DNA rare copy number alterations in Reinke's Edema.

INTRODUCTION: Reinke's Edema (RE) is a laryngeal lesion related to excessive tobacco smoking, voice overuse, and laryngopharyngeal reflux. Although the risk of malignancy has been considered low in literature, RE is classified among precancerous lesions. OBJECTIVES: We investigated DNA Copy Number Alterations (CNAs) in specimens of RE and its potential association with malignant progression. METHODS: We used array-based comparative genomic hybridization (aCGH, Agilent 4 × 180 K platform) to study eight RE cases. All patients were heavy tobacco users for at least 30 years, and none of them progressed to cancer in the follow-up (>8 years). Two RE presented mild dysplasia, one moderate dysplasia, and no histological alterations were found in the remaining five cases. CNAs were compared with the Database of Genomic Variants (DGV) and genes mapped on altered regions had their functions annotated. RESULTS: Six of eight patients showed different rare copy number alterations on chromosomes 2q37.3, 4q13.1, 4q13.3, 7q11.22, 10p14, and 13q34. A gain of the whole chromosome 8 were detected in one case. Of interest, four of eight RE cases showed copy number imbalances involving genes previously described in several tumor types (RASA3, COL6A3, LINC00707, LINP1, SMR3A, and SMR3B). CONCLUSION: The genomic imbalances herein found in RE have the potential to contribute to the phenotype but with limited or no risk of cancer. A long-term follow-up in a large series of patients could clarify the mechanisms involved in the malignant progression of RE.

Un-sedated Office-Based Application of Blue Laser in Vocal Fold Lesions.

INTRODUCTION: Office-based laser procedures in laryngology have gained a lot of popularity in the last decade with the use of the KTP, PDL and Thulium lasers. Preliminary investigations currently report on the use of the 445 nm wavelength Blue laser for the treatment of various laryngeal pathologies, given its dual photoangiolytic and cutting properties. OBJECTIVE: We aim to investigate the safety and efficacy of the Blue laser for the treatment of vocal fold lesions. METHODS: This is a retrospective chart review of eleven patients with a variety of vocal fold lesions (polyps, Reinke's edema, papilloma, and leukoplakia), that underwent un-sedated office-based treatment using the 445 nm blue laser. The primary outcome was to compare preoperative to postoperative Voice Handicap Index (VHI-10) score and self-reported voice improvement using a visual analog scale (VAS). We also compared fiberoptic laryngeal examination before and after treatment. RESULTS: Eleven un-sedated office-based procedures using the blue laser were performed. There was improvement in the mean VHI-10 score (n = 8) with a decrease from 15.13 ± 8.77 to 3.50 ± 3.46 (P= 0.015). Similarly, the mean VAS score (n = 7) decreased from 6.14 ± 1.21 to 1.71 ± 1.60 (P< 0.003). All patients had a complete or partial regression of the vocal fold lesions on fiberoptic laryngeal examination. None of the patients had complications after the procedure. CONCLUSION: Blue laser therapy can be suggested as a safe and effective alternative treatment modality in office-based laryngology procedures for a variety of vocal fold lesions. A larger series is needed to better validate the efficacy of this laser as a new treatment modality.

The Nature and Risk Factors of Minimal Associated Pathological Lesions of Vocal Folds at Two Hospitals in the Gulf Area.

