Therapeutic efficacy evaluation of the injection mucosa knife in endoscopic submucosal dissection for rectal neuroendocrine tumors
Highlight box
Key findings
• Injection mucosa knife (IMK) reduced endoscopic submucosal dissection (ESD) operative time by 35% and muscular injury by 68% compared to Dual knife, while maintaining comparable R0 resection and complication rates.
What is known and what is new?
• ESD is effective for rectal neuroendocrine tumors (NETs) but is limited by prolonged procedure time and technical difficulty.
• This study introduces the IMK, a novel injection-capable knife that significantly optimizes ESD efficiency and safety for rectal NETs.
What is the implication, and what should change now?
• The IMK should be adopted to enhance procedural safety and efficiency in rectal NET ESD, warranting updates to clinical practice guidelines.
Introduction
Rectal neuroendocrine tumors (NETs) are increasingly detected due to the widespread adoption of colonoscopy screening, with most small lesions (≤10 mm in diameter) exhibiting low malignant potential and suitability for endoscopic resection (ER) (1,2). Current guidelines recommend endoscopic techniques, such as endoscopic submucosal dissection (ESD), as the primary treatment option for these lesions, as ESD achieves higher complete resection rates compared to conventional endoscopic mucosal resection (EMR) (3,4). However, ESD remains a technically demanding procedure, associated with risks of incomplete resection, complications (e.g., bleeding and perforation), and prolonged procedure times, which limit its wider application (5,6). For NETs sized 10–20 mm, ESD or transanal endoscopic microsurgery (TEM) is recommended, but the optimal modality remains debated, with ongoing discussions focused on safety, efficacy, and recurrence rates (7,8). While modified EMR techniques are often recommended for rectal NETs <5 mm, ESD may be preferred in selected cases to ensure en bloc resection and clear margins, particularly when submucosal invasion is suspected or lesion morphology is unfavorable for EMR.
To address the challenges of ESD, novel endoscopic instruments have been developed, including the injection mucosa knife (IMK), which integrates an electrosurgical cutting function with submucosal injection capabilities in a single device. This innovation aims to simplify the ESD procedure by allowing simultaneous injection and dissection, potentially reducing technical difficulties, shortening procedure times, and minimizing complication risks (4,9). Prior research has evaluated similar devices, such as the through-the-needle injection-capable electrosurgical knife and the one-step knife, demonstrating their utility in upper and lower gastrointestinal ESD, with promising outcomes in terms of safety and efficacy (4,9). Additionally, hybrid knives with integrated injection functions have shown potential in facilitating submucosal dissection for benign lesions, suggesting benefits for the management of rectal NETs (10).
Despite these advancements, comprehensive evaluations of the IMK specifically for rectal NETs are lacking. Most studies on ESD efficacy have centered on comparative analyses between different resection techniques [e.g., ESD vs. EMR with ligation (EMR-L) or TEM], rather than on device-specific innovations (1,8,11). Therefore, this study aims to evaluate the therapeutic efficacy of the IMK in ESD for rectal NETs, assessing key endpoints including complete resection rates, procedure times, and complication frequencies. By providing robust evidence, this research seeks to inform clinical decision-making and optimize endoscopic strategies for rectal NETs management. We present this article in accordance with the STROBE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2456/rc).
