Li Hu

Biological distinctions between juvenile nasopharyngeal angiofibroma and vascular malformation: an immunohistochemical study.

The exact nature of juvenile nasopharyngeal angiofibroma (JNA) is still in dispute. In recent years, the main controversy of its nature has focused on hemangioma and vascular malformation. In this study, the immunolocalization of vascular endothelial growth factor (VEGF), VEGF receptor-1/fms-like tyrosine kinase-1 (VEGFR-1/Flt-1), VEGF receptor-2/fetal liver kinase-1 (VEGFR-2/Flk-1), proliferating cell nuclear antigen (PCNA), and CD34 was investigated in 28 cases of JNA and 20 cases of orbital cavernous hemangiomas (OCH). The immunostaining levels of VEGF, Flt-1, and Flk-1 were higher and more frequent in vascular endothelial cells of JNA than those of OCH (p<0.05). The average microvessel density (MVD) marked by CD34 in JNA was (49.3 ± 9.1)/HPF (high power field), which was higher than OCH (29.1 ± 6.7)/HPF (p<0.05). Immunoreactivity of PCNA was localized in both endothelial and stromal cell components of JNA, but was predominantly seen in the stromal cells. However, no PCNA immunoreactivity was identified in any of the stromal and endothelial cells in cases of OCH. The immunostaining levels of CD34, VEGF, Flt-1, Flk-1, and PCNA in JNA were higher than those in OCH. These data support the view that JNA has biological characteristics of an angiogenic histogenetic tumor. In the future, anti-angiogenic therapy may represent a novel treatment strategy for JNA.

Endoglin (CD105) expression on microvessel endothelial cells in juvenile nasopharyngeal angiofibroma: tissue microarray analysis and association with prognostic significance.

The purpose of this study was to examine endoglin (CD105) expression on microvessel endothelial cells (ECs) in juvenile nasopharyngeal angiofibroma (JNA) and its relationship with recurrence.

Hormonal receptors and vascular endothelial growth factor in juvenile nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis

Abstract Conclusion: This work demonstrated that juvenile nasopharyngeal angiofibromas (JNAs) express high levels of hormone receptors and vascular endothelial growth factor (VEGF) compared with normal nasal mucosa. The interaction between hormone receptors and VEGF may be involved in the initiation and growth of JNA. Objectives: JNA is a rare benign tumor that occurs almost exclusively in male adolescents. Although generally regarded as a hormone-dependent tumor, this has not been proven in previous studies. The aim of this study was to investigate the role of hormone receptors in JNA and the relationship with clinical characteristics. Methods: Standard immunohistochemical microarray analysis was performed on 70 JNA samples and 10 turbinate tissue samples. Specific antibodies for androgen receptor (AR), estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), progesterone receptor (PR), and VEGF were examined, and the relationships of receptor expression with age, tumor stage, and bleeding were evaluated. Results: Results showed that JNA expressed ER-α (92.9%), ER-β (91.4%), AR (65.7%), PR (12.8%), and VEGF (95.7%) at different levels. High level of VEGF was linked to elevated ER-α and ER-β. There was no significant relationship between hormonal receptors and age at diagnosis, tumor stage or bleeding. However, overexpression of ER-α was found to be an indicator of poor prognosis (p = 0.031).

Endoscopic assisted sublabial and buccolabial incision approach for juvenile nasopharyngeal angiofibroma with extensive infratemporal fossa extension

OBJECTIVE The aim of this study is to evaluate endoscopic assisted sublabial and buccolabial incision approach as treatment option for Juvenile nasopharyngeal angiofibroma (JNA) with extensive infratemporal fossa (ITF) extension. METHODS Seven patients diagnosed as JNA with extensive ITF extension and underwent surgery at our department between 2006 and 2010 were retrospectively reviewed. All patients underwent diagnostic arteriography followed by embolization preoperatively and intratumor injection with N-butyl cyanoacrylate (NBCA). Endoscopic assisted sublabial and buccolabial incision approach was used to remove the tumors. RESULTS Complete resections of the tumors were achieved in all patients. Mean blood loss was 700 ml. The follow-up period ranged from 9 to 20 months, with a mean of 14.3 months. One patient had a recurrent tumor six months after operation. CONCLUSIONS Endoscopic assisted sublabial and buccolabial incision is an optional approach to remove JNA with extensive ITF extension.

