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Original Article Effect of double-layered suturing for mucosal defect closure after colorectal endoscopic submucosal dissection on postoperative adverse events: a propensity score-matched retrospective study in Japan
Kyohei Nishino1orcid, Hiroki Fujita1orcid, Takahiro Yuge1orcid, Masanori Hongo1orcid, Naoko Mori1orcid, Kazumi Shimamoto1orcid, Yu Kobayashi1orcid, Takashi Toyonaga2orcid, Hiromitsu Ban1orcid
Clinical Endoscopy 2025;58(6):881-889.
DOI: https://doi.org/10.5946/ce.2025.053
Published online: November 6, 2025

1Department of Gastroenterology, Omi Medical Center, Shiga, Japan

2Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Hyogo, Japan

Correspondence: Kyohei Nishino Department of Gastroenterology, Omi Medical Center, Yabase-chou 1660, Kusatsu, Shiga 525-8585, Japan E-mail: knishino@seikoukai-sc.or.jp
• Received: February 18, 2025   • Revised: April 18, 2025   • Accepted: April 21, 2025

© 2025 Korean Society of Gastrointestinal Endoscopy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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See letter "Colorectal endoscopic submucosal dissection defect closure: promising but still evolving" in Volume 58 on page 856.
  • Background/Aims
    Prophylactic closure of mucosal defects after colorectal endoscopic submucosal dissection (ESD) can reduce the incidence of postoperative adverse events. However, data on this notion are limited. This study retrospectively evaluated the effect of closure using a double-layered suturing technique on postoperative adverse events.
  • Methods
    A total of 370 lesions in 317 patients who underwent colorectal ESD were included in this analysis. Patients with 197 lesions that were completely closed were then assigned to the closure group. Patients with 173 lesions, including 55 that were partially closed and 118 that were not closed, were assigned to the non-closure group. Propensity score matching was performed, and 136 lesions were selected for each group.
  • Results
    The closure group had a significantly lower overall incidence rate of postoperative adverse events, including delayed bleeding, delayed perforation, and post-ESD electrocoagulation syndrome, than the non-closure group (2.2% vs. 9.6%, p=0.018). The closure group had a significantly lower incidence of abdominal pain on the day after ESD than the non-closure group (2.9% vs. 11.0%, p=0.015).
  • Conclusions
    Prophylactic closure of mucosal defects after colorectal ESD using a double-layered suturing technique could prevent postoperative adverse events and abdominal pain on the day after ESD.
Colorectal endoscopic submucosal dissection (ESD) has become a widely used endoscopic technique for resecting superficial colorectal tumors.1 ESD has a higher en bloc resection rate, particularly for large lesions, than endoscopic mucosal resection (EMR). Thus, ESD is associated with better curability and can facilitate an adequate histological evaluation.2 However, the high incidence of postoperative adverse events, such as delayed bleeding, delayed perforation, and post-ESD electrocoagulation syndrome (PECS), which are associated with larger mucosal defects after ESD, has been a cause of concern.3 Recent meta-analyses have reported that the incidence of postoperative adverse events after ESD is higher than that after EMR.4 Therefore, these events should be controlled. Various techniques have been used to close larger mucosal defects during ESD.5 However, their efficacy in preventing adverse events remains controversial. Furthermore, few studies have evaluated the single-closure technique in a substantial number of cases.
In some cases, closure of mucosal defects after colorectal ESD is performed using a double-layered suturing technique with conventional hemostatic clips.6 In this technique, the muscle layer is first grasped directly with clips and tented inward, and then the mucosal layer is closed (Fig. 1). Therefore, this technique has the potential to provide more reliable closure and prevent the spread of inflammation and abdominal pain compared with methods that merely close the mucosal layer. This study aimed to retrospectively evaluate the effect of prophylactic closure using this technique on the incidence of postoperative adverse events.
Study design and patients
This study included 379 lesions in 326 patients who underwent colorectal ESD at our institution between March 2018 and May 2023. Patients with lesions that were not resected or those who underwent closure using other techniques were excluded from the analysis. The indications for colorectal ESD were based on the Japanese Society of Gastrointestinal Endoscopy guidelines.7 Antithrombotic drugs were discontinued and resumed according to the guidelines of the Japanese Society of Gastrointestinal Endoscopy.8
