Optimizing Endoscopic Submucosal Dissection: A Meta-Analysis of the S–O Clip’s Impact on Procedural Outcomes and Lesion-Specific Applications

Abstract

Background

Endoscopic submucosal dissection (ESD) is a minimally invasive procedure used to treat early-stage gastrointestinal neoplasms. While effective, ESD can be technically challenging due to limited submucosal visibility, prolonged procedure time, and increased risk of adverse events such as perforation and bleeding. The S–O clip, a traction device designed to enhance submucosal exposure, may help overcome these limitations and improve procedural outcomes.

Methods

We conducted a systematic review and meta-analysis of studies comparing ESD with and without the S–O clip in patients with gastrointestinal neoplasms. Primary outcomes included en-bloc resection rate, complete resection rate, and procedure time. Secondary outcomes were dissection speed and adverse events, including intraoperative perforation and post-ESD bleeding. Pooled relative risks (RR) and mean differences (MD) were calculated. Subgroup analyses were performed based on lesion location.

Results

Seventeen studies involving 1,449 patients were included. Use of the S–O clip significantly reduced procedure time (MD: − 19.63 min, 95% CI: − 28.02 to − 11.23, P < 0.001) and increased en-bloc resection rate (RR: 1.05, 95% CI: 1.01–1.09, P = 0.01). Complete resection rates were similar between groups (RR: 1.03, P = 0.23). Dissection speed was significantly higher with the S–O clip (MD: 10.18 mm²/min, P < 0.001). No significant differences were observed in intraoperative perforation or post-ESD bleeding rates.

Conclusions

The S–O clip is a useful adjunct in ESD, improving efficiency and en-bloc resection without increasing adverse events. Its use may enhance outcomes, particularly in gastric and colorectal ESD.

Introduction

Endoscopic Submucosal Dissection (ESD) is a minimally invasive endoscopic resection technique, enabling precise en bloc resection of early-stage gastrointestinal neoplasms [1]. Compared to Endoscopic Mucosal Resection (EMR), ESD allows for the complete removal of lesions regardless of their size [2]. This reduces recurrence rates and minimizes the need for invasive surgery [3]. However, ESD remains technically challenging, often involving prolonged procedure times and increased risks of complications like post-procedural bleeding and intraoperative perforation, particularly during resection of complex lesions [4]. These challenges highlight the need for innovative tools to enhance procedural safety and efficiency.

Traction-assisted devices, such as the S–O (spring and loop with clip) clip system, have evolved to address these technical challenges. The S–O clip enhances visualization and tissue exposure by providing counter-traction, facilitating more precise and efficient dissection [5]. Early evidence suggests that the S–O clip shortens operative time, improves en bloc resection rates, and reduces complications, particularly for lesions in challenging anatomical locations [6].

Despite encouraging results, the current evidence on the S–O clip’s safety and efficacy lacks consensus. To address this gap, we conducted a systematic review and meta-analysis to evaluate the safety and efficacy of the S–O clip. Additionally, we explored whether lesion-specific factors, such as anatomical location and lesion type, influence the effectiveness of the S–O clip in ESD procedures.

Methods

This meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines [7]. A PRISMA flow chart was used to illustrate the review process (Fig. 1). Since this study is based on publicly accessible data, no institutional review board approval or informed consent was required from the patients.

Fig. 1.

PRISMA FLOW diagram for study selection

Data Sources and Search Strategy

A comprehensive search was conducted on several databases including PubMed, Embase, Cochrane and Web of Science to identify relevant studies from inception to November 2024, with no filters applied. We performed our search by combining a variety of relevant keywords such as “SO clip,” “endoscopic submucosal dissection,”and “strip biopsy,”. MeSH terms and Boolean operators like “AND” and “OR” were used to optimize the search. The search strategy used for screening titles and abstracts is provided in the supplementary file Table S1.

Study Selection and Eligibility Criteria

Studies were included in the study if they met all of the following prespecified eligibility criteria: (i) compared SO-clip with a control (ii) included patients with neoplasms in the gastrointestinal (GI) tract undergoing endoscopic submucosal dissection, and (iii) reported at least one predefined outcome of interest.

All observational full-text manuscripts and abstracts (case–control, cohort, and cross-sectional studies) and randomized controlled trials (RCTs) were eligible for inclusion. Case reports, case series, editorials, and review articles were excluded.

