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Objective: Statins have been reported to improve vascular endothelial function and microcirculation, reduce oxidative stress, and exert anti‐inflammatory and protective effects against inner ear damage. Therefore, this study aimed to investigate the effect of statins on hearing prognosis in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: We reviewed the medical records of 149 patients diagnosed with ISSNHL. Clinical characteristics, hearing thresholds, statin medications, and hematological findings were investigated. First, patients with ISSNHL were assigned to the good and poor outcome groups, and factors influencing their prognosis were analyzed. Furthermore, patients with dyslipidemia were investigated to determine whether statins have therapeutic effects on ISSNHL. Results: Significant differences in age (p =.011), days from the onset of ISSNHL to the initiation of treatment (p =.04), and hematological total cholesterol (TC; p =.015) between the good and poor outcome groups were observed. Furthermore, when hearing outcomes were investigated in patients with dyslipidemia, TC was significantly lower in the good outcome group (p =.03). Although no significant therapeutic effects of statins were observed in participants with dyslipidemia, patients in the statin‐treated group were significantly older and experienced more diabetic complications than those in the non‐statin‐treated group. Conclusion: Although our study showed that dyslipidemia is a poor prognostic factor for ISSNHL, statins had no significant therapeutic effects on hearing recovery in ISSNHL patients with dyslipidemia. The patients that received statin medications were significantly older and experienced more diabetic complications, which may have affected their hearing prognosis. Level of Evidence: Level 4. Idiopathic sudden sensorineural hearing loss (ISSNHL) can have a profound impact on quality of life, and its etiology is unknown. Although our study indicated dyslipidemia to be a poor prognostic factor for ISSNHL, any significant therapeutic effects of statins regarding to hearing recovery were not observed in ISSNHL participants with dyslipidemia. [ABSTRACT FROM AUTHOR]

Aim: Fluorescence imaging (FI) using indocyanine green (ICG) is a noteworthy alternative technique for sentinel lymph node (SLN) detection without radiation exposure in oral cavity and oropharynx cancer. However, conventional FI is monochrome, so the visibility is limited. This study assessed whether color FI using the HyperEye Medical System (HEMS) is feasible as an alternative for SLN detection. Methods: Patients with previously untreated cT1‐2N0 oral or oropharyngeal cancer who were to undergo primary tumor resection and elective neck dissection (END) in our hospital were enrolled from November 2012 to March 2016. The patients underwent SLN detection for biopsy via the HEMS following the injection of ICG solution around the primary lesion before neck dissection. The visibility and the diagnostic accuracy of the imaging were evaluated. Results: SLNs were visualized in all eight cases; however, transcutaneous fluorescence detection was not observed in all cases. Utilizing color mode imaging simplified harvest by clearly discriminating SLNs from surrounding structures, while the monochrome mode proved to be more sensitive for detection. Two cases showed occult metastases on both sentinel and regional nodes. The identification and false negative rates were 100% and 0%, respectively. There were no complications incurred due to this method. Conclusion: Our results suggest that color FI with the HEMS allows for the accurate and safe harvest of SLNs with a preparatory skin incision. Although there is room for improvement of sensitivity, this easy‐to‐handle procedure might provide the potential to expand the role of the ICG method for SLN detection in head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: To improve lateral thyroarytenoid (TA) muscle atrophy after laryngeal paralysis, reconstruction of the vascular network of the atrophied muscle is necessary. We therefore evaluated whether the controlled release of basic fibroblast growth factor (bFGF) with autologous fascia implantation could affect vascular reconstruction in the lateral TA muscle. Study Design: Animal experiment. Setting: Laboratory. Methods: Unilateral laryngeal paralysis was induced in 20 rats. The rats were implanted with autologous fascia and a gelatin hydrogel sheet with or without 1 µg of bFGF (fascia and bFGF + fascia groups; n = 5 each) and with only a gelatin hydrogel sheet with bFGF (bFGF group: n = 5). Another group remained untreated (n = 5) at 4 months after paralysis. At 3 months since transplantation, intra- and intergroup comparisons of the muscle volumes and total area of blood vessels in the lateral TA muscle were performed. Results: When compared with the untreated group, the bFGF + fascia group showed a significant increase in muscle volume (P =.0008) and vascular area (P =.0002) in the lateral TA muscle, whereas the other 2 treated groups demonstrated an insufficient effect. Conclusion: bFGF + fascia implantation showed histologic improvement in severe laryngeal paralysis. We demonstrated that the decrease in lateral TA muscle mass after paralysis might be countered by the reconstruction of the vascular network. Our findings indicate that hypovascular and denervated areas of the laryngeal muscle can be regenerated by the implantation of growth factors and scaffolds with surgical stress. Level of evidence: 5. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing hemodialysis (HD) tend to experience hearing loss, including idiopathic sudden sensorineural hearing loss (ISSHL). However, little is known about the relationship between HD and ISSHL. Objective: To investigate the effects of HD on the hearing level and the treatment prognosis of ISSHL. Methods: We reviewed the medical records of 23 patients with ISSHL receiving HD treatment (HD group) and 101 patients with ISSHL not receiving HD treatment (non‐HD group), and assessed clinical features, results of audiometric tests and blood examination results. Results: Statistically significant differences were not observed in pretreatment hearing level and hearing recovery of the ear affected with ISSHL between the two groups (P >.05). Conversely, hearing thresholds in the unaffected ear were statistically different (P <.0001), and the hearing thresholds of the HD groups were significantly increased compared with those of the non‐HD groups, especially at high frequency. In addition, patients with renal dysfunction not receiving HD treatment showed similar hearing thresholds in the unaffected ear when compared with patients receiving HD treatment. Conclusion: HD itself did not influence the treatment prognosis of ISSHL. Renal dysfunction itself, and not HD treatment, worsened the hearing level. As similar treatment results are expected, standard treatment should be administered to patients undergoing HD. Level of Evidence: 3b. [ABSTRACT FROM AUTHOR]

