Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.

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.

How OSA Evolves From Childhood to Young Adulthood: Natural History From a 10-Year Follow-up Study.

BACKGROUND: Understanding the natural history of childhood OSA can help to determine disease prognosis and to guide risk stratification and management strategies. METHODS: To evaluate the natural history of childhood OSA and factors associated with spontaneous remission and persistent and incident OSA from childhood to late adolescence/early adulthood, a longitudinal analysis of a prospective community-based cohort was designed. Subjects from a cohort established for an OSA prevalence study were invited to participate in this 10-year follow-up study. RESULTS: Two hundred and forty-three participants (59% male) took part, and their mean age was 9.8 (SD, ± 1.8) and 20.2 (SD, ± 1.9) years at baseline and follow-up, respectively. The mean follow-up duration was 10.4 (SD, ± 1.1) years. Associations between baseline and follow-up log-transformed obstructive apnea-hypopnea index (OAHI) differed by age; a significant positive association was observed only among participants aged 10 years or older at baseline. Overall polysomnographic remission rate (with OAHI < 1 event/h at follow-up) of childhood OSA was 30%, and 69% had an OAHI < 5 events/h at follow-up. Complete remission of OSA was associated with female sex. Incidence of adolescent/adult OSA with an OAHI ≥ 5 events/h at follow-up was 22%. Male sex and higher baseline BMI z score were associated with incident OSA. CONCLUSIONS: A proportion of children with OSA, particularly female children, had complete resolution during transition to late adolescence or early adulthood. Childhood and adolescent OSA are distinct entities, with the latter more likely to persist into adulthood. Obesity and male sex are consistent key risk factors for incident OSA.

Narrow Band Imaging Endoscopy of the Nasopharynx for Malignancy: An Inter- and Intraobserver Study.

OBJECTIVE: To assess interobserver agreement and intraobserver reproducibility when assessing the nasopharynx for malignancy under white light and narrow band imaging endoscopy because the decision to biopsy hinges on the examiner's perceived chance of malignancy. METHODS: An interobserver and intraobserver agreement study utilizing white light and narrow band endoscopic images of the nasopharynx. The setting was an academic referral hospital. Participants were 156 adults with suspected nasopharyngeal carcinoma who underwent white light and narrow band imaging endoscopy and biopsy. Images of the nasopharynges were subsequently scored for malignancy by four otolaryngologists. The nasopharynx was scored on 4-point scales under white light and narrow band imaging endoscopy for the likelihood of malignancy or abnormality, respectively. RESULTS: Intraclass correlation coefficients for intraobserver agreement for nasopharyngeal malignancy for four observers under white light were 0.86, 0.89, 0.79 and 0.88 (mean 0.855), respectively; and under narrow band imaging they were 0.64, 0.68, 0.64, and 0.66 (mean 0.655), respectively (all P values < 0.001). The coefficient for interobserver reliability under white light was 0.79 (95% confidence interval [CI] 0.76-0.82; P < 0.001), which indicated strong agreement. The coefficient for interobserver reliability under narrow band imaging was 0.56 (95% CI 0.50-0.61; P < 0.001), which indicated moderate agreement. CONCLUSIONS: Intraobserver and interobserver agreement for nasopharyngeal malignancy was strong on white light endoscopy but only moderate on narrow band imaging endoscopy. Agreement may be improved by adopting a standard set of assessment guidelines, including an objective detailed morphological analysis under white light and vasculature analysis under narrow band imaging. LEVEL OF EVIDENCE: 2a Laryngoscope, 129:1374-1379, 2019.

MicroRNA-125b Interacts with Foxp3 to Induce Autophagy in Thyroid Cancer.

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.

If cytology of Warthin tumor is accurate, can management be conservative?

