Introduction
Barrett’s esophagus (BE) is an established risk factor for the development of esophageal
adenocarcinoma (EAC) [1]. Endoscopic treatment of early Barrett’s neoplasia is associated with increased
survival and has a good safety profile [2]. Current guidelines recommend endoscopic resection of visible lesions on Barrett’s
mucosa and ablation of the remaining BE due to risk of synchronous or metachronous
neoplasia in 20–41 % of patients [3]
[4].
Endoscopic mucosal resection (EMR) enables en bloc resection in lesions up to 15 to
20 mm along the gastrointestinal tract. Larger lesions are usually resected with piecemeal
EMR that hampers proper histological assessment and increases the risk for residual
lesions and recurrence.
In most centers, endoscopic resection of Barrett’s neoplasia is performed with EMR
due to its safety profile and feasibility in an outpatient setting. The current strategy
of EMR followed by ablation is associated with complications in up to 12 % of cases,
including pain (3 %), bleeding (1.6 %), stricture (5 %–12 %) and perforation (0.6 %)
[5]
[6] Additionally, buried glands can grow beneath the neosquamous epithelium after ablation
[7]. Endoscopic submucosa dissection (ESD) was developed for en bloc resection of early gastrointestinal neoplasms and its role is established in superficial
esophageal squamous cell neoplasia, early gastric neoplasia and some colorectal lesions
[8]. The role of ESD in the treatment of BE neoplasia has been studied in smaller series
with suboptimal results, mainly due to positive lateral margins and few studies compare
ESD with EMR in this setting [9]. Most previous studies were performed in the West where ESD experience is lower,
and the high rate of positive lateral margins may reflect poor delineation of the
lesion or suboptimal ESD technique [10]. In fact, even in the most specialized centers, with the use of different advanced
endoscopic modalities, full identification, characterization and delineation of neoplastic
BE is suboptimal [11]
[12]. Higher costs of ESD, mainly associated with longer hospital admission, have also
hampered its use in BE. However, it was recently demonstrated that ESD can be safely
performed in an outpatient setting, reducing costs and hospitalization risks [13].
Some authors have advocated a new approach for ESD on BE, based on wider resection
margins (5–10 mm), margins even wider than those described for wide-field colorectal
EMR [14]. This strategy aims to decrease the rate of positive lateral margins, improving
curability and decreasing recurrence. This approach has been advocated by others,
but never tested [15].
The aim of this study was to evaluate the feasibility, safety, and efficacy of wide-field
ESD (WF-ESD) for resection of BE neoplasia, comparing it to conventional ESD (C-ESD).
Patients and methods
This was a cohort study from a prospectively collected database of all patients with
neoplastic BE that were treated with ESD between June 2011 and June 2018 at the Karolinska
University Hospital in Stockholm, Sweden. This study was approved by the Stockholm
Regional Ethical Committee (2020-05737).
Our hospital is a national reference center for the management of esophageal neoplasias
in Sweden. In our center, endoscopic resection of neoplastic Barrett’s esophagus with
ESD started in 2011. Due to early suboptimal results caused by positive lateral margins
in some cases, as previously described in the literature [16], we decided to start performing WF-ESD, for the resection of all Barrett’s neoplastic
lesions from January 2014. The indications for ESD were the presence of a visible
lesion on Barrett’s mucosa with well differentiated neoplasia on biopsy specimens
that engaged the mucosa or superficial submucosa (Sm1, < 500 μm) and with no ulceration.
All cases were discussed in a multidisciplinary team (MDT) conference before the ESD
procedure.
All patients received a detailed explanation regarding the procedure, its risks, benefits,
and alternatives and provided informed consent. Participants’ clinical and demographic
information was obtained and recorded at enrollment. Patients under antiplatelet drugs
or anticoagulants were handled according to published guidelines.
Endoscopic assessment
All Barrett’s mucosa underwent careful endoscopic assessment with high resolution
endoscopy (GIF-HQ190J; Olympus, Hamburg, Germany) with the corresponding transparent
hood (D-201-11804; Olympus). Barrett’s mucosa was classified according to the Prague
criteria and evaluated using white light, narrow band imaging and chromoendoscopy
with acetic acid 1.5 %, in overview and near focus mode. All visible lesions on BE
mucosa were characterized according to the Paris classification and registered accordingly.
