The Expression of Defensin-Associated Genes May Be Correlated With Lymph Node Metastasis of Early-Stage Tongue Cancer.

OBJECTIVES: We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. METHODS: In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. RESULTS: No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P<0.01; fold change >2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. CONCLUSION: . Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

Oncological Outcomes after Pulmonary Metastasectomy for Head and Neck Squamous-Cell Carcinoma and Adenoid Cystic Carcinoma.

INTRODUCTION: Pulmonary metastatic head and neck cancer has a poor prognosis. Pulmonary metastasectomy has been performed but only in carefully selected patients. The aim of this study was to examine the clinical characteristics and oncological follow-up of patients who underwent pulmonary metastasectomy. METHODS: Data of 54 patients with squamous-cell carcinoma (SCC) or adenoid cystic carcinoma (ACC) who underwent metastasectomy between 2003 and 2019 at two tertiary referral centers were retrospectively reviewed. RESULTS: The 3-year and 5-year disease-free survival rates after metastasectomy were 49.9% and 39.9% for SCC and 38.9% and 32.4% for ACC, respectively. Univariate analysis revealed that a disease-free interval (DFI) less than 14 months and R1 resection (hazard ratio [HR] [95% confidence interval]: 2.95 [0.77-5.62], 4.64 [0.99-21.65], respectively) were risk factors for recurrence in SCC and that a high T stage (HR: 5.24 [1.22-22.58]) was a risk factor in ACC. In SCC, a DFI less than 14 months and R1 resection (hazard ratio: 6.35 [1.36-29.54], 12.79 [1.53-106.95], respectively) were risk factors in a multivariate analysis. CONCLUSION: Pulmonary metastasectomy had a fair effect on head and neck SCC and ACC, and the prognosis was better in SCC patients with a DFI greater than 14 months.

Long-term impact of smoking cessation on new glottic cancer events in patients with early glottic cancer.

Objective: Patients with early glottic cancer sometimes exhibit new glottic cancer events after 5 years. This study aimed to analyse the patterns and risk factors of new glottic cancer events in patients with early glottic cancer 5 years after initial treatment. Methods: In total, 209 patients were included in this study. Age, sex, T stage, anterior commissure involvement, smoking pattern and treatment modality were retrospectively analysed. Results: The median follow-up was 91 (range, 60-266) months. The median time for the occurrence of new glottic cancer events was 97 (range, 61-199) months. New glottic cancer events occurred 5 years after initial treatment in 16 (7.6%) patients, among whom 12 (75.0%) had new glottic cancer event lesions overlapping with initial lesions. Smoking cessation after treatment was significantly correlated with fewer new glottic cancer events after 5 years. Conclusions: New glottic cancer events occurring 5 years after initial treatment in patients with early glottic cancer are not negligible. In particular, if smoking is continued after treatment, these patients can experience new glottic cancer events even after 5 years.

Primary versus modified secondary closure techniques for persistent tracheocutaneous fistula in pediatric patients.

PURPOSE: This study aimed at compating two closure techniques for tracheocutaneous fistulas (TCFs) in pediatric patients. METHODS: A total of 106 consecutive pediatric patients who underwent closure of a persistent TCF between April 2007 and February 2021 at a tertiary pediatric hospital were evaluated, and 103 pediatric patients aged between 12 months and 18 years were included. The clinical characteristics, perioperative outcomes, and postoperative outcomes were compared between TCF closure by primary closure (Group 1) and a modified secondary healing technique (Group 2). RESULTS: Of the 103 patients, 58 were classified into Group 1, and 45 into Group 2. The mean age at tracheostomy and TCF closure was significantly younger in Group 2, and the interval between decannulation to TCF closure was significantly shorter in Group 2. Procedural time and hospital stay were significantly shorter in Group 2 than Group 1. Group 2 had a significantly lower complication rate, need for revision surgery, and recannulation rate than Group 1. CONCLUSIONS: Modified secondary healing was more efficient in terms of procedural time and hospital stay, and safer (i.e., fewer complications). It is an effective surgical technique for closing a persistent TCF in younger patients more quickly after decannulation compared to primary closure.

Role of concurrent chemoradiation on locally advanced unresectable adenoid cystic carcinoma.

