Preventing Hemorrhage After Endoscopic Submucosal Dissection Using Polysaccharide Hemostatic Materials

Summary

Here, we present a protocol for using polysaccharide hemostatic materials to manage hemorrhage after endoscopic submucosal dissection (ESD).

Abstract

Endoscopic submucosal dissection (ESD) is a minimally invasive procedure that is widely used for the treatment of early gastric cancer and certain submucosal tumors. ESD often results in large artificial ulcers, leading to a risk of intraoperative and postoperative bleeding, which is a significant complication. Traditional methods to address this bleeding include proton pump inhibitors (PPIs), local hemostatic sprays, hemostatic clips, electrocoagulation, etc. However, this research introduces polysaccharide-based materials as a novel hemostatic solution, demonstrating their effectiveness in preventing upper gastrointestinal tract bleeding associated with ESD. The results of our study, focusing on both gastric and esophageal lesions, suggest that the microporous polysaccharide hemostatic material is effective in preventing bleeding following upper gastrointestinal tract ESD procedures. The key benefits of polysaccharide hemostatic materials include biocompatibility, no immune risk, excellent absorbability, and fast hemostatic speed. Clinical results from the study indicate that patients treated with these materials did not experience delayed bleeding, and follow-up gastroscopy showed good wound healing without negative impacts on the artificial ulcer. This suggests that polysaccharide hemostatic materials are a safe and effective option for patients undergoing gastric ESD surgery.

Introduction

With the development of endoscopic technology, ESD has been widely used in the minimally invasive treatment of early gastric cancer and submucosal tumors¹. This technology can completely remove large areas of lesions and has a low residual and recurrence rate². The main complications of gastric ESD surgery include perforation, bleeding, infection, and stenosis³. Among them, delayed bleeding after ESD surgery is considered one of the most serious and challenging complications of ESD⁴. Despite the use of preventive measures like proton pump inhibitors (PPIs), intraoperative electrocoagulation, and metal clips, the incidence of postoperative bleeding remains a concern; the incidence of gastric ESD postoperative bleeding is still around 0.4%⁵. Therefore, it highlights the need for continued research and development of more effective strategies to prevent this complication.

Polysaccharide hemostatic materials, as natural polymer materials without animal or human-derived ingredients, have the advantages of low cost, good biocompatibility, biodegradability, and absorption⁶. The main components are cellulose, starch, and chitosan⁷. Polysaccharide hemostatic materials can quickly bind with components in the blood, such as coagulation factors and platelets, forming an "instant gel" that seals vascular breaks while simultaneously activating the endogenous coagulation pathway, thereby achieving rapid hemostasis^8,9. Multiple studies have shown that polysaccharide hemostatic materials can be used as a hemostatic method to treat gastrointestinal bleeding and have good clinical evaluation¹⁰. The polysaccharide hemostatic materials can effectively treat non-variceal gastrointestinal bleeding, as well as intraoperative and postoperative bleeding during gastrointestinal endoscopic treatment¹¹. Polysaccharide hemostatic materials are sprayed onto the ulcer wound after ESD surgery through endoscopic channels using a delivery device, which has the advantages of accurate positioning, minimal tissue damage, and easy operation¹¹. This research has demonstrated that polysaccharide hemostatic materials can be used as a hemostatic method for gastric and esophageal ESD surgery to prevent upper gastrointestinal tract bleeding, and it has achieved good clinical results. The use of polysaccharide hemostatic materials in ESD surgeries has shown promising results, with patients experiencing no delayed bleeding and exhibiting good wound healing upon follow-up gastroscopy. This suggests that these materials are not only effective in preventing bleeding but also safe for patients, as they do not interfere with the healing of artificial ulcers.

Protocol

This study was approved by the Shanghai Civil Aviation Hospital Committee (Ethics Approval No: 2023-06), and written informed consent was obtained from all participants prior to their inclusion in the study.

1. Preoperative preparation

1. Confirm that the patient has fasted for 8 h before the procedure.
2. Administer intravenous fluids to prevent hypoglycemia and maintain electrolyte balance.
3. Set up for tracheal intubation to facilitate general anesthesia.
4. Give proton pump inhibitors 1 h prior to the surgery to mitigate bleeding risk.

2. Gastroscopic exploration

1. Perform gastroscopy under general anesthesia with tracheal intubation.
2. Inflate the gastric cavity with gas.
3. Explore and rinse the mucosa and confirm the tumor's location.
   NOTE: Before the surgery, the scope, nature, and invasion depth of the lesions are determined by combining staining and magnifying endoscopic examination.

