Clinical Review & Education

JAMA | Review

Barrett Esophagus
A Review
Prateek Sharma, MD

Multimedia
IMPORTANCE Barrett esophagus is characterized by the replacement of normal esophageal
squamous cell epithelium with columnar metaplasia and affects approximately 5% of people
in the US and approximately 1% worldwide. Approximately 3% to 5% of patients with
Barrett esophagus will be diagnosed with esophageal adenocarcinoma in their lifetime.

OBSERVATIONS Barrett esophagus affects approximately 2.3% to 8.3% of people with

gastroesophageal reflux disease (GERD) and approximately 1.2% to 5.6% of people without
GERD. Characteristics associated with Barrett esophagus include older age (prevalence of
approximately 1.1% in individuals older than 50 years compared with 0.3% in those 50 years
or younger), male sex, and smoking (prevalence of approximately 12% in people who smoke
cigarettes compared with 1.1% in those who do not smoke cigarettes). The histopathology of
Barrett esophagus progresses from metaplasia to dysplasia and, without treatment, can
progress to adenocarcinoma. People with Barrett esophagus have approximately a 0.2% to
0.5% annual rate of developing esophageal adenocarcinoma. Management of Barrett
esophagus primarily consists of acid-suppressive medications to reduce underlying GERD
symptoms and surveillance endoscopy every 3 to 5 years. In patients with Barrett esophagus
and dysplasia or early cancer, endoscopic therapy consisting of resection and ablation
successfully treats 80% to 90% of patients.
Author Affiliation: University of
CONCLUSIONS AND RELEVANCE Barrett esophagus affects approximately 5% of people in the
Kansas School of Medicine, VA
US and approximately 1% worldwide and is associated with an increased risk of esophageal Medical Center, Kansas City, Kansas.
adenocarcinoma. First-line therapy for Barrett esophagus consists of proton-pump inhibitors Corresponding Author: Prateek
for control of reflux symptoms, but their role in chemoprevention is unclear. Surveillance with Sharma, MD, University of Kansas
upper endoscopy is recommended by practice guidelines to monitor for progression to School of Medicine, VA Medical
Center, 4801 E Linwood Blvd,
esophageal adenocarcinoma, but randomized clinical trials are lacking.
Kansas City, MO 64128 (psharma@
kumc.edu).
JAMA. 2022;328(7):663-671. doi:10.1001/jama.2022.13298 Section Editor: Mary McGrae
McDermott, MD, Deputy Editor.

B
arrett esophagus is characterized by the replacement of nor-
mal esophageal squamous cell epithelium with mucus-
secreting columnar cells, also known as columnar metapla-
sia. Barrett esophagus results from reflux of gastric contents into the
esophagus, resulting in inflammation and chronic tissue injury.1 Pa-
tients with Barrett esophagus have approximately a 3% to 5% risk
of developing esophageal adenocarcinoma in their lifetime.2 This re-
view summarizes current evidence regarding diagnosis and man-
agement of Barrett esophagus.
Methods
The PubMed and Cochrane databases were searched for English-
language studies of adults with Barrett esophagus published from
January 2006 to March 2022 using combinations of the following
search terms; Barrett’s esophagus, Barrett's, diagnosis, management,
clinical trial, guideline, meta-analysis, randomized clinical trial, and
systematic review. Randomized clinical trials, meta-analyses, and clini-
cal guidelines were prioritized and articles were selected for inclusion
based on their relevance to the generalist clinician. Of 477 articles iden-
tified, 55 were included, including 21 meta-analyses or systematic re-
views, 7 randomized clinical trials, 19 cohort/population-based stud-
ies, 1 review, and 7 guideline or recommendation statements.
Association of GERD With Barrett Esophagus
A2021systematicreviewandmeta-analysisof44cross-sectionalstud-
ies reported that among 26 521 people with GERD, the pooled preva-
lence of histologically confirmed Barrett esophagus was 7.2% (95% CI,
5.4%-9.3%).3 Despite the known association of GERD with Barrett
esophagus, only 38.4% (95% CI, 28.1%-49.2%) of endoscopically
suspected cases of Barrett esophagus (defined as the presence of
columnar-linedesophagusvisualizedatendoscopybutwithoutbiopsy)
worldwide were confirmed by histology in this report, leading to po-
tential overdiagnosis of Barrett esophagus.3 In this meta-analysis, the
prevalence of histologically confirmed short-segment Barrett esopha-
gus, defined as Barrett esophagus affecting 1 to 3 cm of the esopha-
gus, among people with GERD symptoms was 6.7% (95% CI, 4.6%-
9.1%). The prevalence of histologically confirmed long-segment
Barrett esophagus, defined as Barrett esophagus affecting more than

jama.com (Reprinted) JAMA August 16, 2022 Volume 328, Number 7 663

© 2022 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022

 Clinical Review & Education Review A Review of Barrett Esophagus

Figure. Treatment Algorithm for Patients With Barrett Esophagus

Patient presents with chronic gastroesophageal reflux disease (GERD) ≥5 y

and ≥1 risk factor including

Male sex, age >50 y, smoking, obesity, and diet high in fast food and meat

Endoscopy to confirm Barrett esophagus (BE) diagnosis

BE confirmed BE not confirmed Continue medical treatment for GERD

Determination of BE dysplasia grade

Nondysplastic BE Low-grade dysplasia (LGD) High-grade dysplasia Early esophageal adenocarcinoma

No risk factors ≥1 risk factor present including

Multifocal LGD
LGD confirmed on
subsequent endoscopy
BE length ≥3 cm
Family history of esophageal
adenocarcinoma

Surveillance Surveillance Endoscopic therapy

Every 3 y Every 1 y Endoscopic mucosal resection or submucosal dissection followed by endoscopic ablative therapy
for BE length ≥3 cm or
Every 5 y Endoscopic ablative therapy alone for patients without any lesions
for BE length 1-3 cm

This algorithm has not been validated in randomized clinical trials.

3cmoftheesophagus,amongindividualswithGERDsystemswas3.1% established Barrett esophagus to identify esophageal adenocarci-

(95% CI, 2.0%-4.6%). The proportion of people who progress from
Barrett esophagus to esophageal adenocarcinoma is greater in people
withlong-segmentBarrettesophaguscomparedwiththosewithshort-
segment Barrett esophagus. A meta-analysis of 4097 patients with
Barrett esophagus without dysplasia reported annual rates of progres-
sion to esophageal adenocarcinoma of 0.06% (95% CI, 0.01%-0.10%)
in those with short-segment Barrett esophagus and 0.31% (95% CI,
0.21%-0.40%) in those with long-segment Barrett esophagus.4 In a
cohort study5 of 378 patients undergoing upper endoscopy for evalu-
ation of GERD, short-segment Barrett esophagus was more prevalent
compared with long-segment Barrett esophagus (8.5% vs 4.8%), a
finding that has been reported in other studies.2,4
In a population-based study of 3000 people in Sweden, 1000 of
whomunderwentupperendoscopy,biopsy-confirmedBarrettesopha-
gus was identified in 2.3% of those with GERD symptoms and in 1.2%
of those without GERD symptoms.6 In a US study of 961 volunteers un-
dergoing screening colonoscopy as well as upper endoscopy, Rex et al
reported that Barrett esophagus was present in 8.3% of those with
GERD symptoms and in 5.6% of those without GERD symptoms.7
Evaluating Patients for Barrett Esophagus
Screening refers to evaluating individuals with GERD for Barrett
esophagus and is typically performed using endoscopy (Figure). In
contrast, surveillance consists of periodically evaluating patients with
noma as early as possible. Among patients with GERD, Barrett
esophagus is more common among men than women. From the 12
studies included in a systematic review and meta-analysis of 28 136
people with GERD, the pooled prevalence of histologically con-
firmed Barrett esophagus was 10.8% (95% CI, 6.6%-15.9%) in men
and 4.8% (95% CI, 2.7%-7.5%) in women.3
A large cohort study of 29 374 patients showed that the preva-
lence of Barrett esophagus was higher in patients older than 50 years
than in those 50 years or younger (1.1% vs 0.3%; P = .02).8 There was
also a significant difference in the rates of Barrett esophagus preva-
lence by race (Table 1). In a cohort study of 2100 patients undergo-
ing upper endoscopy, the prevalence of Barrett esophagus in White
individuals was 6.1%, compared with 1.7% for Hispanic individuals
(P = .002) and 1.6% for Black individuals (P = .004)11; however, these
results were from a single-center, retrospective study and require con-
firmation. Tobacco smoking is associated with higher Barrett esopha-
gus prevalence. In a cohort study of 1056 patients undergoing en-
doscopy, Barrett esophagus was diagnosed in 12% of people who
smoked cigarettes compared with 1.1% of people who did not smoke
cigarettes (P < .001).10
A systematic review and meta-analysis of 29 cohort studies
(24 retrospective and 5 prospective) that included 13 434 patients
(mean body mass index range, 39-51.2) undergoing evaluation prior
to bariatric surgery reported a pooled prevalence of Barrett esopha-
gus of 0.9% (95% CI, 0.7%-1.3%). This study showed a positive as-
sociation between mean body mass index and Barrett esophagus