Data Extraction and Quality Assessment

Results were exported to Rayyan, a web-based application designed to facilitate systematic reviews [8], where duplicate entries were removed. The remaining articles underwent initial screening based on their titles and abstracts. Full-text articles were obtained if the abstracts appeared potentially relevant to either investigator. Two reviewers (AA and USB) independently evaluated each study’s eligibility based on the inclusion criteria. Any discrepancies were resolved through discussion and agreement with a third researcher (BZ).

Primary outcomes assessed were en-bloc resection, complete resection, and procedure time. Secondary outcomes included dissection speed and adverse events such as intraoperative perforation and post-ESD bleeding. Additionally, subgroup analyses of the outcomes of interest were performed based on lesion location and study subtype.

Quality assessment of the included observational studies was conducted using the Newcastle–Ottawa Scale (NOS) for non-randomized studies [9] provided in the supplementary file. For RCTs, the Cochrane Risk of Bias tool was utilized [10]. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE assessment to assess the strength of evidence in the study [11]. We also used GRADEPro GDT software to create the summary of findings (SoF) table.

Statistical Analysis

Review Manager (Version 5.4, The Cochrane Collaboration, 2020) was employed for statistical analyses. The effect measure of interest for categorical variables was the risk ratio (RR) with a 95% confidence interval (CI), while for continuous variables, the mean and standard deviation were used. All results were pooled using random-effects models [12]. A p-value < 0.05 was considered statistically significant. The I² statistic was used to assess heterogeneity across the studies, with values of 0%, 25%, 50%, and 75% indicating no, low, moderate, and high levels of heterogeneity, respectively [13]. Forest plots were constructed for all pooled analyses and funnel plots [14] were generated to assess publication bias for outcomes with greater than 10 studies.

Results

Search Results

The search identified 114 records. Following the screening process, 41 studies were excluded based on title and abstract evaluation. A total of 21 full-text articles were reviewed for eligibility. Ultimately, 17 studies [5, 6] [15–29] were included in the analysis. The study selection process is summarized in the PRISMA flow diagram (Fig. 1).

Study Characteristics

The included studies encompassed 1,449 patients undergoing endoscopic submucosal dissection (ESD) for gastrointestinal lesions, focusing on gastric and colorectal neoplasms. The mean age of participants ranged from 58.5 to 75.3 years. The studies included the following lesion distribution: colorectal (n = 10), stomach (n = 6), and duodenum (n = 1). The characteristics of the included studies are summarized in Table 1.

Table 1.

Baseline characteristics of included studies

Author	Study design	Intervention	No of Patients SO- Clip	No of Patients Control	Male n (%) SO-Clip	Male n (%) Control	Mean age in year (SD) SO-Clip	Mean age in year (SD) Control	Specimen size mean(SD) SO-Clip	Specimen size mean(SD) Control	Lesion location	Lesion Pathology
Okamoto 2020	Retrospective cohort study	S–O Clip	33	33	23 (69.7)	24 (72.7)	58.5 ± 2.5	69.5 ± 6.5	37.5 ± 12.5	30 ± 10	colorectal	Colorectal Neoplasm
Hashimoto 2017	Retrospective cohort study	S–O Clip	48	48	36(75)	34(70.8)	72.4 ± 9.5	71.0 ± 11.3	37.4 ± 12.1	35.6 ± 12.9	Stomach	Gastric epithelial neoplasm
Ritsuno 2014	RCT	S–O Clip	27	23	18(66.6)	12(51)	66.2 ± 9.6	66.4 ± 8.9	33.5 ± 12.5	37.8 ± 13.1	Colon Rectum	Colorectal Neoplasm
Fujinami 2021	Retrospective cohort study	S–O Clip	80	47	47(58.7)	32(68)	65.9 ± 37.7	61.1 ± 33.1	30.6 ± 7.5	29.4 ± 9.1	Right Colon Left Colon	Colonic neoplasm
Tanaka 2023	Retrospective cohort study	S–O Clip	16	16	12(75)	12(75)	68.6 ± 5.68	71.3 ± 10.5	17.3 ± 5.6	17.5 ± 7.72	Duodenum	Non-ampullary duodenal tumors
Nagata 2023	Retrospective cohort study	S–O Clip	42	42	NR	NR	74.3 ± 9.97	74.6 ± 8.44	34.4 ± 6.7	32.4 ± 10.9	Stomach	Gastric Neoplasm
Nakatsu 2024	Retrospective cohort	S–O Clip	93	93	70 (75.3)	68 (73.1)	72.2 ± 7.9	72.7 ± 7.3	33.1 ± 11.3	29.7 ± 11.0	Stomach	Gastric neoplasm
Nagata 2021	RCT	S–O Clip	40	40	30 (75)	29 (72.5)	75.3 ± 8.4	74.6 ± 8.4	36.1 ± 9.2	37.0 ± 10.8	Stomach	Gastric neoplasm
Okamoto 2019	Retrospective cohort	S–O Clip	38	38	NR	NR	NR	NR	NR	NR	Colorectal	NR
Sakamoto 2008	Retrospective cohort	Hook knife + S–O clip	19	28	NR	NR	NR	NR	39.8 ± 18	34.2 ± 15.8	Colorectal	Colorectal Neoplasm
Fujinami 2019	Retrospective cohort	S–O Clip	53	46	NR	NR	NR	NR	NR	NR	Colorectal	Colorectal Neoplasm
Yamada 2017	Case–Control	S–O Clip, clip-with-line, and rubber band	40	143	18 (45%)	NR	65.8 ± 15.3	NR	53.8 ± 21.7	NR	Colorectal	Colorectal Neoplasm
Inoue 2021	Retrospective cohort study	S–O + CC	36	36	21(58%)	25(69%)	71 ± 10	71 ± 11	30 ± 7.5	33 ± 7	Colorectal	Colorectal Neoplasm
Fujinami 2018	Retrospective cohort study	S–O Clip	17	45	NR	NR	NR	NR	NR	NR	Colon	Colorectal Neoplasm
Hashimoto (1) 2017	Prospective cohort study	S–O Clip	46	46	NR	NR	NR	NR	NR	NR	Stomach	Gastric neoplasm
Nagata 2020	Retrospective cohort study	S–O Clip (spring and loop w clip)	51	51	32(62%)	29()	73.2 ± 9.6	72.8 ± 10.0	38.33 ± 9.91	35 ± 7.62	Stomach	Gastric neoplasm
Ritsuno 2012	RCT	S–O Clip	22	20	NR	NR	NR	NR	NR	NR	Colorectal	Colorectal Neoplasm

