Objectives/Hypothesis: Vocal fold fibrosis remains a significant clinical challenge. Estrogens, steroid hormones predominantly responsible for secondary sexual characteristics in women, have been shown to alter wound healing and limit fibrosis, but the effects on vocal fold fibrosis are unknown. We sought to elucidate the expression of estrogen receptors and the effects of estrogens on TGF-β1 signaling in rat vocal fold fibroblasts (VFFs).Study Design: In vitro. Methods: VFFs were isolated from 10-week-old, male Sprague-Dawley rats, and estrogen receptor alpha (ERα) and G protein-coupled receptor 30 (GPR30) were examined via immunostaining and quantitative polymerase chain reaction (qPCR). VFFs were treated with estradiol (E2, 10 −7 , 10 −8 or 10 −9 M) AE transforming growth factor beta 1 (TGF-β1, 10 ng/mL). ICI 182,780 (ICI, 10 −7 M) or G36 (10 −7 M) were employed as antagonists of ERα or GPR30, respectively. qPCR was employed to determine estrogen receptor-mediated effects of E2 on genes related to fibrosis.Results: ERα and GPR30 were expressed in VFFs at both the protein and the mRNA levels. E2 (10 −7 M) did not alter Smad3, Smad7, Acta2 mRNA, or extracellular matrix related genes. However, the combination of E2 (10 −8 M) and TGF-β1 significantly increased Smad7 (P = .03) and decreased Col1a1 (P = .04) compared to TGF-β1 alone; this response was negated by the combination of ICI and G36 (P = .009).Conclusions: E2 regulated TGF-β1/Smad signaling via estrogen receptors in VFFs. These findings provide insight into potential mechanisms of estrogens on vocal fold injury with the goal of enhanced therapeutics for vocal fold fibrosis.

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Chondrosarcoma in the head and neck accounts for-% of all chondrosarcomas and chondrosarcoma arising in the nasal septum is rare. Here, we reported a case of chondrosarcoma in the nasal septum in a-year-old man who presented with left nasal obstruction for year. The standard treatment for this tumor is surgical resection, because radiation therapy and chemotherapy have limited roles. Recently, it has been reported that nasal chondrosarcoma could be removed by an endoscopic approach, which has advantages of improved cosmetic appearance and early discharge. Our case did not have evidence of skull base invasion due to intracranial extension, and was considered as a low grade malignancy therefore we resected the tumor via endoscopic approach by use of piecemeal resection. Utilizing the intraoperative frozen section pathological diagnosis, complete tumor resection was finally achieved. There has been no recurrence for years postoperatively. We considered that chondrosarcoma in the nasal septum being low grade malignancy without skull base involvement like our case could be removed by an endoscopic approach.

Objectives/Hypothesis Vocal fold (VF) scar and sulcus cause severe vocal problems, but optimal methods have not been established. Total replacement of the mucosa is required particularly for cases in which the whole lamina propria is occupied by severe fibrosis and vibratory function is totally lost. The amniotic membrane (AM) has been proven to have regenerative potential, as it contains stem cells and growth factors. The current study investigated the biocompatibility and effects of AM for regeneration of the VF mucosa. Study Design In vitro and in vivo studies. Methods Vocal fold fibroblasts (VFFs) from 13 Sprague–Dawley rats were seeded on AM and subjected to histology and immunohistochemistry, and gene expressions in the VFFs on AM were examined in in vitro study. Twelve New Zealand White rabbits were used in in vivo study. VFs were stripped down and were reconstructed with AM. The regenerative effects were examined 3 months later by histological examination. Results In vitro study indicated VFFs survived on AM and stained positively for Ki67, vimentin, and fibronectin. Gene expressions of Has1, Has2, and Hgf were significantly increased in the VFFs on AM compared with the other groups. The in vivo study indicated AM‐transplanted VFs showed a significantly higher density of hyaluronic acid and lower density of collagen compared with sham VFs. Conclusions The current preliminary study suggests biocompatibility and possible regenerative effects of AM for VFs. Level of Evidence NA Laryngoscope, 132:2017–2025, 2022

ObjectivesEffective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF‐β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis.MethodsIn vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF‐β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real‐time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre‐injury day 5 to post‐injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture.ResultsTAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF‐β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF‐β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment.ConclusionsTAM has antifibrotic potential via the regulation of TGF‐β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis.Level of EvidenceNA Laryngoscope, 133:2248–2254, 2023