ESD technique
All ESDs were performed under full anesthesia and orotracheal intubation. Electrosurgical
current was applied using a standard electrosurgical generator (VIO300 D, ERBE, Tϋbingen,
Germany). Tumors were characterized and delineated using narrow band imaging (NBI),
acetic acid and magnification endoscopy. After carefully evaluation, circumferential
marking was performed around the tumor using a Dual knife (KD-650 L, Olympus). In
conventional ESD, marking was performed up to 5 mm from the tumor margins. In the
WF-ESD group, marking was performed approximately 10 mm from the tumor margins ([Fig. 1a], [Fig. 1b], [Fig. 1c], [Fig. 1d], [Fig. 1e], [Video 1]). Hyaluronic acid (Sigmavisc, Life Partners, Europe) was then injected into the
submucosal layer to lift the mucosa. An initial incision was made with the Dual knife
on the distal side followed by an incision on the proximal side ([Fig. 1f]). The tumor was then completely removed by submucosal dissection ([Fig. 1g]). Coagrasper (FD-411QR, Olympus) was used for hemostasis during the procedure or
to coagulate vessels present in the submucosal layer. After resection of the specimen,
a carefully interrogation of the post ESD ulcer was performed in order to detect muscular
tears or bleeding vessels. Resected specimens were mounted on boards with pins and
fixed in 10 % formalin for 24 hours ([Fig. 1h]). After fixation, all resected specimens were cut into longitudinal 2 mm slices
in width and then embedded in paraffin and stained with hematoxylin-eosin.
Fig. 1 a White light endoscopy of a long-segment (C3M9) Barrett’s esophagus (BE) with multifocal
high-grade dysplasia (HGD). Visible lesions were not detected by white light endoscopy.
b, c White light endoscopy with acetic acid chromoendoscopy showing multifocal lesions
with loss of acetowhitening. d Magnified endoscopy with narrow band imaging showing irregular vascular and mucosal
pattern. e Marking with wider (10-mm) free margins with dual knife. f Incision outside the marking dots. g Endoscopic submucosal dissection (ESD) was performed with resection of 4/5 of the
esophageal circumference along 9 cm. h Resected specimen with 9.5 × 5.0 cm in size. Pathology assessment revealed the presence
of Barrett’s mucosa with multifocal low and high-grade dysplasia, with free margins
(R0) and no lymphovascular invasion. i Follow-up endoscopy at 3 months with mucosal healing, neosquamous epithelium and
neither strictures nor macroscopic lesions. Distal esophagus/cardia with similar width
as before ESD.
Video 1 Endoscopic resection of multifocal Barrett’s esophagus neoplasia. Previous endoscopic
resection caused severe fibrosis. Complete resection with free margins was achieved
with wide-field ESD.
Assessment after ESD
Patients were under continuous monitoring for 4 hours after the procedure and kept
nil per os until the following day. Intravenous proton pump inhibitors (PPI) were
administered in the first 24 hours, followed by high-dose of oral PPI for 8 weeks.
From 2014 (when all patients were treated with WF-ESD) oral steroids were prescribed
in all cases with resections larger than 3/4 of the luminal circumference, according
to published literature [17].
Upper endoscopy was performed 2 to 3 weeks after ESD to detect and treat strictures
if they occurred. Afterwards, conventional follow-ups with high-definition chromoendoscopy
were performed at 2, 6, and 12 months and then each year in the case of curative resection
([Fig. 1i]). In the case of non-curative resection or recurrence, the case was discussed again
at an MDT conference. Signs or symptoms of complications, readmission, transfusion
requirements and interventions were checked at the 2–3 weeks and at 2 months assessments.
Follow-up was defined as the period between the ESD and the first following endoscopic
or surgical treatment, or between the ESD and last endoscopic follow-up (in patients
without interventional treatment after ESD).
Outcome parameters
The primary outcomes were the rates of en bloc, R0, curative resection, recurrence
and procedure time. The secondary outcomes were adverse events, namely bleeding, perforation,
stricture, and need for unplanned medical assistance after discharge.
