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.

NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake.

BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).

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.

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.

Clinical outcomes after local anesthesia with monitored anesthesia care during thyroidectomy and selective neck dissection: a randomized study.

Although thyroidectomy under local anesthesia with monitored anesthesia care (LA-MAC) has been reported, reports of neck dissections beyond level VI under LA-MAC in patients with thyroid cancer are rare. We aimed to analyze clinical data and patient satisfaction levels during thyroidectomy and selective neck dissection by comparing LA-MAC and general anesthesia (GA) in adult patients undergoing these surgeries for thyroid cancer. The 60 enrolled patients comprised 50 patients that underwent thyroidectomy and 10 that underwent selective neck dissection; 30 underwent thyroidectomy (n = 25) or selective neck dissection (n = 5) under LA-MAC and 30 (matched patients) underwent thyroidectomy (n = 25) or selective neck dissection (n = 5) under GA. Complaints of postoperative nausea, vomiting, throat discomfort, and voice changes were significantly fewer in the LA-MAC group than in the GA group. Postoperative pain, odynophagia, dyspnea, and patient satisfaction levels were not significantly different between groups. In the thyroidectomy group, postoperative nausea, vomiting, throat discomfort, and voice changes were less common with LA-MAC, whereas postoperative pain, odynophagia, dyspnea, and patient satisfaction levels were similar for both anesthesia methods. The selective neck dissection group showed no differences between the two anesthesia methods. No postoperative complications were reported in all patients. Our results suggest that LA-MAC can be routinely used for select cases of thyroidectomy and is feasible for selective neck dissection beyond level VI with regard to postoperative discomfort, patient satisfaction levels, and safety. However, further investigations are necessary to clarify these findings.

Comparison of the Clinical Outcomes of Patients with Squamous Cell Carcinoma of the Tonsil Receiving Postoperative Ipsilateral Versus Bilateral Neck Radiotherapy: A Propensity Score Matching Analysis (KROG 11-07).

PURPOSE: The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively. MATERIALS AND METHODS: Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patients were identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groups were similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively. CONCLUSION: INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.

Radiofrequency ablation of low-risk small papillary thyroidcarcinoma: preliminary results for patients ineligible for surgery.

PURPOSE: The purpose of this study is to retrospectively evaluate the outcomes of radiofrequency ablation (RFA) of low-risk small papillary thyroid carcinomas (PTCs) in patients who were ineligible for surgery. MATERIALS AND METHODS: Between 2005 and 2009, six PTCs (mean diameter, 0.92 cm; range, 0.6-1.3 cm) in six patients were treated with RFA by three radiologists in two hospitals. The inclusion criteria for this study were (1) pathologically confirmed PTC without cytological aggressiveness, (2) single PTC without extrathyroidal extension, (3) no metastatic tumours and (4) ineligibility for surgery. RFA was performed using a radiofrequency generator and an 18-gauge internally cooled electrode. The medical records were reviewed and analysed, focussing on the procedural profiles of RFA, symptoms and complications during and after RFA, and changes in tumours on follow-up ultrasonography. RESULTS: Before and after RFA, the results of thyroid function tests were normal in all patients. During 48.5 ± 12.3 months (range, 36-65 months) of follow-up, along with a significant reduction in the mean volume (98.5 ± 3.3%), four ablation zones (4/6, 66.7%) completely disappeared. Two ablation zones exhibited only small calcified residues with nearly complete disappearance of the corresponding non-calcified solid portions, and in one of them, malignant cells were absent as assessed by fine-needle aspiration and core-needle biopsy. Transient hypertension with mild headache (n = 1) and mild neck pain (n = 1) developed during the procedure and subsided without any treatment. CONCLUSION: Besides surgery and active surveillance, which are conflicting currently used management plans, RFA might represent an effective and a safe alternative for managing low-risk small PTCs, especially in patients ineligible for surgery.

Role of surgery in the management of anaplastic thyroid carcinoma: Korean nationwide multicenter study of 329 patients with anaplastic thyroid carcinoma, 2000 to 2012.

BACKGROUND: The Korean Society of Thyroid Head and Neck Surgery established a nationwide multicenter registry of anaplastic thyroid carcinoma (ATC) and evaluated the prognostic factors and treatment outcomes of ATC. METHODS: The present study enrolled 329 patients who were diagnosed with ATC between January 2000 and December 2012 at 19 medical centers in Korea. Survival outcomes were evaluated according to various clinical factors and treatments. RESULTS: Multivariate analysis identified age ≥70 years old, the presence of initial clinical symptoms, distant metastasis, and treatment modality as significant risk factors (p <.05). The patients who underwent curative resection and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CRT) showed the best survival on multivariate analysis (p < 0.05). CONCLUSION: Although ATC is a lethal neoplasm, long-term survival may be acquired in cases in which the aggressive management, including curative resection or RT/concurrent CRT, is possible for therapeutic intent. © 2016 Wiley Periodicals, Inc. Head Neck 39: 133-139, 2017.