664 JAMA August 16, 2022 Volume 328, Number 7 (Reprinted) jama.com

© 2022 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022

 A Review of Barrett Esophagus
Table 1. Clinical Characteristics Associated With Barrett Esophagusa
Characteristic
associated with Barrett
esophagus Type of study No. of studies and participants
GERD9 Systematic review and 11 studies (1 cross-sectional and 10
meta-analysis cohort studies); N = 575 756
participants
Sex3 Systematic review and 12 cohort studies
meta-analysis
Age8 Cohort study 29 374 patients undergoing
esophagogastroduodenoscopy
Tobacco smoking10 Cohort study 1056 patients undergoing EGD
Race11 Cohort 2100 patients undergoing EGD
prevalence, in which for each 1-point increase in body mass index
there was a 0.15% increase in prevalence of Barrett esophagus.12
Elevated levels of serum proinflammatory cytokines (adipocyto-
kines) associated with visceral fat in people with obesity is one theory
regarding the association of obesity with Barrett esophagus.13 In a
systematic review of 5 studies that included 1009 patients, central
obesity was associated with esophageal inflammation Barrett
esophagus and esophageal adenocarcinoma (adjusted odds ratio
[OR], 1.88 [95% CI, 1.20-2.95]) (absolute data not provided).14
In a population-based case-control study of 296 patients with Barrett
esophagus and 309 people without Barrett esophagus, a 110-item
food frequency questionnaire was used to evaluate adherence to a
“health-conscious diet” (high in fruits, vegetables, and nonfried fish)
compared with a “Western diet” (high in fast food and meat). Par-
ticipants were categorized into quartiles according to the degree of
their adherence to a healthy diet. Compared with 309 people who
were healthy controls, those with Barrett esophagus had a signifi-
cantly higher proportion of patients in the highest (best) com-
pared with the lowest (worst) quantile of a health conscious diet (15%
vs 25% in the best quantile). However, compared with healthy con-
trols, there was no statistically significant difference between the
proportion of people with Barrett esophagus and healthy controls
in the worst vs the best quantile for adherence to a Western diet (24%
vs 25% in the worst quantile).15
No randomized clinical trials have demonstrated that screen-
ing for Barrett esophagus reduces death rates from esophageal
adenocarcinoma. Despite this, some professional organizations
(eg, American College of Gastroenterology [ACG], American Soci-
ety for Gastrointestinal Endoscopy) recommend screening and
surveillance for Barrett esophagus. A recent analysis suggested
that when determining whether to perform screening or surveil-
lance, the patient’s overall life expectancy (<10 years) should be
considered.16-18
Risk Scoring Tools for Identifying People at Risk
of Barrett Esophagus
Risk-assessment scoring systems may help identify patients who
may benefit from screening for Barrett esophagus and those with
Barrett esophagus who may benefit from surveillance testing. In a
case-control study of 320 patients with Barrett esophagus and 317
jama.com
© 2022 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022
Review Clinical Review & Education
Associations
GERD population: 7.21%
(95% CI, 5.61%-8.81%);
general population: 0.96%
(95% CI, 0.75%-1.18%)
Men: 10.8% (95% CI, Abbreviations: EAC, esophageal
6.6%-15.9%); women: 4.8% adenocarcinoma; EGD,
(95% CI, 2.7%-7.5%)
esophagogastroduodenoscopy;
<50 y: 0.3%; ≥50 y: 1.1%; GERD, gastroesophageal reflux
P = .02
disease.
Smokers: 12%; nonsmokers: a
1.1%; P <.001 Other clinical characteristics that are
thought to be less strongly
White: 6.1%; Hispanic: 1.7%;
Black: 1.6% associated with Barrett esophagus
P value (White vs Hispanic include hiatal hernia, elevated body
individuals) = .0002; mass index, nocturnal reflux
P value (White vs Black symptoms, and family history of
individuals) = .004
Barrett esophagus or EAC.
population controls, any GERD symptoms (93% vs 61%; P < .05)
and weekly GERD symptoms (80% vs 29%; P < .05) were more
prevalent in patients with Barrett esophagus.19 Patients with
Barrett esophagus, compared with controls, were 8 to 16 times
more likely to report severe or very severe GERD symptoms.19 A
prospective observational study of 1241 patients, presenting either
for their first esophagogastroduodenoscopy or their first endo-
scopic therapy of early neoplastic Barrett esophagus (defined as
any dysplasia and/or mucosal cancer) assessed the accuracy of
multiple risk assessment tools (including the Gerson, Locke, Thrift,
Michigan Barrett Esophagus Prediction Tool [M-BERET], Nord-
Trøndelag Health Study [HUNT], Kunzmann tools) for discriminat-
ing patients with Barrett esophagus from those without.20 For
example, the M-BERET incorporates GERD symptoms and risk fac-
tors to calculate a predicted probability of Barrett esophagus in
patients without a diagnosis of GERD, while the Thrift tool is limited
to patients with GERD and relies on additional characteristics such
as age, sex, smoking status, body mass index, highest level of edu-
cation, and frequency of use of acid-suppressant medications.
Although GERD symptom frequency and duration alone had a sen-
sitivity of 56.7% and specificity of 57.9% in identifying patients
with Barrett esophagus, each of the scoring tools tested was more
accurate in identifying Barrett esophagus than the 2 GERD criteria
(frequency and duration) alone (area under the receiver-operating
curve for GERD by symptoms of heartburn and regurgitation vs
range for other tools: 0.579 vs 0.660-0.695).20 However, no ran-
domized clinical trial evidence exists to support these screening
tools in clinical practice to identify patients with Barrett esophagus.
Endoscopic and Pathologic Diagnosis of Barrett Esophagus
Interobserver variability exists in the diagnosis of Barrett esopha-
gus with endoscopy. In a prospective study of 192 patients with
GERD, in which 2 endoscopic examinations were performed 6 weeks
apart, 20% had Barrett esophagus documented on only 1 examina-
tion resulting in an apparent change in diagnosis.21 Similarly, there
is variability in Barrett esophagus length measurement. In a pro-
spective study of 96 patients with Barrett esophagus who under-
went 2 endoscopies 16 to 19 months apart, variability ranged from
1.4 to 1.6 cm in the Barrett esophagus length measurement.22 The
Prague criteria, consisting of criteria for endoscopic grading using
(Reprinted) JAMA August 16, 2022 Volume 328, Number 7 665
 Clinical Review & Education Review
the circumferential and maximal extent of the Barrett esophagus
segment proximal to the top of the gastric folds, is associated with
less interobserver variability in Barrett esophagus diagnosis.16,23 The
American Gastroenterological Association (AGA) recommends that
a diagnosis of dysplasia in Barrett esophagus should be confirmed
by at least 2 pathologists, preferably including 1 with expertise in
esophageal histopathology.24
Swallowed Cell-Collection Methods for Diagnosis
of Barrett Esophagus
Although evaluations for Barrett esophagus are typically per-
formed with conventional white light high-definition upper endos-
copy, newer modalities include swallowed cell-collection devices,
transnasal endoscopy, and esophageal capsule endoscopy that do
not require sedation and can safely be performed in the office set-
ting to screen for Barrett esophagus. The current ACG guidelines25
mention unsedated transnasal endoscopy as an alternative to con-
ventional upper endoscopy, given its comparable performance to
conventional upper endoscopy for screening. In unsedated trans-
nasal endoscopy, an ultrathin endoscope is passed through the nose
to evaluate the upper gastrointestinal tract. This method has a sen-
sitivity of 98% and a specificity of 100% compared with conven-
tional endoscopy for diagnosing Barrett esophagus.25 It is associ-
ated with lower costs and fewer adverse events because of the
absence of sedation. Current ACG guidelines mention use of a swal-
lowable, nonendoscopic capsule sponge device combined with a bio-
marker (eg, protein marker expressed in intestinal metaplasia [tre-
foil factor 3] or methylated DNA markers) as potential methods for
screening those with chronic GERD and other risk factors.25 The cap-
sule is a pill with a spherical sponge compressed inside it. Once swal-
lowed, the capsule dissolves and the sponge emerges. The sponge
is then pulled out by the string and sent to the laboratory for bio-
marker assessment.
Progression of Barrett Esophagus
to Esophageal Adenocarcinoma
A meta-analysis of 24 studies and 2694 patients, followed up for a
mean (range) of 5.3 (3.2-12.8) years, found that patients initially di-
agnosed with Barrett esophagus without dysplasia had a 0.2% to
0.5% annual rate of developing esophageal adenocarcinoma. For
those with Barrett esophagus and low-grade dysplasia, the annual
incidence rate of esophageal adenocarcinoma was 0.54% (95% CI,
0.32%-0.76%) and the annual incidence of either esophageal
adenocarcinoma or high-grade dysplasia was 1.73% (95% CI,
0.99%-2.47%).26
A meta-analysis of 11 studies (prospective and retrospective non-
randomized trials) that included 10 632 patients with Barrett esopha-
gus reported a 3% (95% CI, 2%-5%) pooled prevalence of esopha-
geal adenocarcinoma.2 A large multicenter cohort study of 3643
patients with Barrett esophagus investigated prevalence patterns
of Barrett esophagus–associated dysplasia over 25 years and found
that, while prevalence of low-grade dysplasia on index endoscopy
was relatively stable throughout the study period at approximately
12% to 13%, high-grade dysplasia findings increased by approxi-
mately 148%, from 2.7% in 1990 to 1994 to 10% in 2010 and be-
yond and a 112% increase in esophageal adenocarcinoma, from 3.3%
666 JAMA August 16, 2022 Volume 328, Number 7 (Reprinted)
© 2022 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022
A Review of Barrett Esophagus
in 1990 to 1994 to 7.6% between 2010 and 2016 (P < .001). There
was also a significant increase in the prevalence of visible lesions,
defined as any abnormality of the Barrett esophagus surface pat-
terns suggesting dysplasia or cancer from 5.1% (1990-1994) to 16.3%
(2010-2019) during index endoscopy, indicating the increase in neo-
plastic lesions detected at initial screening endoscopy.27 Data from
large population-based studies with at least 3 years of follow-up re-
ported that approximately 58% to 66% of esophageal adenocarci-
nomas detected by endoscopy were diagnosed within 1 year of an
index Barrett esophagus screening endoscopy and were consid-
ered likely to have been missed during index endoscopy.28 In an-
other cohort of 13 159 patients diagnosed with high-grade dyspla-
sia or esophageal adenocarcinoma, 12.7% (34/267) were identified
within 3 to 12 months after Barrett esophagus diagnosis and were
considered to have possibly been missed during index endoscopy,
with 25% of these occurring among patients with Barrett esopha-
gus with low-grade dysplasia and 9% occurring among those with
nondysplastic Barrett esophagus.29 To improve detection of dys-
plasia, a neoplasia detection rate (rate of high-grade dysplasia or
esophageal adenocarcinoma detection during initial surveillance en-
doscopy) is recommended as a validated quality measure for endo-
scopic evaluation of patients with Barrett esophagus,30 with data
indicating that every 1% increase of neoplasia detection rate leads
to a clinically relevant 3.5% decrease in the rate of later diagnosis
of Barrett esophagus neoplasia presumed to have been missed at
the index endoscopy.31
A high-definition endoscope can improve detection of subtle
lesions in the esophagus. It is also important to ensure that the esoph-
ageal mucosa is clear of bubbles/food debris to improve the Barrett
esophagus surface inspection. A prospective multicenter study of
112 patients with Barrett esophagus showed that longer Barrett in-
spection time during endoscopy was associated with higher rates
of lesion detection. Endoscopists who had a mean Barrett inspec-
tion time longer than 1 minute per centimeter of Barrett esopha-
gus, compared with those with inspection time less than 1 minute
per centimeter of Barrett esophagus, detected more patients with
endoscopically suspicious lesions (54.2% vs 13.3%; P = .04). There
was also a trend toward a higher detection rate of high-grade dys-
plasia/esophageal adenocarcinoma (40.2% vs 6.7%; P = .06).32
Thus, high-quality index endoscopy, consisting of using high-
definition endoscopes, cleaning the esophageal mucosa, and spend-
ing sufficient inspection time, are important in the diagnosis of neo-
plasia in Barrett esophagus patients.
Characteristics Associated With Progression
of Barrett Esophagus to Esophageal
Adenocarcinoma
Several characteristics have been associated with higher rates of pro-
gression from Barrett esophagus to esophageal adenocarcinoma.
A systematic review and meta-analysis of 20 cohort studies that in-
cluded 74 943 patients with Barrett esophagus reported that older
age (OR, 1.027 [95% CI, 1.007-1.046]), male sex (OR, 2.16 [95% CI,
1.84-2.53] vs female sex), history of smoking (OR, 1.47 [95% CI, 1.09-
1.98] vs never smoking), and low-grade dysplasia (OR, 4.25
[95% CI, 2.58-7.00]) were associated with Barrett esophagus
progression to esophageal adenocarcinoma (absolute rates not
jama.com
 A Review of Barrett Esophagus Review Clinical Review & Education

