Detection and Treatment of - etouches...Detection and Treatment of ... Sano Classification IIIb...
Transcript of Detection and Treatment of - etouches...Detection and Treatment of ... Sano Classification IIIb...
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Detection and Treatment of Upper GI Dysplasia
Kenneth K. Wang, MDVan Cleve Professor of Gastroenterology
ResearchDirector Advanced Endoscopy Group
Mayo Clinic, Rochester, MN
Aims
• Understand terminology regarding lesion description
• Identification of dysplastic tissue on magnification
• Describe the new imaging devices
• Understand the application of radiofrequency ablation
• Describe the role of cryotherapy for dysplasia
Case 1
• A 59 year old white male was found to have Barrett’s esophagus after an investigation for anemia 3 years ago
• The segment is described as C3M4
• On surveillance biopsy, a 4 mm lesion described as a Paris IIa lesion is seen with Sano Classification IIIb mucosal appearance
• Biopsies showed adenocarcinoma, moderately differentiated
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What Will You Absolutely Need for this Procedure ?
1. A high resolution white light endoscope
2. A endoscope with high resolution as well as narrow band imaging and autofluorescence
Best Imaging
• Careful observation: Time spent examination
– Polyps
– Dysplasia in Barrett’s
• High resolution white light endoscopy
• Describe lesions carefully
What Does Paris IIa Mean ?
1. A flat lesion that has no noticeable borders that are elevated or depressed beyond 2 mm
2. A lesion that is elevated but less than the width of a closed biopsy forceps
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Paris Classification
Paris Classification: Is
Is : >2.5mm(sessile) 2.5 mm
Biopsy forceps
Paris Classification:: IIa +IIc
IIa+c : Elevated at the edges And depressed centrally
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Modified Sano’s classification
Endoscopic View
How Would You Image this Cancer ?
1. Wide field imaging: NBI, chromoendoscopy
2. Point imaging
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Techniques
• Wide Field Imaging
– Low Tech: Chromoendoscopy
– Higher Tech: Narrow Band Imaging, Autofluorescence Imaging
– Highest Tech: Volume Laser Endomicrosocpy
• Point Imaging:
– High Tech: Confocal laser endomicroscopy, optical coherence tomography
– Spectroscopic techniques
Indigo Carmine 0.2%, 60 cc
Non-dysplastic Barrett’s oesophagus
Regular mucosal pattern
Regular vascular pattern
High-grade Dysplasia
Irregular mucosal pattern
Irregular vascular pattern
Abnormal blood vessels
Kara et al. Gastrointest. Endosc, 2006Yamashina, Dig Endosc. 25 Suppl 2:173-6, 2013
Narrow Band Imaging
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Narrow Band Imaging for DysplasiaStudy Pt #
(HGD/Total)
Sensitivity Specificity
Sharma
2006
7 / 51 100% 98.7%
Kara
(AFI+NBI)
2006
14 / 20 96% 93%
Sharma
2013
14/113 53%* 100%
Giachino(AFI+NBI)
2013
14/42 71% 46%
* For dysplasia
Would You Apply Confocal Laser Endomicroscopy ?
1. Yes
2. No
Probe‐Based Confocal Laser Endomicroscopy
Confocal laser probe
– passed through anyendoscope
Laser scanning unit
– frame rate of 12 images/sec
Control and acquisition software
– real‐time image reconstruction
IV Fluorescein Contrast
Mauna Kea Technologies-Cellvizio
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Endoscopic MicroscopySystems
Confocal
Endoscope
Confocal
Probe
Instrument Dedicated Endoscope
Probe via
any Endoscope
Contrast IV: Fluorescein
Topical: acriflavin, cresyl violet
IV: Fluorescein
Magnification 700-1000x 750x
Image depth 250 microns 70 microns
Resolution 1 micron 1.2 microns
Frame Rate 0.8/sec 12/sec
Schema of Endomicroscopy250µm
7µm
Optical Resolution, lateral 1µm5 ml fluorescein (10% )
Acriflavine 0.05%
Miami Classification
Non dysplastic BE ‐ Uniform villiform architecture‐ Columnar cells (block arrow)‐ Dark “goblet” cells (thin arrow)
Dysplastic BE‐ Villiform structures‐ Dark, irregularly thickened epithelialborders (arrow)
‐ Dilated irregular vessels (block arrow)
Wallace MB et al Endoscopy 2011
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Miami Classification
Adenocarcinoma‐ Disorganized/loss of villiform structure and crypts
‐ Dark columnar cells (thin arrow)‐ Dilated irregular vessels (block arrow)
Accuracy of pCLE for High Grade Dysplasia
• 296 biopsy sites from 38 patients– 95 used to establish criteria (testing set)– 201 used to validate criteria– Images read blinded by 2 MD