ESD procedure
ESD was performed using a conventional colonoscope or a gastrointestinal endoscope with carbon dioxide insufflation. Pethidine and dexmedetomidine were administered for analgesia and sedation, respectively, and midazolam was administered as required. MucoUp (0.4% sodium hyaluronate; Boston Scientific Co.) was used as the local submucosal injection solution. FlushKnife BT (Fujifilm Medical) and a high-frequency device (VIO 3; Erbe Elektromedizin GmbH) were mainly used. ESD duration was defined as the time from submucosal injection to lesion resection. A prophylactic antibacterial agent (cefmetazole) was administered on the day of ESD and the following day. Patients without complications were permitted to drink water on the day after ESD and resume eating on the second day.
Endoscopic closure procedure
The closure of the mucosal defects after ESD was performed at the discretion of the endoscopist. Complete closure was defined as a nonvisible submucosal layer of the ulcer bed in the closure line. Closure was performed using a double-layered suturing technique with hemostatic clips (EZ Clip; Olympus or Sure Clip; MC Medical).6 Briefly, to reduce the size of the mucosal defect (Fig. 1A), the clips were applied longitudinally to the muscular layers in the center of the ulcer floor (Fig. 1B, D). Additional clips were applied to the mucosal layer in the spaces intentionally left between the clips used in the previous procedure for complete closure (Fig. 1C, E, F).
Patients with lesions that underwent complete closure were assigned to the closure group. Meanwhile, patients with lesions, including those that were partially closed only at the site of the perforator vessel or muscular layer injury and those that were not closed, were assigned to the non-closure group.
Histopathological assessment
Curative resection was defined as fulfillment of all the following characteristics in accordance with the 2019 Japanese Society for Cancer of the Colon and Rectum Guidelines for the Treatment of Colorectal Cancer: (1) negative vertical margin (histologically complete resection), (2) papillary adenocarcinoma or tubular adenocarcinoma, (3) a submucosal invasion depth of <1,000 μm, (4) absence of lymphovascular invasion, and (5) grade 1 tumor budding.9
Outcome measures
The primary endpoint was the incidence of postoperative adverse events. The postoperative adverse events included delayed bleeding, delayed perforation, and PECS. Delayed bleeding was defined as overt hematochezia that required endoscopic hemostasis and blood transfusion or a decrease in hemoglobin level by >2 g/dL.10 PECS was defined as localized abdominal pain and fever (>37.5 ℃) or an elevated inflammatory response (as evidenced by a white blood cell [WBC] count of >10,000 cells/μL or a C-reactive protein [CRP] of >0.5 mg/dL) occurring at least 6 hours after ESD and absence of evident perforation.11
The secondary endpoints were abdominal pain, WBC count, CRP level, fever on the day after ESD, and length of hospital stay. The severity of abdominal pain was assessed the morning after ESD using a visual analog scale (VAS). The scale ranged from 0 (no pain) to 10 (maximum pain). Abdominal pain was defined as a VAS score >4 at the site of ESD.12
Statistical analysis
Categorical data were presented as numbers and percentages and were analyzed using Fisher's exact test. Numerical data were expressed as means with standard deviations and were analyzed using the unpaired t-test. Differences among the three groups were compared using a one-way analysis of variance. The propensity score was calculated based on logistic regression, with age, sex, use of antithrombotic agents, lesion location, tumor size, specimen diameter, and ESD duration as covariates. One-to-one nearest neighbor matching was performed within a caliper width equal to 0.20 of the standard deviation of the propensity score logit. The odds ratios for risk factors associated with the development of abdominal pain were calculated by logistic regression, and factors indicating significance (p˂0.05) in the univariate analysis were further analyzed by multivariate analysis for all lesions before propensity score matching. Statistical significance was set at p<0.05. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University; http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html),13 which is a graphical user interface for R ver. 2.13.0 (The R Foundation for Statistical Computing).
