Successful outcomes of a new combined solution of hyaluronic acid, chondroitin sulfate and poloxamer 407 for submucosal injection: animal survival study

Abstract

Background and study aims Endoscopic resection requires use of submucosal injection. This study was conducted to assess efficacy and impact on early healing of hyaluronic acid combined with chondroitin sulfate and poloxamer 407 (Ziverel) when used as a solution for submucosal injection.

Materials and methods Prospective and comparative study of gastric endoscopic mucosal resection (EMR) with three groups of two Yorkshire pigs. Six submucosal cushions were created in each animal by injecting 2 mL of Ziverel (Group 1) or succinylated gelatin (SG) (Group 2), enabling 12 EMR in each group. Submucosal cushions were created with Ziverel in Group 3, without resection. Electrosurgery unit settings were the same in all cases. EMR defects and injection sites were marked with clips. The animals were sacrificed 7 days later. EMR specimen size and duration of procedure were recorded. EMR specimens and EMR scars and injection sites were evaluated by a blinded pathologist.

Results We successfully performed 24 EMR (15 en-bloc and 9 piecemeal, without differences between groups 1 and 2). Mean EMR specimen dimensions were significantly larger in Group 1 (median 19 mm, range 6 – 40 vs 16.6 mm, range 5‑25; P = 0.019), without changing the electrocautery unit settings. Blinded histopathologist assessment of EMR specimens showed less fibrosis in the submucosa and a trend to fewer cautery artifacts with Ziverel and did not identify any significant differences in early healing of resection sites.

Conclusion The combination of Ziverel enables EMR and does not negatively affect early healing.

• References

• 1 Hwang JH, Konda V, Abu Dayyeh BK. et al. Endoscopic mucosal resection. Gastrointest Endosc 2015; 82: 215-226
• 2 Ferreira A, Moleiro J, Torres J. et al. Solutions for submucosal injection in endoscopic resection: a systematic review and meta-analysis. Endosc Int Open 2015; 04: E1-E16
• 3 Moss A, Bourke MJ, Kwan V. et al. Succinylated gelatin substantially increases en bloc resection size in colonic EMR: a randomized, blinded trial in a porcine model. Gastrointest Endosc 2010; 71: 589-595
• 4 Mehta N, Strong AT, Franco M. et al. Optimal injection solution for endoscopic submucosal dissection: A randomized controlled trial of Western solutions in a porcine model. Dig Endosc 2018; 30: 347-353
• 5 Fernández-Esparrach G, Cuatrecasas M, Rodríguez de Miguel C. et al. Efficacy and safety of a combination of hyaluronic acid, chondroitin sulfate, and poloxamer 407 as a submucosal injection solution for endoscopic resection: pilot study on a swine model. Endosc Int Open 2017; 5: E450-E454
• 6 Oka S, Tanaka S, Saito Y. et al. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan. Am J Gastroenterol 2015; 110: 697-707
• 7 Belderbos T, Leenders M, Moons L. et al. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis. Endoscopy 2014; 46: 388-402
• 8 Ferlitsch M, Moss A, Hassan C. et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270-297
• 9 Yamamoto H, Kawata H, Sunada K. et al. Successful en-bloc resection of large superficial tumors in the stomach and colon using sodium hyaluronate and small-caliber-tip transparent hood. Endoscopy 2003; 35: 690-694
• 10 Bureš J, Kopáčová M, Květina J. et al. Different solutions used for submucosal injection influenced early healing of gastric endoscopic mucosal resection in a preclinical study in experimental pigs. Surg Endosc Other Interv Tech 2009; 23: 2094-2101
• 11 Di Simone M, Baldi F, Vasina V. et al. Barrier effect of Esoxx® on esophageal mucosal damage: experimental study on ex-vivo swine model. Clin Exp Gastroenterol 2012; 103
• 12 Uraoka T, Ochiai Y, Fujimoto A. et al. A novel fully synthetic and self-assembled peptide solution for endoscopic submucosal dissection-induced ulcer in the stomach. Gastrointest Endosc 2016; 83: 1259-1264
• 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 Fernández-Esparrach G, Shaikh SN, Cohen A. Efficacy of a reverse-phase polymer as a submucosal injection solution for EMR: a comparative study (with video). Gastrointest Endosc 2009; 69: 1135-1139
• 15 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