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Background: To compare the safety and efficacy between endoscopic sinus surgery and different biologics in treating chronic rhinosinusitis with nasal polyps in adults by reviewing the existing clinical trials. Methods: Data extraction and risk of bias assessment were conducted by 2 independent reviewers according to the PRISMA recommendations and any disagreement was resolved by a third investigator. Outcomes were measured through a random‐effects model. We searched Embase, Web of Science, MEDLINE, Cochrane, and other relevant sources from its inception to April 30, 2022. We included randomized controlled trials(RCTs) involving endoscopic sinus surgery (ESS) or biologics in treating adult patients with chronic rhinosinusitis with nasal polyps. Studies involving other miscellaneous diseases, non‐RCT design, and insufficient participants or follow‐up were excluded. Results: In this systematic review, five RCTs and 1748 patients were included. All the biologics, as well as ESS, could significantly improve key nasal outcomes in CRSwNP both at 6 months and 1 year. Dupilumab exhibited better efficacy than ESS in improving SNOT‐22 scores at one year. However, ESS showed superiority over three biologics in improving nasal congestion scores (NCS) at two various time points, except for better efficacy of Dupilumab at 1 year. For the loss of smell scores, a greater improvement was observed in the Dupilumab cohort compared with other biologics and even ESS counterparts. Safety analysis showed no significant difference between the ESS cohort and biologic treatment. Conclusions: In summary, ESS showed comparable improvement in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab seems to be more effective than ESS in selected items, whereas head‐to‐head trials and real‐world studies are urgent to compare their efficacy. Our findings also showed that biologics could be applied as alternative or adjuvant therapy for uncontrolled severe CRSwNP. [ABSTRACT FROM AUTHOR]

Background: As a cancer stem cells (CSCs) surface marker, Lgr5 plays an important role in the signal transduction of cancer cells and is a potential biomarker for cancer diagnosis and prognosis. However, the expression and prognostic value of Lgr5 in recurrent nasopharyngeal carcinoma (rNPC) remains ambiguous. Materials: We used RNA sequencing to screen differentially expressed mRNAs in eleven specimens of rNPC tissues and five fresh adjacent normal tissue samples and the CSC marker, Lgr5, was identified. The expression level of Lgr5 in rNPC samples was also detected by immunohistochemistry and Western blot assay. The chi-square test was used to analyze the relationship between the clinicopathological variables and the immunostaining of Lgr5. The Log-rank method was used for prognosis analysis. The Cox regression model was used for univariate and multivariate analysis. Results: Significantly elevated expression of Lgr5 in the rNPC tissues was observed compared to the normal tissues using RNA sequencing, Western blot and immunohistochemistry. The expression of Lgr5 was significantly correlated with the T stage (P=0.014). High Lgr5 expression (P=0.007), tumor necrosis (P=0.013) and WHO type II (P=0.043) in rNPC patients exhibited worse overall survival (OS). Lgr5 expression was proved to be an independent risk factor for OS (P=0.035) in multivariate analyses, and had promising predictive value for survival and recurrence in rNPC patients (area under the ROC curve: 0.711 and 0.665, P=0.017 and 0.028, respectively). Conclusion: Lgr5 as a CSC marker is a promising therapeutic target and could be employed to predict the survival prognosis of rNPC patients. [ABSTRACT FROM AUTHOR]

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Objective: Sinonasal melanoma (SMM) is a rare but aggressive malignancy with 5‐year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SMM remain undefined. We aimed to establish a model to predict the survival outcomes of SMM. Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SMM between 1975 and 2016. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. We also developed and validated a nomogram for OS, and compared its performance with that of conventional staging systems. Results: Overall, 305 SMM patients were included in this population‐based study. Multivariate Cox regression showed that primary site, American Joint Committee on Cancer stage, radiotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C‐indices, areas under the receiver operating characteristic curves, calibration plots, and decision curve analysis demonstrated reliable performance of the nomogram. Conclusion: The nomogram predicting survival outcomes of SMM patients based on clinical information showed good discriminative ability and prognostic accuracy compared with conventional stage classifications. Our nomogram could be used to predict the survival probabilities for SMM patients at different timepoints. Level of Evidence: 2b. [ABSTRACT FROM AUTHOR]