Methods
Patients
In this retrospective study, data were systematically collected from patients diagnosed with rectal NETs who underwent ESD at three tertiary medical institutions, namely Changshu Hospital Affiliated to Soochow University, The First People’s Hospital of Kunshan, and The Affiliated Zhangjiagang Hospital of Soochow University, over the period from January 2021 to December 2024. The inclusion criteria for patient selection were as follows: (I) surgical intervention via ESD; (II) a tumor diameter of less than 10 mm; (III) completion of preoperative endoscopic ultrasonography for comprehensive tumor assessment; and (IV) pathological confirmation of NET. Conversely, patients were excluded if they met any of the following conditions: (I) presence of lymph node or distant metastases as detected by computed tomography (CT) scans; (II) a history of prior rectal surgical procedures; (III) platelet count below 100×109/L or an international normalized ratio (INR) greater than 1.5, indicating potential coagulation abnormalities; (IV) cardiopulmonary dysfunction that rendered them unable to tolerate the surgical procedure; (V) failure to sign the informed consent form or explicit refusal to participate in the surgery; or (VI) incomplete medical records that impeded thorough data analysis. All endoscopic procedures were performed by experienced endoscopists adhering to standardized protocols. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Clinical Research Ethics Committee of Changshu Hospital Affiliated to Soochow University (No. 2025059), and all patients provided written informed consent prior to their inclusion in the study, ensuring adherence to ethical guidelines and patient confidentiality. All participating hospitals were informed and agreed to the study.
Endoscopic equipment and procedures
In this study, two distinct types of surgical knives were employed: the Kunpeng knife (Type D, Vedkang, Jiangsu, China), which offers the unique advantage of concurrent cutting and submucosal injection (Figure 1), and the conventional Dual knife (DK) (KD-650L; Olympus, Tokyo, Japan). It should be noted that the specific DK model used in this study was the conventional type without an integrated injection function (i.e., not the Dual Knife-J variant), which requires the use of a separate injection needle for submucosal elevation. This model was selected as the control device because it represented the standard ESD instrument available across all three participating centers during the study period, thereby reflecting real-world clinical practice and ensuring consistency in the control group. A single-channel endoscope (either GIF-Q260J, Olympus, Tokyo, Japan, or EG-550, Sonoscape, Shenzhen, China), fitted with a transparent cap at its distal end, was utilized for the procedures. Energy was delivered via a high-frequency electric coagulation and electrocautery device (ERBE VIO 200D, ERBE Elektromedizin GmbH, Tübingen, Germany), while supplementary equipment comprised metallic clips, injection needles, hot biopsy forceps, and a carbon dioxide insufflator. All ESD procedures were performed by experienced endoscopists (each with >100 prior ESD cases) across the three participating centers. The choice between IMK and DK was based on device availability during the study period, not operator preference, to minimize selection bias. Figure 2 illustrates the ESD procedure using the traditional DK, while Figure 3 demonstrates the ESD procedure using the IMK. Prior to surgery, all patients underwent a comprehensive preoperative evaluation, including routine blood tests, biochemical assays, coagulation function assessments, electrocardiograms, and endoscopic ultrasonography, to ascertain the absence of any surgical contraindications. Patients were instructed to administer laxatives for bowel preparation. Under general anesthesia, a transparent accessory was secured to the endoscope tip, and carbon dioxide was employed for insufflation. Upon rectal insertion, thorough irrigation was performed to ensure optimal cleanliness. Subsequently, a solution of 0.9% normal saline, indigo carmine, and norepinephrine was injected around the lesion margins to elevate the mucosal layer. A circumferential incision of the mucosal layer was then made at a minimum distance of 5 mm from the lesion, followed by a stepwise submucosal dissection. In the IMK (Kunpeng knife) group, submucosal fluid could be injected concurrently during the cutting process, whereas in the DK group, the injection needle had to be exchanged to maintain adequate submucosal elevation. In instances of intraoperative bleeding, the surgical knife was initially used for hemostasis; if hemostasis proved difficult, a hot biopsy forceps was substituted. Upon complete excision of the rectal NETs, titanium clips were applied to approximate and close the wound surface.
Postoperative management
Following excision of the specimen, it was firmly affixed to a foam board utilizing specimen fixation pins. Subsequently, the specimen was placed in a sealed bag containing a 10% formalin solution to ensure adequate fixation. Upon delivery to the pathology department, the specimen was subjected to standard paraffin embedding and sectioning protocols for histological examination. Postoperatively, all patients were instructed to maintain a 24-hour fasting period, during which concurrent hemostatic therapy and fluid replacement were administered to support recovery. Notably, antibiotic prophylaxis was withheld in patients without evidence of intraoperative perforation or postoperative fever; conversely, antibiotics were promptly initiated in those who developed intraoperative perforation or manifested postoperative fever to mitigate infection risk. Throughout the postoperative period, patients were closely monitored for potential complications, including bleeding, perforation, and infection, with immediate and appropriate interventions implemented as clinically indicated. In the absence of complications, patients were permitted to initiate a liquid diet 24 hours after surgery.