Table 2. Randomized Trials of Treatment for Barrett Esophagus

Source Study population Intervention/comparison Outcomes

Chemoprevention
Heath et al,33 2003 100 Patients in the US with Barrett
esophagus with dysplasia
Jankowski et al,34 2557 Patients with Barrett esophagus
2018 from the UK
Endoscopic therapy for Barrett esophagus
Shaheen et al,35 2009 127 Patients with Barrett esophagus
and dysplasia from the US
Phoa et al,36 2014 136 Patients with Barrett esophagus
with low-grade dysplasia
Terheggen et al,37 40 Patients with Barrett esophagus
2017 with focal high-grade dysplasia
or early adenocarcinoma ≤3 cm
Barret et al,38 2021 82 Patients with Barrett esophagus
with low-grade dysplasia
Celecoxib 200 mg (n = 49); placebo (n = 51)
High-dose PPI (esomeprazole 40 mg twice-daily)
with acetylsalicylic acid (n = 577); low-dose PPI
(esomeprazole 20 mg once-daily) with
acetylsalicylic acid (n = 571); high-dose PPI only
(esomeprazole 40 mg twice-daily) (n = 704);
low-dose PPI only (esomeprazole 20 mg daily)
(n = 705)
RFA (n = 84); sham (n = 43)
RFA (n = 68); surveillance (n = 68)
Endoscopic mucosal resection (n = 20);
endoscopic submucosal dissection (n = 20)
RFA (n = 42); surveillance (n = 40)
Change in the proportion of biopsy samples
showing dysplasia at 24 wk: −0.08
(celecoxib) vs −0.06 (placebo); P = .10
Composite end point: time to all-cause
mortality, esophageal adenocarcinoma, or
high-grade dysplasia; at 8.9 y follow-up:
high-dose PPI with acetylsalicylic acid,
52/572 (0.09); high-dose PPI only,
139/1270 (0.11); low-dose PPI with
acetylsalicylic acid, 99/699 (0.14); low-dose
PPI only, 174/1265 (0.14)
CE-IM at 12 mo: 77.4% (RFA) vs 2.3%
(sham); P < .001
CE-IM at 3 y: 88.2% (RFA) vs 0%
(surveillance); P < .001
R0 resection rates: 12% (endoscopic mucosal
resection) vs 59% (endoscopic submucosal
dissection); P = .01
CE-IM at 3 y: 35% (RFA) vs 0% (surveillance);
P < .001

Abbreviations: CE-IM, complete eradication of intestinal metaplasia; PPI, proton-pump inhibitor; RFA, radiofrequency ablation.

reported). Longer length of the Barrett esophagus segment,
measured endoscopically, was associated with higher risk of pro-
gression to esophageal adenocarcinoma. For each additional cen-
timeter of Barrett esophagus segment length (per cm), risk of esoph-
ageal adenocarcinoma increased by an OR of 1.25 (95% CI,
1.16-1.36) (absolute rates not provided).39
A meta-analysis of 4097 patients with Barrett esophagus and
without dysplasia reported annual rates of progression to esopha-
geal adenocarcinoma of 0.06% (95% CI, 0.01%-0.10%) for short-
segment (Barrett esophagus length <3 cm) Barrett esophagus vs
0.31% (95% CI, 0.21%-0.40%) for long-segment (Barrett esopha-
gus length ⱖ3 cm) Barrett esophagus.4 In the retrospective, multi-
center cohort study of 2145 patients with Barrett esophagus, after
adjusting for body mass index, smoking, race, use of aspirin, non-
steroidal anti-inflammatory drugs, and other factors, women had a
lower rate of progression to esophageal adenocarcinoma than men
(12.7% vs 21.4%; P < .001) at a median of 5.7 years of follow-up.40
Several Barrett esophagus and esophageal adenocarcinoma risk
stratification tools have been developed to identify patients at high-
est risk of developing Barrett esophagus–associated cancer. Among
4584 patients with Barrett esophagus in the US and Europe, Parasa
et al developed the 30-Point Progression in Barrett Esophagus (PIB)
score to identify patients most likely to develop high-grade dyspla-
sia or esophageal adenocarcinoma.41 The PIB score combines data
from age, sex, smoking history, length of the Barrett esophagus, and
presence of low-grade dysplasia. The score range is 0 to 45, with
scores greater than 20 indicating the highest risk. Thresholds of 11
to 20 (intermediate risk) and 20 to 45 (high risk) for the PIB score
identified people at meaningfully increased risk of developing high-
grade dysplasia or esophageal adenocarcinoma. Using this tool, those
with a score of 0 to 10 had an annual 0.13% risk of progression, while
those with scores of 11 to 20 had an annual risk of progression of
0.73% and those with scores higher than 20 had a 2.1% annual risk
of Barrett esophagus progression. The PIB score was externally vali-
dated in a group of 1198 patients with Barrett esophagus and dem-
onstrated that the low-risk group (defined as a PIB score of 0-10)
had a 0.2% annual rate of progression, while the intermediate-risk
group (defined as a PIB score of 11-20) had a 0.5% annual rate of pro-
gression and the high-risk group (defined as PIB of >20) had a 1.5%
annual rate of progression.
Preventing Progression of Barrett Esophagus
to Esophageal Adenocarcinoma
Chemoprevention strategies have been studied for their ability to
reduce the risk of progression of Barrett esophagus to esophageal
adenocarcinoma (Table 2). In a randomized, double-blind, phase 3
ASPECT clinical trial34 conducted at 84 centers in the UK and
Canada, 2557 patients with Barrett esophagus (without high-grade
dysplasia/esophageal adenocarcinoma) were randomized to 1 of 4
groups: high-dose esomeprazole (40 mg twice daily) with aspirin
(300 mg in the UK, 325 mg in Canada), low dose esomeprazole
(20 mg daily) with aspirin, 40-mg twice-daily esomeprazole, and
20-mg daily esomeprazole. At 8.9 years of follow-up, high-dose
esomeprazole combined with aspirin significantly reduced rates of
the combined outcome of esophageal adenocarcinoma, all-cause
mortality, and high-grade dysplasia (52 events in 572 patients
[9%]) compared with low-dose proton-pump inhibitor (PPI) with-
out aspirin (99 events in 699 patients [14%]), high-dose PPI alone
(139 events in 1270 patients [11%]), or low-dose PPI alone (174
events in 1265 patients [14%]). Furthermore, there was no signifi-
cant difference in severe adverse events between the high-dose
esomeprazole plus aspirin group (274 events in 571 patients) com-
pared with the high-dose esomeprazole only group (303 events in
704 patients).34
A smaller randomized placebo-controlled clinical trial of 100 pa-
tients with Barrett esophagus and either high- or low-grade dyspla-
sia reported no significant difference in the change in the percent-
age of biopsy samples showing dysplasia (ie, dysplasia progression)
with cyclooxygenase 2 (COX-2) inhibition (n = 49; 200 mg twice daily
of celecoxib) compared with placebo (n = 51) at 48-week follow-up

