Evaluation of the Effectiveness of Longitudinal Incision for Endoscopic Submucosal Excavation of Gastric Subepithelial Lesions

Summary

This protocol describes longitudinal incision endoscopic submucosal excavation, a technique designed to facilitate the resection and defect closure of gastric subepithelial lesions.

Abstract

Endoscopic submucosal excavation (ESE) is an established technique for managing gastric subepithelial lesions (SELs). This article presents a detailed protocol for an improved technique: longitudinal incision ESE. The core innovation involves making a straight-line incision along the central axis of the lesion, rather than a conventional circumferential one, followed by lesion retrieval and primary defect closure with metal clips. The protocol's feasibility and technical outcomes are supported by a retrospective study of 52 patients, where the longitudinal incision group (n=21) showed a 100% procedural success rate and a significantly shorter mean operation time compared to the conventional circular incision group (51.43 ± 5.56 min vs. 70.00 ± 6.96 min, P=0.0179). Furthermore, the longitudinal incision appeared to reduce the necessity for advanced closure devices (5% vs. 28%) and was associated with a low complication profile. This protocol highlights that the longitudinal incision technique may be a safe, effective, and feasible treatment for patients with gastric intracavitary SELs ≤ 2 cm, potentially offering distinct practical advantages in operative efficiency, defect management, and consumable usage.

Introduction

Subepithelial lesions (SELs) of the gastrointestinal tract originate from the deep layers beneath the mucosa^1,2. Although SELs can be found throughout the digestive tract, they are most commonly detected in the stomach during routine endoscopy^3,4,5. Histologically, most SELs are benign⁶; however, neuroendocrine tumors (NETs) and gastrointestinal stromal tumors (GISTs) possess malignant potential^2,7. With advances in endoscopic technology and increased public health awareness, the detection rate of SELs has risen significantly. Standardized endoscopic minimally invasive treatment can improve patients' quality of life, alleviate the burden on families and society, and conserve medical resources. According to the National Comprehensive Cancer Network (NCCN) guidelines for GIST management, lesions smaller than 2 cm without high-risk features may not require immediate resection⁷. In contrast, the European Society for Medical Oncology (ESMO) recommends excision of all GISTs—even those under 2 cm in diameter⁸. Nevertheless, long-term follow-up entails substantial economic and time costs, and a growing number of small lesions have been shown to harbor malignant potential^2,7. Therefore, surgical resection is increasingly preferred when feasible. Current endoscopic treatments for SELs include snare resection, endoscopic submucosal excavation (ESE), submucosal tunnel endoscopic resection (STER), endoscopic full-thickness resection (EFTR), and natural orifice transluminal endoscopic surgery (NOTES)^2,9,10,11,12. Among these, STER requires the creation of a submucosal tunnel, which limits its application to favorable anatomical locations like the esophagus and cardia¹¹. EFTR, while versatile, involves full-thickness wall resection and presents considerable technical difficulties, particularly in achieving reliable defect closure¹¹. On the other hand, ESE is considered feasible for intracavitary SELs ≤ 2 cm. Conventional ESE follows the principles of endoscopic submucosal dissection (ESD), employing a circular incision around the lesion to remove the overlying mucosa, fully expose the lesion, and achieve complete resection⁹. Nonetheless, the substantial mucosal defects created by conventional ESE pose a significant challenge for closure¹³, leading to extended operative times^9,14 and greater utilization of closure devices¹⁵. The circular incision creates a defect with circumferential tension, which often requires multiple clips or advanced closure techniques. In contrast, longitudinal incision follows the natural axial alignment of the gastrointestinal tract, where tissue mobility and biomechanical properties may facilitate easier apposition of the defect edges with less tension^10,11,14. Therefore, there is a clinical need to develop a more convenient, straightforward, effective, and safe endoscopic closure technique.

In this study, we propose an improved technique, longitudinal incision endoscopic submucosal excavation for gastric SELs, in which a longitudinal incision is made through the mucosa and submucosa above the lesion, followed by lesion removal and defect closure with metal clips. The aim of this study is to evaluate the feasibility and technical outcomes of longitudinal incision ESE.

Protocol

This study retrospectively analyzed patients diagnosed with gastric SELs who underwent endoscopic surgery at the Digestive Endoscopy Center. The study was approved by the Ethics Committee of the First Affiliated Hospital of Jinan University (approval number: KY-2025-323), complies with the Declaration of Helsinki, and all patients have provided informed consent.