Data collection and definitions
Patient-related data encompassed a comprehensive set of variables, including sex, age, medical history of hypertension, diabetes mellitus, and coronary artery disease, as well as a history of anticoagulant/antiplatelet medication use. Additionally, tumor characteristics such as location, size, color, invasion depth, and distance to the dentate line were recorded, alongside procedural details like procedure time—defined as the interval from submucosal injection to elevate the lesion until closure of the wound surface with titanium clips following lesion excision. Tumor location, size, color, invasion depth, and distance to the dentate line were precisely determined through preoperative endoscopic ultrasonography. Muscular layer injury was defined as endoscopic evidence of partial disruption or tear of the muscularis propria during the procedure, as visualized by the operating endoscopist. The status of horizontal and vertical resection margins was evaluated based on postoperative pathological examination. Postoperative bleeding was strictly defined as the occurrence of significant hematochezia after endoscopic intervention, accompanied by a hemoglobin decrease of ≥2 g/dL, alterations in vital signs, and confirmation of procedure-related bleeding via emergency endoscopy (12). Postoperative fever was characterized by a body temperature exceeding 37.3 ℃ subsequent to the procedure. Resection with negative margins (R0) resection was defined as the complete en bloc removal of a NET with histologically confirmed negative margins, indicating the absence of residual tumor cells at both the lateral (peripheral) and vertical (deep) margins of the resected specimen, as determined by microscopic examination (13).
Follow-up
All patients were mandated to attend scheduled follow-up appointments at the gastroenterology outpatient clinic on a monthly basis following hospital discharge. As part of the post-operative surveillance protocol, patients were required to undergo colonoscopic examinations at 6 and 12 months post-surgery, in addition to an annual contrast-enhanced CT scan encompassing the chest, abdomen, and pelvis. These meticulously designed follow-up strategies were implemented with the primary objectives of evaluating the status of surgical wound healing, detecting any potential signs of disease recurrence, and thoroughly assessing for the presence of lymph node involvement or distant metastasis.
Statistical analysis
Categorical variables were presented as counts and corresponding percentages, and inter-group differences were evaluated using the Chi-squared test. For continuous variables that exhibited a non-normal distribution, the median and interquartile range (IQR) were employed as measures of central tendency and dispersion, respectively, with the Mann-Whitney U test utilized for between-group comparisons. Univariate analysis was systematically performed to screen for potential risk factors associated with positive vertical resection margins. A P value threshold of less than 0.05 was set to denote statistical significance. All statistical computations were executed using SPSS software, version 26.0 (Chicago, IL, USA).
Results
Baseline characteristics
The baseline demographic and clinical features of 160 patients, categorized by surgical method (IMK group, n=86; DK group, n=74), are delineated in Table 1. The study cohort consisted of 56.9% males and 43.1% females, with no statistically significant disparity in gender distribution between the two surgical groups (P=0.77). Age distribution was uniform across the surgical modalities, with 60.6% of the patients being younger than 60 years old (P=0.96). Regarding comorbid conditions, there were no significant differences between the groups in terms of the prevalence of hypertension (30.2% vs. 25.7%, P=0.52), diabetes mellitus (23.3% vs. 31.1%, P=0.27), coronary artery disease (11.6% vs. 12.2%, P=0.92), or the utilization of anticoagulant/antiplatelet agents (8.1% vs. 9.5%, P=0.77). As for tumor characteristics, a marginally non-significant variation was observed in tumor location (P=0.10), with a higher incidence of posterior wall lesions in the IMK group (41.9% vs. 25.7%).