Ethical statements
A written informed consent for ESD treatment was obtained from all patients. This study was approved by the Ethics Committee of Omi Medical Center (2023-0032). All patients were provided the opportunity to decline participation in the study through the opt-out method on the website.
Characteristics of the patients and lesions before propensity score matching
This study included 379 lesions in 326 patients who underwent colorectal ESD at our institution between March 2018 and May 2023. Seven patients with seven lesions that were not resected and two patients with two lesions that underwent closure using other techniques were excluded from the analysis. Patients with 197 lesions that were completely closed using the double-layered suturing technique were assigned to the closure group. Meanwhile, patients with lesions, including 55 that were partially closed only at the site of the perforator vessel or muscular layer injury and 118 that were not closed, were assigned to the non-closure group (Fig. 2). As shown in Table 1, the median (range) ages of the closure and non-closure groups were 69 (23–92) and 70 (37–93) years, respectively. No significant difference was observed in the use of antithrombotic agents between the two groups (14.7% vs. 18.5%, p=0.400). In addition, no significant differences were found in lesion location (p=0.053), morphology (p=0.594), or histology (p=0.594) between the two groups. The non-closure group had a significantly larger tumor size 28.4±15.5 vs. 23.1±11.7 mm p<0.001) and specimen diameter (39.8±15.9 vs. 35.5±11.3 mm, p=0.003) than the closure group. The non-closure group had a significantly longer ESD duration than the closure group (55.6±40.8 vs. 43.2±32.5 minutes, p=0.013).
The mean number of clips required and the duration of complete closure were 7.8±2.6 and 8.7±3.1 minutes, respectively (Table 2).
Patient outcomes before propensity score matching
As shown in Table 1, the closure group had a significantly lower overall incidence of postoperative adverse events than the non-closure group (2.0% vs. 9.8%, p=0.001). Furthermore, the closure group had a significantly lower incidence of delayed bleeding than the non-closure group (1.0% vs. 5.2%, p=0.028). In addition, the closure group had a lower incidence of PECS than the non-closure group (2.0% vs. 4.6%, p=0.239); however, the results did not differ significantly between the two groups. None of the patients in the two groups presented with delayed perforation (0% vs. 0%, p=1.000). Moreover, the closure group had a significantly lower incidence of abdominal pain on the day after ESD than the non-closure group (2.5% vs. 9.2%, p=0.006). Additionally, delayed bleeding occurred at a median (range) of 9 (7–11) days in the closure group and 4 (2–12) days in the non-closure group.
Characteristics of patients and lesions after propensity score matching
Differences in the characteristics of the patients and lesions could influence patient outcomes. Thus, propensity score matching was performed with age, sex, use of antithrombotic agents, lesion location, tumor size, specimen diameter, and ESD duration as covariates. In total, 136 lesions were selected from each group. As shown in Table 3, the median (range) ages of the closure and non-closure groups were 69 (23–92) and 70 (37–87) years, respectively. The two groups did not differ significantly in terms of the use of antithrombotic agents, lesion location, morphology, histology, tumor size, or specimen diameter.
Further, no significant differences were observed in terms of the ESD duration (46.6±36.6 vs. 50.2±39.0 minutes, p=0.435), en bloc resection rate (100% vs. 100%, p=1.000), curative resection rate (89.0% vs. 90.4%, p=0.842), and incidence of perforation during ESD (4.4% vs. 5.1%, p=1.000).
Patient outcomes after propensity score matching
The closure group had a significantly lower overall incidence of postoperative adverse events than the non-closure group (2.2% vs. 9.6%, p=0.018) (Table 4). Furthermore, the closure group had lower incidences of delayed bleeding (0.7% vs. 4.4%, p=0.120) and PECS (2.2% vs. 5.1%, p=0.335). However, the results did not differ significantly between the two groups. None of the patients in the two groups presented with delayed perforation (0% vs. 0%, p=1.000). The closure group had a significantly lower incidence of abdominal pain on the day after ESD than the non-closure group (2.9% vs. 11.0%, p=0.015). However, the two groups did not differ significantly in terms of the WBC count, CRP level, fever on the day after ESD, or length of hospital stay.