per bx per patient
• Sensitivity 80% 58%• Specificity 94% 75%• PPV 44%• NPV 99% 92%
• Kappa 0.6 (“good” agreement)
Pohl, H et al. Gut 2008;57:1648‐1653
pCLE for BE Surveillance – Interobserver Agreement
• Blinded review of pCLE videos by 11 experts in BE imaging• 40 videos (20 – 30 sec)• Criteria proposed by Pohl et al• Training set (20 videos – 10 HGD/EC and 10 no IEN)• Validation set ( 20 videos – 11 HGD/EC and 9 no IEN)
pCLE ExperiencedObservers (N = 4)
pCLE Inexperienced observer (N = 7)
Sensitivity 91% 87%
Specificity 100% 94%
Accuracy 95% 90%
Agreement 92% 82%
Kappa (95% CI) 0.83 (0.64 – 1.00) 0.64 (0.48 – 0.80)
Wallace MB et al. Gastrointest Endosc 2010
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pCLE versus eCLE for Dysplasia Classification
• 16 eCLE stacks (depth imaging) compared with video pCLE
Leggett, DDW 2013
100% 100%
94%
75%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
eCLE pCLE
Dysplasia Detection Rate Diagnostic Accuracy
Volumetric Laser Endomicroscopy
Volumetric Laser Endomicroscopy
Mucosa
Submucosa
Muscularis mucosa
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Volumetric Laser Endomicroscopy
• Detection of dysplasia in 22 EMR specimens
• VLE versus eCLE
75
80
85
90
95
100Dysplasia Detection Rate (%
)
VLE CLE
Leggett, DDW 2013
Molecular Probes
Images
• In vitro imaging with peptide• Rapid binding• Specific binding to Barrett’s flat dysplasia (C.
Piraka, DDW 2013)
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Light-tissue interactionsLight-tissue interactions
ScatteringScattering
ReflectionReflection Incident lightIncident light
FluorescenceFluorescence
Absorption
Low‐Coherence Enhanced Backscattering Spectroscopy
Clin Cancer Res. 2009 May 1;15(9):3110-7
LEBS
• Nanoscale disruptions in cells nearby cancers (Cancer Res. 2009 Jul 1;69(13):5357‐63)
• Sensitivity of 100%, specificity of 80%, and AUC= 0.895 for colon polyps (rectal biopsy) (Cancer Res. 2009 May 15;69(10):4476‐83)
• AUC for colon polyps using microvascular markers was 0.82 in 157 patients with 17 advanced adenomas (Roy, DDW 2013)
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Advanced Technology
“One Should Use New Therapy Quickly While It Still Works”
Sir William Osler
Case 2
• 72 year old white male with 3 year history of abdominal pain, unresponsive to PPI
• Pain is epigastric, appears to be relieved with eating
• No weight loss
Endoscopy
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Should We Perform Surveillance ?
1. Yes
2. No
Gastric Cancer• Male predominant disease 1.6:1
• 21,320 will be diagnosed in 2012 in US– 10,540 will die (49%)
• Decreasing over last decades (1.5% per decade)
SEER database, seer.cancer.gov
Pathway to Gastric Cancer
Correa, Cancer Res 1992, 52(24):6735‐40.
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Detection of Intestinal Metaplasia with Methylene Blue
• Methylene blue with magnification can identify patterns associated with metaplastictissue (Dinis‐Ribeiro et al, Gastrointestinal Endoscopy 57:498–504, 2003)
Round tubular pattern, IM Irregular pattern
Indigo Carmine
• Indigo carmine has been shown to enhance detection of depressed and flat gastric lesions (Kawahara, Digestive Endoscopy 21:14–19, 2009)
• Intraobserver agreement between observers of pit patterns using indigo carmine is excellent (kappa=0.86) (Dinis‐Ribeiro Gastrointest Endosc
57:498–504, 2003)
• Detect the presence of intestinal metaplasia in the gastric cardia (Guelrud, Amer J Gastro 97, 584–589, 2002)
NBI Classification Mucosa of Gastric Polyps
Omori et al. BMC Gastroenterology 2012, 12:17
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NBI Classification of Capillary Pattern Gastric Polyps
Classification of Gastric PolypsPolyp Classification Fundic gland Hyperplastic Adenoma
Small round pattern ++++ + +
Prolonged pattern ‐ +++ +
Villous or ridged + +++ +++
Honeycomb ++++ + ‐
Dense vascular ‐ ++++ +
Core vascular + + +++
Fine network,unclear
‐ ‐ +
Indigo Carmine
• Type 1 patterns, regular = normal gastric mucosa
• Type 2: Round pits and villi = intestinal metaplasia
• Type 3 = Loss of pattern, dysplasia
Dinis‐Ribeiro Gastrointest Endosc 57:498–504, 2003
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Indigo Carmine (0.4%) and Surface Enhancement
Endoscope Confocal Laser Endomicroscopy
• N=31 males
• Adenoma accuracy: 94%
• Adenocarcinoma: 95%
Jeon, Gastrointestinal Endoscopy, 74:781‐783, 2011
Intestinal metaplasia and gastric cancer.
