TY - JOUR
AU - Gotoda,, Takuji
AB - SUMMARY The Clutch Cutter was invented as a scissor-type knife for endoscopic submucosal dissection (ESD) of gastrointestinal neoplasms. ESD with the scissor-type knife (ESD-S) may be considered a technically easier procedure than ESD with non-scissor-type knives (ESD-NS). Therefore, this study aimed to compare the technical outcomes of ESD-S with those of ESD-NS for superficial esophageal cancer. This was a multicenter retrospective study. Patients with superficial esophageal cancer treated with ESD between October 2015 and March 2018 at three hospitals were retrospectively reviewed. The ESD-S group had 48 patients and the ESD-NS group had 114 patients. A propensity score matching analysis was performed to compensate for the confounding bias between both groups. Multivariate analyses and propensity score matching were used to adjust for age, sex, the tumor size, tumor location, tumor depth, degree of tumor circumference, operator level, usage of the traction method, and the sedation method. The primary outcome was the procedure time of the ESD. Secondary outcomes were the rate of en-bloc/complete resection and the rate of complications including perforation, delayed bleeding, and stricture. Propensity score matching analysis provided 36 matched pairs. Median procedure time in the ESD-S group was significantly shorter than that in the ESD-NS group (44.0 min vs. 66.5 min, P = 0.020). In addition, the treatment outcomes were similar in both groups (en-bloc resection: 100% vs. 97.2%, P = 1; complete resection: 88.9% vs. 86.1%, P = 1; curative resection: 80.6% vs. 77.8%, P = 1; perforation: 0% vs. 5.6%, P = 0.49; delayed bleeding: 0% in both groups; stricture: 2.8% vs. 8.3%, P = 0.61). ESD-S was associated with a shorter procedure time than ESD-NS, without an increase in the incidence of complications. Therefore, the scissor-type knife should be considered as an endo-knife for ESD of superficial esophageal cancers. INTRODUCTION Endoscopic submucosal dissection (ESD) was first developed as a treatment for early gastric cancer; subsequently, ESD has become the gold standard for treatment of superficial esophageal squamous cell carcinoma (ESCC). ESD has enabled us to perform en-bloc resection regardless of the site and size of the neoplastic lesions, as long as the lesions meet the criteria for endoscopic resection.1 The efficacy of ESD in ESCC was shown by many studies, including meta-analyses.2–5 In general, the technique of esophageal ESD is considered more complex than that of gastric ESD, resulting in a greater chance of complications, since the esophageal lumen and walls are narrower and thinner than those of the stomach.6,7 Several different types of endo-knives have been invented and developed so far to make the ESD procedure easier and safer, and the most commonly and widely used endo-knives are either the needle-type or the insulated-tip (IT) knives.8–11 The Clutch Cutter (DP2618DT, Fujifilm Medical, Tokyo, Japan) is a unique endo-knife that has been invented as a scissor-type knife for ESD, and it can grasp and cut the target tissue precisely12,13 (Fig. 1). This procedure is similar to the technique in a standard bite biopsy, which is commonly performed during routine endoscopy. When non-intended tissues such as the muscularis propria are accidentally grasped, the target tissue can be re-grasped. Another advantage of this device is that it can be used for endoscopic hemostasis as well. Therefore, this device can not only make the ESD procedure easier, but also be safer by preventing complications such as perforations and unexpected bleeding. Although a few studies have reported a high en-bloc resection rate and a low complication rate with the use of scissor-type knives, including the Clutch Cutter and the stag-beetle knife, in performing esophageal ESD, the superiority of ESD with scissor-type knives (ESD-S) over ESD with non-scissor-type knives (ESD-NS) has not been fully determined.14–17 These previous studies had the limitation of being single-center studies. Furthermore, there are few studies on the comparison of the technical outcomes of esophageal ESD using scissor-type knives and other endo-knives, including the operator’s level of expertise. Some reports have shown this comparison in gastric or colorectal ESD, but it was limited to performance by trainees.18,19 Therefore, our aim