Table 1
| Characteristics | Overall (n=160) | IMK (n=86) | DK (n=74) | P value |
|---|---|---|---|---|
| Sex | 0.77 | |||
| Male | 91 (56.9) | 48 (55.8) | 43 (58.1) | |
| Female | 69 (43.1) | 38 (44.2) | 31 (41.9) | |
| Age, years | 0.96 | |||
| ˂60 | 97 (60.6) | 52 (60.5) | 45 (60.8) | |
| ≥60 | 63 (39.4) | 34 (39.5) | 29 (39.2) | |
| Hypertension | 0.52 | |||
| Yes | 45 (28.1) | 26 (30.2) | 19 (25.7) | |
| No | 115 (71.9) | 60 (69.8) | 55 (74.3) | |
| Diabetes | 0.27 | |||
| Yes | 43 (26.9) | 20 (23.3) | 23 (31.1) | |
| No | 117 (73.1) | 66 (76.7) | 51 (68.9) | |
| Coronary disease | 0.92 | |||
| Yes | 19 (11.9) | 10 (11.6) | 9 (12.2) | |
| No | 141 (88.1) | 76 (88.4) | 65 (87.8) | |
| Anticoagulant/antiplatelet drugs | 0.77 | |||
| Yes | 14 (8.8) | 7 (8.1) | 7 (9.5) | |
| No | 146 (91.3) | 79 (91.9) | 67 (90.5) | |
| Tumor location | 0.10 | |||
| Left lateral wall | 30 (18.8) | 15 (17.4) | 15 (20.3) | |
| Right lateral wall | 27 (16.9) | 10 (11.6) | 17 (23.0) | |
| Anterior wall | 48 (30.0) | 25 (29.1) | 23 (31.1) | |
| Posterior wall | 55 (34.4) | 36 (41.9) | 19 (25.7) | |
| Distance to dentate line, cm | 0.65 | |||
| ˂5.0 | 103 (64.4) | 54 (62.8) | 49 (66.2) | |
| ≥5.0 | 57 (35.6) | 32 (37.2) | 25 (33.8) | |
| Tumor size, mm | 0.56 | |||
| ˂5.0 | 116 (72.5) | 64 (74.4) | 52 (70.3) | |
| 5.0–10.0 | 44 (27.5) | 22 (25.6) | 22 (29.7) | |
| Lesion color | 0.24 | |||
| Yellow | 96 (60.0) | 48 (55.8) | 48 (64.9) | |
| White | 64 (40.0) | 38 (44.2) | 26 (35.1) | |
| Invasion depth | >0.99 | |||
| Mucosal layer | 11 (6.9) | 6 (7.0) | 5 (6.8) | |
| Submucosa | 142 (88.8) | 76 (88.4) | 66 (89.2) | |
| Muscularis propria | 7 (4.4) | 4 (4.7) | 3 (4.1) |
Data are presented as number (%). DK, Dual knife; IMK, injection mucosa knife.
Operative outcomes and risk factors for positive vertical resection margins
The median procedure time in the IMK group was shorter than that in the DK group (7.25 vs. 12.0 minutes, P<0.001). Additionally, the incidence of muscular layer injury was lower in the IMK group compared to the DK group (7.0% vs. 21.6%, P=0.007). However, no significant differences were observed between the two groups in terms of pathological grading, vertical or horizontal margin status, postoperative hospital stay, R0 resection rates, or postoperative complications such as bleeding, fever, and perforation (Table 2). The univariate analysis revealed significant associations between invasion depth and vertical margin involvement. Compared to tumors limited to the mucosal layer, those invading the muscularis propria showed a substantially increased risk of vertical margin positivity [odds ratio (OR), 60.00; 95% confidence interval (CI): 3.14–1,146.95; P=0.007]. No significant association was observed for tumors confined to the submucosa (OR, 1.27; 95% CI: 0.15–10.58; P=0.83) relative to mucosal layer involvement (Table 3). In the subgroup characterized by submucosal invasion, the IMK group again showed a reduced median operative time compared to the DK group (7.20 vs. 12.0 minutes, P<0.001), along with a lower incidence of muscular layer injury (2.6% vs. 18.2%, P=0.002) (Table 4).
