The n e w e ng l a n d j o u r na l of m e dic i n e

clinical practice

Barrett’s Esophagus
Prateek Sharma, M.D.

This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the author’s clinical recommendations.

A 56-year-old obese man with long-standing gastroesophageal reflux who recently

received a diagnosis of Barrett’s esophagus presents for a follow-up visit. He has been
taking omeprazole at a dose of 20 mg twice daily and currently has no symptoms of
reflux. He has no dysphagia or weight loss. Endoscopic and histopathological exami-
nations show a 4-cm segment of Barrett’s esophagus without dysplasia. How should
Barrett’s esophagus be managed?

The Cl inic a l Probl em

From the Veterans Affairs Medical Cen- Barrett’s esophagus is a premalignant lesion detected in the majority of patients
ter, Kansas City, MO, and the Division of with esophageal and gastroesophageal adenocarcinoma — cancers that are associ-
Gastroenterology and Hepatology, Uni-
versity of Kansas School of Medicine, ated with a low rate of survival (5-year survival rate, 15 to 20%).1 The incidence of
Kansas City, KS. Address reprint requests esophageal adenocarcinoma has been increasing in the United States.2 In 2009, it
to Dr. Sharma at 4801 E. Linwood Blvd., is estimated that 16,400 new cases of esophageal cancer will be diagnosed in the
Kansas City, KS 64129, or at psharma@
kumc.edu. United States, of which approximately 60% will be adenocarcinomas.3 The risk of
esophageal adenocarcinoma is 30 to 40 times as high among patients with Barrett’s
N Engl J Med 2009;361:2548-56. esophagus as among patients without this condition. The progression of Barrett’s
Copyright © 2009 Massachusetts Medical Society.
esophagus may involve the development of low-grade dysplasia and high-grade
dysplasia before the eventual development of cancer.
Barrett’s esophagus is diagnosed in approximately 10 to 15% of patients with reflux
who are undergoing endoscopy; it has also been reported in patients without chronic
reflux symptoms, with a prevalence of 5.6% in one report of endoscopic screening.4
The prevalence of Barrett’s esophagus in the general U.S. population is not known.
In a population-based study conducted in Sweden, Barrett’s esophagus was diagnosed
An audio version
in 1.6% of 3000 study participants.5 If these numbers are applied to the U.S. popu-
of this article
is available at lation, 1.5 to 2.0 million adults may have this premalignant lesion. Risk factors for
NEJM.org Barrett’s esophagus include advanced age, male sex, white race, symptoms of reflux,
and obesity. Studies have reported inverse associations between the presence of
Barrett’s esophagus and consumption of red wine, Helicobacter pylori infection, and
black race.6,7

S t r ategie s a nd E v idence

Evaluation
Although endoscopic screening for Barrett’s esophagus in patients with symptoms
of chronic reflux has been suggested by some gastroenterology societies,8-10 such
screening is controversial. Several cohort and case–control studies have shown that
almost half the patients in whom esophageal adenocarcinoma developed had no previ-
ous symptoms of heartburn.11 Although the risk of esophageal adenocarcinoma is
elevated among persons with heartburn as compared with the general population,

2548 n engl j med 361;26  nejm.org  december 24, 2009

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 clinical pr actice

the absolute risk is still less than 1 case per 1000

person-years. Furthermore, Barrett’s esophagus
may occur in the absence of symptoms of chronic
reflux.4 Finally, data that show a reduction in deaths
from esophageal adenocarcinoma as a result of en-
doscopic screening are lacking.11 A recent Clinical
Practice article in the Journal discussed this issue.12

Diagnosis
Barrett’s esophagus is a metaplastic change in the
esophageal lining from the usual squamous mu-
cosa to columnar epithelium, and is detected on
endoscopic examination as a columnar-lined dis-
tal esophagus (Fig. 1). In healthy persons, the
squamocolumnar junction and the gastroesopha- Figure 1. Endoscopic Detection of Barrett’s Esophagus.
AUTHOR Sharma RETAKE 1st
geal junction are located at the same level, whereas TheICM
red, columnar-lined esophagus (arrow) and the
REG F FIGURE 1 2nd
contrast between the squamous (arrowhead) and co-
in patients with Barrett’s esophagus, the squamo- CASE TITLE
lumnar (arrow) epithelium are characteristicRevised
of Bar-
3rd

