ 20% premature swallows (low DL)
Jackhammer esophagus• ≥ 20% hypercontractile swallows (high DCI)
Absent contractility• 100% failed swallows• Consider achalasia
EGJ outflow obstruction?
Major disorders of peristalsis?
Entities not seen in normal subjects
Minor disorders of peristalsis?
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
Leng
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m)
•Absent peristalsis
•No pressurization
Abnormal LES relaxationMedian IRP > 15 mmHg
0
5
10
15
20
25
30
35
Achalasia• 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 3Type 2Type 1
Abnormal LES relaxationMedian IRP > 15 mmHg
Abnormal LES relaxationMedian IRP > 15 mmHg
•<4.5s
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mmHg30
Achalasia subtypes
EarlyType II or III
EGJOO
LateType I
ChronicType II I
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•Absent peristalsis
•No pressurization
Abnormal LES relaxationMedian IRP > 15 mmHg
0
5
10
15
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30
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Achalasia - subtype implications
•Absent peristalsis•Pan-esophageal pressurization •Spastic
contraction
Type 3Type 2Type 1
Abnormal LES relaxationMedian IRP > 15 mmHg
Abnormal LES relaxationMedian IRP > 15 mmHg
•<4.5s
•Most common•Best response to therapy
•Least common•Worst response to therapy
Achalasia subtypes - prognosis
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(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 Kahrilas
100
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150mmHg
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the
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hagu
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m)
•Absent peristalsis
•No pressurization
Abnormal LES relaxationMedian IRP > 15 mmHg
0
5
10
15
20
25
30
35
Achalasia – subtype implications
•Absent peristalsis•Pan-esophageal pressurization •Spastic
contraction
Type 3Type 2Type 1
Abnormal LES relaxationMedian IRP > 15 mmHg
Abnormal LES relaxationMedian IRP > 15 mmHg
•<4.5s
•Most common•Best response to therapy
•Least common•Worst response to therapy
•Myotomy preferred treatment
Achalasia treatment
• Pharmacologic (off-label uses)− Calcium channel antagonists− Nitrates− Anti-cholinergic− Phosphodiesterase 5 inhibitors
• Botulinum toxin injection-----
•Pneumatic dilation•Heller’s myotomy−With partial fundoplasty
•Per-oral endoscopic myotomy (POEM)
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.
Achalasia treatment
Pneumatic dilation− 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
Achalasia treatment
Laparoscopic Heller’s Myotomy− With Dor Fundoplication (anterior, 1800) or − Toupet fundoplasty (posterior, 2700)
Peters & DeMeesterMinimally Invasive Surgery of the Foregut 1994
Achalasia treatment: European Achalasia Trial
Years since start of studyMoonen, 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 dilation
Achalasia treatmentPer-oral endoscopic myotomy (POEM)1) Enter into the submucosa in the mid esophagus2) Creation of submucosal tunnel ≈ half esophageal circumference3) Myotomy begun ≈ 3 cm distal to entry, ≈ 7 cm above EGJ4) Myotomy completion5) Clipping
Phalanusitthepha, C. et al. Annals of Translational Medicine. 2014; 2(3)
1 2 3 4 5
POEM outcomes
•115 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 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
Northwestern experience
Hungness, E. et al. Annals of Surgery, 2016; 264(3): 508-17
Achalasia treatment: POEMA trial
• Abstract: DDW 2017• 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 POEM
Secondary achalasia• Malignant pseudoachalasia− Gastric adenocarcinoma; metastatic lung, liver, pancreas− Paraneoplastic – rare− Clinical risk factors:
•older age (>60 yrs)•short symptom duration (< 1 year)•weight loss•EGJ appearance
•Evaluation:−Endoscopic ultrasound−CT
Ponds, FA. et al. Aliment Pharmacol Ther. 2017; 45(11)
Yes Yes
No
AchalasiaType I: Absent contractilityType II: Pan-esophageal pressurizationType III: Spastic• ≥ 20% premature swallows (low DL)
EGJ outflow obstruction• May represent evolving achalasia or mechanical obstruction
No
Yes
No
Ineffective esophageal motility (IEM)• ≥50% ineffective (i.e. weak or failed) swallows
Fragmented peristalsis• ≥50% fragmented swallows
Normal motility
Yes
No
Abnormal IRP? 100% failed or ≥ 20% premature?
≥50% weak, failed, or fragmented swallows
≥ 20% premature, ≥ 20% hypercontractile,
or 100% failed?
Distal esophageal spasm (DES)• ≥ 20% premature swallows (low DL)
Jackhammer esophagus• ≥ 20% hypercontractile swallows (high DCI)
Absent contractility• 100% failed swallows• Consider achalasia
EGJ outflow obstruction?
Major disorders of peristalsis?
Entities not seen in normal subjects
Minor disorders of peristalsis?