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.

Recurrence and Survival After Gross Total Removal of Resectable Undifferentiated or Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: This study aimed to evaluate the recurrence and survival after initial curative-intent surgery of resectable anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC). METHODS: A retrospective analysis was conducted on patients with ATC and PDTC who had been treated between 1985 and 2013. Among them, 119 patients who had undergone surgery with curative intent were included in this study. The outcome measures included the clinical response to treatment and the recurrence rates of three separate thyroid cancer groups: ATC, differentiated thyroid cancer (DTC) with anaplastic foci, and PDTC. RESULTS: Initial remission was achieved in 100 (84.0%) patients, with higher percentages in patients with DTC with anaplastic foci (97.8%) and PDTC (96.7%) compared with ATC (60.5%). The overall recurrence rate after initial remission was 30.8% in ATC, 25.9% in PDTC, and 6.7% in DTC with anaplastic foci. Pathologic diagnosis, preexisting goiter or tumors, along with tracheal and lymphatic/vascular invasion were correlated with recurrence (p < 0.001; p = 0.001, 0.006, 0.003, and 0.016, respectively). All patients without initial remission died due to local failure, and most patients with recurrence, apart from two PDTC patients, had distant metastasis. Overall mortality after initial curative-intent surgery was 58.1% in ATC, 8.7% in DTC with anaplastic foci, and 20% in PDTC. CONCLUSIONS: The initial remission of resectable tumors was higher and the recurrence rate was lower in DTC with anaplastic foci and PDTC compared with ATC. Careful monitoring of the development of distant metastasis is necessary, especially in patients with aggressive pathology with tracheal and lymphovascular invasion.

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: a role in organ preservation.

BACKGROUND/AIMS: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. METHODS: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. RESULTS: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). CONCLUSIONS: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.

Predictive and prognostic value of PET/CT imaging post-chemoradiotherapy and clinical decision-making consequences in locally advanced head & neck squamous cell carcinoma: a retrospective study.

BACKGROUND: The accuracy of (18)F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) in predicting immediate failure after radical chemoradiotherapy (CRT) for HNSCC is poorly characterized at present. The purpose of this study was to examine PET/CT as a predictive and prognostic gauge of immediate failure after CRT and determine the impact of these studies on clinical decision making in terms of salvage surgery. METHODS: Medical records of 78 consecutive patients receiving radical CRT for locally advanced HNSCC were reviewed, analyzing PET/CTs done before and 3 months after CRT. Immediate failure was defined as residual disease or locoregional and/or systemic relapse within 6 months after CRT. RESULTS: Maximum standard uptake value (SUV) of post CRT PET/CT (postSUVmax) was found optimal for predicting immediate failure at a cutpoint of 4.4. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 90.0%, 83.8%, 98.3%, and 45.0%, respectively. Of 78 patients studied, postSUVmax ≥ 4.4 prevailed in 20 (25.6%), with postSUVmax <4.4 in 58 (74.4%). At postSUVmax ≥ 4.4 (vs. postSUVmax <4.4) OS was poorer by comparison (3-year OS: 56.9 vs. 87.7%; P = 0.005), as was progression-free survival (3-year PFS: 42.9 vs. 81.1%; P < 0.001). At postSUVmax ≥ 4.4, OS with and without immediate salvage surgery did not differ significantly (3-year OS: 60.0 vs. 55.6%; Log-rank P = 0.913). CONCLUSION: Post CRT PET/CT imaging has prognostic value in terms of OS and PFS and is useful in predicting immediate therapeutic failure, given its high NPV. However, OS was not significantly altered by early salvage surgery done on the basis of post CRT PET/CT findings.

PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma.

Virus-associated malignancies and sarcomatoid cancers correlate with high PD-L1 expression, however, underlying mechanisms remain controversial. We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC).Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+). Interestingly, PD-L1 expression was significantly associated with EMT (P = 0.010), as assessed by low E-cadherin and high vimentin expression. The overall survival of PD-L1+ patients with EMT features was significantly worse than those without EMT features (P = 0.007). In an independent validation cohort (N = 91), as well as in HNSCC cases of The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia, high PD-L1 expression was also associated with the high probability of an EMT signature, referred from the GEO dataset, GSE4824. Survival analysis confirmed PD-L1+/EMT+ patients had a poorer prognosis than PD-L1+/EMT- patients in the TCGA cohort. PD-L1 positivity can thus be divided into two categories according to the absence or presence of EMT. PD-L1 expression is also independently associated with EMT features in HNSCC.

