Reviews

Pirogov Journal of Surgery 2021, No. 9, pp. 77-84

https://doi.org/10.17116/hirurgia202109177

Endoscopic submucosal dissection versus endoscopic mucosal resection

for colorectal tumors: a systematic review and meta-analysis
YU.E. VAGANOV1, M.A. NAGUDOV1, E.A. KHOMYAKOV1, 2, S.I. ACHKASOV1, 2

1
Ryzhikh National Medical Research Centre for Coloproctology, Moscow, Russia;
2
Russian Medical Academy of Continuous Professional Education, Moscow, Russia

ABSTRACT
Objective. To compare early (resection quality, complication rate, surgery time) and long-term (recurrence rate) outcomes of en-
doscopic submucosal dissection versus endoscopic mucosal resection.
Material and methods. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. Data
were analyzed using the Rewiew Manager 5.3 software.
Results. The study included 8 manuscripts including 6 retrospective trials, 1 case-control and only 1 prospective study. These stud-
ies comprised the results of endoscopic resection of 1989 colonic tumors (EMR — 748, ESD — 1241). ESD is associated with high-
er incidence of en-bloc resection (OR 0.13; 95% CI 0.03 0.49; p=0.003) and R0 resection (OR 0.23; 95% CI 0.05 1.02; p=0.05)
compared to EMR. Local recurrence rate is 13 times higher after EMR compared to ESD (OR 13.94; 95% CI 6.3 30.8; p=0.00001).
However, ESD is followed by 4 times higher risk of colon wall perforation (OR 0.25; 95% CI 0.08 0.81; p=0.02).
Conclusion. ESD is more advisable regarding resection quality compared to EMR. However, higher incidence of perforations, sur-
gery time and technical features of ESD do not allow us to unambiguously interpret the results of our meta-analysis and determine
the optimal surgical approach.

Keywords: endoscopic submucosal dissection, mucosal resection, colorectal tumors.

INFORMATION ABOUT THE AUTHORS:

Vaganov Yu.E. — https://orcid.org/0000-0003-4872-4481
Nagudov M.A. — https://orcid.org/0000-0002-0735-2100
Khomyakov E.A. — https://orcid.org/0000-0002-3399-0608
Achkasov S.I. — https://orcid.org/0000-0001-9294-5447
Corresponding author: Nagudov M.A. — e-mail: nagudov-marat@yandex.ru

TO CITE THIS ARTICLE:

Vaganov YuE, Nagudov MA, Khomyakov EA, Achkasov SI. Endoscopic submucosal dissection versus endoscopic mucosal resection
for colorectal tumors: a systematic review and meta-analysis. Pirogov Russian Journal of Surgery = Khirurgiya. Zhurnal im. N.I. Pirogova.
2021;9:77–84. (In Russ.). https://doi.org/10.17116/hirurgia202109177

Introduction Thus, advisability of a particular technology for resec-

Endoscopic resection of colon neoplasms is a topical is-
sue of world health care within the current screening programs
for colorectal cancer and reduction of cancer-related mortali-
ty [1, 2]. Endoscopic mucosal resection (EMR) and endoscopic
submucosal dissection (ESD) are the most common approaches
for endoscopic excision of colon neoplasms. The use of certain
technology depends on surgeon’s preferences, surgical school
and availability of these methods [3, 4].
Endoscopic mucosal resection implies excision of bowel
wall up to submucosa using a diathermic loop [4].
However, technical difficulties arising in EMR of tumors
over 20 mm became an impetus for development of a new tech-
nique — endoscopic submucosal dissection [5]. In 1999, Gotoda
et al. [6] first reported ESD for colon tumor resection. This tech-
nique became popular among endoscopic surgeons in the Asia-
Pacific region, especially in Japan, within a short period. Later,
this approach was approved in European countries [7, 8].
Nevertheless, ESD is a long and energy-intensive manipu-
lation followed by high incidence of complications [9].
tion of large tumors can be determined only in compara-
tive studies. However, modern literature data are presented
by few comparative trials devoted to EMR and ESD. The main
limitation factors are retrospective design and small sample
size [10—17]. In this regard, we performed a systematic review
and meta-analysis of trials devoted to early (resection quali-
ty, morbidity, surgery time) and long-term (recurrence rate)
outcomes of EMR and ESD.
Material and methods
Searching for scientific data was carried out in the MED-
LINE e-database according to the PRISMA criteria regardless
the date of publication. We used the following keywords: "en-
doscopic submucosal dissection", "endoscopic mucosal resec-
tion", "colorectal" [18]. Primary screening revealed 1018 man-
uscripts. The following articles were excluded: 254 reviews, 518
non-comparative studies devoted to one of the methods, 86 case
reports, 152 manuscripts devoted to tumors of upper gastroin-
testinal tract (Fig. 1).

