Overexpression of Neutrophil MMP-9 and HIF-1α May Contribute to the Finger-Like Projections Formation and Histo-Pathogenesis in Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is defined based on its histological characteristic of inverted epithelium growth into the stroma. The inversion can result in epithelial growth in the underlying connective tissue stroma when the basement membrane completely separates from the epithelial layer. To date, such inversion mechanism underlying NIP's pathological phenomenon is unknown. Therefore, we hypothesized that mediators and soluble proteins released by neutrophils, the most predominant infiltrating cells in NIP, is vital in causing the epithelial changes and pathogenesis of NIP. METHODS: We collected 37 NIP tissues from patients who underwent surgical removal of NIP and performed hematoxylin-eosin (HE), immunohistochemical, and immunofluorescence staining to analyze in-depth the basic characteristics of NIP, including detecting the expression and distribution of MMPs and associated factors in NIP. Western blotting and quantitative real-time PCR were further performed to analyze the protein and mRNA expression levels of specific factors including MMPs, HIF-1α, and tissue inhibitors of metalloproteinases (TIMPs). RESULTS: We observed finger-like projections that insert into the epithelium in NIP tissue as its main characteristics. The projections contain fibroblasts, extracellular matrix, capillaries, and infiltrating inflammatory cells. We found abundant neutrophils clustered at the finger-like projection of NIP, and also noted MMP-1 and MMP-9 were up-regulated in NIP (p<0.05), whereas TIMP-1/3 was decreased. The expression level of HIF-1α was also found to be increased in NIP tissue. We further showed that MMP-9 and HIF-1α were mainly expressed by neutrophils and were predominantly observed in the finger-like projections that contribute to the NIP pathology. CONCLUSION: Upregulation and release of MMP-9 and HIF-1α from infiltrating neutrophils may cause damage to the epithelial basement membrane and epithelial clefts, forming finger-like projections with angiogenesis and fibroblasts insertion, resulting in epithelial growth in the tissue stroma, a typical histo-pathological characteristic in NIP.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

Severity of Rhinosinusitis: Comparison Between Visual Analog Scale Given by Patients and Otorhinolaryngologists.

BACKGROUND: Visual Analog Scale (VAS) as determined by the patient is recommended by the European Position Paper on Rhinosinusitis and Nasal Polyps 2012 in evaluation of the total severity of the chronic rhinosinusitis (CRS) patients' symptoms. OBJECTIVE: To evaluate the correlation between evaluations performed by otorhinolaryngologists and CRS patients with commonly used systems. METHODS: Scores of VAS and Sino-Nasal Outcome Test-20 (SNOT-20) Chinese version were obtained from 110 CRS patients with nasal polyps (CRSwNPs, n = 61) and without nasal polyps (CRSsNPs, n = 49) before surgery, which were compared with scores of Lund-Kennedy endoscopic staging system, the Lund-Mackay computed tomography (CT) staging system, and VAS from 3 attending otorhinolaryngologists. RESULTS: The median VAS scores given by CRS patients (6.0; 4.25-7.5) do not correlate significantly with the VAS scores by the 3 otorhinolaryngologists (5.5; 4.83-6.5) with a correlation coefficient of .218 (-0.146 to 0.466). For CRS patients, there was only a moderate correlation between scores of VAS and the SNOT-20 (r = .37), and no significant difference of VAS scores between CRSwNP and CRSsNP, and between unilateral and bilateral nasal polys. For otorhinolaryngologists, a higher median VAS score was found in CRSwNP (6.0; 5.17-7.0), especially in bilateral (6.0; 5.0-7.08) and revision surgery (6.08; 5.33-7.63). The VAS scores of otorhinolaryngologists correlated significantly with the Lund-Mackay CT score (r = .7536) and Lund-Kennedy endoscopic staging (r = .5947). CONCLUSIONS: VAS scores between patients and physicians are not correlated significantly in this study, but they fall within the same therapeutic range and do not change the clinical management of the patients.

Olfactory Change Pattern after Endoscopic Sinus Surgery in Chronic Rhinosinusitis with Olfactory Dysfunction.

OBJECTIVE: To determine the change pattern of olfactory function in chronic rhinosinusitis (CRS) with olfactory dysfunction after endoscopic sinus surgery (ESS), and its association with inspection scores. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Second Hospital of Shandong University, China, from December 2014 to January 2016. METHODOLOGY: Thirty-four CRS with nasal polyps (CRSwNP) patients and 14 CRS without nasal polyps (CRSsNP) patients were evaluated preoperatively by T&T olfactory test, olfactory VAS test, SNOT-20score and Lund-Mackay CT score. Outcomes were re-evaluated at 1 month, 3 months and 6 months postoperatively. RESULTS: Both olfactory and SNOT-20 scores showed significant improvement within 6 months in both CRSwNP and CRSsNP groups. Patients with anosmia in T&T test showed the largest degree of improvement. No significant recovery of olfactory dysfunction was observed at 1 month and 3 months in CRSsNP groups postoperative. In CRSwNP, the olfactory scores were correlated with the CT scores significantly (r=0.649, p<0.001; r=0.625, p<0.001). However, no correlation was found between the SNOT-20 score and olfactory score preoperatively. CONCLUSION: Our study has confirmed that the therapeutic effects of ESS on olfactory function last for up to 6 months, particularly in patients with CRSwNP. Although the therapeutic effects plateaued at 3 months postoperatively, the olfactory function continues to recover between 3 and 6 months.