Introduction
Barrett’s esophagus is a precursor condition that may lead to the development of esophageal
adenocarcinoma (EAC) [1 ]
[2 ]. Visible lesions within Barrett’s esophagus may possess high grade dysplasia (HGD)
or early-stage EAC and should be treated by endoscopic resection [3 ]
[4 ]
[5 ].
Endoscopic mucosal resection (EMR) has traditionally been the standard technique for
resecting Barrett’s neoplasia, and involves a cap-assisted or band ligation technique
to remove pieces of esophageal mucosa. This method typically can only resect small
areas en bloc and requires piecemeal resection for larger lesions [3 ]
[4 ]. Owing to its high efficiency and safety profile, EMR has been widely accepted as
the standard treatment for Barrett’s neoplasia. However, endoscopic submucosal dissection
(ESD) has emerged as a viable alternative. ESD enables the dissection of the submucosal
layer using an endoscopic knife, allowing for en bloc resection of lesions, irrespective
of size. Although ESD is more technically demanding and resource intensive than EMR,
this technique potentially offers tumor-free margins (R0 resection) and curative resection
of larger lesions [5 ].
Both EMR and ESD are effective techniques for achieving complete remission of neoplasia
(CRN), although EMR may require multiple procedures to achieve the same outcome. Recent
guidelines recommend selection of ESD for lesions with suspected submucosal invasion
or for larger lesions exceeding 20 mm in size [4 ]
[5 ]. However, there is limited evidence regarding recurrence rates following CRN achieved
by EMR compared with ESD. Therefore, this study sought to compare the efficacy of
EMR and ESD, focusing on neoplasia recurrence rates post-CRN [4 ]
[5 ].
Methods
Study design and setting
We conducted a retrospective cohort study at a single tertiary referral center in
Toronto, Canada. Eligibility criteria for inclusion required patients to have histologically
confirmed HGD or EAC based on endoscopically resected specimens between July 2019
and December 2023. Endoscopic treatment modalities encompassed both EMR and ESD, with
a mandatory follow-up endoscopy after the initial treatment. Exclusions included low
grade dysplasia histology and patients lacking follow-up. Data collection included
patient demographic details, procedure information, histopathological findings, and
follow-up data. Research Ethics Board approval was obtained from University of Toronto
(REB #08–265). We reported our findings following the Strengthening the Reporting
of Observational Studies in Epidemiology (STROBE) statement [6 ].
Outcomes and definitions
Outcomes measured were the residual neoplasia rate at the first follow-up, the CRN
rate, and the neoplasia recurrence rate following CRN.
En bloc resection was defined as the resection of the entire lesion in a single piece.
R0 resection was defined as tumor-free deep (vertical) and lateral resection margins.
For EMR, deep margin R0 resection was defined as tumor-free deep resection margins,
irrespective of lateral resection margin. For ESD, curative resection (i.e. R0 resection
of low risk lesions) was defined as en bloc and R0 resection with low risk of lymph
node metastasis (i.e. submucosal invasion ≤500 μm, no poor differentiation, and no
lymphovascular invasion) [4 ]
[5 ]. For EMR, deep margin R0 resection of low risk lesions was defined as tumor-free
deep resection margins with low risk of lymph node metastasis.
CRN was defined as complete absence of endoscopic and histological evidence of neoplasia
(HGD/EAC) on follow-up. Complete remission of intestinal metaplasia (CRIM) was defined
as complete absence of histological intestinal metaplasia on follow-up. Recurrence
of neoplasia was defined as reappearance of HGD or EAC after CRN.
Indications for EMR and ESD
As per guideline recommendations [4 ]
[5 ], EMR was indicated for visible lesions ≤20 mm with a low likelihood of submucosal
invasion. ESD was indicated for lesions suspected of submucosal invasion (Paris classification
0-Is, 0-IIc, 0-IIa+IIc, and 0-IIa+Is) and lesions exceeding 20 mm.