Risk factors for abdominal pain on the day after ESD
The incidence of abdominal pain on the day after ESD was 5.7% (n=21) in all the patients before propensity score matching. We performed a logistic regression analysis to determine the risk factors for the development of abdominal pain on the day after ESD. As shown in Table 5, univariate analysis revealed that the following factors were associated with an increased incidence of abdominal pain: age <65 years, proximal lesion, tumor size >40 mm, specimen diameter >50 mm, and ESD duration >60 minutes. Conversely, complete closure was identified as a factor that reduced the incidence of abdominal pain. In the multivariate analysis, age <65 years, proximal lesion, and ESD duration >60 minutes were identified as factors that increased the incidence of abdominal pain. Conversely, complete closure was identified as a factor that reduced the incidence of abdominal pain.
Colorectal ESD is a common treatment for large superficial colorectal tumors. However, owing to large mucosal defects after resection, postoperative adverse events are more frequently observed in ESD than in EMR. Therefore, these events should be controlled. This study aimed to evaluate the effect of mucosal defect closure using a double-layered suturing technique with conventional hemostatic clips on postoperative adverse events. Based on our results, closures using this technique may reduce the incidence of these events and abdominal pain.
Although there was a baseline imbalance in patient characteristics before propensity score matching (Supplementary Table 1), a trend toward a lower incidence of adverse events was observed in the complete closure group than in the partial closure and non-closure groups (Supplementary Table 2). Based on these observations, we hypothesized that complete closure using this technique would effectively reduce postoperative adverse events. Accordingly, we conducted a comparative analysis between the complete closure and non-closure groups, with the non-closure group comprising partial and no closure.
The incidences of delayed bleeding, delayed perforation, and PECS, which are postoperative adverse events, are 2.8% to 4.3%,14,15 0.1% to 0.2%,16,17 and 4.8% to 14%,18,19 respectively. A recent meta-analysis compared the incidence of postoperative adverse events between patients who underwent closure and those who did not. The results showed a significant reduction in the incidence of delayed bleeding in the closure group compared with that in the non-closure group. However, no significant differences were observed in the incidences of delayed perforation and PECS between the two groups.20 In the current study, the overall incidence of postoperative adverse events significantly decreased. In addition, the closure technique reduced the incidence of delayed bleeding and PECS. However, the results did not differ significantly between the closure and non-closure groups. Similarly, Omori et al. showed that the overall incidence of postoperative adverse events, with minor bleeding as the main cause, as shown by a propensity score matching analysis, decreased with closure.21 Based on these findings, the closure technique can be recommended to reduce postoperative adverse events, particularly delayed bleeding. Furthermore, this strategy can be used in high-risk patients, including those receiving antithrombotic agents.22
Additionally, the closure technique used in this study significantly reduced the incidence of abdominal pain on the day after ESD. In patients with severe abdominal pain, a computed tomography (CT) scan should be performed to rule out perforations. Prevention of abdominal pain may reduce the need for CT scans and associated radiation exposure. Fujiwara et al. reported a decrease in abdominal pain after ESD with closure using the over-the-scope clip (OTSC) system and conventional clips.12 The OTSC system can reduce the dead space by directly grasping the muscle layer as in the double-layered suturing technique. Direct grasping of the muscle layer followed by mucosal closure may be effective in preventing abdominal pain. In the current study, multivariate analysis revealed that age <65 years, proximal lesions, and ESD duration >60 min were associated with an increased incidence of abdominal pain. Most of these risk factors were consistent with those associated with PECS.18 Patients who developed abdominal pain but did not meet the PECS criteria may have had a milder condition with the same pathology as PECS. The proposed mechanisms for the development of PECS are