Increasing evidence shows that alterations in microRNA (miRNA) expression are involved in the occurrence and development of various malignant tumors, including colon cancer. MiRNA-524-5p has been reported to have anticancer activity in colon cancer. This study explored the influence of the miRNA-524-5p/CXCR7 axis on angiogenesis using colon cancer cells and further studied the mechanisms involved. We found that changing the expression of miRNA-524-5p can affect colonic proliferation, migration, and angiogenesis. Furthermore, angiogenesis induced by miRNA-524-5p overexpression was reversed by overexpression of CXCR7 in HT-29 cells, while the opposite was observed in Caco-2 cells. Furthermore, miRNA-524-5p inhibited the activation of AKT and ERK signaling by targeting CXCR7. Overall, our results indicated that the miRNA-524-5p/CXCR7 axis regulated angiogenesis in colon cancer cells through the AKT and ERK pathways. [ABSTRACT FROM AUTHOR]

Objective  Temporalis muscle flap (TMF) is widely used in traditional skull base surgery, but its application in endoscopic skull base surgery remains rarely reported. We aimed to investigate the surgical anatomy and clinical application of TMF for reconstruction of skull base defects after expanded endoscopic nasopharyngectomy. Methods  Nine fresh cadaver heads (18 sides) were used for endoscopic dissection at the University of Pittsburgh School of Medicine in the United States. TMF was harvested using a traditional open approach and then transposed into the maxillary sinus and nasal cavity through the infratemporal fossa using an endoscopic transnasal transmaxillary approach. TMF length was then measured. Moreover, TMF was used for the reconstruction of skull base defects of six patients with recurrent nasopharyngeal carcinoma after expanded endoscopic nasopharyngectomy. Results  The length of TMF harvested from the temporal line to the tip of the coronoid process of the mandible was 11.8 ± 0.9 cm. The widest part of the flap was 9.0 ± 0.4 cm. When TMF was dislocated from the coronoid process of the mandible, approximately another 2 cm of reach could be obtained. When the superficial layer of the temporalis muscle was split from the deep layer, the pedicle length could be extended 1.9 ± 0.2 cm. TMF could cover skull base defects in the anterior skull base, sellar, and clivus regions. Conclusion  TMF can be used to reconstruct skull base defects after endoscopic expanded nasopharyngectomy and can effectively prevent the occurrence of serious complications in patients with recurrent nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the world's most common head and neck cancer. However, the immune infiltration phenotypes of LSCC have not been well investigated. Methods: The multi-omics data of LSCC were obtained from the TCGA (n=111) and GEO (n=57) datasets. The infiltrations of the 24 immune cell populations were calculated using the GSVA method. Then LSCC samples with different immune cell infiltrating patterns were clustered, and the multi-omics differences were investigated. Results: Patients were clustered into the high-infiltration and low-infiltration groups. The infiltration scores of most immune cells were higher in the high-infiltration group. Patients with high-infiltration phenotype have high N and TNM stages but better survival, as well as less mutated COL11A1 and MUC17. Common targets of immunotherapies such as PD1, PDL1, LAG3, and CTLA4 were significantly up-regulated in the high-infiltration group. The differentially expressed genes were mainly enriched in several immune-related GOs and KEGG pathways. Based on the genes, miRNAs, and lncRNAs differentially expressed in both the TCGA and GEO cohorts, we built a ceRNA network, in which BTN3A1, CCR1, miR-149-5p, and so on, located at the center. A predictive model was also constructed to calculate a patient's immune infiltration phenotype using 16 genes' expression values, showing excellent accuracy and specificity in the TCGA and GEO cohorts. Conclusions: In this study, the immune infiltration phenotypes of LSCC and the corresponding multi-omics differences were explored. Our model might be valuable to predicting immunotherapy's outcome. [ABSTRACT FROM AUTHOR]

