ABSTRACT 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.
Liu et al. (Wed,) studied this question.