jama.com (Reprinted) JAMA August 16, 2022 Volume 328, Number 7 667

© 2022 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022

 Clinical Review & Education Review
Table 3. Types of Barrett Esophagus and Associated Risk of Progression and Surveillance Recommendations
Type of Barrett esophagus
Characteristic No dysplasia Indefinite for dysplasia
Histology No nuclear abnormalities, Moderate architectural
except focal nuclear changes and nuclear
stratification. Greater abnormalities that are
nuclear alterations still less marked than those
qualify as no dysplasia if seen in dysplasia2
these changes are
associated with
inflammation, erosion,
or ulceration2
Risk of progression to 0.2-0.5 annually 0.1-0.9 annually
adenocarcinoma, %
Frequency of surveillance 3-5 y 12 mo
recommended by guidelines
(−0.08% vs −0.06%). The authors reported difficulty with patient
accrual, thus adjusting the sample size to a lower statistical power,
and still did not meet the expected numbers. 33 Additionally,
compared with the ASPECT trial, this trial had a much smaller sample
size, administered celecoxib without PPI, and included a popula-
tion with combined Barrett esophagus and dysplasia.
The ACG and AGA recommend acid exposure elimination to
prevent progression of Barrett esophagus to esophageal adeno-
carcinoma.16,24 The ACG guidelines cite a meta-analysis of 7 obser-
vational studies demonstrating a reduced risk of high-grade dyspla-
sia and/or esophageal adenocarcinoma from inception to 2013
among PPI users with Barrett esophagus compared with those not
using PPIs (OR, 0.3 [95% CI, 0.1-0.8]).16 Despite the results of the
above-mentioned ASPECT trial, current ACG and AGA guidelines
recommend against routine prescribing of aspirin and/or nonsteroi-
dal anti-inflammatory drugs as chemoprevention for patients with
Barrett esophagus, citing concern for cerebral and gastrointestinal
hemorrhage.4,24
Management of Barrett Esophagus
Surveillance Endoscopy
No randomized clinical trials have demonstrated benefit of surveil-
lance endoscopy for preventing development of esophageal adeno-
carcinoma or death due to esophageal adenocarcinoma. However,
clinical guidelines and expert opinion recommend surveillance en-
doscopy for patients with nondysplastic Barrett esophagus at in-
tervals of 3 to 5 years (Table 3).4,16,23,24,42 Current ACG guidelines
recommend that the length of the nondysplastic Barrett esopha-
gus segment be considered when assigning surveillance intervals
such that longer segments of Barrett esophagus (ⱖ3 cm) are evalu-
ated with endoscopy every 3 years, while shorter segments of Barrett
esophagus (<3 cm) are evaluated with endoscopy every 5 years.4 For
those diagnosed with Barrett esophagus on initial screening exami-
nation, AGA and ACG guidelines cited that there is no need for a 1-year
repeat endoscopy as was suggested previously due to the lack of evi-
dence that a repeat endoscopy in such a short time interval was as-
sociated with better outcomes.16,24
High-definition white light endoscopy, consisting of signal im-
ages with resolutions up to a million pixels, and chromoendoscopy,
consisting of dye spraying using acetic acid or electronic chromo-
endoscopy, which uses imaging technologies to provide contrast
668 JAMA August 16, 2022 Volume 328, Number 7 (Reprinted)
© 2022 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022
A Review of Barrett Esophagus
Low-grade dysplasia High-grade dysplasia
Budded, branched, crowded, or irregularly Architectural and/or
shaped glands, papillary extensions into cytological abnormalities
gland lumina and villiform configuration of listed above are more
the mucosal surface. Nuclear features may prominent2
include marked variation in size and shape,
nuclear and/or nucleolar enlargement,
hyperchromatism, and increased numbers
of abnormal mitoses. Nuclear changes may
involve the mucosal surface3
0.5-0.7 annually 5-7 annually
6-12 mo Endoscopic therapy
preferred
enhancement, have improved the diagnosis and detection of Barrett
esophagus dysplasia. A meta-analysis that included 25 studies with
2304 patients with Barrett esophagus reported a pooled sensitiv-
ity of 97% (95% CI, 95%-98%), negative predictive value of 98%
(95% CI, 95%-99%), and specificity of 85% (95% CI, 69%-93%) for
detecting dysplasia using acetic acid chromoendoscopy and a pooled
sensitivity of 94% (95% CI, 83%-98%), negative predictive value
of 98% (95% CI, 95%-98%), and specificity of 94% (95% CI, 81%-
99%) for electronic chromoendoscopy.43 Wide-area transepithe-
lial sampling, a newer technique that uses an abrasive brush to ob-
tain samples from a larger surface area of the esophagus during
endoscopy, may also be helpful.
The ACG recommends high-definition white light endoscopy for
surveillance and recommends that electronic chromoendoscopy
should be added only as an advanced imaging technique.16 More re-
cently, the American Society for Gastrointestinal Endoscopy recom-
mended chromoendoscopy or virtual chromoendoscopy in addi-
tion to white light endoscopy and biopsy specimens.42 In a systematic
review and meta-analysis that included 12 randomized clinical trials
(2433 Barrett esophagus patients) there was a 9% (95% CI, 4.1%-
14%) absolute increase in dysplasia detection using chromoendos-
copy compared with white light endoscopy.42
Adherence to Guideline Recommendations
for Surveillance
A systematic review and meta-analysis of 19 studies (1 randomized
clinical trial, 1 case-control, and 17 cohort studies) that included pa-
tients with Barrett esophagus who had undergone surveillance com-
pared with those who underwent either no surveillance or inad-
equate surveillance reported that patients who had surveillance
endoscopy, compared with those either without surveillance or with
inadequate surveillance, had better outcomes (35.8% vs 57.8%;
P = .02), all-cause mortality (51.9% vs 81.5%; P = .01), and earlier
stage of esophageal adenocarcinoma diagnosis (55.8% vs 35.8%;
P = .01).44 However, these results were primarily based on obser-
vational data. Another meta-analysis reported variation in rates of
adherence to surveillance interval recommendations according to
country and practice type. Factors associated with improved adher-
ence included shorter Barrett esophagus length, salaried employ-
ment, procedure performed at a university hospital, and the pres-
ence of specific Barrett esophagus clinical programs.45
jama.com
 A Review of Barrett Esophagus
Endoscopic Treatment Interventions
Advances in endoscopic therapy for Barrett esophagus over the past
2 decades have reduced the need for surgical intervention for pa-
tients with early esophageal adenocarcinoma and high-grade dis-
ease. Visible neoplastic lesions in patients with Barrett esophagus
can be resected using endoscopic techniques. If needed, endo-
scopic ablative therapy may be used to eradicate any residual flat
Barrett esophagus segments.46
Endoscopic Mucosal Resection and Submucosal Dissection
