Transcript No Slide Title

Detection & Endotherapy of
Barrett’s HGD & Early
Adenocarcinoma: The Paradigm
Shift
Gary W. Falk, M.D., M.S.
Professor of Medicine
Hospital of the University of
Pennsylvania
Learning Objectives
• HGD-a historical perspective
• Current data on optimal imaging
for detection of early neoplasia
• Current data on therapy of early
neoplasia
Learning Objectives
• HGD-a historical perspective
• Current data on optimal imaging
for detection of early neoplasia
• Current data on therapy of early
neoplasia
The Problem
HGD
Intramucosal Ca
From Namasivayam V et al. Clin Gastroenterol Hepatol 2010;8:743-54.
HGD: The Old
• 0-70% risk of unsuspected cancer
at esophagectomy
• Debates centered on surgery vs.
continued surveillance
• PDT and APC problematic as
alternative treatment strategies
Surgery for Esophageal Cancer
• Technically demanding even in low
risk patients
• Problematic in high risk patients
• Operative mortality
• 5-10% in low volume centers
• 0-2.5% for HGD/early cancer in expert
hands
Surgery for Esophageal Cancer
• Morbidity 30-50%
• 34% complication rate at Mayo Clinic*
–Anastomotic leaks
–Anastomotic strictures
–Cardiopulmonary
–Jejunostomy leaks
• Prolonged recovery + impaired /QOL for
1st year
*Prasad G et al.
Gastroenterology 2009;137:815-23.
Operative Mortality In Surgical Series of
Patients With HGD or Early Adenocarcinoma
From Bennett C et al. Gastroenterology 2012;143:336-46.
Risk of Lymph Node Metastases In HGD
or Intramucosal Ca: Systematic Review
Lesion
HGD
Intramucosal
Carcinoma
Lymph Node
Metastases
0
1.93%
95% CI
1.19-2.66
Note esophagectomy mortality > 2% + morbidity
From Dunbar KB et al. Am J Gastroenterol 2012;107:850-62.
Long Term Survival Endoscopic Vs.
Surgical Treatment of HGD
•EMR preop
•Note 13%
unsuspected
Ca @ surgery
From Prasad GA et al. Gastroenterology 2007;132:1226-33.
Management Of HGD:
BADCAT Consensus
• Endoscopic therapy for HGD
is preferred to surgery or
surveillance
From Bennett C et al. Gastroenterology 2012;143:336-46.
Learning Objectives
• HGD-a historical perspective
• Current data on optimal imaging
for detection of early neoplasia
• Current data on therapy of early
neoplasia
Surveillance of Barrett’s Esophagus: White
Light Endoscopy
White Light Endoscopy
• Standard resolution
• 100,000-300,000 pixels
• High resolution/high definition
• 600,000-1,000,000 pixels
• TV Monitors
• Standard-480 lines
• HD-1080 lines
From Hassan MK & Wallace. ASGE Clinical Update 2009;16:1-4.
Methods of Detection of
Dysplastic Barrett’s Esophagus
High
Resolution
WLE
Acetic acid
Indigo
Carmine
NBI
From Curvers W et al. Gastroenterology 2008;134:670-9.
Methods of Detection of Dysplastic
Barrett’s Esophagus
• Enhanced imaging techniques preferred:
• Image quality
• Mucosal imaging
• Vascular imaging
• Enhanced imaging techniques did not improve:
• Interobserver agreement for mucosal morphology
vs. WLE
• Yield for dysplasia/carcinoma vs. WLE
From Curvers W et al. Gastroenterology 2008;134:670-9.
Dysplasia Detection:
The Challenge
• Most patients never develop
dysplasia
• To detect 1 cancer will need to survey
200 average risk patients
• Dysplasia & early cancer may be flat
with no obvious endoscopic
abnormality
Adherence to Seattle Biopsy Protocol
In Community Setting By Segment
Length
From Abrams JA et al. Clin Gastro Hepatol 2009;7:736-42.
Adherence To Seattle Protocol
Increases Dysplasia Detection
From Abrams JA et al. Clin Gastroenterol Hepatol 2009;7:736-42.
Inspection Time > 1 Minute
Enhances Detection of HGD/Ca
From Gupta N et al. Gastrointest Endosc 2012;76:531-8.
Correlation Between Inspection
Time & Detection of HGD/Ca
From Gupta N et al. Gastrointest Endosc 2012;76:531-8.
Hemisphere Distribution of Early
Cancer in Barrett’s Esophagus.
From Enestvedt BK et al. Gastrointest Endosc 2013;78:462-7.
Barrett’s Imaging 2014
Detection Essentials
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.
Barrett’s Imaging 2014
Detection Essentials
• Clean mucosa
• Carefully inspect with HDWLE for subtle
surface irregularities
• Vary insufflation & desufflation
• Inspect distal segment in retrograde view
• Add cap?
• Look longer & biopsy less
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.