Endoscopic resection protocol
EMR was carried out using the multiband ligation technique, utilizing a therapeutic
gastroscope (GIF-1T190; Olympus Co., Tokyo, Japan) and Duette multiband mucosectomy
device (Cook Medical Inc., Bloomington, Indiana, USA) ([Fig. 1 ]). ESD was carried out utilizing a gastroscope (GIF-HQ190; Olympus Co.) fitted with
a soft plastic cap. Voluven (Fresenius Kabi AG, Bad Homburg, Germany) with methylene
blue was injected submucosally. Incision, dissection, and hemostasis were performed
with DualKnifeJ and Coagrasper (Olympus Co.), and electrosurgical generator (VIO-300D,
Erbe USA Inc., Marietta, Georgia, USA) ([Fig. 2 ]).
Fig. 1 Endoscopic images of endoscopic mucosal resection of a 20-mm 0-IIb lesion. a Marking around the lesion. b Suctioning the lesion into the cap. c Attaching the band and performing resection with a snare. d Resection defect.
Fig. 2 Endoscopic images of endoscopic submucosal dissection of an 80% circumferential 0-IIb
lesion. a Marking around the lesion. b,c Mucosal incision and submucosal dissection with an endoscopic knife. d Resection defect.
Histopathological analysis
Histopathological assessments were performed by two expert gastrointestinal pathologists.
EMR/ESD specimens were evaluated based on the grade of differentiation, depth of tumor
invasion, presence of lymphovascular invasion, and the completeness of resection at
the deep and lateral margins (lateral margins for EMR specimens were not investigated)
[7 ]. The depth of invasion was classified into T1a, T1b SM1, and T1b SM2 or deeper (>500
μm) [8 ].
Post‑EMR/ESD protocol
Patients underwent follow-up endoscopy approximately 3 months after EMR/ESD. In cases
where residual neoplasia was detected, repeat endoscopic resection was performed until
CRN was achieved. Radiofrequency ablation (RFA) (Medtronic, Minneapolis, Minnesota,
USA) was then performed on the remaining Barrett’s esophagus without visible lesions,
aiming to achieve CRIM. Patients then underwent surveillance endoscopy every 3 months
during the first year, every 6 months during the second year, and subsequently on
an annual basis. Surveillance biopsies were systematically collected in four quadrants
at 1-cm intervals along the initial length of the Barrett’s esophagus segment, based
on the Seattle protocol [9 ]. Targeted biopsies were taken from any visually detected abnormalities.
Statistical analysis
Descriptive statistics, encompassing mean with SD, median with interquartile range
(IQR), and percentages were utilized to characterize variables and outcomes. The
Kaplan–Meier method was used to estimate the cumulative probability of neoplasia recurrence
over time. The log-rank test and the generalized Wilcoxon test were used to compare
the
probabilities between groups. Recurrence rates were presented as percentages with
95%CIs.
Statistical analyses were executed using JMP Pro17 software (SAS Institute Inc., Cary,
North
Carolina, USA), with a two-sided significance level of P <0.05.
Results
Study population
A total of 157 patients with Barrett’s esophagus with HGD/EAC were included in the
study. Of these, 87 patients were treated with EMR, while 70 patients were treated
with ESD
(see Fig. 1s in the online-only Supplementary material). In the EMR
group, the mean age was 70.1 (SD 10.6) years with 78.2% male. In the ESD group, the
mean age
was 68.8 (SD 8.6) years with 90% male ([Table 1 ]). Regarding the Prague classification, median circumferential (C) and maximal (M)
extent of Barrett’s esophagus was C1M3 in the EMR group and C2M4 in the ESD group.