was to elucidate whether ESD-S was superior than ESD-NS for superficial esophageal cancers when performed by either experts or trainees in terms of efficacy and safety by propensity score matching analysis in a multi-center study. Fig. 1 Open in new tabDownload slide Clutch Cutter is a scissor-type knife of endoscopic submucosal dissection. Fig. 1 Open in new tabDownload slide Clutch Cutter is a scissor-type knife of endoscopic submucosal dissection. MATERIALS AND METHODS Study population Patients who underwent ESD for ESCC between October 2015 and March 2018 at three institutions (Nihon University School of Medicine, Kitakyushu Municipal Medical Center, and Yuri-Kumiai General Hospital) were analyzed using a prospectively collected ESD database. ESCC was diagnosed as a mucosal lesion without lymph node metastasis using diagnostic endoscopy and CT scan. Circumferential cancer was treated with surgery or chemoradiotherapy because of the high risk of severe stricture following ESD. Patients who underwent chemoradiotherapy previously as a first-line therapy were excluded. Although 174 patients were treated with ESD as the first-line therapy for esophageal tumors, 12 were diagnosed with non-neoplastic lesions on histological assessment. Therefore, 162 patients diagnosed with squamous cell carcinoma were included in the analysis. If two or more lesions were simultaneously treated in a patient, only that with the largest diameter was included in this study. If patients with metachronous lesions were treated with ESD two or more times, the first lesions were included because ulcer scar caused by previous treatment might affect treatment outcomes. The enrolled patients’ flow chart is shown in Fig. 2. We began using the Clutch Cutter from April 2017. Before the Clutch Cutter, non-scissor-type endo-knives including IT-knife nano (KD-612 L; Olympus, in Tokyo, Japan), Dual knife (KD-650 L; Olympus, Tokyo, Japan), Flush knife (DK2620; Fuji Film, Tokyo, Japan), and Splash M-knife (DN-D2718B; HOYA Corp., Pentax, Tokyo, Japan) were used during ESD. This study was conducted in accordance with the Declaration of Helsinki and was approved by each Institutional Review Board. Written informed consent was obtained from all patients before ESD. Fig. 2 Open in new tabDownload slide Flowchart of patients enrolled in the study. Fig. 2 Open in new tabDownload slide Flowchart of patients enrolled in the study. ESD procedure ESD was conducted with the patient under general anesthesia in the operating room or under conscious sedation in the endoscopy room. The conventional ESD techniques have been previously described in detail.3 The ESD technique using the Clutch Cutter has been described in detail.4,20 ESD was conducted using a single-channel endoscope (GIF Q260J, Olympus Medical Systems, Tokyo, Japan) with a transparent hood (D-201-11804, Olympus, Tokyo, Japan) attached to the tip. The Clutch Cutter, Dual knife, Flush knife, and Splash M-knife were used as endo-knives.8,11,21 The electrosurgical unit used in ESD was the VIO300D electrosurgical system (ERBE Elektromedizin, GmbH, Tübingen, Germany). First, the tumor range and circumference were diagnosed endoscopically after spraying an iodine solution. The lesion was marked at about 3 mm away from the edge. Hyaluronic acid with a small amount of 0.8% indigo carmine was injected into the submucosal layer surrounding the lesion area. All injections were administered using a specific injection needle (01841; Top Corporation, Tokyo, Japan). Following the injection, a circumferential mucosal incision was made (Fig. 3A). On completing mucosal incision around the mark, traction was applied for some of the lesions, which has been reported to be beneficial in ESD for gastrointestinal tract tumors.22,23 Next, submucosal dissection was performed after additional injection to elevate the lesion (Fig. 3B). In the Clutch Cutter group, a series of coagulation and sequential cuttings was performed during mucosal incision and submucosal dissection. Coagulation (soft coagulation; effect 5, 80 W or forced coagulation; effect 2, 30 W) prevents intraoperative bleeding and cutting (Endo Cut Q; effect 4, duration 1) prevents over-coagulation, which results in fibrosis and stricture.24 Bleeding or visible vessels were coagulated with the endo-knife itself or were clamped and subsequently coagulated with the hemostatic forceps (Fig. 