Enhancements To Endoscopic
Imaging
• Chromoendoscopy
• Magnification
endoscopy
• Narrow band imaging
• Photodynamic
diagnosis
• Spectroscopy
• Partial wave
spectroscopy
• Polarized scanning
spectroscopy
• Optical coherence
tomography
• Low coherence
interferometry
• Autofluorescence
endoscopy
• Confocal endomicroscopy
• Molecular imaging
Barrett’s Imaging 2014
Detection Essentials
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.
Contrast Enhancement
• Optical
• Narrow band imaging
– Illuminates tissue with special filters
• Electronic post processing
• Fuji intelligent chromoendoscopy (FICE)
• I-Scan
• Bottom line: image enhancement of
mucosal microvasculature
Esophageal Surface Patterns With NBI
Circular
mucosal
Irregular mucosal
Ridged/villous
mucosal
Regular vascular
Absent
mucosal
Irregular vascular
From Sharma P et al. Gut 2013;62:15-21.
Crossover Study of HD White
Light Endoscopy Vs. NBI
IM detection
Neoplasia
detection [pt]
Visible lesions
Any dysplasia
lesion
HDWLE
92%
9 (7%)
NBI
92%
12 (9%)
P-value
NS
NS
22 (17%)
11 (4.9%)
< 0.01
67 (21%)
81 (30%)
0.001
From Sharma P et al. Gut 2013;62:15-21.
Crossover Study of HD White
Light Endoscopy Vs. NBI
• All areas of HGD/Ca had irregular
mucosal/vascular pattern
• No areas with regular
mucosal/vascular pattern had
HGD/Ca
From Sharma P et al. Gut 2013;62:15-21.
Barrett’s Imaging 2014
Confocal Endomicroscopy
• High quality images challenging to
obtain
• Expensive
• Need for fluorescein
• Relevance of real time decision
making questionable
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.
Volumetric Laser
Endomicroscopy
Volumetric Laser
Endomicroscopy
•
•
•
•
OCT technique
7-10 um resolution
In vivo 3D views of the esophagus
Wide field imaging technique with
ability to visualize deeper mucosa
• Now with marking laser for tissue
acquisition
Volumetric Laser
Endomicroscopy System
From Suter MJ et al. Gastrointest Endosc 2014 epub ahead of print
Volumetric Laser
Endomicroscopy: Laser Markings
From Suter MJ et al. Gastrointest Endosc 2014 epub ahead of print
Volumetric Laser Endomicrosopy:
Detection of Subsquamous Cancer After
Ablation Ex Vivo
From Leggett C et al. Am J Gastroenterol 2014;109:298.
AGA Technical Review: Advanced Imaging
Techniques & Dysplasia Detection
• Unclear that any advanced imaging
techniques provide additional
clinically important information
beyond that available by high
resolution white light endoscopy
From Spechler SJ et al. Gastroenterology 2011;140:e18-52.
Learning Objectives
• HGD-a historical perspective
• Current data on optimal imaging
for detection of early neoplasia
• Current data on therapy of early
neoplasia
BADCAT International Consensus For
Management of Early Stage Adenocarcinoma
• Endoscopic therapy preferred to surveillance of
most patients with HGD
• EMR of mucosal lesions followed by ablation of
remaining at risk mucosa
• Endoscopic therapy preferred to surgery of
most patients with HGD
•
•
•
•
Low risk of lymph node metastases
Lower morbidity
Higher recurrence rate
Surgery remains an option if fails
From Bennett C et al. Gastroenterology 2012;143:336-46.
EMR Changes Diagnosis in HGD
& Early Adenocarcinoma
From Moss A et al. Am J Gastroenterol 2010;105:1276-83.
EMR Changes Diagnosis in HGD &
Early Adenocarcinoma
From Moss A et al. Am J Gastroenterol 2010;105:1276-83.
Safety of EMR in Barrett’s
Esophagus at Mayo Clinic
• N=681 patients undergoing 2,513
resections
• Cap technique-77%
• Band snare-18%
• Complications
• Perforation-0%
• Bleeding-1.2%
• Strictures-1%
From Tomizawa Y et al. Am J Gastroenterol 2013;108:1440-47.
Factors Associated With
Recurrence After EMR of Early
Barrett’s Cancer (HGD/IMC)
From Pech O et al. Gut 2008;57:1200-6.
Radiofrequency Ablation
Radiofrequency Ablation of Barrett’s
Esophagus With High Grade Dysplasia
From Shaheen NJ et al. NEJM 2009;360:2277-88.
RFA of Barrett’s Esophagus With High
Grade Dysplasia: Histological Progression
From Shaheen N et al. NEJM 2009; 2009;360:2277-88.
RCT Of Stepwise Radical EMR Vs. EMR +
RFA for HGD/Early Adenoca in Barrett’s
< 5 cm
SRER (N=25)
100%
92%
EMR + RFA (N=22)
96%
96%
Sessions to CR
Total sessions
Acute
complications
2 [IQR 1-3]
6 [IQR 3-9]*
24%
3 [IQR 3-4]
3 [IQR 3-4]
14%
Strictures
88%*
14%
CR HGD/Ca
CR IM
From Van Vilsteren FG et al. Gut 2011;60:765-73.