Aim: This study retrospectively investigated the efficacy and safety of nivolumab for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) classified using age <65 years as the cutoff. Methods: Overall, 88 patients with R/M HNSCC treated with nivolumab were classified into the young group (<65 years; n = 39) and elderly group (≥65 years; n = 49). Efficacy was evaluated using overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Safety was evaluated considering immune‐related adverse events (irAEs). Results: The median OS was 9.7 and 8.6 months in the young and elderly groups, respectively. The 1‐year OS rate was 42.0% and 29.4% in the young and elderly groups, respectively. The median PFS was 3.0 and 4.2 months in the young and elderly groups, respectively. The 1‐year PFS rate was 30.0% and 27.9% in the young and elderly groups, respectively. In the young group, the ORR was 10.3% and DCR was 33.3%. In the elderly group, the ORR was 18.4% and DCR was 53.1%. There were no significant differences in OS, PFS, ORR, and DCR (P = 0.36, 0.53, 0.29 and 0.06, respectively). Interstitial lung disease (ILD) as an irAE occurred in the young group at a significantly higher rate (20.5% vs 4.1%; P = 0.02). Conclusions: There were no significant differences in OS, PFS, ORR, and DCR between the young and elderly groups. DCR tended to be better in the elderly group (P = 0.06). ILD occurred at a significantly higher rate in the young group. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To identify the clinical predictors of descending necrotizing mediastinitis (DNM) secondary to deep neck infections (DNIs) before treatment.Study Design: Retrospective case series.Methods: We reviewed 73 patients with DNIs who had been treated with external drainage at our institute between April 2009 and March 2019. We divided these patients into either a DNI group without mediastinitis (n = 55) or a DNM group secondary to DNI (n = 18). We collected clinical data and compared them between the groups, conducting univariate and multiple logistic regression analysis to identify the predictors of DNM.Results: We identified age, C-reactive protein (CRP), neutrophil percentage, lymphocyte percentage, neutrophil to lymphocyte ratio (NLR), presence of comorbidities, presence of gas, and abscess extension below the hyoid bone as statistically significant by univariate analysis. Moreover, multiple logistic regression analysis showed that age ≥55 years, NLR ≥13, and CRP ≥30 mg/dL were statistically significant.Conclusions: We identified age ≥55, NLR ≥13, and CRP ≥30 before DNI treatment as clinical predictors of a DNM complication.Level Of Evidence: 4 Laryngoscope, 130:E567-E572, 2020. [ABSTRACT FROM AUTHOR]