3C). If the mucosal defect was more than 2/3 of the circumference, oral/injected steroids were used to prevent esophageal stricture, based on the surgeon’s judgment. Fig. 3 Open in new tabDownload slide Step-wise endoscopic submucosal dissection using the scissor-type knife. A. Mucosal incision with the scissor-type knife. B. Submucosal dissection with the scissor-type knife. C. Coagulation for visible vessels with the scissor-type knife. Fig. 3 Open in new tabDownload slide Step-wise endoscopic submucosal dissection using the scissor-type knife. A. Mucosal incision with the scissor-type knife. B. Submucosal dissection with the scissor-type knife. C. Coagulation for visible vessels with the scissor-type knife. Operators in this study included 5 experts and 10 trainees. The experts had experience of performing >50 ESD cases in gastrointestinal tracts and >10 ESD cases in the esophagus. Histological assessment ESD specimens were stretched, pinned to a polystyrene plate in entirety, and totally immersed in 10% neutral buffered formalin for more than 12 hours for fixation. After fixation, the specimens were serially sectioned perpendicularly at 2-mm intervals. Tumor size, depth of invasion, differentiation, and presence or absence of lymphatic invasion and vascular invasion were evaluated. The depth of invasion was classified into the following five groups: M1 (confined to the intra-epithelium), M2 (confined to the lamina propria), M3 (confined to the muscularis mucosa), SM1 (submucosal invasion <200 μm), and SM2 (submucosal invasion ≥200 μm). En-bloc resection was defined as the lesion resected in one piece. Complete resection was defined as en-bloc resection with lateral and vertical margins free of tumor. Curative resection was defined as complete resection without SM invasion, lymphatic invasion, vascular invasion, or poorly differentiated histology. Anatomical regions of the esophagus The esophagus was classified as cervical (Ce), thoracic, or abdominal esophagus (Ae). Furthermore, the thoracic esophagus was subclassified as the upper thoracic (Ut), middle thoracic (Mt), or lower thoracic esophagus (Lt). Study outcomes The primary outcome was procedure time, defined as the time from the start of circumferential incision to the completion of submucosal dissection during the ESD procedure. The secondary outcomes were the en-bloc/complete/curative resection rate and the complication rate (perforation/delayed bleeding). The definition of perforation included micro-perforation and frank perforation. Delayed bleeding was defined as when a transfusion or a hemostatic procedure was needed. Stricture was defined as the presence of dysphagia requiring endoscopic intervention with balloon dilation. Table 1 Characteristics of enrolled patients before propensity score matching ESD-S n = 48 ESD-NS n = 114 *P value ASD Age, years  Mean ± SD 66.15 ± 12.77 68.53 ± 8.60 0.17  Median (range) 67.0 (41–86) 66.0 (42–85) 0.61 0.22 Sex, n (%)  Male 36 (75.0) 96 (84.2) 0.29 0.23  Female 12 (25.0) 18 (15.8) Tumor location, n (%)  Ce/Ut 6 (12.5) 17 (14.9) 0.81 0.070  Mt/Lt/Ae 42 (87.5) 97 (85.1) Morphology, n (%)  Flat or depressed 40 (83.3) 104 (91.2) 0.33 0.24  Protruded 8 (16.7) 10 (8.8) Tumor size (mm)  Mean ± SD 20.40 ± 11.08 18.10 ± 12.50 0.27  Median (range) 18.0 (4–54) 15.0 (3–80) 0.073 0.20 Tumor depth, n (%)  Mucosa 44 (91.7) 104 (91.2) 1 0.016  Submucosa 4 (8.3) 10 (8.8) Degree of tumor circumference, n (%)  <1/2 32 (66.7) 94 (82.5) 0.038 0.37  ≥1/2 16 (33.3) 20 (17.5) Operator skill, n (%)  Experts 31 (64.6) 96 (84.2) <0.001 0.46  Trainees 17 (35.4) 18 (15.8) Traction method, n (%)  Use 26 (54.2) 79 (69.3) 0.074 0.41  Non-use 22 (45.8) 35 (30.7) Sedation method  General anesthesia 16 (33.3) 32 (28.1) 0.57 0.11  Conscious sedation 32 (66.7) 82 (71.9) ESD-S n = 48 ESD-NS n = 114 *P value ASD Age, years  Mean ± SD 66.15 ± 12.77 68.53 ± 8.60 0.17  Median (range) 67.0 (41–86) 66.0 (42–85) 0.61 0.22 Sex, n (%)  Male 36 (75.0) 96 (84.2) 0.29 0.23  Female 12 (25.0) 18 (15.8) Tumor location, n (%)  Ce/Ut 6 (12.5) 17 (14.9) 0.81 0.070  Mt/Lt/Ae 42 (87.5) 97 (85.1) Morphology, n (%)  Flat or depressed 40 (83.3) 104 (91.2) 0.33 0.24  Protruded 8 (16.7) 10 (8.8) Tumor size (mm)  Mean ± SD 20.40 ± 11.08 18.10 ± 12.50 0.27  Median (range) 18.0 (4–54) 15.0 (3–80) 0.073 0.20 Tumor depth, n (%)  Mucosa 44 (91.7) 104 (91.2) 1 0.016  Submucosa 4 (8.3) 10 (8.8) Degree