Comparison of cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant patients in chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by inflammation of the nasal and sinus mucosa. The inflammatory patterns may differ among patients, leading to different subtypes based on the dominant inflammatory cell type. This study aimed to compare the differences in cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant subtypes in patients with CRSwNP. METHODS: This study included 53 CRSwNP patients and 19 control subjects who did not have asthma or a history of cigarette smoking. The expression of cytokines and inflammatory cells was assessed via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. RESULTS: Among the cytokines analyzed, only IL-6 was significantly different between the two subtypes. A greater proportion of mast cells and IgE cells was present in plasma cell-dominant CRSwNP patients than in eosinophil-dominant group. For the three disease severity scores (LMK-CT, TPS and SNOT-22), objective scores (LMK-CT and TPS) were greater in the eosinophil-dominant CRSwNP group, while the opposite result was shown for the subjective score (SNOT-22). Additionally, the percentage of plasma cell-dominant cells was significantly positively correlated with disease severity according to the TPS and SNOT-22 scores. CONCLUSIONS: Our data revealed that plasma cell-dominant inflammation, a subtype of type 2 CRS, was significantly correlated with subjective disease severity. The study also highlights the role of IL-6, IgE and mast cells as distinguishing factors between eosinophil-dominant and plasma cell-dominant CRSwNP. This information could be useful for clinical diagnosis and personalized treatment.

Minimally invasive, single-stage, multilevel surgery for obstructive sleep apnoea: A systematic review and meta-analysis.

OBJECTIVES: Minimally invasive, single-staged multilevel surgery (MISS MLS) could be an optimal treatment for selected patients with obstructive sleep apnea (OSA). We aim to systematically review the efficacy of MISS MLS for patients with OSA, as well as the clinical outcomes and possible complications in OSA patients before and after MISS MLS. DESIGN AND SETTING: Systematic review and meta-analysis. Six databases were searched, and the PRISMA guideline was followed. PARTICIPANTS: Patients with OSA receiving MISS MLS. MAIN OUTCOME MEASURES: The random-effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of MISS MLS for OSA. Subgroup analyses and sensitivity analyses were also performed to identify the heterogeneity among the studies. RESULTS: There were initially 154 articles for identification. Eventually, six studies with a total of 848 OSA patients completely met the inclusion criteria and were further enrolled for analysis. The pooled analysis showed statistically significant lower AHI (apnea/hypopnea index, /hr.; mean difference: -8.931, 95% CI: -11.591 to -6.271, I2 = 87.4%), ESS (mean difference: -2.947, 95% CI: -4.465 to -1.429, I2 = 94.9%), and snoring severity with 0-10 visual analog scale after surgery (mean difference: -4.966, 95% CI: -5.804 to -4.128, I2 = 96.4%). The success rate was 46% in mild/moderate OSA; however, 18% in severe OSA. There were no major complications occurred. CONCLUSIONS: The acceptable surgical outcomes, esp. in mild/moderate OSA, and rare complications are the major advantages of MISS MLS. The evidence of this study could aid the decision making in selecting suitable treatment programs for OSA patients.

The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer.

PURPOSE: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). METHODS: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. RESULTS: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124-2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219-2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001)." CONCLUSION: Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

BACKGROUND: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. METHODS: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. RESULTS: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). CONCLUSION: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

The Prognostic Value of Preoperative Albumin-to-Alkaline Phosphatase Ratio on Survival Outcome for Patients With Locally Advanced Oral Squamous Cell Carcinoma.

