DOI: https://doi.org/10.21203/rs.3.rs-1907935/v1
Esophageal cancer has high incidence globally and is often diagnosed at an advanced stage. This study intends to explore the feasibility and applicability of magnetic anchor technique (MAT)-assisted ESD for early esophageal cancer. Isolated pig esophagus was used as the experimental model, and the magnetic anchor device was designed by us. The soft tissue clip and the target magnet (TM) were connected by a thin wire through a small hole at the tail end of the TM. Under gastroscopic guidance, the soft tissue clip was clamped to the edge of the lesioned mucosa, which was marked in advance. By changing the position of the anchor magnet (AM) outside the esophagus, the pulling force and pulling direction of the TM could be changed, thus exposing the mucosal peeling surface and assisting the ESD. Herein, MAT-assisted ESD was successfully completed for 10 isolated esophageal putative mucosal lesions. During the entire experiment, the TM remained firmly connected with the soft tissue clip and did not affect the opening, closing, and release of the soft tissue clip. The interaction between the TM and AM could provide sufficient tissue tension and completely expose the mucosa, which greatly assists the surgeon with the operation. There was no avulsion of the mucosa, and mucosal lesions were intact when peeled. We found MAT-assisted ESD safe and feasible for early esophageal cancer. It could greatly improve the endoscopic operation experience and showed good clinical application prospects.
According to GLOBOCAN 2020 data, esophageal cancer is among the most common cancers worldwide; it ranks seventh in terms of incidence and is the sixth leading cause of cancer deaths1. In most cases, early esophageal cancer and precancerous lesions can be cured by minimally invasive endoscopic treatment, and the 5-year survival rate can reach 95%2. However, patients with advanced esophageal cancer have a low quality of life and poor prognosis, and their overall 5-year survival rate is < 20%2, 3. Because esophageal cancer is usually not diagnosed until an advanced stage, there are few options available to extend life expectancy beyond several months4. Therefore, it is very important to improve the screening methods for early esophageal cancer.
Endoscopic resection includes endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). ESD was developed on the basis of EMR in Japan and has become the standard of care for managing early tumors of the esophagus, stomach, and colon5. Compared to EMR, ESD can offer better outcomes, lower morbidity, lower cost, higher curative resection rates, and lower recurrence rates5, 6. ESD is performed using an endoscope, which makes the procedure technically challenging7–8. Consequently, ESD has a steep learning curve, longer surgical time, higher risk, and more complications (e.g., bleeding, pain, perforation, and stricture) than EMR9. In addition, for effective and safe dissection, adequate tissue tension and a clear anatomical plane are important10. To overcome these abovementioned challenges associated with the use of ESD, scholars have proposed several auxiliary methods of pulling mucosa, such as percutaneous traction-assisted method11, sinker system traction-assisted method12, mucosal forceps channel-assisted method13, S–O clip traction-assisted method14, “medical ring” traction-assisted method15, a Master and Slave Transluminal Endoscopic Robot (MASTER)16, a novel flexible endoscopic surgical platform17, and dual-scope endoscopic dissection method18. Although these methods play a certain role in ESD operation, their flexibility in controlling mucosal traction direction and traction force is poor, and some endoscopic platforms are still difficult to be clinically used on large scale.
Magnetic anchor guided-endoscopic submucosal dissection (MAG-ESD) is a new type of assistive technology that functions using a special traction force, which confers its potential advantages over other assistive technologies5. In 2004, Kobayashi T et al. 8 applied the principle of magnetic anchor technique to ESD and reported that this technique significantly improved endoscopic operation. MAG-ESD provides dynamic tissue contraction independent of the endoscope, thus mimicking the surgeon’s two hands5. A magnetic anchor comprises three parts: a hand-made magnetic weight made up of magnetic stainless steel, micro forceps, and a connecting thread that connects a hand-made magnetic weight made up of magnetic stainless steel with micro forceps19. Two types of magnets can be used: electromagnets and permanent magnets19. Presently, MAG-ESD is known to have achieved significant results in gastric cancer20 and colorectal cancer21, proving its safety and feasibility for promoting ESD of early cancer. In this article, we will elaborate on the use of MAT-assisted ESD in early esophageal cancer.
