Analysis of HLA-G 14 bp Insertion/Deletion Polymorphism and HLA-G, ILT2 and ILT4 Expression in Head and Neck Squamous Cell Carcinoma Patients.

HLA-G is the checkpoint molecule involved in the suppression of the immune response. Increased expression of HLA-G and its ILTs receptors have been correlated with tumor progression in various cancer types. In head and neck squamous cell carcinoma (HNSCC) tumors, the effect of HLA-G, ILT2 and ILT4 expression on cancer development has to be explained. The 34 HNSCC patients and 98 controls were genotyped for the HLA-G 14 bp ins/del polymorphism. In HNSCC lesions, HLA-G, ILT2 and ILT4 mRNA expression was analysed using real-time PCR. The association between HLA-G, ILT2 and ILT4 mRNA expression and clinical variables (age at onset, TNM staging system and p16 positivity) was also evaluated. No genetic association between the HLA-G 14 bp ins/del and HNSCC risk was detected (p > 0.05). However, in the non-metastatic HNSCC group, a significantly higher HLA-G mRNA expression was noted in tumors in the T4 stage compared to those in the T1 and T2 stages (p = 0.0289). ILT2 mRNA expression was significantly increased in non-metastatic vs. metastatic tumors (p = 0.0269). Furthermore, a significantly higher ILT4 mRNA expression was noted in tumors in the T1+T2 stage compared to those in the T3 stage (p = 0.0495). Our results suggest that the HLA-G molecule creates an immunological microenvironment involved in HNSCC development.

Consensus for voice quality assessment in clinical practice: guidelines of the European Laryngological Society and Union of the European Phoniatricians.

INTRODUCTION: To update the European guidelines for the assessment of voice quality (VQ) in clinical practice. METHODS: Nineteen laryngologists-phoniatricians of the European Laryngological Society (ELS) and the Union of the European Phoniatricians (UEP) participated to a modified Delphi process to propose statements about subjective and objective VQ assessments. Two anonymized voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 3/4. The statements with ≥ 3/4 score by 60-80% of experts were improved and resubmitted to voting until they were validated or rejected. RESULTS: Of the 90 initial statements, 51 were validated after two voting rounds. A multidimensional set of minimal VQ evaluations was proposed and included: baseline VQ anamnesis (e.g., allergy, medical and surgical history, medication, addiction, singing practice, job, and posture), videolaryngostroboscopy (mucosal wave symmetry, amplitude, morphology, and movements), patient-reported VQ assessment (30- or 10-voice handicap index), perception (Grade, Roughness, Breathiness, Asthenia, and Strain), aerodynamics (maximum phonation time), acoustics (Mean F0, Jitter, Shimmer, and noise-to-harmonic ratio), and clinical instruments associated with voice comorbidities (reflux symptom score, reflux sign assessment, eating-assessment tool-10, and dysphagia handicap index). For perception, aerodynamics and acoustics, experts provided guidelines for the methods of measurement. Some additional VQ evaluations are proposed for voice professionals or patients with some laryngeal diseases. CONCLUSION: The ELS-UEP consensus for VQ assessment provides clinical statements for the baseline and pre- to post-treatment evaluations of VQ and to improve collaborative research by adopting common and validated VQ evaluation approach.

Slovak Translation and Cross-Cultural Validation of the Eating Assessment Tool (EAT10®).

Introduction: The objective of the study was the language adaptation and verification of psychometric properties of the Slovak version of the EAT10® questionnaire. Methods: The original English version of the questionnaire was translated into the Slovak language. The research group included 136 control participants and 51 dysphagic patients. Test−retest reliability, item analysis, internal consistency, construct and clinical validity, and Receiver Operating Characteristic (ROC) analysis were performed to verify the psychometric properties of the Slovak EAT10®. Results: The internal consistency assessed with Cronbach's alpha is excellent (α = 0.94). Statistical analysis of the Slovak version of EAT10® showed excellent reliability (0.91, p < 0.001) in the test−retest. Through item-to-total correlation, we found out that all items significantly correlated with the overall score in EAT10®. Factor analysis proved a high construct validity. The EAT10® questionnaire was able to reveal a latent variable: a swallowing disorder, which was affecting a group of patients. The clinical validity results confirmed statistically significant differences in the mean scores of the control and dysphagic groups (z = −10.30; p < 0.001). By dividing the dysphagic group into four subgroups (Head and Neck Cancer, Extraesophageal Reflux, Iatrogenic, and Neurological) there were nonsignificant differences in the mean scores of the subgroups. The cut-off value for the Slovak EAT10® is three points. Conclusion: The Slovak EAT10® is a valid and reliable tool designed for the subjective assessment of oropharyngeal dysphagia in patients.