Background: Juvenile nasopharyngeal angiofibroma (JNA) is a highly recurrent tumor after curative surgery. Objective: The purpose of this study was to evaluate heat shock protein 90 (HSP90) expression in JNA and its association with tumor recurrence. Methods: Immunohistochemistry was performed to assess HSP90 expression using tissue microarrays containing 70 JNA patients and 10 control subjects. The associations of HSP90 expression with clinicopathological features and tumor recurrence were analyzed. Results: Immunohistochemistry revealed high HSP90 expression in JNA compared with normal middle turbinate samples. High expression of HSP90, which correlated with MVD (P =.001), ER-α (P =.001), VEGF (P <.001) and JNA recurrence (P =.009), was an independent prognostic factor of time to recurrence (P =.017). The combination of HSP90 and ER-α had a better power to predict disease recurrence than other clinicopathological features (P =.008). Conclusions: HSP90 may be an independent prognostic marker in JNA patients administered surgical treatment. Combination of HSP90 and ER-α expression may be the best predictor of tumor recurrence among all clinicopathological factors. [ABSTRACT FROM AUTHOR]

Background: Minor salivary gland cancer (MiSGC) is a group of tumors with varied disease course in the head and neck. We evaluated the risk of a second primary malignancy (SPM) in MiSGC patients and identified possible prognostic factors for survival using a large population database. Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data to evaluate the risk and prognosis of SPM in patients diagnosed with MiSGC. Results: The risk of SPM increased in MiSGC patients compared with the endemic rate. The risk of SPM was slightly greater in female patients and who underwent radiotherapy. Age at primary diagnosis, sex, race, year of diagnosis, SEER stage, radiotherapy, SPM, histology, and tumor site were significant survival prognostic indicators of MiSGC patients. Conclusion: Radiotherapy and female sex were risk factors for SPM after MiSGC. Long‐term surveillance for SPM was important in MiSGC patients. [ABSTRACT FROM AUTHOR]

Purpose: Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is a rare nasopharyngeal tumor. This study aimed to analyze the clinical and histopathological features of the disease, and to share our experience of its treatment. Patients and Methods: We collected demographic data, clinical symptoms, tumor location, pathological features, immunohistochemical results, treatments, and outcomes of 28 patients with pathologically confirmed LGNPPA between 2009 and 2019. Results: The median age of the 28 patients was 41.5 years, with a female: male ratio of 1.5:1 (17 females, 11 males). The most common symptom was blood-stained rhinorrhea. The neoplasms were located on the roof of the nasopharynx (RON) in 13 patients, the posterior margin of the nasal septum (PMONP) in 12 patients, the lateral wall of the nasopharynx in one case, and both the RON and PMONP in two patients. Fourteen patients were diagnosed with thyroid-like LGNPPA. Immunohistochemically, the tumors were uniformly positive for cytokeratin 7, cytokeratin 8, vimentin, epithelial membrane antigen, and pan-cytokeratin, and negative for thyroglobulin. Twenty-three patients underwent pure endoscopic surgery, three patients underwent preoperative radiotherapy, and two patients underwent radiotherapy postoperatively. All patients were alive without evidence of lymphatic or distant metastases in the follow-up period (range: 7 to 121 months). Two patients (7%, 2/28) experienced disease recurrence. Conclusion: LGNPPA is an indolent tumor with an excellent prognosis. Endonasal endoscopic excision was an effective treatment. It is important to distinguish thyroid-like LGNPPA from metastatic papillary thyroid carcinoma because these diseases have similar microscopic features but different prognoses. [ABSTRACT FROM AUTHOR]

