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Purpose: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). Methods: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine–Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. Results: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05–1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13–2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23–1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11–2.12; P = 0.009). Conclusion: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Sorafenib is the most widely used first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but such treatment provides only limited survival benefits that might be related to the immune status of distinct tumor microenvironments. A fundamental understanding of the distribution and phenotypes of T lymphocytes in tumors will undoubtedly lead to the development of novel immunotherapeutic strategies that could possibly enhance the efficacy of sorafenib treatments. Methods: Flow cytometry, immunohistochemistry and immunofluorescence analyses were performed to detect the infiltration and distribution of various leukocyte populations, and the expression of different immune checkpoint molecules in fresh HCC tumor tissues. Correlations among indicating genes were calculated in 365 patients with HCC from The Cancer Genome Atlas (TCGA) data set, and the cumulative overall survival time was calculated using the Kaplan–Meier method. Moreover, role of adenosinergic pathway on sorafenib anti-tumor efficacy was investigated using both subcutaneous and orthotopic transplantation tumor model in immune competent C57BL/6 mice. Results: We revealed that levels of CD3+ and CD8+ T cells were significantly downregulated in HCC tumor tissue, so were the infiltration of CD169+ cells (a Mφ subpopulation with T cell activation capacities) and their contact with CD8+ cells in tumor milieus. Moreover, levels of PD-1 and CD39 expression were significantly upregulated in human HCC-infiltrating CD4+ and CD8+ T cells, and CD39+CD8+ T cells exhibited a CD69+PD-1+perforinlowIFNγlow "exhausted" phenotype. Levels of both CD39+ T cells infiltration and adenosine receptor ADORA2B expression in tumor tissues were negatively correlated with overall survival of patients with HCC. Accordingly, mice treated with sorafenib in combination with adenosine A2B receptor blockage reagents exhibited significantly reduced tumor progression compared with control groups. Conclusions: These results suggest that adenosinergic pathway might represent an applicable target for sorafenib-combined-therapies in human HCC. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) mediate immunosuppressive signals that can contribute to the progression of head and neck squamous cell carcinoma (HNSCC). Interleukin-33 (IL-33) is defined as an 'alarmin', an endogenous factor that is expressed during tissue and cell damage, which has been shown to promote Treg proliferation in non-lymphoid organs. However, the interaction between IL-33 and Tregs in the HNSCC tumor microenvironment remains uncertain. In this study, we examined IL-33+ and Foxp3+ cells by immunohistochemistry in 68 laryngeal squamous cell cancer patients, followed by functional analysis of IL-33 in Tregs. In addition, the suppressive function of Tregs was assessed by cell proliferation assays. The level of stromal IL-33 was significantly upregulated in advanced versus early stage HNSCC patients and positively correlated with Foxp3+ Treg infiltration as well as a poor prognosis. ST2 is regarded as the only receptor of IL-33. Infiltrated ST2-expressing Tregs were responsive to IL-33, and the percentage of Tregs was increased upon IL-33 stimulation. Functional investigation demonstrated that IL-33 increased the proportion of Foxp3+GATA3+ Tregs and improved the suppressive functions of Tregs by inducing IL-10 and TGF-β1 as well as decreasing the proliferation of responder T cells. Blockade of ST2 abrogated the immunosuppression caused by IL-33. Our data demonstrate that stromal IL-33 both expands the Treg population and enhances their functions in the tumor microenvironment. Furthermore, stromal IL-33 has prognostic value for tumor progression. Thus, stromal IL-33 is a potential target for future HNSCC immunotherapy. [ABSTRACT FROM AUTHOR]

Background:Foxp3+ regulatory T (Treg) cells and M2 macrophages are associated with increased tumour progression. However, the interaction between Treg cells and M2 macrophages remains unclear.Methods:The expression of FoxP3 and CD163 was detected by immunohistochemistry in 65 cases of laryngeal squamous cell carcinoma (LSCC). In vitro, the generation of activated Treg (aTreg) cells and M2 macrophages by interactions with their precursor cells were analysed by flow cytometry and ELISA. In vivo, the antitumour effects were assessed by combined targeting aTreg cells and M2 macrophages, and intratumoural immunocytes were analysed by flow cytometry.Results:In LSCC tissue, accumulation of aTreg cells and M2 macrophages predicted a poor prognosis and were positively associated with each other. In vitro, aTreg cells were induced from CD4+CD25− T cells by cancer cell-activated M2-like macrophages. Consequently, these aTreg cells skewed the differentiation of monocytes towards an M2-like phenotype, thereby forming a positive-feedback loop. Combined targeting aTreg cells and M2 macrophages led to potent antitumour immunity in vivo.Conclusions:The positive-feedback loop between aTreg cells and M2 macrophages is essential to maintain or promote immunosuppression in the tumour microenvironment and may be a potential therapeutic target to inhibit tumour progression. [ABSTRACT FROM AUTHOR]

