Transcript Barrett’s Esophagus Endoscopic Diagnosis

Barrett’s Esophagus
Endoscopic Diagnosis
Alessandro Repici
Dept of Gastroenterology
Molinette Hospital, Torino
Historical notes
1906, Tileston
“peptic ulcer of the esophagus” with a
close resemblance of the mucous
membrane to that found in the stomach
1957, Barrett
“The lower esophagus lined by columnar
epithelium” (erroneously considered
as congenital)
1975, Naef
“Columnar-lined oesophagus: an acquired
lesion with malignant predisposition”
Barrett’s Esophagus: diagnostic issues
Which length?
Which metaplasia?
2
1998 A.C.G.: …”a change in the
esophageal epithelium of any length
that can be recognized at endoscopy
and is confirmed to have intestinal
metaplasia by biopsy”
Presence of
Goblet Cells
becomes a “must”
Histomorphological changes in Barrett‘s esophagus
A: Damage to the
superficial
compartments
through acid or
bile
B: Damage to the
cellular layers and
activation of totipotential cells
Histomorphological changes in Barrett‘s esophagus
Development of areas with mucin secreting cells with
resistance against acid and bile
Jankowski, AJP 1999
Macroscopic classification
> 3 cm, Barrett
< 3 cm,
Short Barrett
Super Short Barrett
AJG 2000
Easy to identify Long-segment Barrett
Correct definition of OGJ allows detection of short
segments of Barrett’s esophagus
SCJ=„squamocolumnar junction“
OGJ=„oesophagogastric junction“
4
BE: Progression
BE (no dysplasia)
Low-grade dysplasia
High-grade dysplasia
Esophageal adenocarcinoma
Biomarkers in BE
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Multiple genetic lesions occur during the
neoplastic progression of BE
Biomarkers may be used for risk assessment of
patients as well as intermediate endpoints in
trials
17p (p53) LOH and p16 abnormalities seem to
predict progression to cancer in BE patients
No realiable markers of Cancer progression
are currently available
Reid BJ, DDW 2001
Wong DJ, DDW 2001
Endoscopic diagnosis
• Surveillance
• Detection of dysplasia
• Staging of the disease
Endoscopic Surveillance of
Barrett’s Esophagus
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Optimal endoscopic technique
• Biopsies of all mucosal abnormalities (ulcer,
nodule, plaque)
• Four quadrant (jumbo) biopsies at 1 – 2 cm
intervals
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Recommended surveillance intervals
• No dysplasia
• LGD
• HGD
3 yrs after 2 EGD
6m for 1 yr, then 1yr
Confirm and resect vs. 3 m
LIMITATIONS OF SURVEILLANCE STRATEGY
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Cancer/Dysplasia -- multifocal and patchy
“Seattle Protocol” – cumbersome and
tedious
• Compliance is poor
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Unsuspected Cancer -- up to 53% of HGD
Surveillance Intervals - poorly defined
biology
Dilemma with HGD – variable
interpretation
• surveillance vs. surgery?
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Costly with unproven benefit
NEEDED TECHNIQUE
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Highly sensitive to dysplasia – must
detect changes at a nuclear level
High resolution but also able to scan
wide area in real-time
Specific – not affected by esophageal
inflammation
High interobserver agreement
Localize dysplastic area for biopsy
Cost not prohibitive
Alternative Methods for Surveillance
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Blind balloon cytology – sensitivity limited
High Magnification Endoscopy
Confocal Microscopy
Chromoendoscopy (methylene blue)
Endoscopic Ultrasound (EUS)
Laser Induced Fluorescence
Optical Coherence Tomography
Light Scattering Spectroscopy
Raman Spectroscopy
BE SURVEILLANCE --BLIND CYTOLOGY
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Advantages
• Sample larger area
• Quick and Inexpensive
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Disadvantages
• Limited sensitivity (< 25% for LGD)
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Future Hope
• Molecular probes
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Immunostains
FISH
HIGH MAG – DETECTING BE
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Contrast Agents
• Acetic acid
• Indigo carmine
• Methylene blue
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Distinct morphology for IM
High Sensitivity (> 95%) for IM
Still inaccurate for LGD/HGD
HIGH MAG – DETECTING DYSPLASIA
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Sharma et al. – 80 patients
Distinct morphology - Ridged/villous/ Circular/
Irregular&Distorted
All 6 HGD were irregular and distorted
Limitations - Cannot distinguish LGD; Difficult for surveillance
of large area; Results very preliminary
Intestinal Metaplasia
High Grade Dysplasia
METHYLENE BLUE
CHROMOENDOSCOPY
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Rationale
• MB absorption by absorptive columnar
cells (small bowel and colon)
• MB not absorbed by dysplastic cells
Methylene blue selectively stains SCE in
Barrett’s esophagus
Focal
Diffuse
Summary of Studies
Favorable
Mixed
Unfavorable
Canto 96-01
(>250)
Horwhat 1999 A
(42)
Wo 2001 (47)
Kiesslich 2000 (73)
Breyer 2000 A (30)
Jobson 1999 A (33)
Sharma 2001 (75)
Hasan 1998 A (16)
Gangarosa 2000
(10)
Sueoka 2001 (60)
Gossner 1999 A
(61)
Dave 2001 (10)
LIMITATIONS OF MB DIRECTED
SURVEILLANCE
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Stains inflammation
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Staining paradox
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No time saving
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Messy
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Operator dependent; not sensitive enough
EUS For Surveillance
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Theory of Ultrasound Imaging
• Sound reflects at tissue interface
• Higher frequency equals higher
resolution but lower penetration
• Useable frequencies do not provide
cellular resolution
When not to do EMR
20 Mhz probe
EUS at 7.5 MHz
LIMITATIONS OF EUS
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CANNOT DETECT DYSPLASIA
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May or may not identify cancer
reliably in HGD
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Accuracy for identifying malignant
nodal spread is limited.
LASER INDUCED FLUORESCENCE (LIF)
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Theory
• Dysplastic tissue is biochemically different and
thus fluoresces differently from normal;
• Dysplastic tissue may also absorb fluorophores
differentially
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Autofluorescence alone not accurate
enough
Local or systemic ALA (Messman et al.)
absorbed by dysplastic cells
DIFFICULTIES WITH L.I.F.
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Inflammation may cause false positives
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Dysplasia -- sensitivity < 80%, specificity
< 70%
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Cost of fluorophore
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Cost of LIF scopes
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More research; better fluorophores
needed
OPTICAL COHERENCE TOMOGRAPHY
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Theory – Coherent back scattered
light provides imaging resolution at
microscopic level.
Figure 3A
Figure 3B
Figure 4A
DIFFICULTIES WITH OCT
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Limited sensitivity
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Surveillance of large areas
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Further studies of dysplastic tissue
required