of tumor circumference, n (%)  <1/2 32 (66.7) 94 (82.5) 0.038 0.37  ≥1/2 16 (33.3) 20 (17.5) Operator skill, n (%)  Experts 31 (64.6) 96 (84.2) <0.001 0.46  Trainees 17 (35.4) 18 (15.8) Traction method, n (%)  Use 26 (54.2) 79 (69.3) 0.074 0.41  Non-use 22 (45.8) 35 (30.7) Sedation method  General anesthesia 16 (33.3) 32 (28.1) 0.57 0.11  Conscious sedation 32 (66.7) 82 (71.9) ESD-S, endoscopic submucosal dissection with scissor-type knife; END-NS, endoscopic submucosal dissection with non-scissor-type knife; SD, standard deviation; ASD, absolute standardized difference; Ce, cervical esophagus; Ut, upper thoracic esophagus; Mt, middle thoracic esophagus; Lt, lower thoracic esophagus; Ae, abdominal esophagus *P value was calculated using the χ2 test or Fisher’s exact test for categorical data; P value was calculated using the t test or Mann-Whitney’s U test for continuous data distributed abnormally Open in new tab Table 1 Characteristics of enrolled patients before propensity score matching ESD-S n = 48 ESD-NS n = 114 *P value ASD Age, years  Mean ± SD 66.15 ± 12.77 68.53 ± 8.60 0.17  Median (range) 67.0 (41–86) 66.0 (42–85) 0.61 0.22 Sex, n (%)  Male 36 (75.0) 96 (84.2) 0.29 0.23  Female 12 (25.0) 18 (15.8) Tumor location, n (%)  Ce/Ut 6 (12.5) 17 (14.9) 0.81 0.070  Mt/Lt/Ae 42 (87.5) 97 (85.1) Morphology, n (%)  Flat or depressed 40 (83.3) 104 (91.2) 0.33 0.24  Protruded 8 (16.7) 10 (8.8) Tumor size (mm)  Mean ± SD 20.40 ± 11.08 18.10 ± 12.50 0.27  Median (range) 18.0 (4–54) 15.0 (3–80) 0.073 0.20 Tumor depth, n (%)  Mucosa 44 (91.7) 104 (91.2) 1 0.016  Submucosa 4 (8.3) 10 (8.8) Degree of tumor circumference, n (%)  <1/2 32 (66.7) 94 (82.5) 0.038 0.37  ≥1/2 16 (33.3) 20 (17.5) Operator skill, n (%)  Experts 31 (64.6) 96 (84.2) <0.001 0.46  Trainees 17 (35.4) 18 (15.8) Traction method, n (%)  Use 26 (54.2) 79 (69.3) 0.074 0.41  Non-use 22 (45.8) 35 (30.7) Sedation method  General anesthesia 16 (33.3) 32 (28.1) 0.57 0.11  Conscious sedation 32 (66.7) 82 (71.9) ESD-S n = 48 ESD-NS n = 114 *P value ASD Age, years  Mean ± SD 66.15 ± 12.77 68.53 ± 8.60 0.17  Median (range) 67.0 (41–86) 66.0 (42–85) 0.61 0.22 Sex, n (%)  Male 36 (75.0) 96 (84.2) 0.29 0.23  Female 12 (25.0) 18 (15.8) Tumor location, n (%)  Ce/Ut 6 (12.5) 17 (14.9) 0.81 0.070  Mt/Lt/Ae 42 (87.5) 97 (85.1) Morphology, n (%)  Flat or depressed 40 (83.3) 104 (91.2) 0.33 0.24  Protruded 8 (16.7) 10 (8.8) Tumor size (mm)  Mean ± SD 20.40 ± 11.08 18.10 ± 12.50 0.27  Median (range) 18.0 (4–54) 15.0 (3–80) 0.073 0.20 Tumor depth, n (%)  Mucosa 44 (91.7) 104 (91.2) 1 0.016  Submucosa 4 (8.3) 10 (8.8) Degree of tumor circumference, n (%)  <1/2 32 (66.7) 94 (82.5) 0.038 0.37  ≥1/2 16 (33.3) 20 (17.5) Operator skill, n (%)  Experts 31 (64.6) 96 (84.2) <0.001 0.46  Trainees 17 (35.4) 18 (15.8) Traction method, n (%)  Use 26 (54.2) 79 (69.3) 0.074 0.41  Non-use 22 (45.8) 35 (30.7) Sedation method  General anesthesia 16 (33.3) 32 (28.1) 0.57 0.11  Conscious sedation 32 (66.7) 82 (71.9) ESD-S, endoscopic submucosal dissection with scissor-type knife; END-NS, endoscopic submucosal dissection with non-scissor-type knife; SD, standard deviation; ASD, absolute standardized difference; Ce, cervical esophagus; Ut, upper thoracic esophagus; Mt, middle thoracic esophagus; Lt, lower thoracic esophagus; Ae, abdominal esophagus *P value was calculated using the χ2 test or Fisher’s exact test for categorical data; P value was calculated using the t test or Mann-Whitney’s U test for continuous data distributed abnormally Open in new tab Statistical analysis Continuous data were expressed as means (standard deviation; SD) and median (range). Comparisons between continuous data distributed abnormally were performed using the Mann-Whitney’s test. Categorical data were expressed as frequencies. Comparisons between categorical data were performed using Fisher’s exact test. To minimize the effect of selection bias, propensity score matching analysis was performed. Propensity scores were estimated using a multiple logistic regression model to balance both groups in age (≥75 years vs. <75 years), sex (male vs. female), the tumor location (Ce/Ut vs. Mt/Lt/Ae), tumor morphology (flat or depressed vs. others), degree of tumor circumference (≥1/2 vs. <1/2), tumor size (≥20 mm vs. <20 mm), tumor depth (M1/M2 vs. M3/SM1/SM2), operator skill (expert; ≥50 ESD cases vs. trainee; <50 ESD cases), usage of the