PIROGOV JOURNAL OF SURGERY, 9, 2021 77

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Publications found
254 — literature reviews
in a systematic review
518 — noncomparative studies
(n=1018)
focusing on one methodology
86 — clinical case descriptions
152 — tumors with localization
in the upper gastrointestinal
Screening articles tract

Studies included in the

systematic review (n=8)

Fig. 1. Flowchart of the study.

The study included 8 studies including 6 retrospective ones,
1 case-control study and only 1 prospective trial (Tables 1—3).
We found no randomized trials comparing ESD and EMR. In-
clusion criteria for all studies were tumor dimension over 20
mm and epithelial colon tumor.
All studies summarized endoscopic resection of 1989 co-
lon tumors (EMR – 748, ESD – 1241). We analyzed tumor di-
mensions, incidence of en-bloc and R0 resections, complica-
tions (perforations and delayed bleeding), as well as long-term
treatment outcomes (mean follow-up period and recurrence
rate). Statistical analysis was carried out using the Review Man-
ager 5.3 program.
Results
Data on mean dimensions of resected tumors are presented
in all studies. Nevertheless, there were no significant between-
group differences (mean difference was only 3.48 mm (95% CI
-7.9-0.9; p = 0.13)). This parameter emphasizes comparability
of both groups subjected to different treatment strategies (Fig. 2A).

Table 1. Characteristics of studies

Number of patients Tumor dimension, mm Age

Author Year Country Study design
all EMR ESD EMR ESD EMR ESD

Iizuka 2009 Japan retrospective 127 83 43 31±17 39±20 66±12 (32—91) 69±12 (34—86)

Saito 2009 Japan retrospective 373 228 145 28±8 37±14 64± 64±11

Toyonaga 2009 Japan retrospective 492 24 468 20 (13—34) 30 (6—158) No data No data

Lee 2011 Korea prospective 454 140 314 21.7±3.5 28.9±12.7 63 (23—90) 61 (25—85)
(20—40)

Tajika 2011 Japan retrospective 189 104 85 31.6±9.0 25.5±6.8 59,9±10,6 64,3± 9,2

Terasaki 2011 Japan retrospective 125 69 56 37.4±17.7 42.1±17.1 69,4±11,1 65,0 ±

(20—100) (20—100) (39—92) 10,5 (42—86)

Kobayashi 2012 Japan case-control 84 56 28 25 (9.0) 27.1 (10.1) 65,1 (9,7) 65,9 (9,9)

Yang 2017 Korea, USA retrospective 136 34 102 22.3±3.9 22.9±2.4 61,6±8,0 62,2±10,1

Table 2. Characteristics of studies (Continuation)

Male-to-female ratio Surgery time, min En bloc resection R0 resection Adenocarcinoma
Author
EMR ESD EMR ESD EMR ESD EMR ESD EMR ESD
Iizuka No data No data 110±74 (30—360) No data 45 23 31 22 33 24
Saito No data No data 29±25 (3—120) 108±7 (15—360) 74 122 No data No data No data No data
Toyonaga No data No data 19 (3—35) 60 (11—335) 20 468 No data No data 5 307
Lee No data No data No data 54.73±40.9 60 291 46 275 22 119
Tajika 61/39 49/36 29.4±26.1 (3—115) 87.2±49.7 (19—256) 71 50 No data No data 23 54
Terasaki 59/49 38/23 No data 85 (30—360) No data No data No data No data No data No data
Kobayashi 25/31 19/9 11 (2—280) 140 (45—400) 21 27 No data No data 40 20
Yang No data No data 12.7±7.0 45.6±30.1 32 102 26 92 No data No data

