DOI: https://doi.org/10.21203/rs.3.rs-2442778/v1
The incidence of colorectal cancer is high. Early detection, diagnosis and treatment are particularly important. Endoscopic submucosal dissection (ESD) is used to treat early-stage cancer, and the ESD-assisted magnetic anchor technique (MAT) has greatly changed the operating experience of endoscopists. The present study aimed to determine the feasibility of MAT-assisted ESD for the treatment of early-stage colorectal cancer. We designed and manufactured a magnetic anchor device consisting of a target magnet (TM), an anchor magnet (AM), and a soft-tissue clip. The TM was fixed on the diseased mucosa by means of the soft-tissue clip, and the AM was located exterior to the colorectal sample. By changing the position of the AM, the TM was pulled to fully expose the mucosal surface and maintain sufficient tissue tension to assist the ESD. MAT-assisted ESD was successfully completed in all 12 isolated colorectal samples. During the operation, there were no instances of TM detachment or mucosal tears. The interaction between the magnets provided sufficient mucosal tissue tension and a clear mucosal dissection surface, which greatly changed the ESD experience. MAT-assisted ESD is a feasible procedure for the treatment of early-stage colorectal cancer and has great potential for clinical application.
According to a 2020 World Health Organization report [1], there were 1,931,590 new cases of colorectal cancer in 2020, making colorectal cancer the third most common type of cancer in the world, after breast cancer and lung cancer. Additionally, with 935,173 deaths attributed to it, colorectal cancer is the second leading cause of cancer-related deaths. The current literature [2] indicates that more than 86% of patients with colorectal cancer under the age of 50 are symptomatic at the time of diagnosis, and this is associated with more advanced cancer at diagnosis and worse outcomes. The most important predictor of survival after a cancer diagnosis is the stage of the disease [3]. For example, the 5-year relative survival rate of patients with colorectal cancer is 65%; however, the 5-year survival rate of patients with stage-IV colorectal cancer drops to only 12% [4]. Therefore, the early detection and early treatment of colorectal cancer are crucially important. Screening for early-stage colorectal cancer is an important method to improve the low survival rate of colorectal cancer [5–8].
Endoscopic submucosal dissection (ESD) was first used for the non-surgical treatment of early gastric cancer. In recent years, the indications of ESD have expanded to include colorectal lesions, and this technique is particularly attractive as a non-surgical treatment for early-stage colorectal tumors [9]. ESD originated from endoscopic mucosal resection (EMR), and is an advanced endoscopic dissection technique. EMR has been shown to be sufficient for the treatment of most colorectal lesions [10, 11]. Compared with EMR, ESD has a higher complete-resection rate, a higher cure rate, and a lower local tumor-recurrence rate [12–14]. However, due to the lack of a “second hand” to provide countertraction during intraluminal endoscopic surgery [15], there is unclear exposure of the mucosal dissection surface and insufficient tissue tension during the operation [16, 17], which makes ESD a more difficult procedure than EMR, with a longer learning curve, longer operation time, and higher risk of complications (e.g., bleeding, perforation, and stricture) [18, 19]. The magnetic anchor technique (MAT) has been used to provide countertraction during endoscopic dissection, and MAT-assisted ESD (MAT-ESD) has achieved initial success in early gastric cancer [20, 21], proving its safety and efficacy. In the present study, we aimed to determine the feasibility of MAT-ESD for the treatment of early-stage colorectal cancer.
This ex vivo animal experimental study was approved by the animal experiment ethics committee of Xi’an Jiaotong University (approval number: XJTULAC2019-1006). The experimental procedure met the ethical requirements for the care and use of experimental animals. 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).
Based on previous experiments performed by our team, the present experiment was performed on isolated colorectal samples obtained from euthanized Bama miniature pigs. The ages of the pigs ranged from 5 to 15 years, and their weight ranged from 38 to 60 kg. Half the animals were female, and half were male. In total, we used 12 isolated colorectal samples, with the anal part preserved to facilitate the identification of the anatomical location of the colorectum.
We used a self-designed magnetic anchor device. The device was composed of a target magnet (TM), an anchor magnet (AM), and a soft-tissue clip. The TM and AM were machined from N series sintered NdFeB permanent magnet materials (Fig. 1). The surfaces of both magnets were protected by nickel plating, and the magnets were uniformly saturated in the axial direction. The soft-tissue clip was manufactured by Micro-Tech Co. Ltd. (Nanjing, China), and was mainly used to connect with the TM and fix the TM on the diseased mucosa.
The TM weighed 0.946 g. Considering the special colorectal environment, we designed the TM with a core cylinder with a diameter of 4.2 mm, a height of 4.6 mm, and a surface field strength of 2,400 GS on the working surface. The magnetic core jacket had a U-shaped permalloy shell with a thickness of 0.7 mm. The bottom of the permalloy shell was attached to a tail-hanging structure with a 1-mm-wide hole, through which a silk thread was passed to connect the TM with the soft-tissue clip and fix the TM on the diseased mucosa.
The AM weighed 2077 g. The AM was a cylinder with a height of 140 mm and a diameter of 50 mm. The maximum surface field strength at both ends of the magnet could reach 6,000 GS. To avoid mutual attraction between the AM and any ferromagnetic objects during use, the AM was covered with a U-shaped resin shell with a thickness of 5 mm.
After obtaining the isolated colorectum, we ligated the proximal end of the anus with a silk thread. A colonoscope was introduced into the colorectum through the anus and inflated to observe whether the ligature at the proximal end of the anus fell off, whether the colorectal mucosa was intact, and whether the lumen was unobstructed.