The
prevalence of long-segment Barrett’s esophagus was 52.9% in the EMR group and 65.7%
in the
ESD group. The median lesion size in the EMR group was 2 cm (IQR 1–2 cm), whereas
the ESD
group had a larger median lesion size of 3 cm (IQR 2–5.5 cm; P <0.001). Regarding the Paris classification, the ESD group had more protruded,
depressed, and complex types (P <0.001). The distribution of
the Paris classification in the EMR group was as follows: 0-Is (4.6%), 0-IIa (64.4%),
0-IIa+IIc (2.3%), 0-IIb (25.3%), 0-IIc (3.4%). In the ESD group, the distribution
was 0-Is
(12.9%), 0-IIa (41.4%), 0-IIa+IIc (18.6%), 0-IIa+Is (12.9%), 0-IIb (7.1%), 0-IIc
(7.1%).
Table 1 Study population.
EMR (N = 87)
ESD (N = 70)
P value
C, circumferential; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal
dissection; IQR, interquartile range; LSBE, long-segment Barrett’s esophagus; M, maximal;
SSBE, short-segment Barrett’s esophagus.
Age, mean (SD), years
70.1 (10.6)
68.8 (8.6)
0.41
Male sex, n (%)
68 (78.2)
63 (90.0)
0.05
Prague C, median (IQR), cm
1 (0–4)
2 (0–4.25)
0.57
Prague M, median (IQR), cm
3 (1–6)
4 (2–7)
0.24
Barrett’s length, n (%)
0.14
41 (47.1)
24 (34.3)
46 (52.9)
46 (65.7)
Size of lesion, median (IQR), cm
2 (1–2)
3 (2–5.5)
<0.001
Circumferential extent of lesion, median, (IQR), %
50 (25–63)
50 (36.3–70)
0.39
Paris classification, n (%)
<0.001
4 (4.6)
9 (12.9)
56 (64.4)
29 (41.4)
2 (2.3)
13 (18.6)
0 (0)
9 (12.9)
22 (25.3)
5 (7.1)
3 (3.4)
5 (7.1)
Histopathological outcomes
In the EMR group, there were 13 cases (14.9%) of HGD and 74 cases (85.1%) of EAC,
of
which 73% were well differentiated, 23% were moderately differentiated, and 4.1% were
poorly
differentiated ([Table 2 ]). The ESD group had 4 cases (5.7%) of HGD and 66 cases (94.3%) of EAC, comprising
56.1% well differentiated, 33.3% moderately differentiated, and 10.6% poorly differentiated
adenocarcinomas. Regarding invasion depth, the EMR group had 71.6% T1a, 25.7% T1b
SM1, and
2.7% T1b SM2 or deeper, whereas the ESD group had 75.8% T1a, 6.1% T1b SM1, and 18.2%
T1b SM2
or deeper (P <0.001). Lymphovascular invasion was less
prevalent in the EMR group (2.3%) compared with the ESD group (21.4%; P
<0.001). Overall, more advanced lesions were selected for ESD with a greater
likelihood of having deep submucosal invasion or positive lymphovascular invasion.
Table 2 Histopathological and procedure outcomes.
EMR (N = 87)
ESD (N = 70)
P value
Data are n (%).
EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; NA, not
applicable.
1 Out of the 10 esophagectomy patients, only one patient had residual cancer in the
surgical specimen (pT1aN0). The remaining nine patients had no residual cancer and
no lymph node metastasis.
Histopathological outcomes
Histology
0.07
13 (14.9)
4 (5.7)
74 (85.1)
66 (94.3)
Differentiation of adenocarcinoma
0.08
54 (73.0)
37 (56.1)
17 (23.0)
22 (33.3)
3 (4.1)
7 (10.6)
Invasion depth of adenocarcinoma
<0.001
53 (71.6)
50 (75.8)
19 (25.7)
4 (6.1)
2 (2.7)
12 (18.2)
Lymphovascular invasion
2 (2.3)
15 (21.4)
<0.001
Procedure outcomes
Adverse events
0.19
0 (0)
2 (2.9)
1 (1.2)
0 (0)
En bloc resection
32 (36.8)
68 (97.1)
<0.001
R0 resection
NA
58 (82.9)
–
NA
45 (64.3)
NA
13 (18.6)
R1 resection
NA
12 (17.1)
Deep margin R0 resection
85 (97.7)
NA
80 (92.0)
NA
5 (5.7)
NA
Deep margin R1 resection
2 (2.3)
NA
Additional treatment
<0.001
0 (0)
10 (14.3)1
3 (3.4)
7 (10.0)
Procedure outcomes
En bloc resection rate was higher with ESD than with EMR (97.1% vs. 36.8%; P <0.001) ([Table 2 ]). In the ESD group, the R0 resection rate was 82.9% and curative resection (i.e.
