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Background: This study analyzed the expression of CD44 and cystine-glutamate transporter SLC7A11 (xCT) in primary oral cavity squamous cell carcinoma (SCC) and the relationships of expression to tumor recurrence and patient survival., Methods: Associations between CD44 and xCT expression and clinicopathologic results were analyzed in 231 patients with oral cavity SCC. Cox proportional hazard analyses were used to identify factors associated with recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS)., Results: Overexpression of CD44 and/or xCT was associated with advanced T classification, perineural invasion, and lymphovascular invasion (P < .05 each). High expression of xCT was also associated with nodal metastasis and depth of invasion (P < .01 each). Multivariate analysis indicated that high expression of xCT and both xCT and CD44 were independent predictors of poor RFS, DSS, and OS (P < .05 each)., Conclusion: Overexpression of xCT or xCT plus CD44 may predict posttreatment recurrence and survival in patients with oral cavity SCC., (© 2018 Wiley Periodicals, Inc.)

Background: Recurrent laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC) is commonly associated with poor survival outcomes. We evaluated the prognostic role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) parameters quantitatively measured in patients who underwent salvage treatments for recurrent LHSCC., Methods: This study involved 100 consecutive LHSCC patients who underwent 18 F-FDG PET/CT for recurrent staging and subsequent salvage treatments. Maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using 18 F-FDG PET/CT. Cox proportional hazards regression analyses were used to assess the associations between quantitative 18 F-FDG PET/CT parameters and other clinicopathological factors with progression-free survival (PFS) and overall survival (OS)., Results: Two-year postsalvage PFS and OS rates were 67.9% and 74.3%, respectively. All 18 F-FDG PET parameters of SUV max , MTV, and TLG were significantly associated with poor PFS and OS outcomes after salvage treatment (all P < 0.05). Multivariate analyses revealed that recurrence site, MTV (>6.5 mL), and TLG (>17.1 g) were independent variables predictive of PFS. Karnofsky score, SUV max (>4.0), and TLG (>17.1 g) were the independent prognostic factors for OS., Conclusions: 18 F-FDG PET/CT can be useful in predicting postsalvage recurrence and survival in patients with recurrent LHSCC., (© 2018 Wiley Periodicals, Inc.)

Purpose: Intracellular antioxidant enzymes are commonly upregulated in various cancer types and are associated with treatment outcomes. Because the relationship has rarely been examined in oral squamous cell carcinoma (OSCC), we aimed to evaluate the association between the levels of glutathione peroxidase (GPX)1, GPX4, and thioredoxin reductase (TrxR)1 expression and prognosis in patients with OSCC who underwent curative surgical resection., Methods: This study included 233 patients who underwent curative surgery for previously untreated OSCC between 2000 and 2012. Tumour GPX1, GPX4, and TrxR1 expression was evaluated by immunohistochemistry and was dichotomised to low and high values according to defined expression levels. The association between GPX1, GPX4, and TrxR1 expression and clinicopathological results was analysed. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables., Results: High GPX1, GPX4, and TrxR1 expression was observed in 99 (42.5%), 133 (57.1%), and 46 (19.7%) patients, respectively. GPX1 overexpression was significantly correlated with nodal metastasis, advanced overall stage, depth of invasion of >10 mm, high grade and perineural invasion (P < 0.05). High GPX4 expression was also related to nodal metastasis, overall advanced stage and high grade (P < 0.05). Univariate and multivariate analyses showed that increased GPX1 expression was significantly associated with poor disease-free, cancer-specific and overall survival (all P < 0.05), while increased GPX4 or TrxR1 expression was not (all P > 0.1)., Conclusions: Tumour GPX1 expression is a useful biomarker predictive of recurrence and survival in OSCC patients.

The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor α (TNF-α) induced by sepsis. Clonidine administered i.t. or i.p. increased p-AMPKα1 and p-AMPKα2, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of p-AMPKα1 and p-AMPKα2, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflicts of interest.

Objective: Transcutaneous devices have a disadvantage, the dampening effect by soft tissue between the bone and devices. We investigated hearing outcomes with percutaneous and transcutaneous devices using test-bands in an induced unilateral conductive hearing loss., Design: Comparison of hearing outcomes of two devices in the same individuals., Study Sample: The right ear was plugged in 30 subjects and a test-band with devices (Cochlear™ Baha® BP110 Power and Sophono® Alpha-2 MPO™) was applied on the right mastoid tip with the left ear masked. Sound-field thresholds, speech recognition thresholds (SRTs), and word recognition scores (WRSs) were compared., Results: Aided thresholds of Sophono were significantly better than those of Baha at most frequencies. Sophono WRSs (86 ± 12%) at 40 dB SPL and SRTs (14 ± 5 dB HL) were significantly better than those (73 ± 24% and 23 ± 8 dB HL) of Baha. However, Sophono WRSs (98 ± 3%) at 60 dB SPL did not differ from Baha WRSs (95 ± 12%)., Conclusion: Amplifications of the current transcutaneous device were not inferior to those of percutaneous devices with a test-band in subjects with normal bone-conduction thresholds. Since the percutaneous devices can increase the gain when fixed to the skull by eliminating the dampening effect, both devices are expected to provide sufficient hearing amplification.