Lesions with neoplasia in patients with Barrett esophagus can be re-
sected using either mucosal resection, in which small lesions lo-
cated no deeper than the superficial submucosal layer are re-
sected, or submucosal dissection, in which larger lesions within the
deep submucosa are resected. Multiple mucosal resection devices
are available, but multiband mucosectomy is the preferred tech-
nique due to its time and relative cost.46 Endoscopic submucosal
dissection has been associated with higher rates of histologically
complete resection, compared with mucosal resection for the eradi-
cation of early esophageal adenocarcinoma; however, it is techni-
cally more demanding and may cause more adverse events.37 Thus,
endoscopic submucosal dissection may be reserved for lesions with
a bulky intramural component or those with endoscopic features sug-
gestive of submucosal involvement, both of which occur in only ap-
proximately 11% to 36%47,48 of patients with high-grade dysplasia
and esophageal adenocarcinoma.46 In a randomized clinical trial, 40
patients with Barrett esophagus and high-grade dysplasia or early
esophageal adenocarcinoma were randomized to endoscopic mu-
cosal resection or endoscopic submucosal dissection.37 Although pa-
tients with endoscopic submucosal dissection had significantly higher
en-bloc (R0) resection rates compared with those who received en-
doscopic mucosal resection (59% vs 12%; P = .01), the overall rates
of remission at 3 months were similar (93.8% vs 94.1%).
Endoscopic Ablative Therapy
Resection of visible neoplastic Barrett esophagus lesions should be
followed by ablation, consisting of application of energy (hot or cold)
to the esophageal mucosa, to eradicate metaplasia. Ablation of flat
Barrett esophagus can be performed without resection. Although
a number of endoscopic therapy modalities for Barrett esophagus
exist, radiofrequency ablation is the most established method for
patients with confirmed high-grade dysplasia.16,24 A systematic re-
view and pooled analysis of 20 cohort studies (9 studies of resec-
tion followed by ablation and 11 of only resection) found that 73.1%
of patients undergoing endoscopic mucosal resection with subse-
quent radiofrequency ablation had complete eradication of intes-
tinal metaplasia, while strictures occurred in 10.2% of patients, bleed-
ing in 1.1% of patients, and perforations in 0.2% of patients.49
Recurrence of esophageal adenocarcinoma occurred in 1.4% of pa-
tients, dysplasia occurred in 2.6%, and intestinal metaplasia oc-
curred in 16.1% over a follow-up duration ranging from 12 to 67
months. The authors concluded that resection followed by radio-
frequency ablation is effective and safe for patients with high-
grade dysplasia/esophageal adenocarcinoma.49 However, this con-
clusion is based on observational data and the results may be affected
by confounding. The risk of adverse events with radiofrequency ab-
lation and endoscopic mucosal resection was reported in a system-
atic review and meta-analysis of 7 articles including 9200 patients
jama.com
© 2022 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022
Review Clinical Review & Education
treated with radiofrequency ablation with or without endoscopic mu-
cosal resection. Rates of adverse events were significantly higher for
radiofrequency ablation with endoscopic mucosal resection than
radiofrequency ablation without endoscopic mucosal resection
(22.2% vs 5%; relative risk, 4.4; P = .015). Barrett esophagus length
and baseline histology were associated with risk of adverse events.
For every 1-cm increase in the median Barrett esophagus length,
there was a 25% (95% CI, 16%-35%) increase in the rate of adverse
events. Also, with higher proportions of patients with high-grade dys-
plasia/esophageal adenocarcinoma, the rate of adverse events in-
creased by 1.7% (95% CI, 1.4%-2%).50 Despite this, endoscopic mu-
cosal resection remains necessary for visible lesions to achieve
complete eradication of intestinal metaplasia.
A nonrandomized and noncontrolled multicenter prospective
clinical trial of 120 patients reported that a nitrous oxide cryobal-
loon focal ablation system eradicated dysplasia in 97% of patients
and intestinal metaplasia in 91%.51 Postablation pain, assessed by
visual analog scale (0 [no pain] to 10 [most severe pain]) was mild
(median score of 2) and resolved quickly (median visual analog score
1 at day 1 and 0 at day 7), and 15 patients (12.5%) developed stric-
tures at a median (IQR) of 39 (31-45) days follow-up that required
dilation. A randomized pilot study with 65 patients with Barrett
esophagus showed that argon plasma coagulation, compared with
radiofrequency ablation, achieved complete Barrett esophagus ab-
lation in 55.8% of patients vs 48.3% (OR, 1.4 [95% CI, 0.5-3.6]), while
adverse events and quality of life scores after treatment were simi-
lar with the 2 methods.52
Clinical practice guidelines recommend endoscopic therapy for
patients with high grade dysplasia and early esophageal adenocar-
cinoma. Endoscopic therapy can be considered in patients with low
grade dysplasia, but is not recommended for patients with nondys-
plastic Barrett esophagus, because of their low rate of progression
to esophageal adenocarcinoma.16 The management of low-grade
dysplasia with endoscopic therapy for Barrett esophagus remains
controversial given the variable rates of progression of low-grade
dysplasia to esophageal adenocarcinoma (ie, 0.02%-11.4%).53
Patients should be included in the decision-making process and
assessing the risks and benefits of endoscopic therapy for Barrett
esophagus vs surveillance. Endoscopic therapy for Barrett esopha-
gus is preferred over esophagectomy for patients with Barrett
esophagus and high-grade dysplasia46 and is also recommended in
patients with T1a (in the mucosal layer) esophageal adenocarci-
noma. A systematic review and meta-analysis of 7 studies (retro-
spective and prospective) with 870 patients (510 underwent endo-
scopic therapy for Barrett esophagus and 360 underwent
esophagectomy) showed no difference in the rates of complete
eradication of dysplasia (314/334 for endoscopic therapy for
Barrett esophagus vs 237/241 for esophagectomy; relative risk
[RR], 0.96 [95% CI, 0.91–1.01]). Additionally, there were no differ-
ences in survival rates at 1 (97/100 vs 100/102), 3 (111/116 vs
92/99), and 5 years (295/337 vs 136/154) between the endoscopic
therapy for Barrett esophagus and esophagectomy groups (RR,
0.99 [95% CI, 0.94-1.03]), and cancer-related deaths were 0.2%
and 0.3%, respectively (P = .84). Adverse events (stricture forma-
tion, bleeding, and perforation) were significantly lower in the
endoscopic therapy for Barrett esophagus group (66/510) com-
pared with the surgery group (90/360) (RR, 0.38; 95% CI, 0.20-
0.73; P = .004).54
(Reprinted) JAMA August 16, 2022 Volume 328, Number 7 669
 Clinical Review & Education Review A Review of Barrett Esophagus

