Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet

Background: Confocal laser endomicroscopy (CLE) has been shown to reliably predict histology during ongoing endoscopy. To unmask lesions for CLE, chromoendoscopy has been mandated. Usually fluorescein then serves as a contrast agent for CLE, but it does not allow direct nuclear visualization, must be injected, leads to a transient skin discoloration, and may have allergic side effects. Objective: To establish a single topical dye, cresyl violet (CV), for simultaneous chromoendoscopy and in vivo CLE of the lower GI tract. Design: Animal preclinical study, prospective clinical trial. Setting: Mainz University Clinic (tertiary care center). Patients, Methods, and Interventions: To establish the staining characteristics and optimal concentration of CV, the ileum and colon of 7 BL6 mice were stained with CV (0.1%-2%), and in vivo confocal imaging was performed with FIVE1. In a subsequent clinical trial, 67 sites in 36 patients were topically stained with CV 0.13%, and subsurface serial images were generated at different depths with an endomicroscope. Main Outcome Measurements: Prediction of histology according to the Mainz confocal classification and nuclear visualization with topical CV. Results: Endomicroscopy with topical CV yielded (sub-)cellular details of normal mucosa, and regenerative and neoplastic changes at variable imaging depths in high resolution comparable to those with intravenous fluorescein. By cytoplasmic enrichment of CV, nuclear morphology could be negatively visualized. Reliable differentiation of nonneoplastic versus neoplastic changes during ongoing endoscopy and a high interobserver agreement based on the microscopic images generated in vivo could be achieved. Limitations: Single-center study, nonrandomized, limited number of patients. Conclusions: CV can be applied topically and allows simultaneous chromoendoscopy and endomicroscopy with accurate prediction of histology with visualization of nuclear morphology. It may therefore be a single-agent alternative to chromoendoscopy and fluorescein in endomicroscopy.