OBJECTIVE: To identify the possible risk factors related to etiology of the minimal associated pathological lesions (MAPLs) of the vocal folds and their impacts on the recurrence of lesion. METHODS: This analytical cross-sectional study included 200 subjects presented with dysphonia to the Phoniatrics/Voice Clinics in two hospitals in Gulf region (KSA and UAE). Same number of matched voluntaires from the same hospitals (hospital staffs, employees and their relatives) and relatives of subjects with typical voice quality were included as well. Both groups underwent a simple questionnaire consists of 15 items related to previously accused risk factors of MAPLs. RESULTS: The bivariant analysis by Fisher's exact test showed that male gender, presence of kids, misuse of voice, alcohol, gastroesophageal reflux diseases and voice handicapping are associated with significant risk to have MAPLs with P values < 0.001 for all except for alcohol (P = 0.015). Welch's t test revealed higher smoking index in subject than control groups with significant difference (P < 0.001). In contrast, spices, family shouting and nearby industry were not potent risk factors in our study group. CONCLUSION: Vocal trauma especially in females and children is a potent risk factor for vocal fold nodules and cysts. The gastroesophageal reflux is a suggested risk factor for Reinke's edema and contact granuloma. Smoking is the risk factor for MAPLs particularly polyp, contact granuloma, and Reinke's edema. Also, alcohol consumption is a possible risk factors for Reinke's edema. Identification of risk factors of the MAPLs is an important step in planning therapy. Risk factors which are highly related to a specific type of MAPLs should be involved in any planned program for protection, voice rehabilitation and/or prevention of recurrence of that lesion.

First-line treatment of exudative vocal fold-lesions by in-office local corticosteroid injection: A literature review.

OBJECTIVES: There are emerging reports of the effectiveness of in-office awake vocal-fold corticosteroid injection in the treatment of exudative vocal-fold lesions. The aim of this study was to review this therapy and specify indications, practical modalities and outcomes. STUDY DESIGN: Systematic review of the literature without meta-analysis. METHODS: A systematic review by PubMed search for the period January 2000 to December 2018 was carried out. RESULTS: Nine articles were included, for a total of 502 lesions: nodules (46.4%), polyps (31.7%), and Reinke's edema (21.9%). Submucosal injection of low-dose triamcinolone acetonide (0.1 to 0.3mL) was transoral, transcutaneous or transnasal via flexible endoscope with operating channel. Lesion volume was significantly reduced in more than 90% of cases, with significant vocal improvement in all studies. Relapse rates ranged between 4% and 31%, with time to relapse of 1 to 40 months. CONCLUSIONS: First-line treatment of exudative glottic lesions by submucosal corticosteroid injection provides at least transient significant reduction in lesion volume and vocal improvement. It is consensually reserved to moderate-sized mainly exudative lesions without fibrosis. In-office injection provides an immediate therapeutic response in case of vocal impairment, enabling surgery under general anesthesia to be postponed.

Establishment and validation of the LC-MS/MS method for the determination of lincomycin in human blood: Application to an allergy case in forensic science.

An analytical method to quantify lincomycin in human blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated. The selected method was based on a protein precipitation extraction (PPE) with methanol. Instrumental determination was carried out by LC-MS/MS, with quantification based on the internal standard method. Linearity for lincomycin was established in the concentration range of 5-100 ng/mL. The limit of detection (LOD) and limit of quantification (LOQ) were 0.2 and 1 ng/mL, respectively. Analyte recoveries were in the range of 72.70%-84.13% for spiked blood samples. The accuracies ranged between 92.82% and 100.40%, and the intraday and inter-day precisions ranged between 1.19% and 6.40%, respectively. The developed method was applied to an authentic allergy case of lincomycin. By testing the lincomycin content in the venous blood of the deceased and combined with the pathological test results, lincomycin acute allergy appeared to be the most likely cause of death. The acquired results confirm that the developed method is capable of identifying and quantifying lincomycin in human blood and can be suitable for the detection of allergy cases in clinical or forensic science.