Animals
This was an in-vitro animal experiment performed on isolated esophaguses of 10 pigs. The pigs were obtained from Experimental Animal Center of Xi’an Jiaotong University. We used the pigs that were euthanized after other experimental projects of our team. Notably, since these projects were not related to the digestive system, they had no effect on the physiological function and anatomical structure of the esophagus, and the pigs remained suitable for this present experiment. All pigs were Bama miniature pigs aged 1-2 years and weighed 20-25 kg. The male: female ratio of the pigs was 1:1. Besides, the experiment was approved by the animal experiment ethics committee of Xi’an Jiaotong University (NO. XJTULAC2019-1006). All animal experiments complied with the ARRIVE guidelines and were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (eighth edition, 2011).
Magnetic anchor device
The magnetic anchor device used in this experiment was designed by us and fabricated by Shaanxi Jinshan Electric Co., Ltd. It comprises three parts: the target magnet (TM), the anchor magnet (AM), and the soft tissue clip. TM is a “passive force” part located in the esophagus, and its shape and size are limited by the digestive tract’s lumen. The surface field at both ends of the magnet is 3000 GS. The permalloy shell is U-shaped with a 1-mm wall thickness. The diameter of the cylindrical magnetic core is 4 mm, and the height is 5.5 mm. In addition, the tail end also has a tail hanging structure. A tail hanging structure with a 1-mm hole can be connected to the soft tissue clip using a silk wire. The AM is the “active force” part and is located outside the isolated esophagus; its shape and size are less limited since it is not placed inside the lumen. The AM is cylindrical with a diameter of 50 mm and a height of 140 mm, and the surface magnetic field intensity at both ends of the magnet is 6500 GS. In addition, to avoid mutual attraction between the AM and ferromagnetic objects during use, the AM is covered with a layer of a U-shaped resin shell with a thickness of 5 mm. The TM and AM are made of N48 sintered NdFeB permanent magnet material; they are nickel-plated on the surface. The soft tissue clip, also known as the harmony clip (Nanwei Medical Technology Co., LTD.), can be closed to fix the TM on the pathological mucosa (shown in Fig. 1). The variation of magnetic force with distance between AM and TM was measured using an electronic universal testing machine (UTM6202, Shenzhen Suns Technology Stock, shown in Fig. 2).
Operational process
The isolated pig esophagus was placed on the experimental platform, and the lower segment of the esophagus was clamped using an intestinal forceps. Then, a gastroscope was entered into the upper esophagus, and the esophagus was inflated properly to observe the air tightness and integrity of the esophageal mucosa. The esophageal mucosa lesion area was marked using an electric knife through the gastroscopic operation hole. Then, the electric knife was retracted, and a soft tissue clip was inserted into the gastroscope operating hole and extended from the front end of the gastroscope. Then, the TM was fixed on the soft tissue clip with a thin wire through the small hole at the end of the TM such that the opening and closing of the soft tissue clip were not affected. The gastroscope together with the soft tissue clip and the TM was delivered into the esophageal cavity, and the handle of the soft tissue clip was manipulated in a way that the TM and the soft tissue clip were fixed on the mucosa of the lesion. The AM was then slowly placed outside the esophagus on the other side of the mucosal lesion. Under gastroscopy, the TM was slowly sucked up by the AM. By changing the relative position of the magnets and the distance between the AM and TM, the traction direction of and the pulling force exerted on the TM can be adjusted to clearly display and assist the peeling of the pathological mucosa under endoscopy.
The experiment involving the use of MAT-assisted ESD in isolated pig esophaguses was successfully completed. After the gastroscope successfully entered the esophageal cavity before the operation, the isolated esophageal mucosa visibly complete and light pink with good air tightness of the esophageal cavity (shown in Fig. 3A) and complete marking of the diseased mucosa (shown in Fig. 3B). During the entire operation, with the help of gastroscopy, the soft tissue clip and the TM entered the isolated esophagus together. The connection between the two was firm, and the TM did not affect the opening, closing, or release of the soft tissue clip. At the same time, the soft tissue clip could smoothly clamp the esophageal mucosa without easily falling off (shown in Fig. 3C). When the AM was brought close to the other side of the pathological mucosa, the attraction between the AM and TM caused the TM to get pulled, thus exposing the mucosal dissection surface (shown in Fig. 3D). By slowly adjusting the position of the AM, the traction direction and tension of the TM could be changed to maintain good tissue tension on the surface of mucosal dissection and reduce the difficulty of mucosal dissection for the operator under the gastroscopy. Finally, the mucosal surface was completely exfoliated (shown in Fig. 3E, 3F), and no adverse event, such as the shedding of soft tissue clips or mucosal tearing, occurred.