BACKGROUND/AIMS: Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor characterized by indolence, with a high rate of local recurrence and distant metastasis. This study aimed to investigate the effect of concurrent chemoradiation (CCRT) on locally advanced unresectable ACC. METHODS: We retrospectively analyzed clinical data from 10 patients with pathologically confirmed ACC of the head and neck who received CCRT with cisplatin in Seoul National University Hospital between 2013 and 2018. RESULTS: Ten patients with unresectable disease at the time of diagnosis or with positive margins after surgical resection received CCRT with weekly cisplatin. Eight patients (80%) achieved complete remission, of which three later developed distant metastases without local relapse; one patient developed distant metastasis and local relapse. Two patient achieved partial remission without progression. Patients experienced several toxicities, including dry mouth, radiation dermatitis, nausea, and salivary gland inflammation of mostly grade 1 to 2. Only one patient showed grade 3 oral mucositis. Median relapse-free survival was 34.5 months (95% confidence interval, 22.8 months to not reached). CONCLUSION: CCRT with cisplatin is effective for local control of ACC with manageable toxicity and may be an effective treatment option for locally advanced unresectable ACC.

CT-defined visceral adipose tissue thresholds for identifying metabolic complications: a cross-sectional study in the United Arab Emirates.

OBJECTIVES: Visceral adipose tissue (VAT) is closely related to obesity complications. We aimed to determine the optimal sex-specific and age-specific VAT thresholds for predicting metabolic complications among individuals living in the United Arab Emirates (UAE). DESIGN: Retrospective cross-sectional study. SETTING: We reviewed medical records of adults who visited a hospital in the UAE. PARTICIPANTS: A total of 369 subjects were included in the final analysis after application of inclusion and exclusion criteria. PRIMARY OUTCOME MEASURES: The prevalence of metabolic syndrome (MES). RESULTS: MES measures excluding waist circumference were present in 73.4% of women and 78.5% of men. VAT areas adjusted for age were significantly greater in the MES group compared with the non-MES group regardless of sex (p<0.05 for all relations); however, subcutaneous adipose tissue areas adjusted for age were not significantly different. Areas under the curve used to predict MES were statistically significant for VAT and visceral to subcutaneous fat ratios among both men and women. Identified cut-off values of VAT to predict MES were 132.0 cm2 in both sexes for individuals under the age of 50 years. For those over 50 years of age, VAT thresholds were greater in women compared with men (173 cm2 vs 124.3 cm2, respectively). CONCLUSIONS: Optimal VAT cut-offs to predict MES were 132 cm2 for individuals under 50 years old living in the UAE. These measures are potential target visceral fat values that could be used to reduce obesity-related morbidity in populations with pre-existing metabolic complications.

Lung metastasis in adenoid cystic carcinoma of the head and neck.

BACKGROUND: Distant metastasis of adenoid cystic carcinoma (ACC) is most commonly identified in the lung, but risk factors are still on debate. METHODS: Risk factors for lung metastasis were evaluated by using Cox proportional hazards model and Kaplan-Meier curves. RESULTS: Of 112 patients, 48% had distant metastasis; 94.4% of whom had lung metastasis. Univariable analysis revealed sublingual or minor salivary gland, tumor size ≥2.5 cm, and perineural invasion as risk factors (hazard ratio [HR]: 1.99 [1.02-3.91], 2.57 [1.19-5.58], and 2.46 [1.28-4.74], respectively), whereas size, perineural invasion, and local recurrence were risk factors in multivariable analysis (HR: 2.29 [1.05-4.96], 2.32 [1.09-4.96], and 2.68 [1.24-5.79], respectively). CONCLUSION: Sublingual gland or minor salivary glands ACC has a higher risk of lung metastasis. If the site is not considered, the following factors increased the risk of lung metastasis; (a) size ≥2.5 cm, (b) perineural invasion, and (c) local recurrence.

Prognostic value of the association between MHC class I downregulation and PD-L1 upregulation in head and neck squamous cell carcinoma patients.

The purpose of this study was to evaluate the prognostic impact of major histocompatibility complex (MHC) class I expression and programmed death-ligand 1 (PD-L1) expression in patients with head and neck squamous cell carcinoma (HNSCC). A total of 158 patients with HNSCC were evaluated retrospectively. The expression of MHC class I and PD-L1 was analyzed in tumor specimens using immunohistochemistry. The association between MHC class I/PD-L1 expression and clinical outcome was evaluated by Kaplan-Meier and Cox regression analyses. Among 158 patients, 103 (65.2%) showed positive PD-L1 expression, and 20 (12.7%) showed no detectable expression of MHC class I. The frequency of PD-L1 positive expression with concomitant MHC class I loss was 7.0%. In the PD-L1-positive group, MHC class I loss was associated with a significantly worse survival compared with MHC class I positivity (median overall survival 39.3 months vs. not reached; P = 0.005), whereas MHC class I status provided no prognostic impact in the PD-L1 negative group. Neither PD-L1 nor MHC class I alone showed a significant difference in overall survival. The loss of MHC class I expression in PD-L1-positive HNSCC was associated with a poor clinical outcome. This suggested that MHC class I expression status might be useful for the prognosis of tumor progression in HNSCC when combined with PD-L1 expression status. External validation with enough numbers of participants in such subgroup should be needed for validation.

