Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

The prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post-irradiated patients with nasopharyngeal carcinoma (NPC) is unknown. MATERIALS AND METHODS: In a cross-sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24-h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified. RESULTS: 51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD-positive and LPR-positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR-positive and GERD/LPR-negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR. CONCLUSIONS: A high prevalence of GERD/LPR in patients with post-irradiated NPC exists, but reflux symptoms are inadequate for diagnosis.

Early detection of nasopharyngeal carcinoma: performance of a short contrast-free screening magnetic resonance imaging.

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.

A Hybrid Auricular Framework of Autologous Rib Cartilage and a Porous Polyethylene Implant for Reconstruction of Congenital Microtia: A Modification of Nagata's Technique.

Background: An implant (porous polyethylene) is an alternative to rib cartilage for microtia reconstruction but carries a risk of extrusion. Objective: To evaluate the outcome of a hybrid framework of implant with rib cartilage for microtia reconstruction. Methods: Patients who underwent Nagata's technique for microtia reconstruction were reviewed for complications and aesthetic score. In stage 1, a rib cartilage framework or a hybrid framework of implant with rib cartilage was used. In stage 2, the framework was elevated and supported by an implant for projection. Postoperative outcomes were reported for both groups. Results: Forty-four ears of 40 patients underwent surgery. Eleven ears received a rib auricular framework and 33 ears a hybrid auricular framework. The mean postoperative follow-up for the rib and hybrid groups was 76.3 and 43.1 months, respectively. No supporting postauricular implant extruded, whereas stainless-steel wires extruded in seven ears (15.9%). Five (15.2%) hybrid frameworks were removed due to infection or extrusion. Mean operating time was 2 h shorter in the hybrid group. Aesthetic outcomes were similar for both groups. Conclusion: A hybrid framework of rib and implant that requires less harvested cartilage is feasible for microtia reconstruction, but caution should be used due to its higher explantation rate.

Quality of life and swallowing outcomes after early proactive swallowing rehabilitation by either transcutaneous neuromuscular electrical stimulation or exercise-based swallowing training in patients with nasopharyngeal carcinoma after radiotherapy.

Background: Exercise-based swallowing training (EBST) and transcutaneous neuromuscular electrical stimulation (TNMES) are common modalities used to treat late dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). We aimed to investigate and compare the efficacies of EBST and TNMES as proactive treatments administered early after radiotherapy. Methods: Patients with early post-radiotherapy NPC (n = 120) underwent either TNMES or EBST. Flexible endoscopic evaluation of swallowing (FEES), quality of life (QOL), and swallowing function questionnaires were completed before the intervention as well as immediately, 6, and 12 months after the intervention. Outcome measures included the scores for the swallowing function score (SFS), penetration and aspiration scale (PAS), dynamic imaging grade of swallowing toxicity (DIGEST), functional oral intake scale (FOIS), swallowing performance status scale (SPSS), pharyngeal motor impairment (PMI), pharyngeal function impairment (PFI), and functional assessment after cancer therapy-nasopharyngeal (FACT-NP) questionnaire. Results: Three months after radiotherapy, 31 and 34 patients underwent TNMES and EBST, respectively, and completed swallowing assessments at all four assessment timepoints. All patients showed post-radiotherapy impairments in the SFS, PAS, DIGEST, PMI, and PFI. Compared with the EBST group, the TNMES group showed significant improvements in the PFI and PMI scores, with small-to-medium effect sizes. Additionally, compared with the EBST group, the TNMES group demonstrated a trend toward slightly better improvements in the PAS, DIGEST, FOIS, and SPSS scores immediately and 6 months after the intervention. The SFS scores improved from baseline in both groups; however, the TNMES group showed an earlier improvement. Finally, the TNMES group showed better QOL according to the FACT-NP than the EBST group. Conclusion: Proactive TMNES and EBST are safe and feasible modalities for improving swallowing in patients with NPC when administered early after radiotherapy. Although TNMES showed better results than EBST, these results should be interpreted with caution given the study limitations. Level of evidence: 1B.

Autophagy regulates anti-angiogenic property of lenvatinib in thyroid cancer.