Upper airway involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening hypersensitivity conditions associated with epidermal detachment and mucositis. The indication for flexible nasoendoscopy (FNE) and overall predictive factors for early intubation are unclear. OBJECTIVES: To describe the incidence of airway involvement and the key indicators for intubation in our SJS or TEN patient cohort. To determine the association between FNE findings and early intubation. METHODS: A retrospective review of 45 patients with biopsy proven SJS or TEN admitted to an Australian tertiary burns centre from 2010 to 2017. RESULTS: Thirty-five patients were diagnosed with TEN (77.8%), followed by overlap syndrome (SJS-TEN) (n = 6, 13.3%) and SJS (n = 4, 8.9%). Twenty (44.4%) patients were intubated; and all 20 had a diagnosis of TEN (100.0%) (p < 0.05). Intubated patients had a higher increase in total body surface area percentage(%) from day 1-3 [10.0% (IQR 0.0-23.8%)] and a longer length of stay [26.0 days (IQR 12.5-34.0)], compared to non-intubated patients [0.0% (IQR 0.0-4.0%)], [10.0 days (IQR 6.0-14.0)] (p < 0.05) respectively. The main indications for intubation were to facilitate operative and dressing management (47.4%) followed by airway involvement (26.3%). FNE was performed on 32 patients (71.1%), however FNE findings did not significantly influence intubation rates. CONCLUSION: More than half (n = 20, 57.1%) of the 35 patients diagnosed with TEN underwent intubation, mainly to facilitate operative and dressing management. FNE was performed on most patients, however there was no clear association between FNE findings and early intubation.

Cigarette Smoke Exposure to Pig Larynx in an Inhalation Chamber.

OBJECTIVES: This study investigated the effects of cigarette smoke exposure on the pig larynx using an inhalation chamber. Specifically, we compared the effects of cigarette smoke exposure from either 3 cigarettes per day (3cd) or 15 cigarettes per day (15cd) for 20 days. STUDY DESIGN: In vivo prospective design. METHODS: Female pigs were exposed via an inhalation chamber to cigarette smoke (3R4F research cigarettes) from 3cd (n = 6) or 15cd (n = 6) for 20 days. Outcomes included histopathology of vocal fold and airway tissues; gene expression of interleukins, TNF-α, and VEGF; protein levels of TNF-α and IL-6; and number of coughs recorded in the chamber. RESULTS: Pigs exposed to cigarette smoke from 15cd exhibited mild vocal fold edema as compared to the 3cd group on histopathological evaluation. There was also minimal inflammation of nasal and tracheal tissue characterized by presence of more granulocytes in the 15cd group compared to the 3cd group. Cough frequency was significantly greater for the 15cd group compared to the 3cd group. CONCLUSIONS: A custom-designed large animal inhalation chamber successfully challenged pigs repeatedly, to varying levels of cigarette smoke. Future studies will combine such low levels of smoke exposure with other common challenges such as acid reflux to understand the multifactorial causation of laryngeal pathologies.

Does Reinke's Edema Grade Determine Premalignant Potential?

OBJECTIVE: Reinke's edema (RE) is a benign disease of the vocal folds with a wide spectrum of clinical severity. We aim to evaluate the clinical impact of RE grade and determine if RE grade correlates with severity of dysplasia and tobacco exposure. METHODS: Patients with isolated RE who underwent surgical excision between December 2010 and December 2014 were retrospectively reviewed. The RE grade was determined from archived laryngeal videostroboscopy exams. Pathologic severity of dysplasia, categorized by squamous intraepithelial neoplasia (SIN) classification, and tobacco history were extracted from medical records. RESULTS: Of 95 lesions, 3 (3.16%) were RE grade 1, 33 (34.74%) were RE grade 2, 24 (25.26%) were RE grade 3, and 35 (36.84%) were RE grade 4. Fifty-nine lesions (62.11%) had no dysplasia (SIN0), 19 (20.00%) had mild dysplasia (SIN1), 15 (15.79%) had moderate dysplasia (SIN 2), and 2 (2.11%) had severe dysplasia (SIN3). The 2 patients with severe dysplasia had grade 4 lesions. No statistical correlation was identified between RE grade and the severity of dysplasia. Furthermore, no statistical correlation was seen between tobacco exposure and the severity of dysplasia or the RE grade. CONCLUSIONS: Size of RE lesion does not reflect premalignancy. The majority of RE lesions, regardless of size, have little to no premalignant potential. Severe dysplasia/carcinoma in situ may be more likely seen in grade 4 lesions; however, the paucity of severe dysplasia published in RE data and in this cohort preclude any formal inference. Further study of grade 4 lesions is warranted.

