Review Article
Visc Med 2022;38:189–195
DOI: 10.1159/000522512
Today’s Mistakes and Tomorrow’s
Wisdom in Endoscopic Treatment and
Follow-Up of Barrett’s Esophagus
Maximilien Barret a, b  
aGastroenterology
and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;
bFaculté
de Médecine, Université de Paris, Paris, France
Keywords
Barrett’s esophagus · Dysplasia · Endoscopic mucosal
resection · Endoscopic submucosal dissection ·
Radiofrequency ablation
Abstract
Background: Endoscopic therapy has replaced esophagec-
tomy for the management of early Barrett’s neoplasia, allow-
ing for the curative treatment of intramucosal adenocarci-
noma, dysplastic Barrett’s esophagus (BE), and the preven-
tion of metachronous recurrences. Summary: Endoscopic
therapy relies on the resection of any visible lesion, suspi-
cious of harboring cancer, followed by the eradication of the
residual BE, potentially harboring dysplastic foci. Currently,
endoscopic mucosal resection (EMR) using the multiband
mucosectomy technique is the gold standard for the resec-
tion of visible lesions. Endoscopic submucosal dissection
(ESD) is feasible with comparable complication rates to EMR,
but longer procedural times. It is still limited to EMR failures
or suspected submucosal adenocarcinoma. Eradication of
residual BE mainly relies on radiofrequency ablation, with
over 90% efficacy in expert centers. Despite initial complete
eradication of BE, intestinal metaplasia and dysplasia recur
in time, justifying prolonged endoscopic surveillance. Key
Messages: The first step of the therapeutic endoscopy for BE
is a careful diagnostic evaluation, searching for visible(s)
lesion(s). EMR is the recommended resection technique for
visible lesions. ESD has not demonstrated its superiority on
EMR in routine practice. Endoscopic follow-up after Barrett’s
eradication therapy is mandatory. © 2022 S. Karger AG, Basel
Karger@karger.com © 2022 S. Karger AG, Basel
www.karger.com/vis
Received: October 11, 2021
Accepted: February 8, 2022
Published online: March 18, 2022
Introduction
Endoscopic therapy of early Barrett’s neoplasia aims at
resecting early adenocarcinoma and preventing the pro-
gression of dysplastic Barrett’s esophagus (BE) toward in-
vasive adenocarcinoma. The indications for endoscopic
therapy, presented in Table 1, do not include nondysplas-
tic BE, considering the scarcity of the data, and the pos-
sible unfavorable risk to benefit ratio [1]. While the indi-
cations of endoscopic therapy for visible lesions, high-
grade dysplasia (HGD), or early (T1) adenocarcinoma is
consensual, the optimal management of low-grade dys-
plasia (LGD) is still debated. Three randomized trials
have addressed the question of endoscopic therapy for
LGD, concluding to a probable benefit in terms of neo-
plastic progression rate (nonstatistically significant in 2/3
studies) [2]. The spontaneous regression of LGD and the
morbidity of endoscopic therapy have led to cautious rec-
ommendations on the management of patients with LGD
[1]. In clinical practice, the indication for endoscopic
therapy for confirmed and repeated multifocal LGD is
discussed on a case-to-case basis.
The principle of endoscopic therapy is first to resect
any visible abnormality, and then to eradicate intestinal
metaplasia (IM) in the esophagus [1, 3]. Indeed, the pres-
ence of a visible abnormality, either slightly depressed
(Paris 0-IIc), flat (Paris 0-IIb), or elevated (Paris 0-IIa),
associated or not with modifications of the pit pattern or
vascular pattern, is highly predictive of neoplasia, and re-
quires to rule out invasive adenocarcinoma. Logically, en-
doscopic submucosal dissection (ESD), endoscopic mu-
Correspondence to:
Maximilien Barret, maximilien.barret @ aphp.fr
Table 1. Indications of endoscopic therapy for early Barrett’s neoplasia