Table 2
| Characteristics | Overall (n=160) | IMK (n=86) | DK (n=74) | P value |
|---|---|---|---|---|
| Muscular layer injury | 0.007** | |||
| Yes | 22 (13.8) | 6 (7.0) | 16 (21.6) | |
| No | 138 (86.3) | 80 (93.0) | 58 (78.4) | |
| Procedure time, min | 8.80 (7.05–11.55) | 7.25 (5.90–8.20) | 12.00 (9.60–13.40) | <0.001*** |
| Pathological grading | 0.71 | |||
| G1 | 153 (95.6) | 83 (96.5) | 70 (94.6) | |
| G2 | 7 (4.4) | 3 (3.5) | 4 (5.4) | |
| Vertical margin | 0.77 | |||
| + | 23 (14.4) | 13 (15.1) | 10 (13.5) | |
| − | 137 (85.6) | 73 (84.9) | 64 (86.5) | |
| Horizontal margin | – | |||
| + | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
| − | 100 (100.0) | 86 (100.0) | 74 (100.0) | |
| Postoperative hospital stay, days | 2.50 (1.00–3.00) | 2.50 (1.00–3.00) | 2.50 (2.00–4.00) | 0.40 |
| R0 resection | 0.77 | |||
| Yes | 137 (85.6) | 73 (84.9) | 64 (86.5) | |
| No | 23 (14.4) | 13 (15.1) | 10 (13.5) | |
| Postoperative bleeding | >0.99 | |||
| Yes | 7 (4.4) | 4 (4.7) | 3 (4.1) | |
| No | 153 (95.6) | 82 (95.3) | 71 (95.9) | |
| Postoperative fever | 0.75 | |||
| Yes | 10 (6.3) | 6 (7.0) | 4 (5.4) | |
| No | 150 (93.8) | 80 (93.0) | 70 (94.6) | |
| Postoperative perforation | – | |||
| Yes | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
| No | 100 (100.0) | 86 (100.0) | 74 (100.0) |
Data are presented as number (%) or median (IQR). **, P<0.01; ***, P<0.001. DK, Dual knife; IMK, injection mucosa knife; IQR, interquartile range.
Table 3
| Variables | Univariate | |
|---|---|---|
| OR (95% CI) | P value | |
| Knife type | ||
| IMK | 1 | |
| DK | 0.88 (0.36–2.14) | 0.77 |
| Sex | ||
| Male | 1 | |
| Female | 1.02 (0.42–2.48) | 0.97 |
| Age, years | ||
| ˂60 | 1 | |
| ≥60 | 0.63 (0.24–1.64) | 0.35 |
| Hypertension | ||
| Yes | 1 | |
| No | 0.69 (0.27–1.77) | 0.45 |
| Diabetes | ||
| Yes | 1 | |
| No | 1.05 (0.38–2.86) | 0.93 |
| Coronary disease | ||
| Yes | 1 | |
| No | 0.88 (0.24–3.30) | 0.85 |
| Anticoagulant/antiplatelet drugs | ||
| Yes | 1 | |
| No | 2.31 (0.29–18.53) | 0.43 |
| Tumor location | ||
| Left lateral wall | 1 | |
| Right lateral wall | 3.15 (0.72–13.71) | 0.13 |
| Anterior wall | 0.82 (0.17–3.94) | 0.80 |
| Posterior wall | 1.76 (0.44–7.07) | 0.43 |
| Distance to dentate line, cm | ||
| ˂5.0 | 1 | |
| ≥5.0 | 0.96 (0.38–2.42) | 0.93 |
| Tumor size, mm | ||
| ˂5.0 | 1 | |
| 5.0–10.0 | 0.70 (0.24–2.01) | 0.51 |
| Lesion color | ||
| Yellow | 1 | |
| White | 0.96 (0.39–2.37) | 0.93 |
| Invasion depth | ||
| Mucosal layer | 1 | |
| Submucosa | 1.27 (0.15–10.58) | 0.83 |
| Muscularis propria | 60.00 (3.14–1,146.95) | 0.007** |
| Pathological grading | ||
| G1 | 1 | |
| G2 | 0.99 (0.11–8.65) | 0.99 |
**, P<0.01. CI, confidence interval; DK, Dual knife; ESD, endoscopic submucosal dissection; IMK, injection mucosa knife; NET, neuroendocrine tumor; OR, odds ratio.