Primary outcome parameters
We assessed the outcomes of C-ESD and WF-ESD, i. e., before and after January 2014. All
histologic specimens were reviewed by two dedicated gastrointestinal pathologists
and assessment was based on the Vienna classification [18]. En bloc resection was defined as excision of the target lesions in a single specimen.
In up to 82 % of Barrett’s patients with high-grade dysplasia/carcinoma, the dysplastic
lesions are multifocal [19]
[20], being the size assessment of neoplastic lesions difficult to evaluate and compare
in this context. For that reason, we decided to assess the size of the resected specimens
and not the size of the different neoplastic lesions.
R0 or radical resection was defined as the presence of negative lateral (LM) and vertical
margins (VM) for high-grade dysplasia/cancer in the ESD specimens as described before
[15]. Non-radical resection corresponded to R1 resections.
Curative resections were the R0 resections of well/moderately differentiated neoplasias
that engaged the mucosa or superficial submucosa (Sm1) and had no lymphovascular involvement.
Non-curative resections were resections in which one of those parameters were not
fulfilled [8].
The duration of ESD was defined as the time (in minutes) from the first incision until
retrieval of the specimen. A velocity index of time (min) divided by the resected
size (mm) was calculated in all ESDs.
Local recurrence was defined as high-grade dysplasia/cancer detected within 2 cm of
the previous ESD scar [15] and a metachronous recurrence was defined as neoplasia located more than 2 cm away
from the ESD scar [15], at any of the follow-up endoscopies, before ablation treatment. Complete remission
of neoplasia was defined as the absence of suspicious lesions on gastroscopy with
ME-NBI and chromoendoscopy with acetic acid and no histologic evidence of dysplasia/cancer
applying the Seattle protocol on the follow-up endoscopies [15]. After removal of all visible lesions and when curative resection was achieved,
patients were treated systematically with radiofrequency ablation for complete Barrett
eradication, in all patients in both cohorts.
Secondary outcome parameters
Adverse events were defined as any complication in which ESD or related procedures
(such as anesthesia) were a contributing factor and included bleeding, perforation,
stricture and death.
Perforation was defined as a full thickness breach in the esophageal wall with or
without symptoms. Intraprocedural bleeding that led to blood transfusion or premature
termination of endoscopic resection was considered a complication. Delayed bleeding
was defined as bleeding up to 2 weeks after the procedure that required presentation
to the emergency department, hospital admission or any medical intervention. An esophageal
stricture was defined as a narrowing of the esophageal lumen to the point where it
was not possible to pass through with a standard 9.9 mm diameter gastroscope [21]. ESD related mortality was considered as death up to 30 days after the procedure
in which the ESDs or any related procedures were a contributing factor.
Statistical analysis
Demographic and baseline characteristics were summarized as medians with interquartile
ranges (IQR) for continuous data, and as total numbers and percentages for categorical
data. Differences between C-ESD and WF-ESD were analyzed using the Mann-Whitney U
test or Fischer’s exact test as appropriate. Univariable logistic or Cox regression
was used to obtain and hazard ratios (HR) for selected outcomes. We did not perform
multivariable regression due to few outcomes and inherent risk of overfitting [22]. Statistical analyses were performed using SPSS, version 20 (SPSS Japan Inc, Tokyo,
Japan) and STATA version 13.0 (Stata Corp, College Station, Texas, United States).
P < 0.05 was considered as statistically significant.
Results
Patient characteristics
A total of 74 patients, corresponding to 90 neoplastic Barrett’s lesions, 84 % male,
median age 69 (IQR 63–74), fulfilled the inclusion criteria and were treated with
ESD. Of the 90 ESDs, 22 cases corresponded to C-ESD (24 %) and 68 to WF- ESD (76 %).
Regarding previous treatment, three of 22 in C-ESD cohort and 17 of 68 in the WF-ESD
cohort had previous endoscopic treatment. There were no significant differences between
the two groups of patients in terms of gender, age and Barrett’s circular and maximal
lengths (all P > 0.05) ([Table 1]). No significant differences were observed between the two cohorts in terms of location
(P > 0.05), but macroscopic type was significantly different between groups, with elevated/flat/depressed
morphology present in 19/3/0 vs 29/29/10 of cases in C-ESD and WF-ESD groups, respectively
(P < 0.01).