Association Between Inferior Turbinate Hypertrophy and Extraesophageal Reflux.

Importance: To the authors' knowledge, no prior studies have examined the association between inferior turbinate hypertrophy (ITH) and extraesophageal reflux (EER). If EER were a cause or cofactor of ITH, antireflux treatment can be considered prior to surgical intervention. Objective: To evaluate EER presence and severity in patients with different degrees of ITH. Design, Setting, and Participants: Prospective multicentric cohort study conducted at 3 referral centers treating patients with EER and certified for 24-hour monitoring of oropharyngeal pH. The monitoring was performed between October 2020 and October 2021. A total of 94 adult patients with EER symptoms were recruited, 90 of whom were analyzed. Interventions: Nasal endoscopy was performed to determine the degree of ITH, according to the Camacho classification. Presence and severity of EER were examined using 24-hour monitoring of oropharyngeal pH. Main Outcomes and Measures: Primary outcomes were presence of EER according to RYAN Score, total percentage of time below pH 5.5, and total numbers of EER events below pH 5.5. Results: Of the 90 analyzed patients (median [IQR] age, 46 [33-58] years; 36 [40%] male patients), 41 had a maximum of second-degree ITH (group 1), and 49 patients had at least third-degree ITH (group 2), according to the Camacho classification. On the basis of the RYAN Score, EER was diagnosed more often in group 2 (69.4%) than in group 1 (34.1%; difference, 35.3% [95% CI, 13.5%-56.9%]). Moreover, compared with group 1, group 2 exhibited higher median total percentage of time below pH 5.5 (median [IQR], group 1: 2.1% [0.0%-9.4%], group 2: 11.2% [1.5%-15.8%]; difference, 9.1% [95% CI, 4.1%-11.8%]) and higher median total number of EER events (median [IQR], group 1: 6 [1-14] events, group 2: 14 [4-26] events; difference, 8 [95% CI, 2-15] events). Patients with proven EER demonstrated no difference in the degree of ITH between the right and left nasal cavity (Cohen g, -0.17 [95% CI, -0.50 to 0.30]), or between the anterior and posterior parts of the nasal cavity (Cohen g, -0.21 [95% CI, -0.50 to 0.17]). Conclusions and Relevance: In this cohort study, patients with a higher degree of ITH had more severe EER. A possible association between severe ITH and EER was demonstrated.

Appropriateness for SARS-CoV-2 vaccination for otolaryngologist and head and neck surgeons in case of pregnancy, breastfeeding, or childbearing potential: Yo-IFOS and CEORL-HNS joint clinical consensus statement.

PURPOSE: SARS-CoV-2 vaccines are a key step in fighting the pandemic. Nevertheless, their rapid development did not allow for testing among specific population subgroups such as pregnant and breastfeeding women, or elaborating specific guidelines for healthcare personnel working in high infection risk specialties, such as otolaryngology (ORL). This clinical consensus statement (CCS) aims to offer guidance for SARS-CoV-2 vaccination to this high-risk population based on the best evidence available. METHODS: A multidisciplinary international panel of 33 specialists judged statements through a two-round modified Delphi method survey. Statements were designed to encompass the following topics: risk of SARS-Cov-2 infection and use of protective equipment in ORL; SARS-Cov-2 infection and vaccines and respective risks for the mother/child dyad; and counseling for SARS-CoV-2 vaccination in pregnant, breastfeeding, or fertile healthcare workers (PBFHW). All ORL PBFHW were considered as the target audience. RESULTS: Of the 13 statements, 7 reached consensus or strong consensus, 2 reached no consensus, and 2 reached near-consensus. According to the statements with strong consensus otorhinolaryngologists-head and neck surgeons who are pregnant, breastfeeding, or with childbearing potential should have the opportunity to receive SARS-Cov-2 vaccination. Moreover, personal protective equipment (PPE) should still be used even after the vaccination. CONCLUSION: Until prospective evaluations on these topics are available, ORL-HNS must be considered a high infection risk specialty. While the use of PPE remains pivotal, ORL PBFHW should be allowed access to SARS-CoV-2 vaccination provided they receive up-to-date information.