Background: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date.Methods: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality.Results: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients).Conclusions: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 . [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that immunotherapy with nivolumab, an anti‐programmed death 1 monoclonal antibody, is effective in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the predictive role of hematological inflammatory markers such as neutrophil‐to‐lymphocyte ratio (NLR) and the modified Glasgow prognostic score (mGPS) in patients with R/M SCCHN treated with nivolumab remains unclear. Methods: We conducted a multi‐institutional cohort study to evaluate the impact of pretreatment NLR and mGPS on overall survival (OS) and progression‐free survival (PFS) in patients with R/M SCCHN treated with nivolumab in Japan. From 2012 to 2013, 102 patients were eligible, of whom 88 were finally included in the analysis. mGPS was calculated as follows: mGPS of 0, C‐reactive protein (CRP) ≤1.0 mg/dL; 1, CRP > 1.0 mg/dL; and 2, CRP > 1.0 mg/dL and albumin < 3.5 mg/dL. Optimal cutoff point of dichotomized NLR was calculated using the area under the receiver operating characteristic curve (AUROC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models adjusted by potential confounders. Results: Higher NLR was significantly associated with worse survival (1‐year OS: 45.3% vs 16.3%, log‐rank P‐value <.001, adjusted HR: 4.40 (95% CIs: 1.78‐10.88); one‐year PFS: 39.1% vs 9.0%, P‐value =.001, adjusted HR: 3.37 (95% CI: 1.64‐6.92)). In addition, high mGPS (=2) was significantly associated with worse survival compared to low mGPS (=0) (1‐year OS: 37.4% vs 26.1%, P‐value =.004, adjusted HR: 4.20 (95% CI:1.54‐11.49); 1‐year PFS: 41.5% vs 24.8%, P‐value =.007, adjusted HR: 2.01 (95% CI: 0.87‐4.68)). These associations were consistent with subgroup analyses stratified by potential confounders. Conclusions: Pretreatment NLR and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with nivolumab. [ABSTRACT FROM AUTHOR]

Background: This study was designed to assess the therapeutic effect of urokinase‐targeted recombinant oncolytic Sendai virus, termed "BioKnife," on anaplastic thyroid carcinoma (ATC). Methods: Urokinase activity was investigated in human ATC cell lines, and BioKnife cytotoxicity against the cell lines was evaluated in vitro. Orthotopic mouse models of ATC were treated with three intratumoral injections of BioKnife, control virus, or phosphate‐buffered saline (PBS) and were observed daily until >20% weight loss occurred. Results: All three ATC cell lines showed a high level of urokinase activity. BioKnife induced urokinase‐dependent cell fusion and cytotoxicity in all cell lines. Orthotopic models treated with BioKnife showed significantly prolonged survival compared with models treated with control virus or PBS (BioKnife 41.6 ± 15.0, control virus 17.0 ± 2.9, PBS 17.7 ± 6.3 days). Conclusions: BioKnife exerted therapeutic effects in orthotopic ATC mouse models. Thus, BioKnife represents a possible treatment option for ATC. [ABSTRACT FROM AUTHOR]

