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Transnasal endoscopy (TNE) has been proposed to screen for esophageal squamous cell cancer (ESCC) in Asia. This study aimed to assess the feasibility and tolerance of Brazilian patients to undergo unsedated TNE for screening, the prevalence of ESCC in this population, and the effectiveness of white-light endoscopy (WLE) and digital chromoendoscopy [flexible spectral imaging color enhancement (FICE)] to diagnose esophageal neoplasia.This was a diagnostic test study that enrolled patients with head and neck squamous cell cancer (HNSCC) referred to ESCC screening. Patients’ tolerance was rated by a numeric pain intensity scale. Interventions included unsedated TNE with WLE and FICE examination of the esophagus, in a tandem manner with blinded operators, followed by lugol chromoscopy. Performance of WLE and FICE for neoplasia detection was compared with the reference standard (lugol chromoscopy plus histology).A total of 106 patients were recruited. TNE was feasible in 99.1%, and 92% of the patients rated the discomfort as absent or minimal. Thirteen ESCC were detected (12.3%), with 10 early cancers (77%). The tests showed an excellent performance and there was no difference between WLE (sensitivity 92.3%, specificity 98.9%, accuracy 98.1%, area under curve 0.995) and FICE (sensitivity 100%, specificity 98.9%, accuracy 99%, area under curve 0.956) for esophageal neoplasia detection.Unsedated TNE is a feasible, well accepted, and efficient diagnostic tool for the screening of ESCC. The elevated rate of esophageal neoplasia strengthens the recommendations to screen patients with HNSCC. The yields of WLE and FICE were similar for ESCC detection.