Pathogenesis of Retraction Pocket of the Tympanic Membrane-A Narrative Review.

Several theories describe the development of the retraction pocket of the tympanic membrane (RP). Many authors suggest that the negative middle ear pressure is the main reason responsible for developing this condition. A narrative review has been undertaken, and conclusions are drawn reflecting a current knowledge with our new observations in the histological and immunohistochemical study. Recent studies show the important role of inflammation in the development and progression of RP. A review of the available literature shows that the inflammation plays a key role in pathogenesis of the RP and its progression to the cholesteatoma. We support this statement with our new results from histological and immunohistochemical analysis of the RPs.

Functional Results after Larynx-Preserving Treatment of Laryngeal Cancer. Suggestions for follow-up.

ntroduction: Laryngeal cancer and its treatment are associated with both short- and long-term side effects, affecting laryngeal functions and having an impact on the quality of life. Material and methods: Retrospective analysis of the medical records of patients receiving surgical or non-surgical, larynx- -preserving treatment for laryngeal cancer. R esults: After termination of the treatment, the highest proportion of patients with bad voice quality was in the glottic carcinoma group (both in early and late phase), with swallowing dysfunction in the transglottic carcinoma group. Compared to the situation before the treatment, the proportion of patients with impaired voice quality (bad voice quality and loss of voice) initially decreased among all groups (except for supraglottic carcinomas), and during the first post-treatment year either increased or did not change. The proportion of patients with no swallowing dysfunction increased in the supraglottic, subglottic and transglottic carcinoma groups. D iscussion: We consider necessary the implementation of a standard pre- and post-treatment monitoring of the voice and swallowing function in the management of patients with laryngeal cancer.

Improved Thyroid Hypoechogenicity Following Bariatric-Induced Weight Loss in Euthyroid Adults With Severe Obesity-a Pilot Study.

Background: Obesity may affect both biochemical thyroid function tests; and thyroid morphology, as assessed using ultrasound scans (US). The aim of the present pilot study was to explore whether weight loss achieved by bariatric surgery alters thyroid US morphology including gray-scale measurements; and/or function in euthyroid adults with severe obesity. Methods: Euthyroid adults (>18 years) with body mass index (BMI) ≥40 kg/m2 and negative thyroid peroxidase antibodies were assessed at baseline (pre-surgery) and after achieving at least 5% weight loss of their baseline body weight following bariatric surgery. Anthropometric assessments, biochemical/hormonal measurements (TSH, free-T4, free-T3, reverse-T3, and leptin) and thyroid US with gray-scale histogram analysis were performed at the baseline and post-surgery follow-up. Results: Ten Caucasian, euthyroid patients (women/men: 8/2; age: 48.6 ± 3.1 years; BMI: 51.4 ± 1.8 kg/m2) successfully completed this study with significantly decreased body weight (>5% weight loss), waist circumference and serum leptin levels post-surgery (mean post-surgery follow-up duration: 16.5 ± 2.5 months). In parallel to the observed bariatric-induced weight loss, thyroid US echogenicity increased by 25% (p = 0.03), without significant changes in thyroid volume. No significant changes in thyroid function tests were detected. No significant correlations were observed between the increase in thyroid echogenicity and the decreases in anthropometric parameters and circulating leptin. Conclusion: Our results indicate that in euthyroid adults with severe obesity, marked weight loss achieved by bariatric surgery is associated with a parallel significant increase in the thyroid US echogenicity, suggesting that morphological changes of the thyroid in obesity are reversible with weight loss. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03048708.

Voice outcomes after thyroidectomy without superior and recurrent laryngeal nerve injury: VoiSS questionnaire and GRBAS tool assessment.