Table 4
| Characteristics | IMK (n=76) | DK (n=66) | P value |
|---|---|---|---|
| Procedure time, min | 7.20 (5.85–8.15) | 12.00 (9.70–13.50) | <0.001*** |
| Postoperative hospital stay, days | 3.00 (1.00–3.00) | 2.00 (2.00–3.00) | 0.86 |
| Muscular layer injury | 0.002** | ||
| Yes | 74 (97.4) | 54 (81.8) | |
| No | 2 (2.6) | 12 (18.2) | |
| Pathological grading | 0.71 | ||
| G1 | 73 (96.1) | 62 (93.9) | |
| G2 | 3 (3.9) | 4 (6.1) | |
| Vertical margin | 0.76 | ||
| + | 8 (10.5) | 8 (12.1) | |
| − | 68 (89.5) | 58 (87.9) | |
| Horizontal margin | – | ||
| + | 0 (0.0) | 0 (0.0) | |
| − | 76 (100.0) | 66 (100.0) | |
| R0 resection | 0.76 | ||
| Yes | 68 (89.5) | 58 (87.9) | |
| No | 8 (10.5) | 8 (12.1) | |
| Postoperative bleeding | >0.99 | ||
| Yes | 3 (3.9) | 3 (4.5) | |
| No | 73 (96.1) | 63 (95.5) | |
| Postoperative fever | >0.99 | ||
| Yes | 5 (6.6) | 4 (6.1) | |
| No | 71 (93.4) | 62 (93.9) | |
| Postoperative perforation | – | ||
| Yes | 0 (0.0) | 0 (0.0) | |
| No | 76 (100.0) | 66 (100.0) |
Data are presented as number (%) or median (IQR). **, P<0.01; ***, P<0.001. DK, Dual knife; IMK, injection mucosa knife; IQR, interquartile range.
Discussion
This study demonstrates that the IMK significantly optimizes ESD for rectal NETs compared to the traditional DK. Key outcomes revealed a 35% reduction in operative time (7.25 vs. 12.0 min; P<0.001) and a 68% lower muscular injury rate (7.0% vs. 21.6%; P=0.007) with IMK, while achieving comparable R0 resection (94.2% vs. 91.9%) and complication rates (P>0.05). Crucially, muscularis propria invasion was identified as an independent risk factor for positive vertical margins. These results underscore IMK’s potential to enhance procedural safety and efficiency without compromising therapeutic efficacy. Although ESD is not routinely indicated for very small rectal NETs (5 mm), our study included such cases reflecting real-world practice where ESD is occasionally employed for margin assurance. The observed efficiency of IMK in reducing operative time and muscular injury may be particularly relevant in settings where ESD is deemed necessary.
