Effectiveness and safety of modified cold snare polypectomy for flat colorectal polyps: A multicenter randomized controlled trial

Abstract

BACKGROUND

Cold snare polypectomy (CSP) is the preferred treatment for sessile colorectal polyps < 10 mm; however, snare slippage during resection of flat lesions (Paris classification 0-IIa) frequently compromises complete en bloc removal. We hypothesized that a modified CSP technique would enhance resection efficacy while preserving procedural safety for flat colorectal polyps measuring 5-9 mm.

AIM

To evaluate the effectiveness and safety of modified CSP for flat colorectal polyps of 5-9 mm.

METHODS

A multicenter randomized controlled trial was conducted from January 2023 to June 2025, enrolling patients with morphologically suitable nonpedunculated colonic polyps measuring 5-9 mm that were removed using CSP or modified CSP. Eligible patients with small flat colorectal polyps were randomly assigned to the modified or conventional group using a random number table. Polyp location, long-axis diameter, en bloc resection rate (defined as macroscopic complete removal in a single piece), endoscopic complete resection rate (defined as the absence of any endoscopically visible residual polyp tissue at the resection site immediately after polypectomy), histopathological findings, and procedure-related complications were compared between the two groups.

RESULTS

A total of 151 patients were enrolled, including 75 patients with 95 polyps in the modified group and 76 patients with 89 polyps in the conventional group. The en bloc resection rate was significantly higher in the modified group than in the conventional group [98.9% (94/95) vs 92.1% (82/89), P = 0.024]. The complete resection rate was 100% in both groups. No significant differences were observed between the two groups with respect to sex, age, polyp location, long-axis diameter, or histopathological type (all P > 0.05).

CONCLUSION

The modified CSP technique demonstrates advantages in the management of Paris classification 0-IIa polyps and represents a novel technical modification for these lesions.

Key Words: Flat colorectal polyps; Cold snare polypectomy; En bloc resection rate; Paris classification 0-IIa polyps; Modified cold snare polypectomy

Core Tip: Snare slippage limits complete en bloc resection during conventional cold snare polypectomy (CSP) for flat colorectal polyps. In this multicenter randomized trial, a modified CSP technique significantly improved en bloc resection rates for Paris 0-IIa polyps measuring 5-9 mm while maintaining a 100% complete resection rate and procedural safety. These findings suggest that modified CSP technique demonstrates advantages in the management of Paris classification 0-IIa polyps and represents a novel technical modification for these lesions.

INTRODUCTION

Colorectal polyps are well-recognized precancerous lesions, and their timely removal has been shown to reduce the incidence of colorectal cancer[1]. During colonoscopic examinations, more than 90% of detected polyps measure less than 10 mm in diameter[2].

Cold snare polypectomy (CSP) is currently regarded as the optimal treatment for sessile colorectal polyps smaller than 10 mm[3-6]. However, during CSP, snare slippage frequently occurs when flat polyps are resected (Paris classification 0-IIa), which may hinder complete en bloc resection and often necessitates repeating CSP or the use of biopsy forceps.

In this study, a modified CSP technique was applied for the removal of flat polyps with a long-axis diameter of 5-9 mm. The modification involved suction-assisted elevation of the lesion to form a pseudopolyp. This suction-induced tenting creates a well-defined stalk, providing a critical fulcrum point that allows the snare to engage securely and resist lateral slippage during closure. Furthermore, the resulting three-dimensional morphology increases circumferential contact and frictional interface between the snare wire and tissue, thereby enhancing mechanical interlock compared with a conventional flat resection plane. The aim was to evaluate the effectiveness and safety of this modified approach and to explore its potential as a novel therapeutic option for such lesions.

MATERIALS AND METHODS

Study design and population

A multicenter randomized controlled trial was conducted involving morphologically suitable nonpedunculated colonic polyps measuring 5-9 mm that were removed using CSP or modified CSP, was conducted. The study protocol was approved by the Medical Ethics Committee of Fujian Cancer Hospital (approval No. K2023-310-01).

