This document discusses Barrett's esophagus, including its definition, diagnosis, clinical presentation, natural history, epidemiology, pathogenesis, and management. Key points include: - Barrett's esophagus is diagnosed when endoscopy shows columnar-lined esophagus and biopsies confirm intestinal metaplasia. It is associated with increased risk of esophageal adenocarcinoma. - Risk factors include chronic gastroesophageal reflux, white male sex, obesity, and central adiposity. - Surveillance endoscopy is recommended for diagnosed Barrett's esophagus to screen for dysplasia or cancer. Histological confirmation of intestinal metaplasia is needed prior to initiating surveillance.

2.  Barrett’s esophagus is a change in the distal esophageal
epithelium of any length that can be recognized as
columnar type mucosa at endoscopy and is confirmed to
have intestinal metaplasia by biopsy of the tubular
esophagus. (Grade B recommendation).
 “the working definition of BE is displacement of the
squamocolumnar junction proximal to the
gastroesophageal junction” and “endoscopy with multiple
systematic biopsies is needed to establish the diagnosis of
Barrett’s esophagus”

3. Introduction
 Barrett’s oesophagus is a metaplastic change of the lining
of the oesophageal mucosa, such that the normal
squamous epithelium is replaced with specialised or
intestinalised columnar epithelium
 Intestinal metaplasia is clinically signifi cant because it is
associated with heightened risk of oesophageal
adenocarcinoma, which has substantially increased in
incidence in developed populations.
 Barrett’s oesophagus is associated with symptoms of
chronic gastro-oesophageal refl ux disease (GERD), such as
heartburn and regurgitation

4. Clinical presentation
 The diagnosis of Barrett’s oesophagus should satisfy two
criteria.
 First, examination by upper endoscopy should show
cephalad displacement of the squamocolumnar junction
 The second criterion for diagnosis is intestinalised
epithelium, or epithelium containing goblet cells ,in a
biopsy specimen of the tubular oesophagus
 oesophageal epithelium with the endoscopic appearance of
Barrett’s oesophagus, but without histological
confirmation, should be termed endoscopically suspected
oesophageal metaplasia

5.  The length of the displaced squamocolumnar junction
should be measured during endoscopy:
 longer than 3 cm is long-segment Barrett’s oesophagus;
 3 cm or shorter is short-segment Barrett’s oesophagus
 most common current definition of Barrett’s oesophagus is
salmon-coloured mucosa of any length in an oesophagus
harbouring goblet cells.

6.  In patients with GERD symptoms but no endoscopic
evidence of Barrett’s oesophagus, almost 20% had
intestinal metaplasia in a biopsy sample of their Z line
 10–17% of patients undergoing routine upper endoscopy,
without endoscopic irregularity or a history of reflux
symptoms, had intestinal metaplasia in a biopsy sample
 routine endoscopic biopsies of a normal-appearing gastro-
oesophageal junction in patients with GERD symptoms are
not recommended
 cancer overgrows the fertile field of BE so that at
presentation of the patient with EAC,BEmay no longer be
detectable

8. Natural history
 The risk of oesophageal adenocarcinoma in patients with
Barrett’s oesophagus is low, about 0·5% per patient-year,
and most die with the disorder, not as a result of it
 patients with high-grade dysplasia might have cancer rates
of 10% or greater per patient-year
 If Barrett’s oesophagus does progress, it seems to do so
through a series of cellular changes, ranging between non-
dysplastic disease, low-grade dysplasia, high-grade
dysplasia, and oesophageal adenocarcinoma

9. Epidemiology
 A rigorous Swedish study of adults showed that the overall
prevalence was 1·6%, about a third of which was long-
segment disease
 In studies of simultaneous endoscopy in healthy patients
undergoing screening colonoscopy for colorectal cancer,
the prevalence ranged from 5·6% in a US midwestern
population, to 15–25% in elderly people and veterans
 prevalence in the general population is substantial, it is
much higher in patients undergoing upper endoscopy to
investigate chronic reflux symptoms, at 5–15%

10.  The risk and segment length of Barrett’s oesophagus
increase with the amount of acid exposure in the distal
oesophagus, and are both associated with the presence and
size of hiatal hernias
 symptoms of GERD are a poor predictor of Barrett’s
oesophagus, and little or no correlation with heartburn
symptom severity has been recorded.
 Symptom frequency and symptom chronicity (total
number of years with reflux symptoms) are, however,
better predictors of the presence of disease than symptom
severity

