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PurposeThe aim of this study was to retrospectively evaluate the oncologic outcomes of sinonasal malignancies (SNMs) of various histologic subtypes and investigate the impact of multimodality treatment on prognosis of SNM.MethodsSNM patients treated with curative-intent surgery from 2000 to 2018 were included. The primary outcomes were overall survival (OS). Survival was then assessed through Cox proportional hazards models.ResultsThree hundred and three patients were eligible for the analysis. The 5-year OS and event-free survival (EFS) were 61.0% (95% CI: 55.4%–67.1%) and 46.2% (95% CI: 40.4%–52.7%). The 5-year OS was the worst for malignant melanoma and the best for adenocarcinoma. Patients who received surgery had better OS than those who only received radiotherapy and/or chemotherapy. Endoscopic surgery had better OS than the open approach (p < 0.05). Microscopically margin-negative resection (R0 resection) significantly benefited OS and EFS (p < 0.001). No significant difference in OS was observed between patients who received macroscopic complete resection (R1 resection) followed by adjuvant therapy and patients who received R0 resection. Older age (HR = 1.02, p = 0.02), R1 resection (HR = 1.99, p = 0.02), sinonasal surgical history of more than 3 months before diagnosis (HR = 2.77, p = 0.007), and radiotherapy history (HR = 3, p = 0.006) are risk factors for worse EFS.ConclusionsCurative-intent surgery is irreplaceable in the treatment of SNM. The endoscopic approach is an effective alternative to the open approach. EFS is worse among patients with older age, R1 resection, sinonasal surgical history of more than 3 months before diagnosis, and radiotherapy history.

BackgroundPD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade.Materials and methodsPotential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors.ResultsAnalysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers.ConclusionCD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources.

ObjectiveTo investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment.Materials and MethodsA list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein–protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient’s survival were analyzed using GEPIA, the Kaplan–Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells.ResultsAnalysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration.ConclusionsThe ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.

Background: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus surgery (ESS) removal is preferred because of the less invasiveness and minimal morbidity. This study was designed to summarize clinical experience with ESS management of FBSOS. Methods: We retrospectively reviewed clinical manifestations, imaging findings, treatment, and outcomes in consecutive patients with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical center. The Chi-square test was performed to compare the infection rate between wooden and nonwooden FBSOS. Results: There were 23 male and five female patients, with median age of 11 years. FBSOS were located within the sinuses (86%), orbit (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05). Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone, while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical approach. Four of the nine intracranial penetrating FBSOS patients had intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and vision loss). Conclusions: ESS is a minimally invasive, safe, and promising surgical approach for FBSOS removal. Contrast-enhanced CT is effective in preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk of infection, thus antibiotics are recommended.

OBJECTIVE: The therapeutic effect of middle frontal horizontal partial laryngectomy (MFHPL) in treating stage T1b squamous cell carcinoma of the glottic larynx involving anterior vocal commissure (AVC) was compared with that of the anterior frontolateral vertical partial laryngectomy (AFVPL). The feasibility and practical significance of MFHPL in clinical application was discussed in the present study. METHODS: From January 1996 to January 2010, a total of 65 patients diagnosed with stage T1bN0M0 glottic laryngeal cancer were treated with MFHPL or AFVPL. The postoperative complications, glottic reconstruction, recurrence rate, voice quality and survival rates were evaluated and compared between two treatments. RESULTS: AFVPL and MFHPL were performed in 34 and 31 patients, respectively. Flexible fiberoptic laryngoscopy revealed that in the MFHPL-treated patients the reconstructed glottis was spacious and symmetric. In contrast, AFVPL treatment resulted in irregular glottic area with poor symmetry and tubular glottis. The incidence of postoperative laryngeal stenosis significantly differed between the MFHPL- and AFVPL-treated groups (P = 0.025). No significant difference was detected in the 3- and 5-year overall- or tumor-free survival rates between two treatments. The Voice Handicap Index (VHI) and maximum phonation time (MPT) after surgery were 51.0±12.99 and 12.42±3.44 sec in the AFVPL-treated group; while in the MFHPL-treated patients they were 31.81±7.48 and 7.65±1.98 sec, respectively. Both differences in VHI (P = 0.012) and MPT (P = 0.024) were significant between two treatments. CONCLUSIONS: MFHPL was comparable to AFVPL with respect to postoperative complications, recurrence rate and survival rates, but possessed advantages over AFVPL in terms of the incidence of laryngeal stenosis and voice quality. Our study indicated that MFHPL has a potential value in clinical practice of treating stage T1b squamous cell carcinoma of the glottic larynx involving AVC.

Abstract As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.

Background: Dendritic cells (DCs) have been used successfully in clinical pilot studies. However, tumor-specific immunity and clinical responses were only induced in certain cancer patients. It has been well documented that immunotherapy efficacy can be optimized for responses using antigen pulsing. Methods: The human laryngeal squamous cell cancer (LSCC) cell line SNU899 was used to evaluate the in vitro anti-tumor efficacy of three different preparations of dendritic cell (DC) vaccines consisting of either whole tumor cells or their derivatives including: i) DCs pulsed with a tumor cell supernatant (DC-TCS), ii) DCs pulsed with whole-cell tumor stressed lysate (DC-TSL), and iii) DCs pulsed with irradiated tumor cells (DC-ITC). Results: Our results showed that DC-TSL is an effective source of tumor-associated antigens (TAAs) for pulsing DCs. DC-TSL induced the highest expansion of TAA-specific T cells, the strongest Th1 cytokine response, and the most potent cytotoxic T lymphocyte (CTL) activity. DC-TCS and DC-ITC inhibited T cell activation but induced a certain extent of CTL activity. Conclusions: These data suggest that DC-TSL is a more potent inducer of antitumor immunity against laryngeal cancer than other antigen-loading strategies using whole tumor cell materials. This strategy provides an alternative approach for DC-based immunotherapy for laryngeal cancer. [ABSTRACT FROM AUTHOR]