Background: This retrospective cohort study was to assess the prognostic value of preoperative albumin-to-alkaline phosphatase ratio (AAPR) on survival outcome for patients with locally advanced oral squamous cell carcinoma (LAOSCC). Methods: A total of 250 patients with LAOSCC receiving upfront radical surgery at a single institute from January 2008 to December 2017 were enrolled. The primary endpoint was the survival predictability of preoperative AAPR on the 5-year overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Cox proportional hazards model was used for survival analysis. The X-tile software was used to estimate the optimal cut-off value of preoperative AAPR on survival prediction. A predictive nomogram incorporating the clinicopathological factors on OS was further generated. Results: The 5-year OS, CSS, and DFS rates were 68.6%, 79.7%, and 61.7%, respectively. The optimal cut-off of preoperative AAPR to predict the 5-year OS was observed to be 0.51. For those with preoperative AAPR≧0.51, the 5-year OS, CSS, and DFS were statistically significantly superior to those with preoperative AAPR<0.51 (OS: 76.1% vs 48.5%, P < .001; CSS: 84.3% vs 66.4%, P = .005; DFS: 68.9% vs 42.6%, P < .001). In Cox model, we observed that preoperative AAPR<0.51 was a significantly negative prognosticator of OS (HR: 2.22, 95% CI: 1.466-3.361, P < .001), CSS (HR: 2.037, 95% CI: 1.16-3.578, P = .013), and DFS (HR: 1.756, 95% CI: 1.075-2.868, P = .025). After adding the variable of preoperative AAPR, the c-index of the predictive nomogram incorporating assorted clinicopathological factors increases from 0.663 to 0.692 for OS. Conclusion: Our results suggest that preoperative AAPR serves as an independent survival predictor for patients with LAOSCC. The nomogram incorporating preoperative AAPR and various clinicopathological features may be a convenient tool to estimate the mortality risk for patients with LAOSCC.

Expression of Major Lipid Raft Protein Raftlin in Chronic Rhinosinusitis with Nasal Polyps in Smoking and Non-Smoking Patients Correlated with Interleukin-17 and Tumor Necrosis Factor-α Levels.

Raftlin, as an inflammatory biomarker, has been previously reported in chronic inflammatory diseases. This study investigates the expression of Raftlin in cigarette smokers and in chronic rhinosinusitis with nasal polyps (CRSwNP), as well as evaluating its correlation with interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) levels. A total of 30 CRSwNP non-smoking and 16 CRSwNP + SK (smoking) patients undergoing endoscopic sinus surgery were enrolled, while 20 middle turbinate tissue pieces were examined and performed as the control group. In nasal mucosa epithelial staining, Raftlin levels were elevated in the columnar cells and were stained much more intensely in the CRSwNP and CRSwNP + SK groups. Raftlin was located more closely to the apical region of the epithelium in the CRSwNP + SK group; however, the Raftlin levels from whole nasal tissue pieces, according to ELISA data, showed that there was no significant difference between the three different study groups. A positive relationship by Pearson correlation was found between IL-17 or TNF-α levels and Raftlin levels. Taken together, these data indicate that increasing Raftlin expression in columnar cells might involve nasal epithelial remodeling in smokers with CRSwNP.

JMJD3 suppresses tumor progression in oral tongue squamous cell carcinoma patients receiving surgical resection.

Background: Jumonji domain-containing-3 (JMJD3) is reported to be a histone H3 lysine 27 (H3K27) demethylase and a tumor suppressor gene. The present study designed to investigate the crucial role of JMJD3 in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection. Methods: We enrolled a total of 156 OTSCC patients receiving surgical resection, including 73 patients (47%) with high expression of JMJD3 and 83 patients (53%) harboring low expression of JMJD3. Two OTSCC cell lines, SAS and Cal 27, were used to explore the modulation of cancer. GSK-J4, a potent inhibitor of JMJD3, was used to treat the two OTSCC cell lines. The Chi-square test was performed to examine between-group differences in categorical variables; the Kaplan-Meier method was used to investigate survival outcome in univariate analysis, and the Cox regression model was used for multivariate analysis. Results: The median follow-up period was 59.2 months and he five-year disease-free survival (DFS) and overall survival (OS) rates were 46.2% and 50.0%, respectively. Better five-year DFS (59% versus 35%) and five-year OS (63% versus 39%) were mentioned in patients with high expression of JMJD3 compared to those with low expression of JMJD3. High expression of JMJD3 was significantly associated with superior DFS and OS in the univariate and multivariate analyses. Following successful inhibition of JMJD3 by GSK-J4, western blotting analysis showed the decreased expression of Rb and p21. Conclusion: Our study showed that high expression of JMJD3 is a good prognostic factor in OTSCC patients who underwent surgical resection.