Table 1
Patient and lesions characteristics in conventional and wide-field endoscopic submucosal
dissection (ESD), n = 90.
|
Conventional ESD (n = 22)
|
Wide-field ESD (n = 68)
|
P value
|
|
Age (years, median, IQR)
|
68 (66–73)
|
70 (63–74)
|
0.62
|
|
Sex (male, n/%)
|
16 (73 %)
|
60 (88 %)
|
0.10
|
|
Length of extension of BE
|
|
Short segment/long segment BE (n, %)
|
8/14 (63 %)
|
26/42 (61.8 %)
|
0.88
|
|
Circular extent (length of ‘C’) (cm, median, IQR)
|
1 (0–4)
|
1 (0–4)
|
0.89
|
|
Extent of tongue (length of ‘M’) (cm, median, IQR)
|
4 (2–5)
|
3 (1–8)
|
0.92
|
|
Location
|
|
|
|
|
Junction/thoracic esophagus
|
20/2 (9 %)
|
68/14 (21 %)
|
0.34
|
|
Tumor morphology
|
|
|
|
|
Elevated/flat/depressed type
|
19/3/0
|
29/29/10
|
0.001
|
|
Histology of biopsy specimen
|
|
LGD/HGD/EAC
|
1/14/7
|
7/35/26
|
0.71
|
BE, Barrett’s esophagus; IQR, interquartile range; LGD, low-grade dysplasia; HGD,
high-grade dysplasia; EAC, esophageal adenocarcinoma.
Primary outcomes
En bloc resection rate was 95 vs 100 %, R0 rate was 73 vs 90 % and curative resection
rate was 59 vs 76 % in C-ESD and WF-ESD groups, respectively (P > 0.05). The percentage of the circumference surface resected, was < 25 %, 25 % to
50 %, 50 % to 75 %, and > 75 % in 14 %, 45 %, 27 %, and 14 % and in 3 %, 35 %, 40 %,
and 22 % of cases in the c-ESD and WF-ESD groups, respectively. The median procedure
time was 147 (range 32–480) and 96 (range 15–388) minutes in C-ESD and WF- ESD (P < 0.05), corresponding to a velocity of 4.4 and 2.3 (min/mm) (P < 0.01), respectively ([Table 2]). There were no significant differences in histology of the resected specimens in
both groups (all P > 0.05). Positive lateral margins were less likely in WF-ESD (2/68, 3 %) compared
to C-ESD (5/22, 23 %) (P < 0.01), while there was no difference in respect to the vertical margin (2/22 (9 %)
in the C-ESD vs six of 68 (9 %) in the WF-ESD groups, (P = 1.0).
Table 2
Lesion characteristics in conventional and wide-field endoscopic submucosal dissection
(ESD), n = 90.
|
Conventional ESD (n = 22)
|
Wide-field ESD (n = 68)
|
P value
|
|
Mean resected size (mm, IQR)
|
40 (30–70)
|
44 (35–60)
|
0.27
|
|
Resected circumferential lumen
< 25 %/25 %–50 %/50 %–75 %/> 75 %
|
3/10/6/3
|
2/24/27/15
|
0.18
|
|
Histology of ESD specimens
LGD/HGD/EAC
|
2/6/14
|
6/30/32
|
0.37
|
|
Tumor differentiation (EAC)
G1–2/G3
|
21/1
|
64/4
|
1.0
|
|
Tumor depth (EAC)
M-SM1/> SM2
|
18/4
|
62/6
|
0.25
|
|
Positive lateral margin
|
5 (23 %)
|
2 (3 %)
|
0.009
|
|
Positive vertical margin
|
2 (9 %)
|
6 (9 %)
|
1.0
|
|
Positive lymphatic invasion
|
2 (9 %)
|
8 (12 %)
|
1.0
|
|
Positive vascular invasion
|
5 (23 %)
|
11 (16 %)
|
0.53
|
|
Metachronous recurrence
Negative/positive
|
16/6
|
62/6
|
0.04
|
|
Local recurrence
Negative/positive
|
20/2
|
68/0
|
0.06
|
IQR, interquartile range; LGD, low-grade dysplasia; HGD, high-grade dysplasia; EAC,
esophageal adenocarcinoma; G1, well differentiated; G2, moderately differentiated;
G3, poorly differentiated; M, mucosal invasion; SM1, invasion of the superficial layer
of submucosa; > SM2, invasion of the middle layer of submucosa or deeper.