Background: We evaluated the accuracy of endoscopic findings observed by narrow band imaging (NBI) combined with magnifying gastrointestinal endoscopy (GIE) for the differential diagnosis of cancerous and noncancerous laryngeal lesions. Methods: A total of 166 vocal cord lesions for which good images were obtained on NBI with magnifying GIE were evaluated with respect to the following 6 variables: macroscopic type, tumor location, color, white coat, keratinization, and abnormal microvessels. Results: Multivariate analysis showed that white coat (odds ratio [OR], 2.95, P = 0.05), keratosis (OR, 3.14, P = 0.02) and abnormal microvessels (OR, 31.1, P < 0.0001) were significantly related to laryngeal cancer. In the diagnosis of laryngeal cancer, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of abnormal microvessels were 84.4%, 88.6%, 91%, 80.5%, and 86.1%, respectively. Conclusion: The abnormal microvessels on NBI combined with magnifying GIE are useful for the differential diagnosis of laryngeal lesions. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to demonstrate anti‐metastatic effect of BioKnife, uPA activity‐dependent oncolytic Sendai virus, after BioKnife treatment for primary tumor, and analyze its mechanisms in a simulated metastasis mouse model of head and neck squamous cell carcinoma (HNSCC). Methods: We established a simulated metastasis mouse model using a murine HNSCC cell line "SCCVII." We assessed a tumor size and an induction of tumor‐specific immunoresponses using cytotoxic T‐lymphocyte (CTL) assay, flow cytometry (FCM) in spleen and immunohistochemistry (IHC) in secondary tumor. Results: Secondary tumors were significantly smaller in BioKnife‐treated group. CTL activities were significantly improved in BioKnife group. FCM revealed that induction of dendritic cells and CD4+/CD8+ lymphocytes was significantly higher in BioKnife group. IHC showed that CD8+ lymphocytes invaded secondary tumor. Conclusion: Tumor‐specific immunoresponses induced by BioKnife has great potential to be a novel, safe, and less invasive option for control and prevention of metastasis. [ABSTRACT FROM AUTHOR]

Background: Tumors in the parapharyngeal space are rare, and preoperative diagnosis is difficult because of anatomical and histological complexity. Methods: To evaluate the usefulness of preoperative diagnosis, we compared the classification of tumor localization in the prestyloid and retrostyloid compartments by imaging and preoperative cytological diagnosis by fine‐needle aspiration cytology with the postoperative histopathological diagnosis in 120 patients with tumors in the parapharyngeal space. Results: Tumors were located in the prestyloid and retrostyloid compartments in 68 and 52 patients, respectively. The majority of histopathological diagnoses in the prestyloid and retrostyloid compartments were pleomorphic adenoma and schwannoma, respectively. All malignant tumors were in the prestyloid compartment. The preoperative cytological diagnostic rate for benign or malignant tumor was 95.2%, which was not inferior to that for other head and neck lesions. Conclusion: Our results suggested that the preoperative classification of tumor localization and cytological diagnosis improved the accuracy of presumptive diagnosis. [ABSTRACT FROM AUTHOR]