Edema de Reinke obstructivo / Obstructive Reinke edema

Introducción: el edema de Reinke es la acumulación de fluidos en la capa externa de la lámina propia de las cuerdas vocales. Produce disfonía y raras veces obstrucción respiratoria. Las etiologías más frecuentes son el tabaquismo, el reflujo gastroesofágico y el mal uso y abuso vocal. Objetivos: determinar, mediante tratamiento quirúrgico, la tasa de resolución de la disnea inspiratoria severa provocada por edema de Reinke bilateral de cuerdas vocales. Diseño: estudio descriptivo y retrospectivo. Material y métodos: revisión de las historias clínicas electrónicas de todos los pacientes que consultaron y fueron tratados por disnea inspiratoria severa provocada por edema de Reinke bilateral de las cuerdas vocales, en el servicio de Otorrinolaringología del Hospital Italiano de Buenos Aires, entre febrero de 2007 y abril de 2015. Resultados: fueron tratados 4 pacientes de sexo femenino que consultaron por disnea inspiratoria severa. Fumaban más de 30 cigarrillos por día. La técnica quirúrgica consistió en resecar todo el edema polipoideo en forma bilateral, preservando el borde libre de las cuerdas vocales. Conclusiones: el edema de Reinke obstructivo es una patología infrecuente. La tasa de resolución de la disnea inspiratoria severa en las cuatro enfermas tratadas fue del100%. La resección total del edema y de la mucosa excedente, preservando un pequeño sector para que recubra el borde libre de la cuerda vocal (cordectomía vs. cordotomía), fue la técnica quirúrgica preferida. (AU)

Introduction: the Reinke edema is an accumulation of fluid in the outer layer of the lamina propria of the vocal cords. Causes dysphonia and rarely produces respiratory obstruction. Objectives: to determine the rate of resolution of the severe inspiratory dyspnea caused by bilateral Reinke edema of vocal cords with surgical treatment. Design: descriptive and retrospective study. Material and methods: review of the electronic medical records of all patients who consulted and were treated for severe inspiratory dyspnea caused by bilateral Reinke edema of the vocal chords in the Hospital Italiano de Buenos Aires between February 2007 and April 2015. Results: four women were treated, consulted for severe inspiratory dyspnea. Smoked more than 30 cigarettes per day. The surgical technique consisted in to resect all the bilateral polypoid edema, while preserving the free edge of the vocal cords. Conclusions: the obstructive Reinke edema is an infrequent pathology. The rate of resolution of the severe inspiratory dyspnea in the four patients treated was 100%. The total resection of the edema and mucosa excess, preserving a small sector to cover the free edge of the vocal cord (cordectomy vs cordotomy) was the preferred surgical technique. (AU)

Fatal case of cutaneous-sparing orolaryngeal zoster in a renal transplant recipient.

Herpesvirus infections in solid organ transplant (SOT) recipients are a significant cause of morbidity and mortality. We report a case of herpes zoster (HZ) in a kidney transplant recipient while receiving belatacept, a CTLA-4 inhibitor that prevents acute rejection. The patient presented with oropharyngolaryngeal mucosal lesions that subsequently disseminated resulting in pneumonitis and meningo-encephalitis. Very late-onset HZ can occur and can present atypically in SOT recipients. Delayed recognition and treatment may result in poor outcomes, as illustrated by this case.

Voice Quality and Gender Stereotypes: A Study of Lebanese Women With Reinke's Edema.

Purpose: Women with Reinke's edema (RW) report being mistaken for men during telephone conversations. For this reason, their masculine-sounding voices are interesting for the study of gender stereotypes. The study's objective is to verify their complaint and to understand the cues used in gender identification. Method: Using a self-evaluation study, we verified RW's perception of their own voices. We compared the acoustic parameters of vowels produced by 10 RW to those produced by 10 men and 10 women with healthy voices (hereafter referred to as NW) in Lebanese Arabic. We conducted a perception study for the evaluation of RW, healthy men's, and NW voices by naïve listeners. Results: RW self-evaluated their voices as masculine and their gender identities as feminine. The acoustic parameters that distinguish RW from NW voices concern fundamental frequency, spectral slope, harmonicity of the voicing signal, and complexity of the spectral envelope. Naïve listeners very often rate RW as surely masculine. Conclusions: Listeners may rate RW's gender incorrectly. These incorrect gender ratings are correlated with acoustic measures of fundamental frequency and voice quality. Further investigations will reveal the contribution of each of these parameters to gender perception and guide the treatment plan of patients complaining of a gender ambiguous voice.