All patients were followed in the outpatient clinic. The mean follow-up in the C-ESD
cohort was 13.4 (SD 15) months and the in the WF-ESD cohort was 9.4 (SD 9.9) months,
(P = 0.27). Local recurrence was present in 2/22 (9 %) and in none of 68 (0 %) of the
cases in the C-ESD and WF-ESD groups, respectively (P > 0.05). The Cox regression shown no significant differences between the groups in
terms of metachronous recurrence (hazard ratio 0.46, 95 %CI = 0.14–1.46, P = 0.19).
Regarding previous endoscopic treatment, three of 22 in the C-ESD group had previous
treatment, and metachronous lesions were found in two of three of those vs four of
19 in those without previous treatment (P = 0.1). In the WF-ESD group, 17 of 68 had previous treatment, of those there was
metachronous recurrence in four of 17 vs only two of 51 of those with no previous
treatment (P = 0.01). There was no difference in the proportion of multifocal lesions between
the two cohorts (P = 0.51).
In both groups, all but one case with recurrence were successfully treated with a
new ESD resection. There were nine cases (41 %) of non-curative resection in the C-ESD
cohort: eight were treated surgically and only one of those had lymph node metastasis
in the surgical specimen. During follow-up, five of those patients died, one due to
lung metastasis and the others due to unrelated causes. One 68 years-old male patient
from the C-ESD group had lung metastasis and died 3 months after ESD. He had a C1M4
BE with high-grade dysplasia on the biopsy specimens. The ESD specimen showed the
presence of well differentiated adenocarcinoma (invading the muscularis mucosae) R1,
L0V0.
There were sixteen cases (24 %) of non-curative resection in the WF-ESD cohort: six
were treated surgically and two of those had lymph node metastasis in the surgical
specimen. During follow-up, three patients died, one due to peritoneal metastasis
and the others due to unrelated causes. One 74 years-old male patient from the WF-ESD
group had C10M11 BE with adenocarcinoma. The ESD specimen showed the presence of a
well differentiated adenocarcinoma (pT1a), R0, L1V1. He died 17 months after ESD due
to peritoneal metastasis.
Secondary outcomes
There was one case of bleeding and one case of perforation, both in the WF-ESD group
and both were treated conservatively. Strictures were less frequent in the WF-ESD
group, four of 68 (6 %) vs the C-ESD group, six of 22 (27 %) (P = 0.01). In large resections, that engaged > 75 % of the luminal circumference, strictures
were more frequent in the C-ESD group (3/3, 100 %) than in WF-ESD group 4/15 (27 %),
P = 0.04. The later received oral steroids prophylactically ([Table 3]).
Table 3
Study endpoints and technical results in conventional and wide-field endoscopic submucosal
dissection (ESSD endoscopic submucosal dissection (ESD), n = 90.
|
Conventional ESD (N = 22)
|
Wide-field ESD (N = 68)
|
P value
|
|
En bloc resection rate (%)
|
21 (95 %)
|
68 (100 %)
|
0.24
|
|
R0 resection rate (%)
|
16/22(72.7)
|
61/68 (89.7)
|
0.08
|
|
Curative resection rate (%)
|
13/22(59.1)
|
52/68 (76.5)
|
0.17
|
|
Procedure time (min, median, IQR)
|
147 (88–295)
|
96 (77–164)
|
0.04
|
|
time (min) / resected size (mm) (median, IQR)
|
4.4 (2.5–6.6)
|
2.3 (1.7–3.6)
|
0.003
|
|
Complications overall (%)
|
6 (27 %)
|
6 (9 %)
|
0.06
|
|
Bleeding (%)
|
0 (0 %)
|
1 (1.5 %)
|
1.0
|
|
Perforation (%)
|
0 (0 %)
|
1 (1.5 %)
|
1.0
|
|
Stricture (%)
|
6 (27 %)
|
4 (6 %)
|
0.01
|
In the WF-ESD cohort, depth of invasion (presence of deep submucosal cancer relative
to mucosal cancer) was the only identifiable factor for non-radicality (OR 60.0, 95 %
confidence interval [CI] 10.0–361.0, P < 0.001). Lesion histology (presence of EAC relative to absence of adenocarcinoma)
was the only factor associated with non-curability (OR 21.0 95 % CI 14.5–97.2, P < 0.001). Resection of more than 75 % of the circumferential lumen was the only identifiable
factor for the presence of complications, namely strictures (OR 6.4 95 % CI 1.4–29.1
P < 0.02).