Endoscopic Recommended management Follow-up endoscopy

therapy

Nondysplastic BE No Endoscopic follow-up and biopsies following the Every 3 years (BE ≥3 cm), every 5 years (BE
Seattle protocol <3 cm)
Confirmed* LGD On a case-to- Repeat EGD at 3–6 months, then, if LGD is found Every year
case basis again At 1 year and every 3 years
Annual endoscopic FU
Offer endoscopic therapy
Confirmed* HGD, intramucosal Yes Endoscopic resection of all visible abnormality At 3, 6, and 12 months following CE-IM, and
adenocarcinoma Endoscopic therapy of residual BE, aiming at CE-IM annually thereafter
Submucosal adenocarcinoma Yes Discussed on a case-to-case basis (see specific At least yearly if conservative management is
chapter) chosen

CE-IM, complete eradication of intestinal metaplasia; FU, follow-up; BE, Barrett’s esophagus; LGD, low-grade dysplasia; HGD, high-grade dysplasia. *All
diagnoses of dysplasia on BE require confirmation by an expert pathologist.

cosal resection (EMR), and endoscopic mucosal biopsies Multiband Mucosectomy

have decreasing accuracy for the histological diagnosis of
BE-associated lesions [4, 5]. In clinical practice, EMR is
the most widely accepted resection tool for visible lesions
arising in BE. After resection of a dysplastic lesion, the
residual BE is considered to harbor other dysplastic foci,
with up to 21% metachronous recurrence rate at 5 years
[6]. The complete eradication of IM (CE-IM) can be
achieved by means of endoscopic resection, mostly in cas-
es of BE tongues. In cases of circumferential BE, owing to
a significant risk of esophageal strictures, thermal abla-
tion of the residual BE is preferred [7]. Once CE-IM is
achieved, as in 78%–94% of the patients [8, 9], lifelong
endoscopic follow-up is recommended with random bi-
opsies of the neosquamous epithelium and the gastric
cardia. We will present the state of the art in clinical prac-
tice and research in BE endoscopic therapy, and address
commonly made mistakes in the management of Barrett’s
neoplasia.
Multiband mucosectomy (MBM) involves a modified
variceal band ligation device and a polypectomy snare
(Duette MBM system, Cook, Ireland and Captivator Sys-
tem, Boston Scientific, Natick, MA, USA). After a first
diagnostic step – without the cap – and delineation of the
lesions, the lesion is sucked in the cap and a band is re-
leased as during esophageal varices band ligation. This
creates a pseudopolyp, which is resected with a snare.
This technique allows performing six consecutive EMR
without removing the endoscope and replacing the snare
as is the case within endoscopic resection-cap procedure.
Besides the aforementioned randomized controlled
trial [10], large MBM resection cohorts involving over
200 procedures confirmed the safety of the technique,
with less than 1% esophageal perforations, 1.5%–2% de-
layed bleeding, and 3%–4% esophageal strictures [11, 12].
As a consequence, MBM has become the preferred endo-
scopic resection technique for early Barrett’s neoplasia.

The Concept of EMR for Early Barrett’s Neoplasia

Endoscopic Treatment of Barrett’s Esophagus
Endoscopic Mucosal Resection
Endoscopic Resection-Cap
Historically, esophageal EMR was performed using
the endoscopic resection-cap technique, involving a spe-
cifically designed oblique distal attachment cap of 12 mm
with a distal ridge, allowing to place an asymmetrical
snare. After submucosal injection and suctioning of the
lesion in the cap, the snare is tightened and the lesion re-
sected. As demonstrated by a randomized controlled trial
[10], this technique is associated with higher costs, longer
procedural times, and more esophageal perforations, and
is currently abandoned for BE.
Long-term (>5 years) follow-up data show the satisfy-
ing oncological results of EMR for early Barrett’s neopla-
sia, with 96%–97% remission rates of neoplasia after the
EMR of HGD or intramucosal (T1a) carcinomas [6, 13].
Although against the principles of oncologic surgery that
advise en bloc excision of any neoplasia, piecemeal endo-
scopic resection, even of intramucosal adenocarcinoma,
does not result in a pejorative oncological outcome. This
exception to the rule can be explained by the virtual risk
of lymph node metastasis in this disease, and the contri-
bution of the ablative therapies such as radiofrequency
ablation (RFA) that will follow, allowing to destroy re-
sidual dysplastic foci.

