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Barrett’s Esophagus
by Daniel E. Bujanda, MD & Christine Hachem, MD
Chronic reflux esophagitis
leads to the development
of Barrett’s esophagus;
who and when to
conduct surveillance for
adenocarcinoma in patients
with Barrett’s remains
controversial.
Daniel E. Bujanda, MD, (left), is a Fellow
and Christine Hachem, MD, (right), is an
associate professor of internal Medicine
in the division of Gastroenterology and
Hepatology, saint louis University school of
Medicine, st. louis, Mo.
Contact: Christine.Hachem@health.slu.edu
Abstract
The prevalence of Barrett’s
esophagus is increasing in the
United States and is a major
risk factor for esophageal
adenocarcinoma. This review
serves to help primary care
physicians and family practitioners
better understand who should be
screened for Barrett’s esophagus,
know the appropriate surveillance
intervals for repeat endoscopy, and
understand therapeutic options
for the management of Barrett’s
esophagus.
Introduction
Gastroesophageal reflux disease
(GERD) is highly prevalent in the
United States and complaints related
to gastroesophageal reflux disease
constitute a large proportion of the
primary care physicians’ practice.1
However, only a small proportion
of patients with GERD are at risk of
developing Barrett’s esophagus (BE).2
Barrett’s esophagus is a pre-malignant
condition that places patients at
risk for esophageal adenocarcinoma
(EAC).3 Within the last decade, our
understanding of the pathogenesis
of Barrett’s esophagus has increased
substantially, with improved risk
stratification to identify patients
who are at risk for progression to
esophageal adenocarcinoma. Equally
impressive is the ever-expanding
endoscopic armamentarium to treat
dysplastic lesions, obviating the need
for more invasive therapies such as
esophagectomy. Discerning which
patients should be referred for BE
screening and surveillance will enable
optimization of treatment regimens for
Barrett’s esophagus.
Missouri Medicine | May/June 2018 | 115:3 | 211
Definition of Barrett’s
Barrett’s esophagus occurs when
the normal squamous epithelium
of the distal esophagus changes to
columnar-lined intestinal type cells, a
transition known as intestinal metaplasia.
Its importance lies in that it is the
only known precursor to esophageal
adenocarcinoma.4 The transition occurs
when the esophagus is repeatedly
exposed to gastric acid, which in
turn causes mucosal inflammation.
When intestinal metaplasia occurs,
the normal esophageal mucosa will
take on a salmon colored appearance
when viewed endoscopically (Figure
1: Panel A and B). When this is seen
and is greater than one centimeter in
length, endoscopic biopsies should be
obtained to determine if goblet cells or
dysplasia are seen on histological review.
The diagnostic criteria for Barrett’s
esophagus that goblet cells are present
is controversial, but is the accepted
practice in the United States.4 Patients
with intestinal metaplasia less than one
centimeter in length do not have an
increased risk for further complications.
Unfortunately, there is a great deal of
inter-observer variability in the histologic
interpretation of dysplasia and the
diagnosis should be confirmed by two
pathologists, one of whom has extensive
experience in the interpretation of
Barrett’s-associated neoplasia.2
Risk Factors
Although gastroesophageal reflux
disease is highly prevalent in the United
States, only 10-15% of patients with
gastroesophageal reflux disease will
develop Barrett’s esophagus and up
to 50% of subjects with Barrett’s
or esophageal adenocarcinoma will
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Table 1. Risk Factors for Barrett’s Esophagus
report no history of gastroesophageal reflux symptoms.2
Overall, Barrett’s esophagus affects 2-7% of adults in western
countries.4 Shown in Table 1 are the known risk factors for
Barrett’s esophagus and esophageal adenocarcinoma.2
Current guidelines by the American College of
Gastroenterology recommend screening only men with
frequent gastroesophageal reflux disease (at least weekly
symptoms or symptoms that have persisted more than five
years) and two or more of the known risk factors. Routine
screening of women is not recommended except those with
multiple risk factors and a documented family history of
Barrett’s esophagus or esophageal adenocarcinoma in a first-
degree relative.