Background: Extranodal extension (ENE) is a poor prognostic indicator for patients with head and neck squamous cell carcinoma (HNSCC), but pretreatment detection assists with proper treatment planning. This study evaluated whether the ENE of HNSCC is accurately detected by computed tomography (CT) versus fluorine 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT and whether it has any impact on patient prognosis., Methods: In this study, 186 HNSCC patients were preoperatively evaluated using contrast-enhanced CT and (18)F-FDG PET/CT. The histopathologic findings for the neck dissection samples served as a standard reference. McNemar's test and logistic regression using the generalized estimating equations were used to compare the diagnostic value of CT versus (18)F-FDG PET/CT, and Cox proportional hazard regression was used to assess the prognostic value of ENE., Results: Among the 186 study patients, 113 (60.8 %) had a neck metastasis, 44 (23.7 %) had pathologic ENE, and 37 (19.9 %) had macroscopic ENE. Radiologic ENE (rENE) on CT was documented for 48 patients (25.8 %) and 52 neck sides (19.8 %). Using 4.9 as the cutoff value for nodal maximum standardized uptake, (18)F-FDG PET/CT documented rENE for 44 patients (23.7 %) and 48 neck sides (18.3 %). Compared with (18)F-FDG PET/CT, CT detected ENE, with a specificity of 92.1 versus 74.4 % (p < 0.001) and an accuracy of 88.6 versus 75.3 % (p < 0.001). However, rENE was not a significant predictor of recurrence or survival (p > 0.05)., Conclusion: The findings showed that ENE of HNSCC is more accurately detected by using CT than by using (18)F-FDG PET/CT. The accurate pretreatment detection of ENE may help in the planning for HNSCC treatments.

Purpose: To assess diagnostic accuracy of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and computed tomography (CT) in the detection of occult primary tumors and determination of optimal care in patients with cervical metastasis of an unknown primary tumor (CUP) compared with contrast material-enhanced CT alone or combined contrast-enhanced CT and magnetic resonance (MR) imaging (CT/MR imaging)., Materials and Methods: Institutional review board approval and written informed consent were obtained. In total, 56 patients with initially undetected tumors after endoscopic or physical examination were prospectively assessed with (18)F FDG PET/CT and contrast-enhanced CT or contrast-enhanced CT/MR imaging. The contrast-enhanced CT/MR images were read in combination. Results of guided biopsy with general anesthesia served as the reference standard. Diagnostic values of (18)F FDG PET/CT, contrast-enhanced CT, and contrast-enhanced CT/MR imaging were compared with the McNemar test., Results: Primary tumors were detected at 32 sites in 31 (55%) of 56 patients. There were 26 tumors in the palatine tonsil, two in the hypopharynx, two in the base of the tongue, and two in the nasopharynx. PET/CT depicted 22 (69%) of 32 primary tumors, but it failed to depict primary tumors in 10 (31%) of 32 cases. Overall, sensitivity of PET/CT (69%) in detection of primary tumors was higher than that of contrast-enhanced CT (16%) (P < .001) or contrast-enhanced CT/MR imaging (41%) (P = .039), while specificity of these methods did not differ (88%, 76%, and 59% for PET/CT, contrast-enhanced CT, and contrast-enhanced CT/MR imaging, respectively; P > .4). Diagnostic performance (area under the receiver operating characteristics curve [AUC] = 0.759) of PET/CT in tumor detection was significantly better than that of contrast-enhanced CT alone (AUC = 0.531) (P = .001) or contrast-enhanced CT/MR imaging (AUC = 0.537) (P = .036). PET/CT depicted primary tumors in eight (50%) of 16 cases of false-negative CT/MR imaging findings, one distant metastatic case, and two cases of synchronous cancer., Conclusion: (18)F FDG PET/CT is more sensitive in detection of primary tumors than is contrast-enhanced CT or contrast-enhanced CT/MR imaging in patients with CUP; therefore, it may lead to improved therapeutic planning in these patients.

Objectives: We evaluated vestibular function test results in vestibular migraine (VM) patients, including caloric, vestibular evoked myogenic potential (VEMP), and dynamic posturography measurements and assessed their relationship with treatment responses., Study Design: Retrospective case series review., Setting: Tertiary referral center., Methods: We investigated a cohort of 80 VM patients who had suffered recurrent vertigo attacks for more than 6 months. A combination of lifestyle modifications and prophylactic medications were used to treat these subjects. The patients were asked to score the treatment success by ranking symptom score from 0% to 100% for the improvement in overall severity of headache and vertigo. Patients were then classified as complete remission, symptomatic improvement 50% or more, or less than 50% improvement after 6 months of treatment. The periods needed for symptomatic improvement in the 50% or more patient group were recorded, and the responsiveness to medications and the vestibular test result metrics were analyzed to identify clinical outcome predictors., Results: A symptomatic improvement of 50% or more in vertigo and headache was observed in 71% and 75% of the study subjects across mean periods of 2.3 and 2.2 months, respectively. Improvements in vertigo and headache did not coincide in all. Abnormal caloric, VEMP, and vestibular ratio measurements were found in 25%, 29%, and 58%, respectively. Abnormal vestibular ratios on posturography showed a significant correlation with a poor treatment response of vertigo, and a normal VEMP was significantly related to complete remission from headache, although abnormal caloric results showed no significant correlation with treatment responses. A poor response of vertigo symptoms was observed in 6% of patients with a normal vestibular ratio and 48% of patients with abnormal vestibular ratio. Complete remission from headache was observed in 61% of patients with a normal VEMP and 30% in patients with an abnormal VEMP., Conclusion: More than 70% of the patients with VM experienced improvements in both headache and vertigo through a combination of lifestyle changes and prophylactic medications. Abnormal vestibular ratios on posturography and abnormal VEMP responses were frequent findings in VM patients with recurrent attacks for more than 6 months and were indicators of a poor prognosis. The pathophysiology of VM appears to be closely related to vestibular abnormalities, especially in vestibulospinal pathways. Further study with a large population is needed to establish the relationship exactly., Level of Evidence: 2b Individual retrospective cohort study.