AIM Dysplasia Trial: Durability of Epithelial
Reversion Including Retreatment
Year 2
Year 3
All patients
CE-D
CE-IM
101/106 99/106
(95%)
(93%)
55/56
(98%)
LGD
HGD
CE-D CE-IM CE-D CE-IM
51/52 51/52 50/54 48/54
(98%) (98%) (93%) (89%)
51/56
(91%)
•4/14 with recurrent IM-subsquamous
•5/119 (4%) treated patients had disease progression
From Shaheen N et al. Gastroenterology 2011;141:460-8.
Sustained Remission of
HGD/IMC After EMR + RFA
• N=54
• 5 yr dysplasia/IM free
survival 90%
• 3 recurrent neoplasia
• All seen on HDWLE
• All managed
endoscopically
• Buried IM in 0.08%
biopsies
From Phoa KN et al. Gastroenterology 2013;145:96-104.
Effectiveness of RFA: BETERNET
Study
• N=448 patients underwent RFA
• Mean length 4.1 + 3.1 cm
• 71% HGD/Ca
• Median time to CRIM-22 mos
• CRIM = no IM on 2 consecutive endoscopies
in esophagus & GEJ
• Only 56% achieved CRIM by 24 mos
• 71% with CRIM by 36 mos
From Gupta M et al. Gastroenterology 2013;145:79-86.
Recurrence of IM After RFA:
BETERNET Study
• CRIM recurrence rate
• Yr 1-20%
• Yr 2-33%
• 22% of recurrences
dysplastic
• GEJ most common site
of recurrent dysplasia
• No factors predicted
recurrence
From Gupta M et al. Gastroenterology 2013;145:79-86.
Efficacy of RFA For Eradication
of IM & Dysplasia
From Kaimakliotis PZ et al. Current Opinion in Gastroenterology 2014 (In press)
RFA Durability
From Kaimakliotis PZ et al. Current Opinion in Gastroenterology 2014 (In press)
Safety of RFA: Systematic
Review
Complication
Stricture
Pain
Bleeding
% (95%CI)
5% (3-7%)
3% (1-6%)
1% (1-2%)
From Orman ES et al. Clin Gastroenterol Hepatol 2013;11:1245-55.
Subsquamous Cancer After RFA
From Titi M et al. Gastroenterology 2012;143:564-6.
Esophagectomy After Failed
Endoscopic Therapy of HGD/IMC
• Case series of N=15
• Prior endoscopic therapy for HGD or IMC
• EMR +/- RFA
• Median EMR sessions-1 (0-3)
• Median RFA session-3 (0-6)
• Median attempt at endotherapy-13 mos
From Hunt BM et al. Dis Esoph 2014;27:362-7.
Pathology After Esophagectomy
For Failed Endoscopic Therapy of
HGD/IMC
From Hunt BM et al. Dis Esoph 2014;27:362-7.
Follow Up Protocol After
Ablation
• No standards
exist
• Seattle protocol
of neosquamous
segment + cardia
• HGD/IMC
• Q 3 mos X 1 yr
• Q 6 mos X 1 yr
• Annual
• LGD
• Q 6 mos X 1 yr
• Annual
BADCAT International Consensus For
Management of Early Stage Adenocarcinoma
From Bennett C et al. Gastroenterology 2012;143:336-46.
Cryotherapy of Barrett’s
Esophagus
From Johnston MH et al. Gastrointest Endosc 2005;62:842-8.
Liquid Nitrogen Cryotherapy in 60 Barrett’s
Esophagus HGD Patients: A Cohort Study
From Shaheen N et al. Gastrointest Endosc 2010 71:680-5.
CryoBalloon Ablation
From Friedland S et al. Gastrointest Endosc 2011;74:182-8.
Summary
• Careful high definition white light
endoscopy remains cornerstone of
detection of dysplasia
• Adequate time
• Attention to 12-6 o’clock hemisphere
• Retroflexion into distal segment + cardia
Summary
• Narrow band imaging
• Increases inspection time
• Retrains white light eye
• New generation equipment role to be
determined
• Other enhanced imaging techniques of
uncertain clinical value
Summary
• EMR critical to adequate staging of
dysplasia
• RFA
• Effective in most but not all patients
• Safe but not complication free
• Durability promising but not perfect
Summary
• RFA is a commitment not a cure*
• No procedure is perfect*
*From Bergman JJ & Corley DA.
Gastroenterology 2012;143:524-6.
BADCAT International Consensus For
Management of Early Stage
Adenocarcinoma
• High resolution endoscope > 850,000
pixels should be used for surveillance
• Targeted biopsies of suspicious lesions
• 4 quadrant biopsies at 1-2 cm intervals
From Bennett C et al. Gastroenterology 2012;143:336-46.
ASGE Barrett’s Esophagus PIVI
on Barrett’s Esophagus Imaging
• Thresholds for adoption for new
imaging technology with targeted
biopsies
• Sensitivity > 90%
• NPV > 98%
• Specificity > 80%
From Sharma P et al. Gastrointest Endos 2012;76:252-4.