Endoscopic Vital Nerve Staining in Gastrointestinal Diseases

In Vivo Evaluation of Tumor Neurogenesis in Gastrointestinal Diseases by Topical Submucosal Chromoendoscopy

In this study, methylene blue (MB) was used as vital nerve staining agent. During gastroenteroscopy, mucosal nerve staining was achieved by endoscopic submucosal injection of MB solution. To observe the staining of nerve fibers, neurons and glial cells in mucosa and submucosa, as well as the morphological changes, density differences and function of mucosal nerve tissues in different gastrointestinal lesions, in order to explore the role of endoscopic vital nerve staining in the diagnosis of gastrointestinal lesions.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Neoplasms; Abnormality of Enteric Nervous System Morphology
• Intervention / Treatment: Drug: Sodium thiosulfate and Methylene blue solution

Detailed Description

This study is a prospective experimental study. The baseline data of the patients were recorded objectively: sex, age, vital signs, body weight, some laboratory examination results (blood routine, liver function, blood coagulation function and electrolytes, etc.) and related medical history (comorbidities, treatment history and life history). Mucosal nerve staining was achieved by endoscopic submucosal injection of methylene blue (MB) solution. The following features were identified and then compared between normal, adenoma and neoplastic mucosa on magnifying endoscopy images in vivo: nerve morphology (straight or irregular), nerve diameter, branching patterns and nerve density. Immunohistochemistry was used to further confirm the presence and to study the morphology of neural structures (PGP9.5 and GFAP staining) and neural attribute (VIP, nNOS, TH, ChAT and SOM staining) on tumor, adenoma and normal mucosal sections.The aim of this study was to explore the role of MB based topical submucosal chromoendoscopy in the identification of neural architecture and special morphology in normal gastrointestinal mucosa, adenomas and malignant lesions during routine endoscopy.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yan Liu, MD; Phone Number: +8613911798288; Email: 13911798288@163.com
• Study Contact Backup: Name: Liang Wu, MD; Phone Number: +8618110076598; Email: wuliangdoc@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • The First Medical Center of Chinese PLA General Hospital
      • Contact: Yan Liu; Phone Number: +8613911798288; Email: 13911798288@163.com
      • Principal Investigator: Yan Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis or suspected diagnosis of one of the following common gastrointestinal diseases: chronic non-atrophic gastritis, chronic atrophic gastritis, gastric polyps, gastric early cancer, advanced gastric cancer; colonic polyps, colonic Melanosis, early colon cancer, advanced colon cancer
2. Written informed consent

Exclusion Criteria:

1. Those who are allergic to nerve dye components (such as methylene blue, etc.)
2. Complicated with cardiovascular and cerebrovascular diseases, or severely impaired liver, kidney and hematopoietic system.
3. Psychopath
4. There are hemorrhagic diseases
5. Platelet count < 50 × 10 ^ 9 / L
6. Those who are allergic to body mass are
7. Unable to tolerate or cooperate with endoscopy
8. Patients with serious complications, such as severe infection, gastrointestinal bleeding, obstruction and perforation, etc.
9. Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Endoscopic nerve staining; Methylene blue (MB) solution was used as nerve staining agent. Routine endoscopic submucosal injection of MB solution for mucosal nerve staining was used to identify and evaluate the neural architecture and special morphology of normal gastrointestinal mucosa, adenoma and malignant lesions.

Drug: Sodium thiosulfate and Methylene blue solution; Take a methylene blue injection (2ml:20mg), add 18ml distilled water and mix well. Add NaS2O3.5H2O800mg to the methylene blue solution 10ml, add 4 drops of dilute hydrochloric acid, heat the water bath until the dark blue fades, the solution is milky and turbid, adjust the PH to about 3.5. Put the prepared solution into a glass bottle with a rubber stopper, which is wrapped in tin foil, sealed and protected from light, and stored in a refrigerator at-20 ℃. It can be used after high-pressure sterilization before operation. Sodium thiosulfate-Methylene blue (DMB) staining solution was used as nerve staining agent. During gastroenteroscopy, DMB staining solution was locally sprayed on the surface of gastrointestinal lesion mucosa or injected into the lesion mucosa.; Other Names: NaS2O3.5H2O and Methylene blue injection (2ml:20mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphological characteristics of mucosal nerves in different gastrointestinal lesions	Mucosal nerve staining was achieved by endoscopic submucosal injection of MB solution. The following features were identified and then compared between normal, adenoma and neoplastic mucosa on magnifying endoscopy images in vivo: nerve morphology (straight or irregular), nerve diameter, branching patterns and nerve density.	Immediately after operation
Expression levels of PGP9.5, GFAP, VIP, nNOS, TH, ChAT and SOM of different gastrointestinal lesions	Immunohistochemistry was used to further confirm the presence and to study the morphology of neural structures (PGP9.5 and GFAP staining) and neural attribute (VIP, nNOS, TH, ChAT and SOM staining) on tumor, adenoma and normal mucosal sections.	1 to 3 days after operation

Collaborators and Investigators

• Sponsor: Affiliated Hospital to Academy of Military Medical Sciences
• Investigators: Principal Investigator: Yan Liu, MD, Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 15, 2022

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 30, 2022
• First Posted (Actual): February 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Endoscopy; Methylene blue; Gastrointestinal Neoplasms; Enteric Nervous System; Gastric nervous system; nerve staining
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Digestive System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protective Agents; Anti-Bacterial Agents; Antioxidants; Antidotes; Antitubercular Agents; Chelating Agents; Sequestering Agents; Methylene Blue; Sodium thiosulfate
• Other Study ID Numbers: Endoscopic nerve staining

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No