When choosing submucosal injection solutions for EMR, tissue damage should be considered, as well as the lesion-lifting ability. The objective of the study was to find out the potential tissue damage of submucosal injection solutions.

The submucosal injection solutions examined were the following: normal saline solution (NS), 3.75% NaCl, 20% and 50% dextrose water (DW), a glycerin solution (Glyceol; 10% glycerin with 0.9% NaCl plus 5% fructose), and two hyaluronic acid (HA) solutions (0.25% 1900 kDa/NS solution and 0.125% 1900 kDa/ Glyceol solution). Furthermore, DW with different concentrations (5%, 10%, 15%, 30%, 40%) also was examined to find out the tolerable concentration without tissue damage. A total of 2 mL of each solution per stomach were injected by endoscopy into the submucosal layer at the separate sites of 4 living minipigs. Two minipigs were euthanized after 30 minutes of endoscopic observations, and the others were euthanized after additional endoscopic observations a week after injection.

There was no apparent tissue damage in NS, 5% and 10% DW, Glyceol, or two solutions of HA, whereas, hypertonic solutions, except Glyceol and 10% DW, have more or less potency of tissue damage. In 3.75% NaCl and DW with concentrations of ≥20%, considerable tissue damage was observed, which might affect resected EMR specimens and ulcer healing.

Use of hypertonic solutions except Glyceol is not recommended with respect to tissue damage. A combination of HA and Glyceol is the most favorable submucosal injection solution, considering tissue damage and lesion-lifting ability.