Advancements in endoscopic resection of subepithelial tumors: toward safer, recurrence-free techniques
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Subepithelial tumors (SETs) in the upper gastrointestinal tract are often incidentally found during esophagogastroduodenoscopy, and are observed in the form of a mass or protrusion covered by normal mucosa. They include all tumors except those originating from mucosal epithelial cells, and encompass benign tumors such as leiomyomas, cysts, fibromas, lipomas, hemangiomas, and lymphangiomas, as well as malignant tumors such as leiomyosarcomas, lymphomas, fibrosarcomas, and malignant melanomas.1 Endoscopic ultrasonography (EUS) is a highly valuable tool for diagnosing SETs that are difficult to distinguish using conventional endoscopy. It allows for three-dimensional or morphological assessment of the tumor, differentiation from extrinsic compression, and identification of the layer of origin of SETs. EUS findings are helpful in the diagnosis of extrinsic compression and provide detailed information on the exact size, originating layer, and shape of the subepithelial lesions. Additionally, the echogenicity pattern, whether homogeneous or heterogeneous, hyperechoic or hypoechoic, is valuable for the differential diagnosis of SETs and aids in planning future treatment strategies.2
Although EUS provides valuable information for the diagnosis of SETs, it has limitations because it is not a definitive histological diagnostic tool. There are often discrepancies between the diagnosis suggested by EUS and the final histopathological results.3 Therefore, histological examination is essential for a confirmatory diagnosis.4,5 With advancements in endoscopic techniques, endoscopic resection can now serve both diagnostic and therapeutic purposes for certain cases. For example, gastrointestinal stromal tumors (GISTs), which previously required surgical resection, can now be resected endoscopically. Although technically challenging, this approach is effective and relatively safe when performed by skilled endoscopists. Endoscopic resection of SETs is possible using various therapeutic techniques. In addition to endoscopic submucosal dissection (ESD), the standard method for endoscopic resection, submucosal tunnel endoscopic resection (STER), has been adapted from peroral endoscopic myotomy, originally developed for treating esophageal achalasia. Endoscopic full-thickness resection (EFTR) was introduced to achieve curative resection of SETs originating from the muscularis propria layer, overcoming the limitations of ESD and STER.6 However, major adverse events, such as perforation, are a concern following endoscopic resection of SETs. Adverse events, including perforation and pneumoperitoneum resulting in abdominal pain, occur in 6.0% to 19.7% in ESD, 4.7% to 26.3% in STER, and 10.4% to 12.5% in EFTR for SETs originating from the muscularis propria layer, such as GISTs.7 Although adverse events such as perforation, bleeding, pneumoperitoneum, and intra-abdominal infection that arise before or after endoscopic procedures are generally manageable with conservative treatment, in severe cases, emergency situations such as peritonitis may develop, necessitating close collaboration with surgeons.8 To mitigate such risks, endoscopists must have a high level of technical proficiency and be well-versed in the use of various tools that ensure safe procedures.
In a recent study, Akahoshi et al. evaluated the safety and efficacy of ESD using a clutch-cutter (ESD-CC) for the resection of esophagogastric SETs. They resected 18 SETs in 15 patients using the ESD-CC technique and evaluated short-term clinical outcomes, including en bloc resection rate, R0 resection rate, procedure time, and adverse event rate. The en bloc resection rate was 94.4% (17/18) and the R0 resection rate was 88.9% (16/18) with no major adverse events such as bleeding or perforation, demonstrating the safety and efficacy of the ESD-CC technique. Among the 18 resected tumors, 6 (33.3%) were neuroendocrine tumors, 6 (33.3%) were granular cell tumors, and 1 (5.6%) was a leiomyosarcoma, indicating that over two-thirds of the tumors had malignancy potential.9 The safe removal of these tumors without significant adverse events highlights the promising advantages of this technique. CC uses electrosurgical currents to grasp, pull, coagulate, and incise the target tissue. The authors suggested that ESD-CC offers safety advantages for endoscopic resection of SETs due to (1) accurate targeting through tissue fixation, (2) reliable hemostasis via tissue compression, (3) reduced electrical tissue injury to the muscularis propria by elevating the grasped tissue, and (4) minimal external electrical damage through external insulation.9 However, the fact that only one case involved a muscularis propria-originating SET suggests that further studies are needed to confirm the safety advantages of this technique, and long-term oncologic outcomes such as recurrence need to be shown in the future.10
The endoscopic resection of SETs in the upper gastrointestinal tract has moved beyond the question of feasibility and has entered an era demanding procedures that are “safe and recurrence-free”, techniques such as ESD-CC, along with various instruments and innovative methods, are expected to contribute remarkably to advancing this new era of refined endoscopic procedures.
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Conflicts of Interest
The authors have no potential conflicts of interest.
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Author Contributions
Conceptualization: all authors; Investigation: all authors; Supervision; MKJ; Validation: all authors; Writing–original draft: all authors; Writing–review & editing: all authors.