Gastric endoscopic submucosal dissection using novel 2.6-mm articulating devices: an ex vivo comparative and in vivo feasibility study

• Introduction
• Materials and methods
• Novel articulating devices
• Experiment 1: ex vivo comparative study
• Experiment 2: in vivo feasibility study
• Results
• Experiment 1
• Experiment 2
• Discussion
• References

Background and study aims: The conventional procedure of endoscopic submucosal dissection (ESD) is technically demanding. This study investigated the efficiency of novel articulating devices (maximum diameter 2.6 mm), which can be used with commercially available, standard endoscopes.

Patients and methods: In an ex vivo comparative study, eight endoscopists were divided into novices and experienced operators, and performed ESD using new devices and the conventional setup. An in vivo animal experiment was performed by two experts. Procedure times for incision and dissection were recorded, and unit times for circumferential length and area of specimens were calculated.

Results: All procedures were successfully completed with en bloc resection. In the ex vivo study, the unit procedure times for incision and dissection by novices were significantly shorter using the new system (P < 0.01 and P < 0.05), whereas there was no significant difference for experienced endoscopists. Perforation occurred during one procedure in which the new system was used. The in vivo experiments were successfully completed without adverse events.

Conclusions: ESD using novel articulating devices was feasible. These devices were able to reduce the procedure time for novices.

Introduction

Endoscopic submucosal dissection (ESD) is the current standard technique for en bloc resection of early-stage gastrointestinal tumors. Since the first development of ESD in Japan [1] [2], the use of this method has increased rapidly every year, particularly in Asian countries. However, one of the major problems of ESD is that the operators require a high level of skill [3]. The difficulty is mainly due to the limited degree of freedom of existing devices, and the absence of counter-traction during the procedure [4]. Thus, an articulating device with an easy control system and a second device for raising the tissue would be desirable.

Previous studies have developed several types of such articulating devices for ESD [5] and/or natural orifice transluminal endoscopic surgery (NOTES) [6] [7] [8]. However, all of these devices had large maximum diameters and could not be inserted directly into the channels of standard gastrointestinal endoscopes, which have diameters of 2.8 – 3.8 mm. Therefore, the devices required special sheaths, customized endoscopes, or assembly of the device with an endoscope.

We have recently developed an articulating device with a 2.6-mm diameter, which can be used with standard endoscopes [9]. The aims of the present study were to assess the effectiveness of the new system for ESD in an ex vivo porcine stomach model for endoscopists with different skill levels, and to evaluate the feasibility of ESD in an in vivo experiment.

Materials and methods

Novel articulating devices

The novel devices were developed at the Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan ([Fig. 1]). The devices include forceps and electric knives that have an articulating part for up/down and right/left directions ([Fig. 2 a]). These devices are manually driven by a wire system connected to the handles, which are fixed to a sliding base plate for back and forward motion. The joystick-type handle ([Fig. 2 b]) allows intuitive control by the operator, who can move the device up/down/right/left/back/forward. A sliding knob in the middle of the handle can be pushed/pulled by the thumb, and corresponds to the open/close motion of the forceps and length adjustment of the knife. The articulating forceps is inserted into the original channel of the endoscope, and the articulating electric knife is inserted into an additional channel, which is made from elastic material and is attached to the endoscope. The endoscope is fixed onto the same base structure, and can be fully manipulated (two angle dials, twisting, back/forward) by a single operator without removing the endoscope from the base structure. In the present study, a standard endoscope for gastric ESD was used (GIF-Q260J; Olympus Medical Systems, Tokyo, Japan).

Experiment 1: ex vivo comparative study

As the new devices were expected to reduce the cost of ESD training, the purpose of Experiment 1 was to examine whether the devices could be effectively manipulated by endoscopists who were not familiar with them. Eight endoscopists from Kyushu University Hospital, Fukuoka, Japan, excluding the authors, participated in this experiment. All participants had performed > 500 standard esophagogastroduodenoscopy examinations but none had experience of using the novel system of articulating devices prior to the study. The participants were divided into groups according to their experience of human and animal gastric ESD: “novice” group (experience of 0 – 4 cases, n = 3) and “experienced” group (experience of 5 – 40 cases, n = 5).