Voice symptoms are frequently reported early after thyroidectomy, even in the absence of laryngeal nerves injury. We evaluated the short-term outcomes of these functional alterations. Thirty-nine patients were enrolled in a prospective observational trial, evaluating voice function before and 3 months after uncomplicated thyroidectomy, using VoiSS as assessed using a validated patient rated questionnaire; and perceptual voice analysis using GRBAS scale (Grade, Roughness, Breathiness, Asthenia, Strain). Impact of dysphonia on patient's life using VoiSS questionnaire revealed differences between pre- and postoperative assessment. There was statistically significant worsening in the impairment subgroup of VoiSS (p = 0.027). GRBAS evaluation was consistent between the three independent raters but showed differences between pre- and postoperative voice assessment. Age, TSH and a preoperative finding of laryngopharyngeal reflux significantly predicted quality of voice after thyroid surgery (all p < 0.004), as identified by the GRBAS assessment tool, but not type of surgery, gender or smoking status; although prediction of total variance in changes of voice was modest (r 2 = 0.07). Voice changes may occur after thyroidectomy without evident laryngeal nerve injury. Patients should be made aware of possible mild changes in voice even after uncomplicated thyroid surgery and this might be considered to be part of the informed consent.

External beam radiotherapy in differentiated thyroid carcinoma: A systematic review.

External beam radiotherapy (EBRT) is not a first line treatment in differentiated thyroid carcinoma (DTC), but is recommended as an adjuvant treatment in certain cases. The evidence for EBRT in DTC is limited. A comprehensive literature search was performed. Data on patient demographics, disease stage, treatment characteristics, and outcomes were collected from included articles after quality appraisal. Sixteen articles met the inclusion criteria, with a pooled population of 5114. Only 1 study was prospective and there were no randomized controlled trials. Most of the evidence suggests that EBRT improves locoregional control in patients at high risk of locoregional recurrence. This was corroborated by analysis of pooled patient data. Available evidence suggests an improvement in locoregional control when EBRT is used in patients over the age of 45 at high risk for locoregional recurrence. However, there is a need for long-term prospective multicenter research on the subject. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2297-E2305, 2016.

Laser arytenoidectomy and posterior cordotomy in a patient with bilateral vocal cord paralysis due to multiple system atrophy.

Bilateral vocal cord paralysis leading to stridor is a known but rare complication of Parkinson's disease (PD) and a recognised complication of multiple system atrophy (MSA). Tracheostomy is a commonly offered treatment, leading to substantial adaptations and lifestyle changes for the patient. Patients can struggle to manage a tracheostomy due to the tremor and bradykinesia associated with their parkinsonism. We report a case of bilateral vocal cord paralysis leading to significant stridor in a patient with atypical parkinsonism (probable MSA). To avoid tracheostomy, our patient underwent successful right-sided laser arytenoidectomy and posterior cordotomy as a day-case procedure. At follow-up, he had a weaker voice but complete recovery from the shortness of breath and stridor. He was very satisfied with the outcome. We conclude that, despite resulting in a weaker voice, this procedure offers an option to the patient that improves quality of life.

Intravascular papillary endothelial hyperplasia of larynx: case report and literature review of all head and neck cases.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign lesion of a vascular origin that is caused by excessive proliferation of endothelial cells in blood vessels or vascular malformations. It is a rare entity that can present in any region of the body, but with particular predilection to the head and neck region and the extremities. We also present the results of the English literature search, which to our knowledge are all the published cases of IPEH in the head and neck region (No=213). IPEH has not been reported to arise from the glottic region previously. We present a first case of IPEH arising from the vocal fold of a 48-year-old male. Histological differential diagnosis of IPEH includes several entities, most importantly angiosarcoma. Presentation and histology are discussed. The main treatment option is a complete surgical resection. Prognosis of IPEH is excellent, with the exception of some intracranial cases.

Triggering receptor expressed on myeloid cells-1 and 2 in bronchoalveolar lavage fluid in pulmonary sarcoidosis.