thermal damage to the serosa during ESD and local bacterial infection due to the exposure of mucosal defects to contaminated materials.23 A similar mechanism is anticipated for the development of abdominal pain after ESD. Complete and reliable closure by grasping the muscular layer in addition to the mucosa may suppress abdominal pain by reducing the spread of inflammation and exposure of mucosal defects to contaminants. Furthermore, this study identified younger age (<65 years) as a risk factor for abdominal pain. Visceral pain sensitivity reportedly tends to diminish with age,24 and a similar mechanism may contribute to the lower incidence of abdominal pain after ESD in older adult patients.
Various techniques have been used to close mucosal defects after colorectal ESD.5 In this study, the double-layered suturing technique was used. This strategy offers several advantages. For example, conventional hemostatic clips are used, and no special equipment is required. Additionally, it is cost-effective and minimally invasive. To achieve closure, the average number of clips required is 7.8±2.6, and the average procedural duration was 8.7±3.1 minutes. In terms of cost-effectiveness, complete closure may be more beneficial in patients at high risk of delayed bleeding, PECS, and abdominal pain. Moreover, this technique can be used to close larger mucosal defects using anchor-pronged clips25 or a modified method.26 However, this technique cannot be used in some cases such as lesions located over the anal canal.
This study had some limitations. First, this was a single-center, retrospective study. Second, the decision to perform complete closure was made by an endoscopist, which might have introduced bias. Before propensity score matching, the non-closure group had a larger lesion size than the closure group. Hence, lesions that were challenging to close could have been included in the non-closure group. Propensity score-matching was performed to adjust for these factors. Third, our sample size was relatively small. The incidence of delayed bleeding and PECS was lower in both groups than previously reported rates. Consequently, this study might have lacked sufficient power to detect significant differences between delayed bleeding and PECS. Nevertheless, a large-scale prospective randomized trial should be conducted to evaluate the efficacy of this technique.
In conclusion, the efficacy of closure of mucosal defects after colorectal ESD using a double-layered suturing technique was evaluated using propensity score matching analysis. The results showed that this technique reduced the incidence of postoperative adverse events and abdominal pain.
Supplementary Table 1. Characteristics of patients and lesions (before matching).
ce-2025-053-Supplementary-Table-1.pdf
Supplementary Table 2. Patient outcomes (before matching).
ce-2025-053-Supplementary-Table-2.pdf
Supplementary materials related to this article can be found online at https://doi.org/10.5946/ce.2025.053.
Fig. 1.
Double-layered suturing technique. (A) A large mucosal defect after endoscopic submucosal dissection. (B) The clips were applied longitudinally to the submucosal and muscular layers in the center of the ulcer floor. (C) Additional clips were applied to the mucosal layer for complete closure. (D–F) Illustrations of the procedure.
ce-2025-053f1.jpg
Fig. 2.
Flow chart of the current study. ESD, endoscopic submucosal dissection.
ce-2025-053f2.jpg
ce-2025-053f3.jpg
Table 1.
Characteristics and outcomes of patients and lesions (before matching)
Characteristic Closure group (n=197) Non-closure group (n=173) p-value
Age (yr) 69 (23–92) 70 (37–93) 0.685
Sex (male/female, n) 131/66 105/72 0.279
Antithrombotic agents 29 (14.7) 32 (18.5) 0.400
Antiplatelet agents 21 (10.7) 20 (11.6) 0.869
Anticoagulants 12 (6.1) 13 (7.5) 0.680
Location (colon/rectum) 157/40 (79.7/20.3) 122/51 (70.5/29.5) 0.053
Morphology, LST-G/LST-NG/0-Ⅰ/other 62/70/60/9 (29.5/35.5/30.5/4.6) 64/63/39/7 (37.0/36.4/22.5/4.1) 0.594
Histology, adenoma/M/SM1/SM2 or more/other 112/52/4/23/6 (56.9/26.4/2.3/8.7/4.6) 87/59/4/15/8 (50.3/34.1/2.3/8.7/4.6) 0.594
Tumor size (mm) 23.1±11.7 28.4±15.5 <0.001
Specimen diameter (mm) 35.5±11.3 39.8±15.9 0.003
ESD duration (min) 43.2±32.5 55.6±40.8 0.013
En bloc resection 197 (100) 173 (100) 1.000
Curative resection 180 (91.4) 157 (90.8) 0.857
Perforation during ESD 7 (3.6) 7 (4.0) 1.000
Adverse events 4 (2.0)a) 17 (9.8) 0.001
 Delayed bleeding 2 (1.0) 9 (5.2) 0.028
 Delayed perforation 0 (0) 0 (0) 1.000
 PECS 4 (2.0) 8 (4.6) 0.239
Abdominal pain 5 (2.5) 16 (9.2) 0.006
Day of bleeding (day) 9 (7–11) 4 (2–12) NA

