A Training Course for Simulating Head and Neck Ultrasound-Guided Procedures Using a Gelatin Phantom Model.

OBJECTIVES: Ultrasound (US)-guided procedures can be used in the evaluation and treatment of neck masses. However, these procedures need to be practiced before being executed on humans. The aim of this study is to evaluate the efficacy of a training program using a gelatin phantom to practice US-guided procedures. METHODS: This program included a lecture and practice with a gelatin phantom. We recruited doctors from different hospitals to practice US-guided procedures, including fine-needle aspiration (FNA), core needle biopsy (CNB), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA). We used a questionnaire with a 5-point scale to evaluate the effectiveness of practicing US-guided procedures under a gelatin phantom. RESULTS: Forty-four doctors participated, and 37 of them completed the questionnaires. After training, the mean (SD) scores of the doctors were 4.68 (0.47) for "Satisfaction with this course," 4.54 (0.61) for "Ease in practicing FNA&CNB using the phantom," 4.49 (0.61) for "Ease in practicing PEI using the phantom," 4.49 (0.65) for "Ease in practicing RFA using the phantom," and 4.57 (0.55) for "The course effectively familiarizing participants with US-guided procedures." Participants without experience in US examination had higher scores than those with previous US experience, but the difference was not statistically significant. CONCLUSION: A combination of lectures and hands-on practice of US-guided procedures using a gelatin phantom is an effective educational method for doctors interested in head and neck US. After the training program, doctors gained a better understanding of the necessary steps and skills required for these procedures. They can correctly insert the instruments into the target lesion and perform different US-guided procedures.

A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

PURPOSE: To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5 years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. METHODS: This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. RESULTS: The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12 g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12 g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. CONCLUSIONS: The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

A Novel Prediction Model Based on Quantitative Texture Analysis of Sonographic Images for Malignant Major Salivary Glandular Tumors.

Background: The aim of this study was to compare multiple objective ultrasound (US) texture features and develop an objective predictive model for predicting malignant major salivary glandular tumors. Methods: From August 2007 to May 2018, 144 adult patients who had major salivary gland tumors and subsequently underwent surgery were recruited for this study. Representative brightness mode US pictures were selected for texture analysis and used to develop a prediction model. Results: We found that the grayscale intensity and standard deviation of the intensity were significantly different between malignant and pleomorphic adenomas. The contrast, inverse difference (INV) movement, entropy, dissimilarity, and INV also differed significantly between benign and malignant tumors. We used stepwise selection of predictors to develop an objective predictive model, as follows: Score = 1.138 × Age - 1.814 × Intensity + 1.416 × Entropy + 1.714 × Contrast. With an optimal cutoff of 0.58, the diagnostic performance of this model had a sensitivity, specificity, overall accuracy, and area under the curve of 83% (95% confidence interval [CI]: 74%-92%), 74% (65%-84%), 78% (72%-85%), and 0.86 (0.80-0.92), respectively. Conclusion: We have developed a novel computerized diagnostic model based on objective US features to predict malignant major salivary gland tumor. Further improving the computer-aided diagnosis model might change the US examination for major salivary gland tumors in the future.

Ultrasound Is Beneficial to Determine Lymphadenopathy in Oral Cancer Patients after Radiotherapy.

The present study aimed to investigate whether the addition of ultrasound (US) +/- fine needle aspiration (FNA) to magnetic resonance imaging (MRI) or computed tomography (CT) improves the diagnostic accuracy in assessing neck lymphadenopathy in oral cancer patients after neck irradiation. We retrospectively reviewed oral cancer patients who had neck lymphadenopathy after radiotherapy (RT) or chemoradiation therapy (CRT) from February 2008 to November 2019. The following diagnostic modalities were assessed: (1) MRI/CT, (2) MRI/CT with a post-RT US predictive model, and (3) MRI/CT with US + FNA. The receiver operating characteristic (ROC) curves were used to assess the diagnostic performance. A total of 104 irradiation-treated oral cancer patients who subsequently had neck lymphadenopathy were recruited and analyzed. Finally, there were 68 (65%) malignant and 36 (35%) benign lymphadenopathies. In terms of the diagnostic performance, the area under the ROC curves (C-statistics) was 0.983, 0.920, and 0.828 for MRI/CT with US + FNA, MRI/CT with a post-RT US predictive model, and MRI/CT, respectively. The addition of US to MRI/CT to evaluate cervical lymphadenopathy could achieve a better diagnostic accuracy than MRI/CT alone in oral cancer patients after neck irradiation.