We conducted a retrospective study to assess the accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of Warthin tumor and to evaluate the subsequent risk of conservative nonsurgical management. We reviewed the records of 75 patients (76 tumors) with a parotid mass that had been diagnosed as a Warthin tumor by FNAC. This patient population was made up of 64 men and 11 women, aged 46 to 93 years (mean: 67). Of the 76 tumors, 40 were treated with surgical excision and 36 with conservative measures. Histology of the 40 excised parotid masses revealed that 38 (95%) were indeed Warthin tumors, 1 (2.5%) was a low-grade adenocarcinoma, and 1 was benign-not otherwise specified. None of the 36 tumors underwent malignant transformation either clinically or on repeat FNAC (if performed) during a follow-up of 4 to 120 months (mean: 55.5 ± 32.2). We conclude that conservative management of Warthin tumors confidently diagnosed on FNAC may be an option for patients who are unwilling or unable to undergo surgical excision.

Expression of Antioxidant Molecules and Heat Shock Protein 27 in Thyroid Tumors.

Oxidative stress-induced DNA damage is a known causing factor for many types of tumors, but information on the role of oxidants and antioxidants in thyroid tumors is limited. The aim of this study was to determine antioxidant levels in thyroid tumors. In this study, tumor and its matched non-tumor thyroid tissue samples were obtained from 53 patients with thyroid tumors. The levels of manganese superoxide dismutase (MnSOD), thioredoxin reductase 2 (TXNRD2), glutathione (GSH), glutathione peroxidase (Gpx), catalase (CAT), and 27 kd heat-shock protein (hsp27) were determined in both thyroid tissue samples and cultured thyroid cells by immunohistochemical staining and western blot. Hydrogen peroxide (H2 O2 ) was used to generate oxidant stress in the cell culture experiments. We found that the levels of MnSOD, TXNRD2, GSH, Gpx, and Hsp27 were increased in both malignant and benign tumors, while the level of CAT was decreased. To verify the results of the tissue study, we treated cultured thyroid cells with H2 O2 and found the same pattern of antioxidant changes. Hsp27 was also increased after H2 O2 treatment. The expression of hsp27 was upregulated by 8.24-, 6.96-, and 3.09-fold in thyroid cancer, follicular adenoma, multinodular goiter, respectively. Collectively, our study demonstrated that the levels of hsp27 together with MnSOD, TXNRD2, GSH, and Gpx were significantly upregulated by H2 O2 in thyroid tumors. The increase of these antioxidants is observed in both malignant and benign tumors, particularly in the former. The upregulation of antioxidants is likely a protective mechanism of tumor cells to maintain their survival and growth. J. Cell. Biochem. 117: 2473-2481, 2016. © 2016 Wiley Periodicals, Inc.

Non-nasopharyngeal head and neck lymphoepithelioma-like carcinoma in the United States: A population-based study.

BACKGROUND: Non-nasopharyngeal head and neck lymphoepithelioma-like carcinoma (LELC) is a rate entity. The purpose of this study was to analyze its demographic, clinicopathologic, and survival characteristics. METHODS: A cohort from the Surveillance, Epidemiology, and End Results (SEER) database of cases with non-nasopharyngeal head and neck LELC between 1973 and 2011. RESULTS: There were 378 cases with 5-year overall survival (OS) of 70.5% and disease-specific survival (DSS) of 77.7%. The majority of cases were <60-year-old white men. Salivary gland LELC had the highest OS (80.8%) and DSS (85.7%) at 5 years. Multivariate analysis showed that older age, no surgery, and no radiation were independently significantly associated with worse survival (p < .05). CONCLUSION: Non-nasopharyngeal head and neck LELC is uncommon in the United States with salivary gland LELC having the highest OS and DSS compared with other head and neck sites. The optimal treatment with surgery and/or radiotherapy needs to be further investigated. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1294-E1300, 2016.

Estrogen receptor α induces prosurvival autophagy in papillary thyroid cancer via stimulating reactive oxygen species and extracellular signal regulated kinases.