190 Visc Med 2022;38:189–195 Barret

DOI: 10.1159/000522512
 Common Mistakes in EMR
Omitting the Specific Technical Aspects of Esophageal
EMR. The most important step of the endoscopic proce-
dure is the diagnostic evaluation. The routine use of chro-
moendoscopy (including virtual chromoendoscopy)
during BE endoscopic surveillance is recommended, to
improve the detection of neoplastic lesions [14] and to
detect residual IM during BE eradication therapy [1, 3,
14]. Chromoendoscopy (particularly virtual chromoen-
doscopy) is also used to help delineating the neoplastic
lesions before resection. Although not recommended in
the latest guidelines, the use of a distal attachment cap can
help to examine the folds of the gastric cardia. In addition,
the cap allows to check that the target lesion is actually
suctionnable in the cap and not fixed to the deeper layers
of the esophageal wall. During MBM, some specific as-
pects of the technique, such as avoiding submucosal lift-
ing, cutting below the band, and using pure coagulation
current are often overlooked. This can result in major
bleeding and small resection specimens with a creation of
mucosal bridges. In the case of mucosal bridges between
the resections, they should be resected with submucosal
lifting and conventional EMR without suction to avoid
perforation [15].
Performing Circumferential Endoscopic Resections.
Performing complete circumferential EMR is technically
feasible and gives the endoscopist the feeling of having
“solved the problem” by resecting all IM and early neo-
plasia in one to three endoscopic treatment sessions.
However, this approach is unadvisable and results in
40%–50% stricture rates [16, 17]. Although some small
studies have reported a beneficial effect of local or sys-
temic steroid therapy for esophageal stricture prevention,
these results have not been confirmed by prospective and
controlled studies [18]. Currently, there is no effective
stricture prevention technique after extensive esophageal
mucosal resection [19]. Similarly, single-session EMR
and RFA of the residual BE may result in esophageal per-
foration by inadvertent ablation of the exposed submu-
cosa and muscularis propria [20].
Performing EMR for all Early Barrett’s Neoplasia. In
2021, the management of early Barrett’s neoplasia is per-
formed in expert centers in which ESD is easily accessible
and safe. Considering the poor diagnostic performances
of endosonography to stage T1 adenocarcinomas and the
uncertainty of the endoscopic prediction for T1a versus
T1b lesions, performing ESD of all T1 esophageal adeno-
carcinomas is conceivable. Indeed, en bloc resection al-
lows an optimal histological analysis and prediction of
the risk of lymph node metastasis [5]. In this perspective,
the indications for EMR could become restricted to nod-
ular BE, LGD or HGD on BE, or residual BE after initial
endoscopic resection, as an alternative to ablative thera-
pies.
Endoscopic Treatment of Barrett’s
Esophagus
Endoscopic Submucosal Dissection
ESD in Barrett’s Esophagus-Related Neoplasia?
ESD has become the standard of care for the resection
of esophageal squamous cell neoplasia and gastric adeno-
carcinoma, considering the virtual local recurrence rate,
but also the optimal histological analysis allowed by an en
bloc-resected specimen [21]. While an underpowered
randomized controlled trial demonstrated the absence of
clinical benefit of ESD in the routine management of ear-
ly Barrett’s neoplasia [22], a number of large retrospective
studies confirmed the safety of ESD in this indication
with 89%–93% en bloc, 73%–79% R0, and 65%–66% cu-
rative resection rates, at the cost of 0%–1.5% perforations,
1.4–2.1% delayed bleeding, and 2.1%–16% stricture rates
[23–25]. Thus, the safety profile is similar to EMR, with a
possible benefit in terms of histological analysis of esoph-
ageal adenocarcinomas [5], but longer procedural times
(over 60 mn in most publications). Since the benefit of
ESD over EMR mostly relies on the management of high-
risk adenocarcinomas (T1b, lymphovascular involve-
ment, poorly differentiated lesions), and these lesions are