Enormous Asymptomatic Intraoral Sialolithiasis: A Case Report.

Sialolithiasis is one of the most common diseases of salivary glands. More than 80% of the sialoliths occur in the submandibular gland. While most of the calculi are less than 10 mm in size, 7.6% are larger than 15 mm and are classified as giant sialoliths. We demonstrate a rare case of asymptomatic giant sialolith in the left Wharton's duct with a total atrophy of the left submandibular salivary gland. A 48-year-old female patient presented with lumping sensation for 1 month. A left mouth floor mass was found accidentally during examination and was later revealed to be a painless sialolithiasis. Image study revealed a giant sialolith in the left Wharton's duct with duct dilatation and left submandibular gland total atrophy. She underwent transoral sialolithotomy with removal of a huge stone, measuring 3.5 × 1.4 cm in size. Sialolithiasis usually presents with typical symptoms of the involved salivary gland, and the size of calculi is usually less than 20 mm. This is a rare case report of an asymptomatic giant sialolith in the Wharton's duct, causing left submandibular salivary gland total atrophy, and its diagnosis and management.

Postchemoradiotherapy systemic inflammation response index predicts treatment response and overall survival for patients with locally advanced nasopharyngeal cancer.

BACKGROUND/PURPOSE: To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal cancer (NPC). METHODS: A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival. RESULTS: Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p = 0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p = 0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p = 0.017). CONCLUSION: The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.

Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer.

In this study, we determined the diagnostic performance of adding ultrasound (US) with/without fine-needle aspiration cytology (FNAC) to computed tomography (CT)/magnetic resonance imaging (MRI) in evaluating neck lymphadenopathy (LAP) in patients with head and neck cancer treated with irradiation. We included 269 patients who had neck LAP after radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) resulting from cancers of the head and neck region between October 2008 and September 2018. The diagnostic methods consisted of the following: 1) CT/MRI alone, 2) CT/MRI combined with a post-RT US predictive model, and 3) CT/MRI combined with US + FNAC. We compared their diagnostic performance using receiver operating characteristic (ROC) curves. In total, 141 (52%) malignant and 128 (48%) benign LAPs were observed. Regarding the diagnostic accuracy, the area under the ROC curves was highest for the combined CT/MRI and US + FNAC (0.965), followed by the combined CT/MRI and post-RT US predictive model (0.906) and CT/MRI alone (0.836). Our data suggest that the addition of a US examination to CT/MRI resulted in higher diagnostic performance than CT/MRI alone in terms of diagnosing recurrent or persistent nodal disease during the evaluation of LAP in patients with irradiation-treated head and neck cancer.

Vocal Fold Steroid Injection for Benign Vocal Lesions in Professional Voice Users.

OBJECTIVES: Current treatments for benign vocal lesions consist mainly voice therapy and phonomicrosurgery. However, these options are not always suitable for professional voice users because of their tight performance schedule and limited time for voice rest. This study investigated vocal fold steroid injection (VFSI) as an alternative treatment. STUDY DESIGN: Matched case series. METHODS: We retrospectively enrolled 28 professional voice users (i.e., singers, actors and news anchors) who received VFSI for vocal nodules and polyps in an office setting of a tertiary teaching hospital. Outcomes were evaluated using videolaryngostroboscopy (VLS), the 10-item Voice Handicap Index (VHI-10), maximum phonation time, and acoustic and perceptual analyses before and 1 month after VFSI. Study results were compared with 56 patients of nonprofessional voice users (i.e., routine or high occupational vocal demands), matched in a 1:2 ratio by age, sex, and treatment date. RESULTS: After VFSI, VLS revealed substantial lesion resolution in 82% professional voice users. One professional voice user developed a self-limited vocal fold hematoma after VFSI. VHI-10 scores in the professional group decreased from 21 to 14 points, compared with 23 to 16 points in the non-professional group, demonstrating a significant within-group effect (P < 0.01, GEE) and a nonsignificant between-group effect (P = 0.86). Other outcomes also improved significantly after VFSI (P < 0.05), without significant differences between the two groups. CONCLUSION: VFSI can be an effective and safe alternative treatment for professional voice users with benign vocal lesions.