Natural History
The incidence of esophageal adenocarcinoma has
increased substantially over the past four decades with
an estimated incidence of 2.8 cases per 100,000 in the
United States.3 Esophageal adenocarcinoma in Barrett’s
esophagus develops through a progressive sequence of
histologic and molecular events that begin with metaplasia
and then progresses through various stages of dysplasia before
development of adenocarcinoma.4 The specific cell type at the
squamocolumnar junction responsible for the development
of Barrett’s was recently described.5 Dysplasia is defined
as neoplastic epithelium that is confined to the basement
membrane and the use of the descriptors low grade or high
grade is based upon the severity of architectural distortion
seen histologically. Advancing age, increasing Barrett’s
segment length, and endoscopic irregularities of the mucosa
(e.g. nodules, ulcers) are risk factors for dysplasia. The risk
of esophageal adenocarcinoma is proportional to the degree
of dysplasia and survival in esophageal adenocarcinoma is
stage dependent.6 Malignant progression in patients with
non-dysplastic Barrett’s is low with an annual incidence of
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0.33% per year,2 however, Barrett’s esophagus with high grade
dysplasia has an annual incidence rate of 7% for developing
EAC.7 Unfortunately, more than 90% of diagnosed esophageal
adenocarcinoma cases occur in patients without a prior history
of Barrett’s esophagus.2 Nevertheless, given the low five year
survival rates of patients with esophageal adenocarcinoma,
screening and surveillance strategies have been proposed to
decrease rates of EAC.
Therefore, the best hope for survival in esophageal
adenocarcinoma remains endoscopic screening and
surveillance of Barrett’s esophagus patients to detect
dysplasia and esophageal adenocarcinoma at an early stage
where potentially curable interventions exist.2 Patients with
esophageal adenocarcinoma detected in a surveillance program
have their cancers detected at an earlier stage with markedly
improved five-year survival compared with similar patients not
undergoing routine surveillance.6 However, only 7% of patients
with Barrett’s esophagus die of esophageal adenocarcinoma.
Most will die of non-intestinal causes such as heart disease and
pulmonary disease.2
Treatment of Barrett’s Esophagus
All patients with Barrett’s esophagus should be on once
daily proton pump inhibitor therapy as this may reduce the risk
of progression to dysplasia and esophageal adenocarcinoma.
The use of H2 blockers has not shown to reduce this risk.
Twice daily dosing is not routinely recommended and should
only be used for poorly controlled gastroesophageal reflux
disease or evidence of persistent inflammation. Currently there
is not enough evidence to advocate the use of medications such
as statins, aspirin or non-steroidal anti-inflammatory drugs
as a chemoprevention strategy. Antireflux surgery should not
be recommended for treatment of Barrett’s alone but may be
considered for GERD management.
Surveillance endoscopy intervals are currently determined
by the presence and grade of dysplasia. As the risk is low for
esophageal adenocarcinoma in patients with non-dysplastic
Barrett’s esophagus, surveillance upper endoscopy with
biopsies should occur every three to five years in these
patients. Patients with low or high-grade dysplasia or stage
T1a esophageal adenocarcinoma (defined as being limited to
the mucosa with no extension to the submucosa) should be
managed with endoscopic therapy. Endoscopic management
has been shown in multiple randomized controlled trials to
effectively eliminate dysplastic and metaplastic epithelium,
as well as greatly reduce cancer incidence.4 Currently the
preferred endoscopic therapy for low grade dysplasia is
radiofrequency ablation (Figure 1, Panel C). Radiofrequency
ablation has largely replaced most other forms of ablation
such as argon plasma coagulation and photodynamic therapy
because of its high efficacy rate and low complication rate.

Figure 1. A, Endoscopic view of salmon-colored mucosa typical of Barrett’s esophagus in white light; B, Narrow band imaging highlighting the
squamous cell epithelium (white mucosa) and tongues and islands of Barrett’s mucosa (arrows); C, Burned patch of esophageal mucosa after one
session of radiofrequency ablation (white colored mucosa).