Discussion
We found that wide-field ESD for the treatment of BE neoplasia, is associated with
reduction of tumor-positive lateral margins and reduction of local recurrence. Wide-field
ESD also enables a faster dissection and is associated with a lower stricture rate,
although that might be a consequence of steroid prophylaxis that was introduced together
with the WF-ESD protocol.
In Barrett’s neoplasia, endoscopic resection is recommended when lesions are limited
to the mucosa or superficial submucosa, are well or moderately differentiated and
have no lymphatic or vascular invasion. These cases harbor a low risk of lymph node
metastasis (1.4 %) and endoscopic treatment is considered curative. European and American
guidelines recommend EMR as the first treatment for visible Barrett’s neoplasia [23]
[24]. Using the standard therapy with EMR plus ablation, 2.4 % of patients do not respond
to therapies and 4 % have recurrence of neoplasia [25]. Those limitations lead our center to adopt a resection strategy of Barrett’s neoplasia
based on en bloc resection, similar to the one widely used for gastric lesions. ESD
enables en bloc resection of lesions > 20 mm, as reflected in a recent meta-analysis
showing that the mean specimen size with EMR is 20.4 mm compared to 37 mm in ESD (P < 0.001) [26]. In our center and since 2011, all neoplastic lesions larger than 15 mm were resected
en bloc with ESD irrespective of grade of dysplasia, after MDT conference. Later,
the remaining Barrett’s mucosa is ablated with RFA. In our study, it was possible
to resect specimens with median size of 44 mm using WF-ESD. In comparison to C-ESD,
WF-ESD was associated with a significant increase in the rate of free lateral margins.
The fact that there was a tendency for larger resections with WF-ESD, but not statistically
significant, may be explained by the detection of smaller lesions by the referring
centers, due to the advances in endoscopic technologies and increasing awareness of
the referring endoscopists with mapping of Barrett’s mucosa, along the study period.
Another advantage of ESD is that it enables resection of lesions with submucosal fibrosis,
being EMR difficult in that context. Different causes may be associated with submucosal
fibrosis on BE, namely esophagitis, previous biopsies or endoscopic treatment. Fibrotic
lesions were excluded from most studies on BE ESD, but have recently been associated
with a slight decreased rate of R0 and curative resections [15]. Despite the large size of the lesions, the presence of deep fibrosis due to previous
endoscopic treatment in 17 of 68 cases and the presence of deep submucosal invasion
in six of 68 cases, WF-ESD was feasible in all, with en bloc resection rate of 100 %,
and R0 and curative resection in 61 of 68 (90.0 %) and in 52 of 68 cases (76 %), respectively.
These are the highest rates reported so far in long segment BE [27]. Considering just fibrotic lesions, WF-ESD enabled en bloc, R0 and curative resection
in 17 of 17, 15 of 17 and in 14 of 17 of the cases. Deep submucosal invasion has been
associated with decreased R0 rates [15]. That was the case in our series in which deep lesions (≥ SM2) were present in six
of 68 cases, contributing to six of seven of the R1 resections.