Speech and Swallowing Rehabilitation Potentially Decreases Body Weight Loss and Improves Survival in Head and Neck Cancer Survivors.

This retrospective observational cohort study aims to assess the outcomes and associated factors in head and neck cancer (HNC) survivors with dysphagia, and to investigate the relationship between outcomes and speech and swallowing rehabilitation (SSR). We enrolled patients who were diagnosed with HNC between October 2016 and July 2018; we included 393 patients who developed dysphagia after definite treatment and were referred to speech-language pathologists (SLPs). We then classified patients into groups according to whether they received SSR. We used the clinical variables-including age, sex, site of malignancy, cancer stage, treatment modality, SSR, initial ECOG score, initial KPS, initial body weight (BW), and initial BMI-to evaluate the association between the percentage of BW change and overall survival (OS). There were 152 (39%) and 241 (61%) patients who received and did not receive SSR, respectively. In multivariate linear regression, SSR was significantly associated with percentage change in BW at 3 months post-treatment. Having SSR was positively associated with the percentage change in BW and decreased the BW loss [ß coefficient (95% CIs) = 2.53 (0.92 to 4.14)] compared to having no SSR. In the multivariate Cox regression, SSR was an independent factor for OS. Compared to no SSR, the hazard ratio (95% CIs) for patients who received SSR was 0.48 (0.31 to 0.74). SSR helps to avoid BW loss and increases overall survival. HNC patients who develop dysphagia after treatment should be encouraged to participate in SSR.

Screening and surveillance of esophageal cancer by magnifying endoscopy with narrow band imaging improves the survival of hypopharyngeal cancer patients.

Introduction: Patients with head and neck cancer may develop a second primary neoplasm (SPN) of the esophagus due to field cancerization. This study investigated the impacts of esophageal cancer screening using magnifying endoscopy with narrow-band imaging (ME-NBI) on the outcomes of hypopharyngeal cancer patients. Methods: Patients with hypopharyngeal cancer diagnosed from 2008 to 2021 in a tertiary hospital were reviewed retrospectively. Screening and surveillance using ME-NBI examination of the esophagus were divided into three patterns: (1) ME-NBI never performed or more than 6 months after diagnosis of index primary hypopharyngeal cancer, (2) ME-NBI within 6 months only, and (3) ME-NBI within 6 months and regular surveillance. Results: A total of 261 were reviewed and 21 (8%) patients were in stage I, 20 (8%) in stage II, 27 (10%) in stage III, 116 (44%) in stage IVA, 65 (25%) in stage IVB, and 12 (5%) in stage IVC. Sixty-seven (26%) patients had SPN (50 esophagus, 10 oral cavity, 3 oropharynx, 2 nasopharynx, 1 larynx and 1 lung). Among esophageal SPN, 35 (70%) and 15 (30%) patients developed synchronous and metachronous neoplasia, respectively. In multivariate Cox regression analysis, advanced stages III and IV (compared with stages I and II, HR: 1.86, 1.18-2.95, p=0.008), ME-NBI examination of the esophagus received within 6 months and regular surveillance (HR: 0.53, 0.36-0.78, p=0.001) were independent factors affecting the overall survival of patients with hypopharyngeal cancer. Discussion: Our findings demonstrated that screening and surveillance of esophageal SPN by ME-NBI improves the survival of patients with hypopharyngeal cancer.

Spotted Temporal Lobe Necrosis following Concurrent Chemoradiation Therapy Using Image-Guided Radiotherapy for Nasopharyngeal Carcinoma.