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Table 3. Characteristics of studies (Continuation)

Delayed bleeding Perforation Subsequent resection Recurrence Mean follow-up, months
Author
EMR ESD EMR ESD EMR ESD EMR ESD EMR ESD
Iizuka No data No data 1 8 7 9 No data No data No data No data
Saito 7 2 3 9 No data No data 33 3 26±17 (6—68) 20±13 (6—61)
Toyonaga 0 7 0 7 No data No data No data No data No data No data
Lee 0 2 0 25 9 26 29 2 26 (13—41) 17 (10—23)
Tajika 3 2 0 5 No data No data 16 1 53.8±44.6 (3—191) 14.3±13.4 (3—53)
Terasaki 5 7 1 0 1 5 1 0 No data No data
Kobayashi 1 2 0 3 No data No data 12 0 19.8 (6.4—45) 38 (2.8—112)
Yang 1 1 2 3 No data No data No data No data No data No data

Mean surgery time (data are available in 7 studies) was sig-
nificantly higher by 57 min for ESD compared to EMR (95%
CI -87 – -28; p = 0.0001) (Fig. 2B).
Data on en bloc resection as the main indicator character-
izing resection quality were available in 7 reports. We found sig-
nificantly higher probability of en bloc resection for ESD (91.3
vs. 48 %, OR 0.13; 95% CI 0.03 — 0.49; p = 0.003) (Fig. 3).
Incidence of R0-resection was reported only in 3 out of 8
studies. This value was 84.7% for ESD that was more than 2
times higher than in EMR (40%) (OR 0.23; 95% CI 0.05 1.02;
p = 0.05) (Fig. 4).
Incidence of delayed bleeding was similar in both groups
(2.5% for EMR and 1.9% for ESD, 95% CI 0.44 — 1.87;
p = 0.79) (Fig. 5C). However, risk of intraoperative perforation
was 4 times lower in endoscopic mucosectomy (0.9%) com-
pared to ESD (4.8%) (OR 0.25; 95% CI 0.08 — 0.81; p = 0.02)
(Fig. 5A).

Fig. 2. Forest plot for tumor dimensions (a) and surgery time (b).

Fig. 3. Forest plot for en-bloc resection rate.

PIROGOV JOURNAL OF SURGERY, 9, 2021 79

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We found no differences in the incidence of additional re-
sections in accordance with morphological characteristics of tu-
mor (data are available in 3 studies). However, the ESD group
was characterized by higher risk of salvage surgery (9.6%) com-
pared to EMR (5.8%) (OR 0.48; 95% CI 0.22 — 1,03; p = 0.02)
(Fig. 6).
Follow-up period was reported in 4 out of 8 studies (mean
17 — 53 months). There were no significant differences in pa-
tient-years between the EMR and ESD groups (p = 0.25). Local
recurrence (available data in 5 studies) was more common after
endoscopic mucosectomy (15.2%) compared to ESD (0.9%) (OR
13.94; 95% CI 6.3 — 30,8; p = 0.00001) (Fig. 7—8).

Fig. 4. Forest plot for R0 resection rate.

Fig. 5. Forest plot for incidence of perforation (a) and delayed bleeding (b).

Fig. 6. Forest plot for incidence of redo surgery ensuring adequate resection quality.