The ex vivo porcine stomach model is shown in [Fig. 3]. Fresh porcine stomach, bought from a meat market, was attached to the human head phantom (Medical Training Manikin CLA4; Global Technologies, Atlanta, Georgia, USA) using a custom-made joint. The full procedure of ESD was first carried out using the new system. Subsequently, another ESD procedure was performed using conventional electric knives (an insulation-tipped knife [KD-611L], and a hook-knife [KD-620LR]; Olympus Medical Systems, Tokyo, Japan) and transparent hood (D-201-11804; Olympus Medical Systems).

Before starting, all participants received a short training session using open porcine stomachs. The training session lasted no more than 30 minutes and included an explanation of how to use the articulating devices. During the experiment, an experienced clinician gave verbal instruction in general ESD technique, as some of the participants were performing ESD for the first time.

After insertion of the endoscope into the stomach model, the first two dots were applied by one author (R.N.) at the nearest and furthest points, which were at a distance of ~20 mm, to represent the position and size of the lesion. The devices were then passed to the participant for the rest of the ESD procedures. The two areas selected for use of the new and conventional systems, respectively, were positioned as close as possible.

After completion of the whole procedure, the lengths of the long and short axes of the specimen were measured. The stomach was filled with water to inspect for perforation. The procedure time for circumferential incision and submucosal dissection were recorded in minutes; times per unit length/area were then calculated using the formulae π(a + b)/2 (circumferential length) and πab/4 (area), respectively, where a is the length of the long axis and b is the short axis, as described in Sakurazawa et al. [10].

Statistical analysis was performed using R version 3.0.1 (R Foundation for Statistical Computing, Vienna, Austria). The procedure times were compared between the new and conventional systems using a paired t test. A P value of < 0.05 was considered to be statistically significant.

Experiment 2: in vivo feasibility study

In vivo animal experiments were performed to investigate the feasibility of the new system in a realistic situation. ESD was performed on a female pig with a body weight of ~35 kg under general anesthesia. The experimental protocol was approved by the Animal Care and Use Committee, Kyushu University, Japan. The study animal was handled according to national and institutional guidelines.

Two expert endoscopists (T.M. and T.I; both with experience of > 300 human ESDs) performed gastric ESD in the anterior and posterior walls of the gastric corpus. The endoscopists had used the new ESD system on five and two occasions, respectively, prior to the present study. The procedure times for circumferential incision and submucosal dissection, as well as specimen sizes and adverse events, were recorded.

Results

Experiment 1

All 16 trials of ESD using new and conventional systems were successfully completed with en bloc resection. Procedure times and specimen sizes for all trials are shown in [Table 1]. Procedure time of the circumferential incision per length, and procedure time per area for dissection are summarized in [Fig. 4].

For the novice endoscopists, the unit procedure time using the new system was significantly shorter than for the conventional method for both circumferential incision (P < 0.01) and dissection (P < 0.05). For experienced endoscopists, however, there was no significant difference between the new and conventional systems (circumferential incision P = 0.53; dissection P = 0.12). Perforation occurred during one procedure by an experienced endoscopist using the new system at the beginning of the circumferential incision. The perforation was not closed because it was only found after completion of the study.

Experiment 2

Both ESD procedures were successfully completed with en bloc resection, without any adverse events. The procedure duration and specimen sizes are shown in [Table 2]. The unit procedure time for incision and dissection was 0.6 min/cm and 1.5 min/cm², respectively, which was faster than for ex vivo experiments.

Discussion

The study showed that the new devices could be used effectively by all participants after only 30 minutes of training. As shown in [Fig. 4], the novice endoscopists performed ESD using the new devices with a speed that was similar to experienced endoscopists. During ESD with the conventional system, most of the novice endoscopists experienced technical difficulties, especially when using the transparent hood to open the mucosal flap and access the submucosal layer. By contrast, they found the new articulating forceps to be helpful in lifting the mucosal flap during dissection.

For experienced participants, there was no significant difference in the procedure time between the new and conventional systems. However, this does not mean that the new system has fewer benefits for experienced endoscopists. These operators had past experience of ESD using the conventional system (5 – 40 cases), whereas the present study represented their first use of the new articulating devices. The learning curve for this new system should be investigated in a future study.