traction method (use vs. non-use), and the sedation method (general anesthesia vs. conscious sedation). The balance was verified by checking the P value and the absolute standardized difference (ASD) between both groups. ASD within 1.96√2/n after matching was considered to be well balanced.25 Caliper width (0.2) was equal to one-fifth of the standard deviation of the logit of the propensity score. Then, 1:1 matching using the nearest neighbor matching method was performed. Estimated area under the receive-operating characteristics curve was 0.82, indicating good predictive power to validate the model of this study. Values of P < 0.05 were considered statistically significant. All analyses were performed using the JMP Pro 11.0 software (SAS Institute, Cary, NC). RESULTS Characteristics Characteristics of enrolled patients before propensity score matching are provided in Table 1. The proportion of cases with tumor circumference ≥1/2 was significantly higher in the ESD-S group than in the ESD-NS group (33.3% vs. 17.5%, P = 0.038). The median tumor size in the ESD-S group (18.0 mm, range 4–54 mm) was greater than in the ESD-NS group (15.0 mm, 3–80 mm), but the difference was not statistically significant (P = 0.073). The proportion of trainee operators in the ESD-S group (35.4%) was significantly higher than in the ESD-NS group (15.8%) (P < 0.001). The usage rate of the traction method tended to be higher in the ESD-S group, but the difference was not statistically significant (45.8% vs. 30.7%, P = 0.074). Matching factors A total of 34 pairs were created using propensity score matching. The matching factors between both groups following propensity score matching are shown in Table 2. All P values were not significant. In addition, all ASDs were within 1.96√2/n. Table 2 Matching factors between the two groups after propensity score matching ESD-S n = 36 ESD-NS n = 36 *Pvalue ASD Variable matching between the groups  Age, y; <75/≥75 25/11 26/10 1 0.061  Sex; Male/Female 29/7 33/3 0.31 0.33  Tumor location; Ce, Ut/Mt, Lt, Ae 6/30 4/32 0.74 0.16  Morphology; Flat or depressed/Others 31/5 29/7 0.75 0.15  Degree of circumference; <1/2/≥1/2 8/28 12/24 0.43 0.25  Tumor size; <20/≥20 mm 22/14 20/16 0.81 0.11  Tumor depth; M1, M2/M3, SM1, SM2 29/7 30/6 1 0.072  Operator skill; expert/trainee 17/19 20/16 0.64 0.17  Traction method; use/non-use 21/15 25/11 0.46 0.23  Sedation; general anesthesia/conscious sedation 13/23 12/24 1 0.058 ESD-S n = 36 ESD-NS n = 36 *Pvalue ASD Variable matching between the groups  Age, y; <75/≥75 25/11 26/10 1 0.061  Sex; Male/Female 29/7 33/3 0.31 0.33  Tumor location; Ce, Ut/Mt, Lt, Ae 6/30 4/32 0.74 0.16  Morphology; Flat or depressed/Others 31/5 29/7 0.75 0.15  Degree of circumference; <1/2/≥1/2 8/28 12/24 0.43 0.25  Tumor size; <20/≥20 mm 22/14 20/16 0.81 0.11  Tumor depth; M1, M2/M3, SM1, SM2 29/7 30/6 1 0.072  Operator skill; expert/trainee 17/19 20/16 0.64 0.17  Traction method; use/non-use 21/15 25/11 0.46 0.23  Sedation; general anesthesia/conscious sedation 13/23 12/24 1 0.058 ESD-S, endoscopic submucosal dissection with scissor-type knife; ESD-NS, endoscopic submucosal dissection with non-scissor-type knife; ASD, absolute standardized difference; Ce, cervical esophagus; Ut, upper thoracic esophagus; Mt, middle thoracic esophagus; Lt, lower thoracic esophagus; Ae, abdominal esophagus. M1, confined to the intra-epithelium, M2, confined to the lamina propria, M3, confined to the muscularis mucosa, SM1, submucosal invasion <200 μm, SM2, submucosal invasion ≥200 μm *P value was calculated using the χ2 test or Fisher’s exact test for categorical data Open in new tab Table 2 Matching factors between the two groups after propensity score matching ESD-S n = 36 ESD-NS n = 36 *Pvalue ASD Variable matching between the groups  Age, y; <75/≥75 25/11 26/10 1 0.061  Sex; Male/Female 29/7 33/3 0.31 0.33  Tumor location; Ce, Ut/Mt, Lt, Ae 6/30 4/32 0.74 0.16  Morphology; Flat or depressed/Others 31/5 29/7 0.75 0.15  Degree of circumference; <1/2/≥1/2 8/28 12/24 0.43 0.25  Tumor size; <20/≥20 mm 22/14 20/16 0.81 0.11  Tumor depth; M1, M2/M3, SM1, SM2 29/7 30/6 1 0.072  Operator skill; expert/trainee 17/19 20/16 0.64 0.17  Traction method; use/non-use 21/15 25/11 0.46 0.23  Sedation; general anesthesia/conscious sedation 13/23 12/24 1 0.058 ESD-S n = 36 ESD-NS n = 36 *Pvalue ASD Variable matching between the groups  Age, y; <75/≥75 