Efficacy and safety of endoscopic subserosal dissection treatment for gastrointetinal submucosal tumors in the upper gastrointestinal tract

Abstract

Objective

To investigate the safety and efficacy of endoscopic subserosal dissection for patients with submucosal tumors in the upper gastrointestinal tract.

Methods

This retrospective single-center study included 16 patients who underwent ESSD. All patients were enrolled from July 2018 to Dec 2021. Parameters such as demographics, size, resection margin, complications, pathological features, procedure time and follow-up were investigated and analyzed.

Results

Our study achieved 100% en bloc resection and 100% R0 resection. The most common location was the corpus with a mean tumor size of 2.78 ± 1.56 cm. The mean age, procedure time, were 53.4 ± 10.3 years, 85.31 ± 46.64 min respectively. Acocording to National Institutes of Health classification, 7 (13, 53.85%), 5 (13, 38.46%) ,and 1 (13, 7.69%) objects belonged to the very low, low, and intermediate classification, respectively. Immunohistochemistry results showed a 100% positive rate of CD34, DOG-1, CD117, and Ki67. A mean follow-up of 9.3 ± 2.5 months showed no recurrence or metastasis.

Conclusions

ESSD is effective and safe surgical procedure for curative removal of gastrointestinal submucosal tumors in the upper gastrointestinal tract, and it can be preferred for patients with no metastasis.

Submucosal tumors (SMT) are solid tumors that develop from the tissue beneath the epithelium of the digestive tract. Common types include leiomyoma, stromal tumor, cyst, neuroendocrine tumor, ectopic pancreas, and lipoma [1,2,3]. With the advancement of endoscopic technology, particularly in ESD-related technologies, an increasing number of early digestive tumors can now be treated endoscopically [4]. Endoscopic submucosal dissection (ESD) has been utilized in the minimally invasive treatment of gastric submucosal tumors. However, its drawback lies in ensuring complete resection of the tumor body and capsule, preventing residual tumor cells, and avoiding intraoperative perforation. Consequently, endoscopic full-thickness resection (EFR) has emerged. EFR can completely remove GIST originating in the deep gastric mucosa, effectively preventing residual tumor cells, and is particularly suitable for treating GIST originating in the muscularis propria of the stomach [5, 6]. Given that the tumor is located in the muscularis propria, with only a serous membrane covering it and the abdominal cavity, complete resection of the tumor often results in digestive tract perforation. Perforation is a significant complication during these procedures, especially when removing SETs originating from the muscularis propria layer. Once digestive tract perforation occurs, it can lead to pneumoperitoneum or even peritonitis. Retaining the serous layer can effectively prevent these complications. In this study, we introduce endoscopic subserosal dissection (ESSD) for the treatment of upper GI SETs originating from the muscularis propria layer and evaluate the efficacy, safety, and clinical outcomes of this resection technique [7].

Materials and methods

Patients

16 patients with submucosal tumors of intrinsic muscular origin who were resected by ESSD were retrospectively analyzed from July 2018 to Dec 2021. All patients underwent ultrasound endoscopy and CT examination of the upper abdomen before surgery to exclude hemangioma and submucosal bulge caused by extracavity compression, cardio-cerebrovascular diseases, coagulopathy, and organ dysfunction were excluded. Post-abdominal surgery and tumors with irregular margins were excluded.

ESSD device

ESSD was performed by an experienced endoscopist. A single-channel endoscope (Q-260 J, Olympus) was used during procedures. A transparent cap (ND-201-11802, Olympus) was attached to the front of the endoscope. Other equipments and accessories included a high-frequency electronic cutting device (Vio 300D, Erbe, Tubingen, Germany), an injection needle (NM-4 L-1, Olympus), a dual knife (KD-650 L, Olympus), an insulated-tip knife (KD-611 L, IT2, Olympus), hemostatic clips (Sure clip, Microin-vasion company, China), a snare (SD-230U-20, Olympus), hot biopsy forceps (FD-410LR, Olympus), and a carbon dioxide insufflator (Olympus).

ESSD procedure

Surgical Procedure: The Dual knife was utilized to mark the area surrounding the lesion, followed by a submucosal injection of 100 mL of normal saline, 2 mL of acacia blue, and 1 mL of epinephrine. Once the lesion was elevated, a circular incision was made around it using the Dual knife. The lesions were then carefully separated layer by layer, with any small blood vessels encountered during the procedure being electrocoagulated to control bleeding. As the lesion approached the serosa, the area between the tumor and the serosa was adequately injected, and the serosa was meticulously separated from the tumor using the Dual knife or IT knife, ensuring the cutting edge was kept close to the tumor to avoid damage to the serous membrane layer. Following complete separation of the tumor body, the wound surface was closed using nylon sutures and hemoclips (Fig. 1).

Fig. 1

The Endoscopic ultrasonography results and ESSD procedure. A&B Endoscopic ultrasound showed homogeneous hypoechoic lesions, and elastic imaging suggested a slightly hard texture. C: White light endoscope showed gastric body bulge lesions with smooth surface. D: Exfoliate the lesion and expose the tumor. E&F: Exposed serous membrane layer. G&H: performed pouch suture on the lesion with hemostatic clamp

Postoperative treatment and follow-up

The gastric tube was placed under the endoscope and placed in the gastric antrum after after ESSD surgery. The patient was placed in a semi-recumbent position after fasting, intermittent negative pressure drainage, prevention of infection, suppression of gastric acid secretion, and fluid replacement. Observe for delayed bleeding, abdominal infections, etc. Generally, the stomach tube is removed on the 5th day of surgery, and the liquid and semi-liquid diets are gradually eaten. Endoscopic follow-up was performed 1 month later to observe the wound healing status. The patients were reexamined once every 3, 6, and 12 months after the operation. Afterwards, patients were advised to reexamine each year.