NOTE: Figure 1 shows a typical endoscopic image of gastric SELs.

1. Patient selection

1. Inclusion criteria: Include patients with a preoperative diagnosis of gastric SELs by endoscopic ultrasound (EUS) or computed tomography (CT); maximum lesion diameter ≤ 2 cm; absence of high-risk endoscopic features (including irregular border, ulceration, heterogeneous echogenicity, cystic spaces, or hyperechoic nodules).
2. Exclusion criteria: Exclude patients with lesions preoperatively assessed to involve the serosal layer or significantly protrude outward, making endoscopic treatment unfeasible; evidence of lymph node or distant metastasis; severe primary diseases of the heart, cerebrovascular system, liver, kidneys, or hematopoietic system; severe gastrointestinal bleeding or life-threatening perforation requiring immediate surgical intervention.

2. Patient preparation

1. Conduct preoperative evaluations
   1. Perform blood tests, including a complete blood count, coagulation profile, liver and kidney function tests, electrolyte panel, and screenings for infectious diseases (Hepatitis B/C, HIV, Syphilis). These assess bleeding risk, coagulation status, and the patient's general health.
   2. Obtain an electrocardiogram to evaluate cardiac function and rule out severe arrhythmia or other contraindications to surgery.
   3. Acquire a chest X-ray​ to establish a baseline assessment of cardiopulmonary status.
2. Preoperative informed consent
   1. The attending physician must explain in detail the procedure's necessity, process, and expected outcomes to the patient and family. Discuss potential risks and complications, such as bleeding, perforation, infection, and incomplete resection or recurrence of the lesion.
   2. Have the patient or their legal representative sign the procedural and anesthesia consent forms​ after ensuring they fully understand the information provided.
3. Prepare the patient
   1. Instruct the patient to fast​ for 8-12 h and refrain from clear liquids for 4-6 h prior to the procedure to ensure an empty stomach.
4. Operating setting and anesthesia
   1. Position the patient in the left lateral decubitus position under general anesthesia with endotracheal intubation. Use carbon dioxide for endoscopic insufflation during the operation.

3. Surgical methods^16,17

1. For the improved group, perform endoscopic resection using a novel longitudinal incision. For the conventional group, perform endoscopic resection using the conventional circular incision.
2. Marking
   1. Mark several dots along the lesion margin using a single-use electrosurgical knife, forming a circular pattern 3-5 mm outside the lesion edge to define the resection boundaries. Set the high-frequency electrosurgical system to: Forced Coag, Effect 2, 20 W.
      CAUTION: Improper use of the high-frequency electrosurgical system may cause serious injury to patients and staff. Always inspect the return electrode and cable before each use.
3. Submucosal injection
   1. Prepare a mixture of 250 mL of normal saline and 2 mL of 0.2% indigo rouge.
   2. Using a 23G single-use injector with a 4 mm needle, perform the injection from distal to proximal at an angle of 15° to 30°. Place injections just outside the pre-marked dots to achieve maximum elevation directly adjacent to the markings.
   3. Advance the needle deep into the tissue, then inject while slowly withdrawing to ensure the tip remains within the mid-submucosal layer. The mucosal surface should elevate rapidly, uniformly, and persistently, forming a smooth, dome-shaped mucosal elevation. This ensures adequate lifting of the lesion from the underlying muscle layer, creating a safety cushion to prevent perforation.
      NOTE: The blue dye enhances visualization of the submucosal layer throughout the procedure.
4. Mucosal incision
   1. Improved group: Make a longitudinal incision through the mucosa and submucosa along the central axis of the lesion using the single-use electrosurgical knife, ensuring it surpasses the lesion's entire longitudinal dimension.
   2. Conventional group: Make a circular incision approximately 3 mm outside the pre-marked points. Fully incise the submucosal tissue to expose the lesion.
   3. Set the high-frequency electrosurgical system to: Endo Cut Q, Effect 3, Cut Duration 2, Cut Interval 4; Forced Coag, Effect 2, 50 W.
5. Submucosal excavation
   1. Carefully dissect and separate the submucosal connective tissue beneath the lesion using the electrosurgical knife.
   2. Fully expose the lesion and completely free it from its attachments, while preserving the underlying muscle layer as much as possible.
   3. If bleeding is detected during the separation process, use the knife to coagulate minor bleeding vessels.
6. Hemostasis
   1. Thoroughly inspect the resection defect for active bleeding or visible vessels. Treat any bleeding points or high-risk vessels with the single-use electrosurgical hemostatic forceps to prevent delayed bleeding. Set the high-frequency electrosurgical system to: Soft Coag, Effect 2, 80 W.
7. Defect closure
   1. First, moderately aspirate intragastric gas to approximate the defect edges and reduce the tissue gap for clipping. Engage the mucosal edge on the proximal side of the defect with one jaw of the clip and then hook the distal mucosal edge with the opposite jaw. Close the clip while maintaining continuous suction.
   2. Next, apply clips sequentially to approximate the mucosal edges until the entire defect is fully apposed.
   3. For larger defects, consider combined techniques using a single-use ligating device with clips for complete closure. If hemostasis or defect closure is ineffective, refer the patient for laparoscopic intervention.
8. Specimen management
   1. Retrieve the resected specimen using a snare or retrieval net. Figure 2 and Figure 3 show the endoscopic resection procedure.
   2. Fix the specimens in 10% formaldehyde solution for 24h and send for pathological examination, including HE staining and immunohistochemistry (for CD117, CD34, DOG-1, Ki-67, actin, S-100, desmin, vimentin, and other indicators).
      CAUTION: Formaldehyde is a hazardous chemical used for tissue fixation. It is a known carcinogen, sensitizer, and irritant. Handle formaldehyde solutions only in a well-ventilated area.
   3. Use closed-system containers for specimen transfer and storage whenever possible. Wear appropriate chemical-resistant gloves when handling formaldehyde.