11.  Even after controlling for the severity of reflux disease,
white men have increased risk of disease, as do elderly
people
 Other potential risk factors include tobacco use and dietary
habits.
 Unlike squamous cell carcinoma of the oesophagus,
alcohol abuse and chronic tobacco use are at best minor
risk factors
 Use of non-steroidal anti-inflammatory drugs (NSAID) is
associated with a decreased risk of Barrett’s oesophagus is
also unclear, although some cohort and case-control data
suggest that the prevalence is diminished by past chronic

12. Pathogenesis
 Several reports suggest that a higher proportion of first-
degree relatives of patients with Barrett’s oesophagus have
the condition than might be expected by chance, but no
gene has been identified and such data are probably
subject to detection bias
 Increasing BMI is also associated with a statistically
significant rise in the risk of GERD symptoms and erosive
oesophagitis, progressively heightening the risk of GERD
complications,and even a small rise in BMI increases the
probability of reflux symptoms.
 A cross-sectional study estimated that visceral abdominal
tissue was on average 1·5-fold greater in patients with
Barrett’s oesophagus than in controls

13.  Case-control studies also showed the importance of central
adiposity in development of the condition.
 A population-based case-control study recorded a strong
association between Barrett’s oesophagus and increasing
waist-to-hip ratio

14.  In general, these patients have greater decreases in lower
oesophageal sphincter pressures and more oesophageal
dysmotility than do patients with erosive oesophagitis or
non-erosive disease, and more than 90% have substantially
abnormal pH tests
 patients with Barrett’s oesophagus have long exposure to
caustic concentrations of gastric acid (pH<3·0 or 2·0), high
proximal extent of acid reflux in long-segment disease, and
high frequency of hiatal hernias (76% in Barrett’s
oesophagus vs 36% in reflux patients).
 Bile in the stomach and bile reflux, which is usually
associated with acid reflux, is more common in Barrett’s
oesophagus patients than in other forms of GERD

15.  The diminishing prevalence of H pylori infection in
developed countries is temporally associated with an
increased incidence of GERD complications, including
Barrett’s oesophagus
 The dramatic metaplastic changes in the intercellular
protein composition of the tight junctions in the
epithelium result in a more acid-resistant lining in Barrett’s
oesophagus patients than in healthy individuals.
 Therefore, development of the condition might actually
represent short-term adaption, by decreasing the
complications of chronic reflux such as bleeding and
structuring

16.  The progenitor cell from which Barrett’s oesophagus
develops is unclear.
 Candidates include progenitor cells resident in the
submucosal glands or the interbasal layer of the
epithelium, bone-marrow-derived stem cells, or transdiff
erentiated squamous cells

17.  a strategy to decrease the recent rise in esophageal cancer would
be earlier diagnosis of Barrett’s esophagus.
 The diagnosis should be made with endoscopy and biopsy of
columnar lined esophagus only (Grade B Recommendation).
 Histological changes of intestinal metaplasia (goblet cells) are
needed for the diagnosis prior to recommendations of
surveillance.
 Ideally, erosive esophagitis should be healed prior to biopsy to
increase the yield and avoid missing short segments of columnar
lining (Grade B Recommendation).
 Endoscopic descriptions of a Barrett’s esophagus should be
precise and ideally followestablished classification systems
(Grade D Recommendation).

18. Diagnosis
 Standard endoscopic screening
 Patients with chronic reflux symptoms should be screened
for Barrett’s oesophagus by upper endoscopy only after the
patient has been on acid suppression with a proton pump
inhibitor for at least 4 weeks
 As much as 12% of short-segment disease can be missed
because of severe erosive oesophagitis

19.  An international working group proposed and validated an
endoscopic classification system for Barrett’s oesophagus.
 The Prague C and M criteria assess the circumferential (C)
and maximum (M) extent of the endoscopically visualised
Barrett’s oesophagus segment, above the gastro-
oesophageal junction, assessed with minimum insufflation
 The reliability coefficients (RC) for C 0.95, M 0.94, the
gastroesophageal junction 0.88 and the location of the
hiatus 0.85 were excellent.
 The overall RCfor the endoscopic recognition of BE ≥1cm
was 0.72. However, for less than 1cm of columnar lining the
coefficient was only 0.22

20.  Histological confirmation of disease varies with the length
of columnar appearing mucosa identified at endoscopy,
with suspected short-segment disease confi rmed in only
about 25% of cases and long-segment disease confi rmed in
44–80% of cases.
 More than 20% of patients without confirmation of
intestinal metaplasia at initial endoscopy have it at later
endoscopy, probably because of sampling error or interim
development of intestinal metaplasia after the first
examination