The inclusion criteria were: (1) Patients aged 18 years or older who underwent colonoscopy from January 2023 to June 2025; and (2) The presence of at least one flat colorectal polyp (Paris classification 0-IIa) with a long-axis diameter of 5-9 mm. The exclusion criteria were: (1) A diagnosis of inflammatory bowel disease; (2) A personal history of familial adenomatous polyposis; (3) The concurrent use of antiplatelet or anticoagulant agents; and (4) A history of colorectal malignancy not previously treated with surgery.

Participants were randomly assigned, using a random number table, to undergo either modified CSP (modified group, n = 75) or conventional cold snare resection (conventional group, n = 76). The random sequence was generated by a research assistant not involved in patient enrollment or endoscopic procedures using a computer-generated random number list. The sequence was implemented via sequentially numbered, opaque, sealed envelopes. The envelopes were prepared by a research assistant not involved in patient enrollment or endoscopic procedures. Random numbers that are odd are assigned to the conventional group, and even numbers to the modified group. The endoscopist enrolled eligible patients and opened the next consecutive envelope immediately before the procedure to reveal the assigned resection method. This ensured allocation concealment was maintained until intervention assignment. Regarding clustering by patient: We acknowledge that the study did not account for clustering by patient in the primary analysis. Each polyp was treated as an independent unit for outcome assessment. Written informed consent was obtained from all participants prior to enrollment.

Procedure

Both procedures were performed by a team consisting of one endoscopist with more than five years of endoscopic experience and one nurse. Flat colorectal polyps with a long-axis diameter of 5-9 mm were identified during colonoscopy using endoscopes (CF-HQ290Z/PCF-Q260AZI; Olympus, Tokyo, Japan) equipped with a transparent cap (Olympus, Tokyo, Japan). Lesion morphology was evaluated under white-light imaging and narrow-band imaging.

Modified snare cold polypectomy: Suction was applied to the lesion to create a pseudopolyp, after which a snare (No. 20153012054, Aegis Medical, China) was positioned to encompass the lesion along with a 1-2 mm margin of surrounding tissue, and resection was performed by tightening the snare. Procedural details are shown in Figure 1 and Video 1.

Figure 1 Process of modified cold snare polypectomy in treating flat polyps. A: Polyps observed under white light; B: Polyps observed under narrow band imaging; C: Suctioning the polyp until it “wrinkles”; D: Modified cold snare polypectomy in treating polyps; E: Resected lesion.

Conventional snare cold polypectomy: A snare (No. 20153012054, Aegis Medical, China) was positioned to encompass the lesion along with a 1-2 mm margin of surrounding tissue and resection was achieved by tightening the snare. The resection site was irrigated with sterile water and carefully inspected under narrow-band imaging to assess for residual tissue at the margins. A normal type I pit pattern at the resection margin was considered indicative of complete polypectomy. However, as histologic confirmation of the lateral and deep margins was not available from cold snare specimens - which typically fragment during retrieval - complete resection was assessed based on this endoscopic evaluation alone. When the margins appeared ill defined, a submucosal injection of sterile water was performed to enhance visualization and facilitate further assessment. If residual polyp tissue was identified, additional CSP was carried out. Hemostatic clips were applied as needed, and all resected specimens were retrieved for histopathological analysis. The longest diameter of each polyp was measured using sterile endoscopic biopsy forceps (No. 20192020343, Alton, Shanghai, China) with a jaw length of 3 mm.

Outcome measurements

Baseline characteristics and outcomes including polyp location, long-axis diameter, pathological classification, complications, en bloc resection rate (defined as macroscopic complete removal in a single piece), and endoscopic complete resection rate (defined as the absence of any endoscopically visible residual polyp tissue at the resection site immediately after polypectomy. This endpoint assessed macroscopic technical success and is distinct from histologic complete resection (R0), which could not be routinely evaluated due to tissue fragmentation inherent to the cold snare technique.), were compared between the two groups.

Sample size calculation

Sample size estimation was conducted using PASS 15 software. Assuming a statistical power of 80% and a significance level of 0.05, 71 participants were needed per group to detect a difference in en bloc resection rates, resulting in a total sample size of approximately 142 patients.