Systematic review and updated meta-analysis of multi-level surgery for patients with OSA.

OBJECTIVES: To perform an updated systematic review for determining the surgical success rate of multilevel upper airway surgery for patients with obstructive sleep apnea/hypopnea syndrome (OSA). METHODS: A systematic review was performed to identify English-language studies that evaluated the treatment of adult OSA patients with multilevel OSA surgery up to January, 2018. We used polysomnography as a metric of treatment success. Articles were only included if the surgery intervention involved at least two of the frequently involved anatomic sites: nose, oropharynx and hypopharynx. Eighty-seven studies fit the inclusion criteria and a meta-analysis was performed to determine the overall success. RESULTS: The meta-analysis included 3931 subjects with a mean age of 46.1 years. The originally reported success rate in the included literature was 59.9%. A meta-analysis was performed to redefine the success rate to be consistent with the commonly agreed upon criteria - namely "a reduction in apnea/hypopnea index (AHI, /hr.) of 50% or more and an AHI of less than 20". The recalculated success rate was 60.2%. Standard meta-analytic techniques for combining p-values between studies after weighting for sample size found significant improvements in AHI, apnea index, % of rapid eye movement sleep, lowest saturation of oxygen (%), and Epworth Sleepiness Scale. CONCLUSION: This study shows the significant improvement of treatment outcomes with multilevel surgery for OSA patients.

Stereotactic body radiotherapy plus cetuximab for previously irradiated un-resectable head and neck cancer.

BACKGROUND: The aim of the study was to explore the treatment outcomes and prognostic factors for patients with previously irradiated but unresectable recurrent head and neck squamous cell carcinoma (rHNSCC) treated by stereotactic body radiotherapy (SBRT) plus cetuximab at a single institute in Taiwan. METHODS: From February 2016 to March 2019, 74 patients with previously irradiated but unresectable rHNSCC were treated with SBRT plus cetuximab. All patients received irradiation to the gross tumor and/or nodal area with 40-50 Gy in five fractions, with each fraction interval ≥2 days over a 2-week period by using the CyberKnife M6 machine. An18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan was performed before treatment for treatment target delineation (n = 74) and 2 months later for response evaluation (n = 60). The median follow-up time was 9 months (range 1-36 months). RESULTS: The treatment response rate was complete response: 25.0%, partial response: 41.7%, stable disease: 11.7%, and progressive disease: 21.7% based on the criteria of the Response Evaluation Criteria in Solid Tumors (n = 72) and complete metabolic response: 21.7%, partial metabolic response: 51.7%, stable metabolic disease: 13.3%, and progressive metabolic disease: 13.3% based on PET-CT (n = 60), respectively. The 1-/2-year overall survival (OS) and progression-free survival (PFS) rates were 42.8%/22.0% and 40.5%/19.0%, respectively. In the logistic regression model, a re-irradiation interval >12 months was observed to be the only significant prognostic factor for a favorable treatment response. In the Cox proportional hazards model, a re-irradiation interval >12 months and gross tumor volume (GTV) â‰¦ 50 ml were favorable prognostic factors of OS and PFS. CONCLUSION: SBRT plus cetuximab provides a promising salvage strategy for those patients with previously irradiated but unresectable rHNSCC, especially those with a re-irradiation interval >12 months or GTV â‰¦ 50 ml.

Radiofrequency Ablation a Safe and Effective Treatment for Pediatric Benign Nodular Thyroid Goiter.