Aim It has been well established that patients with head and neck cancer (HNC) have an elevated risk of developing a second primary cancer (SPC), owing to the common carcinogenic risk factors, including tobacco and alcohol consumption, and inactive aldehyde dehydrogenase-2 genotype. Here we investigated the current state of SPC in Japanese HNC patients. Methods We retrospectively investigated the incidence and treatment outcomes of synchronous and metachronous SPCs among 434 newly diagnosed HNC patients. Moreover, the associations between various carcinogenic risk factors and SPC were also assessed. Results Fifty-two (12.0%) and 104 patients (24.0%) had synchronous and metachronous SPCs, respectively. The cases with SPC were associated with high rates of smoking and alcohol histories (81.1% and 74.6%, respectively). Immunohistochemical analysis revealed that 47.5% of all oropharyngeal cancer cases showed positive p16 expression, and there was no significant difference between p16-positive and -negative cases in terms of the proportions of patients with SPC. The 3-year overall survival rates were 78.8%, 75.3% and 75.9% in patients without, with synchronous, and with metachronous SPC, respectively ( P = 0.4048). Conclusion Given the distinct features of the carcinogenic risk factors for HNC in Japan, care should be taken not to underestimate the frequency of SPC, even for human papillomavirus-related oropharyngeal cancer patients. Considering the high incidence of SPC associated with HNC, the appropriate diagnostic strategy to allow for early detection of SPC and a treatment strategy aimed at avoiding unnecessary radiotherapy for the index tumor would contribute to improving the prognosis for HNC. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Nerbridge (Toyobo Co., Ltd., Osaka, Japan) is a novel polyglycolic acid (PGA) tube that is filled with collagen fibers and that facilitates nerve fiber expansion and blood vessel growth. It is biocompatible and commercially available, with governmental approval for practical use in Japan. We hypothesized that the PGA-collagen tube would promote regeneration of the recurrent laryngeal nerve (RLN). This hypothesis was examined in a rat axotomy model of the RLN.Study Design: Prospective animal study.Methods: The axotomy model was established by transection of the left RLN in adult Sprague-Dawley rats. The cut ends of the nerve were bridged using Nerbridge (Toyobo Co., Ltd.) with a 1-mm gap (tube-treatment group) or direct sutures (sutured-control group). Left vocal fold mobility, nerve conduction velocity, morphology, and histology were assessed after 15 weeks.Results: Fifteen weeks after treatment, nerve fiber connections were observed macroscopically in both groups, and more clear myelinated fibers and better prevention of laryngeal muscle atrophy were observed in the tube-treatment group compared with the sutured-control group. However, vocal fold movement recovery was not observed in either group, and the conduction velocity of the RLN did not differ between the two groups.Conclusions: Better nerve regeneration was observed in the tube-treatment group. The combination therapy with molecular or gene therapy might be an effective strategy to improve vocal fold movement. The PGA-collagen tube has the potential to promote regeneration of the RLN and to be a scaffold for drug administration in these combination therapies.Level Of Evidence: N/A. Laryngoscope, 126:E233-E239, 2016. [ABSTRACT FROM AUTHOR]