Background: To explore spotted temporal lobe necrosis (TLN) and changes in brain magnetic resonance imaging (MRI) after image-guided radiotherapy (IGRT) in a patient with nasopharyngeal carcinoma (NPC). Case presentation: a 57-year-old male was diagnosed with stage III NPC, cT1N2M0, in 2017. He underwent concurrent chemoradiation therapy (CCRT) with cisplatin (30 mg/m2) and 5- fluorouracil (5-FU, 500 mg/m2) plus IGRT with 70 Gy in 35 fractions for 7 weeks. The following MRI showed a complete response in the NPC. However, the patient suffered from fainting periodically when standing up approximately 3 years after CCRT. Neck sonography showed mild atherosclerosis (< 15%) of bilateral carotid bifurcations and bilateral small-diameter vertebral arteries, with reduced flow volume. The following MRI showed a 9 mm × 7 mm enhancing lesion in the right temporal lobe without locoregional recurrence, and TLN was diagnosed. The lesion was near the watershed area between the anterior temporal and temporo-occipital arteries. The volume of the necrotic lesion was 0.51 c.c., and the mean dose and Dmax of the lesion were 64.4 Gy and 73.7 Gy, respectively. Additionally, the mean dose, V45, D1 c.c. (dose to 1 ml of the temporal lobe volume), D0.5 c.c. and Dmax of the right and left temporal lobes were 11.1 Gy and 11.4 Gy, 8.5 c.c. and 6.7 c.c., 70.1 Gy and 67.1 Gy, 72.0 Gy and 68.8 Gy, and 74.2 Gy and 72.1 Gy, respectively. Conclusion: Spotted TLN in patients with NPC treated by IGRT may be difficult to diagnose due to a lack of clinical symptoms and radiological signs. Endothelial damage may occur in carotid and vertebral arteries within the irradiated area, affecting the small branches supplying the temporal lobe and inducing spotted TLN. Future research on the relationship between vessels and RT or CCRT and the development of TLN is warranted.

Advances in Image-Guided Radiotherapy in the Treatment of Oral Cavity Cancer.

Image-guided radiotherapy (IGRT) is an advanced auxiliary radiotherapy technique. During cancer treatment, patients with oral cavity cancer (OCC) experience not only disease but also adverse effects due to RT. IGRT provides the relevant advantages of RT by precisely delivering tumoricidal doses via real-time knowledge of the target volume location and achieves maximal tumor control with minimal complications as recommended for cancer treatment. Additionally, studies have shown that IGRT can improve clinical outcomes in terms of not only treatment side effects but also survival benefits for cancer patients. IGRT can be performed alongside various imaging methods, including computed tomography and magnetic resonance imaging, and at different times during the radiotherapy regimen. This article reviews the literature to discuss the effects and importance of IGRT for patients with OCC, examines the rationale underlying the advantages of IGRT, discusses the limitations of IGRT with respect to different techniques, and summarizes the strategies and future prospects of IGRT in the treatment of OCC.

The Applications and Potential Developments of Ultrasound in Oral Cancer Management.

Oral cancer is endemic and causes a great burden in Southern Asia. It is preferably treated by surgery with/without adjuvant radiotherapy (RT) or chemoradiation therapy, depending on the stage of the disease. Close or positive resection margin and cervical lymph node (LN) metastasis are important prognostic factors that have been presented to be related to undesirable locoregional recurrence and poor survival. Ultrasound (US) is a simple, noninvasive, time-saving, and inexpensive diagnostic modality. It can depict soft tissues very clearly without the risk of radiation exposure. Additionally, it is real-time and continuous image is demonstrated during the exam. Furthermore, the clinician can perform US-guided fine needle aspiration (FNA) or core needle biopsy (CNB) at the same time. US with/without US-guided FNA/CNB is reported to be of value in determining tumor thickness (TT), depth of invasion (DOI), and cervical LN metastasis, and in aiding the staging of oral cancer. DOI has a relevant prognostic value as reported in the eighth edition of the American Joint Committee on Cancer staging of oral cancer. In the present review, we describe the clinical applications of US in oral cancer management in different phases and potential applications in the future. In the pretreatment and surgical phase, US can be used to evaluate TT/DOI and surgical margins of oral cancer in vivo and ex vivo. The prediction of a malignant cervical LN (nodal metastasis) by the US-based prediction model can guide the necessity of FNA/CNB and elective neck dissection in clinical early-stage oral cancer. In the posttreatment surveillance phase, US with/without US-guided FNA or CNB is helpful in the detection of nodal persistence or LN recurrence, and can assess the possibility and extent of carotid artery stenosis after irradiation therapy. Both US elastography and US swallowing assessment are potentially helpful to the management of oral cancer.

Comparisons among the Ultrasonography Prediction Model, Real-Time and Shear Wave Elastography in the Evaluation of Major Salivary Gland Tumors.