For patients with high-grade dysplasia or stage T1a esophageal
adenocarcinoma, endoscopic mucosal resection followed by
radiofrequency ablation is the preferred treatment. Endoscopic
mucosal resection is a procedure designed to remove mucosa
and superficial submucosal tissue and serves as both a
diagnostic and a therapeutic procedure.
If there are advanced features such as nodularity, ulcers,
or strictures seen in the segment of Barrett’s esophagus,
endoscopic mucosal resection of these lesions should be
performed first and treatment based upon histological
assessment. These more advanced endoscopic features
have been shown to be associated with an increased risk of
esophageal adenocarcinoma.4 Patients with stage T1b (tumor
with extension to submucosa) or more advanced esophageal
adenocarcinoma should be managed by a multidisciplinary
team consisting of oncology, surgical oncology, and advanced
endoscopy. These patients likely need adjuvant chemoradiation
and consideration of esophagectomy.
In patients who are treated endoscopically and have
complete elimination of intestinal metaplasia, subsequent
surveillance is based on the severity of the initial disease. In
patients with low-grade dysplasia, surveillance endoscopy is
performed every six months in the first year and then annually
thereafter. In patients with high grade dysplasia or stage T1a
esophageal adenocarcinoma surveillance endoscopy is done
every three months for the first year, every 6 months in the
second year, and then yearly thereafter. For recurrent disease,
treatment follows the same histological algorithm that was used
before treatment.
Future Technologies
Conventional endoscopy is still considered the gold
standard for diagnosing BE. However, current surveillance
programs are expensive and time-consuming, creating the need
for less invasive and more cost effective screening methods.6
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Newer technologies such as unsedated transnasal
endoscopy,8 capsule endoscopy, chromoendoscopy, biomarkers,
and Cytosponge (esophageal samples are obtained using a
sponge at the end of a wire), and risk prediction models will
likely become more prevalent and useful as diagnostic and risk
stratification tools in the future.
Summary
Barrett’s esophagus is a risk factor for EAC. Unfortunately,
EAC has a poor prognosis if diagnosed late. Understanding the
screening and surveillance practices will help identify patients
at increased risk for EAC. Best practices will likely continue
to evolve as increased emphasis on risk stratification helps to
target those who are most likely to progress to EAC. An ever-
expanding armamentarium of therapeutics is now available to
help tackle the progression of Barrett’s to EAC.
References
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2. Shaheen NJ, Falk GW, Iyer PG, Gerson LB, American College of G. ACG
Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J
Gastroenterol 2016;111:30-50; quiz 51.
3. Qumseya BJ, Wani S, Gendy S, Harnke B, Bergman JJ, Wolfsen H. Disease
Progression in Barrett’s Low-Grade Dysplasia With Radiofrequency Ablation
Compared With Surveillance: Systematic Review and Meta-Analysis. Am J
Gastroenterol 2017;112:849-865.
4. Naini BV, Souza RF, Odze RD. Barrett’s Esophagus: A Comprehensive and
Contemporary Review for Pathologists. Am J Surg Pathol 2016;40:e45-66.
5. Jiang M, Li H, Zhang Y, Yang Y, Lu R, Liu K, et al. Transitional basal cells
at the squamous-columnar junction generate Barrett’s oesophagus. Nature
2017;550:529-533.
6. Wani S, Gaddam S. Editorial: Best Practices in Surveillance of Barrett’s
Esophagus. Am J Gastroenterol 2017;112:1056-1060.
7. Rastogi A, Puli S, El-Serag HB, Bansal A, Wani S, Sharma P. Incidence of
esophageal adenocarcinoma in patients with Barrett’s esophagus and high-grade
dysplasia: a meta-analysis. Gastrointest Endosc 2008;67:394-398.
8. Syed A, Kyprianou A. Unsedated Transnasal Endoscopy (uTNE): Not
Quite Ready to Replace Sedated Esophagogastroduodenoscopy (sEGD). Am J
Gastroenterol 2015;110:936-937.
Disclosure
None reported. MM
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