Introduction
Endoscopic polypectomy and endoscopic mucosal resection (EMR) have been the standard
of care for many years; however, these methods should be avoided when challenging
lesions are encountered. Lesions >20 mm, with severe submucosal fibrosis, or residual/recurrent
lesions on scars after previous resection require advanced endoscopic resection techniques
to achieve en bloc resection. In this regard, endoscopic submucosal dissection (ESD)
has been introduced to overcome these challenges and improve resection results. Notably,
according to Japanese guidelines and the Japanese medical health insurance system,
superficial colonic neoplastic lesions >20 mm that are expected to be intramucosal
or slightly invasive submucosal cancer should be considered for ESD [11 ]. However, colorectal ESD is still considered a challenging technique [22 ]
[33 ]
[44 ].
In order to manage lesions with severe submucosal fibrosis, we have developed the
pocket-creation method (PCM) [55 ]
[66 ]. PCM is one of the techniques recommended for colorectal ESD in the 2023 technical
review from the European Society of Gastrointestinal Endoscopy [77 ]. However, during opening of the pocket, the surrounding mucosa gradually loses traction,
and the lesion becomes very unstable, making PCM-assisted ESD technically challenging.
To overcome this, we developed a novel technique named the pocket-creation method
with single-clip traction (PCM-CT) [88 ]
[99 ]. No prospective study has compared the efficacy of PCM-CT with that of conventional
PCM; therefore, we prospectively compared the two techniques in this multicenter,
randomized, controlled trial.
Methods
Study design
This randomized controlled clinical trial was carried out at four Japanese institutions.
The trial followed the Declaration of Helsinki, and the trial protocol received the
approval of the ethics committee at each of the four participating institutions: Jichi
Medical University Hospital (B20–153), Fukushima Medical University Aizu Medical Center
(RK2021–001), Kansai Medical University Medical Center (2021247), and Jyoban Hospital
of Tokiwa Foundation (JHTF-2021–003). The manuscript was prepared according to the
checklist of the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement
(see the online-only supplementary material) [1010 ].
Patient inclusion and exclusion criteria
Patients were enrolled if they had superficial colonic neoplastic lesions >20 mm that
were expected to be intramucosal or slightly invasive submucosal cancer according
to Japanese guidelines for colorectal cancer [11 ]. Before study enrollment, all patients underwent preoperative colonoscopy. The lesion
size was estimated with an endoscopic measuring device (M2–3U; Olympus, Tokyo, Japan).
The tumor invasion depth was evaluated based on nonmagnifying endoscopic findings
and magnifying endoscopic findings using Japan Narrow Band Imaging Expert Team (JNET)
classification [1111 ] and/or Kudo’s pit pattern [1212 ]. Additionally, endoscopic ultrasonography was performed when submucosal invasive
cancer was suspected. Patients were excluded if they had: lesions extending to the
appendiceal orifice, colonic diverticula, or ileocecal valve; patients with diagnosed
ulcerative colitis, Crohn’s disease, hematological abnormalities, or severe organ
failure; and patients with lesions >100 mm in diameter. We excluded these very challenging
lesions to ensure patient safety, as trainees participated in the trial. Patients
with rectal lesions were also excluded. When a patient had multiple lesions, only
the lesion located most orally was registered in the trial to prevent operator selection
bias for a lesion treated with PCM or PCM-CT. Patients under the age of 20 years or
over 91 years, and patients unable to consent to the procedure were excluded from
the study. All patients provided written informed consent after receiving a detailed
explanation of endoscopic procedures and study participation by researchers.