We aimed to validate the diagnostic accuracy of a novel sonographic scoring model and compare it with other methods in the evaluation of malignant major salivary gland tumors. We enrolled 138 patients who received neck ultrasound (US) with fine needle aspiration (FNA) and further operations or core needle biopsies for major salivary gland tumors from June 2015 to October 2021. The sonographic scoring model was presented as 2.08 × (vague boundary) + 1.75 × (regional lymphadenopathy) + 1.18 × (irregular or speculated shape) + 1.45 × (absence of posterior acoustic enhancement) + 2.4 × (calcification). We compared the diagnostic accuracy of the sonographic scoring model with shear wave elastography (SWE), real-time elastography (RTE), and US-FNA cytology for differentiating between benign and malignant lesions. The sensitivity, specificity, and accuracy were 58%, 89%, and 85% for the sonographic scoring model, 74%, 62%, and 64% for the SD of SWE with optimal cutoff value of 31.5 kPa, 69%, 70%, and 70% for the 4-point scoring system of RTE, and 74%, 93%, and 91% for US-FNA cytology, respectively. The sonographic scoring model is feasible as assistance in the evaluation of major salivary gland tumors. US-FNA cytology remains the tool of choice in diagnosing malignant salivary gland tumors.

A predictive model for advanced oropharyngeal cancer patients treated with chemoradiation.

BACKGROUND: To analyze clinical characteristics in the prediction of death within 1 year in advanced oropharyngeal cancer patients treated with chemoradiation. METHODS: One hundred forty-seven advanced oropharyngeal cancer patients who underwent curative-intent chemoradiation treatment were retrospectively enrolled. The pre-treatment clinical parameters including inflammatory markers were reviewed. RESULTS: The 1-year death rate for all patients was 29% [95% confidence interval (CI): 23-37%]. In multivariate logistic regression analysis, hemoglobulin (Hb) < 13.5 g/dl was an independent indicator of death within 1-year [Odds ratio (OR) 5.85, 95% CI 2.17-15.75, p < 0.001]. Systemic immune inflammation (SII) ≥ 1820 was also a significant factor for prediction of death within 1 year (OR 4.78, 95% CI 1.44-15.85, p = 0.011). We further used gander, age, Hb and SII to develop a nomogram to predict death within 1 year. The c-index of the model was 0.75 (95%CI 0.66-0.83). For patients with low nomogram score (< 14) versus high nomogram score (≥ 14), the 1-year and 2-year OS rates were 91 and 71% versus 53 and 29%, respectively. (p < 0.001). A difference in the disease persistence or recurrence rate between patients with high and low nomogram score was significant (73 and 28%, respectively; p < 0.001). CONCLUSIONS: The pre-treatment Hb < 13.5 g/dl and SII ≥ 1820 are associated with higher risks of death within 1-year in patients with advanced oropharyngeal cancers. Nomogram can aid in patient counseling and treatment modality adjustment. The development of a more effective treatment protocol for patients with high nomogram score will be essential.

Endoscopic Screening for Second Primary Tumors of the Esophagus Among Head and Neck Cancer Patients.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol's chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs.

Risk of CVD Following Radiotherapy for Head and Neck Cancer: An Updated Systematic Review and Meta-Analysis.

Background: The relative risk for cerebrovascular disease (CVD) is increased in patients with head and neck cancer (HNC) treated with radiotherapy (RT). However, the current relative risk for CVD following RT has not been well clarified. The purpose of this study was to analyze the effect of RT and update the risk of CVD following RT in HNC patients through a systematic review and meta-analysis. Material and Methods: We conducted an online database search and systematic review of observational studies that reported on CVD and extracranial carotid stenosis in patients with HNC who had undergone RT. Articles published in Medline and PubMed from 1980 to 2021 were identified and collected. Results: Of the forty-seven articles identified from PubMed and forty-four articles identified from 3 systematic reviews, twenty-two studies were included. We found that neck RT was a significant risk factor for CVD (HR 3.97, 95% CI: 2.89-5.45). Patients with HNC treated by RT had an increased OR (7.36, 95% CI: 4.13-13.11) for CVD, and approximately 26% (95% CI: 22%-31%) of HNC patients treated with RT were at risk for CVD with more than 50% reduction in carotid diameter. Conclusion: The risk of CVD is increased in patients with HNC treated by RT, and recent improvements in RT techniques may have contributed to the decreased risk of CVD. These results suggest that regular follow-up and appropriate screening for CVD should be required for patients with HNC.