Perforation occurred in one case during circumferential incision when using the articulating devices. It was probably caused by insufficient submucosal injection of glycerol and by pushing the electrosurgical knife against the mucosa before activation ([Fig. 5]). These are elementary mistakes often seen in the use of a needle-knife in the conventional system. However, this result implies that a needle-type knife should be used only by experts. A future study planned by our group will include a scissor-type knife, which is reported to be safe [11] [12].

The results from the in vivo experiments are promising. Compared with the ex vivo experiment, the operators adjusted the position of the endoscope more frequently, which is one of the important features of this single-operator system. The most striking novelty of the new devices is that they can be used with commercially available standard endoscopes. Therefore, hospitals do not have to invest in new endoscopes for ESD. Compared with the other NOTES/ESD platforms [5] [6] [7] [8], the initial cost of the new system is low. In addition, the system requires only one operator. This is important for the clinical cost of ESD because the conventional procedure is normally performed by an endoscope operator and an assistant who opens and closes the forceps or knife. If the endoscope was not fixed to the base structure, two clinicians would be required to operate the endoscope and articulating devices [5] [8].

The controller is intuitive because the vertical–horizontal axes of the control grip always correspond to the same axes of the bending section. The distance between the lens and the tip of the knife in conventional ESD is short, and nearly the same as the hood length (4 – 7 mm) during dissection, which is good for keeping a clear visual field. The articulating forceps and knives have a small radius of bending ([Fig. 2 a]); therefore, operation close to the lens is possible. The articulating devices can be used in the retroflex position without problems ([Video 1]).

The current study has some limitations. The sample number was small, and thus the statistical significance was limited. In addition, it is not known by how much the operating time would increase when using these devices in vivo.

Current developments include further improvements in the usability, safety, and alignment of the electrosurgical devices, such as a scissor-shape knife. For future study, the learning curve must be investigated; it is expected to be shorter than that for the conventional method. Further studies should also investigate whether the novel devices are useful not only for straightforward cases, but also for difficult cases performed by experienced clinicians, such as ulcerative, scar, and/or large lesions, ESD for colonic lesions, management of hemorrhagic events, and closure of the perforated sites.

In conclusion, the ESD procedure using novel articulating devices is feasible, even by novices who have no experience of ESD, and these devices reduce the procedure time for novice endoscopists. The provisional effectiveness of the new system for experienced endoscopists needs further investigation, such as evaluation of the learning curve.

Competing interests: Drs. Nakadate, Nakamura, Arata, Ohuchida, and Hashizume have received research funding from Hogy Medical Co. Ltd., Japan.

Acknowledgment

The authors thank Prof. Takayuki Matsumoto, Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan, for his valuable comments.

• References

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Corresponding author

• References

• 1 Gotoda T, Kondo H, Ono H et al. A new endoscopic mucosal resection procedure using an insulation-tipped electrosurgical knife for rectal flat lesions: report of two cases. Gastrointest Endosc 1999; 50: 560-563
  CrossrefPubMedSearch in Google Scholar
• 2 Yahagi N, Fujishiro M, Kakushima N et al. Endoscopic submucosal dissection for early gastric cancer using the tip of an electrosurgical snare (thin type). Dig Endosc 2004; 16: 34-38
  CrossrefPubMedSearch in Google Scholar
• 3 Deprez PH, Bergman JJ, Meisner S et al. Current practice with endoscopic submucosal dissection in Europe: position statement from a panel of experts. Endoscopy 2010; 42: 853-858
  Search in Google Scholar
• 4 Fukami N. What we want for ESD is a second hand! Traction method. Gastrointest Endosc 2013; 78: 274-276
  CrossrefPubMedSearch in Google Scholar
• 5 Wang Z, Phee SJ, Lomanto D et al. Endoscopic submucosal dissection of gastric lesions by using a master and slave transluminal endoscopic robot: an animal survival study. Endoscopy 2012; 44: 690-694
  Thieme ConnectPubMedSearch in Google Scholar
• 6 Thompson CC, Ryou M, Soper NJ et al. Evaluation of a manually driven, multitasking platform for complex endoluminal and natural orifice transluminal endoscopic surgery applications (with video). Gastrointest Endosc 2009; 70: 121-125
  CrossrefPubMedSearch in Google Scholar
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  CrossrefPubMedSearch in Google Scholar
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