Submucosal tumours (SMTs) are a kind of lesion that originates below the mucosal layer (1). The incidence of gastric SMTs (G-SMTs) is lower than that of gastric mucosal tumours, and the related clinical symptoms appear later (2). G-SMTs generally do not produce clinical symptoms in the early stage of onset. Most of them are found by physical examination or for other reasons (3). Most G-SMTs are benign, and only some are malignant (4,5). The most common type of SMT is a gastrointestinal stromal tumour (GIST), followed by leiomyoma and ectopic pancreas (6). All GISTs have the potential for malignant transformation, with 10–30% becoming malignant tumours, so it is of great significance to diagnose and treat them early (7–9). GISTs are the most common mesenchymal tumours in the gastrointestinal tract and are widely located, especially in the stomach (10). In GISTs, endoscopic ultrasonography (EUS) showed hypoechoic lesions in the muscularis propria (MP) of the stomach (11). At present, the clinical treatment of G-SMTs, including GISTs, is mainly surgical resection (12).

With the development of endoscopic technology, early carcinoma of the digestive tract and some SMTs can now be resected endoscopically (13,14). In recent years, endoscopic submucosal dissection (ESD) has been widely used to treat gastrointestinal tumours, including SMTs (15–17). The feasibility, safety, and effectiveness of endoscopic therapy have been proven by many studies (18–22). ESD can completely remove gastric lesions with a diameter smaller than 3 cm, which is conducive to postoperative recovery and reduces body damage (23). If the tumours originate deep in the MP or adhere to the serosa layer, perforation and incomplete resection more easily occur during ESD (24,25). In this case, exposed endoscopic full-thickness resection (Eo-EFTR), derived from ESD, is used to address the problem and reduces the incidence of residual tumours (26,27). Based on ESD, Eo-EFTR is a treatment method involving completely removing the tumours by actively manufacturing digestive tract perforations and then closing the perforation sites (28). Eo-EFTR effectively removes the tissue of SMTs, reduces the risk of recurrence, and does not increase the incidence of complications (29,30).

The effect of surgical resection is easily affected by the location and size of the tumours (31). For example, the gastric fundus is a difficult area in which to operate because of its peculiar anatomical location. The lesions in the gastric fundus are difficult to access with the front end of the endoscope, especially when they have extraluminal growth (32–34). Therefore, our study selected a method called clip- and snare-assisted traction to promote the resection of SMTs. Clip- and snare-assisted traction is performed by clamping the edge of the cut lesion mucosa with the snare device and metallic clip and then pushing or pulling the snare device to achieve traction and expose the submucosa, providing a better surgical field of vision (35). Clip- and snare-assisted traction technology can effectively shorten the operation time and reduce complications (36).

Therefore, our study recorded and reported 20 consecutive cases to explore the safety and effectivity of Eo-EFTR with clip- and snare-assisted traction for G-SMTs in the fundus.

Most G-SMTs are identified by chance with endoscopy because of atypical symptoms (37). G-SMTs include GISTs, leiomyomas, calcifying fibroma lipoma, ectopic pancreas, and so on (38). Among these, GISTs are the most common mesenchymal tissue-derived tumours in the gastrointestinal tract (39). Nevertheless, GISTs have a certain probability of malignant transformation (7). It is estimated that the annual incidence of GIST is approximately 11–15 per million individuals (40,41). Therefore, early diagnosis and treatment are quite significant for GISTs. According to the National Comprehensive Cancer Network (NCCN) guidelines, EUS-guided fine-needle aspiration biopsy is the preferred method to use in the diagnosis of GISTs owing to the risk of tumour haemorrhage or rupture with other methods, such as endoscopic biopsy and hollow-core needle biopsy (42). GISTs can usually be successfully diagnosed based on histopathological morphology, immunohistochemistry, and molecular biology (43,44). The treatment for GISTs includes surgical treatment, drug treatment, and endoscopic treatment (43). When the diameter is ≥2 cm, surgical resection with or without targeted therapy is usually the first choice for GISTs. When the GIST diameter is <2 cm, the NCCN guidelines recommend active follow-up if there is no sign of high-risk malignant transformation (45). Studies in Japan and Europe suggest that once a GIST is confirmed histologically, resection should be performed regardless of the diameter (43,46,47).