rare, it is unlikely that prospective comparative evidence
will be published demonstrating the superiority of ESD
over EMR in early Barrett’s neoplasia. Currently, ESD is
therefore restricted to EMR failures (bulky, scarred, and
poorly lifting lesions) or lesions >15 mm with a high sus-
picion of submucosal adenocarcinoma.
Common Mistakes in ESD
Performing ESD for Unselected Lesions. ESD is a pow-
erful treatment tool designed to resect en bloc early diges-
tive cancers. “Just because you can does not mean you
should”: a liberal use of ESD for any dysplastic lesion aris-
ing on BE could be considered as an overtreatment. In-
deed, ESD puts the patient at risk of complications result-
ing from longer anesthesia time and extensive mucosal
resections.
Performing “Small” ESDs. Conversely, once an ESD is
planned, the endoscopist should aim for an R0 resection
for adenocarcinoma and HGD; therefore, large resection
margins, guided by virtual chromoendoscopy and mag-
nification, are advisable.
Endoscopic Ablation
Argon Plasma Coagulation
Argon plasma coagulation (APC) (Erbe, Tübingen,
Germany) is a cheap and broadly available technique al-
lowing to ablate flat dysplastic or residual (and potential-
ly dysplastic) BE after endoscopic resection. In a random-
ized trial involving 63 patients, Manner et al. [26] showed
that APC ablation after ER achieved CE-IM in 79% of the
patients, and reduced the neoplastic recurrence rate from
37% to 3% at 2 years follow-up. The technique is how-
ever limited by its heterogeneity of application (depend-
Visc Med 2022;38:189–195 191
DOI: 10.1159/000522512
ing on the distance to the mucosa, the ablation settings,
the time of application), the long procedural time when
ablating circumferential BE segments. As a result, the use
of APC is restricted to the ablation of small residual Bar-
rett’s islands or tongues in centers without access to RFA.
Hybrid Argon Plasma Coagulation
A modified APC probe called Hybrid APC allows to
inject saline in the submucosal space via an integrated
waterjet channel. The aim of the submucosal lifting is to
allow high power and more homogeneous ablation in or-
der to improve the outcomes of APC ablation. A 2016
retrospective study reported the results of hybrid APC in
BE, reporting more similar efficacy (78% CE-IM after a
median 3.5 treatment sessions) than conventional APC,
but lower stricture rates (2% vs. 9%) [27]. Recently, a large
prospective multicenter study found an 87% rate of CE-
IM (71% at 2 years) after a mean of 1.2 endoscopic resec-
tions and 2.7 ablation sessions, with a 4% esophageal
stricture rate [28]. Considering the availability and ease
of use of APC, particularly in the scarred and narrow
esophagus, these data could promote the adoption of hy-
brid APC for the ablation of dysplastic or residual BE.
Radiofrequency Ablation
RFA allows a reproducible and controlled in-depth abla-
tion of BE on the whole surface of a 3 cm, balloon-based
over the wire, electrode, or a 20 × 13 mm focal, endoscope-
fitting electrode (Barrx 36 Express and Barrx 90, Medtron-
ic, Minneapolis, MN, USA). The technique has been exten-
sively and rigorously studied since the early 2010s, in terms
of power settings, short and long-term outcomes [8, 9, 29].
When performed in expert centers, CE-IM is achieved in
94% of the patients, at the cost of 21% adverse events, in-
cluding 15% esophageal strictures. Following CE-IM, the
annual recurrence rate of IM and dysplasia range from 2%
to 4% and 1% to 2%, respectively [9, 30]. Of note, this rate
excludes recurrent nondysplastic IM at the gastric cardia, of
which the clinical significance is debated.
Currently, it is recommended to wash the esophageal
mucosa prior to the procedure, and then perform two 10
J/cm2 ablations with a gentle scraping of the mucosal co-
agulum between the procedures when performing cir-
cumferential RFA, and to perform three consecutive 12 J/
cm2 ablations, including the esophagogastric junction at
least once, when performing focal RFA. Typically, an
RFA treatment follows an initial endoscopic resection; it
is performed every 3–4 months, under double-dose pro-
ton pump inhibitors, and includes one circumferential