There are some factors that would hamper the use of WF-ESD namely high complications
rate and longer procedure time. The stricture rate for C-ESD was 27 % and higher than
some of previous reports in the field. That might be explained by the size of the
resected specimens that were larger than in those studies. The stricture rate with
WF-ESD (6 %) is lower than most previously reported series of C-ESD. These results
might be surprising considering the large resected areas (median size of 44 mm, and
engagement > 3/4 circumference in 15 of 68 cases) and the presence of severe fibrosis
in 25 % (17/68) of WF-ESD cases. The low stricture rate may be related with the systematic
use of oral steroids after WF-ESD engaging > 75 % of the luminal circumference. First
reports of high stricture rates after esophageal ESD were followed by recent rates
as low as 2 % (mostly after prophylaxis with oral steroids) [17]. Oral steroids have been used in several squamous cell carcinoma ESD series from
Japan, but not reported in the largest BE ESD series from the West [15]
[28]. Another reason for the lower stricture rate might be the use of hyaluronic acid
for submucosal lifting. Hyaluronic acid has anti-inflammatory, anti-fibrotic and regenerative
proprieties and we used it in all patients [29]. Due to its high costs, it is seldom used for BE ESD. In fact, hyaluronic acid was
not used in series with reported high stricture rates after BE ESD/EMR [27]
[29]
[30]
[31]. All four cases of esophageal stricture in the WF-ESD group had near circumferential
ESD, with endoscopic treatment successful in them. In three patients, patency was
achieved with balloon dilation and in the other, seven sessions of balloon dilation
followed by temporary stent placement were needed for patency. With WF-ESD the rates
of bleeding and perforation were both 1.9 %, making those rates similar to the ones
reported in the biggest series on C-ESD for BE [15]
[28]. This reassures the safety of this technique in the appropriate setting. The procedure
length is one of the factors that hampers the dissemination of the ESD technique.
In our study, WF-ESD procedure time was shorter than that of the C-ESD procedure,
and shorter than previously published ESD series [15]
[16]
[27]
[28]
[32]. Endoscopists engaged on ESD procedures (FBS, MO) had extensive experience on ESD
with a total of more than 500 previous ESDs) previous to this study. Part of these
difference on procedure length may be explained by improvement in techniques such
as tunneling, along the study. With C-ESD, high caution should be taken with the lesions’
margins and the maneuverability of the endoscope and knife may be limited due to the
small fragment sizes. With wider margins, dissection can be faster and auxiliary techniques
such as tunneling be more easily performed, especially in cases with fibrosis/submucosal
invasion.
Most patients underwent endoscopic or surgical treatment after the ESD. Those treatments
reduce or eliminate the remaining Barrett’s mucosa and consequently the risk for metachronous
recurrence. For that reason, we used a strict definition of follow-up, considering
the period between the ESD and following surgical or endoscopic treatment (in treated
patients). Using the Cox regression, it was possible to detect a trend for lower risk
for metachronous recurrence in the WF-ESD cohort, but there were no significant differences
between groups. This might be the result of an underpowered analysis due to the big
pool of patients with surgical or endoscopic treatment after the ESD, in both cohorts.
This analysis should be replicated in further studies in the field.
There are limitations to this study. The study was limited by its uncontrolled design,
but it includes all the consecutive BE patients treated with ESD, and the switch from
C-ESD to WF-ESD was well demarked in time, reducing the risk of selection bias. This
was a single-center study and ESDs were conducted by endoscopists with significant
experience with the technique before entering the study. Therefore, our results might
not be generalizable to other endoscopy centers. The lower rate of strictures in the
WF-ESD group might be associated with the introduction of steroid prophylaxis that
did occur with initiation of WF-ESD. Endoscopic, surgical or chemoradiotherapy treatment
after ESD have strong impact on the recurrence of neoplasia. In order to avoid bias,
we used a stricter definition of follow-up than in previous published studies. That
caused a reduction of the follow-up period. So, results on metachronous recurrence
should be interpreted with caution, considering the short follow-up periods in both
groups. Finally, it is reasonable to assume that besides endoscopists’ experience,
there is always a learning curve in terms of diagnostic and therapeutic endoscopy
that might have influenced the outcomes.
Conclusions
In summary, WF-ESD is associated with favorable clinical and technical outcomes comparing
with our previous results and published studies of C-ESD. High en bloc resection in
WF-ESD can provide a more precise histologic assessment and favorable lateral R0 is
associated with reduced local recurrence. Furthermore, WF-ESD enables a faster dissection
with high safety profile. Overall, these results suggest that WF-ESD may be an option
in cases of BE neoplasia. Further prospective, multicentric studies are warranted
in order to evaluate the role of WF-ESD in clinical practice, preferably using randomized,
controlled trial designs.