We aimed to explore the role of lenvatinib-mediated autophagy in papillary thyroid cancer (PTC). K1 and BCPAP, were tested for cell viability, proliferation, and apoptosis after treatment with lenvatinib or chloroquine (CQ) or both. The levels of angiogenesis vascular endothelial growth factor A (VEGFA) were measured by ELISA. Transwell and wound-healing assays were performed using endothelial HUVECs cells. The dynamics of microvessels were detected by tubular formation assay. Western blotting was used to determine the expression of LC3-I/II and Atg-7 and alterations in the PI3K/Akt/mTOR and MEK/ERK pathways. In vivo tumor growth assay and immunohistochemical staining (IHC) was also performed. The results showed that lenvatinib inhibited the viability of K1 and BCPAP cells and caused apoptosis. We further showed that lenvatinib also upregulated autophagy levels in thyroid cancer cells in a dose-dependent manner through the PI3K/Akt/mTOR and MEK/ERK pathways. Co-administration of lenvatinib with CQ resulted in a greater decrease of VEGFA in the tumor supernatant than with either lenvatinib or CQ alone. Autophagy inhibition enhanced the cytotoxicity and anti-angiogenic ability of lenvatinib, which was supported by the HUVECs migration, wound healing, and tube formation assays. Inhibiting autophagy chemically or genetically enhanced lenvatinib's cytotoxic effects and anti-angiogenic efficacy in thyroid cancer cells in vitro and in vivo. In conclusion, lenvatinib inhibited cell viability and induced apoptosis and autophagy in human PTC cells. Significantly, the combination of lenvatinib and autophagy inhibition may represent a novel and effective treatment option for PTC, which may be able to overcome drug resistance.

Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.

Discriminating between benign and malignant salivary gland tumors using diffusion-weighted imaging and intravoxel incoherent motion at 3 Tesla.

PURPOSE: The purpose of this study was to retrospectively evaluate the diagnostic performances of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) for discriminating between benign and malignant salivary gland tumors (SGTs). MATERIALS AND METHODS: Sixty-seven patients with 71 SGTs who underwent MRI examination at 3 Tesla were included. There were 34 men and 37 women with a mean age of 57 ± 17 (SD) years (age range: 20-90 years). SGTs included 21 malignant tumors (MTs) and 50 benign SGTs (33 pleomorphic adenomas [PAs] and 17 Warthin's tumors [WTs]). For each SGT, DWI and IVIM parameters, mean, skewness, and kurtosis of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion volume fraction (f) were calculated and further compared between SGTs using univariable analysis. Areas under the curves (AUC) of receiver operating characteristic of significant parameters were compared using the Delong test. RESULTS: Significant differences in ADCmean, Dmean and D*mean were found between SGTs (P < 0.001). The highest AUC values were obtained for ADCmean (0.949) for identifying PAs and D*mean (0.985) for identifying WTs and skewness and kurtosis did not outperform mean. To discriminate benign from malignant SGTs with thresholds set to maximize Youden index, IVIM and DWI produced accuracies of 85.9% (61/71; 95% CI: 75.6-93.0) and 77.5% (55/71; 95% CI: 66.0-86.5) but misdiagnosed MTs as benign in 28.6% (6/21) and 61.9% (13/21) of SGTs, respectively. After maximizing specificity to 100% for benign SGTs, the accuracies of IVIM and DWI decreased to 76.1% (54/71; 95% CI: 64.5-85.4) and 64.8% (46/71; 95% CI: 52.5-75.8) but no MTs were misdiagnosed as benign. IVIM and DWI correctly diagnosed 66.0% (33/50) and 50.0% (25/50) of benign SGTs and 46.5% (33/71) and 35.2% (25/71) of all SGTs, respectively. CONCLUSION: IVIM is more accurate than DWI for discriminating between benign and malignant SGTs because of its advantage in detecting WTs. Thresholds set by maximizing specificity for benign SGTs may be advantageous in a clinical setting.

Radiomics for Discriminating Benign and Malignant Salivary Gland Tumors; Which Radiomic Feature Categories and MRI Sequences Should Be Used?

