Barretts 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

Barretts Esophagus: diagnostic issues

Which length?
Which metaplasia?

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 Barretts 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 Barretts 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 Barretts esophagus

SCJ=squamocolumnar junction
OGJ=oesophagogastric junction

BE: Progression
BE (no dysplasia)
Low-grade dysplasia
High-grade dysplasia
Esophageal adenocarcinoma

Biomarkers in BE

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
Barretts Esophagus

Optimal endoscopic technique

Biopsies of all mucosal abnormalities (ulcer,
nodule, plaque)
Four quadrant (jumbo) biopsies at 1 2 cm
intervals

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

Cancer/Dysplasia -- multifocal and patchy

Seattle Protocol cumbersome and tedious
Compliance is poor

Unsuspected Cancer -- up to 53% of HGD

Surveillance Intervals - poorly defined biology
Dilemma with HGD variable interpretation
surveillance vs. surgery?

Costly with unproven benefit

NEEDED TECHNIQUE

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

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

Advantages
Sample larger area
Quick and Inexpensive

Disadvantages
Limited sensitivity (< 25% for LGD)

Future Hope
Molecular probes

Immunostains
FISH

HIGH MAG DETECTING BE

Contrast Agents
Acetic acid
Indigo carmine
Methylene blue

Distinct morphology for IM

High Sensitivity (> 95%) for IM
Still inaccurate for LGD/HGD

HIGH MAG DETECTING DYSPLASIA

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

Rationale
MB absorption by absorptive columnar
cells (small bowel and colon)
MB not absorbed by dysplastic cells

Methylene blue selectively stains SCE in

Barretts 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

Stains inflammation

Staining paradox

No time saving

Messy

Operator dependent; not sensitive enough

EUS For Surveillance

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

CANNOT DETECT DYSPLASIA

May or may not identify cancer

reliably in HGD

Accuracy for identifying malignant

nodal spread is limited.

LASER INDUCED FLUORESCENCE (LIF)

Theory
Dysplastic tissue is biochemically different and
thus fluoresces differently from normal;
Dysplastic tissue may also absorb fluorophores
differentially

Autofluorescence alone not accurate

enough
Local or systemic ALA (Messman et al.)
absorbed by dysplastic cells

DIFFICULTIES WITH L.I.F.

Inflammation may cause false positives

Dysplasia -- sensitivity < 80%, specificity

< 70%

Cost of fluorophore

Cost of LIF scopes

More research; better fluorophores needed

OPTICAL COHERENCE TOMOGRAPHY

Theory Coherent back scattered

light provides imaging resolution at
microscopic level.

Figure 3A

Figure 3B

Figure 4A

DIFFICULTIES WITH OCT

Limited sensitivity

Surveillance of large areas

Further studies of dysplastic tissue

required