2.5% Hydroxypropyl Methylcellulose Solution Provides a Superior Submucosal Fluid Cushion for Endoscopic Submucosal Dissection

Abstract

Purpose: The choice of submucosal agent in endoscopic submucosal dissection (ESD) is extremely important. The submucosal agent forms an adequate cushion, lifting and separating the tissue to be resected, thereby decreasing the rate of perforation or hemorrhage. Hydroxypropyl methylcellulose (HPMC) is inexpensive and readily available. Prior studies have demonstrated the feasibility of 0.83% HPMC in creating a secure cushion. This study evaluates the use of 1.25% and 2.5% HPMC solutions as compared to 0.83% HPMC and normal saline with epinephrine in submucosal cushion durability, viscoelasticity, ease of dissection, size of en-bloc specimen, and rate of perforations. Methods: ESD was performed on two ex-vivo pig stomachs on consecutive days. Various solutions consisting of 5 mL of normal saline with epinephrine (NS), 0.83%, 1.25%, and 2.5% HPMC were injected into the submucosa using a 23-gauge injection needle through a standard single-channel upper endoscope. The size of resected en-bloc specimen, rate of perforations, time to submucosal cushion dissipation, size of submucosal cushion (measured by an endoscopic ruler, Olympus Corporation), and ease of dissection were measured. Histologic specimen damage was assessed by a pathologist who was blinded to the solution utilized. Results: The size of resected specimen was largest for 2.5% HMPC solution. The length, width, height (LWH) measured was 3.0 × 2.4 × 0.45 cm, respectively. LWH for NS, 0.83%, 1.25% HPMC solutions was 1.4 × 1.6 × 0.2 cm, 1.6 × 1.3 × 0.2 cm, 2.6 × 1.8 × 0.35 cm, respectively. Perforation was observed in only the NS group. Time to dissipation was 6 minutes and 40 seconds in NS group while all other solutions kept their cushion size with minimal dissipation for at least 30 minutes. The size of the submucosal cushion was largest in the 2.5% HPMC group with LWH of 3.5 × 2.0 × 2.5 cm, while the 0.83% and 1.25% HPMC solutions had similar cushion sizes but much larger than NS. Repeating the experiment with different ex-vivo stomachs yielded similar results. No histological damage to specimens was observed as reviewed by pathologist. Conclusion: The superior size of submucosal cushion formation, size of resected specimen, and ease of resection makes the 2.5% HMPC solution a very attractive submucosal agent for ESD. The outstanding visibility of cushion borders and the ease of submucosal resection in 2.5% HPMC were likely due to increased viscosity of solution and ease of manipulating/molding of the en-bloc specimen. Further studies are needed comparing 2.5% HPMC solution to hyaluronic acid.