25/11 26/10 1 0.061  Sex; Male/Female 29/7 33/3 0.31 0.33  Tumor location; Ce, Ut/Mt, Lt, Ae 6/30 4/32 0.74 0.16  Morphology; Flat or depressed/Others 31/5 29/7 0.75 0.15  Degree of circumference; <1/2/≥1/2 8/28 12/24 0.43 0.25  Tumor size; <20/≥20 mm 22/14 20/16 0.81 0.11  Tumor depth; M1, M2/M3, SM1, SM2 29/7 30/6 1 0.072  Operator skill; expert/trainee 17/19 20/16 0.64 0.17  Traction method; use/non-use 21/15 25/11 0.46 0.23  Sedation; general anesthesia/conscious sedation 13/23 12/24 1 0.058 ESD-S, endoscopic submucosal dissection with scissor-type knife; ESD-NS, endoscopic submucosal dissection with non-scissor-type knife; ASD, absolute standardized difference; Ce, cervical esophagus; Ut, upper thoracic esophagus; Mt, middle thoracic esophagus; Lt, lower thoracic esophagus; Ae, abdominal esophagus. M1, confined to the intra-epithelium, M2, confined to the lamina propria, M3, confined to the muscularis mucosa, SM1, submucosal invasion <200 μm, SM2, submucosal invasion ≥200 μm *P value was calculated using the χ2 test or Fisher’s exact test for categorical data Open in new tab Table 3 Treatment outcomes between the two groups after propensity score matching ESD-S n = 36 ESD-NS n = 36 *Pvalue Procedure time, min  Mean ± SD 56.39 ± 35.32 72.50 ± 40.05  Median (range) 44.0 (17–163) 66.5 (24–227) 0.020 En-bloc resection 36 (100%) 35 (97.2%) 1 Complete resection 32 (88.9%) 31 (86.1%) 1 Curative resection 29 (80.6%) 28 (77.8%) 1 Complication 1 (2.8%) 5 (13.9%) 0.20 Perforation 0 (0%) 2 (5.6%) 0.49 Delayed bleeding 0 (0%) 0 (0%) — Steroid use for preventing stricture 10 (27.8%) 6 (16.7%) 0.40 Stricture 1 (2.8%) 3 (8.3%) 0.61 ESD-S n = 36 ESD-NS n = 36 *Pvalue Procedure time, min  Mean ± SD 56.39 ± 35.32 72.50 ± 40.05  Median (range) 44.0 (17–163) 66.5 (24–227) 0.020 En-bloc resection 36 (100%) 35 (97.2%) 1 Complete resection 32 (88.9%) 31 (86.1%) 1 Curative resection 29 (80.6%) 28 (77.8%) 1 Complication 1 (2.8%) 5 (13.9%) 0.20 Perforation 0 (0%) 2 (5.6%) 0.49 Delayed bleeding 0 (0%) 0 (0%) — Steroid use for preventing stricture 10 (27.8%) 6 (16.7%) 0.40 Stricture 1 (2.8%) 3 (8.3%) 0.61 ESD-S, endoscopic submucosal dissection with scissor-type knife; ESD-NS, endoscopic submucosal dissection with non-scissor-type knife; SD, standard deviation *P value was calculated using the χ2 test or Fisher’s exact test for categorical data; P value was calculated using the t test or Mann-Whitney’s U test for continuous data Open in new tab Table 3 Treatment outcomes between the two groups after propensity score matching ESD-S n = 36 ESD-NS n = 36 *Pvalue Procedure time, min  Mean ± SD 56.39 ± 35.32 72.50 ± 40.05  Median (range) 44.0 (17–163) 66.5 (24–227) 0.020 En-bloc resection 36 (100%) 35 (97.2%) 1 Complete resection 32 (88.9%) 31 (86.1%) 1 Curative resection 29 (80.6%) 28 (77.8%) 1 Complication 1 (2.8%) 5 (13.9%) 0.20 Perforation 0 (0%) 2 (5.6%) 0.49 Delayed bleeding 0 (0%) 0 (0%) — Steroid use for preventing stricture 10 (27.8%) 6 (16.7%) 0.40 Stricture 1 (2.8%) 3 (8.3%) 0.61 ESD-S n = 36 ESD-NS n = 36 *Pvalue Procedure time, min  Mean ± SD 56.39 ± 35.32 72.50 ± 40.05  Median (range) 44.0 (17–163) 66.5 (24–227) 0.020 En-bloc resection 36 (100%) 35 (97.2%) 1 Complete resection 32 (88.9%) 31 (86.1%) 1 Curative resection 29 (80.6%) 28 (77.8%) 1 Complication 1 (2.8%) 5 (13.9%) 0.20 Perforation 0 (0%) 2 (5.6%) 0.49 Delayed bleeding 0 (0%) 0 (0%) — Steroid use for preventing stricture 10 (27.8%) 6 (16.7%) 0.40 Stricture 1 (2.8%) 3 (8.3%) 0.61 ESD-S, endoscopic submucosal dissection with scissor-type knife; ESD-NS, endoscopic submucosal dissection with non-scissor-type knife; SD, standard deviation *P value was calculated using the χ2 test or Fisher’s exact test for categorical data; P value was calculated using the t test or Mann-Whitney’s U test for continuous data Open in new tab Technical outcomes after propensity score matching Table 3 shows all technical outcomes after propensity score matching. Median dissection time of the ESD-S group (44.0 min, 17–163) was significantly shorter than that of the ESD-NS group (66.5 min, 24–227) (P = 0.020). The en-bloc, complete, and curative resection rates of the ESD-S group were 100, 88.9, and 80.6%, respectively, and those of the ESD-NS group were 97.2, 86.1, and 77.8%, respectively. There were no significant differences in the en-bloc, complete, and curative resection rates between both groups. In