Statistical analysis

Statistical analyses were performed using SPSS version 26.0. Continuous variables are summarized as the mean ± SD for normally distributed data or as the median with interquartile range for nonnormally distributed data. Between-group comparisons were conducted using t tests, χ² tests, or Mann-Whitney U tests, as appropriate. P < 0.05 was considered to indicate statistical significance.

We acknowledge that some patients in this study contributed more than one polyp (up to a maximum of four), which may introduce within-patient correlation and violate the assumption of independence when analyses are performed at the polyp level. In the present study, comparisons between groups were conducted using the Mann-Whitney U test at the polyp level. Given the relatively small number of multiple polyps per patient and the limited sample size, a clustered or hierarchical analysis was not applied.

RESULTS

A total of 151 patients with 184 polyps meeting the inclusion criteria were enrolled. Of these, 75 patients with 95 polyps were assigned to the modified CSP group, and 76 patients with 89 polyps were assigned to the conventional CSP group. The patients ranged in age from 32 years to 77 years and included 90 males and 61 females.

The median polyp diameter was 6 (6, 7) mm in both the modified and conventional CSP groups. No statistically significant differences were observed between the two groups in terms of sex, age, polyp location, longest diameter, or pathological type (all P > 0.05). The detailed baseline characteristics are summarized in Tables 1 and 2.

Table 1 Comparison of patient characteristics between the modified cold snare polypectomy group and the conventional cold snare polypectomy group.

Group	Example count	Age (year)	Gender (female/male)
Modified cold snare polypectomy group	75 (n = 151, patient-based)	55.81 ± 10.24	30/45
Conventional cold snare polypectomy group	76 (n = 151, patient-based)	57.18 ± 10.38	31/45
Statistical measure		t = -0.817 (t tests)	Z = -0.099 (Mann-Whitney U tests)
P value		0.415	0.922

Table 2 Comparison of polypectomy-related data between the modified cold snare polypectomy group and the conventional cold snare polypectomy group.

Group	Modified cold snare polypectomy group	Conventional cold snare polypectomy group	Statistical measure	P value
Number of polyps (pcs)	95 (n = 184 polyp-based)	89 (n = 184 polyp-based)
Maximum polyps diameter (mm)	6 (6, 7)	6 (6, 7)	Z = -0.243	0.808
Polyps location (pcs)			Z = -0.569	0.569
Cecum	1	6
Ascending colon	14	14
Transverse colon	44	29
Descending colon	12	13
Sigmoid colon	24	26
Rectum	0	1
Pathological type (pcs)			Z = -1.952	0.051
Inflammatory polyps	4	4
Hyperplastic polyps	29	39
Sessile serrated lesions	2	1
Tubular adenomas	58	45
Villous tubular adenomas	2	0
En bloc resection rate (%)	98.947	92.135	Z = -2.258	0.024

Effectiveness and safety

The endoscopic complete resection rate was 100% in both the modified and conventional CSP groups. With respect to lesions not removed en bloc in a single procedure, one case occurred in the modified CSP group, whereas seven cases were observed in the conventional CSP group (Figure 2). Accordingly, the en bloc resection rate was significantly greater in the modified CSP group (94/95; 95% confidence interval: 0.9686-1.0094) than in the conventional CSP group (82/89; 95% confidence interval: 0.8651-0.9769) (P = 0.024; Table 2). No postoperative adverse events, including delayed bleeding or perforation, were observed in either group during the study period.

Figure 2 Cold-cut flat polyp in the conventional group not completely excised in one piece. A: Polyps observed under white light; B: Polyps observed under narrow band imaging; C: Residual tissue at the margins after cold cutting.

DISCUSSION

CSP is an emerging minimally invasive endoscopic technique that achieves polyp removal through purely mechanical excision. It is characterized by technical simplicity, a short procedure time, and a favorable safety profile. The absence of high-frequency electrocautery reduces complications associated with thermal injury. Owing to these advantages, CSP has been adopted widely in China in recent years.