Validation of a rhinologic virtual surgical simulator for performing a Draf 3 endoscopic frontal sinusotomy.

BACKGROUND: We recently introduced a patient-specific rhinologic virtual surgical environment (VSE) that has shown potential for surgical rehearsal of various skull base lesions. Our aim in this study was to validate the usefulness of the rhinology VSE in performing the Draf 3 procedure. METHODS: An outside-in Draf 3 procedure was performed on 4 cadaver heads. Computed tomography (CT) scans were obtained before and after cadaver dissection (CD). Pre-dissection CT scans were used to construct a cadaver-specific VSE. A virtual Draf 3 dissection (VD) was performed using the same technique. Validation was conducted by comparing the final common frontal outflow tract. A subjective comparison of the post-dissection endoscopic findings (CD vs VD) and an objective measurement using the post-dissection CT scan for the CD and the reconstructed CT scan obtained from the data after the VD was performed. RESULTS: Subjective overall resemblance of the 2 dissections (CD vs VD) assessed by the 4-point Likert scale (0-3) was 2.5 (median interquartile range [IQR], 0.25) for the 4 cadavers. The median difference for the anteroposterior dimension of the frontal neo-ostium (CD vs VD) assessed in the midsagittal view was 0.11 mm, whereas the median difference for the lateral dimension assessed in the coronal view was 2.71 mm. Thus, no statistical difference was observed. CONCLUSION: VD showed nearly matching results with the actual cadaver dissection. With further validation, our rhinologic VSE may be used for presurgical planning and rehearsal before the actual Draf 3 procedure is performed in the operating room.

Long-term oncological and functional outcomes of induction chemotherapy followed by (chemo)radiotherapy vs definitive chemoradiotherapy vs surgery-based therapy in locally advanced stage III/IV hypopharyngeal cancer: Multicenter review of 266 cases.

OBJECTIVE: The aim of this study was to evaluate the treatment outcomes for stage III/IV locally advanced hypopharyngeal squamous cell carcinoma (SCC), comparing induction chemotherapy followed by (chemo)radiotherapy (ICT), definitive chemoradiotherapy (CRT) and surgery-based therapy (SRT). SUBJECTS AND METHODS: Two hundred sixty-six patients with stage III/IV locally advanced hypopharyngeal squamous cell carcinoma (SCC) who underwent ICT (n = 74), CRT (n = 53) or SRT (n = 139) from 1997 through 2014 at the Seoul National University Hospital (n = 127) and the Hallym University Medical Center (n = 139) were enrolled in the study. All surgical procedures in the SRT group were performed by a single surgeon to eliminate surgeon bias. RESULTS: The 5-year disease-free survival (DFS) and overall survival (OS) of all patients (n = 266) were 59.4% and 44%, respectively. The 5-year DFS rates after salvage treatment were 52.7% for ICT, 52.8% for CRT and 65.5% for SRT (p = 0.194). The OS rates were 44.6% for ICT, 39.6% for CRT and 45.3% for SRT group (p = 0.106). The salvage rates were 12.5% for ICT, 15.6% for CRT and 3.8% for SRT group. The final laryngeal preservation rate was significantly lower in the SRT group (44.6%) than in the ICT (71.6%) or CRT (71.7%) groups. All major postoperative complications were significantly higher in the salvage surgery group. CONCLUSION: Treatment outcomes in the ICT and CRT groups were comparable to that of the SRT group for stage III/IV hypopharyngeal SCC. However, the relatively low chance of cure and high risk of complications should be taken into account when considering salvage surgery.

Poor prognostic factors in human papillomavirus-positive head and neck cancer: who might not be candidates for de-escalation treatment?

BACKGROUND/AIMS: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. METHODS: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed. RESULTS: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3-4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001). CONCLUSION: Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

Optimal timing for salvage surgery after definitive radiotherapy in hypopharyngeal cancer.