R0
resection with low risk pathology) was achieved in 64.3% of patients. Meanwhile, 18.6%
of
patients in the ESD group had R0 resection of lesions with high risk pathology and
17.1% had
R1 resection with positive margins. In comparison, 97.7% of patients in the EMR group
had
deep margin R0 resection with 92.0% having low risk pathology considered curative
and 5.7%
with high risk pathology considered noncurative. Finally, 2.3% of patients in the
EMR group
had R1 resection with positive deep margin.
Three patients (3.4%) in the EMR group underwent subsequent chemoradiotherapy due
to high risk pathology and none underwent esophagectomy ([Table 2 ], Fig. 1s ). In contrast, 10 patients (14.3%) underwent esophagectomy in the ESD group and 7
patients (10.0%) received chemoradiotherapy following potentially noncurative pathology.
Interestingly, only one of the 10 patients who underwent esophagectomy because of
high risk pathological findings following ESD resection had residual cancer in the
surgical specimen (pT1aN0). Patients who received these additional treatments were
excluded from the follow-up outcome analysis, whereas eligible patients who declined
subsequent surgery or chemoradiotherapy were enrolled into surveillance and included
in the follow-up outcomes. Among the EMR group, these included two patients with R0
high risk pathology and two patients with positive deep margin R1 pathology. Within
the ESD group, these included three patients with R0 high risk pathology and five
patients with R1 resections.
Follow-up outcomes
All patients were enrolled in the follow-up cohort except those who underwent esophagectomy
or chemoradiotherapy or were lost to follow-up. Follow-up was completed for 124 patients,
including 71 from the EMR group and 53 from the ESD group. The EMR group comprised
94.4% with negative deep margins and low risk pathology considered curative, 2.8%
with deep margin R0 resection but high risk pathology considered insufficiently curative,
and 2.8% with positive deep margins ([Table 3 ]). The ESD group comprised 84.9% with R0 resection of lesions with low risk pathology
considered curative, 5.7% with R0 resection of lesions with high risk pathology considered
noncurative, and 9.4% with R1 resections.
Table 3 Patient outcomes at follow-up.
EMR (N = 71)
ESD (N = 53)
P value
Data are n (%) unless otherwise stated.
CRIM, complete remission of intestinal metaplasia; CRN, complete remission of neoplasia;
EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; IQR, interquartile
range; NA, not applicable; RFA, radiofrequency ablation.
1 The pathological results of the esophagectomy showed no residual cancer and no lymph
node metastasis.
2 The pathological result of the esophagectomy was pT1aN1.
3 None of the patients under surveillance following ESD required an esophagectomy. The
number of esophagectomies for patients with noncurative resections based on initial
ESD pathology is shown in [Table 2 ].