In patients with T1b esophageal adenocarcinoma (extending Limitations

beyond the mucosa into the submucosal tissue), consultation with
a multidisciplinary surgical oncology team is recommended before en-
doscopic therapy.16 In an observational study of 61 patients with
low-risk T1b cancers (macroscopically polypoid or flat, superficial sm1
invasion, good-to-moderate differentiation [G1/2], and no lympho-
vascular invasion) undergoing endoscopic resection, dysplasia was
completely eradicated in 87% of patients and maintenance of eradi-
cation occurred in 84% of all patients over a mean (SD) follow-up of
47 (29.1) months. The estimated 5-year survival rate was 84%. The
rate of major complications from endoscopic therapy for Barrett
esophagus was 1.5% with no deaths from the procedure reported.55
Endoscopic therapy for Barrett esophagus is preferred over
esophagectomy for patients with T1a esophageal adenocarcinoma
and is a reasonable alternative to esophagectomy in patients with
T1b esophageal adenocarcinoma with low-risk features, such as less
than 500-mm invasion in the submucosa cancer, good to moder-
ate differentiation, and no lymphatic invasion, and for those who are
poor surgical candidates.46
This review has several limitations. First, the review was restricted
to English-language articles. Second, 7 of the articles included in this
review were clinical practice guidelines. Clinical practice guidelines
may rely on expert opinion. Third, the literature search may have
missed some relevant publications. Fourth, much of the evidence
is based on observational data.
Conclusions
Barrett esophagus affects approximately 5% of people in the US
and approximately 1% worldwide and is associated with an
increased risk of esophageal adenocarcinoma. First-line therapy for
Barrett esophagus consists of PPIs for control of reflux symptoms,
but their role in chemoprevention is unclear. Surveillance with
upper endoscopy is recommended by practice guidelines to moni-
tor for progression to esophageal adenocarcinoma, but random-
ized clinical trials are lacking.