columnar junction is displaced proximally. The EMail

rett’s esophagus. Line 4-C
Enon SIZE
gastroesophageal junction is evident endoscopi- FILL
ARTIST: mst H/T
Combo
H/T
16p6
cally as the top of the gastric folds; the squamo- AUTHOR, PLEASE NOTE:
columnar junction is seen as a transition from the cancer Figure
detected by redrawn
has been meansandoftypeendoscopic surveil-
has been reset.
Please check carefully.
light pink squamous mucosa of the esophagus to lance (48%), as compared with none of the pa-
the red columnar mucosa of the stomach. tientsJOB:
with36125
cancer who presented clinically, were
ISSUE: 12-24-09
Historically, Barrett’s esophagus was arbitrarily alive at 2 years of follow-up (P = 0.001); however,
classified as short-segment disease (<3 cm) or the possibility of lead-time bias makes it impos-
long-segment disease (≥3 cm) according to the sible to conclude from these findings that sur-
length of the metaplastic epithelium on endo- veillance prolongs life.15 Surveillance of patients
scopic examination. However, it is not clear that with Barrett’s esophagus is recommended by all
such classification is clinically meaningful or al- major gastroenterology societies and published
ters management.1 The extent of Barrett’s esoph- guidelines.1,9,10,16,17 However, no randomized, con-
agus on endoscopic examination can also be trolled trials have evaluated the efficacy of sur-
graded with the use of the Prague circumference veillance, and it is not clear whether surveillance
and maximum (C and M) criteria,13 a standard- reduces the mortality from esophageal cancer. Fur-
ized and validated system based on the circumfer- thermore, several factors limit the expected ben-
ential and maximal extent of the columnar-lined efits of current surveillance strategies, including
esophagus. Mucosal biopsy specimens are ob- the low overall incidence of cancer in patients with
tained from the columnar segment to confirm the Barrett’s esophagus, the absence of a previous di-
presence of metaplastic or neoplastic epithelium. agnosis of Barrett’s esophagus in the majority of
patients with esophageal adenocarcinoma, and dif-
Endoscopic Surveillance ficulties in the diagnosis of dysplasia (a high miss
Given the strong association between Barrett’s rate on evaluation of random biopsy specimens
esophagus and esophageal adenocarcinoma and and high variation among pathologists in the in-
the high proportion of patients with esophageal terpretation of biopsy findings).1,18
carcinoma who present with advanced disease, en- Although the precise incidence of cancer in
doscopic surveillance programs have been estab- patients with Barrett’s esophagus is unknown,
lished in an effort to diagnose cancer at an early cancer does not develop in most patients; recent
stage in patients with Barrett’s esophagus. Case– studies suggest a risk of 0.5% or less annually. In
control and cohort studies have shown that endo- a large multicenter cohort of patients with Bar-
scopic surveillance is significantly associated with rett’s esophagus, the incidence of cancer was
both an earlier stage of esophageal adenocarcino- 1 case in 212 patient-years of follow-up (0.5% per
ma at diagnosis and improved survival.14 In a pop- year).19 In patients with low-grade dysplasia, inci-
ulation-based cohort study, 11 of 23 patients with dence rates for esophageal adenocarcinoma range

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l of m e dic i n e

from 0.6% to 1.6% per year.20,21 The lower end

of this range is similar to the incidence in patients A
with Barrett’s esophagus who do not have dyspla-
sia, whereas cases in which the diagnosis of low-
grade dysplasia is based on a consensus by two or
more expert pathologists may be associated with
progression rates that are higher than those for
cases in which consensus is lacking.22 Moreover,
the majority of patients with low-grade dysplasia
detected on endoscopic surveillance do not have
evidence of dysplasia on the subsequent endo-
scopic examination. In contrast, the risk of the
development of esophageal adenocarcinoma is
high among patients with high-grade dysplasia,
B
with an estimated incidence of 6.6 cases per 100
patient-years (95% confidence interval, 4.9 to 8.2)
in a recent meta-analysis.23
A detailed inspection of the metaplastic epithe-
lium with the use of a high-quality video endo-
scope should be performed. After obtaining target
biopsy specimens from any visible mucosal abnor-
malities (Fig. 2), a systematic four-quadrant biopsy
protocol, with specimens obtained every 2 cm
along the extent of the Barrett’s esophagus, can
in­crease the yield of both low-grade dysplasia
(by 17%) and high-grade dysplasia (by 3%) as
compared with randomly obtained biopsy spec- Figure 2. Early Adenocarcinoma in a Patient
imens.24 with Barrett’s Esophagus.
Recommendations regarding surveillance inter- Panel A shows nodular areas (arrows) that are visible
withICM AUTHOR Sharma
high-resolution, RETAKE
white-light endoscopy. Panel B1st
vals are largely based on longitudinal case series F FIGURE
REG the 2a&bof the distal esophagus after2nd
shows appearance en-
and expert opinion.9 For patients without dyspla- CASE
doscopic TITLE
resection of the nodular area. Revised
3rd