Operators and assistants
Seven endoscopists performed all procedures. Endoscopists with experience of 20–100
colonoscopies were selected as operators to eliminate bias based on ESD skills; these
endoscopists were not able to perform colorectal ESD independently, but did have significant
ESD experience in the upper gastrointestinal tract, where they could operate without
supervision. In institutions with multiple operators, an equal number of trial cases
was assigned to each operator. If an operator exceeded the predetermined number of
100 cases of colorectal ESDs during the study period, the additional cases were also
included in the study. The participating ESD operators were independent endoscopists
with experience of total colonoscopy, polypectomy, EMR, more than 20 gastric ESDs,
and certification from the Japanese Society of Gastrointestinal Endoscopy, or equivalent
skills. In addition to the above, participating endoscopists had experience of at
least 20 colorectal ESDs to ensure patient safety and research quality. Participating
endoscopists were assisted by expert endoscopists who had experience of more than
100 colorectal ESDs and of supervising ESD procedures. The assistants were randomly
assigned.
ESD procedures
A colonoscope (EC-580RD/M [Fujifilm, Tokyo, Japan] or PCF-H290TI [Olympus]), a carbon
dioxide insufflation regulation unit (GW-1 [Fujifilm] or UCR, [Olympus]), and a mechanical
water pump (JW-2 [Fujifilm] or OFP-2 [Olympus]) were used for all procedures. VIO-300D
(ERBE Elektromedizin GmbH, Tübingen, Germany) or ESG-400 (Olympus) were used for diathermy.
The settings of these diathermy devices were mucosal incisions (Endo-Cut I, effect
1, duration 1–4, interval 1), submucosal dissection (swift coagulation, effect 4,
25–30 W), and coagulation (soft coagulation, effect 4, 80 W) for VIO-300D, and mucosal
incisions (Pulse cut fast, effect 1, 50 W), submucosal dissection (forced coagulation,
effect 3, 30 W), and coagulation (soft coagulation, effect 3, 50 W) for ESG-400. Either
the DualKnife (KD-650Q; Olympus) or Flushknife (DK2620J-B15S-; Fujifilm) was used
as an electrosurgical knife. In both groups, a conical cap (ST hood, DH-33GR; Fujifilm)
and 0.4% sodium hyaluronate solution (MucoUp; Seikagaku Corp., Tokyo, Japan) for submucosal
injection were used. When performing PCM-CT, a general purpose, reopenable clip with
16 mm opening width (SureClip Plus, ROCC-F-26–235-C; Micro-Tech Co., Ltd. Nanjing,
China) was used as the traction device.
The assistant (expert endoscopist) was allowed to take over from the operator for
patient safety in the event of intraoperative perforation, intraoperative uncontrollable
bleeding, or when the operator was unable to continue the procedure appropriately.
In addition, when the procedure time exceeded 2 hours, the assistant was allowed to
take over to avoid operator fatigue and diminished concentration; these decisions
were made by the assistant of the procedure.
Pocket-creation method with/without single-clip traction
The PCM was performed as previously reported [55 ]
[66 ]
[1313 ]
[1414 ]
[1515 ]. PCM-CT was also performed as previously reported [88 ]
[99 ] ([Fig. 1Fig. 1 ], [Fig. 2Fig. 2 ]).
Fig. 1
Fig. 1 Pocket-creation method with single-clip traction (PCM-CT). First, 0.4% sodium hyaluronate
solution is injected into the submucosa. a Mucosal incision. b Creation of a submucosal pocket under the tumor in the same manner as for the pocket-creation
method (PCM). c Circumferential mucosal incision around the lesion. d Normal mucosa from the anal side of the partially resected tumor is grasped with
a reopenable clip, without deploying it. e The entrapped mucosa is pulled toward the opposite wall and the clip further captures
the opposing mucosa. Capture of both the tumor and opposing mucosa is visually confirmed
and the clip is then deployed. f PCM-CT stretches the submucosa, exposing the appropriate submucosal dissection plane.