Values are presented as median (range), number (%), or mean±standard deviation.

LST, laterally spreading tumor; G, granular; NG, non-granular; M, mucosal; SM, submucosal; ESD, endoscopic submucosal dissection; PECS, post-ESD electrocoagulation syndrome; NA, not analyzed.

a)Two patients developed both delayed bleeding and PECS.

Table 2.
Closure outcomes
Closure group (n=197)
No. of clips 7.8±2.6
Closure duration (min) 8.7±3.1

Values are presented as mean±standard deviation.

Table 3.
Characteristics of patients and lesions (after matching)
Characteristic Closure group (n=136) Non-closure group (n=136) p-value
Age (yr) 69 (23–92) 70 (37–87) 0.641
Sex (male/female, n) 85/51 88/48 0.801
Antithrombotic agents 22 (16.2) 21 (15.4) 1.000
Antiplatelet agents 15 (11.0) 13 (9.6) 0.842
Anticoagulants 10 (7.4) 9 (6.6) 1.000
Location (colon/rectum) 101/35 (74.3/25.7) 107/29 (78.7/21.3) 0.475
Morphology, LST-G/LST-NG/0-Ⅰ/other 39/41/50/6 (28.7/30.1/36.7/4.4) 46/54/32/4 (33.4/39.7/23.5/2.9) 0.062
Histology, adenoma/M/SM1/SM2 or more/other 72/36/3/19/6 (52.9/26.5/2.2/14.0/4.4) 74/41/3/12/6 (54.4/30.1/2.2/8.8/4.4) 0.746
Tumor size (mm) 24.2±12.8 25.1±12.8 0.531
Specimen diameter (mm) 35.4±12.5 37.0±13.6 0.312
ESD duration (min) 46.6±36.6 50.2±39.0 0.435
En bloc resection 136 (100.0) 136 (100.0) 1.000
Curative resection 121 (89.0) 123 (90.4) 0.824
Perforation during ESD 6 (4.4) 7 (5.1) 1.000

Values are presented as median (range), number (%), or mean±standard deviation.

LST, laterally spreading tumor; G, granular; NG, non-granular; M, mucosal; SM, submucosal; ESD, endoscopic submucosal dissection.

Table 4.
Patient outcomes (after matching)
Closure group (n=136) Non-closure group (n=136) p-value
Adverse events 3 (2.2)a) 13 (9.6) 0.018
 Delayed bleeding 1 (0.7) 6 (4.4) 0.120
 Delayed perforation 0 (0) 0 (0) 1.000
 PECS 3 (2.2) 7 (5.1) 0.335
Abdominal pain (POD1) 4 (2.9) 15 (11.0) 0.015
WBC count (POD1) (/μL) 6,903±2,299 7,195±2,444 0.313
CRP (POD1) (mg/dL) 0.48±1.51 0.58±1.43 0.576
Fever (POD1) 20 (14.7) 18 (13.2) 0.861
Length of hospital stay (day) 6.2±1.6 6.4±1.4 1.000

Values are presented as number (%) or mean±standard deviation.

PECS, post-endoscopic submucosal dissection electrocoagulation syndrome; POD, post operative day; WBC, white blood cell; CRP, C-reactive protein.

a)One patient developed both delayed bleeding and PECS.