A population-based study on the association between rheumatoid arthritis and voice problems.

The objective of this study was to investigate whether rheumatoid arthritis increases the frequency of organic laryngeal lesions and the subjective voice complaint rate in those with no organic laryngeal lesion. We performed a cross-sectional study using the data from 19,368 participants (418 rheumatoid arthritis patients and 18,950 controls) of the 2008-2011 Korea National Health and Nutrition Examination Survey. The associations between rheumatoid arthritis and organic laryngeal lesions/subjective voice complaints were analyzed using simple/multiple logistic regression analysis with complex sample adjusting for confounding factors, including age, sex, smoking status, stress level, and body mass index, which could provoke voice problems. Vocal nodules, vocal polyp, and vocal palsy were not associated with rheumatoid arthritis in a multiple regression analysis, and only laryngitis showed a positive association (adjusted odds ratio, 1.59; 95 % confidence interval, 1.01-2.52; P = 0.047). Rheumatoid arthritis was associated with subjective voice discomfort in a simple regression analysis, but not in a multiple regression analysis. Participants with rheumatoid arthritis were older, more often female, and had higher stress levels than those without rheumatoid arthritis. These factors were associated with subjective voice complaints in both simple and multiple regression analyses. Rheumatoid arthritis was not associated with organic laryngeal diseases except laryngitis. Rheumatoid arthritis did not increase the odds ratio for subjective voice complaints. Voice problems in participants with rheumatoid arthritis originated from the characteristics of the rheumatoid arthritis group (higher mean age, female sex, and stress level) rather than rheumatoid arthritis itself.

Activation of K(+) channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca(2+) ionophore-induced cell death.

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca(2+) ([Ca(2+)]i)-dependent signaling affects the fate of cancer cells. Here we investigate the role of Ca(2+)-activated K(+) channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 µM ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of Ca(2+)-activated Cl(-) channels (Ano-1) and Ca(2+)-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward K(+) current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Consistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the Ca(2+) overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.

Changes of Clinicopathologic Characteristics and Survival Outcomes of Anaplastic and Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: This study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC). METHODS: A retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci. RESULTS: The five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; p < 0.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; p < 0 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, p = 0.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (p = 0.013). CONCLUSIONS: The choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer.

VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma.

PURPOSE: The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). MATERIALS AND METHODS: A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS). RESULTS: In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. CONCLUSION: High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.

Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma.

PURPOSE: We performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response. METHODS: Patients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC were divided into two groups: good responders and poor responders by tumor response and progression-free survival. Targeted gene sequencing for 2404 somatic mutations of 44 genes was performed on HNSCC tissues. Mutations with total coverage of <500 were excluded, and the cutoff for altered allele frequency was >10 %. RESULTS: Of the 71 patients, 45 were treated upfront with IC. Mean total coverage was 1941 per locus, and 42.2 % of tumors had TP53 mutations. Thirty-three mutations in TP53, NOTCH3, FGFR2, FGFR3, ATM, EGFR, MET, PTEN, FBXW7, SYNE1, and SUFU were frequently altered in poor responders. Among the patients who were treated with IC, those with unfavorable genomic profiles had significantly poorer overall survival than those without unfavorable genomic profiles (hazard ratio 6.45, 95 % confidence interval 2.07-20.10, P < 0.001). CONCLUSIONS: Comprehensive analysis of mutation frequencies identified unfavorable genomic profiles, and the patients without unfavorable genomic profiles can obtain clinical benefits from IC in patients with HNSCC.

Effect of induction chemotherapy on survival in locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy: Single center experience.

BACKGROUND: Although induction chemotherapy can reduce distant metastases in locally advanced head and neck squamous cell carcinoma (HNSCC), overall survival (OS) improvement because of induction chemotherapy has not been confirmed. METHODS: We reviewed medical records of 224 patients diagnosed with locally advanced HNSCC who were treated with induction chemotherapy followed by concurrent chemoradiotherapy (CRT; induction chemotherapy/CRT; N = 144) and CRT alone (N = 80) from 2005 to 2013. We analyzed OS and progression-free survival (PFS). RESULTS: The 3-year OS rate was significantly higher in the induction chemotherapy/CRT group compared to the CRT group (74.0% vs 62.7%; p = .045). The 3-year PFS rate was 64.6% in the induction chemotherapy/CRT group and 54.1% in the CRT group (p = .060). Subgroup analysis showed patients with high N classification (N2 or N3) oropharyngeal cancer had greater benefits when treated with induction chemotherapy/CRT. CONCLUSION: Induction chemotherapy plus CRT improved OS, compared to CRT alone in locally advanced HNSCC, especially with high N classification.