21.  One analysis suggested that, although one screening
endoscopy was highly cost-effective, subsequent
surveillance endoscopies in patients whose biopsies
showed only Barrett’s oesophagus with no dysplasia were
very cost-ineffective, adding only a few extra days of life
expectancy at an extra cost of thousands of US dollars
 Nasal endoscopy - More than 70% of the patients
preferred small-calibre endoscopy, which can eliminate the
need for monitoring, recovery time, loss of work time, and
an accompanying driver.
 One difficulty with this approach is the absence of
adequate tissue sampling for histological confirmation of
the diagnosis

22.  Capsule endoscopy - A specialised capsule has been
designed to obtain large numbers of photographs (up to
14/s) from both ends of the capsule, as it passes through
the oesophagus
 capsule endoscopy was 67% sensitive and 84% specific for
identification
 the diagnostic accuracy of this non-invasive technique is
limited by excessive debris or bubbles obscuring the Z line,
and the small number of frames in which the gastro-
oesophageal junction is clearly visible
 the technique might not be cost-effective compared with
standard endoscopy for the detection of Barrett’s
oesophagus in patients with chronic GERD

23.  Advanced endoscopic imaging
 Chromoendoscopy is a simple technique involving the
application of chemical agents to improve the
characterisation of mucosal surfaces either by selective
uptake (vital staining with methylene blue or Lugol’s
solution) or enhancement of mucosal surface pattern
(contrast staining with indigo carmine and acetic acid).
 Of these stains, methylene blue is the most popular,
staining non-dysplastic intestinal metaplasia blue but not
binding to the mucosa if there is high-grade dysplasia or
cancer present

24.  methylene blue chromoscopy to be no better, and in some
cases worse, than random four-quadrant biopsies for the
detection of dysplasia.
 Problems associated with this technique include difficulty
in achievement of complete and even coating of the
mucosa, the additional time required for dye spraying, and
an inability to detect superficial vascular patterns

25.  Narrow-band imaging.
 This technique improves contrast by narrowing the band of
white light, filtering it into two major colours (blue and
green) which are then better absorbed by blood vessels in
the mucosa and submucosa
 Narrow-band imaging combined with high-resolution
endoscopy produces detailed images of the mucosal and
vascular surface patterns within the Barrett’s oesophagus
segment, and identifies characteristic patterns for non-
dysplastic intestinal metaplasia, high-grade dysplasia, and
early cancer.
 Narrow-band imaging was unable to distinguish intestinal
metaplasia from low-grade dysplasia

27.  Autofluorescence, which uses blue light to detect naturally
occurring fluorescence from tissue.
 Neoplastic mucosa in Barrett’s oesophagus tends to appear
blue–violet, whereas non-dysplastic tissue appears green
 narrow-band or autofluorescence imaging, in combination
with standard endoscopy, might provide accurate
visualisation of inapparent or subtle mucosal abnormalities
associated with high-grade dysplasia or cancer, without the
inconvenience or mess of chromoendoscopy

28.  Optical coherence tomography produces high-resolution
cross-sectional images of tissue in vivo.
 The technique is analogous to ultrasound imaging, but
uses infrared light rather than acoustic energy, and has a
ten-fold higher resolution than does high-frequency
ultrasound, though the maximum depth of optical
coherence tomography is lower than with ultrasound
imaging
 accuracy of 78% for the detection of dysplasia in patients
with Barrett’s oesophagus

29.  Laser confocal microscopy can magnify the mucosa more
than 1000-fold and actually image cellular structures
 accuracy of 97·4% for detection of neoplasia

30. Screening
 Screening for Barrett’s esophagus remains controversial
because of the lack of documented impact on mortality from
EAC.
 The large number of patients that lack reflux symptoms but
have Barrett’s esophagus provides a diagnosis challenge.
 The highest yield for Barrett’s is in older (age 50 or more)
Caucasian males with longstanding heartburn.
 Predictors included age >40, heartburn , long duration
GERD symptoms (more than 13 years) , and male gender

31.  screening for Barrett’s esophagus in the general population
cannot be recommended at this time. (Grade B
recommendation)
 The use of screening in selective populations at higher risk
remains to be established (Grade D recommendation) and
therefore should be individualized

32. SURVEILLANCE
 The grade of dysplasia determines the appropriate
surveillance interval.
 Any grade of dysplasia by histology should be confirmed by
an expert pathologist
 surveillance program should include age, likelihood of
survival over the next five years, patient’s understanding of
the process and its limitations for detection of cancer, and
the willingness of the patient to adhere to the
recommendations (Grade B Recommendation).