Table 5.
Risk factors for abdominal pain on the day after ESD
Univariate
Multivariate
OR (95% CI) p-value OR (95% CI) p-value
Age (<65 yr) 5.50 (2.08–14.60) <0.001 5.89 (2.01–17.20) 0.001
Sex (male) 0.74 (0.31–1.81) 0.516
Location (proximal) 3.63 (1.43–9.23) 0.006 4.99 (1.74–14.30) 0.003
Histology (adenocarcinoma) 0.85 (0.34–2.09) 0.717
Tumor size (>40 mm) 3.29 (1.26–8.59) 0.015 1.51 (0.39–5.84) 0.554
Specimen diameter (>50 mm) 4.05 (1.59–10.30) 0.003 1.56 (0.38–6.31) 0.535
ESD duration (>60 min) 6.88 (2.59–18.30) <0.001 3.84 (1.17–12.60) 0.027
Complete closure 0.18 (0.069–0.48) <0.001 0.26 (0.083–0.84) 0.024

ESD, endoscopic submucosal dissection; OR, odds ratio; CI, confidence interval.

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    • Colorectal endoscopic submucosal dissection defect closure: promising but still evolving
      Yunho Jung
      Clinical Endoscopy.2025; 58(6): 856.     CrossRef

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      Effect of double-layered suturing for mucosal defect closure after colorectal endoscopic submucosal dissection on postoperative adverse events: a propensity score-matched retrospective study in Japan
      Clin Endosc. 2025;58(6):881-889.   Published online November 6, 2025
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    Effect of double-layered suturing for mucosal defect closure after colorectal endoscopic submucosal dissection on postoperative adverse events: a propensity score-matched retrospective study in Japan
    Image Image Image
    Fig. 1. Double-layered suturing technique. (A) A large mucosal defect after endoscopic submucosal dissection. (B) The clips were applied longitudinally to the submucosal and muscular layers in the center of the ulcer floor. (C) Additional clips were applied to the mucosal layer for complete closure. (D–F) Illustrations of the procedure.
    Fig. 2. Flow chart of the current study. ESD, endoscopic submucosal dissection.
    Graphical abstract
    Effect of double-layered suturing for mucosal defect closure after colorectal endoscopic submucosal dissection on postoperative adverse events: a propensity score-matched retrospective study in Japan
    Characteristic Closure group (n=197) Non-closure group (n=173) p-value
    Age (yr) 69 (23–92) 70 (37–93) 0.685
    Sex (male/female, n) 131/66 105/72 0.279
    Antithrombotic agents 29 (14.7) 32 (18.5) 0.400
    Antiplatelet agents 21 (10.7) 20 (11.6) 0.869
    Anticoagulants 12 (6.1) 13 (7.5) 0.680
    Location (colon/rectum) 157/40 (79.7/20.3) 122/51 (70.5/29.5) 0.053
    Morphology, LST-G/LST-NG/0-Ⅰ/other 62/70/60/9 (29.5/35.5/30.5/4.6) 64/63/39/7 (37.0/36.4/22.5/4.1) 0.594
    Histology, adenoma/M/SM1/SM2 or more/other 112/52/4/23/6 (56.9/26.4/2.3/8.7/4.6) 87/59/4/15/8 (50.3/34.1/2.3/8.7/4.6) 0.594
    Tumor size (mm) 23.1±11.7 28.4±15.5 <0.001
    Specimen diameter (mm) 35.5±11.3 39.8±15.9 0.003
    ESD duration (min) 43.2±32.5 55.6±40.8 0.013
    En bloc resection 197 (100) 173 (100) 1.000
    Curative resection 180 (91.4) 157 (90.8) 0.857
    Perforation during ESD 7 (3.6) 7 (4.0) 1.000
    Adverse events 4 (2.0)a) 17 (9.8) 0.001
     Delayed bleeding 2 (1.0) 9 (5.2) 0.028
     Delayed perforation 0 (0) 0 (0) 1.000
     PECS 4 (2.0) 8 (4.6) 0.239
    Abdominal pain 5 (2.5) 16 (9.2) 0.006
    Day of bleeding (day) 9 (7–11) 4 (2–12) NA
    Closure group (n=197)