80 PIROGOV JOURNAL OF SURGERY, 9, 2021


Fig. 7. Forest plot for mean follow-up period.
Fig. 8. Forest plot for recurrence rate.
Conclusion
Endoscopic dissection of colon tumors was introduced into
clinical practice in the late 1990s. This technique is character-
ized by more precise manipulations, deeper capture of submu-
cosa layers and need for additional technical equipment com-
pared to more traditional mucosectomy.
According to the results of our meta-analysis, incidence of en-
bloc resection is 6 times higher for ESD compared to EMR (OR
0.13; 95% CI 0.03 — 0.49; p = 0.003). R0 resection rate was as-
sessed only in 3 studies. However, this value was also significantly
higher for ESD (OR 0.23; 95% CI 0.05 — 1.02; p = 0.05). As a re-
sult, we obtained 13-fold higher incidence of local recurrence af-
ter mucosectomy (OR 13.94; 95% CI 6.3 — 30.8; p = 0.00001).
Despite higher resection quality following ESD, there are al-
so other important parameters of quality of surgical treatment
favorably distinguishing EMR. Thus, duration of EMR is sig-
nificantly less by 57 min compared to ESD (95% CI -87 – -28;
p = 0.0001). Incidence of delayed bleeding was similar (0.91 95%
CI 0.44 — 1.87; p = 0.79). However, ESD is associated with 4
times higher risk of colon wall perforation compared to EMR
(OR 0,25; 95% CI 0.08 — 0.81; p = 0.02).
According to meta-analysis by Ceglie A. et al. [19], inci-
dence of en-bloc resections following EMR is significantly lower
(62.8%) compared to submucosal dissection (90.5%) (OR = 0.18;
p <0.0001; 95% CI 0.16–0.2) that directly affects recurrence rate
(OR = 8.19; 95% CI: 6.2–10.9; p <0.0001) [19]. The authors al-
so found higher incidence of complications after ESD compared
to EMR procedure (p <0.0001, OR = 0.19, 95% CI 0.15–0.24).
Our data are similar to the results of meta-analysis by Zhao
H. et al. [20]. These authors pooled 12 English- and Chinese-
language retrospective studies. According to their data, inci-
dence of en-bloc resection was 95% in the ESD group. This val-
ue was significantly higher than in the EMR group (42.8%) (OR
0.07; 95% CI 0.02 — 0.07, p <0.00001). Higher recurrence rate
was also obtained in the EMR group (15.9% versus 0.5%) (OR
23.06; 95% CI 11.11 — 47.85; p <0.00001). Moreover, the au-
PIROGOV JOURNAL OF SURGERY, 9, 2021
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thors revealed significant between-group differences in the in-
cidence of perforation. This complication was more common
in case of submucosal dissection (2.4%) (OR 0.56; 95% CI
0.32 — 0.97; p = 0.04).
However, the results of this systematic review are limit-
ed by inclusion of not only full-text articles, but also abstracts
and articles in Chinese. These features explain difference
in the number of articles analyzed. Nevertheless, similar con-
clusions indicate reproducibility and regularity of data. It is al-
so important that the authors did not adjust for tumor dimen-
sion as a main factor compromising the results of mucosectomy.
A common disadvantage of meta-analyses is no adjustment
for dimension of neoplasms. Mucosectomy is limited by di-
mension of endoscopic loop and does not allow total resection
of large colon neoplasms.
The limitations of our meta-analysis are small number
of studies (retrospective as a rule) and no randomized trials.
Another significant limitation is inclusion of the results of en-
doscopic treatment of patients with early colorectal cancer de-
spite their even between-group distribution.
Conclusion
Thus, mucosectomy does not allow en-bloc resection
of large colon tumors that is significant limitation of this meth-
od. In this case, endoscopic submucosal dissection is prefera-
ble regarding resection quality compared to mucosectomy. How-
ever, higher incidence of perforations, surgery time and techni-
cal features of ESD do not allow us to unambiguously interpret
the results of our meta-analysis and determine the optimal surgi-
cal approach for large colon tumors. The limitations of our me-
ta-analysis are small number of studies (retrospective as a rule)
and no randomized trials. Thus, comparative studies including
randomized trials are required.
The authors declare no conflicts of interest.
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Received 14.12.2020
Accepted 15.01.2021
PIROGOV JOURNAL OF SURGERY, 9, 2021