[Rehabilitation of phonosurgically treated patients with edematous-hypertrophic changes of larynx]. / Rehabilitacja pacjentów leczonych fonochirurgicznie z powodu zmian obrzekowo-przerostowych krtani.

UNLABELLED: Advanced change of organic dysphonia are an indication for phonosurgery. Edematous-hypertrophic changes are cause of serious disturbances of voice. High-speed digital imaging (HSDI) technique is the unique method, allowing for assessment the effects of therapy and rehabilitation. AIM: The aim of the study is evaluation the usefulness of vibratory method in voice rehabilitation of patients with edematous-hypertrophic changes treated phonosurgically. MATERIALS AND METHODS: The group I contained 40 patients with edematous-hypertrophical changes phonosurgically treated. Type of clinical dysphonia was diagnosed with HSDI technique. Glottal closure was evaluated according to Committee on Phoniatrics of the European Laryngological Society (ELS) classification, postoperative material was pathomorphologically verified by Transmission Electron Microscopy (TEM). Patients with hyperfunction of larynx were rehabilitated for 21 days using massage device and after that visualization of larynx by HSDI technique was made again. Control group contains people with physiological voice. RESULTS: Severe dysphonia with oedematous-hypertrophic changes was found by HSDI technique in group I. Postoperative material was evaluated histopathological by TEM and confirmed the existing clinical morphological changes of larynx. Hyperfunction of phonation organ were diagnosed in 30 patients (75%). After 21 days of rehabilitation using massage device, hyperfunction was reduced as confirmed by HSDI. Normalization of amplitude, regularity, synchrony of vibration and physiological glottal closure were found at 67% cases. CONCLUSIONS: HSDI technique in digital sequence is useful in the diagnosis of edematous-hypertrophic changes of the larynx and monitoring the effects of the rehabilitation. Pathomorphological evaluation of postoperative material made by TEM confirmed the rightness of clinical diagnosis of the edematous-hypertrophic changes by HSDI. The consequence of phonosurgical procedures in edematous-hypertrophic changes of larynx is hyperfunction of larynx, confirmed objectively by HSDI technique. The use of massage device causes relaxation of laryngeal structures, normalizing parameters of visualizing evaluation.

Correlation Between Clinical Diagnosis and Pathological Diagnosis in Laryngeal Lesions.

OBJECTIVES: To evaluate the degree of agreement between the clinical and the pathological diagnosis in patients undergoing laryngeal microsurgery due to epithelial or edematous lesions of the vocal folds. STUDY DESIGN: This is a retrospective study. METHODS: The study was developed in the ear, nose, and throat clinic of a tertiary hospital, through chart review. We included all patients who underwent microsurgery of the larynx, whose videolaryngoscopic tests showed vocal fold lesions, from January 2003 to August 2014. During the study period, we identified 48 patients with epithelial and edematous lesions. The patients were divided into two groups. In group A, patients with edematous lesions with clinical diagnosis of polyps and Reinke edema were included. Group B comprised patients with epithelial lesions, as leukoplakic injuries. A correlation between histopathological findings and clinical hypothesis between these two groups of lesions was performed. RESULTS: In group B, there was agreement in 88.9% of cases between the clinical and pathological diagnosis. In group A, compatibility occurred in only 46.4% of cases. We observed a statistically significant difference between the compatibility of the clinical and pathological diagnosis just in edematous lesions (P = 0.029). CONCLUSIONS: The study showed the limitation of the pathological examination on edematous laryngeal lesions. On the other hand, on the epithelial lesions, there was more agreement between those diagnosis.