    No. of clips 7.8±2.6
    Closure duration (min) 8.7±3.1
    Characteristic Closure group (n=136) Non-closure group (n=136) p-value
    Age (yr) 69 (23–92) 70 (37–87) 0.641
    Sex (male/female, n) 85/51 88/48 0.801
    Antithrombotic agents 22 (16.2) 21 (15.4) 1.000
    Antiplatelet agents 15 (11.0) 13 (9.6) 0.842
    Anticoagulants 10 (7.4) 9 (6.6) 1.000
    Location (colon/rectum) 101/35 (74.3/25.7) 107/29 (78.7/21.3) 0.475
    Morphology, LST-G/LST-NG/0-Ⅰ/other 39/41/50/6 (28.7/30.1/36.7/4.4) 46/54/32/4 (33.4/39.7/23.5/2.9) 0.062
    Histology, adenoma/M/SM1/SM2 or more/other 72/36/3/19/6 (52.9/26.5/2.2/14.0/4.4) 74/41/3/12/6 (54.4/30.1/2.2/8.8/4.4) 0.746
    Tumor size (mm) 24.2±12.8 25.1±12.8 0.531
    Specimen diameter (mm) 35.4±12.5 37.0±13.6 0.312
    ESD duration (min) 46.6±36.6 50.2±39.0 0.435
    En bloc resection 136 (100.0) 136 (100.0) 1.000
    Curative resection 121 (89.0) 123 (90.4) 0.824
    Perforation during ESD 6 (4.4) 7 (5.1) 1.000
    Closure group (n=136) Non-closure group (n=136) p-value
    Adverse events 3 (2.2)a) 13 (9.6) 0.018
     Delayed bleeding 1 (0.7) 6 (4.4) 0.120
     Delayed perforation 0 (0) 0 (0) 1.000
     PECS 3 (2.2) 7 (5.1) 0.335
    Abdominal pain (POD1) 4 (2.9) 15 (11.0) 0.015
    WBC count (POD1) (/μL) 6,903±2,299 7,195±2,444 0.313
    CRP (POD1) (mg/dL) 0.48±1.51 0.58±1.43 0.576
    Fever (POD1) 20 (14.7) 18 (13.2) 0.861
    Length of hospital stay (day) 6.2±1.6 6.4±1.4 1.000
    Univariate
    Multivariate
    OR (95% CI) p-value OR (95% CI) p-value
    Age (<65 yr) 5.50 (2.08–14.60) <0.001 5.89 (2.01–17.20) 0.001
    Sex (male) 0.74 (0.31–1.81) 0.516
    Location (proximal) 3.63 (1.43–9.23) 0.006 4.99 (1.74–14.30) 0.003
    Histology (adenocarcinoma) 0.85 (0.34–2.09) 0.717
    Tumor size (>40 mm) 3.29 (1.26–8.59) 0.015 1.51 (0.39–5.84) 0.554
    Specimen diameter (>50 mm) 4.05 (1.59–10.30) 0.003 1.56 (0.38–6.31) 0.535
    ESD duration (>60 min) 6.88 (2.59–18.30) <0.001 3.84 (1.17–12.60) 0.027
    Complete closure 0.18 (0.069–0.48) <0.001 0.26 (0.083–0.84) 0.024
    Table 1. Characteristics and outcomes of patients and lesions (before matching)

    Values are presented as median (range), number (%), or mean±standard deviation.

    LST, laterally spreading tumor; G, granular; NG, non-granular; M, mucosal; SM, submucosal; ESD, endoscopic submucosal dissection; PECS, post-ESD electrocoagulation syndrome; NA, not analyzed.

    Two patients developed both delayed bleeding and PECS.

    Table 2. Closure outcomes

    Values are presented as mean±standard deviation.

    Table 3. Characteristics of patients and lesions (after matching)

    Values are presented as median (range), number (%), or mean±standard deviation.

    LST, laterally spreading tumor; G, granular; NG, non-granular; M, mucosal; SM, submucosal; ESD, endoscopic submucosal dissection.

    Table 4. Patient outcomes (after matching)

    Values are presented as number (%) or mean±standard deviation.

    PECS, post-endoscopic submucosal dissection electrocoagulation syndrome; POD, post operative day; WBC, white blood cell; CRP, C-reactive protein.

    One patient developed both delayed bleeding and PECS.

    Table 5. Risk factors for abdominal pain on the day after ESD

    ESD, endoscopic submucosal dissection; OR, odds ratio; CI, confidence interval.


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