Activator protein-1 (AP-1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP-1 inhibitor, T-5224, in preventing lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T-5224 on HNSCC cell invasion, migration, proliferation, and MMP activity by carrying out an in vitro study using an invasion assay, scratch assay, WST-8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time-lapse microscopy. Furthermore, cervical lymph node metastasis was assessed using an orthotopic tumor model of human oral squamous cell carcinoma cells (HSC-3-M3) injected in the tongue of a BALB/c nude mouse. T-5224 (150 mg/kg) or vehicle was given orally every day for 4 weeks. Animals were killed and assessed for lymph node metastasis by H&E staining of resected lymph nodes. T-5224 significantly inhibited the invasion, migration, and MMP activity of HNSCC cells in a dose-dependent manner; there was no significant influence on cell proliferation. The antimetastatic effect of T-5224 was also confirmed in our animal study. The rate of cervical lymph node metastasis in the model was 40.0% in the T-5224-treated group ( n = 30) versus 74.1% in the vehicle-treated group ( n = 27; P < 0.05). In conclusion, T-5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model. [ABSTRACT FROM AUTHOR]

Improved therapies for individuals with head and neck squamous cell carcinoma ( HNSCC) may be developed by identification of appropriate biomarkers. The aim of this study was to evaluate the usefulness of serum midkine measurement as a biomarker for HNSCC. Pretreatment serum midkine concentrations were measured in 103 patients with HNSCC and 116 control individuals by enzyme-linked immunosorbent assay. Midkine expression in tumor tissues from 33 patients with HNSCC who underwent definitive surgical resection without preoperative treatment was examined by immunohistochemistry. The cut-off serum midkine concentrations for predicting the presence of head and neck malignancy and chemosensitivity to induction chemotherapy, as determined using receiver operating characteristic curves, were 482 and 626 pg/mL, respectively. Spearman bivariate correlations showed positive correlations between serum midkine levels and immunohistochemistry staining score ( r = 0.612, P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serum midkine concentration for detection of HNSCC were 57.3, 85.3, 77.6, 69.2, and 72.1%, respectively. However, for predicting the response to induction chemotherapy, the values were 84.6, 60.9, 71.0, 77.8, and 73.5%, respectively. Serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, using Cox's proportional hazards model ( P = 0.027). Overexpression of serum midkine yielded a relative risk of death of 3.77, with 95% confidence limits ranging from 1.15 to 17.0. Serum midkine levels in patients with HNSCC were associated with malignancy, chemosensitivity, and prognosis. Serum midkine may be a useful, minimally invasive biomarker for early detection, therapeutic decision-making, and predicting prognosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Transoral surgery is gaining attention as a minimally invasive treatment option for laryngeal and pharyngeal cancer. Postoperative swallowing function is satisfactory in most cases, but occasionally dysphagia persists. Methods Swallowing function of 86 patients who underwent transoral videolaryngoscopic surgery (TOVS) for laryngeal and pharyngeal cancers was evaluated by the Functional Outcome Swallowing Scale (FOSS) and risk factors for dysphagia were identified. Results FOSS stage was 0 to 1 in 90%, 2 in 5.8%, 3 in 3.5%, and 4 in 1.2% of the patients. Only 1 patient had indication for percutaneous endoscopic gastrostomy (PEG). Univariate analysis revealed that resection of the pyriform sinus ( p = .0280) and arytenoid ( p = .0139), pulmonary dysfunction ( p = .0353), and large mucosal defect ( p = .0223) were associated with postoperative dysphagia. Conclusion Although the rate of PEG dependency is low in transoral surgery, surgeons should mention the risk of postoperative dysphagia when counseling patients preoperatively. © 2015 Wiley Periodicals, Inc. Head Neck 38: 196-201, 2016 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Acquired laryngotracheal stenosis is a challenging problem for otolaryngologists. Several studies suggest tacrolimus may inhibit post-transplant airway stenosis that occurs with coronary drug-eluting stents. The objective of the present study was to determine whether tacrolimus modulates wound healing of the airway mucosa and prevents laryngotracheal stenosis in an acute injury animal model. Study Design Basic science. Methods The laryngotracheal mucosa of rats was scraped with a nylon brush through the tracheostoma. Tacrolimus (0.2 mg/kg or 1.0 mg/kg) was systemically administered intramuscularly for 5 days. Nine days after scraping, the pathological changes and the degree of stenosis were assessed by hematoxylin and eosin staining or by immunohistochemical staining for nuclear factor of activated T cell and interleukin 2. Results Lumen stenosis resulted from hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition. There was a significant preventive effect on airway stenosis at the tracheal and cricoid levels in the low-dose (0.2 mg/kg) tacrolimus-treated animals, compared to the untreated animals ( P < .05). This effect was insignificant with treatment by high-dose tacrolimus (1.0 mg/kg). Immunohistochemistry showed that, after tacrolimus treatment, the expressions of nuclear factor of activated T cell and interleukin 2 were downregulated in submucosal fibroblasts, neovascular cells, and glandular cells. Conclusions This study suggests that low-dose systemic tacrolimus has a preventive effect on laryngotracheal stenosis by inhibiting the activation of immune cells in the injured airway mucosa via the calcineurin/nuclear factor of activated T cell/interleukin 2 pathway. Level of Evidence NA Laryngoscope, 125:E210-E215, 2015 [ABSTRACT FROM AUTHOR]