ARTICLE INFORMATION
Accepted for Publication: July 14, 2022.
Author Contributions: Dr Sharma had full access to
all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
data analysis.
Concept and design: Sharma.
Acquisition, analysis, or interpretation of data:
Sharma.
Drafting of the manuscript: Sharma.
Critical revision of the manuscript for important
intellectual content: Sharma.
Administrative, technical, or material support:
Sharma.
Conflict of Interest Disclosures: Dr Sharma
reported receiving research grants from ERBE,
Ironwood Pharmaceuticals, Olympus, and
Medtronic; being a consultant for Takeda, Samsung
Bioepis, Olympus, and Lumendi; and receiving
other funding from Medtronic, Fujifilm Medical
Systems USA, and Salix.
Additional Contributions: I acknowledge David
Wild, BS, and Jordanna Bermack, PhD, for
assistance in guiding the search and critical review
of the manuscript. Neither were compensated for
this work.
Submissions: We encourage authors to submit
papers for consideration as a Review. Please
contact Mary McGrae McDermott, MD, at
mdm608@northwestern.edu.
REFERENCES
1. Lam S, Hart AR. Does physical activity protect
against the development of gastroesophageal
reflux disease, Barrett’s esophagus, and esophageal
adenocarcinoma? a review of the literature with
a meta-analysis. Dis Esophagus. 2017;30(11):1-10.
doi:10.1093/dote/dox099
2. Parasa S, Desai M, Vittal A, et al. Estimating
neoplasia detection rate (NDR) in patients with
Barrett’s oesophagus based on index endoscopy:
a systematic review and meta-analysis. Gut. 2019;
68(12):2122-2128. doi:10.1136/gutjnl-2018-317800
3. Eusebi LH, Cirota GG, Zagari RM, Ford AC. Global
prevalence of Barrett’s oesophagus and
oesophageal cancer in individuals with
gastro-oesophageal reflux: a systematic review and
meta-analysis. Gut. 2021;70(3):456-463. doi:10.
1136/gutjnl-2020-321365
4. Chandrasekar VT, Hamade N, Desai M, et al.
Significantly lower annual rates of neoplastic
progression in short- compared to long-segment
non-dysplastic Barrett’s esophagus: a systematic
review and meta-analysis. Endoscopy. 2019;51(7):
665-672. doi:10.1055/a-0869-7960
5. Westhoff B, Brotze S, Weston A, et al. The
frequency of Barrett’s esophagus in high-risk
patients with chronic GERD. Gastrointest Endosc.
2005;61(2):226-231. doi:10.1016/S0016-5107(04)
02589-1
6. Ronkainen J, Aro P, Storskrubb T, et al.
Prevalence of Barrett’s esophagus in the general
population: an endoscopic study. Gastroenterology.
2005;129(6):1825-1831. doi:10.1053/j.gastro.2005.
08.053
7. Rex DK, Cummings OW, Shaw M, et al. Screening
for Barrett’s esophagus in colonoscopy patients
with and without heartburn. Gastroenterology.
2003;125(6):1670-1677. doi:10.1053/j.gastro.2003.
09.030
8. Macdonald CE, Wicks AC, Playford RJ. Ten years’
experience of screening patients with Barrett’s
oesophagus in a university teaching hospital. Gut.
1997;41(3):303-307. doi:10.1136/gut.41.3.303
9. Marques de Sá I, Marcos P, Sharma P,
Dinis-Ribeiro M. The global prevalence of Barrett’s
esophagus: a systematic review of the published
literature. United European Gastroenterol J. 2020;8
(9):1086-1105. doi:10.1177/2050640620939376
10. Balasubramanian G, Gupta N, Giacchino M,
et al. Cigarette smoking is a modifiable risk factor
for Barrett’s oesophagus. United European
Gastroenterol J. 2013;1(6):430-437. doi:10.1177/
2050640613504917
11. Abrams JA, Fields S, Lightdale CJ, Neugut AI.
Racial and ethnic disparities in the prevalence of
Barrett’s esophagus among patients who undergo
upper endoscopy. Clin Gastroenterol Hepatol.
2008;6(1):30-34. doi:10.1016/j.cgh.2007.10.006
12. Qumseya B, Gendy S, Wallace A, et al.
Prevalence of Barrett’s esophagus in obese patients
undergoing pre-bariatric surgery evaluation:
a systematic review and meta-analysis. Endoscopy.
2020;52(7):537-547. doi:10.1055/a-1145-3500
13. Kamat P, Wen S, Morris J, Anandasabapathy S.
Exploring the association between elevated body
mass index and Barrett’s esophagus: a systematic
review and meta-analysis. Ann Thorac Surg. 2009;
87(2):655-662. doi:10.1016/j.athoracsur.2008.08.
003
14. Singh S, Sharma AN, Murad MH, et al. Central
adiposity is associated with increased risk of
esophageal inflammation, metaplasia, and
adenocarcinoma: a systematic review and
meta-analysis. Clin Gastroenterol Hepatol. 2013;11
(11):1399-1412.e7. doi:10.1016/j.cgh.2013.05.009
15. Kubo A, Levin TR, Block G, et al. Dietary
patterns and the risk of Barrett’s esophagus. Am J
Epidemiol. 2008;167(7):839-846. doi:10.1093/aje/
kwm381
16. Shaheen NJ, Falk GW, Iyer PG, Gerson LB;
American College of Gastroenterology. ACG clinical
guideline: diagnosis and management of Barrett’s
esophagus. Am J Gastroenterol. 2016;111(1):30-50.
doi:10.1038/ajg.2015.322
17. Muthusamy VR, Lightdale JR, Acosta RD, et al;
ASGE Standards of Practice Committee. The role of
endoscopy in the management of GERD.
Gastrointest Endosc. 2015;81(6):1305-1310. doi:10.
1016/j.gie.2015.02.021
18. Omidvari AH, Hazelton WD, Lauren BN, et al.
The optimal age to stop endoscopic surveillance of
patients with Barrett’s esophagus based on sex and
comorbidity: a comparative cost-effectiveness
analysis. Gastroenterology. 2021;161(2):487-494.e4.
doi:10.1053/j.gastro.2021.05.003
19. Bakr O, Zhao W, Corley D. Gastroesophageal
reflux frequency, severity, age of onset, family
history and acid suppressive therapy predict Barrett
esophagus in a large population. J Clin Gastroenterol.
2018;52(10):873-879. doi:10.1097/MCG.
0000000000000983
20. Rubenstein JH, McConnell D, Waljee AK, et al.
Validation and comparison of tools for selecting