addition, the complication rate of ESD-S (2.8%) was also not significantly different from that of ESD-NS (13.9%). No events of perforation and delayed bleeding were observed in the ESD-S group. The rates of steroid use after ESD were 27.8% in ESD-S and 16.7% in ESD-NS. The stricture rate with ESD-S (2.8%) was not statistically different from that with ESD-NS (8.3%). In ESD-S, there were no significant differences in the median procedure time of the experts and trainees (42.0 min, 17–112 vs. 46.0 min, 21–163, P = 0.47, not shown in tables). DISCUSSION To the best of our knowledge, this is the first multicenter study to evaluate the efficacy and safety of ESD-S for superficial esophageal cancer and compare them with those of ESD-NS by propensity score matching analysis. Although ESD-S enabled a shorter procedure time than ESD-NS, there were no differences in the resection rates and complication rates between the two. This was a retrospective study, but not a randomized control trial. Therefore, there were some biases owing to the different background characteristics of both groups. Several factors are associated with the outcomes of ESD for esophageal neoplasms. First, larger lesions were associated with a lower complete resection rate.26 Second, submucosal fibrosis was associated with difficulty in ESD.27 Tumor length greater than 20 mm and depressed tumor type have been reported as predictive factors for submucosal fibrosis in ESD of superficial squamous esophageal neoplasia.28 Third, the circumference of the lesion and the tumor size were significantly associated with the occurrence of post-operative strictures.23,29,30 Fourth, the learning curve for ESD of neoplasms affected the technical outcomes.31 Fifth, traction methods such as the dental floss traction method reportedly shorten the procedure time of esophageal ESD.11,23,32 Finally, esophageal ESD with the patient under general anesthesia was reported to be associated with better clinical outcomes.33,34 Therefore, we conducted a propensity score matching analysis to compensate for these biases. Following propensity score matching, significant differences in the background characteristics between both groups could be compensated well, which we thought was suitable for performing an analysis. Many endo-knives are currently clinically used for ESD procedures in gastrointestinal tract tumors.8–10,13,15,35 It is unclear which endo-knife is the most appropriate for ESD; the choice of endo-knife usually depends on the attending operator’s preference and decision. The currently available endo-knives can be classified into two groups based on their shape and concept: scissor-type and non-scissor type. Colorectal ESD-S is reportedly a time-consuming procedure, although this was a retrospective observational study, not a comparison study.35 Moreover, the time required for ESD-NS with IT knife for early gastric cancer was reportedly shorter than that required for ESD-S with Clutch Cutter under the conditions of non-expert operators and lesions smaller than 20 mm.19 In contrast, the superiority of Clutch Cutter in gastric ESD has been recently reported.36,37 There have been no previous comparison studies regarding the technical outcomes of superficial esophageal cancer between scissor-type knife and non-scissor-type knife procedures. Contrary to the results seen in tumors of the colon, the procedure time of ESD-S for superficial esophageal cancer was significantly shorter than that of ESD-NS after propensity score matching. Scissor-type knife might be more suitable for esophageal ESD rather than for gastric and colorectal ESD possibly due to the anatomic features of the esophagus, which has a narrower and thinner lumen than the stomach and colon. Scissor-type knife can be rotated. Therefore, it is possible to control the incision or dissection line without moving the endoscope despite the smaller working space. It appears that ESD-S is a time-saving procedure when treating superficial esophageal cancers. Another advantage of ESD-S is possibly the prevention of procedure-related complications, including perforation, bleeding, and stricture.38 First, perforation is one of the most severe complications during esophageal ESD, since it can cause life-threatening mediastinitis.3,4 Perforation did not occur with ESD-S in the present study, while it occurred in 5.6% (2/36) of the patients after