R0 resection
NA
45 (84.9)
–
NA
3 (5.7)
R1 resection
NA
5 (9.4)
Deep margin R0 resection
67 (94.4)
NA
–
2 (2.8)
NA
Deep margin R1 resection
2 (2.8)
NA
Residual neoplasia at first follow-up
10 (14.1)
6 (11.3)
0.78
Total number of endoscopic resections until CRN, median (IQR)
1 (1–1)
1 (1–1)
0.92
CRN
69 (97.2)
53 (100)
0.21
Non-CRN
2 (2.8)
0 (0)
Treatment for non-CRN
1 (1.4)1
0
1 (1.4)
0
RFA
50 (70.4)
29 (54.7)
0.090
CRIM
24 (33.8)
21 (39.6)
0.50
Recurrence of neoplasia after CRN
9/69 (13.0)
1/53 (1.9)
0.042
Treatment for recurrence
8
1
12
03
Total follow-up, mean (SD), days
437 (301)
362 (304)
0.28
During the first follow-up, residual neoplasia was observed in 14.1% (10 cases) of
the EMR group and 11.3% (6 cases) of the ESD group (P = 0.78) ([Table 3 ]). Residual neoplastic lesions (HGD or EAC) were treated with additional endoscopic
resection, which ultimately resulted in CRN in all 53 patients (100%) in the ESD group
and 69 patients (97.2%) in the EMR group. Two patients in the EMR group had residual
neoplasia and did not achieve CRN, of whom one underwent esophagectomy (pathology:
no residual cancer, negative lymph nodes) and the other received palliative care.
Following resections of all visible lesions, 70.4% of the EMR group and 54.7% of the
ESD group underwent RFA, with 7.0% of EMR patients and 20.8% of ESD patients already
achieving CRIM at the completion of the resection procedures without needing subsequent
ablation. A further 22.5% of EMR patients and 24.5% of ESD patients did not undergo
RFA therapy due to decompensation of medical comorbidities, need to manage complex
esophageal strictures following near-circumferential endoscopic resection, or because
of “noncurative” endoscopic resection with pathological findings considered high risk
for lymph node metastasis, in which case endoscopic follow-up was often performed
without initiation of RFA. In the subgroup of patients targeted for CRIM, CRIM was
achieved in 43.6% of the EMR group and in 52.5% of the ESD group, with the remainder
continuing with ongoing RFA therapy at the time of this analysis. Overall, CRIM was
achieved in 33.8% of the EMR group and 39.6% of the ESD group (P = 0.50) ([Table 3 ]).
Among patients who achieved CRN, there was a significantly higher rate of recurrent
neoplasia in the EMR group compared with the ESD group (13.0% vs. 1.9%; P = 0.04) ([Table 3 ]). The mean follow-up period was similar: 437 (SD 301) days for the EMR group and
362 (SD 304) days for the ESD group (P = 0.28). In the EMR group, eight cases of neoplastic recurrence were successfully
managed with endoscopic treatment (seven by repeat EMR and one by hot avulsion), whereas
one case failed repeat EMR due to recurrence in severe fibrosis and subsequently underwent
esophagectomy (pathology: pT1aN1). There was only one case of recurrent neoplasia
in the ESD group, which was successfully treated by EMR ([Table 3 ], Fig. 1s )
A Kaplan–Meier curve showing the cumulative probability of neoplasia recurrence following
CRN is presented in [Fig. 3 ]. The probability of neoplasia recurrence between the EMR group and the ESD group
was notably different (log-rank test P = 0.049 and generalized Wilcoxon test P = 0.04). In the EMR group, the 1-year neoplasia recurrence rate was 14.4% (95%CI
6.4%–22.4%), which increased to 18.3% (95%CI 6.6%–30.0%) at both the 2-year and 3-year
marks. In contrast, the ESD group maintained a consistent recurrence rate of 4.2%
(95%CI 0.0–12.2%) at the 1-year, 2-year, and 3-year time points ([Table 4 ]).
Fig. 3 Kaplan–Meier curve. Cumulative probability of neoplasia recurrence after complete
remission of neoplasia.
Table 4 Cumulative probability of neoplasia recurrence after complete remission of neoplasia.
EMR
ESD
EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection.
Recurrence rate (95%CI), %
14.4 (6.4–22.4)
4.2 (0.0–12.2)
18.3 (6.6–30.0)
4.2 (0.0–12.2)
18.3 (6.6–30.0)
4.2 (0.0–12.2)
Discussion
This study compared neoplasia recurrence rates of EMR and ESD following complete remission
of neoplasia in Barrett’s esophagus. Notably, the neoplasia recurrence rate after
CRN was significantly higher with EMR, occurring in 13% of patients following EMR
but in only 1.9% of patients following ESD. These findings suggest that ESD may be
superior to EMR in completely eradicating microscopic dysplasia, thereby reducing
the risk of neoplasia recurrence in follow-up.