With the development of endoscopic technology, endoscopic surgery has gradually begun to be applied to the treatment of SMTs such as GISTs. Most studies have shown that the en bloc resection rate for endoscopic resection of tumours originating from the MP can reach up to 96–100% (34,48–51). Compared with surgery, endoscopic treatment has the advantages of equivalent curative effects, less trauma, rapid recovery, and less impact on organ function (52). A retrospective study comparing the efficacy of surgery and endoscopic treatment showed that EFTR has the advantage of less blood loss, shorter bowel function restoration time, and lower hospital costs. The lower en bloc resection rate and higher tumour capsule rupture rate of EFTR should be notable (48,53). To date, the main indications for endoscopic treatment of GISTs include i) GISTs with tumour enlargement in a short time and a strong willingness for endoscopic treatment; ii) preoperative evaluation excluding lymph nodes or distant metastasis; and iii) low-risk GISTs with diameters between 2 and 5 cm (54). However, when the tumour diameter is less than 2 cm, regular follow-up may increase the economic burden and anxiety. Once the tumour suddenly increases, the opportunity for timely treatment may be lost, resulting in increased risks. Therefore, patients who cannot be followed up regularly may choose elective endoscopic resection (55). The commonly used endoscopic treatments for GISTs include ESD, submucosal tunnelling endoscopic resection, EFTR and laparoscopic and endoscopic cooperative surgery (56–58). EFTR should be selected when EUS and abdominal enhanced CT identify that the tumour originates from the MP adhering to the serosa layer or with the exophytic growth pattern (27,59). Therefore, 20 cases of gastric SMTs in the fundus originating from the MP were treated with Eo-EFTR. Due to the need for retroflexion of the endoscope when tumours are located in the gastric fundus, the gastroscope has difficulty getting close to the deep part of lesions, which increases the difficulty of complete resection (36,60,61). Given this, plenty of auxiliary traction options have been developed for use during endoscopic treatment, including the clip-with-line method, snare traction, clip-snare traction, grasping forceps traction, transparent cap traction, the suture loop needle-T tag tissue anchors method, the robot-assisted method, and magnetic anchor technology (62).

The advantages of the clip- and snare-assisted traction featured in our study consist of the following: i) Simple device: Clips and snares are common devices that are available in most hospitals. ii) Widespread application: Clip- and snare-assisted traction can be used in multiple parts of the gastrointestinal tract. For difficult parts, the surgical field of vision can be effectively expanded by applying auxiliary traction to improve the success rate of the operation. iii) Flexible traction: Different directions can be selected by pushing or pulling the snare. The snare can also be used to adjust the traction force to meet the different needs of the treatment (36,63).

However, there are also some knacks and pitfalls in the clip- and snare-assisted traction. First, the operation of clip- and snare-assisted traction is difficult, which requires endoscopists to have rich experience and competent operative ability. Second, the traction force is affected by the hardness of the snare, and the softer snare is not easy to change the direction of the tumour during the operation. Finally, excessive traction force or clamping too little gastric mucosa will easily cause the titanium clip to fall off from the mucosa, consuming the operation time and increasing mucosal damage (64).

Compared with traditional ESD, EFTR involves an iatrogenic perforation. The larger the postoperative wound is, the slower the wound healing. Therefore, it is critical to effectively close the lesion defect (65). In this study, two methods were used to repair the perforation. When the perforation was <1 cm, conventional metallic clip closure was used. When the defect was ≥1 cm, purse-string suturing was selected. The advantages of purse-string suturing are as follows: i) It is suitable for perforations with a relatively large diameter. ii) It is easily controlled. iii) The spacing between metallic clips is more than 5 mm, which can reduce the need for additional clips. iv) By tightening the nylon rope, mucosal aggregation can promote wound closure without leaving gaps and prevent the leakage of gastrointestinal contents into the abdominal cavity (66,67). There are other methods of defect closure after Eo-EFTR, such as over-the-scope clips (OTSCs), which are suitable for closing larger defects after Eo-EFTR than endoscopic purse-string sutures, but the equipment is expensive and limited to lesions <3 cm, resulting in limitations to their clinical application (68–73). Omental patches, fibrin glue, endoscopic puncture suture devices, and the overstitch system are also used to repair therapeutic perforations (74–77).

The operation time in our study was 62.9 min (range 25–130 min). Tan et al reported that the mean procedure time for conventional EFTR (n=32) for GISTs was 69.1±27.0 min (78). In addition, Hu et al showed a procedure time of 130.6±51.9 min in the traditional EFTR group (n=20) (61), indicating that our study had a shorter operative time than other studies that did not use traction. Li et al found that the mean time for EFTR assisted by dental floss and a haemoclip for G-SMTs in the fundus was 44.2±24.4 min (79). In a retrospective study consisting of 13 patients treated with thread-traction-assisted EFTR, the mean procedure time was 71.9±30.5 min (80). Effective traction methods can reduce the difficulty of endoscopic surgery, reduce the operation time to a certain extent, and reduce the risk of complications, while the efficacy and safety of surgery are also affected by the experience of the endoscopist and the size and location of the lesions (81,82).