BACKGROUND AND OBJECTIVE: Pulmonary sarcoidosis (PS) is characterized by the formation of granulomas in the lungs and has been associated with infection by microorganisms. Triggering receptor expressed on the surface of myeloid cells (TREM)-1 is overexpressed in response to infection while TREM-2 is involved in granuloma formation. We hypothesized that these receptors are overexpressed in PS and might be useful for diagnostic testing. METHODS: Cell surface TREM-1 and TREM-2 expression in cells obtained at bronchoalveolar lavage (BAL) was measured in individuals with sarcoidosis (n = 26) and compared with that seen in individuals with other interstitial lung diseases (ILD) (n = 27). RESULTS: TREM-1 and TREM-2 expression was significantly increased in sarcoidosis compared with other ILD: total number of TREM-1, P = 0.0039 (23.81 vs 13.50 cells/µl), TREM-2, P < 0.0001 (32.81 vs 7.76 cells/µl); percentage of TREM-1: P = 0.0002 (41.30% vs 15.70%), TREM-2: P < 0.0001 (34% vs 9.60%); and mean fluorescence of TREM-1: P = 0.0005 (5.43 vs 1.96), TREM-2: P = 0.0011 (6.85 vs 2.77). Increase in both of these receptors seems to be typical for PS. In discriminating sarcoidosis from other ILD, the specificity (96%) and sensitivity (72%) of the combination of TREM-1 and TREM-2 was high. CONCLUSIONS: Increased TREM-1 and TREM-2 cell surface expression is observed in sarcoidosis. Evaluation of BAL cell expression of both of these receptors may serve as a diagnostic marker for sarcoidosis.

Malignancy risk analysis in patients with inadequate fine needle aspiration cytology (FNAC) of the thyroid.

BACKGROUND: Thyroid fine needle aspiration cytology (FNAC) is the standard diagnostic modality for thyroid nodules. However, it has limitations among which is the incidence of non-diagnostic results (Thy1). Management of cases with repeatedly non-diagnostic FNAC ranges from simple observation to surgical intervention. We aim to evaluate the incidence of malignancy in non-diagnostic FNAC, and the success rate of repeated FNAC. We also aim to evaluate risk factors for malignancy in patients with non-diagnostic FNAC. MATERIALS AND METHODS: Retrospective analyses of consecutive cases with thyroid non diagnostic FNAC results were included. RESULTS: Out of total 1657 thyroid FNAC done during the study period, there were 264 (15.9%) non-diagnostic FNAC on the first attempt. On repeating those, the rate of a non-diagnostic result on second FNAC was 61.8% and on third FNAC was 47.2%. The overall malignancy rate in Thy1 FNAC was 4.5% (42% papillary, 42% follicular and 8% anaplastic), and the yield of malignancy decreased considerably with successive non-diagnostic FNAC. Ultrasound guidance by an experienced head neck radiologist produced the lowest non-diagnostic rate (38%) on repetition compared to US guidance by a generalist radiologist (65%) and by non US guidance (90%). CONCLUSIONS: There is a low risk of malignancy in patients with a non-diagnostic FNAC result, commensurate to the risk of any nodule. The yield of malignancy decreased considerably with successive non-diagnostic FNAC.

Impact of radiotherapy on laryngeal intrinsic muscles.

Ionizing radiation as a cancer therapy is associated with a variety of undesirable side effects. Consequently, radiotherapy can negatively affect neuromuscular function. Clinical observations have identified problems with swallowing and voice function. Our study aims to evaluate the impact of radiotherapy on laryngeal soft tissues using image analysis to quantify its effect on the structure of the vocalis and thyroarytenoid muscles. Case control study, retrospective analysis. We collected total laryngectomy specimens from six patients with persistent or recurrent cancer who had received preoperative radiotherapy (60-66 Gy). The control group consisted of total laryngectomy specimens from six patients who underwent surgery as primary treatment. Sampling of the specimens only included non-cancerous laryngeal tissue. Laryngeal histological slices were evaluated using digital morphometric analysis system. Percentage of fibrosis and density of muscle fibers within the thyroarytenoid muscle were evaluated in both groups. We found no significant quantitative differences in muscle fibrosis (7.92% vs. 7.52%, P > 0.1). Changes were rather qualitative and included changes in the organization of the muscular fibers. A significant reduction in muscle fibers, however, was observed in the samples from irradiated larynges (66.45% vs. 42.03%, P < 0.01). Our analysis suggests that radiotherapy is responsible for a significant reduction in muscle fibers in the thyroarytenoid muscle and that these changes occur during treatment or relatively early after its completion. Loss of muscle mass after irradiation correlates with clinical observations of muscle weakness and decreased function in patients who undergo radiotherapy.