sia in whom two carefully performed endoscop- EMail Line 4-C

Enon SIZE
ic examinations a year apart have shown no evi- FILL
ARTIST: mst H/T
Combo
H/T
16p6
dence of disease progression, the surveillance ly compared with standard endoscopy, preliminary
AUTHOR, PLEASE NOTE:
interval may be extended up to 3 years. For pa- results Figure
with has
thebeen
useredrawn
of narrow-band imaging
and type has been reset. (elec-
Please check carefully.
tients with low-grade dysplasia in whom an ad- tronic chromoendoscopy) and confocal laser en-
vanced lesion has been ruled out, annual surveil- domicroscopy
JOB: 36125
suggest a high rate of accuracy (85
ISSUE: 12-24-09
lance is typically recommended (Fig. 3). to 92%) in the diagnosis of neoplasia in patients
with Barrett’s esophagus.25,26 Preliminary results
Advanced Imaging Techniques from a randomized, controlled crossover trial in-
The current practice of endoscopic surveillance in volving 123 patients with Barrett’s esophagus
patients with Barrett’s esophagus has limitations. showed that, as compared with a strategy of per-
Biopsies are performed randomly and sample only forming four-quadrant biopsies every 2 cm with
4 to 6% of the surface area of the metaplastic epi- the use of high-definition endoscopy, the use of
thelium, although it is recognized that dysplastic targeted biopsies with narrow-band imaging iden-
and cancerous lesions within the Barrett’s segment tified similar proportions of patients with meta-
have a focal and patchy distribution. More recently, plastic lesions (85% with each procedure) and neo-
enhanced optical imaging techniques have been plastic lesions (71% with targeted biopsies and
suggested to improve the efficiency and accuracy 55% with four-quadrant biopsies, P = 0.15) but in-
of endoscopic surveillance (Table 1). Although the volved fewer biopsy specimens per procedure (3.6
majority of these techniques have not been direct- vs. 7.6, P<0.001).27

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 clinical pr actice

Diagnosis of Barrett’s esophagus

during endoscopy

Careful examination and grading

(e.g., with the use of Prague criteria)

Endoscopic biopsies (targeted

and four-quadrant every 2 cm)

Nondysplastic Barrett’s Acid-suppressive Dysplasia, cancer,

esophagus therapy or both

Endoscopic surveillance Confirmation by two expert

every 3 yr pathologists

Low-grade dysplasia High-grade dysplasia Early cancer

Endoscopic surveillance
twice every yr
Staging endoscopic
mucosal resection

High-grade
Mucosal cancer Invasive cancer
dysplasia

Endoscopic
Surgery
therapy

Figure 3. Proposed Treatment Algorithm for Patients with Barrett’s Esophagus.

AUTHOR: Sharma RETAKE: 1st
2nd
Management FIGURE: 3 of 4
mucosa; data showing that these interventions re-
3rd
Revised
Antireflux Interventions ARTIST: MRL duce the risk SIZE of esophageal carcinoma among
In patients with Barrett’s esophagus,
TYPE: Lineantireflux
Combo these
4-C patients
H/T
6are
col lacking. Indications for antire-
33p9
interventions are intended to control symptoms flux surgery in patients with Barrett’s esophagus
AUTHOR, PLEASE NOTE:
of reflux and promote healing ofFigure
the has
esophageal aretype
been redrawn and thehassame as those in patients with chronic re-
been reset.
Please check carefully.

JOB: 36126 ISSUE: 12-24-09

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 1. Advanced Imaging Techniques for Barrett’s Esophagus.