Serial cytokine levels during wound healing in rabbit maxillary sinus mucosa

Abstract Conclusion: Collagen deposition was increased in regenerative rabbit maxillary mucosa, and the elevated collagen deposition during wound healing was associated with increased interleukin (IL)-6 and IL-8, and decreased IL-10. Objectives: To observe the natural progression of wound healing in rabbit maxillary sinus mucosa and to detect the expression of relevant cytokines. Methods: A rabbit wound-healing model was established in the maxillary sinus. At different times after injury, the sizes of maxillary ostia were recorded, and histological changes in the sinus mucosa were examined by means of hematoxylin and eosin (H&E) and Masson trichrome staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of IL-6, IL-8, IL-10, and collagen types I and III. Results: A large amount of immature spindled collagen deposition was observed in the basal lamina and lamina propria of regenerative mucosa. IL-6 was increased significantly in regenerative mucosa after injury, especially at 14 days post wounding when compared with normal mucosa. IL-8 was also increased significantly in regenerative mucosa; however, IL-10 was decreased significantly when compared with normal mucosa. IL-6 and IL-8 showed a significant correlation with the expression level of collagen type I.

Endoscopic surgical treatment of neurogenic tumor in pterygopalatine and infratemporal fossae via extended medial maxillectomy.

Abstract Conclusion: The endoscopic extended medial maxillectomy approach for the management of lesions of the pterygopalatine and infratemporal fossa provides excellent exposure and results with good hemostasis and low morbidity. This approach is a viable alternative to the open approaches to these areas. Objectives: To describe an endoscopic extended medial maxillectomy approach for the treatment of nonmalignant tumors in the pterygopalatine and infratemporal fossa. Methods: From January 2004 to June 2007, five patients who had tumors in the pterygopalatine fossa and/or infratemporal fossa, and underwent surgical resection of the tumors with the endoscopic extended medial maxillectomy approach, were reviewed regarding demographics, preoperative images, tumor cell type, surgical techniques, and outcomes. Results: Five patients underwent the procedure mentioned above; three females and two males with a mean age of 38 and a range of 21–58 years. All patients had adequate exposure and total tumor resection with the endoscopic extended medial maxillectomy approach. None of the patients required an external approach for tumor extirpation. There were no major postoperative complications. No evidence of tumor recurrence was noted after follow-up for 12–78 months.

A Randomized, Double-Blind, Placebo Controlled Trial of Sublingual Immunotherapy with House-Dust Mite Extract for Allergic Rhinitis

Objective This study was designed to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) with house-dust mite (HDM) extract in Chinese patients with HDM-induced allergic rhinitis (AR). Methods A randomized, double-blind, placebo controlled trial was conducted with the outpatients of the Eye, Ear, Nose, and Throat Hospital, Fudan University. Forty-eight patients were eligible for randomization to SLIT with a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae extract or placebo for 1 year. The primary outcome measures for efficacy were the total nasal symptom score (TNSS) and the individual nasal symptom score. Secondary end points were allergic conjunctivitis scores (ACS) and medication scores (MS). Adverse events (AE) also were monitored. Results Intragroup analysis demonstrated a significant improvement in the active treatment group for individual nasal symptom score and TNSS (p < 0.05), although no improvement was observed in the placebo group of congestion, sneezing, and itching (p > 0.05). Furthermore, the ACS and MS in the active treatment group also statistically decreased (p < 0.05). In addition, the active treatment had significant effects on relieving nasal symptoms both in adults and children (p < 0.05), and no statistical difference was observed between these two subgroups (p > 0.05). AEs that occurred ranged from mild to moderate, and no severe systematic reactions were observed. Conclusion SLIT with a mixture of HDM extract significantly relieved allergy symptoms and reduced the need for antiallergic drugs, which indicated the superiority of active treatment over placebo for patients with HDM-induced AR. However, due to the limited sample size, the findings need to be further confirmed.

Prognostic value of matrix metalloproteinase 9 expression in patients with juvenile nasopharyngeal angiofibroma: tissue microarray analysis.

OBJECTIVE Although JNA is a benign neoplasm histopathologically, it has a propensity for locally destructive growth and remains a higher postoperative recurrence rate. The aim of this study was to analyze the expression and localization of MMP-9 in JNA using tissue microarray to elucidate its correlation with clinicopathological features and recurrence. MATERIALS AND METHODS The expression of MMP-9 was assessed by immunohistochemistry in a tissue microarray from 70 patients with JNA and 10 control subjects. Correlation between the levels of MMP-9 expression and clinicopathologic variables, as well as tumor recurrence, were analyzed. RESULTS MMP-9 was detected in perivascular and extravascular less differentiated cells and stromal cells of patients with JNA but not in the matured vascular endothelial cells of these patients. The presence of MMP-9 expression in JNA was correlated with patients age (p=0.001). Spearman correlation analysis suggested that high expression of MMP-9 in JNA had negative correlation with patients age (r=-0.412, p<0.001). The recurrence rate in JNA patients with high MMP-9 expression was significantly higher than those with low MMP-9 expression (p=0.002). In multivariate and ROC curve analysis, MMP-9 was a good prognostic factor for tumor recurrence of JNA. CONCLUSION Higher MMP-9 expression is a poor prognostic factor for patients with JNA who have been surgically treated.