The lack of a consistent MRI radiomic signature, partly due to the multitude of initial feature analyses, limits the widespread clinical application of radiomics for the discrimination of salivary gland tumors (SGTs). This study aimed to identify the optimal radiomics feature category and MRI sequence for characterizing SGTs, which could serve as a step towards obtaining a consensus on a radiomics signature. Preliminary radiomics models were built to discriminate malignant SGTs (n = 34) from benign SGTs (n = 57) on T1-weighted (T1WI), fat-suppressed (FS)-T2WI and contrast-enhanced (CE)-T1WI images using six feature categories. The discrimination performances of these preliminary models were evaluated using 5-fold-cross-validation with 100 repetitions and the area under the receiver operating characteristic curve (AUC). The differences between models' performances were identified using one-way ANOVA. Results show that the best feature categories were logarithm for T1WI and CE-T1WI and exponential for FS-T2WI, with AUCs of 0.828, 0.754 and 0.819, respectively. These AUCs were higher than the AUCs obtained using all feature categories combined, which were 0.750, 0.707 and 0.774, respectively (p < 0.001). The highest AUC (0.846) was obtained using a combination of T1WI + logarithm and FS-T2WI + exponential features, which reduced the initial features by 94.0% (from 1015 × 3 to 91 × 2). CE-T1WI did not improve performance. Using one feature category rather than all feature categories combined reduced the number of initial features without compromising radiomic performance.

The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer.

The incidence of thyroid cancer was predominant in women, indicating that the sex hormone may have a role in thyroid cancer development. Generally, the sex hormone exerts its function by binding to the correspondent nuclear receptors. Therefore, aberrant of these receptors may be involved in the development of thyroid cancer. Estrogen receptor alpha (ERα) and beta (ERß), two main estrogen receptors, have been reported to have an important role in the pathogenesis of thyroid cancer. When the ERα and ERß genes undergo the alternative RNA splicing, some ERα and ERß isoforms with incomplete functional domains may be formed. To date, several isoforms of ERα and ERß have been identified. However, their expression and roles in thyroid cancer are far from clear. In this review, we summarized the expressions and roles of ERα and ERß isoforms in thyroid cancer, aiming to provide the perspective of modulating the alternative RNA splicing of ERα and ERß against thyroid cancer.

Oro-pharyngo-esophageal radionuclide scintigraphy predicts aspiration pneumonia risk and associated survival in post-irradiated nasopharyngeal carcinoma patients.

OBJECTIVE: To demonstrate that oro-pharyngo-esophageal radionuclide scintigraphy (OPERS) not only detects tracheobronchial aspiration after swallowing, but also quantifies the amount of aspiration and subsequent clearance. METHODS: Data collected between 2014 and 2019 were reviewed for aspiration pneumonia at 12 and 24-months after OPERS. The predictive value for aspiration pneumonia on flexible endoscopic evaluation of swallowing (FEES), videofluoroscopic swallowing study (VFSS), and OPERS, and the overall survival of patients with or without aspiration were determined. RESULTS: Thirty-seven patients treated with radiotherapy for nasopharyngeal carcinoma (NPC) were reviewed. The incidence of aspiration detected on FEES, VFSS, and OPERS was 78.4%, 66.7%, and 44.4%, respectively. Using VFSS as a gold standard, the sensitivity and specificity of OPERS for aspiration was 73.7% and 100%. The positive and negative predictive values for aspiration were 100% and 66.7%, respectively, with an overall accuracy of 82.8%. A history of aspiration pneumonia was one factor associated with a higher chance of subsequent aspiration pneumonia within 12 months (odds ratio: 15.5, 95% CI 1.67-145.8, p < .05) and 24 months (odds ratio: 23.8, 95% CI 3.69-152.89, p < .01) of the swallowing assessment. Aspiration detected by OPERS was a significant risk factor for future aspiration pneumonia at 12 and 24 months respectively. Significantly, better survival was associated with an absence of aspiration on OPERS only, but not on FEES or VFSS. CONCLUSION: OPERS predicts the safety of swallowing, the incidence of subsequent aspiration pneumonia, and the survival prognosis in post-irradiated NPC dysphagia patients. LEVEL OF EVIDENCE: 3.

Differential Effects of Estrogen Receptor Alpha and Beta on Endogenous Ligands of Peroxisome Proliferator-Activated Receptor Gamma in Papillary Thyroid Cancer.