and two focal RFA treatments.
Cryoablation
Cryoablation of dysplastic or residual BE has been in-
troduced in 2010, but has not gained wide acceptance
192 Visc Med 2022;38:189–195
DOI: 10.1159/000522512
around the world, considering the outstanding outcomes
of RFA. One type of device is liquid nitrogen through the
scope spray catheter (TruFreeze, Steris Medical, Mentor,
OH, USA) that has been mostly studied in the USA, with
suboptimal results in terms of CE-IM (66% after a me-
dian of 4 treatment sessions in a recent study involving 62
patients) [31]. Of note, the technique requires the place-
ment of a nasogastric decompression tube to prevent
stomach overinsufflation. A second type of device, also
based on nitrous oxide spraying, but inside a through the
scope balloon that both stabilizes the application and pre-
vents oversinsufflation, has been studied in Europe and
in the USA since 2016 [32, 33]. Although the first studies
are encouraging, with up to 88% CE-IM in one study in-
volving 41 patients [32], the device itself is still evolving
[33], and, the implementation of the Cryoballoon abla-
tion system (Pentax Medical, Redwood City, CA, USA) in
the therapeutic armamentarium of BE is still at an early
stage.
Common Mistakes on Ablation
Not Performing Ablation. Because of the multifocal na-
ture of dysplasia in BE, metachronous neoplasia occurs in
up to 21% of the patients following endoscopic resection
of a neoplastic lesion. Therefore, the first mistake of abla-
tion is to forget to ablate the residual BE. When a patient
is sent to a referral center for the resection of a visible le-
sion, both the therapeutic endoscopist and the referring
gastroenterologist must make sure that the patient will be
scheduled for controls and ablation procedures usually
over a whole year following endoscopic resection.
Ablating Visible Lesions. Ablation is meant to treat flat
dysplastic BE. This is the case for residual BE and BE with
LGD, but very uncommon for BE with HGD, where a vis-
ible lesion is almost always detected, requiring initial en-
doscopic resection. Therefore, the presence of a visible
lesion should lead to cancel the ablation procedure, and
switch to endoscopic resection. Occasionally, “visible” le-
sions, characterized by a regular enlarged pit pattern and
Paris 0-IIa appearance, usually at the limit of a recent en-
doscopic resection or in patients with portal hyperten-
sion, turn out to be purely inflammatory or hyperplastic
and only require postponing the ablation procedure and
intensifying the acid suppression therapy (Fig. 1).
Performing Unindicated Ablations. Even in expert
hands, 6% of the patients do not reach CE-IM after endo-
scopic resection and ablation [9]. In less experienced cen-
ters, this rate reaches 25%–44% [34–36]. First, this under-
lines the paramount importance of expert centers in the
management of early Barrett’s neoplasia. The latest ESGE
position statement, suggesting that all cases of dysplasia
should be handled in expert centers should help improv-
ing this point [3]. Second, performing ablation in a pa-
tient with peptic esophagitis or poor healing from the last
Barret
Fig. 1. Endoscopic aspects encountered during endoscopic therapy
for early Barrett’s neoplasia. LGD presenting as a Paris 0-IIb lesion
mainly visible at 6 o’clock, reddish in white light (a), and with
modified pit pattern in narrow-band imaging (b). Early (T1) ad-
enocarcinoma arising in a BE, presenting as a Paris 0-Is lesion at 6
o’clock position with slightly eroded surface, in white light (c) and
ablation is doomed to fail, and should be avoided: instead,
increasing acid suppression therapy, postponing the abla-
tive procedure, and in some instances performing antire-
flux surgery based on 24 h ambulatory pH-impedance
measurement is advisable. Finally, although ablation
spares the patient the morbidity of many endoscopic re-
section procedures, “escape resection” should be used
when ablation fails after repeated procedures. Indeed, the
increased risk of neoplastic progression of the patients
with poor squamous regeneration after ablation should
be kept in mind [37].
