Endoscopic lower esophageal sphincter bulking for the treatment of GERD: safety evaluation of injectable polymethylmethacrylate microspheres in miniature swine

Abstract

Endoscopic therapy for GERD is an appealing, minimally invasive alternative to medical treatment and surgery. Various materials have been tested to augment the lower esophageal sphincter (LES), with limited success. To our knowledge, safety and migration of polymethylmethacrylate (PMMA) microspheres has never been evaluated. To assess the safety, migration, inflammatory reaction, and durability of PMMA injected into the LES of miniature swine to create a reflux barrier. Animal study. Approved animal research facilities. Injection of the LES of miniature swine with PMMA. Histopathology of the injected site at certain intervals and postnecropsy microsphere counts of various organs. Minimal inflammatory reaction at the injection site, persistent bulking effect of the material, and no migration of microspheres. Injection of LES with PMMA caused a mild inflammatory reaction. The bulking effect of the injected material was persistent. Migration of microspheres was eliminated with the use of larger-sized microspheres. Animal model. Our phase I study documented that 40-microm polymethylmethacrylate microspheres are biocompatible and that PMMA microspheres are resistant to degradation when injected submucosally into the wall of the esophagus. The detection of 40-microm PMMA microspheres in local lymph nodes, liver, and lungs of some animals in the phase I study clearly documented transport of PMMA away from the injection site. This finding was eliminated by increasing the size of microspheres to 125 microm. The potential therapeutic effects of these larger microspheres for humans with GERD remains to be evaluated.