Detection of Sessile Serrated Adenomas in the Proximal Colon Using Wide-Field Fluorescence Endoscopy

摘要: Background & Aims Many cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. SSA cells V600E mutation BRAF. We investigated whether this feature could be used imaging methods SSAs patients. Methods phage display identify a peptide binds specifically SSAs, using subtractive hybridization HT29 colorectal cancer containing BRAF and Hs738.St/Int as control. Binding of fluorescently labeled was evaluated confocal fluorescence microscopy. Rats received intra-colonic 0.0086 mg/kg, 0.026 or 0.86 mg/kg vehicle morbidity, mortality, injury were monitored twice daily assess toxicity. In clinical safety study, topically administered, spray catheter, 25 subjects undergoing routine outpatient colonoscopies (3 given 2.25 μmol/L 22 patients 76.4 μmol/L). performed blood cell count, chemistry, liver function, urine analyses approximately 24 hours after administration. 38 colonoscopies, at high risk for cancer, suspected unresected colonic polyp, first by endoscopy suspicious regions. The (76.4 μmol/L) administered colon, unbound washed away, white-light, reflectance, videos recorded digitally. Fluorescence intensities compared those normal mucosa. Endoscopists resected identified lesions, analyzed histologically gastrointestinal pathologists (reference standard). also ability vs adenomas, hyperplastic polyps, mucosa specimens obtained tissue bank University Michigan. Results sequence KCCFPAQ measured an apparent dissociation constant K d  = 72 nM association time  = 0.174 min −1 (5.76 minutes). During during endoscopy, regions had 2.43-fold higher mean intensity than labeling distinguished 89% sensitivity 92% specificity. no observed toxic effects animals analysis ex vivo specimens, bound significantly polyps. Conclusions has humans can wide-field lesions colon. It distinguishes This targeted method might early detection premalignant colonoscopies. ClinicalTrials.gov ID: NCT02156557.