Pathological diagnosis

Postoperative tissue specimens were stained for histopathology and immunohistochemistry such as CD34、CD117、DOG-1 and Ki-67 (Fig. 2).

Fig. 2

Immunohistochemistry of CD34(A)、CD117(B)、DOG-1(C) and Ki-67(D)

Results

Surgical treatment

Patient information is summarized in Table 1. 16 lesions were treated with ESSD. The male-to-female ratio was 10/6. The median age was 58 (range 33–69) years. Mean size (the maximum diameter) of resected tumors was 2.78 ± 1.56 (range 1.50-7.00) cm. The location of the lesions were fundus(6/16), corpus(9/16), and stomach angle(1/16). The median ESSD operation time was 85.31 ± 46.64 (range 34–191)min. None of the patients had immediate or delayed bleeding during the procedures. Minor bleeding occurred in all cases, but hemostasis was achieved by nonsurgical endoscopic treatment, such as hot biopsy forceps electrocoagulation, argon plasma coagulation, and hemoclipping. None of the patients required a blood transfusion. Open surgery repair was not required.

Table 1 Information of the research object

Complications

In these cases, the serosal membrane was intact, no delayed bleeding, no infection, no secondary cardia tear, no iatrogenic metastasis perforation, and no transfer to surgery.

Pathological type

The immunohistochemistry of 16 patients was consistent with the diagnosis of stromal tumors. 13 cases were gastrointestinal stromal tumors (GIST), and were all spindle cell subtypes, and 7/5 of 12 cases showed very low grade and low grade. The risk of invasion, 1 case was moderate risk of invasion.

Postoperative follow-up

All patients were followed up for 12–24 months. All patients underwent the initial endoscopic follow-up 3 months after the operation, and also received CT examination of the upper abdomen. The follow-up showed that the wounds were basically healed, and there were 3 patients with residual metal clips on the wounds. During the follow-up period, no local tumor recurrence and abdominal metastasis were found in all patients.

Discussion

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors originating from the muscularis layer of the gastrointestinal tract, mainly composed of spindle cells and epithelial cells, accounting for 1-4% of gastrointestinal tumors [8]. These tumors are not sensitive to radiotherapy and chemotherapy, and surgical resection remains the primary treatment method [9]. Traditionally, surgical resection was the main approach for treating GISTs, but it was associated with high costs and significant trauma, impacting the patients’ post-surgery quality of life. However, in recent years, endoscopic treatment technology, particularly endoscopic submucosal dissection (ESD) and related technologies, has been rapidly advancing, providing new options for patients with GISTs [5, 6]. EMD (Endoscopic Mucosal Dissection) involves the dissection of the mucosal layer of the gastrointestinal tract, which is the innermost layer of the digestive system [10]. This technique is typically used for the removal of superficial lesions and has the advantage of preserving the deeper submucosal layer. The emergence of endoscopic full-thickness resection (EFR) has allowed for complete endoscopic resection of gastrointestinal submucosal tumors with a diameter of less than 5 cm, and various improved versions of EFR have since been developed. Nonetheless, EFR has inherent drawbacks. Due to its full-thickness resection nature, EFR may compromise the integrity of the digestive tract, leading to perforation, which can result in tumor spread within the abdominal cavity during surgery or induce peritonitis due to abdominal infection [11,12,13,14]. Additionally, perforation can cause an increase in abdominal cavity pressure and related symptoms such as abdominal distension and discomfort. Endoscopic muscularis dissection (EMD) have technical limitations for the resection of gastric neoplasms with mixed or exophytic patterns [15]. In response to these challenges, endoscopic subserosal dissection (ESSD) has emerged as an alternative approach [7, 14]. In our study, all 16 lesions were successfully and completely resected using ESSD, and none required surgical intervention. This demonstrates the safety and effectiveness of ESSD in completely removing tumors. Furthermore, ESSD allows for the acquisition of complete tumor specimens, providing accurate and reliable pathological data for prognosis assessment and follow-up.

In our endoscopy center, we have identified several key operating points that should be carefully considered during ESSD treatment, based on our experience and literature data. These include thorough pre-surgery evaluation, careful selection of pre-incision, precise identification of tumor borders, meticulous peeling along the subserosa (using subserosal injection with Acacia blue, IT knife, Dual knife), effective management of bleeding during stripping (using appropriate hemostatic forceps and parameter selection), complete removal of the tumor, and proper wound closure (using nylon ring purse, metal clip, etc.).

ESSD offers several advantages over other treatment methods, including complete serous membrane, a clear visual field during operation, no risk of abdominal organ damage, no risk of secondary abdominal infection, and no risk of tumor metastasis to the abdominal cavity. Compared to EFR, ESSD may take longer for tumor dissection, but wound closure time is shorter, wound closure quality is higher, postoperative recovery is faster, postoperative fasting time is shorter, less antibiotics are required, and hospital stays are shorter.

While there are few literature reports on ESSD treatment for GIST, the results of this study suggest that ESSD is a safe, effective, and reliable treatment option for GISTs. However, this study has some limitations, including the fact that ESSD is a relatively new technology and this was a single-center retrospective study with a small sample size. Therefore, large-scale, multi-center randomized controlled studies are needed in the future to further evaluate the long-term efficacy and safety of ESSD. As the technology continues to mature, ESSD is expected to further expand the space for minimally invasive treatment of gastrointestinal tumors.