33.  The finding of low grade dysplasia (LGD) warrants a
follow-up endoscopy within six months to ensure that no
higher grade of dysplasia is present in the esophagus.
 If none is found, then yearly endoscopy is warranted until
no dysplasia is present on two consecutive annual
endoscopies. LGD should be confirmed by an expert GI
pathologist because of the problem of reading variability
 When two pathologists agree on the diagnosis of LGD, the
patient has a greater likelihood of neoplastic progression
 Forty percent of biopsies following the recognition of LGD
will be negative

34.  The finding of high grade dysplasia (HGD) in flat mucosa
should lead to confirmation by an expert GI pathologist
and a subsequent endoscopy within three months.
 HGD with mucosal irregularity should undergo endoscopic
mucosal resection.
 Although the natural history of HGD is variable, there is a
five year risk of EAC exceeding 30%

35.  Patient’s who appear to have lost their dysplasia on surveillance
should be treated according to the highest degree of dysplasia
previously found
 If ablative therapy has been applied, patients should be followed
and biopsied in the entire area of prior Barrett’s mucosa at
intervals appropriate for their prior grade of dysplasia until there
is reasonable certainty of complete ablation is documented on at
least three consecutive endoscopies. (Grade D recommendation)
 Periodic surveillance is still recommended since Barrett’s mucosa
has been known to occur again.
 Precise recommendations regarding these intervals are not made

37. Management
 Barrett’s oesophagus is associated with a decreased quality
of life compared with the general population
 fewer than 10% of patients progress to high-grade dysplasia
or cancer
 consensus among recommending organisations is that
patients with non-dysplastic disease or low-grade dysplasia
should be managed conservatively, with periodic
surveillance endoscopy

38.  debate surrounds the most appropriate management for
patients with high-grade dysplasia, since they are at
considerably increased risk of the disease progressing to
cancer, with yearly rates of 4%, 2·2%, and 11·8% in some
studies
 Three strategies are in common use:
1. Surgical oesophagectomy,
2. Observation with frequent surveillance endoscopy,
3. Endoscopic therapy.

39.  surgical series have reported occult cancer rates in such
specimens of 10–50%.
 oesophagectomy can carry a high morbidity and mortality,
with reported 30-day mortality as high as 20% in low-
volume centres

40.  endoscopic therapy, either by endoscopic resection of the
inner lining of the oesophagus (endoscopic mucosal
resection or endoscopic submucosal dissection), or
ablation of the inner lining of the oesophagus
 Endoscopic therapies to ablate the epithelium are
multipolar electrocoagulation, laser therapy, argon plasma
coagulation, photodynamic therapy, cryotherapy with
sprayed liquid nitrogen, and radio frequency wave ablation

41.  Photodynamic therapy, in which a photosensitising agent is
given before laser treatment of the oesophagus, has proved
to reduce the risk of cancer in patients with high-grade
dysplasia by more than 50%
 Radiofrequency wave ablation has been shown to eradicate
both non-dysplastic and highgrade dysplastic Barrett’s
oesophagus very effectively.
 Endoscopic resection of some or all of the Barrett’s
oesophagus tissue might be used before ablation to remove
nodular disease, or as a stand-alone therapy

42.  The best management for Barrett’s oesophagus with high-
grade dysplasia is dependent on the patient’s
characteristics and preferences, and local expertise
 In patients with multiple comorbidities, endoscopic
ablation or endoscopic surveillance might result in the best
life expectancy.
 In young patients with extensive, multifocal high-grade
dysplasia, surgical intervention or endoscopic therapy
might be preferable to intensive endoscopic surveillance.