670 JAMA August 16, 2022 Volume 328, Number 7 (Reprinted) jama.com

© 2022 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022

 A Review of Barrett Esophagus
individuals to screen for Barrett’s esophagus and
early neoplasia. Gastroenterology. 2020;158(8):
2082-2092. doi:10.1053/j.gastro.2020.02.037
21. Kim SL, Waring JP, Spechler SJ, et al;
Department of Veterans Affairs Gastroesophageal
Reflux Study Group. Diagnostic inconsistencies in
Barrett’s esophagus. Gastroenterology. 1994;107
(4):945-949. doi:10.1016/0016-5085(94)90217-8
22. Dekel R, Wakelin DE, Wendel C, et al.
Progression or regression of Barrett’s esophagus—is
it all in the eye of the beholder? Am J Gastroenterol.
2003;98(12):2612-2615. doi:10.1111/j.1572-0241.2003.
07680.x
23. Sharma P, Katzka DA, Gupta N, et al. Quality
indicators for the management of Barrett’s
esophagus, dysplasia, and esophageal
adenocarcinoma: international consensus
recommendations from the American
Gastroenterological Association Symposium.
Gastroenterology. 2015;149(6):1599-1606. doi:10.
1053/j.gastro.2015.08.007
24. Spechler SJ, Sharma P, Souza RF, Inadomi JM,
Shaheen NJ; American Gastroenterological
Association. American Gastroenterological
Association technical review on the management of
Barrett’s esophagus. Gastroenterology. 2011;140
(3):e18-e52. doi:10.1053/j.gastro.2011.01.031
25. Shaheen NJ, Falk GW, Iyer PG, et al. Diagnosis
and management of Barrett’s esophagus: an
updated ACG guideline. Am J Gastroenterol. 2022;
117(4):559-587. doi:10.14309/ajg.
0000000000001680
26. Singh S, Manickam P, Amin AV, et al. Incidence
of esophageal adenocarcinoma in Barrett’s
esophagus with low-grade dysplasia: a systematic
review and meta-analysis. Gastrointest Endosc.
2014;79(6):897-909. doi:10.1016/j.gie.2014.01.009
27. Desai M, Lieberman DA, Kennedy KF, et al.
Increasing prevalence of high-grade dysplasia and
adenocarcinoma on index endoscopy in Barrett’s
esophagus over the past 2 decades: data from a
multicenter U.S. consortium. Gastrointest Endosc.
2019;89(2):257-263.e3. doi:10.1016/j.gie.2018.09.
041
28. Visrodia K, Singh S, Krishnamoorthi R, et al.
Magnitude of missed esophageal adenocarcinoma
after Barrett’s esophagus diagnosis: a systematic
review and meta-analysis. Gastroenterology. 2016;
150(3):599-607.e7. doi:10.1053/j.gastro.2015.11.040
29. van Putten M, Johnston BT, Murray LJ, et al.
‘Missed’ oesophageal adenocarcinoma and
high-grade dysplasia in Barrett’s oesophagus
patients: a large population-based study. United
European Gastroenterol J. 2018;6(4):519-528. doi:
10.1177/2050640617737466
30. Dhaliwal L, Codipilly DC, Gandhi P, et al.
Neoplasia detection rate in Barrett’s esophagus and
its impact on missed dysplasia: results from a large
population-based database. Clin Gastroenterol
Hepatol. 2021;19(5):922-929. doi:10.1016/j.cgh.2020.
07.034
31. Hamade N, Kamboj AK, Krishnamoorthi R, et al.
Systematic review with meta-analysis: neoplasia
detection rate and post-endoscopy Barrett’s
neoplasia in Barrett’s oesophagus. Aliment
Pharmacol Ther. 2021;54(5):546-559. doi:10.1111/
apt.16531
jama.com
© 2022 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a Mexico | Access Provided by JAMA User on 08/17/2022
32. Gupta. Longer inspection time is associated
with increased detection of high-grade dysplasia
and esophageal adenocarcinoma in Barrett’s
esophagus. Gastrointest Endosc. 2012;76.
33. Heath EI, Canto MI, Piantadosi S, et al;
Chemoprevention for Barrett’s Esophagus Trial
Research Group. Secondary chemoprevention of
Barrett’s esophagus with celecoxib: results of a
randomized trial. J Natl Cancer Inst. 2007;99(7):
545-557. doi:10.1093/jnci/djk112
34. Jankowski JAZ, de Caestecker J, Love SB, et al;
AspECT Trial Team. Esomeprazole and aspirin in
Barrett’s oesophagus (AspECT): a randomised
factorial trial. Lancet. 2018;392(10145):400-408.
doi:10.1016/S0140-6736(18)31388-6
35. Shaheen NJ, Sharma P, Overholt BF, et al.
Radiofrequency ablation in Barrett’s esophagus
with dysplasia. N Engl J Med. 2009;360(22):2277-
2288. doi:10.1056/NEJMoa0808145
36. Phoa KN, van Vilsteren FGI, Weusten BLAM,
et al. Radiofrequency ablation vs endoscopic
surveillance for patients with Barrett esophagus
and low-grade dysplasia: a randomized clinical trial.
JAMA. 2014;311(12):1209-1217. doi:10.1001/jama.2014.
2511
37. Terheggen G, Horn EM, Vieth M, et al.
A randomised trial of endoscopic submucosal
dissection versus endoscopic mucosal resection for
early Barrett’s neoplasia. Gut. 2017;66(5):783-793.
doi:10.1136/gutjnl-2015-310126
38. Barret M, Pioche M, Terris B, et al. Endoscopic
radiofrequency ablation or surveillance in patients
with Barrett’s oesophagus with confirmed
low-grade dysplasia: a multicentre randomised trial.
Gut. 2021;70(6):1014-1022. doi:10.1136/gutjnl-2020-
322082
39. Krishnamoorthi R, Singh S, Ragunathan K, et al.
Factors associated with progression of Barrett’s
esophagus: a systematic review and meta-analysis.
Clin Gastroenterol Hepatol. 2018;16(7):1046-1055.e8.
doi:10.1016/j.cgh.2017.11.044
40. Allen JE, Desai M, Roumans CAM, et al. Low
risk of progression of Barrett’s esophagus to
neoplasia in women. J Clin Gastroenterol. 2021;55
(4):321-326. doi:10.1097/MCG.
0000000000001362
41. Parasa S, Vennalaganti S, Gaddam S, et al.
Development and validation of a model to
determine risk of progression of Barrett’s
esophagus to neoplasia. Gastroenterology. 2018;
154(5):1282-1289. doi:10.1053/j.gastro.2017.12.009
42. Qumseya B, Sultan S, Bain P, et al; ASGE
STANDARDS OF PRACTICE COMMITTEE; ASGE
Standards of Practice Committee Chair. ASGE
guideline on screening and surveillance of Barrett’s
esophagus. Gastrointest Endosc. 2019;90(3):335-
359.e2. doi:10.1016/j.gie.2019.05.012
43. Thosani N, Abu Dayyeh BK, Sharma P, et al;
ASGE Technology Committee. ASGE Technology
Committee systematic review and meta-analysis
assessing the ASGE Preservation and Incorporation
of Valuable Endoscopic Innovations thresholds for
adopting real-time imaging-assisted endoscopic
targeted biopsy during endoscopic surveillance of
Barrett’s esophagus. Gastrointest Endosc. 2016;83
(4):684-98.e7. doi:10.1016/j.gie.2016.01.007
(Reprinted) JAMA August 16, 2022 Volume 328, Number 7
Review Clinical Review & Education
44. Codipilly DC, Chandar AK, Singh S, et al. The
effect of endoscopic surveillance in patients with
Barrett’s esophagus: a systematic review and
meta-analysis. Gastroenterology. 2018;154(8):
2068-2086.e5. doi:10.1053/j.gastro.2018.02.022
45. Roumans CAM, van der Bogt RD, Steyerberg
EW, et al. Adherence to recommendations of
Barrett’s esophagus surveillance guidelines:
a systematic review and meta-analysis. Endoscopy.
2020;52(1):17-28. doi:10.1055/a-0995-0134
46. Sharma P, Shaheen NJ, Katzka D, Bergman
JJGHM. AGA clinical practice update on endoscopic
treatment of Barrett’s esophagus with dysplasia
and/or early cancer: expert review. Gastroenterology.
2020;158(3):760-769. doi:10.1053/j.gastro.2019.09.
051
47. Van Den Eynde M, Jouret-Mourin A, Sempoux
C, Piessevaux H, Deprez PH. Endoscopic mucosal or
submucosal resection of early neoplasia in Barrett’s
esophagus after antireflux surgery. Gastrointest
Endosc. 2010;72(4):855-861. doi:10.1016/j.gie.2010.
06.069
48. Pech O, May A, Manner H, et al. Long-term
efficacy and safety of endoscopic resection for
patients with mucosal adenocarcinoma of the
esophagus. Gastroenterology. 2014;146(3):652-
660.e1. doi:10.1053/j.gastro.2013.11.006
49. Desai M, Saligram S, Gupta N, et al. Efficacy
and safety outcomes of multimodal endoscopic
eradication therapy in Barrett’s esophagus-related
neoplasia: a systematic review and pooled analysis.
Gastrointest Endosc. 2017;85(3):482-495.e4.
doi:10.1016/j.gie.2016.09.022
50. Qumseya BJ, Wani S, Desai M, et al. Adverse
events after radiofrequency ablation in patients
with Barrett’s esophagus: a systematic review and
meta-analysis. Clin Gastroenterol Hepatol. 2016;
14(8):1086-1095.e6. doi:10.1016/j.cgh.2016.04.001
51. Canto MI, Trindade AJ, Abrams J, et al.
Multifocal cryoballoon ablation for eradication of
Barrett’s esophagus-related neoplasia:
a prospective multicenter clinical trial. Am J
Gastroenterol. 2020;115(11):1879-1890. doi:10.14309/
ajg.0000000000000822
52. Peerally MF, Bhandari P, Ragunath K, et al.
Radiofrequency ablation compared with argon
plasma coagulation after endoscopic resection of
high-grade dysplasia or stage T1 adenocarcinoma in
Barrett’s esophagus: a randomized pilot study
(BRIDE). Gastrointest Endosc. 2019;89(4):680-689.
doi:10.1016/j.gie.2018.07.031
53. Srinivasan S, Sharma P. Real-world data for
endoscopic therapy in LGD: not looking so good. Gut.
2022;71(8):1457-1458.
54. Wu J, Pan YM, Wang TT, Gao DJ, Hu B.
Endotherapy versus surgery for early neoplasia in
Barrett’s esophagus: a meta-analysis. Gastrointest
Endosc. 2014;79(2):233-241.e2. doi:10.1016/j.gie.
2013.08.005
55. Manner H, Pech O, Heldmann Y, et al. Efficacy,
safety, and long-term results of endoscopic
treatment for early stage adenocarcinoma of the
esophagus with low-risk sm1 invasion. Clin
Gastroenterol Hepatol. 2013;11(6):630-635. doi:10.
1016/j.cgh.2012.12.040
671