Duodenal Contents Reflux-Induced Laryngitis in Rats: Possible Mechanism of Enhancement of the Causative Factors in Laryngeal Carcinogenesis

Abstract

Objectives: The main factors considered responsible for the onset of laryngeal cancer are tobacco smoking and alcohol abuse. Recently, gastroesophageal reflux has also been implicated as a causative factor in several laryngeal disorders, including laryngeal cancer. However, the significance of gastroesophageal reflux in laryngeal cancer is controversial. Methods: We investigated the histologic features of the esophagus and larynx in a rat model of reflux of the duodenal contents. Cell proliferation was also evaluated in laryngeal samples by detection of Ki67 antigen. Results: In this reflux model, laryngitis with infiltration of inflammatory cells and proliferation of small mucous glands was evident from 10 weeks after operation, and basal cell hyperplasia around the epiglottis and hyperplastic changes in the larynx were detected at 30 weeks. No dysplastic or malignant lesions were detected in the laryngeal samples within the duration of the experiment, in spite of detection of malignancy in 31.3% of lesions in esophageal samples at 30 weeks. The Ki67 index at each week was significantly higher than that of the control animals. Conclusions: Previous studies have shown smoking and alcohol abuse to have refluxogenic effects. Reflux of duodenal contents causes laryngitis. Reflux does not appear to be an independent risk factor for laryngeal carcinogenesis, but it may enhance the acknowledged etiologic risk factors, namely, smoking and alcohol abuse, by promoting cell proliferation.