4. Postoperative management

1. Monitor vital signs, symptoms, and abdominal signs postoperatively.
2. Maintain patient fasting for the first day, then provide a semiliquid diet for 3 days, and gradually advance to a normal diet within 2 weeks.
3. For patients who experienced perforation or full-thickness resection during surgery, advise fasting for 3 days postoperatively and resume oral intake gradually based on clinical condition.
4. Routinely administer proton pump inhibitors (PPIs) and gastric mucosal protectants intravenously.
5. Administer antibiotics in cases of intraoperative perforation or full-thickness resection to prevent infection.
6. Provide symptomatic treatment for postoperative pain, fever, or other complaints.

Results

Demographic and clinical characteristics of patients
Quantitative data are presented as mean ± standard deviation, and between-group comparisons were made using the t-test. Qualitative data are presented as numbers (percentages) and compared using the Chi-squared test or Fisher's exact test, as appropriate. A two-tailed p-value < 0.05 was considered statistically significant.

A total of 52 patients were included in this study. There were 21 patients in the improved grou...

Discussion

The critical determinants of success in endoscopic treatment for SELs are the completeness of lesion resection, the ability to effectively close the resulting defect, and the capacity to manage complications such as bleeding and perforation endoscopically^9,18. This study focused on comparing a conventional circular incision ESE with a modified longitudinal incision ESE.

The key procedural innovation of the longitudinal incision techniq...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Disposable Distal Attachment	Olympus, Japan	D-201-11804	Transparent cap for mucosal dissection and traction
Endoscope	Fujinon, Japan	EG-580RD	Therapeutic gastroscope with a 3.2 mm working channel
Endoscope host: Fujinon	Fujinon, Japan	ELUXEO 7000	Video processor system
High-frequency Electrosurgical System	Erbe Elektromedizin GmbH, Germany	VIO 200D	Used for all cutting and coagulation procedures, including mucosal incision, submucosal dissection, and hemostasis. Specific modes (Endo Cut Q, Forced Coag, Soft Coag) and power settings were applied as per the protocol.
Indigo Rouge	Nanwei Medical, China	MTN-DYZ-15	0.2% indigo carmine solution for submucosal staining
Metal clip	Anri Medical, China	AMH-HCG-165-135	Rotatable; Defect closure
Single Use Electrosurgical Hemostatic Forceps	Olympus, Japan	FD-410LR	Hemostasis and defect managemen
Single Use Electrosurgical Knife	Olympus, Japan	KD-655L;KD-611L	Include needle knife and IT knife; Mucosal incision and submucosal dissection
Single Use Injector	Olympus, Japan	NM-400U-0423	23G, 4mm needle length for submucosal injection
Single Use Ligating Device	Olympus, Japan	HX-400U-30	Nylon loop for large defect closure or purse-string suture