Purpose: To evaluate the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules in pediatric patients. Materials and Methods: Twelve pediatric patients (11 female, 1 male; mean age 15.54 ± 2.8 years, range 10-19 years) with benign thyroid nodules (mean longest diameter 4.1 ± 1.4 cm, range 1.5-5.9 cm) treated by RFA from 2017 to 2020 were evaluated. The inclusion criteria for RFA therapy were (i) age < 20 years; (ii) benign cytological confirmation by 2 separate ultrasound guided fine-needle aspiration cytology (FNAC) or core needle biopsies; (iii) pressure symptoms or cosmetic problems caused by thyroid nodules; (iv) absence of any sonographic suspicious feature; and (v) follow-up for >6 months. Under local anesthesia, RFA was performed with the use of an RF generator and an 18-gauge internally cooled electrode. Volume changes in nodules on follow-up ultrasonography (US), changes in symptomatic and cosmetic scores, and complications arising during or after RFA were evaluated. Results: Mean follow-up period was 24.9 ± 13.9 months (range 6-43 months). At the last follow-up visits, volume of the nodule had decreased significantly (15.34 ± 11.52 mL vs. 4.07 ± 4.99 mL; P < 0.05), whereas volume reduction rate was 74.31% ± 19.59%. Both cosmetic and compressive symptoms were also significantly improved (2.91 ± 0.79 vs. 0.92 ± 0.67 and 1.5 ± 1.93 vs. 0.17 ± 0.39; P < 0.05). The mean number of ablation sessions was 1.4 ± 0.6 (range 1-3 sessions), and one of the patients suffered from transient vocal cord palsy which was spontaneously resolved 53 days later. Conclusions: RFA is a safe and effective treatment for benign thyroid nodules in pediatric patients, and can thus serve as an alternative treatment for thyroidectomy.

Quality of Life as a Mediator between Cancer Stage and Long-Term Mortality in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Radiotherapy.

BACKGROUND: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer (NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny's method were used to assess the investigated effects. RESULTS: Advanced AJCC stage (III-IV) patients revealed a 2.26-fold (95% CI-1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I-II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8-9.8% at pre-IMRT but at 2 years post-IMRT were 39.4-49.4% by global health QoL and QoL-HN35 symptoms. CONCLUSIONS: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.

Overexpression of UTX promotes tumor progression in Oral tongue squamous cell carcinoma patients receiving surgical resection: a case control study.

BACKGROUND: Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been identified as a histone 3 lysine 27 (H3K27) demethylase and acted as a tumor suppressor gene or oncogenic function. The current study was to explore the significance of UTX in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection. METHODS: A total of 148 OTSCC patients who underwent surgical resection were identified, including 64 patients (43%) with overexpression of UTX and 84 patients (57%) harboring low expression of UTX. We also used two OTSCC cell lines, SAS and Cal 27, to determine the modulation of cancer. Chi-square test was used to investigate the difference of categorical variables between the groups; survival outcome was analyzed using the Kaplan-Meier method in univariate analysis, and a Cox regression model was performed for multivariate analyses. RESULTS: Univariate and multivariate analyses showed overexpression of UTX were significantly related to worse disease-free survival (P = 0.028) and overall survival (P = 0.029). The two OTSCC cell lines were treated with GSK-J4, a potent inhibitor of UTX, and transwell migration and invasion assays showed an inhibitory effect with a dose-dependent manner. In addition, western blot analyses also revealed the inhibition of cell cycle and epithelial-mesenchymal transition. CONCLUSION: Our study suggests that UTX plays an important role in the process of OTSCC and overexpression of UTX may predict poor prognosis in OTSCC patients who received surgical resection.

Long-Term Outcomes of Radiofrequency Ablation for Treatment of Cystic Warthin Tumors versus Solid Warthin Tumors.