ESD endoscopic submucosal dissection, EMR endoscopic mucosal resection, NR not reported, RCT randomized controlled trial, CC clutch cutter, CWL clip-with-line

Primary Outcomes

Procedure Time

The S–O clip group demonstrated a significant reduction in overall procedure time compared to control, with a mean difference (MD) of − 19.63 min (95% CI: − 28.02 to − 11.23, P < 0.001). High heterogeneity was observed (I² = 75%) (Fig. 2). Given the significantly high heterogeneity, a sensitivity analysis was run by removing Okamoto et al. and Inoue et al., which dropped the heterogeneity to moderate (I² = 46%). (Supplementary Figure S2).

Fig. 2.

Forest plot of procedure time

Complete Resection

Complete resection rate was comparable between the S–O clip and control groups, with no statistically significant difference (RR: 1.03, 95% CI: 0.98–1.08, P = 0.23, I² = 39%) (Fig. 3).

Fig. 3.

Forest plot of complete resection

En-bloc Resection

En-bloc resection rate was significantly higher in the S–O clip group compared to the control group (RR: 1.05, 95% CI: 1.01–1.09, P = 0.01) (Fig. 4). High heterogeneity was observed (I² = 77%). Given the high heterogeneity, we performed a sensitivity analysis by removing Fujinami et al. and Sakomoto et al. Despite removing two studies, heterogeneity remained high (I² = 60%). (Supplementary Figure S3).

Fig. 4.

Forest plot of en-bloc resection

Secondary Outcomes

Dissection Speed

The S–O Clip group demonstrated a significant improvement in dissection speed compared to the control group, with a mean difference (MD) of 10.18 mm²/min (95% CI: 8.21 to 12.15, P < 0.001). No heterogeneity was observed amongst the included studies (I² = 0%, P = 0.97) (Fig. 5).

Fig. 5.

Forest plot of dissection speed

Intraoperative Perforation

The risk of intraoperative perforation was lower in the S–O clip group; however, the difference did not reach statistical significance (RR: 0.43, 95% CI: 0.17 to 1.06; p = 0.07, I² = 0%) (Fig. 6).

Fig. 6.

Forest plot of intraoperative perforation

Post-ESD Bleeding

The risk of post-procedural bleeding was comparable between the two groups (RR: 0.83, 95% CI: 0.40 to 1.73; p = 0.62, I² = 0%) (Fig. 7).

Fig. 7.