An electrocautery was inserted through the operating port of the colonoscope. The colonoscope and electrocautery were inserted together into the intestinal cavity through the anus. According to the field of view provided by the colonoscope, an annular mucosal lesion with a diameter of 1 cm to be dissected was marked with the electrocautery.
The soft-tissue clip was extended proximally from the operating port of the colonoscope and out of the distal end of the colonoscope. A silk thread was passed through the small hole at the end of the TM and connected to the soft-tissue clip. It should be noted that this connection should be neither too loose nor too tight, otherwise the opening and closing of the soft-tissue clip will be affected. The connection between the TM and the soft-tissue clip is shown in Fig. 2.
The colonoscope, soft-tissue clip, and TM were delivered from the anus into the diseased mucosa. The soft-tissue clip was retained on the diseased mucosa by using the operating handle of the soft-tissue clip. The AM was slowly moved toward the external colorectal wall, to pull the TM. ESD was assisted by changing the position of the AM until the mucosal dissection surface was well exposed, and the tension on the diseased mucosal tissue was maintained.
We successfully completed MAT-ESD in all 12 cases. Before the surgery, the obtained isolated colorectal samples were confirmed to be anatomically complete (Fig. 3a). The ligature did not fall off; the mucosa appeared smooth and intact under the colonoscope; and the range of the mucosal lesion was successfully marked (Fig. 3b). The TM and soft-tissue clip were tightly connected, and the TM did not affect the opening and closing of the soft-tissue clip. During the surgery, the TM and soft-tissue clip were successfully advanced toward the mucosal lesion by means of the endoscope. The soft tissue was clamped tightly on the lesioned mucosa without falling off (Fig. 3c). The external AM could directly attract the TM, thereby providing sufficient mucosal tension and a clear peeling surface, without causing mucosal avulsion or tearing (Fig. 3d). Finally, the mucosa was completely peeled off without perforation (Fig. 3e, f).
The surgery was successfully completed with the magnetic anchor device that we designed and manufactured. Throughout the procedure, the interaction force between the magnets provided the required mucosal exposure and mucosal tension for the surgery. In addition, by changing the position of the AM, the magnitude and direction of the pulling force on the TM could be flexibly changed to obtain the most suitable mucosal surface exposure and tension. This experiment showed that MAT-ESD is a potentially feasible procedure for the treatment of early-stage colorectal cancer.
ESD has become the standard of care for early-stage cancer. This endoscopic procedure can enable the early detection and diagnosis of cancer and improve the survival rate of patients. However, ESD also has many disadvantages, such as a difficult operation procedure, a long learning curve, a long operation time, and a higher risk of complications (e.g., bleeding, perforation, and stricture) [18, 19]. To overcome these shortcomings, a series of assistive technologies have emerged, such as the percutaneous traction-assisted method [22], S–O clip traction-assisted method [23], mucosal forceps channel-assisted method [24], clip-band traction-assisted method [25], sinker system traction-assisted method [26], ‘medical ring’ traction-assisted method [27], dual-scope endoscopy [28] (which is a novel flexible endoscopic surgical platform) [29], and a Master And Slave Transluminal Endoscopic Robot (MASTER) [30]. Although the above procedures can assist endoscopic operations, they cannot flexibly adjust and change the traction direction and traction force on the mucosa, and some endoscopic platform technologies are difficult to apply on a large scale in clinical practice.
MAT is a type of magnetic surgery, and is an ESD-assist technology with broad application prospects. The application of the mutual attraction between magnets has great potential in controlling the direction of traction and the magnitude of the traction force. The application of this technique not only reduces surgical trauma and interference between surgical instruments but also improves the exposure of the surgical field and the maneuverability of the surgical instruments [31]. The magnetic materials originally used for magnetic anchor devices were mainly electromagnets and permanent magnets [32], but because electromagnets are large, bulky objects, permanent magnets are now widely used for the special structure of the digestive tract [33].
MAT-ESD has been applied in the treatment of early-stage colorectal cancer [34]. Our magnetic device not only meets the magnetic requirements of surgery but also minimizes the volume of the TM and allows it to adapt to the special structure of the alimentary canal provided the ratio of the diameter to the height of the bottom of the TM cylinder is 1:2–1:1.5. The TM is covered with a permalloy shell, which can eliminate the interference of other instruments during surgery. In addition, a round hole with a diameter of 1 mm is present in the tail of the TM, which is convenient for connecting the TM to the soft-tissue clip.
Some limitations of this experiment must be acknowledged. First, the experiment was an ex vivo experiment, which cannot evaluate the tolerance of the operation in vivo and the risk of postoperative complications, such as bleeding and strictures. Second, the influence of the abdominal wall thickness, abdominal circumference, lesion location, and lesion size on the surgery could not be assessed. However, this study successfully completed the ex vivo experiments using an optimized MAT, thereby laying the foundation for subsequent in vivo animal experiments and human clinical trials.
The experiment demonstrated the feasibility of MAT-ESD for the treatment of early-stage colorectal cancer. The magnetic force between the TM and AM provided the endoscopist with a “second hand,” which greatly changed the operation experience under the endoscope. Thus, MAT-ESD has great potential for clinical application.
Acknowledgements
We appreciated all people who participate in or help with this research.
Author contributions
Conceptualization: Y. L., X. Y.; Data curation: M. P., M. Z.; Formal analysis: M. P., M. Z.; Investigation: M. P., M. Z.; Methodology: M. P., X. Y.; Project administration: X. Y.; Supervision: Y. L., X. Y.; Validation: M. P., M. Z., Y. L., X. Y.; Writing – original draft: M. P., M. Z.; Writing- review & editing: Y. L., X. Y.
Data availability statement
All generated raw data from the current study can be available from the corresponding author on reasonable request.
Additional Information
The authors declare that they have no competing interests.