CONTEXT: The incidence of papillary thyroid cancer (PTC) shows a predominance in females, with a male:female ratio of 1:3, and none of the known risk factors are associated with gender difference. Increasing evidence indicates a role of estrogen in thyroid tumorigenesis, but the mechanism involved remains largely unknown. OBJECTIVE: This study aimed to assess the contribution of autophagy to estrogen receptor α (ERα)-mediated growth of PTC. DESIGN: The expression of ERα in thyroid tissue of patients with PTC tissues was analyzed. Cell viability, proliferation, and apoptosis were evaluated after chemical and genetic inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERα was assessed. RESULTS: ERα expression was increased in PTC tissues compared with the adjacent nontumor tissues. Estrogen induced autophagy in an ERα-dependent manner. Autophagy induced by estrogen/ERα is associated with generation of reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC cells. Chemical and genetic inhibition of autophagy dramatically decreased tumor cell survival and promoted apoptosis, confirming the positive role of autophagy in the growth of PTC. CONCLUSIONS: ERα contributes to the growth of PTC by enhancing an important prosurvival catabolic process, autophagy, in PTC cells. The inhibition of autophagy promotes apoptosis, implicating a novel strategy for the treatment of ERα-positive PTC.

Inhibition of Foxp3 in cancer cells induces apoptosis of thyroid cancer cells.

Foxp3+ regulatory T cells (Tregs) in lymphocytes facilitate the thyroid tumor growth and invasion. Very limited information is available on Foxp3 expression in thyroid cancer cells and its function is totally unknown. This study demonstrated that Foxp3 expression was increased in thyroid cancer cells. Inhibition of Foxp3 decreased cell proliferation and migration, but increased apoptosis, suggesting a positive role of Foxp3 in cancer growth. Interestingly, Foxp3 inhibition enhanced PPARγ expression and activity. In addition, Foxp3 inhibition downregulated NF-κB subunit p65 and cyclin D1 but upregulated caspase-3 levels. These molecular changes are in line with Foxp3 shRNA-mediated alteration of cell functions. Collectively, our study demonstrates that thyroid cancer cells express a high level of functional Foxp3 and that the inhibition of the Foxp3 suppresses the proliferation and migration but promotes apoptosis, suggesting that targeting Foxp3 in thyroid cancer cells may offer a novel therapeutic option for thyroid cancer.

The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer.

BACKGROUND: Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied. METHODS: The impact of ER over-expression or down-expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERß agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated by Western blot analysis. RESULTS: PPARγ protein and activity were reduced by the over-expression of either ERα or ERß, whereas repression of ERα or ERß increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERß activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERß and PPARγ enhanced the expression of proapoptotic molecules, such as caspase-3 and apoptosis-inducing factor. CONCLUSIONS: This study provides evidence supporting a cross-talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERß significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer.

One-stop evaluation of globus pharyngeus symptoms with transnasal esophagoscopy and swallowing function test.

OBJECTIVE: To evaluate the feasibility of a one-stop assessment of patients complaining of globus sensation with transnasal esophagoscopy (TNE) and functional endoscopic evaluation of swallowing (FEES). DESIGN: Prospective, nonrandomized, experimental investigation. SETTING: Tertiary referral centre. METHODS: Sixty-three consecutive patients complaining of a lump in the throat were evaluated by this combined approach. MAIN OUTCOME MEASURES: The safety and feasibility of performing a one-stop TNE plus FEES were explored by subjective measurement of the patients' tolerance and satisfaction and comments from surgeons. The possible therapeutic effects were also assessed 2 months after the procedure. RESULTS: All 63 patients completed the TNE and FEES without any complications. The average duration of the examination was 6.27 ± 2.52 (95% CI 5.63-6.91) minutes. The findings included arytenoid cyst, epiglottic cyst, vocal cord nodules, vocal cord palsy, esophageal reflux, and foveolar gland hyperplasia. Two patients (3.2%) demonstrated some degree of fluid penetration or aspiration. Nine specialists all scored highly on a visual analogue scale on the manipulation, visualization, and satisfaction of the TNE procedure (median  =  8 of 10). Patients also rated a low pain score (median  =  1 of 10) and a high satisfaction score (median  =  9 of 10). CONCLUSION: The combined technique of TNE and FEES can be used safely as a one-stop examination tool for patients with globus pharyngeus symptoms.

