Preventing Hemorrhage After Endoscopic Submucosal Dissection Using Polysaccharide Hemostatic Materials

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

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.

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.

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.

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 converted to open surgery. The average age was 64 years. The location of the tumor in patients were as follows: Two cases were esophageal mucosal lesions, one case was a submucosal mass of the cardia, two cases of gastric mucosal lesions, 1 at the cardia and the other at the lesser curvature of the gastric antrum. The average operation duration was 49 min, and the average intraoperative blood loss was 7 mL. All patients resumed oral fluid consumption 24-48 h after surgery, and the average postoperative hospital stay was 4 days. All cases had negative tumor margins, and there were no perioperative complications. Every patient received regular follow-up, including gastroscopy. There were no gastric lesions (Figure 1) recurrences.

Figure 1: Gastroscopy of the patient demonstrated in the video intraoperative. (A) The red arrow indicates the mucosal lesions under blue light imaging (BLI). (B) The red arrow indicates the wound after ESD surgery. (C) The red arrow indicates the hemostasis of the lesion using the polysaccharide hemostatic material after surgery. (D) The red arrow indicates the reexamination of the gastroscopy image 6 months after surgery. Please click here to view a larger version of this figure.

Table 1: Clinical parameters of 5 cases.

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 also develop up to a week later^3,12. Severe bleeding may require blood transfusions or other medical interventions^3,12. Therefore, addressing delayed bleeding after ESD remains a clinical challenge. Polysaccharide hemostatic materials applied to the ulcer site through endoscopic delivery devices offer several advantages, including precise targeting, minimal tissue damage, and ease of use¹³. These materials represent a promising approach to the prevention and management of post-ESD bleeding.

Polysaccharide hemostatic materials are recognized as fast, safe, and efficient solutions for hemostasis, widely applied in surgical wounds and other areas⁸. As a plant-based material, they work by rapidly absorbing water from the blood, concentrating visible components (such as platelets, red blood cells, albumin, thrombin, fibrin, etc.) around the application site⁹. This process forms a viscous gel that acts as a protective barrier⁹. Simultaneously, by increasing the concentration of active blood components, these materials accelerate the activation of endogenous coagulation factors, significantly shortening coagulation time and achieving hemostasis within seconds¹⁰. The administration method involves local spraying, which is simple and requires minimal technical expertise or operational skill⁸. It can achieve complete coverage of the entire wound, which has significant advantages compared to other hemostatic methods¹¹. Furthermore, polysaccharide hemostatic materials are free of animal- or human-derived protein components, minimizing the risk of allergic reactions¹¹. In summary, polysaccharide hemostatic powder rapidly forms an "instant gel" and accelerates the physiological coagulation cascade, enabling quick and effective bleeding control^8,9,10,11. Polysaccharide-based hemostatic materials can be effectively used to control bleeding in a variety of surgical procedures, including neurosurgery, cardiothoracic surgery, general surgery, dermatological surgery, and urological interventions¹⁴.

Several technical considerations are worth noting when using microporous polysaccharide hemostatic powder. Firstly, apply the microporous polysaccharide hemostatic powder evenly over the ulcerated area to promote hemostasis. When using microporous polysaccharide hemostatic powder, attention should be paid to avoiding excessive use. Secondly, wait for a moment for the hemostatic powder to fully absorb the blood and form a clot. Thirdly, ensure that the material is not introduced into blood vessels, as this could lead to embolism. Lastly, pay attention to individual differences and allergies, and use with caution for patients with a history of allergies. All patients in this cohort received excellent oncological results with minimal invasiveness and reservation of stomach function, no positive tumor margin or recurrence, intraoperative blood loss of less than 10 mL, and an operation duration of less than 1 h. Postoperatively, all patients experienced enhanced recovery, and the average length of hospital stay was four days.

This study has several limitations. Theoretically, there may be risks of allergic reactions, embolism, and intestinal obstruction associated with the characteristics of polysaccharide hemostatic materials. However, none of the patients in this study experienced these complications, which may be attributed to the small sample size. To better assess the safety of polysaccharide hemostatic materials, a large-scale, multicenter study is necessary. In this study, we primarily focused on the role of polysaccharide hemostatic material as a sole intervention. However, electrocoagulation of the vessels was used as a routine step during the intervention phase, and no other preventive measures, such as metal clips, were applied. We believe that combining polysaccharide hemostatic material with other hemostatic techniques could be a promising area for future exploration. Additionally, while traditional hemostatic agents are relatively inexpensive, an economic analysis is needed to evaluate the cost-effectiveness of using polysaccharide hemostatic materials for managing postoperative bleeding in gastric ESD. The future development of advanced hemostatic materials is expected to further enhance the outcomes of ESD procedures.

The authors have nothing to disclose.

This work was supported by the Scientific research project of Health and Wellness Committee Changning District Shanghai (No. 2023QN30; No. 20214Y050), the Scientific research project of Health and Wellness Committee Changning District Shanghai (No. 20233010) and the Foundation of Shanghai Civil Aviation Hospital Project (No. 2024mhyk001).