Use OF NBI for the assessment of clinical signs of rhino-pharyngo-laryngeal reflux in pediatric age: Preliminary results.

OBJECTIVES: Laryngopharyngeal reflux (LPR) is a complex problem in pediatric population: diagnosis and clinical presentation are still controversial. Classic white light endoscopy shows some pathognomonic signs of LPR in children, such as thickening of pharyngo-laryngeal mucus, the cobblestoning aspect of pharyngeal mucosa, arytenoid edema/hyperemia, nodular thickening/true vocal cord edema, hypertrophy of the posterior commissure, subglottic edema. The NBI (Narrow Band Imaging) technology, generally used in oncology, allows to study neoangiogenesis and hypervascularization of the mucosa, common aspects in both chronic inflammation and neoplastic transformation. The aim of our study was to evaluate the added value of this technology in identifying the main laryngopharyngeal reflux sign in a pediatric population. METHODS: We evaluated at the Otolaryngology Unit of the "Fondazione Policlinico A. Gemelli" hospital and the Airway Surgery Unit of the "Bambino Gesù" Children's Hospital 35 patients aged from 2 months to 16 years divided into two groups in the period between November 2017 and May 2018. Group A included patients with clinical suspicion of LPR after gastroenterologist evaluation and Group B included patients who underwent an endoscopic evaluation for the assessment of recurrent respiratory symptoms such as stridor, recurrent croup, wheezing and persistent cough. We performed an endoscopic evaluation by white light and NBI for each patient, comparing the results of both methods to evaluate signs of pharyngo-laryngeal reflux and to calculate the value of reflux finding score (RFS). RESULTS: The analysis of the data showed: for Group A an average value of RFS with white light of 11,84 (range 8-17, standard deviation 2,52 ±â€¯0,57) and with NBI of 13,63 (range 10-17, standard deviation 2,13 ±â€¯0,49); for Group B the analysis of the data showed an average value of RFS with white light of 10,06 (range 8-14, standard deviation 2,32 ±â€¯0,58) and with NBI of 12,50 (range 9-18, standard deviation 2,63 ±â€¯0,65). The comparison between the two methods resulted significant. Furthermore evaluation by NBI allowed to highlight other signs of pharyngo-laryngeal reflux, characteristic of pediatric age and not included in RFS, in particular cobblestone aspect of the hypopharingeal mucosa, phlogosis of the tonsillar crypts and adenoid surface, hyperemia and hypervascularization of subglottic and tracheal mucosa. CONCLUSION: Although still preliminary our results represent an interesting starting point for further studies, because they underline the potentiality of NBI endoscopy in LPR evaluation and how this technology could improve the identification of reflux signs.

[Narrow band imaging for evaluation of laryngeal mucosal lesions]. / "Narrow band imaging" zur Beurteilung laryngealer Schleimhautläsionen.

The use of narrow band imaging (NBI) and further technological achievements concerning the resolution and magnification of endoscopic images have revolutionized laryngology in the past 10 years. The diagnosis and therapy of dysplasia and early laryngeal carcinoma have become significantly easier. There are also clear benefits for benign laryngeal lesions. Central to these techniques is the assessment of epithelial, connective tissue and vascular changes caused by diverse diseases.

Practice variations in voice treatment selection following vocal fold mucosal resection.

OBJECTIVES/HYPOTHESIS: To characterize initial voice treatment selection following vocal fold mucosal resection in a Medicare population. STUDY DESIGN: Retrospective analysis of a large, nationally representative Medicare claims database. METHODS: Patients with > 12 months of continuous Medicare coverage who underwent a leukoplakia- or cancer-related vocal fold mucosal resection (index) procedure during calendar years 2004 to 2009 were studied. The primary outcome of interest was receipt of initial voice treatment (thyroplasty, vocal fold injection, or speech therapy) following the index procedure. We evaluated the cumulative incidence of each postindex treatment type, treating the other treatment types as competing risks, and further evaluated postindex treatment utilization using the proportional hazards model for the subdistribution of a competing risk. Patient age, sex, and Medicaid eligibility were used as predictors. RESULTS: A total of 2,041 patients underwent 2,427 index procedures during the study period. In 14% of cases, an initial voice treatment event was identified. Women were significantly less likely to receive surgical or behavioral treatment compared to men. From age 65 to 75 years, the likelihood of undergoing surgical treatment increased significantly with each 5-year age increase; after age 75 years, the likelihood of undergoing either surgical or behavioral treatment decreased significantly every 5 years. Patients with low socioeconomic status were significantly less likely to undergo speech therapy. CONCLUSION: The majority of Medicare patients do not undergo voice treatment following vocal fold mucosal resection. Further, the treatments analyzed here appear disproportionally utilized based on patient sex, age, and socioeconomic status. Additional research is needed to determine whether these observations reflect clinically explainable differences or disparities in care. LEVEL OF EVIDENCE: 2c. Laryngoscope, 126:2505-2512, 2016.

Recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare, benign disease with no known cure. RRP is caused by infection of the upper aerodigestive tract with the human papillomavirus (HPV). Passage through the birth canal is thought to be the initial transmission event, but infection may occur in utero. HPV vaccines have helped to provide protection from cervical cancer; however, their role in the prevention of RRP is undetermined. Clinical presentation of initial symptoms of RRP may be subtle. RRP course varies, and current management focuses on surgical debulking of papillomatous lesions with or without concurrent adjuvant therapy.

Assessment of canine vocal fold function after injection of a new biomaterial designed to treat phonatory mucosal scarring.

OBJECTIVES: Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration-approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. METHODS: We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. RESULTS: High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. CONCLUSIONS: The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.

Laryngeal sensory testing in the assessment of patients with laryngopharyngeal reflux.

Laryngopharyngeal reflux is commonly encountered in the ENT out-patient setting. It leads to impaired sensory capacity of the laryngeal mucosa. The sensory integrity of the laryngopharynx can be evaluated through endoscopic administration of pulsed air, which stimulates the laryngeal adductor reflex. The pressure of air needed to elicit this reflex indicates the degree of sensory impairment. Such laryngeal sensory testing gives a quantifiable means of assessment in patients with laryngopharyngeal reflux, and can be used to measure the response to treatment. Laryngeal sensory testing is safe and well tolerated by patients.

[Chronic ENT pathology in employees of tobacco and pharmaceutical industries in conditions of small-dispersion pollution of the working zone air]. / KT visochnoi kosti v diagnostike priobretennoi kholesteatomy srednego ukha.

Incidence rate of chronic ENT diseases was compared in workers of tobacco and pharmaceutical industries. Using representative samples of workers employed in both industries exposed to industrial dust hazards, the rate and structure of chronic ENT pathology were compared. Damage to the upper airways (UA) consists in dystrophic changes in ENT mucosa (subatrophic isolated and combined forms). Chronic combined UA lesions in workers of the tobacco factories occur more frequently than in workers of pharmaceutical factories. It is necessary to conduct ENT examinations in applicants for jobs in factories with industrial dust hazards to detect basic diseases, especially in those with nasal septal defects and related respiratory problems.

[Nuclear shape assessment of the cells in precancerous lesions and laryngeal cancer]. / Morfometryczna analiza ksztaltu jader komórkowych w stanach przedrakowych i raku krtani.

The authors assessed morphometrically the nuclei shape of the normal mucosa, precancerous lesions (dysplasia, keratosis) and laryngeal cancer in the postoperative samples of 12 patients treated in the Laryngology Department Silesian Medical Academy in Zabrze. Five slides from the same patient, each 4 um thick were assessed. The histologic samples were measured by system Quantimet 500 + Color Option with magnification 2100x. Roundness, aspect ratio and fullness ratio were evaluated. The relationship among the morphologic lesions using shape descriptors was assessed. In some cases there were no significant differences between the nuclei of mild dysplasia cells and the cells of the normal epithelium. The results indicate significant karyometric shape differences of the normal mucosa, precancerous lesions and cancer of the larynx.

Underdosage of the upper-airway mucosa for small fields as used in intensity-modulated radiation therapy: a comparison between radiochromic film measurements, Monte Carlo simulations, and collapsed cone convolution calculations.

Head-and-neck tumors are often situated at an air-tissue interface what may result in an underdosage of part of the tumor in radiotherapy treatments using megavoltage photons, especially for small fields. In addition to effects of transient electronic disequilibrium, for these small fields, an increased lateral electron range in air will result in an important extra reduction of the central axis dose beyond the cavity. Therefore dose calculation algorithms need to model electron transport accurately. We simulated the trachea by a 2 cm diameter cylindrical air cavity with the rim situated 2 cm beneath the phantom surface. A 6 MV photon beam from an Elekta SLiplus linear accelerator, equipped with the standard multileaf collimator (MLC), was assessed. A 10 x 2 cm2 and a 10 x 1 cm2 field, both widthwise collimated by the MLC, were applied with their long side parallel to the cylinder axis. Central axis dose rebuild-up was studied. Radiochromic film measurements were performed in an in-house manufactured polystyrene phantom with the films oriented either along or perpendicular to the beam axis. Monte Carlo simulations were performed with BEAM and EGSnrc. Calculations were also performed using the pencil beam (PB) algorithm and the collapsed cone convolution (CCC) algorithm of Helax-TMS (MDS Nordion, Kanata, Cahada) version 6.0.2 and using the CCC algorithm of Pinnacle (ADAC Laboratories, Milpitas, CA, USA) version 4.2. A very good agreement between the film measurements and the Monte Carlo simulations was found. The CCC algorithms were not able to predict the interface dose accurately when lateral electronic disequilibrium occurs, but were shown to be a considerable improvement compared to the PB algorithm. The CCC algorithms overestimate the dose in the rebuild-up region. The interface dose was overestimated by a maximum of 31% or 54%, depending on the implementation of the CCC algorithm. At a depth of 1 mm, the maximum dose overestimation was 14% or 24%.

Stroboscopic assessment of vocal fold keratosis and glottic cancer.