PURPOSE: Use of radiotherapy combined with chemotherapy is increasing in hypopharyngeal cancer. However, many show residual tumor after radiotherapy. Timing for treatment evaluation and salvage therapy is essential. However, optimal timing for salvage surgery has not been suggested. In this study, we tried to evaluate optimal timing for salvage surgery. METHODS AND MATERIALS: Patients who were diagnosed with hypopharyngeal squamous cell carcinoma between 2006 and 2015 were retrospectively analyzed. All patients received definitive radiotherapy with or without chemotherapy. Response of all treated patients were analyzed at 1, 3, and 6 months after radiotherapy. Any patients with progression before 6 months were excluded. RESULTS: A total of 54 patients were analyzed. Complete remission (CR) rates at 1 month (CR1), 3 months (CR3) and 6 months (CR6) were 66.7%, 81.5%, and 90.7%, respectively. Non-CR at 1 month (NCR1), 3 months (NCR3), and 6 months (NCR6) showed poor locoregional recurrence-free survival rates (1-year rates of 63.7%, 66.7%, and 0.0%, respectively) compared to CR1, CR3, and CR6 (1-year rates 94.3%, 88.0%, and 91.5%, respectively). Particularly significant differences were seen between CR6 and NCR6 (p < 0.001). Of 10 patients with NCR3, 5 showed CR at 6 months (NCR3/CR6). There was no statistical difference in locoregional recurrence-free survival between CR3 and NCR3/CR6 group (p = 0.990). CONCLUSION: Our data suggest half of patients who did not show CR at 3 months eventually achieved CR at 6 months. Waiting until 6 months after radiotherapy may be appropriate for avoiding additional salvage therapy.

Genotypic characteristics and their association with phenotypic characteristics of hereditary medullary thyroid carcinoma in Korea.

BACKGROUND: Hereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level. METHODS: A total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13-16. These patients were diagnosed during the years 1982-2012 at 2 Korean tertiary hospitals. Patients were analyzed according to the route of diagnosis (screened versus index cases) or the mutational site of rearranged during transfection gene (the American Thyroid Association risk group). RESULTS: Rearranged during transfection mutation was found in 23.8% of patients tested, showing a decreasing trend with time. The most commonly mutated codon was codon 634 (37.1%), followed by codon 918 (14.3%). rearranged during transfection-positive patients were younger than rearranged during transfection-negative patients, although no other clinicopathologic characteristics differed. Screened cases were younger and had smaller tumors than index cases. Among rearranged during transfection-positive patients, pheochromocytoma manifested in 35.1% and hyperparathyroidism in 7.0%. Notably, pheochromocytoma and hyperparathyroidism emerged at any time after the diagnosis of medullary thyroid carcinoma. The American Thyroid Association risk-group analysis demonstrated that medullary thyroid carcinoma patients in the highest risk group were younger, had larger tumors, and higher disease-specific mortality. Similar results for pheochromocytoma were found, according to the American Thyroid Association risk group, although the results were not significant. CONCLUSIONS: Korean patients who have medullary thyroid carcinoma showed a similar distribution of rearranged during transfection gene mutation with those in Western countries. The American Thyroid Association risk classification was shown to be useful for pheochromocytoma, as well as for medullary thyroid carcinoma. Familial screening for rearranged during transfection mutation and lifelong monitoring for associated pheochromocytoma should be emphasized in hereditary medullary thyroid carcinoma.

Correlation between computed tomography imaging and histopathology in pleomorphic adenoma of parotid gland.

OBJECTIVE: The purpose of this study was to correlate the CT imaging features and histopathological findings of pleomorphic adenomas (PA), and also try to identify its clinical significance. METHODS: Totally 262 PAs in the parotid gland including 18 recurrent cases were retrospectively reviewed with preoperative CT and pathologic slides. Each pathologic slide was reviewed by two pathologists to calculate mean value of epithelial/mesenchymal component, and the results were correlated with features of CT scans. RESULTS: PAs showing high contrast enhancement were correlated with high proportion of epithelial components in histopathologic findings. PAs with smooth border tend to have high proportion of epithelial components. The margin on CT imaging did not consisted with pathologic margin of resected specimens. In recurrent PAs, there was a significant difference on CT contrast enhancement, not in proportion of epithelial component. CONCLUSION: The histopathology and CT imaging features of PAs were variable, but we can find the correlation of epithelial component and CT contrast enhancement. Further large scale study would be expected to identify the clinical significance of CT imaging features and histopathologic findings of PAs.

Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma.