The presence of tumor-infiltrating IL-17-producing cells in juvenile nasopharyngeal angiofibroma tumor microenvironment is a poor prognostic factor

BACKGROUND Although juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor histologically, it demonstrates aggressive propensity of locally destructive growth causing bone erosion. The patients with JNA remain high recurrence rate after surgical excision. Th17 cells secrete the proinflammatory cytokine interleukin-17 (IL-17), and play an important role in carcinogenesis and tumor progression. So far, no studies have focused on the significance of IL-17-producing cells in the JNA tumor microenvironment. The current study was designed to investigate the localization and level of tumor-infiltrating IL-17-producing cells in JNA microenvironment. The presence and number of IL-17-producing cells were further analyzed for a possible association with clinicopathological features and disease outcome. MATERIALS AND METHODS Immunohistochemistry was used to analyze the expression of IL-17 in a tissue microarray from 70 patients with JNA and 10 control subjects. Correlations between the levels of IL-17 expression and clinicopathologic variables, as well as tumor recurrence, were assessed. RESULTS In vessels, the IL-17-producing cells were identified in pericytes and irregular smooth muscle cells, but the matured vascular endothelial cells showed no IL-17 reactivity. The expression of IL-17 in stromal cells was concentrated in the less differentiated and plump cells that contained a central hypochromatic nucleus and single small nucleolus. Chi-square test showed that tumor stage (p=0.09), operation history (p=0.828), operation approach (p=0.159), and volume of intraoperative hemorrhage (p=0.352) were not associated with the expression of IL-17 in JNA patients. However, intratumoral IL-17-producing cells were negatively associated with patients age (p=0.004). Furthermore, we found that patients with extensive infiltration of IL-17-producing cells had significantly higher recurrence rates than those with less infiltration of IL-17-producing cells (p=0.028). Log rank analysis showed that JNA patients with high levels of IL-17 had significantly shorter disease free survival (DFS) than those with low levels of IL-17 (p=0.004). Univariate Cox regression analysis suggested that IL-17 and patients age were significantly associated with DFS. Multivariate analysis indicated that high infiltration with IL-17-producing cells was associated with poor DFS. Of all clinicopathological features, IL-17 level was an independent factor predicting the patients prognosis. CONCLUSION In JNA patients, a high level of IL-17-producing cells was negatively associated with patients age. Patients with extensive infiltration of IL-17-producing cells had significantly higher tumor recurrence rates. High infiltration of IL-17-producing cells in JNA microenvironment is an independent poor prognostic factor for shorter disease-free survival. Future studies further focusing on the role of IL-17 may provide more promising therapeutic methods for extensive JNA tumors.

Organized Hematoma: An Analysis of 84 Cases with Emphasis on Difficult Prediction and Favorable Management.

Objective To characterize features of organized hematoma (OH) that may cause considerable diagnostic difficulties. Study Design Case series with chart review. Setting Tertiary medical center. Subjects and Methods Eighty-four patients with pathologically confirmed OH over a 10-year period were retrospectively reviewed for clinical features, imaging findings, pathologic characteristics, and treatment modalities. Results This study included 39 males and 45 females who presented with frequent epistaxis and nasal obstruction. There were 62 (74%) patients >40 years old (mean, 50; range, 9-81). OH mainly originated in the maxillary sinus (n = 82) or nasal cavity (n = 2) unilaterally, and most were expansile masses (n = 73) that extended into nasal cavity (n = 71) or choanae (n = 17). Several lesions were locally aggressive and simulated a malignant process that involved the ethmoid sinus (n = 22), orbit (n = 11), pterygopalatine fossa (n = 16), infratemporal fossa (n = 9), cheek (n = 3), and hard palate (n = 3). Internal architecture on computed tomography (CT) scans showed OH with expansile remodeling of the maxillary wall (82.1%) and smooth bony destruction (70.2%), whereas T2-weighted magnetic resonance (MR) images showed inhomogeneity with a notable hypointense peripheral rim in all lesions. CT and MR contrast-enhanced images revealed patchy heterogeneous enhancement that could be interpreted according to histopathologic findings of hemorrhage and neovascularization. OH was successfully removed with endoscopic surgery, although 5 cases recurred. Conclusions OH can be successfully treated by endoscopic surgery. CT and MR examination provide characteristic findings for prediction and careful surgical planning.