The findings from our study demonstrate a notable increase in recurrent HGD/EAC over
time among patients in whom all apparent neoplasia was successfully resected by EMR.
Specifically, the recurrence rates in the EMR group at 1, 2, and 3 years post-procedure
were 14.4%, 18.3%, and 18.3%, respectively. In contrast, there was a 4.2% recurrence
rate in the ESD group at 1 year with no further recurrences over time at 2 and 3 years.
These recurrences of HGD/EAC are described among a cohort of patients in whom there
had been no apparent residual dysplasia on detailed endoscopic examination or on biopsies,
and CRN was believed to have been achieved. Furthermore, these recurrences occurred
despite a higher rate of subsequent treatment with RFA in the EMR group.
The key difference between EMR and ESD is the anticipated extent and depth of resection.
EMR typically involves piecemeal resection while ESD enables en bloc excision of larger
lesions with likely deeper submucosal planes, ideally achieving higher rates of R0
resection (negative vertical and lateral margins). Piecemeal EMR requires lining up
each cut so that there are no bridges of intervening tissue and may lead to indistinct
lateral margins, increasing the risk of leaving residual neoplastic cells. A possible
explanation for our findings is that residual neoplastic cells may be left behind
at the lateral margins of piecemeal EMR resections, which are more definitively removed
by en bloc resection with ESD. This effect persists despite the fact that a greater
proportion of patients underwent RFA in the EMR group than in the ESD group (70.4%
vs. 54.7%; P = 0.09), which would be expected to eradicate dysplasia if it was arising from the
remaining Barrett’s segment. Furthermore, despite the rates of CRN being similar in
both groups, our results demonstrate significantly higher neoplasia recurrence rate
in the EMR group. This suggests that even after complete endoscopic resection of all
visible neoplasia followed by RFA with the achievement of CRN, the likelihood of neoplasia
recurrence is higher with EMR than with ESD. This is likely because residual metaplastic
and dysplastic cells are left behind following piecemeal EMR and RFA. Therefore, even
when short-term follow-up esophagogastroduodenoscopy shows no visible dysplasia and
negative Seattle protocol biopsies, there may be a higher chance of persistent dysplastic
cells following piecemeal EMR than after ESD. In addition, previous literature has
shown that achieving CRIM is a factor in reducing neoplasia recurrence [10 ]. Our results showed a low rate of CRIM (likely due to ongoing RFA therapy that has
not yet been completed), which may have contributed to the recurrence rate observed
in both groups, but would not account for the observed difference in recurrence rate
between EMR and ESD.
Several studies have compared the outcomes of EMR and ESD in Barrett’s esophagus,
but ours
is the first report to explore true neoplasia recurrence rates following the achievement
of
CRN. Terheggen et al. conducted a prospective randomized controlled trial with a small
patient
cohort, consisting of 20 patients with EMR and 20 patients with ESD [11 ]. At the 3-month follow-up, there was no significant difference in the rate of complete
remission of dysplasia between the two groups (ESD 15/16 vs. EMR 16/17, P
> 0.99). Similarly, the recurrence rates did not differ significantly (ESD 1/16 vs.
EMR 0/17, P >0.99). However, the limited sample size and short
follow-up period of this study are likely to be insufficient to evaluate the recurrence
rate.