In this study, we determined that MAT-ESD is a feasible and safe technique in an in vitro model. A magnetic anchor device designed by us was used to assist endoscopic esophageal submucosal dissection with special traction between the AM and TM. During the entire operation, the TM remained firmly connected to the soft tissue clip without affecting the opening and closing of the soft tissue clip. The TM was manipulated using the AM to expose the mucosal dissection surface and maintain the tissue tension of the mucosa. This helped the surgeon complete the operation, and no shedding of soft tissue clips or mucosal tearing occurred in the entire process. This assistive technology can greatly improve the operator’s experience and shorten the operation time.
Magnetic surgery (MS) is an emerging surgical technique that uses the “non-contact” magnetic field force between magnets and uses specially designed magnetic devices to achieve several functions, such as cavity organ anastomosis and reconstruction as well as tissue and organ traction and exposure22. Currently, this is a clinical application system mainly comprising the magnetic compression technique, magnetic anchor technique (MAT), magnetic navigation technique, magnetic levitation technique, magnetic tracer technique, and magnetic drive technique (MDT)22. MS has been implemented in gastrointestinal anastomosis reconstruction23, vascular anastomosis reconstruction24, and recanalization of biliary tract occlusion after liver transplantation25. Being one of the core clinical techniques of MS, MAT is a non-contact spatial anchor technique involving an AM and a TM which works via the magnetic attraction between magnets or of magnets with paramagnetic materials22. At present, MAT has been used in general surgery26] gynecology27, urology28, and thoracic surgery29. In addition to the application of MAT in organ traction under laparoscopic and thoracoscopic surgeries, it has shown significant application in assisted endoscopic surgery as well30.
A significant differentiating advantage of our research compared to other research on this subject is that we have optimized the structure of the TM. Because the TM is located in the digestive tract, the connection between the TM and the soft tissue clip needs to be considered in the design, and the volume of the TM should be minimized while ensuring it meets the magnetic requirements. In this study, we used magnetic shielding technology, wherein the magnetic attraction of the non-working surface could be significantly reduced by adding a permalloy shell to the TM to eliminate the interference of the TM during endoscopic operation. In addition, the tail hanging structure of the permalloy shell allows for a connection of the target magnet with the soft tissue clip. According to different anchor positions, MAT can be divided into external anchor technology and internal anchor technology, with both having different applications. This study uses the internal anchor technology, which provides endoscope-independent traction by primarily creating an invisible hand for the operator. Unlike other auxiliary methods, MAT-ESD does not interfere with ESD operation and provides dynamic traction. Herein, the AM can be moved to manipulate the TM such that it exposes the mucosal dissection surface and provides the tissue tension required for endoscopic resection.
As an in-vitro experiment, the condition of this experiment is different from those of internal animal experiments and clinical experiments. We could not assess the risk of postoperative complications, such as bleeding, perforation, and stenosis. Nevertheless, we believe that the results of this study lay a solid foundation for internal animal experiments, particularly in terms of the operation process, the precise control of the pulling direction, and the pulling force between the AM and the TM.
This experiment showed that MAT has significant advantages and can be used for endoscopic esophageal submucosal dissection. With the development of further internal animal experiments and the accumulation of operational experience, this technique has broad clinical application prospects.
Acknowledgements
This work was supported by the Key Research & Development Program-Social Development of Shaanxi Province of China (2021SF-163) and the Innovation Capability Support Plan of Shaanxi Province of China (2020KJXX-022).
Author Contribution:
Conception and design, Y.L. and X.Y.; Performed the research and acquired the data, M.P., M.Z., and S.X.; Manuscript writing, M.P., and M.Z.; Manuscript revision, Y.L. and X.Y.; Final approval of manuscript, All authors.
Competing interests
The authors declare no competing interests.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
The reporting in the manuscript follows the recommendations in the ARRIVE guidelines.