Purpose: The inhibition of estrogen receptor alpha (ERα) or the activation of ERß can inhibit papillary thyroid cancer (PTC), but the precise mechanism is not known. We aimed to explore the role of ERα and ERß on the production of endogenous peroxisome proliferator-activated receptor gamma (PPARγ) ligands in PTC. Methods: 2 PTC cell lines, 32 pairs of PTC tissues and matched normal thyroid tissues were used in this study. The levels of endogenous PPARγ ligands 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), and15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) were measured by ELISA. Results: The levels of PGJ2 and 15(S)-HETE were significantly reduced in PTC, but 13(S)-HODE was not changed. Activation of ERα or inhibition of ERß significantly downregulated the production of PGJ2, 15(S)-HETE and 13(S)-HODE, whereas inhibition of ERα or activation of ERß markedly upregulated the production of these three ligands. Application of endogenous PPARγ ligands inhibited growth, induced apoptosis of cancer cells, and promoted the efficacy of chemotherapy. Conclusion: The levels of endogenous PPARγ ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. The inhibition of ERα or activation of ERß can inhibit PTC by stimulating the production of endogenous PPARγ ligands to induce apoptosis in cancer cells.

The Knockdown of Nrf2 Suppressed Tumor Growth and Increased the Sensitivity to Lenvatinib in Anaplastic Thyroid Cancer.

Papillary thyroid cancer can dedifferentiate into a much more aggressive form of thyroid cancer, namely into anaplastic thyroid cancer. Nrf2 is commonly activated in papillary thyroid cancer, whereas its role in anaplastic thyroid cancer has not been fully explored. In this study, we used two cell lines and an animal model to examine the function of Nrf2 in anaplastic thyroid cancer. The role of Nrf2 in anaplastic thyroid cancer was investigated by a series of functional studies in two anaplastic thyroid cancer cell lines, FRO and KAT-18, and further confirmed with an in vivo study. The impact of Nrf2 on the sensitivity of anaplastic thyroid cancer cells to lenvatinib was also investigated to evaluate its potential clinical implication. We found that the expression of Nrf2 was significantly higher in anaplastic thyroid cancer cell line cells than in papillary thyroid cancer cells or normal control cells. Knockdown of Nrf2 in anaplastic thyroid cancer cells inhibited their viability and clonogenicity, reduced their migration and invasion ability in vitro, and suppressed their tumorigenicity in vivo. Mechanistically, knockdown of Nrf2 decreased the expression of Notch1. Lastly, knockdown of Nrf2 increased the sensitivity of anaplastic thyroid cancer cells to lenvatinib. As knockdown of Nrf2 reduced the metastatic and invasive ability of anaplastic thyroid cancer cells by inhibiting the Notch 1 signaling pathway and increased the cancer cell sensitivity to lenvatinib, Nrf2 could be a promising therapeutic target for patients with anaplastic thyroid cancer.

Assessment of pharyngeal motor function using a novel velopharyngeal squeeze maneuver and a novel endoscopic pharyngeal contraction grade scale in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: To investigate a novel velopharyngeal squeeze maneuver (VPSM) and novel endoscopic pharyngeal contraction grade (EPCG) scale for the evaluation of pharyngeal motor function. METHODS: During endoscopic examination of 77 post-irradiated nasopharyngeal carcinoma patients and control subjects, VPSM was rated and lateral pharyngeal wall movement graded with EPCG scale during swallowing. Pharyngeal constriction ratio (PCR) measured by videofluoroscopy was used for correlation. RESULTS: VPSM and EPCG scale showed almost perfect intra-rater and inter-rater reliability (Kappa: >0.90). VPSM was present in 61% of patients suggesting good pharyngeal motor function. VPSM was predictive of EPCG scale (Wald statistic = 29.99, p < 0.001). EPCG scale also correlated strongly with PCR (r: 0.812) and was predictive for aspiration (odds ratio: 22.14 [95% CI 5.01-97.89, p < 0.001]). CONCLUSIONS: VPSM and EPCG scale are two novel tools to assess pharyngeal motor function, and both correlate well with pharyngeal contractility and aspiration.