Programmed death-ligand 1 (PD-L1) expression is regarded as a predictive marker for anti-PD-1/PD-L1 therapy. The purpose of study was to explore the changes in PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) during treatment. Paired HNSCC tissues prior to and after cisplatin-based treatment were evaluated to determine PD-L1 protein expression by immunohistochemistry. Among the 35 HNSCC patient samples, PD-L1 expression status changed after treatment in 37.1% (13/35) of samples. Among the 13 patients whose baseline PD-L1 was negative, PD-L1 expression was increased in 9 cases (69.2%) and remained negative in 4 cases (30.8%, P = 0.003). Patients exposed to cisplatin generally showed PD-L1 up-regulation (83.3%, P = 0.037) compared to those not exposed to cisplatin (57.1%, P = 0.072). To validate these findings in vitro, changes in PD-L1 expression in HNSCC cell lines (Detroit-562, PCI-13, SNU-1041, SNU-1066, SNU-1076, and FaDu) were analyzed by western blotting and flow cytometry after treatment with cisplatin and interferon-gamma. In HNSCC cell lines, PD-L1 expression was significantly up-regulated after cisplatin, along with phosphor-MAPK/ERK kinase up-regulation. In conclusion, PD-L1 expression in HNSCC may be altered during cisplatin treatment, activating the MAPK/ERK kinase pathway.

Celecoxib enhances the inhibitory effect of 5-FU on human squamous cell carcinoma proliferation by ROS production.

OBJECTIVES: The role of celecoxib in preventing and treating tumors has attracted broad attention in recent years because of its selective and specific inhibition of COX-2 activity. We investigated the inhibitory effects and mechanisms of celecoxib combined with 5-fluorouracil (5-FU) on proliferation of squamous cell carcinoma cells in vivo and in vitro. STUDY DESIGN: Animal study and basic research. METHODS: SNU-1041 and SNU-1076 squamous cell lines and an orthotopic tongue cancer mouse model were used to study growth inhibition with 5-FU enhanced by celecoxib. Sensitivity of cells to drug treatment was analyzed by the MTT assay, and generation of reactive oxygen species (ROS) was measured using dichlorofluorescein diacetate. Phosphorylation of AKT was detected by Western blotting. Survival analysis in the mouse model was assessed according to combination treatment with 5-FU and celecoxib. RESULTS: Reactive oxygen species production in vitro was highest when celecoxib was administered 48 hours after 5-FU treatment. 5-FU-induced inhibition of cell proliferation was enhanced when combined with celecoxib, which was positively correlated with ROS production. Antioxidant treatment reversed 5-FU-inhibited cell proliferation by up to 60%. Cotreatment with celecoxib and 5-FU partially blocked AKT phosphorylation, although no significant changes in total AKT protein levels were detected. An increased survival time was observed in an orthotopic mouse model treated with a combination of celecoxib and 5-FU compared to treatment with either agent alone. CONCLUSION: Celecoxib may have an enhanced anticancer effect in combination with 5-FU. Reactive oxygen species production may be a key mechanism in this combination therapy by inhibiting the AKT pathway. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:E117-E123, 2017.

Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM) grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM) and methylcellulose (MC) for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

Is There Any Age Cutoff to Treat Elderly Patients with Head and Neck Cancer? Comparing with Septuagenarians and Octogenarians.

With the increase in life expectancy, age is no longer considered as a limitation for treatment. Nevertheless, the treatment of elderly patients with head and neck cancer (HNC) remains controversial. Here, we aimed to review our experience with the treatment for elderly patients, while particularly focusing on the differences among older old patients (septuagenarians vs. octogenarians). We retrospectively reviewed the records of 260 elderly patients who were assigned to 3 groups according to age: 70 years old ≤ group 1 < 75 years old, 75 years old ≤ group 2 < 80 years old, and group 3 ≥ 80 years old. The patients were assessed for comorbidities using the Adult Comorbidity Evaluation (ACE)-27, and the American Society of Anesthesia (ASA) physical status was also compared. Group 1, 2, and 3, consisted of 97, 102, and 61 patients, respectively. No significant difference in demographic data was noted among the groups. However, group 3 showed more comorbidities than groups 1 and 2. With regard to the initial treatment for HNC, radiation therapy (RT) was more frequently performed in group 3 than in groups 1 and 2. Among 7 patients of non-compliant to treatment in group 3, 6 patients had have performed RT. In group 3, a total of 18 patients underwent surgery, including microvascular free flap reconstruction and no significant difference in complications was observed postoperatively compared with group 1 and 2. Moreover, no significant difference was noted in overall survival between the groups, regardless of the treatment modality chosen. In conclusion, octogenarians with HNC should be more carefully managed than septuagenarians with HNC. Surgical treatment can be considered in octogenarians with HNC, if it can be tolerated.

5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

BACKGROUND: Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. METHODS AND RESULTS: DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. CONCLUSIONS: From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it.