BACKGROUND: To describe the long-term outcomes of radiofrequency ablation (RFA) of parotid Warthin tumors that have different consistencies and locations. METHODS: We reviewed ten patients with Warthin tumors undergoing RFA treatment from 2016 to 2019. The mean follow-up was 24.3 ± 13.1 months (range 7-42 months). RESULTS: RFA was performed on 11 tumors in ten patients. Cystic tumors (n = 4) had better volume reduction ratios (VRR) than solid tumors (n = 7) at month one and month six, following RFA (77.9% vs. 47.3%, 95.1% vs. 80.6%, respectively, p = 0.003). Tumors in both superficial lobes and deep lobes (n = 7) were larger than tumors in superficial lobes alone (n = 4), though there was no difference in VRR after treatment. All residual tumors were found in superficial lobes. There was no increase in residual tumor size. Every patient showed marked cosmetic improvements, with visible tumors becoming non-palpable masses. CONCLUSIONS: RFA is a safe and effective treatment for Warthin tumors, with better volume reduction in cystic tumors. Results remained satisfying over the long-term for all residual tumors found in superficial lobes, making it easier for re-intervention if necessary.

Radiofrequency ablation for treatment of thyroid follicular neoplasm with low SUV in PET/CT study.

OBJECTIVES: To evaluate the feasibility of radiofrequency ablation (RFA) on follicular neoplasm with low standard uptake value (SUV) in a Positron emission tomography (PET/CT) study. METHODS: From January 2018 to July 2019, 86 consecutive patients were diagnosed with follicular neoplasm. Of the patients, 28 with PET/CT scans were enrolled in this study. All patients received ultrasound, fine/core needle aspiration, and PET/CT scan prior to treatment. In accordance with previous studies, we recommended 6 patients who had follicular neoplasm with SUVmax ≥5 undergo surgical resection due to an elevated suspicion of malignancy. For 22 patients SUVmax <5, RFA was performed using the moving shot technique. Ultrasound was performed 6 to 12 months after each procedure. RESULTS: Statistically significant volume reductions during follow-up between values prior to RFA and 12 months post RFA were demonstrated (12.6 ± 20.9 vs. 2.4 ± 3.0 cm3, p < 0.001). Volume reduction ratios at 6-12 months (mean: 10.1 months) after RFA were 73.3% ± 17.7%. One patient presented with vocal cord palsy and recovered within 3 months after RFA. No postprocedural hypothyroidism occurred in the RFA patients. CONCLUSIONS: By using PET/CT, we can select patients with low SUV follicular neoplasm. RFA offers a safe and feasible alternative treatment option for patients unsuitable or unwilling to undergo surgery.KEY POINTSBy using positron emission tomography-computed tomography, we can distinguish low SUV follicular neoplasm for radiofrequency ablation.For low SUV follicular neoplasm, RF ablation offers a safe and effective alternative treatment option for patients unsuitable or unwilling to undergo surgery.

Efficacy and safety of single-session radiofrequency ablation for intrathoracic goiter: preliminary results and short-term evaluation.

BACKGROUND: An intrathoracic goiter (ITG) is defined as a thyroid extension below the sternal notch. Compared to cervical goiters, surgery for ITG is more challenging, with a higher risk of an extracervical approach. Ultrasound (US)-guided radiofrequency ablation (RFA) is a minimally invasive treatment modality. The purpose of this study was to prospectively evaluate the safety and efficacy of RFA in patients with ITG. METHODS: From a total of 324 patients who underwent thyroid RFA at a single medical center, 15 patients (mean age 52.2 years; 73.3% female) with 16 ITGs were included and classified into three grades and three types using the cross-section imaging CT system. Clinical features and demographics, degree of extension, RFA details, goiter volume, and complications were analyzed. RESULTS: Mean pre- and post-RFA goiter volumes as measured by US were 106.62 ± 61.82 and 25.09 ± 14.22 mL respectively, with a volume reduction rate (VRR) of 75.5% (p < 0.001) at 6 months. The VRR as measured by CT/MRI was 57.0 ± 10.0% (p < 0.001) at 6 months. The intrathoracic length reduction rate at 6 months was 44.9 ± 39.2% (p = 0.001). In addition, 4 (25%) ITGs had total regression of the intrathoracic extension, with a downgrade from grade 1 to cervical goiter. Mean pre- and post-RFA symptom and cosmetic scores were 1.53 and 0.15 (p = 0.001), and 2.67 and 2.00 (p = 0.001), respectively. One patient had transient vocal cord palsy and another had perithyroidal and mediastinal hemorrhage. CONCLUSION: US-guided RFA is an effective treatment for ITG in terms of both cervical and intrathoracic reductions with an acceptable complication rate.

