The Impact of Acid-Free Reflux on Vocal Cord Granuloma.

OBJECTIVES: To examine the types and characteristics of acid-free reflux in vocal cord granuloma (VCG). METHODS: A retrospective analysis was conducted on the VCG patients and those with benign unilateral vocal cord lesions between October 2017 and January 2025. Prior to treatment, all patients underwent 24-h hypopharyngeal-esophageal multichannel intraluminal impedance-pH (HEMII-pH) monitoring, high-resolution esophageal manometry assessment, and electronic laryngoscopy examination. Furhermore, granuloma tissue samples from the VCG patients were obtained for detection of pepsin, pepsinogen A, pepsinogen C and trypsin, using immunohistochemical analysis. RESULTS: The proportion of the VCG group experiencing acid-free reflux was significantly higher than that observed in the benign lesion group (65.57% ± 23.26% vs. 30.43% ± 18.53%, t = 4.134, p < 0.001). Furthermore, the lower esophageal sphincter (LES) length in the VCG group was significantly shorter than that in the benign lesion group (2.25 cm vs. 2.60 cm, Z = -1.977, p = 0.047). Additionally, no pepsin expression was detected in any granuloma tissue samples. However, both pepsinogen A and pepsinogen C were positively expressed. Notably, the percentage of pepsinogen A-positive cells in granuloma tissue exhibited a significant positive correlation with the size of the granulomas in the VCG patients (r = 0.691, p = 0.027). CONCLUSION: Acid-free reflux could potentially play a significant role in the development of granulomas in VCG patients. LEVEL OF EVIDENCE: 4.