CC BY-NC-ND 4.0 · Endosc Int Open 2023; 11(11): E1026-E1034
DOI: 10.1055/a-2161-2100
Original article

Development of a hybrid hydrogel for submucosal injection in endoscopic resection of gastrointestinal neoplasm: From laboratory to clinical trial

Jui-Wen Kang
1   Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Ringgold ID: RIN38026)
2   Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
,
Po-Jun Chen
1   Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Ringgold ID: RIN38026)
2   Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
,
Chiung-Yu Chen
1   Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Ringgold ID: RIN38026)
,
Guillermo Riley
1   Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Ringgold ID: RIN38026)
2   Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
,
Yao-Sheng Wang
1   Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Ringgold ID: RIN38026)
2   Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
,
Hsin-Yu Kuo
1   Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Ringgold ID: RIN38026)
2   Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
,
1   Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Ringgold ID: RIN38026)
› Author Affiliations
Supported by: National Science and Technology Council MOST 106-3114-8-006-002
Supported by: National Cheng Kung University Hospital NCKUH-11204024
Supported by: Ministry of Health and Welfare MOHW 112-TDU-B-211-144003
Supported by: National Science and Technology Council MOST 107-2823-8-006-003

TRIAL REGISTRATION: Registration number (trial ID): NCT 03321396, Trial registry: ClinicalTrials.gov (http://www.clinicaltrials.gov/), Type of Study: Interventional (Clinical Trial)


Abstract

Background and study aims Submucosal injection solution is essential for successful endoscopic resection of the early gastrointestinal tumor. We evaluated a new endoscopic hydrogel for submucosal injection and its clinical feasibility.

Patients and methods A hydrogel (AceGel) containing 0.4% sodium alginate and 2% calcium lactate was developed for ex vivo and animal studies. Subsequently, a prospective, single-arm study was conducted to assess its feasibility and safety in humans. Patients with gastrointestinal neoplasms undergoing endoscopic resection were enrolled. All patients underwent endoscopic surveillance after 4 weeks and outpatient follow-up at week 6. Afterward, they received endoscopic follow-up according to the medical routine.

Results In the ex vivo experiments, the submucosal elevation height of AceGel was equivalent to sodium hyaluronate and superior to saline or glycerol. Animal studies showed that the excised wounds healed well without surrounding tissue damage. Twelve patients participated in the clinical trial, including three, two, and seven patients with esophageal, gastric, and colonic lesions, respectively. The mean neoplasm size and submucosal injection volumes were 24.0±8.6 mm and 22.8±19.9 mL, respectively. All patients had adequate wound healing on 4-week surveillance endoscopy, and none had serious adverse events during 6-week follow-up. Moreover, endoscopic follow-up showed complete wound healing after 6 to 46 months without local mucosal inflammation in all patients.

Conclusions AceGel is good for endoscopic submucosal injection and demonstrated its usefulness in durable mucosal elevation for endoscopic therapy in preclinical tests. This clinical trial shows its safety and feasibility in all participating patients.

Graphical abstract

Supporting information



Publication History

Received: 15 June 2023

Accepted after revision: 25 August 2023

Accepted Manuscript online:
28 August 2023

Article published online:
09 November 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Draganov PV, Wang AY, Othman MO. et al. AGA Institute Clinical Practice Update: Endoscopic Submucosal Dissection in the United States. Clin Gastroenterol Hepatol 2019; 17: 16-25.e11
  • 2 Pimentel-Nunes P, Libânio D, Bastiaansen BAJ. et al. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy 2022; 54: 591-622
  • 3 Tanaka S, Kashida H, Saito Y. et al. Japan Gastroenterological Endoscopy Society guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection. Dig Endosc 2020; 32: 219-239
  • 4 Ono H, Yao K, Fujishiro M. et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition). Dig Endosc 2021; 33: 4-20
  • 5 Nishizawa T, Yahagi N. Endoscopic mucosal resection and endoscopic submucosal dissection: technique and new directions. Curr Opin Gastroenterol 2017; 33: 315-319
  • 6 Abe S, Bhatt A, Saito Y. The journey to develop the ideal submucosal injection solution for endoscopic submucosal dissection. Gastrointest Endosc 2021; 93: 514-516
  • 7 Maple JT, Abu Dayyeh BK, Chauhan SS. et al. Endoscopic submucosal dissection. Gastrointest Endosc 2015; 81: 1311-1325
  • 8 Uraoka T, Saito Y, Yamamoto K. et al. Submucosal injection solution for gastrointestinal tract endoscopic mucosal resection and endoscopic submucosal dissection. Drug Des Devel Ther 2009; 2: 131-138
  • 9 Landin MD, Guerrón AD. Endoscopic mucosal resection and endoscopic submucosal dissection. Surg Clin North Am 2020; 100: 1069-1078
  • 10 Hirasaki S, Kozu T, Yamamoto H. et al. Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid "cushion" for endoscopic resection of colorectal mucosal neoplasms: a prospective multi-center open-label trial. BMC Gastroenterol 2009; 9: 1
  • 11 Fujishiro M, Yahagi N, Kashimura K. et al. Comparison of various submucosal injection solutions for maintaining mucosal elevation during endoscopic mucosal resection. Endoscopy 2004; 36: 579-583
  • 12 Feitoza AB, Gostout CJ, Burgart LJ. et al. Hydroxypropyl methylcellulose: A better submucosal fluid cushion for endoscopic mucosal resection. Gastrointest Endosc 2003; 57: 41-47
  • 13 Fujishiro M, Yahagi N, Kashimura K. et al. Tissue damage of different submucosal injection solutions for EMR. Gastrointest Endosc 2005; 62: 933-942
  • 14 Uraoka T, Fujii T, Saito Y. et al. Effectiveness of glycerol as a submucosal injection for EMR. Gastrointest Endosc 2005; 61: 736-740
  • 15 Kusano T, Etoh T, Akagi T. et al. Evaluation of 0.6% sodium alginate as a submucosal injection material in endoscopic submucosal dissection for early gastric cancer. Dig Endosc 2014; 26: 638-645
  • 16 Akagi T, Yasuda K, Tajima M. et al. Sodium alginate as an ideal submucosal injection material for endoscopic submucosal resection: preliminary experimental and clinical study. Gastrointest Endosc 2011; 74: 1026-1032
  • 17 Hirose R, Nakaya T, Naito Y. et al. An innovative next-generation endoscopic submucosal injection material with a 2-step injection system (with video). Gastrointest Endosc 2021; 93: 503-513
  • 18 Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Prog Polym Sci 2012; 37: 106-126
  • 19 Eun SH, Cho JY, Jung IS. et al. Effectiveness of sodium alginate as a submucosal injection material for endoscopic mucosal resection in animal. Gut Liver 2007; 1: 27-32