Perceptual Voice and Speech Analysis after Supraglottic Laryngeal Closure for Chronic Aspiration in Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: To evaluate the voice and speech outcomes after tubed supraglottic laryngeal closure (TSLC) surgery to treat chronic aspiration after radiotherapy for head and neck cancer. STUDY DESIGN: A retrospective case-control study. METHODS: The data of patients who underwent radiotherapy for head and neck cancer and who later required total laryngectomy or TSLC for chronic aspiration between 2004 and 2017 were retrieved from a dysphagia clinic. Preoperative and postoperative voice and speech were assessed by the GRBAS and INFVo rating scales. Control subjects who underwent radiotherapy alone or total laryngectomy with a tracheoesophageal prosthesis for other indications were recruited for comparison. RESULTS: Of 15 patients who underwent a TSLC with a mean age of 57.3 years (45-75 years), 13 were male and 2 female. All patients had a history of nasopharyngeal carcinoma. The success rate of speech production using their own larynx following an intact TSLC was 64%. There was no statistically significant difference in voice and speech ratings between preoperative and TSLC subjects on the GRBAS (P = .32) and INFVo scales (P = .57), although the quality of voice appeared to deteriorate after TSLC. However, the INFVo scale for impression, intelligibility and unsteadiness of the voice after TSLC was statistically significantly better than for laryngectomy with tracheoesophageal speech. CONCLUSIONS: A tubed supraglottic laryngeal closure controls chronic aspiration while preserving the larynx for phonation, and results in a better voice and speech quality than a laryngectomy with a voice prosthesis. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1616-E1623, 2021.

Tubed Supraglottic Laryngeal Closure to Treat Chronic Aspiration After Radiotherapy for Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: To evaluate the long-term swallowing outcomes after surgical treatment for chronic aspiration in patients treated with radiotherapy for head and neck cancer. STUDY DESIGN: This was a retrospective study. METHODS: The data of patients who underwent radiotherapy for head and neck cancer and who subsequently required a laryngectomy or a tubed supraglottic laryngeal closure (TSLC) for recurrent aspiration pneumonia between 2004 and 2017 were retrieved from a tertiary referral hospital dysphagia clinic. The Functional Oral Intake Scale (FOIS) and the Swallowing Performance and Status Scale (SPSS) were used to assess swallowing function. RESULTS: Of the 17 patients who required surgery for chronic aspiration secondary to radiotherapy for head and neck cancer, two underwent a laryngectomy and 15 a TSLC. During a mean follow-up of 77 months, the FOIS and SPSS scores significantly improved at 12, 24, and 36 months after laryngectomy and TSLC relative to the baseline (P < .05). Both patients who underwent laryngectomy and 11 of the 15 (73.3%) who underwent a TSLC resumed oral feeding. Both laryngectomy patients had episodes of recurrent aspiration pneumonia after surgery due to leakage through the tracheoesophageal puncture or prosthesis, whereas none of the TSLC patients had these episodes. CONCLUSION: A tubed supraglottic laryngeal closure, which is a reversible procedure that preserves the larynx and allows for natural phonation, should be considered an alternative to laryngectomy for the control of chronic aspiration. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1234-E1243, 2021.

A useful landmark to locate the external branch of the superior laryngeal nerve during thyroidectomy.

BACKGROUND: To determine whether the insertion of the sternothyroid muscle onto the oblique line of the thyroid cartilage can be used to reliably locate the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy. METHODS: This is a prospective descriptive case series. The EBSLN was identified and confirmed with a nerve stimulator during thyroid surgery. The entry point of the EBSLN into the inferior constrictor/cricothyroid muscle was measured in relation to the insertion and anterior border of the sternothyroid muscle. The perpendicular distance from the insertion of the sternothyroid muscle onto the oblique line was designated the vertical distance (VD) of the nerve entry point (NEP), and the perpendicular distance from the anterior border of the sternothyroid muscle was designated the horizontal distance. RESULTS: Ninety patients underwent 130 thyroid lobectomies (60 female, 30 male) (mean age 53.5 years, range, 18-91 years). An attempt to identify the nerve was made in 127 thyroid lobectomies. The EBSLN was identified in 111 cases (87.4%). The mean VD of the NEP from the muscle insertion was 1.1 mm (SD 1.1 mm, range, 0-5 mm) and the mean horizontal distance (HD) was 9.5 mm (SD 3.8 mm, range, 2-21 mm). CONCLUSIONS: The EBSLN muscle entry point usually lies 1.1 mm from the sternothyroid insertion onto the oblique line, and 5-12 mm from the anterior border of the muscle. These useful landmarks allow the nerve to be consistently located, identified and preserved during thyroid surgery prior to ligating the superior thyroid vessels.

The role of microRNA in cisplatin resistance or sensitivity.