ESD-NS. The Clutch Cutter has two steps for processing the target tissues, namely grasp and cut. We can repeat grasping of the target tissue as many times as desired to avoid miscutting. Second, although the frequency of procedure-related bleeding was not noted in this study, the Clutch Cutter might play a role in the prevention and control of ESD procedure-related bleeding. The Clutch Cutter can be used as a device for endoscopic hemostasis in a manner similar to that of hemostatic forceps. Since the control of ESD procedure-related bleeding is a key factor to obtain a successful treatment,39 it might have contributed to shortening the procedure time in the present study. Finally, only one patient in the ESD-S group compared with three patients in the ESD-NS group presented with a stricture following the procedure for circumferential lesions (P = 0.61). Although steroid use for preventing stricture might have affected this outcome (27.8% in ESD-S vs. 16.7% in ESD-NS, P = 0.40), there was no significant difference in steroid use and stricture occurrence between both groups. Regarding the operator experience level, this study included both non-expert and expert operators. The proportion of trainee operators in the ESD-S group was significantly higher than that in the ESD-NS group. Furthermore, there were no significant differences in the median procedure time for ESD-S between the experts and trainees. The scissor-type knife might contribute to reducing the difficulty of ESD and increase the number of cases that can be treated by trainees. This study has some limitations. First, this was a retrospective study. Therefore, there remains the possibility of selection bias. Second, although this was a multicenter study, the number of institutions was three, and thus, the sample size was relatively small. Third, as for the operator experience level, the proportion of trainees in the ESD-S group was significantly higher than that in the ESD-NS group. Operator experience level was included as one of the covariate factors of the propensity score; therefore, this did not affect the outcomes of this study. Finally, there is a possibility of bias in the institutional learning curve. Almost all lesions were treated with the Clutch Cutter after starting its use in April 2017. Before the Clutch Cutter was used, non-scissor-type endo-knives were used in the former phase of this study, while a scissor-type knife was used in the latter phase, which might have affected the outcomes of this study. Prospective randomized controlled studies with a larger sample size should be conducted in the future. In conclusion, the procedure time for ESD-S was shorter than that for ESD-NS for superficial esophageal cancer, while there were no significant differences in the resection rate and complication rate between ESD-S and ESD-NS. The scissor-type knives show an advantage over non-scissor-type knives in ESD for superficial esophageal cancer. Funding information: This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. ACKNOWLEDGEMENT The authors thank Azusa Yokoyama for data collection. DISCLOSURES Takuji Gotoda received a lecture fee from the Fujifilm company. Mitsuru Esaki, Yasuyo Hayashi, Hisatomo Ikehara, Eikichi Ihara, Toshiki Horii, Yu Tamura, Ryoji Ichijima, Shun Yamakawa, Akira Irie, Hitoshi Shibuya, Sho Suzuki, Chika Kusano, Yosuke Minoda, Hirotada Akiho and Yoshihiro Ogawa have no conflicts of interest or financial ties to disclose. References 1 Ono H , Kondo H , Gotoda T et al. Endoscopic mucosal resection for treatment of early gastric cancer . Gut 2001 ; 48 : 225 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Kim J S , Kim B W , Shin I S . Efficacy and safety of endoscopic submucosal dissection for superficial squamous esophageal neoplasia: a meta-analysis . Dig Dis Sci 2014 ; 59 : 1862 – 9 . 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Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - The effect of scissor-type versus non-scissor-type knives on the technical outcomes in endoscopic submucosal dissection for superficial esophageal cancer: a multi-center retrospective study
JF - Diseases of the Esophagus
DO - 10.1093/dote/doz077
DA - 2020-04-15
UR - https://www.deepdyve.com/lp/oxford-university-press/the-effect-of-scissor-type-versus-non-scissor-type-knives-on-the-sJbW3rmHlH
SP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -