Eosinophil-derived interferon-γ drives transmembrane protein 119-induced new bone formation in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory sinonasal disease characterized by eosinophilic infiltration and new bone formation. These changes indicate the severity and prognosis of CRSwNP and may be closely linked to each other. METHODS: We performed RNA sequencing to screen specific osteogenic molecules and validated transmembrane protein 119 (TMEM119) expression by quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses. TMEM119 knockdown was performed to observe the downregulation of bone mineralization. We validated the bone-forming activity of interferon-γ (IFN-γ) and its signaling pathways in cultured primary sinus bone cells. Cellular sources of IFN-γ were identified using immunohistochemistry and immunofluorescence analyses. Interleukin-4-eosinophil-IFN-γ axis and the effect of dupilumab were investigated in Eol-1 cells. RESULTS: We observed elevated IFN-γ levels and eosinophils in the nasal fluid and predominantly eosinophil-derived IFN-γ in the sinus mucosa of patients with CRSwNP. TMEM119 expression and bone-forming activities were increased in the osteitic and primary sinus bone cells of CRSwNP. IFN-γ treatment enhanced bone mineralization and TMEM119 expression via signal transducer and activator of transcription 1 (STAT1) signaling. Moreover, TMEM119 knockdown inhibited sinus bone cell mineralization and dupilumab attenuated IFN-γ secretion by IL4-stimulated Eol-1 cells. CONCLUSION: Eosinophil-derived IFN-γ promotes the bone-forming activities of sinus bone cells via the STAT1-TMEM119 signaling pathway. Interleukin-4-eosinophil-IFN-γ axis may be crucial for TMEM119-mediated new bone formation in CRSwNP.

Characteristics and significance of minimal and maximal extrathyroidal extension in papillary thyroid carcinoma.

OBJECTIVES: Maximal extrathyroidal extension (ETE) is known to be an important prognostic factor in papillary thyroid carcinoma (PTC). However, the significance of minimal ETE is controversial. The aim of this study was to investigate the clinicopathologic characteristics and prognostic significance of minimal vs maximal ETE in PTC. MATERIALS AND METHODS: A group of 967 patients who underwent thyroidectomy for PTC in a tertiary hospital between January 2000 and December 2011 were studied retrospectively. Patients were classified into three groups: absence of ETE, and minimal and maximal ETE. The minimal ETE group was further categorized into two subgroups according to invasion of strap muscles or no invasion (STI+ and STI-). RESULTS: Gender did not differ between the three groups of patients. The mean age of the patients with maximal ETE was significantly higher than in those belonging to the other groups. Tumor size, bilaterality, lymph node metastasis and stage increased significantly according to the degree of ETE. Recurrence and survival rates did not differ between the absence and minimal ETE groups, or between the STI- and STI+ subgroups of minimal ETE. However, the maximal ETE group had significantly higher recurrence and lower survival rates than the other groups (P<0.001). CONCLUSION: Maximal ETE is a significant factor for poor prognosis. However, minimal ETE is not associated with increased recurrence or decreased survival in patients with PTC.

The role of laryngopharyngeal reflux as a risk factor in laryngeal cancer: a preliminary report.

OBJECTIVES: To evaluate the significance of laryngopharyngeal reflux (LPR) as a risk factor in laryngeal cancer. METHODS: We performed a case-control study with 29 consecutive laryngeal cancer patients who had undergone 24-hour ambulatory double pH monitoring from 2003 to 2006. The control group included 300 patients who had undergone 24-hour ambulatory double pH monitoring due to LPR-related symptoms. We analyzed the prevalence of LPR and numerous parameters from the 24-hour ambulatory double pH monitoring in the laryngeal cancer patient and control groups. Pathologic LPR is defined when more than three episodes of LPR occur in 24 hours. RESULTS: The prevalence of pathologic LPR was significantly higher in the laryngeal cancer group than the control group (P=0.049). The reflux number of the upper probe was significantly higher in the laryngeal cancer group (P<0.001). However the effects of pathologic LPR on laryngeal cancer risk were diluted after adjusting for smoking and alcohol consumption in the multivariable logistic regression. CONCLUSION: The pathologic LPR might be a possible risk factor in the development of laryngeal cancer. A further study should be necessary to verify the exact role of LPR in laryngeal cancer.

Expression of EGFR and Microvessel Density in Middle Ear Cholesteatoma.

OBJECTIVES: Cholesteatoma destructs bony tissue by the interactions between hyperproliferative epithelial cells and subepithelial inflammatory cells. The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and microvessel density (MVD) in middle ear cholesteatoma tissue in an effort to determine the relationship between expression of EGFR and neovascularization. METHODS: We evaluated the expression of EGFR and MVD by immunohistochemical staining for CD31 and Factor VIII in 32 cholesteatoma tissue samples and 7 normal postauricular skin samples. We also analyzed the correlation between EGFR expression and MVD. RESULTS: The expression of EGFR was higher in cholesteatoma than in postauricular skin, but the difference was not statistically significant. EGFR was more highly expressed in the suprabasal layer than in the basal layer. Using CD31 and Factor VIII, we analyzed the MVD and found that it was significantly higher in cholesteatoma than in postauricular skin, and significantly correlated with the expression of EGFR. CONCLUSION: Our results suggest that overexpression of EGFR and neovascularization are correlated with the growth of cholesteatoma.

CSF Otorrhea Resulting from Osteoradionecrosis of the Temporal Bone in a Patient with Recurrent Meningioma.

Osteoradionecrosis of the temporal bone is a very rare but potentially lethal complication of radiotherapy for head and neck or skull base tumors. Only two cases of osteoradionecrosis of the temporal bone complicating cerebrospinal fluid (CSF) otorrhea have been reported in the literature. This report describes a case of CSF otorrhea and osteoradionecrosis of the temporal bone in a patient with meningioma who was treated with tympanomastoid surgery and autologous fat obliteration in the mastoid.

Orbital apex syndrome in a patient with sphenoid fungal balls.

Orbital apex syndrome (OAS) is a rare disease that presents with a complex of symptoms, including ophthalmoplegia, ptosis and visual loss. Due to the poor prognosis, making a prompt diagnosis and administering the appropriate treatment must be initiated without delay if OAS is suspected. We report here on a case of a patient with sphenoid fungal balls, and he presented with acute visual loss and ophthalmoplegia.