Disruption of the normal viscoelastic properties of the superficial lamina propria (SLP) results in aberrant vocal fold vibration and mucosal wave propagation. Therefore, an investigation was performed to determine whether stroboscopy is a reliable method for 1) differentiating invasive glottic carcinoma from intraepithelial atypia or 2) determining the depth of cancer invasion. An analysis was done on the preoperative vocal fold vibration characteristics of 62 keratotic (intraepithelial, 45; cancer, 17) lesions that were subsequently resected by means of microlaryngoscopy. Histopathology and intraoperative mapping were used to specify the depth of invasion. A panel of 4 blinded judges was used to assess the amplitude of vocal fold vibration and the magnitude of mucosal wave activity in the region of the lesion from videostroboscopic recordings. The final comparative data set comprised only those ratings that achieved at least 75% interjudge agreement. Of the 28 intraepithelial lesions that could be reliably evaluated for amplitude of vocal fold vibration, only 2 were normal, with the amplitude reduced in 24 and absent in 2. Of the 30 intraepithelial lesions in which mucosal wave activity could be reliably assessed, only 2 were normal, with the wave reduced in 24 and absent in 4. Furthermore, amplitude of vocal fold vibration and magnitude of mucosal wave propagation were absent in 2 of 4 carcinomas in which the depth of microinvasion did not reach the vocal ligament. According to the findings herein, reduced amplitude of vocal fold vibration and/or mucosal wave propagation associated with keratosis did not reliably predict the presence of cancer or the depth of cancer invasion into the laminae propriae. However, the presence of a flexible mucosal wave probably indicates that there is not extensive vocal ligament invasion. Reductions in the amplitude of vocal fold vibration and in mucosal wave magnitude were usually noted in intraepithelial atypia, despite the fact that there was no invasion into the SLP. The reduced epithelial pliability could be due to bulky keratosis and/or alteration of the SLP occurring as a result of inflammation or fibrovascular scarring.

[Morphometric assessment of the precancerous lesions and laryngeal cancer]. / Ocena morfometryczna stanów przedrakowych i raka krtani.

The authors assessed morphometrically nuclei of the normal mucosa, precancerous lesions and laryngeal cancer in the postoperative samples of 12 patients treated in the II Laryngology Clinic, Silesian Medical Academy in Zabrze. The results indicate significant cariometric differences of the normal mucosa, precancerous mucosal lesions and cancer of the larynx.

Morphological assessment of malignant potential of epithelial hyperplastic lesions.

The spectrum of conventional and advanced morphological methods for the assessment of malignant potential of precancerous lesions of the laryngeal mucosa is discussed.

The Kambic-Gale method of assessment of epithelial hyperplastic lesions of the larynx in comparison with the dysplasia grade method.

Sections of vocal cord biopsies from 47 cases in whom had been previously assessed by a dysplasia grading system at from I to III, were reclassified according to the Ljubljana system. The majority of the Grade I lesions were reclassified as "non-risky", but a small number were put into the risky or even carcinoma in situ groups. While most of the Grade III cases were reclassified as "risky" there were a few who were assigned to a non-risky category. It is suggested that with the Ljubljana histological grading system a more clear-cut separation of cases with risk of developing vocal cord malignancy from those with no such risk, is possible. Attention is drawn to a lesion denoted as "large cell hyperplasia", which is not covered in the grading or Ljubljana categorization of vocal cord lesions. The malpighian cells in this lesion are enlarged to over 30 microm in diameter, and show prominent nucleoli: apoptotic cells are prominent. Evidence is presented that this may be a categorical risk for the development of malignant changes.

[The quantitative study of nucleolar organizers (AgNOR) in the diagnosis of laryngeal dysplasias and in the assessment of the prognosis in invasive carcinoma]. / Studio quantitativo degli organizzatori nucleolari (AgNOR) nella diagnosi delle displasie laringee e nella valutazione della prognosi del carcinoma invasivo.

Nucleolar organiser regions (AgNOR) are chromosomal segments in which ribosomal RNA is codified. These structures can be identified in the nuclei of cells in routine histological sections using a silver staining technique which reveals the proteins associated with transcription RNA. The number of AgNOR identified depends on the state of cell proliferation. The purpose of the present study was to evaluate the distribution of AgNOR in normal laryngeal mucosa, dysplastic and neoplastic, in order to establish a possible correlation with the degree of dysplasia and/or the entity of the malignant lesions. Ten slides each of specimens of laryngeal carcinoma, serious dysplasia and middle dysplasia were prepared with the silver staining technique. A count of the NOR in the basal, parabasal, intermediate and superficial levels was made. Findings show an increase in the average value of NOR proceeding from normal tissue to carcinoma in situ and malignant carcinomas. The number of AgNOR was lower always than that observed in the parabasal level. In the intermediate cell section the number of AgNOR was inferior to that in the parabasal level in normal tissue as well as in middle dysplasia, while it remained high in serious dysplasia and in carcinomas, thus indicating a great deal of biological activity in these cases. This method can be employed in order to better individualize those dysplastic lesions which, because of their tendency towards malignancy, must be kept under observation by means of an extremely accurate follow-up.