Technique Description Comments

High-resolution, white-light Uses a charge-coupled device with up to 1 mil- Becoming the default standard, given improve-
endoscopy lion pixels and high-resolution components ments in the quality, clarity, and resolution
of white-light imaging
Magnification endoscopy Uses optical magnification (up to ×70–100) Evaluated in case series; not directly compared
to visualize subtle mucosal patterns and with standard endoscopy and tedious to
lesions within the Barrett’s segment use, since it allows visualization of very
focal areas
Chromoendoscopy Sprays various stains (e.g., methylene blue, indi- Has been tested in randomized, controlled trials
go carmine), over the esophageal mucosa to with varying results; relatively inexpensive to
accentuate the contrast between the meta- use; challenges include variability in use of
plastic and nonmetaplastic epithelium stains and spray catheter, and lack of stan-
dardization of technique
Narrow-band imaging (electronic Uses spectral narrow-band optical filters with Relatively easy to use and tested in randomized,
chromoendoscopy) predominance of blue light rather than the controlled trials showing yield that is similar
complete white-light spectrum; this high- to that of routine biopsies; difficulty with pat-
lights mucosal and vascular patterns indica- tern recognition and learning curve
tive of neoplastic tissue
Autofluorescence imaging Detects change in fluorescence from alteration Allows broad-based imaging; high false positive
in the content of cellular molecules such as rates, subjective color interpretation, and
NADPH and collagen, with neoplastic tissue lack of commercial availability
showing differential fluorescence (color)
Confocal microscopy Uses a single plane of focus with laser micro- High-quality and detailed imaging of Barrett’s
scopes, allowing for real-time viewing of cel- glands and cells; challenges include imaging
lular details of very focal areas, intravenous fluorescence
agent, and image interpretation

flux (e.g., a lack of response to or an inability to thelium.31 Furthermore, a meta-analysis of 34

tolerate proton-pump inhibitors); the presence of studies of antireflux interventions in patients with
Barrett’s esophagus should not be viewed as an Barrett’s esophagus showed no significant differ-
indication for antireflux surgery.12 In a multicenter ence in the risk of esophageal cancer between pa-
trial in Europe, 554 patients with symptoms of tients who underwent antireflux surgery and those
chronic reflux, including 60 patients with Barrett’s who received medical therapy.32
esophagus, were randomly assigned to either lap-
aroscopic antireflux surgery or a proton-pump in- Management of Neoplastic Barrett’s Esophagus
hibitor (esomeprazole at a dose of 20 to 40 mg Multimodal endoscopic eradication therapy in-
daily, adjusted according to symptoms). At 3 years, volves the removal of visible neoplastic lesions by
symptoms and quality-of-life measures did not means of endoscopic mucosal resection (Fig. 4),
differ significantly between the groups, although followed by eradication of the remaining meta-
the surgical group had significantly better esoph- plastic epithelium with the use of mucosal ablative
ageal pH control.28 Progression of Barrett’s esoph- techniques such as photodynamic therapy, radio-
agus was not studied. The primary goal of both frequency ablation, cryoablation, and argon plasma
treatment with proton-pump inhibitors and sur- coagulation.33 Endoscopic mucosal resection has
gery is symptom control; 24-hour pH monitoring been used for both diagnostic and therapeutic pur-
to document normalization of exposure to esoph- poses. As a diagnostic tool, this procedure has
ageal acid is not routinely recommended. been shown to be superior to mucosal biopsies and
Whereas some retrospective cohort studies have results in a change in the histologic diagnosis and
shown associations between the use of more rig- clinical management in approximately 25% of pa-
orous acid suppression (with proton-pump in- tients.34 The patients with Barrett’s esophagus who
hibitors) and a decreased risk of or delay in the are most likely to benefit from endoscopic eradi-
progression to neoplasia,29,30 the data are incon- cation therapy are those with esophageal adeno-
sistent. Proton-pump–inhibitor therapy does not carcinoma limited to the mucosa and those with
reliably lead to regression of the metaplastic epi- high-grade dysplasia. Esophagectomy has tradi-

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 clinical pr actice

Esophagus
Mucosal
layer
Muscular
layer

Endoscope

Snare
is placed
over the
lesion

Lesion
Saline is injected
is sucked Snare
below the lesion
into the resects
cap the lesion

Figure 4. Endoscopic Mucosal Resection.