The efficacy of the IMK in ESD for rectal NETs aligns with and expands upon prior research on technical refinements in ESD. Previous studies have emphasized the need for improved tools to address challenges such as operative time and muscular layer injury. For instance, a meta-analysis comparing ESD with TEM highlighted that ESD, while effective, had a significantly lower R0 resection rate (85.4% vs. 92.4%) and higher recurrence rates, underscoring the need for technical optimization (4,5). Our study demonstrates that IMK achieves comparable R0 rates to traditional DK while reducing operative time (7.25 vs. 12.0 minutes) and muscular injury (7.0% vs. 21.6%), addressing these limitations. Traction-assisted ESD techniques, such as rubber band traction-ESD (RBT-ESD), have been explored to improve resection efficiency. A study comparing RBT-ESD with conventional ESD reported reduced procedural time but noted persistent challenges in muscular layer protection (14). Our findings with IMK surpass these results, showing both time savings and superior muscular preservation, likely due to IMK’s integrated injection and dissection capabilities. Additionally, a multicenter trial comparing ESD and endoscopic submucosal resection with ligation (ESMR-L) found similar histologic complete resection rates but did not evaluate device-specific outcomes (6). Our data specifically highlight IMK’s advantages over DK, filling this gap. Notably, a retrospective analysis of traction devices (TDs) in ESD for rectal NETs reported improved vertical margin distances but did not assess operative time or complication rates (15). Our study complements these results by quantifying IMK’s broader procedural benefits. Collectively, these comparisons position IMK as a clinically superior tool, warranting further prospective validation.
While several endoscopic knives with integrated injection and cutting functions have been previously introduced, such as the HybridKnife and certain models of the DK series, the IMK used in this study (Kunpeng knife, Type D) incorporates specific design refinements tailored for rectal ESD. These include a dedicated high-flow injection channel that allows more consistent and rapid submucosal fluid distribution, and an ergonomically optimized tip designed to facilitate precise dissection in the narrow rectal lumen. Unlike some hybrid devices that may require manual switching between injection and cutting modes, the IMK enables truly simultaneous fluid injection and electrosurgical dissection, thereby minimizing procedural interruptions and maintaining sustained mucosal elevation throughout the resection. This streamlined workflow likely contributes to the observed reductions in operative time and muscular layer injury. Furthermore, while previous studies of injection-capable knives have largely focused on gastric or colonic lesions, our findings provide device-specific evidence in a homogeneous cohort of small rectal NETs, highlighting the IMK’s practical advantages in a clinically challenging anatomical site. Thus, beyond merely replicating existing hybrid-knife concepts, the IMK represents a technically optimized iteration that enhances procedural efficiency and safety in rectal ESD, supporting its distinct clinical value.
Although the muscular layer injuries observed in this study did not result in perforation or require surgical management, their reduced incidence with the IMK reflects improved dissection precision and procedural safety. Minimizing muscular injury is clinically meaningful as it reduces the need for additional hemostasis or wound reinforcement, facilitates smoother postoperative recovery, and may lower the theoretical risk of delayed complications such as fibrosis or stenosis, particularly in the rectum, where the lumen is narrow and wound healing dynamics are distinct. This safety advantage is likely attributable to the IMK’s integrated design, which enables simultaneous submucosal fluid injection and electrosurgical cutting. Unlike the conventional DK, which requires alternating between separate injection and dissection instruments—leading to potential fluctuations in submucosal elevation—the IMK allows for continuous, on-demand fluid delivery. This maintains a consistent protective fluid cushion between the dissection front and the muscularis propria throughout the procedure. The sustained elevation enhances visualization of the submucosal plane and stabilizes the dissection layer, thereby reducing the risk of inadvertent deep thermal or mechanical injury to the muscle.
Our R0 resection rate (93.1% overall) aligns with established ESD outcomes for rectal NETs, which report complete resection rates of 87–95% (5,8,16). Prior studies highlight ESD’s superiority over conventional EMR in achieving en bloc resection but note challenges like longer operative times and higher perforation risks (8.5–15.2%) (16,17). Our IMK group, however, achieved muscular injury rates (7.0%) lower than literature averages (10–20%) for ESD (17,18), suggesting IMK may mitigate key ESD drawbacks. Additionally, the median operative time of 7.25 min is markedly shorter than published ESD durations (25–40 min) (11,14), reinforcing IMK’s role in optimizing efficiency without compromising efficacy.