Angiotensin II receptor blockers valsartan and losartan improve survival rate clinically and suppress tumor growth via apoptosis related to PI3K/AKT signaling in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common type of head and neck cancer in Asia. Adverse effects occur in over 90% of NPC patients treated with radiotherapy or chemoradiation. Angiotensin II receptor blockers (ARBs) are commonly used to treat hypertension without serious adverse effects. However, the anticancer activity of ARBs in NPC remains unclear. METHODS: We investigated the survival impacts of ARBs among NPC patients in a retrospective study. The anticancer effects and related signaling pathways of the ARBs valsartan and losartan were also evaluated in vitro and in vivo. RESULT: A total of 927 patients with NPC who had hypertension were enrolled in the study, 272 (29.3%) of whom received ARBs. Kaplan-Meier analysis revealed that patients who used ARBs had higher rates of 5-year overall survival (OS; 87.8% vs 75.1%; P = .002) and disease-specific survival (DSS; 95.4% vs 77.7%; P < .001) than those who did not receive this treatment. Additionally, ARBs inhibited cell proliferation and induced apoptosis by increasing levels of cleaved caspase-3, cleaved caspase-9, and cytochrome C; the cell population in the sub-G1 phase; and caspase-3 activity in NPC-TW01 cells. ARBs inhibited tumor growth and angiogenesis via apoptosis in an NPC xenografts model. Interestingly, ARBs inhibited phosphorylation of PI3K/AKT signaling in vitro and in vivo, which is markedly attributed to their antitumor effects in NPC. CONCLUSION: These data indicate that ARBs not only improve 5-year OS and DSS among patients with NPC but also exert antiproliferative and antiangiogenesis effects by inducing apoptosis in NPC, supporting that ARBs may be promising agents for treatment of NPC.

Efficacy and safety of single-session radiofrequency ablation for benign thyroid nodules of different sizes: a retrospective study.

PURPOSE: To compare the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules (BTNs) among groups presenting with different nodule volumes. MATERIALS AND METHODS: This retrospective study evaluated 186 patients with BTNs who underwent ultrasound guided RFA treatment. The BTNs were categorized into small (≤10 ml); medium (10-30 ml); and large (>30 ml) according to the initial volume of BTNs before ablation. The RFA procedures were performed using the moving shot technique. The volume reduction ratio (VRR) of each nodule, cosmetic score, symptomatic score, and complications were analyzed at 1, 3, and 6 months after RFA treatment and the three groups compared. RESULTS: At 1-month follow-up, the large nodules group showed significantly greater VRR compared to the other two groups (small, 31.88% ± 37.91; medium, 38.9% ± 19.18; large, 48.7% ± 20.43, p = .03). At 6-month follow-up, there was no significant difference of VRR among the three groups (small, 74.6% ± 20.92; medium, 68.1% ± 17.07; large, 75.0% ± 11.88). The most common presented complication was temporary vocal palsy (6 patients; small, n = 1; medium, n = 1; large, n = 3). Additionally, one skin burn, one hematoma, and one nodular rupture of BTNs occurred after the procedures. The complication rate of the large nodules group was highest among the three groups and showed a considerable difference (8 patients; small, n = 1, 2.1%; medium, n = 2, 4.5%; large, n = 5, 11.4%, p = .061). CONCLUSIONS: RFA was confirmed as effective in patients with large thyroid nodule (>30ml), with therapeutic efficacy similar to patients with smaller thyroid nodules.