Forest plot of post-ESD bleeding

Subgroup Analysis Based on Lesion Location

Subgroup analysis revealed notable benefits of the S–O clip for colorectal neoplasms with higher en-bloc resection rates (RR: 1.11, 95% CI: 1.04 to 1.19, P = 0.002), increased dissection speed (MD 9.60 mm²/min 95% CI: 5.83 to 13.37, P < 0.001) and shorter procedure time (MD: − 15.22 min, 95% CI: − 30.72 to 0.27, P = 0.05) compared to control. Other outcomes, such as complete resection rate, intraoperative perforation, or post-ESD bleeding were non-inferior to control (Table 2). For gastric neoplasms, the clip significantly reduced procedure time (MD: − 21.07 min, 95% CI: − 26.96 to − 15.18, P < 0.001) and increased dissection speed (MD: 10.40 mm²/min, 95% CI: 8.09 to 12.71, P < 0.001) while being comparable for other outcomes (Table 3). For duodenal neoplasms, only procedure time showed a significant improvement (MD: − 43 min, 95% CI: − 58.35 to − 27.65, P < 0.001).

Table 2.

Subgroup analysis of colorectal neoplasm

Outcome	No. of studies	Statistical method	Effect size	P-value	I2
Procedure time	7	MD (IV, Random, 95% CI)	− 15.22 [− 30.72, 0.27]	0.05	83%
En-bloc resection	10	RR (IV, Random, 95% CI)	1.11 [1.04, 1.19]	0.002	67%
Complete resection	4	RR (IV, Random, 95% CI)	1.07 [0.94, 1.22]	0.28	63%
Dissection speed	1	MD (IV, Random, 95% CI)	9.60 [5.83, 13.37]	< 0.001	NA
Intraoperative perforation	7	RR (IV, Random, 95% CI)	0.58 [0.19, 1.76]	0.34	0%
Post-ESD bleeding	5	RR (IV, Random, 95% CI)	3.85 [0.46, 32.32]	0.21	0%

Table 3.

Subgroup analysis of gastric neoplasm

Outcome	No. of studies	Statistical method	Effect size	P-value	I2
Procedure time	6	MD (IV, Random, 95% CI)	− 21.07 [− 26.96, − 15.18]	< 0.001	0%
En-bloc resection	6	RR (IV, Random, 95% CI)	1.00 [0.98, 1.02]	1.00	0%
Complete resection	5	RR (IV, Random, 95% CI)	1.01 [0.97, 1.06]	0.57	17%
Dissection speed	4	MD (IV, Random, 95% CI)	10.40 [8.09, 12.71]	< 0.001	0%
Intraoperative perforation	6	RR (IV, Random, 95% CI)	0.33 [0.05, 2.09]	0.24	0%
Post-ESD bleeding	6	RR (IV, Random, 95% CI)	0.58 [0.26, 1.31]	0.19	0%

Quality Assessment and Certainty of Evidence

The quality assessment of non-randomized studies, conducted using the Newcastle–Ottawa Scale (NOS), revealed that all included studies fell within the low-risk category (scores of 7–9). The quality assessment of included studies is presented in Supplementary Table S3.

Detailed risk assessment for RCTs in the form of a traffic light and summary plot is given in Supplementary Figure S1.

The GRADE approach, using the ROBINS-I tool, was used to assess the certainty of evidence. A detailed assessment is shown in Supplementary Table S2.

Publication Bias and Validation of Results

To assess whether any one study had a dominant effect on the meta-analysis, we excluded one study at a time and analyzed its effect on the main summary estimate. Funnel plots are shown in Supplemental Figures S4-S9.

Discussion

This systematic review and meta-analysis present valuable insights into the efficacy and safety of ESD using the S–O clip. Our findings highlight the S–O clip as an effective adjunct in ESD, significantly reducing procedural time while improving dissection speed and en-bloc resection rates for gastric and colorectal neoplasms. Furthermore, our analysis shows that the use of the S–O clip yields comparable complete resection rates and adverse event profiles, including intraoperative perforation and post-ESD bleeding when compared to control.

While no prior studies have exclusively focused on the S–O clip, several have investigated the use of traction-assisted ESD, offering useful points of comparison. For instance, Niu et al. [30] found that traction-assisted ESD for early gastric neoplasms reduced mean procedural times without affecting en-bloc or complete resection rates. Similarly, Xia et al. [31] reported that traction-assisted ESD for superficial gastrointestinal neoplasms did not significantly improve en-bloc resection, complete resection, or delayed bleeding rates, though it did result in a lower incidence of perforation. Conversely, Lopimpisuth et al. [32] noted shorter procedural times and higher R0 resection rates with traction-assisted ESD, but no differences in en-bloc resection rates or bleeding risks. A meta-analysis by da Silva et al. [33] on scissors-assisted ESD found no significant differences in procedural time or en-bloc resection rates compared to conventional ESD. In contrast, our study demonstrates that the S–O clip significantly improves both procedural efficiency and resection outcomes, setting it apart from other methods.