Endoscopic Follow-Up of Barrett’s Esophagus
Follow-Up of Barrett’s Esophagus
The follow-up of BE appears in Table 1 and will be ad-
dressed in a specific chapter of the issue.
Follow-Up after Treatment of Early Barrett’s
Neoplasia
The goal of the treatment of early Barrett’s neoplasia is
to prevent the occurrence of a T ≥ 2 adenocarcinoma re-
quiring surgery or an advanced adenocarcinoma with fa-
tal outcome. Reaching CE-IM was hoped to be a defini-
tive treatment of BE; however, IM and dysplasia do recur
in 2%–4% and 1%–2% per year, respectively [9, 30]. Ad-
vanced adenocarcinomas are also observed in 0.4%–0.7%
of the patients following initial CE-IM after 3–5 years fol-
Endoscopic Treatment of Barrett’s
Esophagus
narrow-band imaging (d). This lesion is a typical indication for en
bloc excision by ESD. e, f Examples of “visible,” yet inflammatory
and non-neoplastic lesions seen arising in BE during endoscopic
therapy. Aspect of recurrent nondysplastic IM at the gastric cardia
after initial CE-IM, in white light (g) and narrow-band imaging
(h).
low-up. Most dysplastic recurrences are diagnosed in
random biopsies of the gastric cardia [9, 38]. In addition,
dysplastic recurrences are observed up to 4 years after
CE-IM [39].
Current endoscopic surveillance protocol following
CE-IM includes a careful endoscopic examination of the
neosquamous epithelium and gastric cardia in direct and
retroflexed position, and random quadrantic biopsies of
the gastric cardia and of the neosquamous epithelium ev-
ery 1–2 cm to search for buried glands. The surveillance
intervals are 3, 6, 12 months, and annually thereafter in
case of initial HGD or adenocarcinoma; 1 and 3 years, and
every 3 years thereafter in case of initial LGD [1]. Consid-
ering the poor diagnostic yield of performing random bi-
opsies of the neosquamous epithelium (1% buried IM
with no dysplasia and no neoplastic progression observed
in the Dutch registry), these biopsies could be abandoned
in the future. Furthermore, considering the median 25–
31 months’ time to diagnose recurrent dysplasia, surveil-
lance intervals during the first year following CE-IM
might be broadened [9].
Common Mistakes on Follow-Up
Omitting Retroflexion to Examine the Gastric Cardia
While the interest of random biopsies of the gastric
cardia is currently debated, a careful inspection of the gas-
tric cardia, in direct and retroflexed position, is para-
mount to detect neoplastic recurrences that typically oc-
cur at this site [40].
Visc Med 2022;38:189–195 193
DOI: 10.1159/000522512
 Over Interpreting Residual or Recurrent Intestinal
Metaplasia at the Gastric Cardia
IM of the gastric cardia is found in up to 20% of pa-
tients undergoing upper digestive endoscopy and does
not justify surveillance [41]. Following CE-IM for early
Barrett’s neoplasia, IM of the gastric cardia is found in
14%–21% of the patients (Fig. 1), however, reproduced in
subsequent endoscopies in only a third of the cases [9,
38]. This casts doubt on the clinical relevance of this find-
ing, and should not lead to the diagnosis of recurrent BE
or justify therapy in the absence of dysplasia.
tion toolbox has incorporated ESD, which might become,
as in every other organ of the digestive tract, the treatment
of choice of early carcinoma. The long-term follow-up
data after CE-IM confirms the durable and excellent re-
sults achieved in expert centers, underlining the impor-
tance of centralized care for the management of BE; while
questioning the clinical and oncological relevance of re-
current IM at the gastric cardia, these data still prompt for
prolonged endoscopic surveillance after BE eradication
therapy.

Conflict of Interest Statement

Conclusion
The author has no conflicts of interest to declare.
The principles of the management of early Barrett’s
neoplasia, consisting in a thorough endoscopic assess- Funding Sources
ment, followed by the resection of all visible abnormali-
ties, and the eradication of the residual BE has not changed There is no funding source for this work.
much for the last decade. However, the endoscopic resec-

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