Search

A salivary fistula is a relatively uncommon but troublesome complication after parotid surgery. Most cases are self-limiting and respond well to conservative therapy (compression dressings). However, this treatment may require weeks before its effect becomes evident. We present the first report of direct administration of botulinum toxin type A as an effective primary treatment for an acute salivary fistula after parotid surgery, in the absence of other, more conservative treatment. A 47-year-old man with a 7-day history of sore throat was found to have a parapharyngeal tumor originating from the deep lobe of the parotid gland. He underwent tumor removal via a trans-paroticocervical approach. However, on postoperative day 7, the patient was noted to have massive salivary discharge from the surgical incision during a meal. We administered a transcutaneous botulinum toxin type A injection without a pressure dressing. One day after the injection, the salivary discharge from the incision line disappeared completely and there was no evidence of recurrent sialorrhea in the 6 months following the procedure. This report suggests that the injection of botulinum toxin type A is a highly effective and relatively safe primary method of treatment for an acute postparotidectomy salivary fistula, and not merely an alternative to more conservative therapy. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) cultures recapitulate the microenvironment of tissue-resident stem cells and enable them to modulate their properties. We determined whether salivary gland-resident stem cells (SGSCs) are primed by a 3D spheroid culture prior to treating irradiation-induced salivary hypofunction using in-vitro coculture and in-vivo transplant models. Methods: 3D spheroid-derived SGSCs (SGSCs3D) were obtained from 3D culture in microwells consisting of a nanofiber bottom and cell-repellent hydrogel walls, and were examined for salivary stem or epithelial gene/protein expression, differentiation potential, and paracrine secretory function compared with monolayer-cultured SGSCs (SGSCs2D) in vitro and in vivo. Results: SGSCs3D expressed increased salivary stem cell markers (LGR5 and THY1) and pluripotency markers (POU5F1 and NANOG) compared with SGSCs2D. Also, SGSCs3D exhibited enhanced potential to differentiate into salivary epithelial cells upon differentiation induction and increased paracrine secretion as compared to SGSCs2D. Wnt signaling was activated by 3D spheroid formation in the microwells and suppression of the Wnt/β-catenin pathway led to reduced stemness of SGSCs3D. Enhanced radioprotective properties of SGSCs3D against radiation-induced salivary hypofunction was confirmed by an organotypic 3D coculture and in-vivo transplantation experiments. Conclusion: The 3D spheroid culture of SGSCs in nanofibrous microwells promotes stem cell properties via activation of Wnt signaling. This may contribute to SGSC priming prior to regenerative therapy to restore salivary hypofunction after radiotherapy. [ABSTRACT FROM AUTHOR]

Transforming growth factor β (TGFβ) ligands, including TGFβ1, are multifunctional cytokines known as key regulators of cell growth, differentiation and inflammation. Dysregulated TGFβ signaling is common in numerous solid tumors, including head and neck squamous cell carcinoma (HNSCC). Previously, TGFβ ligands were also reported to be associated with an enhancement of stemness in glioma stem-like cells. However, their role in HNSCC cancer stem cells (CSCs) has not been explored. The present study demonstrated that TGFβ1 enriches the properties of HNSCC CSCs. TGFβ1 promoted sphere formation and increased stemness-associated gene expression (Oct4 and Sox2) of primary HNSCC CSCs. Additionally, the population of aldehyde dehydrogenase (ALDH)-positive cells was increased subsequent to exogenous treatment of cells with TGFβ1. In addition, following stimulation with TGFβ1, the cells exhibited more resistance to cisplatin and elevated expression of Twist, Snail and Slug. Mechanistically, TGFβ1 acts as an upstream stimulator of Wnt/β-catenin signaling. Collectively, the present findings provide insights toward the development of TGFβ1 signaling inhibition strategies for treating HNSCC CSCs. [ABSTRACT FROM AUTHOR]

Background:It has been reported that patients with papillary thyroid carcinoma (PTC) have a high incidence of background Hashimoto thyroiditis (HT); however, the linkage of HT to PTC is controversial. Recent studies have shown that the prevalence of activating point mutations in BRAFV600Eis much higher (73–86%) in Korea than in Western countries (29–69%), and associated with a poor prognosis in PTC. The purpose of the present study was to investigate the frequency of the BRAFV600Emutation in PTC with and without HT, and to determine clinical and pathological features that were associated with concomitant HT and PTC.Methods:Fine-needle aspiration slides from 101 patients with surgically confirmed PTC were studied. The DNA was extracted from the atypical cells that were scraped from slides. It was then analyzed for the BRAFV600Emutation by pyrosequencing. In addition, the presence of background HT in surgical specimens and other clinical and pathological features of the patients were characterized.Results:HT was present in 37 (36.6%) of the patients. The BRAFV600Emutation was present in 27 (72.9%) of patients with HT but was present in 61 (95.3%) of patients without HT (p≤ 0.01). The inverse correlation of concurrent HT with the BRAFV600Emutation was significant for both males and females (p< 0.01). The presence of background HT was not associated with tumor size, extrathyroidal invasion, lymph node (LN) metastasis, or tumor stage. The patients were younger in the group without background HT (44.1 ± 13.2 vs. 49.8 ± 13.9, p= 0.05). The BRAFV600Emutation was present in 88 (87.1%) of the 101 patients with PTC. The presence of the BRAFV600Emutation was significantly associated with LN metastasis (p< 0.02; odds ratio, 6.24; 95% confidence interval, 1.51–25.79).Conclusion:In Korean patients with PTC, the BRAFV600Emutation is associated with a lower frequency of background HT and a high frequency of LN metastasis. [ABSTRACT FROM AUTHOR]