Mejia Perez et al. conducted a retrospective study comparing EMR and ESD in 243 patients
at 8
centers in the USA and Brazil [12 ]. The main outcome was the incidence of residual/recurrent lesions following a single
session of either EMR or ESD for the treatment of HGD or T1a EAC. This study showed
a
significantly lower rate of residual/recurrent lesions of 3.5% (3/85) with ESD compared
with
31.4% (44/140) for EMR. However, the methodology of this study did not isolate the
true
recurrence rate, as the outcomes included residual HGD found on first follow-up. This
is not
surprising given that EMR was performed to resect HGD without EAC in 55% of cases
in the EMR
group and 25% of cases in the ESD group, and such lesions often have poorly defined
margins in
Barrett’s esophagus. In contrast, the vast majority of patients in our study had EAC,
comprising 85% and 94% of cases in our EMR and ESD groups, respectively. Furthermore,
it is
unlikely that the need for repeat EMR sessions for residual HGD should be considered
a
treatment failure of EMR relative to ESD, as such iterative treatments by EMR followed
by RFA
are an established standard of care in Barrett’s esophagus. Another study that compared
EMR
with ESD in Barrett’s esophagus was performed by Doumbe-Mandengue et al., who conducted
a
single-center retrospective study of 28 cases of EMR and 57 cases of ESD [13 ]. Over a median follow-up period of 27.5 months, the rate of neoplasia recurrence
was
23% in the ESD group vs. 18% in the EMR group (P = 0.63). However,
this study likely confounded cases of residual lesions as “recurrence,” as the recurrence
assessment was not conducted after the confirmation of CRN, meaning that lesions that
were
reported as recurrences may have in fact been residual dysplasia. In our study, 14.1%
of
patients in the EMR group and 11.3% in the ESD group were found to have residual neoplasia
at
first follow-up and repeat endoscopic resections were performed before achieving CRN.
Our
analysis was then focused on patients who ultimately achieved CRN, establishing a
follow-up
cohort to assess for recurrence. By this approach, we were able to assess the true
recurrence
rate, explicitly excluding residual dysplasia. To the best of our knowledge, this
study is the
first to report the true recurrence rates after EMR and ESD in Barrett’s esophagus.
Finally, a
recently completed meta-analysis confirms that ESD is associated with increased rates
of
curative resection and reduced recurrence, seemingly in support of our findings [14 ].
This study has several limitations. First, it is a single-center, retrospective analysis,
which may limit the generalizability of the results. Second, current guidelines provide
criteria guiding the choice between EMR and ESD for treating Barrett’s neoplasia,
which introduces an inherent selection bias [4 ]
[5 ]. Consequently, the ESD group tended to have larger lesions, a higher incidence of
adenocarcinoma, and deeper invasion depths, similarly to other previous studies [12 ]
[13 ]. Therefore, the ESD group comprised a higher proportion of patients at increased
risk for local recurrence and lymph node metastasis. Despite this, the ESD group demonstrated
a lower recurrence rate, confirming that this selection bias does not compromise the
interpretation of our findings, and if anything, strengthens the observed difference
between resection methods. In addition, the association between treatment choice (EMR/ESD)
and recurrence could not be adjusted for confounding factors due to the small sample
size of this study. The ESD group had larger lesions and more cases with suspected
submucosal invasion, which are confounding factors associated with a higher risk of
recurrence, potentially exaggerating the association between ESD and increased recurrence.
Despite this, our findings showed a lower recurrence risk in the ESD group. Therefore,
adjusting for these confounding factors would likely further reduce the relative risk
of recurrence in the ESD group. Consequently, whether or not we adjust for these factors,
the interpretation remains that ESD is associated with a lower risk of recurrence.
To more accurately evaluate the recurrence rates after EMR and ESD in similar lesions,
a large-scale, randomized trial would be necessary. Finally, metachronous lesions
are common in Barrett’s esophagus and distinguishing between local recurrence of the
resected neoplasia and new metachronous lesions is difficult. However, regardless
of whether patients have recurrence from resected neoplasia or develop de novo lesions,
the ESD group had significantly fewer cases over time despite having more advanced
cancers to begin with, indicating that ESD should be beneficial in reducing recurrence.
In summary, this study examined the neoplasia recurrence rates in Barrett’s esophagus
following EMR and ESD, and found significantly lower recurrence rates with ESD. This
suggests that ESD may be superior in reducing the recurrence of neoplasia when treating
Barrett’s neoplasia.