This manuscript investigates the strength reduction factor of single degree of freedom system with constant ductility performance subjected to the mainshock-aftershock sequence-type ground motions. The recorded and artificial sequence-type ground motions are used. The aftershock ground motions in sequence are scaled to have different relative intensity levels. Four hysteretic models are used to simulate the different type of structures. The effects of period, ductility factor, site condition, aftershock, hysteretic behavior and damping are studied statistically. The results indicate that the strong aftershock ground motion has more obvious influences on strength reduction factors in short period region than on those in long period region. The degrading behavior would decrease the strength reduction factor of structure with short period at a magnitude of <20 %, while it would increase that of structure with medium-long period at a maximum level of 20 %. Finally, a predictive model, incorporating the effect of aftershock, is proposed to determine the strength reduction factor in the seismic design. [ABSTRACT FROM AUTHOR]

The purpose is to summarize the experience in full endoscopic transsphenoidal resection of pituitary adenoma in 28 patients by rhinologist, and introduce the surgical skill of otolaryngologist, especially skills and cautions when operating inside nose. We removed pituitary adenoma in 28 patients via entirely endoscopic transsphenoidal approach with the help of special-designed instruments; we performed the procedure bloodlessly within limited time. The skill emphasized bilateral nostrils and four hands technique which was as delicate as possible not to scratch nasal mucosa or injure nasal frame. The special instruments included curette with suction, monopolar electrotome and bipolar coagulation forceps with suction, powered surgical equipments (Diamond Bur, Irrigation Tubing for Blades and Burs for nasal endoscopic surgery). Among 28 patients, there were 16 total resections, 8 subtotal resections, 3 partial resections, and 1 only biopsy due to excessive bleeding and hard nature. Of 19 patients with preoperative visual impairment, 12 patients had postoperative improvement in visual acuity and visual field. All the procedures were finished within 60 to 90 min. Complications seldom occurred except transient diabetes insipidus, especially no nasal-related signs or complications but 1 had epistaxis. The full endoscopic transsphenoidal surgery is a promising approach for pituitary adenoma resection. Multidisciplinary collaboration will lead to optimal cure for the patients. New technique and special-designed instruments can facilitate greatly this procedure. [ABSTRACT FROM AUTHOR]

This study attempted to explore suitable anesthetic methods used for removal of tracheobronchial foreign body (FB) via self-retaining laryngoscopy and Hopkins telescopy in children. 92 cases had undergone FB removal via self-retaining laryngoscopy and Hopkins telescopy or rigid bronchoscopy in our hospital since 2006, of which 56 cases were under intravenous anesthesia and endotracheal intubation with muscle relaxation (IAEI with MR), and the other 36 cases were under intravenous anesthesia with spontaneous breathing (IASB). Operative parameters and intraoperative vital signs were analyzed. Tracheobronchial foreign body was successfully removed in 87 cases, and not found in the other 5 cases. SpO was below 90% transiently in 41 cases, 29 cases of which were under IAEI with MR and 12 cases were under IASB. Laryngospasm and choke were found in 12 cases under IASB. Vital signs including PCO and heart rate were stable in all the cases. The mean surgical time, anaesthetic induction and recovery time of IAEI with MR via self-retaining laryngoscopy group were (5.69 ± 3.43) min, (9.68 ± 1.66) min and (26.13 ± 6.94) min, IASB via self-retaining laryngoscopy group were (21.35 ± 17.25) min, (13.71 ± 3.79) min and (24.64 ± 5.44) min, IAEI with MR via rigid bronchoscopy group were (10.20 ± 5.01) min, (10.31 ± 3.56) min and (25.13 ± 6.21) min, and IASB via rigid bronchoscopy group were (25.35 ± 13.25) min, (14.71 ± 3.61) min and (26.22 ± 5.65) min. It's a new and wonderful surgical procedure that combining self-retaining laryngoscopy and Hopkins telescopy for removal of tracheobronchial foreign body. IAEI with MR is suitable for bronchial FBA cases via them, while IASB is better for tracheal FBA or complicated cases. [ABSTRACT FROM AUTHOR]