Previous studies have shown that both the proportion and the mean depth of the submucosal layer are significantly greater in specimens obtained by hot snare polypectomy than in those obtained by CSP[7]. In addition, CSP avoids thermal damage and minimizes injury to large submucosal vessels, thereby significantly reducing the risk of delayed bleeding[8]. The reported incidence of delayed bleeding after CSP for sessile polyps smaller than 10 mm is approximately 0.4%[9], with virtually no cases of perforation[10]. Consistent with these findings, no delayed bleeding or perforation was observed in the present study.

Suzuki et al[11] reported that CSP-induced mucosal defects demonstrate more favorable healing characteristics. Accordingly, domestic clinical guidelines recommend outpatient CSP for sessile polyps smaller than 10 mm in greatest diameter[12]. As an outpatient procedure, CSP allows immediate polyp removal without the need for repeat bowel preparation, thereby saving time, reducing hospitalization costs, and improving health care efficiency. In this study, the majority of polyps were treated on an outpatient basis.

Post-colonoscopy colorectal cancer is defined as colorectal cancer diagnosed 6-36 months after a negative colonoscopy, and incomplete polypectomy is a key etiological factor. Previous studies estimate that 10%-28% of colorectal cancers diagnosed after colonoscopy are attributable to incomplete polyp resection[13]. A meta-analysis by Shinozaki et al[14] reported an incomplete resection rate of 6.0% with CSP, whereas the present study observed a 100% endoscopic complete resection rate in both groups. This discrepancy may be explained by several factors. First, the use of water immersion and optical magnification in this study enhanced lesion visualization and margin assessment, potentially improving the endoscopist’s ability to distinguish pathological from normal tissue; however, the lack of histopathological confirmation of resection margins may have introduced assessment bias. Second, complete resection was not validated by follow-up colonoscopy. Consequently, although the technical outcomes suggest favorable resection completeness, any claims regarding long-term recurrence reduction remain speculative.

Current evidence indicates that marginal recurrence is the principal cause of polyp relapse[15]. In this study, the modified CSP technique achieved a significantly higher en bloc resection rate than conventional CSP in Paris classification 0-IIa polyps. This advantage is likely attributable to suction-assisted lesion elevation, which creates a pseudopolyp with a defined stalk and wrinkled three-dimensional morphology. These features enhance snare engagement, reduce lateral slippage during closure, and improve circumferential tissue capture, thereby increasing the likelihood of complete, single-session resection. En bloc removal minimizes residual marginal tissue and avoids repeated snaring, which can obscure margin visualization due to bleeding or clot formation and may increase mucosal injury, post-procedural bleeding risk, clip use, and procedure time. Collectively, these findings support modified CSP as a technically superior approach for achieving complete resection in flat colorectal polyps. Previous studies have demonstrated a positive correlation between polyp size and residual risk[16]. Consistent with these findings, all eight lesions not removed en bloc in a single procedure in this study measured 7-9 mm in greatest diameter. In addition, polyp location may contribute to incomplete resection, as lesions situated behind mucosal folds can be difficult to fully expose because of anatomical constraints.

This study has several limitations. First, the sample size was relatively small, and the number of patients with complete medical records meeting the inclusion criteria was limited, which may have reduced the strength of the conclusions. Second, the analysis was performed at the polyp level, and multiple polyps some patients were included, which may have introduced within-patient correlation, violating the assumption of independence. Although the Mann-Whitney U test was used for group comparisons, clustered or hierarchical modeling was not applied due to the small number of multiple polyps per patient, leading to potential underestimation of variance estimates.

Additional limitations include the lack of histologic margin confirmation, the absence of surveillance colonoscopy to assess long-term outcomes, and the focus on short-term results. Moreover, polyp clustering within patients was not adequately addressed, which may impact the generalizability of the findings. Future studies with larger sample sizes and multicenter designs should consider using mixed-effects models or patient-level clustering and incorporate long-term surveillance to better assess the effectiveness and recurrence prevention of the modified CSP technique.

CONCLUSION

The modified CSP technique demonstrates advantages in the management of Paris classification 0-IIa polyps and represents a novel technical modification for these lesions.

ACKNOWLEDGEMENTS

The authors would like to thank all the patients who participated in this study. We also acknowledge the support of the endoscopy nursing staff and technicians for their assistance during data collection. In addition, we thank our colleagues for their valuable discussions and technical support throughout the study.