Removal of early cancer with the use of endoscopic mucosal resection is shown in a patient with Barrett’s esophagus.

tionally been the primary treatment in patients one trial involving 208 patients, the proportion of
with high-grade dysplasia because of a high re- patients in whom high-grade dysplasia remained
ported prevalence of coexisting esophageal adeno- completely eradicated at 5 years was significantly
carcinoma (up to 40% in some surgical series)35 higher in the group of patients randomly assigned
and a high risk of progression of high-grade dys- to photodynamic therapy and omeprazole (20 mg COLOR FIGURE

plasia to cancer. However, a recent systematic twice daily) than in the group randomly assigned Draft 3 11/25/09
Author Sharma
review showed a 12.7% prevalence of invasive to omeprazole alone (77% vs. 39%, P<0.001) 39
Fig # ; 4
esophageal cancer among patients undergoing the group receiving photodynamic therapyTitlealsoEndoscopic
resection
muscosal

esophagectomy for high-grade dysplasia; this prev- had lower rates of progression to cancer (15% ME vs.

alence was lower than previous estimates. In the 29%, P = 0.03), although the trial was notDE de- Solomon
Artist Knoper
absence of visualization of abnormal mucosal le- 40
signed to test this outcome. In a multicenter,AUTHOR PLEASE NOTE:
sions during endoscopy, the prevalence decreased randomized, sham-controlled trial involving 63 Please check carefully
Figure has been redrawn and type has been reset

to 3.0%.36 Furthermore, metaplastic epithelium patients, the rate of complete eradication of high-
Issue date 12/24/09

may recur after removal of the entire Barrett’s grade dysplasia was significantly higher in the
esophagus segment by means of radical subtotal group of patients assigned to radiofrequency
esophagectomy; in one surgical case series, 47% treatment than in the control group (81% vs.
of patients had subsequent evidence of a columnar- 19%, P<0.001), as was the rate of complete eradi-
lined esophagus.37 Moreover, even in centers with cation of the entire Barrett’s esophagus (74% vs.
expertise in performing the procedure, esophagec- 0%, P<0.001).41 Among patients with esophageal
tomy is associated with substantial morbidity adenocarcinoma, endoscopic eradication therapy
(with complications in 30 to 50% of patients, should be considered only for those with mucosal
including cardiac complications, pneumonia, disease, in whom the rate of lymph-node metasta-
and anastomotic leak or stricture) and mortality sis is extremely low (≤3%); once the cancer in-
(1 to 5%).35,38 vades the submucosa, the risk of lymph-node
The use of endoscopic eradication therapy in metastasis at diagnosis increases to 20 to 25%. In
patients with high-grade dysplasia is supported by a cohort of more than 200 patients with mucosal
the results of two randomized, controlled trials. In esophageal adenocarcinoma who were followed

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 2. Guidelines for the Management of Barrett’s Esophagus.*

Surveillance Intervals
Screening Histologic Examination for Nondysplastic
Organization Recommended Required for Diagnosis Barrett’s Esophagus
American College of Gastroenterology No† Yes 3 yr
American Society for Gastrointestinal Endoscopy Yes Yes 3 yr
British Society of Gastroenterology No No 2 yr
French Society of Digestive Endoscopy Not indicated Yes <3 cm, 5 yr; 3–6 cm,
3 yr; >6 cm, 2 yr
Society for Surgery of the Alimentary Tract Yes Yes 2 yr

* For patients with Barrett’s esophagus, proton-pump–inhibitor therapy, antireflux surgery, or both are generally recom-
mended for the control of symptoms of reflux and treatment of esophagitis.
† Screening is not recommended for the general population. In selective populations at increased risk, the decision about
screening should be individualized.

