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Objective: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date., Methods: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed., Results: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease ( p <.001), distant metastasis ( p <.001), perineural invasion ( p  = .027), and lymphovascular invasion ( p  = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p  = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p  = .047) were associated with decreased OS., Conclusion: Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size., Level of Evidence: Level 3., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: This study aimed to assess if Nigella sativa oil (NSO), a health supplement containing thymoquinone as a major component, can act as a protective agent in salivary gland stem cells following radiotherapy (RT) damage., Methods: Forty, 10-week-old, male C3H/HeJ mice were randomized to four experimental groups: sham RT + H 2 O gavage (control) ( N  = 4); 15 Gy RT + H 2 O gavage ( N  = 12); sham RT + NSO gavage ( N  = 12); and 15 Gy RT + NSO gavage ( N  = 12). Weight changes, saliva production, and salivary gland histopathologic staining were recorded for each group over the course of the experiment., Results: All mice in the sham RT + H 2 O gavage and sham RT + NSO gavage groups demonstrated 100% 60-day survival. RT + H 2 O compared to RT + NSO gavaged mice were significantly underweight by an average of 6.4 g ( p  < .001). Salivary output showed significant decline in RT + H 2 O gavaged mice at days 3 and 16, whereas salivary output in RT + NSO during these same time periods was comparable to the control. At day 60, all mice that survived recovered salivary function regardless of their treatment arm. Salivary specimens from the RT + NSO gavage group demonstrated early signs of recovery of Kr 5+ salivary gland stem cells in both submandibular and sublingual glands at day 16 with complete recovery by day 60, marked by strong histopathologic staining, whereas the RT + H 2 O gavage group did not recover as effectively., Conclusion: NSO may help preserve salivary function in mice treated with RT and may mitigate xerostomia by accelerating the recovery of salivary gland stem cells., Level of Evidence: Not applicable., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: Thymoquinone (TQ), the active constituent of Nigella sativa , has been shown to have anticancer effects in head and neck squamous cell carcinoma (HNSCC). This review aims to outline the properties of TQ, the known drivers in HNSCC formation, and summarize the anticancer effects of TQ in SCC., Data Sources: Three databases (PubMed, Embase, and Google Scholar) were queried for the key words "thymoquinone squamous cell carcinoma.", Review Methods: Publications that were not original research and publications that did not have full-text available for review were excluded., Results: Sixteen research articles met the inclusion criteria. Our review demonstrates that TQ-induced cytotoxicity is associated with increased expression and activity of the tumor suppressor p53, proapoptotic proteins Bax and caspases, as well as decreased expression and activity of antiapoptotic proteins Bcl-2 and Mdm2. Additionally, TQ modulates cell-survival pathways such as the PI3k/Akt pathway. TQ synergizes with therapeutics including cisplatin and radiation. Early TQ administration may prevent carcinogenesis via upregulation of antioxidant enzymes, and TQ administration in the presence of cancer can result in disease mitigation via induction of oxidative stress., Conclusion: TQ acts as an upregulator of proapoptotic pathways and downregulator of antiapoptotic pathways, modulates the oxidative stress balance in tumor development, and works synergistically alongside other chemotherapeutics to increase cytotoxicity. TQ has the potential to prevent carcinogenesis in patients who are at high-risk for SCC and adjuvant treatment for SCC patients undergoing conventional treatments. Future studies should aim to identify specific populations in which TQ's effects would be the most beneficial., Level of Evidence: Not available., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objectives: Vocal fold (VF) scarring, manifested by increased collagen, decreased glycosaminoglycans (GAGs), and disrupted elastic fibers, remains a negative consequence of VF injury or resection. The objective of this study is to compare four reconstructive options after Vf mucosal resection in rabbits. A Cell-Based Outer Vocal fold Replacement (COVR) using human adipose-derived mesenchymal stromal cells (hASCs) in fibrin scaffold is directly compared with a decellularized scaffold implant, hASC injection, and resection alone without reconstruction. The primary hypothesis is that the cells-in-scaffold construct better reconstitutes the VF structure than either cells or scaffold alone, or than healing by secondary intention., Methods: A total of49 rabbits received bilateral VF cordectomy, followed by either COVR implant, decellularized scaffold implant, hASC injection, or no reconstruction (injured control group). Larynges were harvested after 6 weeks., Results: Histology demonstrated greater lamina propria thickness, less collagen deposition, and more GAGs in COVR animals versus all other treatment groups. Evidence of persistent human cells was found in about half of the cell-treated animals. RNA levels of fibrosis pathway and macrophage phenotype markers were statistically unchanged among treatment groups at 6 weeks., Conclusion: These data support the efficacy of COVR implantation in restoring VF microstructure in rabbits. The intact COVR was required; isolated components of decellularized scaffold or injected hASC still produced histologic scarring. We propose that the unique bilayered cell structure within fibrin enables controlled matrix remodeling to minimize wound contraction and fibrosis, and to promote GAG deposition., Level of Evidence: Basic science study., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)