Background: It was recently suggested that the upregulation of podoplanin (PDPN) in cancer cells plays a significant role in tumor invasion and metastasis and that it is significantly associated with poor prognosis in oral, cutaneous, and esophageal squamous cell carcinoma. The aim of this study was to investigate the expression pattern of PDPN in sinonasal squamous cell carcinoma (SNSCC) and to evaluate its role as a prognostic factor for survival outcome. Patients and methods: This study included 59 subjects with SNSCC. We retrospectively collected the clinical features of these patients from medical records and retrieved the associated formalin-fixed, paraffin-embedded tissues for PDPN immunohistochemical staining. Furthermore, PDPN expression was analyzed in relation to the patients' clinicopathological features and prognosis. Results: We observed positive staining for PDPN in both cancer cells and stromal cancer-associated fibroblasts (CAFs). Positive expression of PDPN in cancer cells of patients with SNSCC was significantly correlated with the primary tumor site (p = 0.009) and local recurrence (p = 0.024). In addition, patients with PDPN-positive cancer cells had significantly lower overall survival (OS) and disease-free survival (DFS) rates than did patients with PDPN-negative cancer cells (both p < 0.05). Multivariate analysis revealed that PDPN expression in cancer cells was an independent prognostic factor for both OS (p = 0.038) and DFS (p = 0.039). Conclusions: Our findings demonstrated that PDPN overexpression may be both an independent prognostic biomarker and a therapeutic target in SNSCC. [ABSTRACT FROM AUTHOR]

Background: Recurrent nasopharyngeal carcinoma (rNPC) is mainly managed with re‐irradiation or salvage surgery. Endoscopic resection is generally considered as the preferred surgical treatment, whereas a standard treatment modality has yet to be established. This article is aimed to summarize the treatment outcomes of endoscopic rNPC resection. Methods: Major medical databases including PubMed, EMBASE, Cochrane Central Library, Web of Science, and 2 major Chinese databases, CNKI and Wanfang, were searched for studies on endoscopic rNPC resection. Main characteristics of study and outcomes of interest were retrieved from articles meeting the selection criteria for meta‐analysis. Results: A total of 761 articles were identified through the initial systematic research. The combined 1‐year, 2‐year, and 5‐year overall survival (OS) rates were 97%, 92%, and 73% with random effect model, respectively. The combined 2‐year and 5‐year disease‐free survival (DFS) rates were 81% and 62%, respectively. Meta‐regression analysis showed that high recurrent tumor (rT) stage (rT3 to rT4) case proportion was a correlative factor of heterogeneity. Combined 2‐year OS rate in rT1, rT2, rT3, and rT4 patients were 100%, 87%, 78%, and 38%, respectively. Combined 2‐year DFS rate in rT1 and rT2 patients were and 96% and 86%, respectively. Conclusion: The combined OS and DFS rates of rNPC patients treated with endoscopic nasopharyngectomy were summarized and reported in our study. This meta‐analysis indicated that endoscopic nasopharyngectomy has comparable and possibly better treatment outcomes than intensity‐modulated radiotherapy (IMRT). Therefore, the result of our study indicated that randomized controlled trials (RCTs) are needed in rNPC patients to compare treatment outcomes of endoscopic nasopharyngectomy vs IMRT. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of fast acupuncture combined with exercise therapy on elderly patients with lumbar disc herniation. Methods: A total of 80 cases of elderly patients with lumbar disc herniation were randomly divided into treatment and control groups, 40 cases in each. The patients were treated with fast acupuncture combined with exercise therapy in the treatment group, and traditional acupuncture in the control group. The curative effect and the changes of serum TNF-α and IL-6 were compared between the two groups. Results: The treatment group (92.5%) showed higher total effective rate than the control group (82.5%), as well as lower serum TNF-α and IL-6 level than the control group, with statistically significant difference (P < 0.05). Conclusion: Fast acupuncture combined with exercise therapy can provide better efficacy than traditional acupuncture on elderly patients with lumbar disc herniation, and reduce the level of serum TNF-α and IL-6. [ABSTRACT FROM AUTHOR]

Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients' prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.