Fig. 2
Fig. 2 Sequential pictures of the pocket-creation method with single-clip traction. a A 20-mm laterally spreading tumor, nongranular, pseudo-depressed type in the sigmoid
colon; 0.4% hyaluronic acid was injected. b An initial mucosal incision was made 1 cm distant from the tumor. c Creating the submucosal pocket in the same manner as for the pocket-creation method.
d A circumferential incision was made after creation of the submucosal pocket under
the tumor. e Grasping the anal edge of the partially dissected specimen with a reopenable clip.
f Attaching the specimen to the mucosa of the opposite intestinal wall. g The remaining submucosa is stretched to facilitate resection. h The connecting reopenable clip is finally removed with grasping forceps after completion
of the submucosal dissection. i Pinned resected specimen. Pathology reported a T1 cancer of well differentiated adenocarcinoma
with 900 µm submucosal invasion, positive lymphovascular invasion, and negative margins.
Randomization and blinding
Tumor morphology and the institution were used for randomization. Tumor morphology
was used to assign protruded lesions (0-I) and laterally spreading tumors of granular
type as sessile types, and nongranular laterally spreading tumors as flat types. Randomization
was performed using Research Electronic Data Capture (Vanderbilt University, Nashville,
Tennessee, USA) as the electronic data capture system, and a stratified permuted block
randomization method. Blinding to study participants and pathologists was conducted.
Histopathological diagnosis followed the World Health Organization classification
[1616 ]: low grade adenoma, high grade dysplasia, and T1 cancer. Colonic ESD operators and
assistants were determined before the start of ESD, and the operator and assistant
were not informed of the PCM or PCM-CT group assignment based on randomization until
the start of ESD.
Definition of recorded data
ESD completion was defined as completion of ESD with an en bloc resection using the
assigned ESD method without changing to the other method or changing operator during
the procedure.
The procedure time was defined as the time from the start of the first mucosal incision
to the end of the lesion excision. The dissection speed was defined as “short diameter
of excised specimen × long diameter of excised specimen × 0.25 × 3.14/procedure time”
[1717 ].
En bloc resection was defined as the resection of the lesion in one single piece.
R0 resection was defined as the histopathological affirmation of an en bloc resection
with negative vertical and horizontal margins.
Postoperative bleeding and perforation were documented as adverse events. Delayed
bleeding was defined as overt bleeding occurring within 14 days after ESD, that resulted
in a hemoglobin level drop of at least 2 g/dL and required endoscopic hemostasis or
blood transfusion [1818 ]. Perforation was defined as a deep mucosal injury that resulted in direct exposure
between intraperitoneal and intestinal lumen during or after the procedure; the former
was defined as intraoperative perforation, and the latter as delayed perforation.
Intraoperative perforation was diagnosed when the intraperitoneal cavity was confirmed
by endoscopic visualization. Delayed perforation was diagnosed when evidence of free
air was seen at computed tomography scan or X-ray.
In addition, the following information specific to the current study was defined (Fig. 1s ). The time from the first mucosal incision to completion of the submucosal pocket
was defined as the pocket-creation time. The remaining time until the complete excision
of the lesion was defined as the pocket-opening time. The procedure time was the total
of the pocket-creation time and pocket-opening time.
The following information was additionally defined in the PCM-CT group. The time from
the appearance of the clip on the endoscopic view to the completion of clip deployment
prior to PCM-CT was defined as the clip deployment time. If a clip fell off during
the procedure and had to be redeployed, the additional clip deployment time was added.
Outcomes
The primary outcome of this study was the dissection speed, which is commonly used
to estimate the efficiency of ESD. The procedure time, pocket-opening time, rate of
en bloc resection, rate of R0 resection, and rate of adverse events were analyzed
as secondary outcomes. Subgroup analyses were conducted for tumor location, morphology,
and size (<30 mm or ≥30 mm).