Objective: Sentinel node navigation surgery using real-time, near-infrared imaging with indocyanine green is becoming popular by allowing head and neck surgeons to avoid unnecessary neck dissection. The major drawback of this method is its quick migration through the lymphatics, limiting the diagnostic time window and undesirable detection of downstream nodes. We resolved this problem by mixing indocyanine green (ICG) with phytate colloid to retard its migration and demonstrated its feasibility in a nude mouse study.Study Design: Experimental prospective animal study.Settings: Animal laboratory.Subjects and Methods: Indocyanine green at 3 concentrations was tested to determine the optimal concentration for sentinel lymph node detection in a mouse model. Effect of indocyanine green with phytate colloid mixture solutions was also analyzed. Indocyanine green or mixture solution at different mixing ratios were injected into the tongue of nude mice and near-infrared fluorescence images were captured sequentially for up to 48 hours. The brightness of fluorescence in the sentinel lymph node and lymph nodes further downstream were assessed.Results: Indocyanine green concentration >50 μg/mL did not improve sentinel lymph node detection. The addition of phytate colloid to indocyanine green extended the period when sentinel lymph node was detectable. Second echelon lymph nodes were not imaged in mice injected with the mixture, while these were visualized in mice injected with indocyanine green alone.Conclusion: This novel technique of ICG-phytate colloid mixture allows prolonged diagnostic time window, prevention of downstream subsequent nodes detection, and improved accuracy for the detection of true sentinel lymph nodes. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Vocal cord scar formation and laryngotracheal stenosis (LTS) are challenging problems for otolaryngologists. Sendai virus (SeV) vectors have been shown to transduce airway epithelium efficiently, and are thus ideal for modulating airway wound-healing therapy. To assess the potential utility of SeV gene therapy for laryngotracheal diseases, we established a novel LTS model and examined the transduction efficiency of SeV vectors in normal and LTS model tissue. Study Design Basic science. Methods Fusion (F) gene-deleted, nontransmissible SeV vectors were used. First, the route dependency and transduction efficiency of SeV vectors for normal mucosa in the larynx were examined. Next, the novel LTS rat model was established and evaluated. Finally, the transduction efficiency of SeV vectors in injured mucosa of the LTS model was evaluated. Results Simple spray delivery of the SeV vector resulted in significant and persistent expression of the reporter gene in normal laryngotracheal epithelium. Transgenic SeV-mediated expression was maximal at 3 days, decreased over time, but remained detectable for 14 days after administration. No serious side effects were observed in the larynx or trachea. The model achieved an average of 60% tracheal stenosis in the cross-sectional area. Efficient SeV-mediated transgene expression was observed in the injured mucosa at the levels of the trachea, cricoid cartilage, and vocal cord. Conclusion A novel animal model for LTS was established. We successfully demonstrated SeV-mediated transgene expression in normal tissue and in the injured mucosa of the LTS model. SeV might be a promising strategy for gene therapy in laryngotracheal diseases. Level of Evidence N/A. [ABSTRACT FROM AUTHOR]

Surgery plays an important role in the treatment of head and neck cancer (HNC), and surgical margin status is a key prognostic factor. Molecular imaging (MI) can be applied to identify tumor extensions intraoperatively. We applied this technique in a murine HNC model to determine whether it improves outcomes from surgical intervention. An orthotopic murine model with HNC was established with SCC VII cells expressing a green fluorescent protein. To determine the diagnostic accuracy of MI, 20 murine models undergoing standard surgical resection were assessed with MI to identify residual tumor, which was compared to histology as the gold standard. Then, to assess the effect of MI as a therapeutic intervention for survival, 65 mice were randomly divided into standard surgical resection, MI-assisted surgical resection, and control groups. In the MI-assisted surgery group, residual signals identified by MI underwent further tissue excision to eliminate the signal positivity. In diagnostic accuracy analysis, sensitivity and specificity of intraoperative MI in the HNC murine model were 86% and 100%, respectively. The mice undergoing MI-assisted surgery showed a significantly improved 60-day survival rate compared to standard surgery, 37% versus 5%, respectively. Intraoperative MI guidance is a promising technique in oncologic surgery, which could increase the efficacy of tumor resection and the survival of patients with HNC. The hurdles in applying this technique in clinical practice are still considerable, and further research and development is warranted. [ABSTRACT FROM AUTHOR]

Background Recently, several transoral approaches for minimally invasive surgery have been developed for oropharyngeal cancer. However, all approaches have certain disadvantages. Therefore, we built and examined new surgical environments for improving the situation. Methods Endoscopic transoral resection using a pharyngeal retractor or distending laryngoscope, rigid videoendoscope, and laparoscopic surgical instruments was performed in 17 patients with oropharyngeal squamous cell carcinoma. Postoperative results regarding oncology and function as well as complications were documented. Results The 2-year relapse-free survival rate was 100%. Postoperative swallowing and speech function were satisfactory: 94.1% of cases scored ≤1 on the functional outcome swallowing scale (FOSS) and ≤1 on the communication score. Further, no perioperative mortality occurred. Conclusions The improved surgical environment made it possible to perform a safe and reliable en bloc resection with a wide field of view and sufficient working space. Our system can be useful, although further studies on additional cases are required. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

The article presents a study focusing on transoral videolaryngoscopic surgery (TOVS) for en bloc resection of supraglottic and hypopharyngeal cancers. It states that during the study several patients underwent TOVS for T1, T2, and selected T3 supraglottic and hypopharyngeal cancers. It concludes that TOVS may serve as a minimally invasive treatment option for supraglottic and hypopharyngeal cancers with satisfactory outcomes.