This study investigated whether microbubbles activated by low-frequency ultrasound enhanced the anti-tumor effects of curcumin in glioma cells. CCK8 proliferation assay, scratch migration assay, and transwell invasion assay were performed to estimate the proliferation, migration, and invasion rates of the glioma cells in blank control and different treatment groups, respectively. Quantitative RT-PCR (qRT-PCR) analysis was performed to determine the relative expression levels of VEGF and NCAM mRNAs in the various experimental groups. Western blotting was performed to determine the activity status of the TGF-β1/Smad signaling pathway in various groups of glioma cells by estimating the expression levels of p-SMAD2/3, VEGF, and NCAM proteins. Combined treatment (Cur-Us-MBs) with microbubbles activated by low-frequency ultrasound and curcumin significantly reduced the in vitro proliferation, migration, and invasiveness of glioma cells compared to the control and other treatment groups. Furthermore, Cur-Us-MBs significantly reduced the expression levels of VEGF and NCAM mRNAs and proteins and p-Smad2/3 proteins , including those cells stimulated with rhTGF-β. These suggested that microbubbles activated by low-frequency ultrasound enhanced the inhibition of TGF-β1/Smad/VEGF/NCAM signaling pathway by curcumin，and enhanced the antitumor effects of curcumin by significantly reducing in vitro proliferation, migration, and invasiveness of glioma cells through this pathway.

Purpose: Serum/glucocorticoid-regulated kinase 1 (SGK1) has recently emerged as a critical regulator of inflammatory diseases. In this study, we examined SGK1 expression and its possible pathogenic roles in chronic rhinosinusitis (CRS)., Methods: Immunohistochemistry, western blotting, Bio-Plex assay, enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction were performed to assess protein and gene expression levels. The mRNA expression levels of SGK1 and interleukin-6 (IL-6) were extracted from a CRS database to perform correlation analysis. Stable cell lines with SGK1 overexpression (16HBE) and knockdown (A549) were constructed to investigate the interaction between SGK1 and IL-6 in vitro ., Results: SGK1 exhibited strong cytoplasmic and nuclear staining in the epithelial layers and the lamina propria of nasal polyps (NPs) and in the mucosal tissues of CRS without nasal polyps (CRSsNP). The mRNA and protein expression levels of SGK1 and IL-6 were significantly increased in NPs and CRSsNP tissues, compared to control tissues. SGK1 phosphorylation was significantly greater in NPs than in CRSsNP tissues ( P < 0.01). The mRNA levels of SGK1 and IL-6 were significantly correlated ( P < 0.001, r = 0.649). Exposure to IL-6 significantly increased SGK1 expression in cultured dispersed NP cells, 16HBE cells, and A549 cells. IL-6 expression was significantly down-regulated in SGK1-overexpressing 16HBE cells ( P < 0.01) and significantly up-regulated in SGK1-knockdown A549 cells ( P < 0.05). Administration of GSK650394, a SGK1 inhibitor, significantly increased IL-6 self-induced mRNA expression in cultured dispersed NP cells and 16HBE cells., Conclusions: The interaction between SGK1 and IL-6 may play an anti-inflammatory role in IL-6-induced inflammation in the pathogenesis of CRS., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Checkpoint blockade immunotherapy has made tremendous progress in the treatment of a variety of cancers in recent years. Costimulatory molecules constitute the foundation of cancer immunotherapies and are deemed to be promising targets for cancer treatment. This study attempted to evaluate the potential value of costimulatory molecule genes (CMGs) in HNSCC., Materials and Methods: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, we identified the prognostic value of CMGs in HNSCC. Subsequently, CMGs-based signature (CMS) to predict overall survival of HNSCC patients was established and validated. The differences of downstream pathways, clinical outcomes, immune cell infiltration, and predictive immunotherapy responses between different CMS subgroups were investigated via bioinformatic algorithms. We also explored the biological functions of TNFRSF12A, one risk factor of CMS, by in vitro experiments., Results: Among CMGs, 22 genes were related to prognosis based on clinical survival time in HNSCC. Nine prognosis-related CMGs were selected to establish CMS. CMS was an independent risk factor and could indicate the survival of HNSCC patients, the component of tumor-infiltrating lymphocytes, and the immunotherapy response rate. Functional enrichment analysis confirmed that CMS might involve immune-relevant processes. Additionally, TNFRSF12A was related to poor prognosis and enhanced malignant phenotype of HNSCC., Conclusion: Collectively, CMS could accurately indicate prognosis, evaluate the tumor immune microenvironment, and predict possible immunotherapy outcomes for HNSCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aye, Song, Yang, Hu, Sun, Zhou, Liu, Yu and Wang.)