Goetz M , Kiesslich R Am J Physiol Gastrointest Liver Physiol 2010;298:G797-G806
©2010 by American Physiological Society
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Sampling Protocols
• Devries et al 2010: 12 non‐targeted biopsies and additional biopsies of any lesions– Primarily found in incisura
– Second most common antrum
– Third was less curve
• A protocol of 7 biopsies found 97% of IM/dysplasia– 3 antrum
– 1 incisura
– 3 body (1 greater, 2 lesser curve)
Management of BE
Resect the Neoplastic Lesion
Eradicate the Remaining BE
Manage Complications and Recurrences
EMR Changes Diagnosis in Visible and Flat Dysplasia
• Multicenter US study
• 148 patients with HGD/ Cancer
• 24% without visible lesions
10%
31%
41% 40%43%
0%
10%
20%
30%
40%
50%
Upstaging Downstaging OverallChange
Visible lesionspresent
Visible lesionsabsent
Wani S et al. DDS 2013
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RadiofrequencyEradication
CircumferentialFocal
A Randomized, Multicenter, Sham Controlled Trial of RF Ablation
• 128 patients with BE and dysplasia (LGD/HGD)• Mean BE length 5 cm; 12 month follow up
Shaheen N et al. NEJM 2009
6.0%3.6% 2.4%1.7% 3.6%
0.9%0%
20%
40%
60%
80%
100%
Any RFA Procedure Primary RFAProcedure
Secondary RFAProcedure
% Incidenceper Patient
% Incidenceper Procedure
Stricture Occurrence
• 5 Strictures in 84 patients
– 5 of 84 patients (6.0%)
– 5 of 297 cases (1.7%)
• All strictures resolved with mean of 2 dilations
• All patients now complete response for IM (CR‐IM)
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Eradication of all BE by EMR
• 49 patients with HGD/ Cancer
• Average length: 3.2 cms
• 106 EMR procedures
Chennat J et al. Am J Gastroenterol 2009
ESD vs EMR
EMR‐Cap ESD p
En‐bloc resection None (1‐11 pieces) 96% <0.0001
Surface resected (mm2) 1488 (185‐3194) 2453 (600‐5400) <0.01
Proc time (min) 61 (20‐130) 154 (64‐334) <0.001
Device costs (€) 264 (60‐515) 486 (247‐1019) <0.001
Deprez et al. GIE 2010
R0 24%
CE Neoplasia 100% 100% NS
CE‐IM 84 84 NS
Perforations 1 2
Strictures 20% 44%
• 50 patients (25 each with ESD and EMR)• HGD 25; Cancer 25• Average extent: C2M5
Cryotherapy HGD
• N=98 with HGD
• 333 treatments cryotherapy
• Complications
– Strictures 3%
– Pain 2%
– No perforations
Gastrointest Endosc 2010;71:680‐5N=60, completed Rx
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PDT
Absolute Risk Reduction: 45% versus 69%Number Needed to Treat Versus RFA: 1.5 versus 2.2
Strictures versus RFA: 36% versus 6%
Endoscope
Fiber OpticGuide
High‐GradeDysplasia
LaserLight
CenteringBalloon
Long term RFA results
86
95 96
77
93 91
0
25
50
75
100
1 year 2 years 3 years
Dysplasia
Barrett's
Recurrence Rates
Study Patient Number Recurrence %
Pech 2008 337 21.5%
Baddredine 2010 172 17%
Shaheen 2010 99 25%
Gupta 2013 592 16%
Ginsberg 2013 156 42%
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What Else Determines Ablation Success
37 BE patients underwent RFA
Complete eradication60% (n=22)
Incomplete eradication 40% (n=15)
PredictorsBE lengthHernia
Frequency of reflux
Krishnan K et al. Gastroenterology 2012
Post Ablation Follow up
• Every 3 months X 4
• 6 months x 2
• Then yearly
Barrett’s Esophagus Treatment Algorithm
Barrett’s Esophagus with dysplasia
Mucosal Abnormality: EMR
Flat Mucosa, No Cancer
Ablative Therapy
Cancer found, Assess Margins, lymphovascularinvasion, Differentiation,
Ulceration
Flat Mucosa
Ablative Therapy
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Summary• Describe Barrett’s esophagus lesions
carefully• Chromoendoscopy and narrow band
imaging can increase recognition of mucosal and vascular patterns
• pCLE and VLE have a role in further defining BE lesions
• Mucosal resection techniques can be used for any mucosal abnormalities
• Complete eradication of all BE should be performed using RFA
• Post-ablation requires careful vigilence