Objective: Chemoradiation has been recognized as one of the standard therapies for head and neck cancer. However, recent intensified chemoradiation can cause serious adverse events and influence treatment completion. We investigated the effect of Hange‐Shashin‐To, an herbal medicine, against chemoradiation‐induced mucositis in the context of the completion of chemoradiation. Method: Subjects were 10 head and neck cancer patients who underwent whole neck irradiation between May and November 2011. The patients gargled with 2.5 g Hange‐Shashinto‐To mixed with tap water 3 times a day during and after chemoradiation period, prohibiting eating and drinking for 30 minutes after the gargling. Results: Two patients started gargling with Hange‐Shashin‐To after grade III mucositis appeared, and the other 8 began it on the commencing date of chemoradiation. In 1 of the former 2 patients, the mucositis improved until grade I despite continued chemoradiation. Although the other remained grade III until the end of radiation, the gargling was useful for treatment completion without interruption. Of the latter 8 patients, 6 had grade I and 2 had grade II as the worst mucositis level in the chemoradiation period. Grade III or IV mucositis was not observed in this case series. Conclusion: Our results suggest that Hange‐Shashin‐To can alleviate mucositis from chemoradiotherapy and contribute to treatment completion without interruption. Although further studies in a large number of patients are needed to confirm our findings, Hange‐Shashin‐To may be a useful adjunctive therapy in chemoradiation for head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: 1) Understand the molecular pathway of cisplatin‐based chemoresistance with head and neck cancer. 2) Investigate if p63 plays an important role in regulating MRE11/RAD50/NBS1 (MRN) complex that contributes to cisplatin‐based chemoresistance. Method: Both JHU006 and JHU020 HNSCC cell lines were characterized as either sensitive or resistant to cisplatin. MRN and p63 expression levels were examined. The p63‐mediated MRN regulation was studied by introducing mutant NBS1 and siRNA. Cell growth was evaluated in response to cisplatin treatment and regulation of p63 and MRN. Results: IC50 to cisplatin for JHU006 and JHU020 was 8.76 and 0.61, respectively, suggesting that JHU006 is a cisplatin‐resistant cell line. Increased expression levels of MRN were found after cisplatin treatment in JHU006 as compared with JHU020. The p63 expression level, which is a positive transcriptional factor for RAD50 and MRE11, was up‐regulated after cisplatin treatment in JHU006 but not in JHU020. The knockdown of p63 resulted in the down‐regulation of MRN, and therefore there were interrupted DNA repair and sensitized resistant tumor cells to cisplatin. The introduction of mutant NBS1 could down‐regulate MRN, but was not effective on the p63 expression. Conclusion: Our study suggested that p63 may play an important role in regulating cisplatin‐based chemoresistance via MRN. The understanding of the molecular pathway of cisplatin‐based chemoresistance could help us to design an efficient treatment strategy for head and neck cancer. [ABSTRACT FROM AUTHOR]

Human MTH1 (hMTH1) is an enzyme that hydrolyses several oxidized purine nucleoside triphosphates to their corresponding nucleoside monophosphates. Crystallographic studies have shown that the accurate mode of interaction between 8-oxoguanine and hMTH1 cannot be understood without determining the positions of the H atoms, as can be observed in neutron and/or ultrahigh-resolution X-ray diffraction studies. The hMTH1 protein prepared in the original expression system from Escherichia coli did not appear to be suitable for obtaining high-quality crystals because the hMTH1 protein had heterogeneous N-termini of Met1 and Gly2 that resulted from N-terminal Met excision by methionine aminopeptidase from the E. coli host. To obtain homogeneous hMTH1, the Gly at the second position was replaced by Lys. As a result, mutant hMTH1 protein [hMTH1(G2K)] with a homogeneous N-terminus could be prepared and high-quality crystals which diffracted to near 1.1 Å resolution using synchrotron radiation were produced. The new crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.36, b = 47.58, c = 123.89 Å.