Evaluation of Outcomes following Radiofrequency Ablation for Treatment of Parotid Tail Warthin Tumors.

PURPOSE: To evaluate efficacy and safety of radiofrequency (RF) ablation for parotid Warthin tumor. MATERIALS AND METHODS: From September 2016 to August 2017, 7 consecutive patients with biopsy-proven parotid Warthin tumors who did not undergo surgery presented with symptoms or cosmetic concerns and underwent US-guided percutaneous RF ablation treatment. RF ablation procedures were performed using the moving shot technique. US, contrast-enhanced CT, or MR imaging was performed 6-12 months after each procedure. Complications and cosmetic scale improvement after RF ablation were also evaluated. RESULTS: There was a significant reduction in mean tumor volume from 14.6 cm3 ± 13.1 (range, 1.9-35.5 cm3) to 0.8 cm3 ± 0.5 (range, 0.2-1.54 cm3) and a mean cosmetic scale improvement (from 4 to 1) on imaging studies 6-12 months after RF ablation compared with before RF ablation (P < .05). Volume reduction ratios at 1-2 months, 5-6 months, and 10-12 months after RF ablation were 51.2% ± 18.1%, 87.8% ± 10.6%, and 94.3% ± 2.0%. There was no facial nerve injury. One patient with parotitis and hematoma recovered in 1 week. CONCLUSIONS: RF ablation using the moving shot technique could be an effective and safe alternative treatment for parotid tail Warthin tumors in patients unsuitable for or unwilling to undergo surgical resection.

Nox4 Overexpression as a Poor Prognostic Factor in Patients with Oral Tongue Squamous Cell Carcinoma Receiving Surgical Resection.

BACKGROUND: Nox4 has been reported to promote tumor progression of various types of cancer through many different pathways. The current study was designed to evaluate the prognostic significance of Nox4 in patients with oral tongue squamous cell carcinoma (OTSCC) receiving surgical resection. METHODS: We retrospectively analyzed the 161 patients with OTSCC treated with surgical resection, including 81 patients with high expression of Nox4 and 80 patients with low expression of Nox4. Two OTSCC cell lines, SAS and SCC4, were used to investigate the proliferation activity. RESULTS: The univariate and multivariable analyses showed that negative nodal metastasis and low expression of Nox4 were significantly associated with superior disease-free survival (DFS) and overall survival (OS). Western blotting analysis indicated that Nox4 was highly expressed in these two OTSCC cell lines and knockdown of Nox4 was successful by transfecting with Nox4 shRNA. In addition, these cell lines were also treated with a Nox4 inhibitor (GKT-137831) and the results showed GKT-137831 could inhibit the proliferation of OTSCC tumor cells in a dose-dependent manner. CONCLUSION: Our study suggests that Nox4 plays an important role in disease progression of OTSCC and Nox4 overexpression is a poor prognostic factor for patients with OTSCC who received surgical resection.

Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma.

Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival. Univariate analysis revealed that p-mTOR overexpression (P = 0.006) was associated with inferior overall survival. In multivariate comparison, p-mTOR overexpression (P = 0.002, hazard ratio = 2.082) remained independently associated with worse overall survival. In vitro study, tongue cancer cells treated with everolimus, the specific mTOR inhibitor, or transfected with mTOR-mediated siRNAs dramatically attenuated the abilities of cell proliferation by MTT and BrdU assays. In 4-NQO-induced tongue cancer murine model, mTOR inhibitors significantly decreased the incidence of tongue SCC. In conclusion, p-mTOR overexpression was independently associated with poor prognosis of patients with tongue SCC. In vitro and vivo, mTOR inhibition showed the promising activity in tongue SCC. Our results suggest that inhibition of mTOR signaling pathway may be a novel therapeutic target for tongue SCC.