Normative Values and Interrelationship of MDVP Voice Analysis Parameters Before and After Endotracheal Intubation.

PURPOSE: The Multi-Dimensional Voice Program (MDVP) is used for assessment of voice quality. A simple procedure for MDVP recordings was used in a randomized clinical trial (RCT) on induced vocal fold trauma due to intubation. This secondary study compares the common MDVP parameters with other normative values for adults and investigates the correlation between these MDVP parameters in relation to the "standardized" trauma of endotracheal intubation. METHODS: Preoperative and postoperative assessments of vocal fold pathology with flexible videolaryngoscopy and voice analysis with MDVP using the best-of-three standardized recording were performed in 121 patients with normal voices included consecutively in the RCT. The procedures of anesthesia were standardized. RESULTS: The normative MDVP values of this study are consistently lower compared with most normative values presented in other studies. The preoperative to postoperative differences in jitter values (jitter and relative average perturbation) were closely correlated to the shimmer values for patients with postoperative vocal fold edemas. In the patients with edema, the preoperative to postoperative differences in jitter had a correlation coefficient of 0.95 (P < 0.0001) to the difference in shimmer, compared with a correlation coefficient of 0.39 (P < 0.0001) in the patients without edema. CONCLUSIONS: This study supports the use of the "Best-of-Three" procedures for precise and relevant MDVP parameter calculations. The MDVP parameters, with closely correlated changes in jitter and shimmer values, accurately reflect the induced vocal fold edema when using the preoperative to postoperative changes.

Death due to obstruction of the upper airways caused by edema of the laryngeal mucosa in the course of hereditary angioedema.

A rare case of death of a young man due to airway obstruction in the course of angioedema (Quincke's edema). Type I hereditary angioedema due to C1 esterase inhibitor deficiency had been diagnosed in the man while he was alive. The information concerning the man's health state was given in the Public Prosecutor's decision ordering medico legal autopsy, which was extremely helpful in recognizing the cause of death.

Dysphagia Caused by Chronic Laryngeal Edema.

A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

[The morphology of vocal fold polyps and mucosa in Reinke's edema].

OBJECTIVE: To investigate the morphogenesis of vocal fold polyps and Reinke's edema on the basis of clinical and morphological analyses of the histological and immunohistochemical data characterizing the state of the local microcirculatory bed and the mechanisms of its permeability impairment. SUBJECTS AND METHODS: Polyps of the vocal folds and their mucosal tissue samples in Reinke's edema mucosa, which had been obtained after microsurgical treatment of 31 patients (13 men and 18 women) aged 23 to 75 years, were studied using a wide panel of peroxidase-labeled monoclonal and polyclonal antibodies (DAB chromogen), including T and B cell differentiation markers, Toll-like receptors (TLR2, TLR4, and TLR9), the costimulatory molecule CD80 (B7- 1), and markers for angiogenesis (CD34), vascular and tissue permeability (matrix metalloproteinases (MMP-1 and MMP-9)), and vascular cell adhesion molecule-1 (VCAM-1). Results. All types of the examined polypoid hyperplasia were ascertained to realize through the impaired permeability of the wall of microcirculatory vessels in the membranous vocal fold portion called Reinke's space. The expression of molecules, such as CD34, VCAM-1, MMP-1 and MMP-9, as well as TLR4 and TLR9 was revealed on the endothelial cells of microcirculatory vessels. The epithelial lining cells simultaneously expressed the above-mentioned Toll-like receptors and the costimulatory molecule CD80 (B7-1) that modulated T cell lymphocyte activity (through CD28) or attenuation (through CTLA-4), ensuring the interaction of structures of innate and adaptive immunity. CONCLUSION: The morphogenesis of polypoid hyperplasia of the vocal folds is a result of an epithelial stromal interaction under poor etiological factors, such as high vocal loads, exogenic intoxications, and viral infections. The integumentary lining cells carrying Toll-like receptors initiate reactive alterations in Reinke's space.