Objective  Temporalis muscle flap (TMF) is widely used in traditional skull base surgery, but its application in endoscopic skull base surgery remains rarely reported. We aimed to investigate the surgical anatomy and clinical application of TMF for reconstruction of skull base defects after expanded endoscopic nasopharyngectomy. Methods  Nine fresh cadaver heads (18 sides) were used for endoscopic dissection at the University of Pittsburgh School of Medicine in the United States. TMF was harvested using a traditional open approach and then transposed into the maxillary sinus and nasal cavity through the infratemporal fossa using an endoscopic transnasal transmaxillary approach. TMF length was then measured. Moreover, TMF was used for the reconstruction of skull base defects of six patients with recurrent nasopharyngeal carcinoma after expanded endoscopic nasopharyngectomy. Results  The length of TMF harvested from the temporal line to the tip of the coronoid process of the mandible was 11.8 ± 0.9 cm. The widest part of the flap was 9.0 ± 0.4 cm. When TMF was dislocated from the coronoid process of the mandible, approximately another 2 cm of reach could be obtained. When the superficial layer of the temporalis muscle was split from the deep layer, the pedicle length could be extended 1.9 ± 0.2 cm. TMF could cover skull base defects in the anterior skull base, sellar, and clivus regions. Conclusion  TMF can be used to reconstruct skull base defects after endoscopic expanded nasopharyngectomy and can effectively prevent the occurrence of serious complications in patients with recurrent nasopharyngeal carcinoma., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: Juvenile nasopharyngeal angiofibroma (JNA) is non-metastasizing but potentially locally destructive tumor of the nasopharynx. It can destroy the skull base and invade into the cerebrum. Surgical management is the primary standard but residual disease is always a risk factor. We aimed to determine the risk factors for residual disease and usual sites for these residual tumors., Methods: The medical records of 131 patients (mean age 17.6 ± 6.8, range 9-71 years) with histologically proven JNA were retrospectively analyzed. The surgeries were all nasal endoscopic approaches, with or without assistant incision., Results: The prevalence of residual disease was 16.8%. Risk factors associated with JNA recurrence included tumor stage, intraoperative bleeding, and the year in which the operation was performed. The pterygoid canal, pterygoid process, and pterygopalatine foramen were the most frequent locations for residual tumor., Conclusion: Surgical management should take particular care for the pterygoid canal, petrygoid process, and pterygopalatine foramen. Contrast-enhanced CT and MRI are effective tools to evaluate complete JNA excision in the first two days after primary surgery. Careful exploration of these areas may be the key to avoid residual JNA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To examine the expression of hypoxia-inducible factor-1α (HIF-1α) and its related molecules (cellular repressor of E1A-stimulated genes [CREG], osteopontin [OPN], proto-oncogene tyrosine-protein kinase Src [c-Src], and vascular endothelial growth factor [VEGF]) in juvenile nasopharyngeal angiofibroma (JNA) and explore the correlation between clinical prognosis and HIF-1α expression., Methods: The study performed a retrospective review of the clinical records of patients with JNA treated between 2003 and 2007. Specimens were analyzed by immunohistochemistry for HIF-1α, CREG, OPN, c-Src, and VEGF expression, and microvessel density (MVD) was assessed by tissue microarray. The correlation between expression levels and clinicopathological features including age, tumor stage, intraoperative blood loss, and recurrence was analyzed., Results: HIF-1α, CREG, OPN, c-Src, and VEGF were upregulated in endothelial cells (ECs) of patients with JNA, and strong correlations in the expression of these molecules were observed. HIF-1α expression was higher in young patients ( P = .032) and in recurrent cases ( P = .01). Survival analysis showed that low HIF-1α levels in ECs predicted longer time to recurrence (log rank test P = .006). Receiver operating characteristic curve analysis showed that HIF-1α was a prognostic factor for recurrence (area under the curve = 0.690, P = .019). No correlation was found between the expression of molecules and Radkowski stage or intraoperative blood loss., Conclusion: In cases of JNA treated surgically, HIF-1α expression in ECs is a useful prognostic factor for tumor recurrence.