for a mean of 5.1 years after endoscopic eradica- tial role of nonsteroidal antiinflammatory drugs,
tion therapy, the 5-year survival rate was 87%.42 aspirin, and selective cyclooxygenase-2 inhibitors
Endoscopic eradication therapy is not currently in preventing esophageal cancer, confirmatory data
recommended in patients with nondysplastic Bar- from large randomized trials are not available.43
rett’s esophagus. Because of the overall low risk A randomized, controlled trial investigating the
of esophageal adenocarcinoma among patients effects of aspirin and proton-pump–inhibitor ther-
with Barrett’s esophagus, if the procedure is con- apy on neoplastic progression in patients with
firmed to be preventive, the estimated number of Barrett’s esophagus is ongoing (ClinicalTrials.gov
patients who would need to be treated to prevent number, NCT00357682).44
one case of esophageal adenocarcinoma would be Given the low overall risk of neoplastic progres-
250 or more. In addition, the potential complica- sion of Barrett’s esophagus, there is an interest in
tions of endoscopic eradication therapy (an over- biomarkers that might identify persons at partic-
all rate of 10 to 15%, with complications including ular risk for the development of cancer. Among
chest pain, odynophagia, strictures, perforation, biomarkers reported to be predictive of neoplastic
and bleeding), as well as the lack of evidence that progression are abnormalities in the tumor-sup-
endoscopic eradication therapy prevents the devel- pressor genes CDKN2A (which encodes the cyclin-
opment of cancer and that the eradication is du- dependent kinase inhibitor p16INK4a) and TP53
rable, underscore the need for more data. (which encodes tumor protein p53), and the pres-
ence of tetraploidy or aneuploidy in epithelial
A r e a s of Uncer ta in t y cells.45 In two large prospective studies, the 5-year
cumulative incidence of esophageal adenocarci-
Data are lacking from randomized, controlled tri- noma among patients with Barrett’s esophagus
als assessing the benefits of screening to detect was 43% in patients with aneuploidy, 56% in pa-
Barrett’s esophagus among patients with gastro­ tients with tetraploidy, and 5% in patients with-
esophageal reflux or of surveillance endoscopic ex- out aneuploidy or tetraploidy.46,47 However, data
aminations among patients with a diagnosis of are needed from large prospective studies to con-
Barrett’s esophagus. Data from placebo-controlled firm the predictive value of these and other mark-
or sham-controlled trials of the effects of medi- ers, and they are not currently used in routine
cal, surgical, and endoscopic therapies on the in- clinical management.
cidence of esophageal adenocarcinoma and mor-
tality are also lacking. In addition, the optimal Guidel ine s
techniques for surveillance and the optimal sur-
veillance intervals for patients with and those with- Guidelines for the management of Barrett’s esoph-
out dysplasia are unclear. Although epidemiologic agus have been published by the American Col-
and experimental studies have suggested a poten- lege of Gastroenterology,9 the American Society

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 clinical pr actice

for Gastrointestinal Endoscopy,8 the British Soci- that such therapies reduce the risk of neoplastic
ety of Gastroenterology,16 the French Society of progression. Endoscopic surveillance with detailed
Digestive Endoscopy,17 and the Society for Surgery inspection and systematic biopsies is recommend-
of the Alimentary Tract.10 The strategies proposed ed for most patients with Barrett’s esophagus, but
in this article are generally consistent with these decision making should take into account the pa-
guidelines (Table 2). tient’s age, coexisting conditions, life expectancy,
and the lack of conclusive evidence that surveil-
lance reduces mortality from esophageal adeno-
C onclusions a nd
R ec om mendat ions carcinoma. In patients with nondysplastic Barrett’s
esophagus, after at least two endoscopic exami-
Patients with Barrett’s esophagus, such as the pa- nations with no evidence of disease progression,
tient described in the vignette, should be informed surveillance periods can probably be extended to
that they are at increased risk for the development 3 years. In patients with high-grade dysplasia, en-
of esophageal adenocarcinoma but that this risk doscopic therapies or surgical resection should be
is low. Acid-suppressive therapy (proton-pump in- considered.
hibitors), antireflux surgery, or both are useful in Dr. Sharma reports receiving consulting fees from AstraZen-
controlling symptoms of reflux and healing ero- eca, Santarus, and Takeda and grant support from Given Imag-
ing, Barrx Medical, Olympus, Cogentus, Mauna Kea Technolo-
sive esophagitis in patients with Barrett’s esoph- gies, and Takeda. No other potential conflict of interest relevant
agus, but there is currently no conclusive evidence to this article was reported.

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decrease the incidence of esophageal ad- 40. Overholt BF, Wang KK, Burdick JS, et Copyright © 2009 Massachusetts Medical Society.

collections of articles on the journal’s web site

The Journal’s Web site (NEJM.org) sorts published articles into
more than 50 distinct clinical collections, which can be used as convenient
entry points to clinical content. In each collection, articles are cited in reverse
chronologic order, with the most recent first.

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