The main complications of EFTR were delayed bleeding and perforation. Related studies have reported that complications after EFTR also include peritonitis, abdominal abscess, subcutaneous emphysema, and mediastinal emphysema (59). Granata A et al reported that the pooled estimates for overall delayed bleeding and delayed perforation were 0.14 and 0.14%, respectively (83). Appropriate haemostasis measures and defect repair are important means to preventing postoperative bleeding and perforations. Additionally, the time of resumption of a normal diet, gastrointestinal decompression, and the use of PPIs and antibiotics also have a certain impact on the occurrence of postoperative complications (84). When conservative treatment is ineffective, endoscopic exploration should be carried out in a timely manner to effectively treat bleeding points or perforation sites. If endoscopic treatment is ineffective, further surgery is required (59). Most studies reported no major complications in EFTR (51,61,73,85). None of our patients experienced delayed perforation or haemorrhage. In a study reported by Tan et al where 32 patients with tumours originating from the MP were treated with EFTR, delayed bleeding was seen in 1 patient, and abdominal pain with low-grade fever was seen in 4 patients (78). Another study including 192 patients by Li et al (79) reported that pneumoperitoneum was seen in 7 (3.6%) patients, hydrothorax was seen in 6 (3.1%) patients, and post-EFTR electrocoagulation syndrome was seen in 18 (9.4%). No significant pneumoperitoneum occurred in our study. The reasons may be: i) The use of carbon dioxide insufflation during the operation could reduce the incidence of pneumoperitoneum; ii) The exposure time of abdominal cavity is controlled by endoscopists. iii) During the exposure of the patient's abdominal cavity, the endoscopy physician will try to reduce the gas injection to avoid excessive gas entering the abdominal cavity. In our study, after the endoscopic suture, the patients' abdomen will be palpated to assess the abdominal tension. If the tension is judged to be high, a Veress needle will be used for decompression.

The postoperative pathology of the 19 patients was GISTs, including 18 cases with mitotic images <5/50 HPF and 1 case with mitotic images of 8/50 HPF. Medium- and high-risk patients are advised to undergo additional treatment, such as molecular targeted therapy or additional surgery, according to the guidelines (43). The NIH grading standard divides the risk of postoperative recurrence into four grades by considering the size, location, and mitotic image of the patient's tumour (86). In our study, 16 cases were very low risk, 2 cases were low risk, and 1 case was medium risk. The patient with a moderate risk was given imatinib targeted therapy and followed up regularly. The last follow-up showed that the tumour had healed well without signs of recurrence or distant metastasis.

The success rate, complete resection rate, and R0 resection rate in this study were 100%. There was no conversion to surgery, and there were no serious adverse events or complications during or after the operation. During postoperative follow-up, all patients healed well without recurrence or distant metastasis. Our results show the feasibility, safety, and effectiveness of Eo-EFTR with clip- and snare-assisted traction for G-SMTs in the fundus. Most of the studies compared the effectiveness of EFTR and surgery, showing the advantages of EFTR, such as a shorter operation time and faster cure time (53,87). Some studies have indicated that when the lesions are too large (more than 3 cm) or there are contraindications (distant metastasis), the recurrence rate and complete resection rate of endoscopic treatment are lower than those of surgery (53). At this time, surgery is a more appropriate choice.

This study had several limitations. First of all, it is a single-centre and retrospective study, which may cause selection bias and retrospective bias. Secondly, this study was descriptive and lacked a control group. Due to the difficulty of traditional Eo-EFTR in the gastric fundus, it is difficult to collect cases in the control group. So more data need to be further collected in the future. Moreover, the object of this study are the G-SMTs, which does not involve gastric cancer cases. If possible, auxiliary traction can be applied to the endoscopic resection of gastric cancers in the future, and the effectiveness and safety of endoscopic therapy combined with auxiliary traction in gastric cancer cases can be evaluated. Finally, a prospective or retrospective study with a larger sample size is needed to further confirm the feasibility and efficacy of Eo-EFTR with clip- and snare-assisted traction for G-SMTs in the fundus, as the sample size of this study is small.

After this study, we will conduct a retrospective case-control study to compare the traditional and assisted traction Eo-EFTR and identify the specific advantages (such as less operative time and complications) of traction methods in Eo-EFTR through data analysis. In addition, we will also learn and study other traction methods, such as multiple clips- and snare-assisted traction, clip-with-line method, etc. Through the collection of data, the characteristics of different traction methods will be compared to find a more suitable and effective traction method for Eo-EFTR.

In conclusion, Eo-EFTR with clip- and snare-assisted traction appears to be a relatively safe and effective treatment for gastric SMTs in the fundus. The traction method can shorten the operative time to a certain extent and don't increase the incidence of complications.