3. Scope marking and exposure of lesions

1. Use a disposable high-frequency cutting knife (golden knife) to clearly define and mark the lesion boundary, maintaining a 5 mm distance from the lesion edge.
2. Perform multi-point submucosal injections outside the marked boundary to lift and separate the lesion from the muscularis propria.
3. Inject glycerol fructose, rouge, and adrenaline beneath the lesion for optimal lifting.
   NOTE: Proper lifting of the lesion is crucial to avoid damage to the muscularis propria, thereby reducing complications like perforation and bleeding. All ESD procedures were performed by a well-experienced gastroenterologist with extensive training and practice in performing upper gastrointestinal ESDs. Specifically, the gastroenterologist had more than 10 years of experience performing ESD and had completed over 150 procedures annually.

4. Endoscopic submucosal dissection

1. Use the disposable high-frequency cutting knife to incise the mucosa around the lesion and penetrate the submucosa.
2. Re-lift the base of the lesion, then carefully separate and peel off the lesion completely.
3. Utilize hot biopsy forceps for local electrocoagulation hemostasis during dissection.
   NOTE: Assess lesion lifting before dissection. Maintain sufficient elevation to completely remove the lesion in one attempt. The settings used during the ESD procedures were as follows: Mode: Endocut (for cutting): 40 w, effect 3, cutting width 3, cutting interval time 3.

5. Closure of the gastric wall defect

1. Spray hemostatic material directly onto the postoperative wounds, ensuring full coverage.
2. Connect the device containing the hemostatic material to the powder dispenser.
3. Insert the front end of the powder dispenser into petroleum jelly, ensuring that 1 cm of the powder dispenser's tip is coated with the jelly.
4. Pass the tube of the powder dispenser through the biopsy channel of the endoscope to reach the wound site.
5. Under direct vision, spray 1 g or 2 g of polysaccharide hemostatic powder onto the wound and observe for 5 min.
   NOTE: Coating 1 cm of the powder dispenser's tip with petroleum jelly helps prevent the hemostatic powder from coming into contact with any liquid and solidifying prematurely, which could render it ineffective before use. The settings used during the procedures were as follows: Mode: Forced Coagulation (for hemostasis): 40 w, effect 2

6. Surgical wound check

1. Inspect the wound surface to confirm the absence of active bleeding.
2. Completely remove gas and fluid from the stomach.
   NOTE: Rinse excess hemostatic material if over-applied.

7. Specimen harvest

1. For large lesions, use an endoscopic basket to withdraw the specimen from the stomach.

8. Specimen management

1. After the procedure, visually confirm the condition of the specimen.
2. Use tweezers and stainless steel needles to spread the specimen flat and affix it to a mounting plate.
3. Record the specimen size through photography.
4. Completely immerse the specimen in a 4% neutral formalin solution for fixation.
   NOTE: Promptly fix the specimen post-extraction to prevent tissue ischemia and drying, which can affect pathological analysis.

9. Postoperative recovery

1. Use continuous proton pump inhibitor infusion to promote healing and minimize bleeding risk.
2. Ensure the patient remains in bed for 24 h post-surgery with electrocardiogram (ECG) monitoring.

Results

On May 2024, 5 patients undergoing esophageal and gastric mucosal ESD surgery received polysaccharide hemostatic materials for local hemostasis of wounds (Table 1). In this study, 1 g of microporous polysaccharide hemostatic material was uniformly applied to each ulcer. However, for ulcers located in the cardia, 2 g of the material was used, due to the abundant blood vessels in this region. Every esophageal and gastric mucosal lesion diagnosis was confirmed through pathological examination. None were con...

Discussion

Although endoscopic submucosal dissection (ESD) is considered a relatively safe treatment method, it is not without potential risks and complications³. These include bleeding, perforation, infection, anesthesia-related risks, postoperative pain, etc³. Bleeding is a particularly significant concern, especially in cases involving large or deeply located tumors⁴. Postoperative bleeding is most likely to occur within 24 h after surgery, although it can a...

Materials

Name	Company	Catalog Number	Comments
Argon electrode	ERBE Elektromedizin GmbH	20132-177
Digestive endoscopy argon plasma coagulation (APC) knife system	ERBE Elektromedizin GmbH	VIO200
Disposable high-frequency cutting knife	Micro-Tech (Nanjing) CO, Ltd	MK-T-2-195
Endoscopic therapy device	Fujifilm (China) Investment Co., Ltd	BL-7000
Gastroscope	Fujifilm (China) Investment Co., Ltd	EG-760CT
Hot biopsy forceps	Nanwei Medical Technology Co., Ltd	N/A
Petroleum jelly	Qingdao Jinqi Biotechnology Co., Ltd	N/A
Polysaccharide hemostatic powder	Jiangsu Deviceland Medical Devices Co., LTD	N/A
Powder dispenser	Jiangsu Deviceland Medical Devices Co., LTD	N/A