Combined ultrasound/endoscopy-assisted vocal fold injection for unilateral vocal cord paralysis: a case series.

OBJECTIVE: Transcutaneous vocal cord injection is a popular treatment choice for patients suffering from unilateral vocal cord paralysis. Transcutaneous transcartilaginous (through the thyroid cartilage) approach abolishes any anatomical constraint to reach the vocal cord. However it is a largely blind procedure as the needle should stay submucosal. Herein we report our experience in employing ultrasound guidance to circumvent this problem. METHODS: Retrospective review of a series of 8 patients who underwent combined ultrasound/endoscopy-assisted vocal cord injection for unilateral vocal cord paralysis. RESULTS: Vocal cord injections were successfully completed in all but one patient. There were no associate complications. CONCLUSION: The use of ultrasound in aiding transcutaneous transcartilaginous vocal cord injection is safe and feasible. KEY POINTS: • Vocal cord injection is effective in treating unilateral vocal cord paralysis • A number of transcutaneous approaches with the patient awake have been described • Transcutaneous transcartilaginous approach theoretically has minimal anatomical restraint to reach the vocal cord • Disadvantage of that approach is the difficulty to accurately position the needle • Our experience of using ultrasound to circumvent this problem is positive.

Second branchial fistula with unusual presentation--a case report.

Complete second branchial fistula is a rare clinical entity. The classical presentation of second branchial fistula is recurrent discharge from the external opening with or without recurrent painful neck swelling. We report an unusual case whose presenting symptom was a long-standing history of throat discomfort with recurrent blood stained saliva. Her symptoms resolved after her branchial fistula was excised.

Reproducibility of clinical grading of tonsillar size.

OBJECTIVE: To determine the reproducibility of the Brodsky grading scale and the modified 3-grade and 5-grade scales in reporting the size of the tonsils. DESIGN: Retrospective review of 60 video recordings of tonsil examination by 12 independent observers with different clinical backgrounds and various levels of training. The sizes of the tonsils were graded using different grading scales. SETTING: Tertiary care university hospital. PARTICIPANTS: The video recordings were chosen from an ongoing epidemiologic study of sleep-related breathing disorder in children in Hong Kong. Main Outcomes Measures The intraobserver and interobserver reproducibility of each grading scale was determined using intraclass correlation. An intraclass correlation coefficient (ICC) exceeding 0.75 was set a priori to indicate an acceptable level of reliability. RESULTS: The mean intraobserver ICCs for the Brodsky grading scale and the modified 3-grade and 5-grade scales were 0.858, 0.830, and 0.865, respectively. The mean interobserver ICCs for the Brodsky grading scale and the modified 3-grade and 5-grade scales were 0.763, 0.739, and 0.783, respectively. CONCLUSION: The Brodsky grading scale and the modified 5-grade scale achieved acceptable intraobserver and interobserver reproducibility.

Autograft ossiculoplasty in cholesteatoma surgery: is it feasible?

OBJECTIVE: To investigate whether autologous ossicles can be safely used in ossicular reconstruction in cholesteatoma surgery after attempting cholesteatoma removal under the operating microscope. STUDY DESIGN: A prospective fine-section histological study of formalin-stored ossicles, harvested from cholesteatomatous ears, to evaluate for existence of residual cholesteatoma after surface disease clearance under the operating microscope. METHODS: One hundred four ossicles were harvested from 76 patients with cholesteatoma for the study. These malleus heads and includes were categorized into three groups: group 1, ossicles with retained shape and useful bulk, treated by microscopic stripping alone; group 2, ossicles with retained shape and useful bulk, treated by microscopic stripping and drilling; and group 3, badly eroded ossicles, treated by microscopic stripping alone. These treated ossicles were then subjected to 4 microm histopathological study. RESULTS: Residual disease was identified in 6 of the 104 ossicles. Residual disease was found only in badly eroded ossicles that are not suitable for reconstruction. All the usable ossicles were free of disease. CONCLUSIONS: Autologous ossicles that have retained body and bulk are safe to use for reconstruction after surface stripping under the operating microscope. Additional burring probably adds a further margin of safety.