Esophageal motility disordersChicago Classification v3.0
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
EGJ outflow obstruction
• 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
Distal latency 8s
DCI 900 mmHg-s-cm
100500 150
mmHg30
EGJ outflow obstruction
• “Real” EGJOO?• HRM:− Degree of IRP elevation
• 15-mmHg IRP = 95th percentile of asymptomatic controls
EGJ outflow obstruction
• “Real” EGJOO?• HRM:− Degree of IRP elevation− Contractile/peristaltic pattern
7s
IRP 28 mmHg IRP 18 mmHg
DCI 9000mmHg-cm-s
5s
100500 150
mmHg30
IRP 32 mmHg
DCI 215mmHg-cm-s
6s
EGJ outflow obstruction
• “Real” EGJOO?• HRM:− Degree of IRP elevation− Contractile/peristaltic pattern− Elevated intra-bolus pressure
• Compartmentalized pressurizationIRP 32 mmHg
100500 150
mmHg30
IRP 35 mmHg
7s
DCI 4000mmHg-s-cm
IRP 30 mmHg
8s
DCI 900 mmHg-s-cm
EGJ outflow obstruction
• “Real” EGJOO?• HRM:− Degree of IRP elevation− Contractile/peristaltic pattern− Elevated intra-bolus pressure − Upright swallows
• Normalization of IRP• < 12 mmHg
IRP 23 mmHg
100500 150
mmHg30
IRP 5 mmHg
UPRIGHT
SUPINE
EGJ outflow obstruction
• “Real” EGJOO?• HRM:− Degree of IRP elevation− Contractile/peristaltic pattern− Elevated intra-bolus pressure − Upright swallows
• Normalization of IRP
• Supplementary testing− Esophagram
•Timed barium esophagram•Barium tablet
− EndoFLIP®− Endoscopic ultrasound
100500 150
mmHg30
Yes Yes
No
AchalasiaType I: Absent contractilityType II: Pan-esophageal pressurizationType III: Spastic• ≥ 20% premature swallows (low DL)
EGJ outflow obstruction• May represent evolving achalasia or mechanical obstruction
No
Yes
No
Ineffective esophageal motility (IEM)• ≥50% ineffective (i.e. weak or failed) swallows
Fragmented peristalsis• ≥50% fragmented swallows
Normal motility
Yes
No
Abnormal IRP? 100% failed or ≥ 20% premature?
≥50% weak, failed, or fragmented swallows
≥ 20% premature, ≥ 20% hypercontractile,
or 100% failed?
Distal esophageal spasm (DES)• ≥ 20% premature swallows (low DL)
Jackhammer esophagus• ≥ 20% hypercontractile swallows (high DCI)
Absent contractility• 100% failed swallows• Consider achalasia
EGJ outflow obstruction?
Major disorders of peristalsis?
Entities not seen in normal subjects
Minor disorders of peristalsis?
Esophageal motility disorders
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
Chicago Classification v3.0
Distal esophageal spasm
• Rare• Premature contractions• Simultaneous contractions• Normal LES relaxation• Achalasia variant?
IRP < 15 mmHg
Distal latency < 4.5s
Yes Yes
No
AchalasiaType I: Absent contractilityType II: Pan-esophageal pressurizationType III: Spastic• ≥ 20% premature swallows (low DL)
EGJ outflow obstruction• May represent evolving achalasia or mechanical obstruction
No
Yes
No
Ineffective esophageal motility (IEM)• ≥50% ineffective (i.e. weak or failed) swallows
Fragmented peristalsis• ≥50% fragmented swallows
Normal motility
Yes
No
Abnormal IRP? 100% failed or ≥ 20% premature?
≥50% weak, failed, or fragmented swallows
≥ 20% premature, ≥ 20% hypercontractile,
or 100% failed?
Distal esophageal spasm (DES)• ≥ 20% premature swallows (low DL)
Jackhammer esophagus• ≥ 20% hypercontractile swallows (high DCI)
Absent contractility• 100% failed swallows• Consider achalasia
EGJ outflow obstruction?
Major disorders of peristalsis?
Entities not seen in normal subjects
Minor disorders of peristalsis?
Esophageal motility disorders
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
Chicago Classification v3.0
Hypercontractile esophagus
• Jackhammer esophagus− DCI > 8,000 mmHg-cm-s
• +/- Normal LES relaxation• Secondary manifestation?• Achalasia variant?