Galvanic vestibular-evoked myogenic potentials in evaluating damaged sites of vestibular neuritis.

Objectives: To test the possibility of pure otolithic organ deficits and validate the histopathological evidence of retrovestibular neural impairment in vestibular neuritis (VN), the authors adopted a topographic survey combining cervical vestibular-evoked myogenic potential (cVEMP) and ocular vestibular-evoked myogenic potential (oVEMP) using various stimulation modes and caloric tests. Methods: Forty patients with VN were enrolled in this study. All patients underwent pure tone audiometry, acoustic cVEMP, galvanic cVEMP, vibratory oVEMP, galvanic oVEMP, and caloric tests. Different combinations of vestibular tests were further compared and analyzed. Results: According to vestibular test results in affected VN ears, the proportion (10%) of pure saccular dysfunction was significantly less than that (52.5%) of saccular nerve deficit. The proportion (2.5%) of pure utricular dysfunction was significantly less than that (37.5%) of utricular nerve deficit. The percentage (82.5%) of VN involving the ampullar vestibulo-ocular reflex (VOR) pathway was significantly higher than that (40%) involving the utriculo-ocular reflex (UOR) pathway. The superior, inferior, and total VN percentages were 37.5%, 17.5%, and 45%, respectively. The proportion of inferior VN was significantly less than that of VN involving the superior vestibular nerve. Conclusion: There were significantly fewer cases of pure otolithic organ dysfunction than vestibular nerve involvement in VN patients. The damage to the ampullar VOR pathway was more significant than that to the UOR pathway, and both pathways might be independent of each other. In addition, the incidence of isolated inferior VN was significantly less than that of VN involving the superior vestibular nerve. Level of Evidence: Level 3.

Quercetin induces tongue squamous cell carcinoma cell apoptosis via the JNK activation-regulated ERK/GSK-3α/ß-mediated mitochondria-dependent apoptotic signaling pathway.

Tongue squamous cell carcinoma (SCC) is a most common type of oral cancer. Due to its highly invasive nature and poor survival rate, the development of effective pharmacological therapeutic agents is urgently required. Quercetin (3,3',4',5,7-pentahydroxyflavone) is a polyphenolic flavonoid found in plants and is an active component of Chinese herbal medicine. The present study investigated the pharmacological effects and possible mechanisms of quercetin on apoptosis of the tongue SCC-derived SAS cell line. Following treatment with quercetin, cell viability was assessed via the MTT assay. Apoptotic and necrotic cells, mitochondrial transmembrane potential and caspase-3/7 activity were analyzed via flow cytometric analyses. A caspase-3 activity assay kit was used to detect the expression of caspase-3 activity. Western blot analysis was performed to examine the expression levels of proteins associated with the MAPKs, AMPKα, GSK3-α/ß and caspase-related signaling pathways. The results revealed that quercetin induced morphological alterations and decreased the viability of SAS cells. Quercetin also increased apoptosis-related Annexin V-FITC fluorescence and caspase-3 activity, and induced mitochondria-dependent apoptotic signals, including a decrease in mitochondrial transmembrane potential and Bcl-2 protein expression, and an increase in cytosolic cytochrome c, Bax, Bak, cleaved caspase-3, cleaved caspase-7 and cleaved poly (ADP-ribose) polymerase protein expression. Furthermore, quercetin significantly increased the protein expression levels of phosphorylated (p)-ERK, p-JNK1/2 and p-GSK3-α/ß, but not p-p38 or p-AMPKα in SAS cells. Pretreatment with the pharmacological JNK inhibitor SP600125 effectively reduced the quercetin-induced apoptosis-related signals, as well as p-ERK1/2 and p-GSK3-α/ß protein expression. Both ERK1/2 and GSK3-α/ß inhibitors, PD98059 and LiCl, respectively, could significantly prevent the quercetin-induced phosphorylation of ERK1/2 and GSK3-α/ß, but not JNK activation. Taken together, these results suggested that quercetin may induce tongue SCC cell apoptosis via the JNK-activation-regulated ERK1/2 and GSK3-α/ß-mediated mitochondria-dependent apoptotic signaling pathway.