The S–O clip’s design facilitates better visualization and consistent traction, which are essential for achieving precise dissection [6]. Its compact structure minimizes visual obstruction, and includes a mechanism for controlled adjustment, allowing for fine-tuning of tissue positioning before dissection. The S–O clip can be passed through the working channel, enabling independent traction of the lesion apart from the endoscope. By pulling the lesion toward the lumen, the clip facilitates direct visualization of the submucosal layer. The traction effect, combined with adequate dissection depth, ensures efficient dissection [17, 34]. This advancement reduces procedure time while also decreasing operator fatigue, an essential aspect when considering procedural efficiency since operator fatigue can impact decision-making and precision when performing lengthy ESDs [35]. This is further highlighted by Kim et al. [36], who contended that operator fatigue caused by long procedure time may have been one of the reasons for the high perforation rate in their study. Importantly, the S–O clip maintains a comparable safety profile, with no increase in perforation or bleeding risks, reassuring clinicians to consider its adoption.

Our analysis also reveals site-specific efficacy, with the S–O clip reducing procedure times more effectively for gastric neoplasms than colorectal neoplasms. This discrepancy may stem from anatomical differences, as the colon’s thinner walls and more fibrotic submucosa pose greater challenges to endoscopic maneuverability [37]. Additionally, the higher rates of perforation and bleeding in the colorectal subgroup underscore the need for lesion-specific strategies to optimize resource use and patient outcomes.

Beyond its clinical utility, the S–O clip has broader implications for training and accessibility. By simplifying technical aspects of ESD, the S–O clip could empower less experienced endoscopists to perform the procedure safely and effectively, democratizing access to advanced endoscopic techniques. This could significantly enhance patient care, enabling earlier and more precise interventions for gastrointestinal neoplasms across diverse healthcare settings. Furthermore, shorter procedure times and potentially fewer complications may offset the device’s cost, improving overall cost-effectiveness [21]. Future studies should explore these financial considerations in greater depth, particularly for both high-volume centers and smaller institutions.

Our review has several strengths. First, its robust sample size enhances the reliability of the findings. Second, stratification by lesion location provides nuanced insights to guide clinical decisions based on anatomical contexts. Additionally, we conducted sensitivity analyses to improve the reliability of our results. Furthermore, the certainty of evidence is high for half of the assessed outcomes. However, this review also has limitations. Notably, it does not directly compare the S–O clip with other traction devices, leaving its relative superiority unclear. Furthermore, we were unable to assess long-term outcomes, such as infection rates, associated with the S–O clip.

Conclusion

In conclusion, this analysis demonstrates that the S–O clip significantly enhances the efficiency of endoscopic submucosal dissection by reducing procedural time, improving dissection speed, and maintaining high en-bloc resection rates while preserving a comparable safety profile. While further research is needed to directly compare the S–O clip with other traction and counter traction devices and assess long-term outcomes, its potential to streamline procedures, reduce operator fatigue, and facilitate training makes it a promising tool for expanding access to advanced endoscopic techniques and improving patient care.

Abbreviations

AE

Adverse event

CI

Confidence interval

ESD

Endoscopic submucosal dissection

EMR

Endoscopic mucosal resection

GI

Gastrointestinal

GRADE

Grading of recommendations assessment, development, and evaluation

MD

Mean difference

MeSH

Medical subject headings

NOS

Newcastle–ottawa scale

OR

Odds ratio

PRISMA

Preferred reporting items for systematic review and meta-analysis

RCT

Randomized controlled trial

ROBINS-I

Risk of bias in non-randomized studies of interventions

RR

Risk ratio

S–O Clip

Spring-and-loop with clip

SoF

Summary of findings

Author Contributions

F.H., H.A., and S.C. contributed to the conception and design of the study. F.H., H.A., S.C., and M.K.G. provided administrative support. A.A., U.S.S.B., B.Z., R.K., M.A.B., D.S.D., and U.H. were responsible for data collection and assembly. F.H. performed the statistical analysis. All authors contributed to the review of literature, drafting of the manuscript, revision of key components, and provided final approval of the manuscript. All authors agree to be accountable for all aspects of the work.

Funding

Open access funding provided by the Carolinas Consortium.

Declarations

Conflicts of interest

The authors declare no competing interests.