MicroRNA (miR)-9 has been demonstrated to regulate the radiosensitivity of tumor cells. In the present study, the mechanism by which miR-9 modulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to ultraviolet (UV) radiation was investigated. The results demonstrated that exposure of NPC cells to UV light resulted in a significant increase in the expression of miR-9, and that CNE2 cells overexpressing miR-9 exhibited reduced levels of DNA damage and increased levels of total glutathione upon UV exposure. Accordingly, the inhibition of the expression of miR-9 promoted UV-induced DNA damage and apoptosis. Although miR-9 inhibited the expression of E-cadherin in the CNE2 cells and increased their resistance to UV radiation, the use of small interfering RNA to inhibit the expression of E-cadherin was not sufficient to decrease the radiosensitivity of the NPC cells. These data demonstrated that miR-9 did not modulate the sensitivity of the CNE2 cells to UV radiation through E-cadherin, but suggested that miR-9 regulated radiosensitivity through its effects on glutathione. These findings suggest that miR-9 may be a potential target for modulating the radiosensitivity of NPC cells. [ABSTRACT FROM AUTHOR]

Objective: To compare the real-time diagnostic accuracy of conventional white-light imaging (WLI) endoscopy with that of narrow-band imaging (NBI) endoscopy in patients at high risk for nasopharyngeal carcinoma (NPC). Design: Prospective study. Setting: A university tertiary care center. Patients: From July 28 through October 27, 2009, a total of 211 consecutive patients at high risk for NPC were enrolled. A high-performance endoscopic system equipped with WLI and NBI modes was used for a detailed examination of the nasopharynx during the same endoscopy. Main Outcome Measures: Diagnostic efficacies of WLI and NBI were compared with pathologic findings. Lesions were classified according to the detailed morphologic epithelial microvessel observations during NBI. Results: A total of 285 lesions were detected, including 66 cancerous lesions. The sensitivity and negative predictive values of NBI in NPC screening were significantly higher than those of WLI (93.9% vs 71.2%, P=.001; and 98.1% vs 91.7%, P=.003; respectively); specificity and positive predictive value were not significantly different. During NBI, the presence of superficial, distorted, irregularly shaped microvessels indicated malignant lesions; 53 of 55 lesions (96.4%) with type IV intrapapillary capillary loops were confirmed on histologic testing as malignant. The false-negative and false-positive rates for NBI were 4.5% and 3.6%, respectively. Conclusions: Narrow-band imaging endoscopy is a promising tool to differentiate nonmalignant from malignant nasopharyngeal lesions on the basis of the morphologic findings of mucosal capillary vessels in vivo. In addition, NBI may increase the diagnostic value of endoscopy in populations at high risk for NPC. [ABSTRACT FROM AUTHOR]

Background: DJ-1 can induce the tumor cell proliferation and invasion via down-regulating PTEN in many malignant tumors, and correlated to prognostic significance. However, the tumorigenesis role and clinical significance of DJ-1 in supraglottic squamous cell carcinoma (SSCC) is unclear. We aimed to evaluate the DJ-1 the relationship between DJ-1 and clinicopathological data including patient survival. Methods: The expression of DJ-1 and PTEN in SSCCs (52) and adjacent non-cancerous tissues (42) was assessed by immunohistochemistry (IHC), and the relationship between DJ-1 and clinicopathological data was analyzed. Results: DJ-1 was detected mainly in SSCCs (88.5%) and less frequently in adjacent non-cancerous tissues (21.0%). PTEN expression was detected in 46.2% of SSCCs and in 90.5% of adjacent non-cancerous tissues. DJ-1 expression was linked to nodal status (P = 0.009), a highly significant association of DJ-1 expression with shortened patient overall survival (5-year survival rate 88.0% versus 53.9%; P = 0.007; log rank test) was demonstrated. Conclusions: Our data suggested that DJ-1 over-expression was linked to nodal status, and might be an independent prognostic marker for patients with SSCC. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Nasopharyngectomy for residual/recurrent nasopharyngeal carcinoma (NPC) using an endoscopic technique is less invasive than traditional methods. Our objective was to identify the important anatomic landmarks so that the endoscopic surgeon can avoid injury to the internal carotid artery and perform a nasopharyngectomy safely. Study Design: Anatomical study. Methods: Transnasal endoscopic dissection was carried out on three fresh adult cadaver specimens (six sides) after arterial latex injection. Measurements were made in 50 adult skulls (100 sides), detailing the distances between orienting critical landmarks and the internal carotid canal (external aperture). Results: Adequate exposure for endoscopic nasopharyngectomy is available by removing portions of the inferior turbinate, nasal septum, and medial pterygoid plate. Anatomy of the operative field (endoscopic view) is described. Orientating topical landmarks include: posterior portions of the inferior turbinate and nasal septum, fossa of Rosenmuller, and the torus tubarius. The deep landmarks include: medial pterygoid plate–posterior margin at the skull base, eustachian tube isthmus, foramen lacerum, and the longus capitis. All topical and deep landmarks were identified from the endoscopic point of view and their distances to the internal carotid canal (external aperture) were measured. Conclusions: This anatomic study provides novel orienting landmarks for endoscopic nasopharyngectomy. Surgeons can efficiently and safely deal with residual and/or recurrent NPC endoscopically. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]