Sample size
PCM had a dissection speed of 16.0 mm2 /min in a previous multicenter trial [1414 ], and PCM-CT had a dissection speed of 20 mm2 /min in 30 consecutive cases in a recent retrospective study [99 ]. Therefore, we expected that PCM-CT could increase the efficiency of pocket opening
by about 20% compared with PCM. To detect a significant difference between the groups
with a significance level of 0.05 (two sided) and a power of 80%, 45 patients in each
group were required and 90 patients in total; considering 10% dropouts, the study
population was set at 100 patients. EZR (Saitama Medical Center, Jichi Medical University,
Saitama, Japan) [1919 ], a graphical user interface for R (The R Foundation for Statistical Computing, Vienna,
Austria), was used for the calculation.
Statistical analysis
The primary outcomes were analyzed based on the intention-to-treat analysis. Categorical
data were analyzed using the chi-squared test or Fisher’s exact test. Continuous variables,
which are quantitative data, were compared using the Mann–Whitney U test or t test. P < 0.05 (two sided) was considered significant. All statistical analyses were performed
using EZR.
Results
Participant flow and recruitment
From May 2021 to May 2023, 100 patients with 100 colonic tumors were included in the
trial and randomly assigned to the PCM-CT group (n = 49) or PCM group (n = 51) ([Fig. 3Fig. 3 ]).
Fig. 3
Fig. 3 Flow chart of the study. ITT, intention to treat; PCM-CT, pocket-creation method with
single-clip traction; PCM, pocket-creation method.
Baseline data
Baseline characteristics of patients, lesions, and experience of each operator are
presented in [Table 1Table 1 ]. A total of 70 men and 30 women, with a mean age of 67.8 (SD 11.3) years, were included.
Table 1
Table 1 Baseline characteristics of patients and procedures.
Characteristics
PCM-CT
(n = 49)
PCM
(n = 51)
PCM-CT, pocket-creation method with single-clip traction; PCM, pocket-creation method.1 ERBE Elektromedizin GmbH, Tübingen, Germany.2 Olympus, Tokyo, Japan.3 Fujifilm, Tokyo, Japan.4 Flat type: laterally spreading tumor (LST), nongranular type; elevated type: protruded
lesion (0-I) and LST, granular type.
Age, mean (SD), years
67.9 (12.8)
67.7 (9.8)
Sex
9 (18)
21 (41)
40 (82)
30 (59)
Antithrombotic medication
8 (16)
6 (12)
41 (84)
45 (88)
Diathermy
43 (88)
46 (90)
6 (12)
5 (10)
Electrosurgical knife
40 (82)
39 (77)
9 (18)
12 (24)
Tumor location
5 (10)
8 (16)
21 (43)
16 (31)
10 (20)
10 (20)
2 (4)
5 (10)
11 (22)
12 (24)
Morphology4
23 (47)
23 (45)
26 (53)
28 (55)
Operators [previous colorectal ESDs]
11 (22)
11 (22)
6 (12)
5 (10)
13 (27)
11 (22)
8 (16)
11 (22)
6 (12)
9 (18)
4 (8)
4 (8)
1 (2)
0 (0)
ESD completion rate
One of the 49 patients in the PCM-CT group had their ESD discontinued due to abdominal
pain associated with intraoperative perforation and was excluded from any further
analysis ([Fig. 3Fig. 3 ]). In the PCM-CT group, four patients had a change of operator during the procedure,
including one case of overtime and three cases of procedural difficulties. In the
PCM group, seven patients had a change of operator during the procedure, including
two cases of overtime and five cases of procedural difficulties. In addition, one
patient who had an operator switch due to procedural difficulties also had a change
of assigned procedure, from PCM to PCM-CT.
Treatment results and outcomes
ESD data were collected from 99 patients and are shown in [Table 2Table 2 ]. The mean (SD) dissection speeds were 27.0 (14.5) and 21.4 (10.8) mm2 /min in PCM-CT and PCM groups, respectively, which were significantly different (95%CI
0.5 to 10.7, P = 0.03). In the PCM-CT group, both the pocket-opening time and procedure time were
lower compared with the PCM group, but the differences were not statistically significant.