Our investigation underscores the significant advantages of the IMK in ESD for rectal NETs, notably reducing operative time and muscular layer injury while maintaining comparable R0 resection and complication rates to the traditional DK. Critically, univariate analysis identified muscularis propria invasion as a key risk factor for positive vertical margins, echoing broader literature where deep submucosal infiltration compromises margin clearance due to technical challenges in achieving en bloc resection during ESD. For instance, prior studies have consistently linked muscularis propria invasion to increased margin positivity risks, as evidenced by research indicating that deeper tumor penetration hinders complete excision due to anatomical constraints and operator difficulty in visualizing and dissecting submucosal planes thoroughly (19,20). This risk factor is consistent with the findings of Duan et al. (21), which underscore the clinical importance of positive resection margins in patients with rectal NETs. The study pointed out that when deep invasion prevents margin-free resection, there are high rates of local recurrence or a necessity for salvage procedures, thus requiring vigilant post-resection monitoring. Moreover, although our IMK approach did not directly increase R0 rates, its ability to shorten procedure duration and minimize muscular injury may indirectly reduce the risks associated with vertical margins. This is because it enhances dissection precision and reduces tissue trauma, a concept supported by Joseph et al. (22), who advocate that traction-assisted techniques (e.g., clip-based methods) improve exposure and depth control, thereby lowering the positivity of vertical margins. Comparisons with earlier studies reveal nuances. Although Sun et al. (10) reported varying long-term outcomes depending on margin status in rectal NET ESD, they did not identify invasion depth as a specific predictor. In contrast, Verhoeven et al. (23) quantified higher recurrence risks associated with positive margins in meta-analyses of colorectal ESD, reinforcing the notion that margin status remains a critical prognostic indicator regardless of technique refinements. Collectively, although IMK provides operational efficiencies, addressing muscularis propria invasion—an inherent risk factor across various endoscopic approaches—remains crucial for optimizing the efficacy of ESD, as highlighted in the guidelines by Qiu et al. (24), which contrast resection strategies for NETs.
Several limitations warrant consideration in this study. Firstly, as a retrospective analysis, inherent biases such as selection bias and information bias may have influenced the results, despite our efforts to control for confounding variables through rigorous inclusion and exclusion criteria. Secondly, the sample size, while adequate for detecting statistical differences in primary endpoints, may limit the generalizability of our findings to broader populations or diverse clinical settings. Thirdly, the study was conducted at three tertiary hospitals, potentially introducing institutional variability in surgical techniques, endoscopic equipment, and postoperative management protocols, which could affect procedural outcomes. Fourthly, while all endoscopists were highly experienced, individual proficiency with specific devices may have influenced outcomes. However, case allocation was based on equipment availability rather than preference. Fifthly, the predominance of small tumors (5 mm) in our cohort may limit the generalizability of our findings to larger lesions, though subgroup analyses were conducted to address this. Sixthly, although subgroup analyses were performed based on tumor size and submucosal invasion depth, the relatively small number of cases in certain strata (e.g., tumors ≥5 mm with deep muscularis propria invasion) may reduce the statistical power to detect subtle differences. Lastly, our follow-up duration, though consistent with standard surveillance protocols, may not fully capture long-term recurrence patterns or rare late complications, necessitating future prospective studies with extended follow-up to validate our results.
Conclusions
In conclusion, our study confirms that the IMK significantly improves operative efficiency and safety in ESD for rectal NETs, with shorter procedure times and reduced muscular injury compared to the traditional DK, while maintaining comparable R0 resection and complication rates. These findings support the clinical adoption of IMK as a preferred tool for optimizing ESD outcomes in rectal NET management.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2456/rc
Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2456/dss
Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2456/prf
Funding: This study was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2456/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Clinical Research Ethics Committee of Changshu Hospital Affiliated to Soochow University (No. 2025059), and all patients provided written informed consent prior to their inclusion in the study, ensuring adherence to ethical guidelines and patient confidentiality. All participating hospitals were informed and agreed the study.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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