IRP < 15 mmHg
Distal contractile integral > 8000 mmHg-cm-s
Management of spastic esophageal motility disorders
• Type III achalasia• Distal esophageal spasm• Hypercontractile esophagus
• LES +/- extended myotomy− POEM
• Botulinum toxin injection• Pharmacologic agents (**off label use)− Smooth muscle relaxants
• CCB• Nitrates• Anti-cholinergics• PDE5-inhibitors
− Secondary manifestation?• Treat underlying cause
− Trazodone− TCAs - amitriptyline
Yes Yes
No
AchalasiaType I: Absent contractilityType II: Pan-esophageal pressurizationType III: Spastic• ≥ 20% premature swallows (low DL)
EGJ outflow obstruction• May represent evolving achalasia or mechanical obstruction
No
Yes
No
Ineffective esophageal motility (IEM)• ≥50% ineffective (i.e. weak or failed) swallows
Fragmented peristalsis• ≥50% fragmented swallows
Normal motility
Yes
No
Abnormal IRP? 100% failed or ≥ 20% premature?
≥50% weak, failed, or fragmented swallows
≥ 20% premature, ≥ 20% hypercontractile,
or 100% failed?
Distal esophageal spasm (DES)• ≥ 20% premature swallows (low DL)
Jackhammer esophagus• ≥ 20% hypercontractile swallows (high DCI)
Absent contractility• 100% failed swallows• Consider achalasia
EGJ outflow obstruction?
Major disorders of peristalsis?
Entities not seen in normal subjects
Minor disorders of peristalsis?
Esophageal motility disorders
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
Chicago Classification v3.0
Absent contractility
• Failed swallows/absent peristalsis• Normal LES relaxation• Association with connective
tissue disease (not diagnostic of CTD)
• Consider achalasia• Borderline IRP
• Management− Dietary modifications− Reflux therapies
IRP < 15 mmHg
Yes Yes
No
AchalasiaType I: Absent contractilityType II: Pan-esophageal pressurizationType III: Spastic• ≥ 20% premature swallows (low DL)
EGJ outflow obstruction• May represent evolving achalasia or mechanical obstruction
No
Yes
No
Ineffective esophageal motility (IEM)• ≥50% ineffective (i.e. weak or failed) swallows
Fragmented peristalsis• ≥50% fragmented swallows
Normal motility
Yes
No
Abnormal IRP? 100% failed or ≥ 20% premature?
≥50% weak, failed, or fragmented swallows
≥ 20% premature, ≥ 20% hypercontractile,
or 100% failed?
Distal esophageal spasm (DES)• ≥ 20% premature swallows (low DL)
Jackhammer esophagus• ≥ 20% hypercontractile swallows (high DCI)
Absent contractility• 100% failed swallows• Consider achalasia
EGJ outflow obstruction?
Major disorders of peristalsis?
Entities not seen in normal subjects
Minor disorders of peristalsis?
Chicago Classification v3.0Esophageal motility disorders
Kahrilas, et al. Neurogastroenterology and Motility. 2015; 27(2)
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
HRM beyond the Chicago Classification
• 10 supine, 5-ml liquid swallows− Basis for Chicago Classification of esophageal motility diagnoses
• Supplementary maneuvers− Upright, 5-ml liquid swallows− Multiple rapid swallows (2ml liquid x 5 q2-3 seconds)− Viscous swallows− Solid swallows− 200 ml free drink− Test meal +/- post-prandial monitoring
• High-resolution impedance manometry (HRIM)
High-resolution IMPEDANCE manometry
• Bolus clearance/transit− Complete/incomplete
• Automated impedance analysis− Pressure-flow metrics
• Bolus flow time− Measures esophageal emptying
• Esophageal impedance integral ratio− Measure bolus retention
• Impedance bolus height− 200 ml drink− Measures esophageal retention
• Akin to TBE 100500 150
mmHg
Bolus presentBolus absent
30
Post-prandial studies
• For regurgitation and belching +/- PPI-unresponsive reflux symptoms• Protocol:− High-resolution impedance manometry− Swallow protocol (to exclude achalasia)− Refluxogenic meal (patient choice)− Monitor for 60-90 minutes after meal
• Annotated symptomatic events•Interpretation:−Transient LES relaxations: GERD−Rumination−Supra-gastric belching
1. Increase in gastric pressure
− > 30 mmHg2. Followed by retrograde
flow of gastric contents3. Increase in intra-
esophageal pressure4. Relaxation of UES
Rumination
100500 150
mmHg30
3s
Supragastric belching
3s
1. Negative intra-thoracic pressure2. UES relaxation3. Antegrade air flow (impedance increase)4. Retrograde air flow5. May be repetitive
Post-prandial HRIM
• 94 patients with PPI-non-responsive symptoms
−20% rumination (+/- TLESRs)
−42% supragastric belching (+/- TLESRs)
−14% GERD (TLESRs only)−24% “normal”
• Implications:−Management of rumination and supragastric belches
with behavioral therapies−Direct TLESR inhibitors use?
Yadlapati, R. et al. Clin Gastroentol Hepatol. 2017; epub Sept 12.
Thank You
Questions?• [email protected]