The rate of en bloc resection, R0 resection, and adverse events were not significantly
different between the groups. Clinicopathological features of the resected lesions
are shown in [Table 2Table 2 ].
Table 2
Table 2 Endoscopic submucosal dissection-related data (intention-to-treat analysis).
PCM-CT
(n = 48)
PCM
(n = 51)
95%CI
P value
PCM-CT, pocket-creation method with single-clip traction; PCM, pocket-creation method;
N/A; not applicable.
Data are mean (SD) unless otherwise stated.
Hyaluronic acid, mL
57.8 (29.8)
62.3 (37.8)
–18.2 to 9.1
0.51
Procedure time, minutes
64.8 (47.6)
81.8 (57.9)
–38.2 to 4.3
0.12
Dissection speed, mm2 /min
27.0 (14.5)
21.4 (10.8)
0.5 to 10.7
0.03
25.6 (12.5)
16.3 (9.2)
–0.5 to 19.0
0.06
18.9 (6.6)
21.9 (10.0)
–14.5 to 8.3
0.56
41.0 (14.7)
32.9 (13.4)
–3.9 to 20.1
0.17
21.1 (12.0)
18.7 (6.6)
–6.9 to 11.6
0.60
18.6 (8.6)
17.2 (4.7)
–6.0 to 8.8
0.69
25.6 (6.9)
19.8 (7.1)
–6.4 to 17.9
0.29
5.6
N/A
N/A
N/A
22.6 (11.1)
18.3 (8.3)
–1.2 to 9.7
0.13
31.3 (16.3)
24.8 (12.3)
–1.8 to 14.9
0.12
Pocket-creation time, minutes
34.9 (22.1)
44.0 (29.0)
–19.4 to 1.3
0.08
Pocket-opening time, minutes
30.0 (28.9)
37.8 (33.0)
–20.2 to 4.6
0.22
En bloc resection, n (%)
48 (100)
51 (100)
0
>0.99
Delayed perforation, n (%)
0 (0)
0 (0)
0
>0.99
Delayed bleeding, n (%)
2 (4)
5 (10)
0.04 to 2.6
0.44
R0 resection, n (%)
48 (100)
49 (96)
0.2 to Inf
0.50
Tumor size, mm
32.4 (10.8)
34.4 (15.1)
–7.2 to 3.3
0.45
Specimen size, mm
44.7 (11.7)
46.3 (16.4)
–7.4 to 4.1
0.57
Operators switched, n (%)
4 (8)
7(14)
0.1 to 2.5
0.53
Histology, n (%)
21 (44)
16 (31)
0.46
21 (44)
28 (55)
6 (13)
5 (83)
1 (17)
7 (14)
5 (71)
2 (29)
1 (2)
2 (4)
0.08 to 96.4
>0.99
2 (4)
0 (0)
0 to 4.1
0.19
0 (0)
1 (2)
0.02 to Inf
>0.99
0 (0)
1 (2)
0.02 to Inf
>0.99
We also performed a per protocol analysis ([Table 3Table 3 ], [Fig. 3Fig. 3 ]) in 88 patients with completed ESD. This analysis of PCM-CT vs. PCM showed mean
(SD) dissection speeds of 28.3 (14.3) vs. 22.8 (10.6) mm2 /min (95%CI 0.1 to 10.8, P = 0.045), procedure times of 58.3 (39.8) vs. 70.3 (42.7) minutes (95%CI –29.5 to 5.4,
P = 0.17), and pocket-opening times of 27.1 (25.1) vs. 31.8 (25.5) minutes (95%CI –15.4
to 6.0, P = 0.39). In this subgroup analysis, the difference in dissection speed between PCM-CT
and PCM group was statistically significant (P = 0.045).
Table 3
Table 3 Endoscopic submucosal dissection-related data (per protocol analysis).