INTRODUCTION: Cisplatin is a chemotherapy drug that has been used to treat a number of cancers for decades, and is still one of the most commonly used anti-cancer agents. However, some patients do not respond to cisplatin while other patients who were originally sensitive to cisplatin eventually develop chemoresistance, leading to treatment failure or/and tumor recurrence. AREAS COVERED: Different mechanisms contribute to cisplatin resistance or sensitivity, involving multiple pathways or/and processes such as DNA repair, DNA damage response, drug transport, and apoptosis. Among the various mechanisms, it appears that microRNAs play an important role in determining the resistance or sensitivity. In this article, we analyzed and summarized recent findings in this area, with the aim that these data can aid further research and understanding, leading to the eventual reduction of cisplatin resistance. EXPERT COMMENTARY: microRNAs can positively or negatively regulate cisplatin resistance by acting on molecules or/and pathways related to apoptosis, autophagy, hypoxia, cancer stem cells, NF-κB, and Notch1. It appears that the modulation of relevant microRNAs can effectively re-sensitize cancer cells to cisplatin regimen in certain types of cancers including breast, colorectal, gastric, liver, lung, ovarian, prostate, testicular, and thyroid cancers.

Persistence and clearance of oral human papillomavirus infections: A prospective population-based cohort study.

OBJECTIVE: This study aimed to evaluate the incidence of and factors associated with persistence and clearance of oral human papillomavirus (HPV) infections. METHOD: A prospective cohort study invited 458 subjects (231 HPV-positive and 227 HPV-negative at baseline) to attend follow-ups at 12 months. Those 231 HPV-positive subjects and 10 new infections were invited to reassessment at 24 months. We used next-gen sequencing for detection and genotyping of HPV. RESULTS: α-HPV infections showed higher persistence rates than ß/γ-HPV (22.7% vs 9.2% at 12 months [P < .05], 10.6% vs 6.8% at 24 months [P = .30]). Clearance rates of α-HPV were lower than ß/γ-HPV at 12 months (31.8% vs 45.1%; P = .05) and higher at 24 months (7.6% vs 4.8%; P = .36). Persistence of ß/γ-HPV was positively associated with males (crude odds ratio [COR] = 3.8, 95% confidence interval [CI] = 1.3-11.2), elderly (51-65 vs 16-50 years; COR = 5.1, 95% CI = 1.2-22.3), and smoking (COR = 4.3, 95% CI = 1.9-9.6). Drinking (COR = 0.5, 95% CI = 0.3-0.9), handwashing less than 90% of times before meals (COR = 0.6, 95% CI = 0.3-0.9), and using public bath more than once per month (COR = 0.5, 95% CI = 0.2-0.9) were risk factors hindering ß/γ-HPV clearance. CONCLUSIONS: This study identified factors associated with persistence and clearance of oral HPV infections among Chinese. Studies on other ethnogeographic groups may further inform prevention strategies of oral HPV infection and immunization programmes.

Neck lymph node status on survival of regionally recurrent or persistent nasopharyngeal carcinoma.

The aim of this study was to evaluate the impact of lymph node status from neck dissection pathological specimens on the survival for isolated regional nodal recurrence or persistence after primary treatment of nasopharyngeal carcinoma. Through a retrospective cohort study performed in an academic tertiary referral hospital in Hong Kong. Forty-six patients who underwent a salvage neck dissection between June 2001 and January 2013 for isolated regionally recurrent or persistent nasopharyngeal carcinoma was performed. Informed consent was waived for this retrospective study by The Joint CUHK-NTEC CREC. In the study forty-six patients had a salvage neck dissection for nodal failure with a mean age of 53 and 74% (34) were male. With a mean follow-up of 45.3 months, Overall survival, disease specific survival, loco-regional recurrence free survival, and regional recurrence free survival were 56.5%, 73.9%, 87.0%, and 91.3% respectively. For both univariate and multivariate analysis, patients with a number of positive lymph nodes more than 5 and a lymph node density more than 20% were significantly associated with poorer overall survival. Extracapsular spread and pathological cervical lymph node staging did not have an association with poorer survival. In conclusion, an absolute number of positive lymph nodes more than five and a lymph node density more than 20% were potentially useful prognostic factors affecting survival following a neck dissection for regional residual or recurrent nasopharyngeal carcinoma.