43.  Does chemoprevention have a role in the prevention of
Barrett’s oesophagus development or the progression of
Barrett’s oesophagus to dysplastic disease?
 NSAID use has been postulated to diminish the incidence
of Barrett’s oesophagus or at least delay its progression to
cancer.
 Unfortunately, a recently reported randomised controlled
trial of 200 mg each day of celecoxib—a COX-2-selective
NSAID—in patients with Barrett’s oesophagus, and either
low-grade or high-grade dysplasia, did not show a
protective effect against disease progression

44.  antireflux surgery should not be pursued as an
antineoplastic measure

45.  Low grade dysplasia requires expert pathologist confirmation and
more frequent endoscopy and biopsy.
 High grade dysplasia (HGD) also requires confirmation by an
expert pathologist and represents a threshold for intervention.
 A more intensive biopsy protocol is necessary to exclude the
presence of concomitant adenocarcinoma.
 Any mucosal irregularity, such as nodularity or ulcer, is best
assessed with endoscopic resection for a more extensive
histologic evaluation and exclusion of cancer.
 Management of patients with high grade dysplasia is dependent
on local expertise, both endoscopic and surgical and the patient’s
age, comorbidity and preferences.
 Esophagectomy is no longer the necessary treatment response to
HGD

46.  Photodynamic therapy has been the only therapy shown in
a randomized prospective control trial to significantly
decrease cancer risk in Barrett’s esophagus
 Thermal ablation techniques were originally utilized for
the treatment of Barrett’s esophagus lacking dysplasia
 Argon plasma coagulation
 Multipolar coagulation has been used to treat primarily
low-grade dysplasia and nondysplastic Barrett’s.
 Success rates of ablating the entire Barrett’s mucosa usually
are in the 80–90% range with multiple applications of the
devices

47.  Photodynamic therapy with 5-aminolevulinic acid, an oral
agent with superficial effects, has been utilized in Europe.
 It is very successful in eliminating high-grade dysplasia and
early EAC in case series
 It does have drawbacks of hypotension and even reported
patient death
 Radiofrequency ablation using a balloon based catheter
system has been reported to be of value in elimination of
Barrett’s esophagus in 70% 12 months after initiation of
treatment

48.  targeted radiofrequency application device mounted on the
endoscope has enabled treatment of focal areas with this
technique.
 This device was created to target the superficial mucosal of
the esophagus with high power radiofrequency energy.
 Though infrequent, stricture formation and esophageal
perforation have been reported
 Endoscopic application of cryotherapy has also been
reported to eliminate Barrett’s esophagus, although there is
very limited data about its efficacy

49. BIOMARKERS IN BARRETT’S ESOPHAGUS
 There is promise in the use of nuclear DNA content
abnormalities such as aneuploidy and tetraploidy in biopsy
specimens in predicting cancer risk, as well as loss of
heterozygosity of specific genes such as P16 and P53.
 In addition, recent studies demonstrate that methylation of
P16, RUNX3 and HPP1, as well as demographic
characteristics of the patients and BE length are indicators
of cancer risk.
 No biomarkers or panel is currently ready for routine
clinical use.

50. CHEMOPREVENTION
 Chemoprevention represents a promising future strategy
 The best evidence for any chemoprevention agent lies with
non-steroidal anti-inflammatory agents that have been
shown in multiple epidemiological studies to be associated
with a significantly reduced risk of cancer with an odds
ratio of 0.57
 Data from two retrospective cohort studies suggest that PPI
therapy significantly reduces the likelihood of developing
dysplasia
 This provides a rationale to treat even asymptomatic BE
patients with PPI.
 No recommendation can be made to use these drugs as
chemoprevention agents.

51.  currently no data that directly support the use of high dose
antisecretory therapy to delay or prevent the development
of EAC
 vast majority of data do not provide support that
fundoplication prevents EAC

52. ANTICIPATED DEVELOPMENTS
 Non-endoscopic detection of B: It is anticipated that in the short
termnon-endoscopic methods may become available that
identify Barrett’s mucosa based on high resolution,
spectroscopic or colorimetric means.
 A randomized trial assessing impact of surveillance endoscopy.
 A multicenter randomized controlled trial of surveillance is
needed to determine the validity of this practice.
 Optical recognition of dysplasia: Various techniques are
available that can distinguish degrees of dysplasia. These range
from fluorescence, light scattering, reflectance, and Raman
spectroscopy to imaging devices such as laser confocal
microscopy, endomicroscopy, and optical coherence
tomography. One or more of these technologies will become
clinically available.

53.  Prospective definition of risk of diffuse versus focal dysplasia.
 Advances in the technology of endoscopic ablation therapy:
Further evaluation of the most recent technology;
radiofrequency ablation is awaited. Cryotherapy is beginning
clinical trials and older technologies are becoming more refined
e.g.: photodynamic therapy with the development of new agents.
 Documentation of the frequency and duration of the
surveillance protocol after endoscopic ablation therapy requires
careful study.
 Validation of a biomarker panel to risk stratifies BE patients:
There are many potential biomarkers but few clinical trials that
validate their use. This undoubtedly will change given the many
markers currently being investigated