The ex vivo pilot study
This was a prospective, block-randomized, comparative study that used a resected porcine stomach model (Tokyo Shibaura Zouki Co., Ltd., Tokyo, Japan) to evaluate the utility of the MLTD in ESD. Twenty-four lesions (four lesions/endoscopist among three expert endoscopists, and four lesions/endoscopist among three trainees inexperienced in clinical ESD) were assigned in a 1:1 ratio between a group that undertook ESD using the MLTD (M-ESD group) and a group that undertook conventional ESD (C-ESD group). Expert endoscopists were defined on the basis of being a Japan Gastroenterological Endoscopy Society medical specialist with > 50 instances of clinical experience in ESD. Trainees were defined as gastroenterologists with no clinical experience with ESD (Additional file 1: Table S1).
Before participation in this study, trainees undertook training consisting of performing ESD on two lesions in a resected porcine stomach model. In this study, trainees performed ESD procedures under the supervision of expert endoscopists.
Randomization method
Lesions were assigned to endoscopists using MS Excel (Microsoft, Redmond, WA, USA) to assign a random number to each lesion and then randomly allocate to either the M-ESD group or C-ESD group. The lesion site (anterior or posterior wall) was also used as a random block factor.
ESD procedure
ESD was performed with a distal tip attachment (D-201-10704; Olympus Co. Ltd., Tokyo, Japan) attached to a GIF-Q260 endoscope (Olympus Co. Ltd., Tokyo, Japan). All circumferential incisions and submucosal dissections were performed using DualKnife (KD-655L; Olympus Co. Ltd., Tokyo, Japan). The fluid injected into the local submucosa was a mixture of 0.4% hyaluronic acid solution (MucoUp®, Boston Scientific Co. Ltd.) and a small amount of indigo carmine. A high-frequency generator (ESG-100, Olympus Co. Ltd., Tokyo, Japan) was used for this study, which was set to the ForcedCoag mode (50 W) and PulseCut fast mode (70 W).
Before starting the ESD procedure, a 20-mm diameter disk was placed in the resected porcine stomach to mark the stomach and create a 20-mm diameter mock lesion. Next, a mixture of hyaluronic acid and a small amount of indigo carmine was injected into the submucosal layer to elevate the lesion. Up to this point, the ESD procedure was identical in the M-ESD and C-ESD groups.
In the C-ESD group, dissection of the submucosal layer was performed after completion of the circumferential incision around the lesion. In the M-ESD group, the MLTD was attached between the mucosa around the lesion and the porcine gastric wall contralateral to the lesion after the circumferential incision, using a short-type clip (EZ clip, Olympus Co. Ltd., Tokyo, Japan), which was reloadable (Fig. 1a, b). First, the MLTD was snagged at the base of the clip; thereafter, the clip with the MLTD attached was delivered into the porcine stomach model through a forceps channel using a rotatable clip device (HX-201LR-135; Olympus Co. Ltd., Tokyo, Japan). The clip was then attached to the edge of the proximal side of the lesion mucosa (Fig. 1c). Another reloadable short clip was used to snag the ring on the other end of the MLTD and create countertraction by attaching it to the gastric wall contralateral to the lesion, enabling good visualization of the submucosa (Fig. 1d). Finally, submucosal dissection was performed (Fig. 1e), and the lesion was resected, identical to how it was performed in the C-ESD group (Fig. 1f).
After resection, the MLTD was retrieved together with the lesion using biopsy forceps to grasp the MLTD and pull it out. After resection of the lesion, the lesion specimen was retrieved from the porcine stomach model using an endoscope, and the size of the specimen was measured. Video recordings were performed for all endoscopy procedures (Additional file 2: Video S1).
MLTD
The MLTD is a detachable and commercially available traction device for ESD that consists of three connected rings of a unique linear biocompatible low-density polyethylene plastic. The device is 0.3 mm thick, and each ring is 6 mm in diameter. The MLTD can be delivered to the lesion site from the forceps channel of an endoscope using a clip device. is easily cut and removed by lightly grasping the loop of the MLTD with biopsy forceps and pulling it away. MLTD is easily cut and removed by lightly grasping the loop that is attached to the gastrointestinal (GI) tract wall by the clip, with biopsy forceps and pulling it away. When the tension on the MLTD decreases or the direction of tension becomes inadequate, re-tensioning or re-direction is allowed by reattaching the middle ring of the MLTD to the GI tract wall. For clinical use, MLTD has to be retrieved from the GI tract together with the lesion or through the forceps channel using biopsy forceps after completion of ESD.
Endpoints
The primary endpoint in this study was the submucosal dissection speed (mm2/min), which was compared between the M-ESD and C-ESD groups. The secondary endpoints were the rate of procedure completion, rate of en bloc resection, rate of R0 resection, rate of perforation, overall procedure time, injection time, perimeter incision time, submucosal dissection time, total local injection volume, resected specimen area, and number of additional local injections during submucosal dissection.
The rate of MLTD attachment, rate of successful MLTD attachment, rate of specimen retrieval with biopsy forceps, MLTD attachment time, and MLTD retrieval time were also analyzed in the M-ESD group.
In the C-ESD group, the overall procedure time was defined as the time from first submucosal injection to completion of specimen removal; in the M-ESD group, it was defined as the time from first submucosal injection to MLTD retrieval. When all markings on the mock lesion were identified in the resected and retrieved specimens, we recognized that the lesion was resected as R0. Successful MLTD attachment was defined as achieving good traction with clips attached to the lesion and the gastric wall contralateral to the lesion.
Sample size calculation
A previous report [7] noted that the mean dissection speed of gastric ESD in living pigs without traction was 0.6 ± 0.1 cm2/min. Assuming that the dissection speed will be 20% faster with the MLTD, to detect a significant difference compared to C-ESD with an alpha error of 0.05, and a statistical power of 80%, each group required 12 lesions.
Statistical analysis
All variables are presented as median and interquartile (IQR) range (first quartile—third quartile [IQR]) or median with range, with a two-sided significance level of 5%. Categorical variables were compared using the chi-squared test and Fisher’s exact test, and continuous variables were compared using the Mann–Whitney U test. A p value less than 0.05 was considered statistically significant. All analyses were performed using Stata 14.0 (StataCorp LP, College Station, TX, USA).
Clinical feasibility evaluation of gastric ESD using MLTD
To clarify the inaugural clinical outcomes of gastric ESD using MLTD, the data of consecutive patient who received gastric ESD using MLTD from September to December 2020 at our institution was collected using electronic medical record. The gastric lesion resected by gastric ESD with partial use of MLTD for submucosal dissection was excluded from the evaluation. The study was approved by the ethics committee of the Jikei University School of Medicine, Tokyo, Japan (no. 31–109(9608)), and it conforms to the provisions of the Declaration of Helsinki.