PCM-CT
(n = 44)
PCM
(n = 44)
95%CI
P value
PCM-CT, pocket-creation method with single-clip traction; PCM, pocket-creation method;
N/A, not applicable; Inf, infinity.
Data are mean (SD) unless otherwise stated.
Hyaluronic acid, mL
56.8 (28.3)
58.4 (36.2)
–15.5 to 12.1
0.81
Procedure time, minutes
58.3 (39.7)
70.3 (42.7)
–29.5 to 5.4
0.17
Dissection speed, mm2/min
28.3 (14.3)
22.8 (10.6)
0.1 to 10.8
0.045
25.9 (13.1)
18.8 (8.1)
–3.7 to 17.8
0.18
20.6 (5.6)
21.9 (10.0)
–13.2 to 10.5
0.80
41.0 (14.7)
32.9 (13.4)
–3.9 to 20.1
0.17
22.6 (12.4)
21.6 (6.4)
–11.7 to 13.7
0.87
18.6 (8.6)
17.2 (4.7)
–6.0 to 8.8
0.69
25.6 (6.9)
19.8 (7.1)
–6.4 to 17.9
0.29
N/A
N/A
N/A
N/A
23.7 (11.3)
20.4 (7.9)
–2.9 to 9.4
0.29
32.5 (15.7)
24.8 (12.3)
–0.6 to 15.9
0.07
Pocket-creation time, minutes
31.2 (17.5)
38.5 (21.2)
–15.6 to 0.9
0.08
Pocket-opening time, minutes
27.1 (25.1)
31.8 (25.5)
–15.4 to 6.0
0.39
En bloc resection, n (%)
44 (100)
44 (100)
0
>0.99
Delayed perforation, n (%)
0 (0)
0 (0)
0
>0.99
Delayed bleeding, n (%)
2 (5)
4 (9)
0.3 to 24.2
0.68
R0 resection, n (%)
44 (100)
42 (95)
0.2 to Inf
0.49
Tumor size, mm
32.1 (10.4)
33.5 (13.7)
–6.6 to 3.7
0.58
Specimen size, mm
44.3 (11.2)
45.6 (14.9)
–6.9 to 4.2
0.64
Histology, n (%)
20 (46)
14 (32)
0.36
18 (41)
24 (55)
6 (14)
5 (83)
1 (17)
6 (14)
4 (67)
2 (33)
1 (2)
2 (5)
0.08 to 101
>0.99
2 (5)
0 (0)
0 to 4.2
0.19
0 (0)
1 (2)
0.03 to Inf
>0.99
0 (0)
1 (2)
0.03 to Inf
>0.99
Subgroup analysis
Subgroup analyses were conducted for tumor location, morphology, and size (<30 mm
or ≥30 mm) in relation to the dissection speed. There was a significant difference
in mean (SD) dissection speed in favor of the PCM-CT group for lesions in the right
colon (28.5 [15.7] vs. 21.4 [9.5] mm2 /min [95%CI 0.8 to 13.3], P = 0.03)] and especially in the ascending colon (31.4 [17.8] vs. 21.3 [9.9] mm2 /min [95%CI 0.1 to 20.2], P = 0.048)].
Adverse events
One patient in the PCM-CT group had their ESD discontinued due to intraoperative perforation
with uncontrollable abdominal pain. The patient was excluded from any further analysis
as no ESD data were collected. He was managed by endoscopic clip closure of the muscle
defects and conservative treatment with fasting and prophylactic intravenous antibiotics.
There was no delayed perforation or intraprocedural uncontrolled bleeding in either
group. Delayed bleeding was documented in two patients in the PCM-CT group and in
five patients in the PCM group. There were no fatal adverse events during the study
period.
Discussion
ESD has been accepted worldwide as minimally invasive treatment of superficial colorectal
cancer [44 ]. Although it is still a clinically challenging procedure, it is gradually becoming
safer and easier due to the development of dedicated attachments [2121 ]
[2222 ], traction methods [2323 ]
[2424 ]
[2525 ]
[2626 ]
[2727 ], and resection strategies such as PCM [55 ]
[66 ]
[1313 ]
[2828 ]. Overall, effective cancer management requires complete local resection and assessment
of metastasis risk. In particular, the risk factors are associated with the submucosa
of the resected specimen. Therefore, the goal of endoscopic treatment is to achieve
complete local excision of the tumor with submucosa of sufficient depth to ensure
negative margins.
The PCM procedure secures an adequate depth of submucosa in the resected specimen,
with minimal thermal injury, to allow the risk of lymph node metastasis to be determined
[2828 ]
[2929 ]. PCM-CT and PCM both achieved high R0 resection rates in the present study ([Table 2Table 2 ]). Given these advantages, PCM has proven to be effective in colorectal ESD regardless
of tumor size, morphology [1313 ]
[1515 ], or location [3030 ], and is a useful strategy among other techniques available in ESD [1414 ]
[3131 ]. In addition, the effectiveness of PCM has also been reported for gastric [3232 ]
[3333 ] and duodenal [3434 ] ESD. However, during pocket opening in PCM procedures, the submucosal pocket can
be challenging, as the more the pocket is opened, the less stable the endoscope tip
becomes.
PCM-CT was developed to overcome the technical difficulty associated with opening
the submucosal pocket. Our results revealed that PCM-CT had significantly better performance
than conventional PCM in dissection speed (27.0 [14.5] vs. 21.4 [10.8] mm2 /min [95%CI 0.5 to 10.7], P = 0.03). The mean clip deployment time in PCM-CT was 2.3 minutes, and the overall
procedure time was much shorter than that with PCM (64.8 vs. 81.8 minutes). As a side
note, we cannot accurately calculate the dissection speed for opening the pocket because
we cannot measure only the area around the pocket on a resected specimen.
This study shows that the addition of clip traction reproducibly improves the conventional
PCM procedure. Most conventional traction techniques are dedicated devices or hand-made
combinations of clip and a connecting part. Most PCM-CTs were completed using only
a single general purpose reopenable clip as a traction device for each procedure,
indicating that PCM-CT was also cost-effective. The SureClip Plus that was used, costs
3500 Japanese Yen (JPY), and is cheaper than other dedicated traction devices; for
example, the S-O clip (TC1H05; Zeon Medical Inc. Tokyo, Japan) is 5000 JPY, SureClip
Traction Band (ETD00005, ETD00006; Micro-Tech Co., Ltd.) is 5200 JPY, ProdiGI Traction
Wire (ERD-TW20, ERD-TW35; Medtronic, Minneapolis, USA) is 20 500 JPY, and FlexLifter
(LA-400; Olympus) is 35 000 JPY. Furthermore, the single-clip traction could connect
the specimen to the contralateral wall by decreasing the amount of luminal gas, and
adjust the traction force by increasing or decreasing the gas. The application of
a traction clip from the early stages of the ESD could be useful. However, based on
our experience, achieving sufficient submucosal elevation through local injection
of sodium hyaluronate, followed by mucosal incision and several superficial submucosal
dissections while gently lifting the mucosa with the sheath portion of the knife,
facilitates easy insertion of the tip of the ST hood into the submucosal layer in
most cases. In contrast, if traction clips are placed immediately after incision this
could interfere with the subsequent procedure, and could also damage the specimen
owing to unintentional traction force. In PCM, traction is usually necessary only
when the pocket is opened, as the endoscopic manipulation becomes unstable. Recently,
double-clip traction ESD reported by Bordillon et al. [2020 ] achieved a significantly faster dissection speed (39.4 mm2 /min) than PCM-CT (27.0 mm2 /min). These excellent outcomes might be due to participating endoscopists having
more ESD experience compared with our nonindependent operators. Meanwhile, a Japanese
multicenter randomized controlled trial of traction-assisted ESD (CONNECT-C trial)
[2626 ] showed a slower dissection speed (16 mm2 /min) than in our study. The CONNECT-C trial concluded that the traction method did
not significantly shorten ESD time but could be useful for large tumors or nonexpert
operators.
Subanalysis of the present study revealed that PCM-CT had a significantly faster dissection
speed than PCM in the right colon (28.5 [15.7] vs. 21.4 [9.5] mm2 /min [95%CI 0.8 to 13.3], P = 0.03), especially in the ascending colon (31.4 [17.8] vs. 21.3 [9.9] mm2 /min [95%CI 0.1 to 20.2], P = 0.048). This could be due to the stretchability and thickness of the submucosal
tissue in the ascending colon, an observation based on our extensive experience with
colonic ESD. Therefore, traction force will stretch the submucosal tissue more effectively
and secure good visibility of the submucosa, thus facilitating submucosal dissection.
Histopathology of the ESD specimens revealed 37% (37/99) low grade adenoma. According
to Japanese guidelines and the medical health insurance system, ESD should be offered
to patients with endoscopically suspected early cancer including high grade dysplasia
regardless of the final histopathological report. This might account for some cases
of overestimation at optical diagnosis when a large lesion was considered too big
for a proper en bloc resection with conventional EMR. Additionally, it should be noted
that the diagnostic yield of JNET type 2B is still controversial [3535 ].
This study has some limitations. First, the operating endoscopists were not blinded,
although patients and pathologists were completely blinded to the assigned group.
Nevertheless, we cannot exclude that some operating endoscopists unconsciously preferred
one technique over the other. Notwithstanding this lack of blinding, all operators
were trainees and as such, they were evaluated on their speed, effectiveness, and
performance, and regardless of their preferred technique they were always focused
on the best outcome for every lesion. Second, the decision to change the operators
was subjective and it was done only after consultation with the assistant endoscopist;
however, switching was based on definite criteria. We think that this was an adequate
measure to support the fairness of this study bias when comparing ESD completion rates
between the two groups. Third, the skill level of the operating endoscopists could
not be completely equal, although only endoscopists with experience of between 20
and 100 colorectal ESDs at the beginning of the study were included. Rectal lesions
were excluded, as rectal ESD is considered less challenging; the procedure is naturally
assisted by the gravity traction of changing a patient’s body position. Fourth, the
rate of delayed bleeding (7/99 [7%]) in this study was higher than previously reported
[99 ]
[1616 ]. Six of the seven patients with delayed bleeding underwent endoscopic hemostasis
despite there being no hemoglobin drop of ≥2 g/dL or the need for blood transfusion.
Moreover, in 5/6 patients, the bleeding had already stopped spontaneously at the time
of endoscopic intervention. Only one patient in the PCM group had a hemoglobin drop
of 3.0 g/dL that required blood transfusion. Fifth, although both “dissection speed”
and “procedure time” had been registered as primary outcomes in the University Hospital
Medical Network Clinical Trials Registry, we decided to change the “procedure time”
to a secondary outcome. Sixth, adjustment factors should have also included lesion
size and location; however, when this study was designed, the population was not large
enough, and thus these two factors were reserved for a secondary analysis. Finally,
one patient in the PCM-CT group was excluded from the analysis after discontinuation
of the procedure due to uncontrollable abdominal pain caused by intraoperative perforation
during pocket opening. It is important to note that intraoperative perforation with
mucosal incision in the pocket opening is not specific to PCM-CT. The patient was
discharged after conservative treatment following immediate clip closure of the perforation;
laparoscopic surgery was performed subsequently to remove the lesion.
Conclusion
According to this study, PCM-CT appeared to further improve PCM by increasing the
resection speed. Additionally, both PCM-CT and PCM achieved high R0 resection rates
in the present study, thus reinforcing the pre-existing knowledge that PCM is highly
effective for colonic ESD.
