From laryngeal epithelial precursor lesions to squamous carcinoma of the larynx: the role of cell cycle proteins and β-catenin

Novel markers to accurately predict the risk of malignant transformation in laryngeal epithelial precursor lesions (EPL) are needed. We tried to identify some molecular alterations occurring in laryngeal tumorigenesis. In this study, 60 paraffin-embedded EPL and 17 metachronous invasive carcinomas were immunostained for markers associated with proliferation (Ki67), cell cycle control (p53, p21, p16, p27, cyclin D1), and cell adhesion and invasion (laminin and β-catenin). Aberrant expression of p16 and p53 and positivity at cytoplasm for β-catenin and cyclin D1 were detected significantly in EPL with progression to invasive laryngeal carcinoma. All cases with basal and suprabasal reactivity of p53 showed β-catenin overexpression. We found that β-catenin protein expression increased significantly with the grade of dysplasia. This is one of the studies with the largest number of laryngeal EPL and invasive carcinoma studied sequentially. Our data confirm the role of some cell cycle regulatory proteins in the development of laryngeal carcinoma. Cytoplasmic retention of β-catenin in EPL seems to be related with more aggressive biological behavior. Combined increased p53 and cytoplasmic β-catenin protein expression could be biologically important in laryngeal tumorigenesis. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues.     

Prevalence of bilateral ‘mirror-image’ lesions in patients with oral potentially malignant epithelial lesions

Early detection of oral potentially malignant epithelial lesions (PMELs) is aimed at improving survival rates as carcinogenesis is a multistep process and prevention is possible if these lesions are detected at an early and reversible stage of the disease. A prospective clinical study aimed at determining the prevalence of bilateral ‘mirror-image’ oral PMELs was carried out. Sample consisted of 32 (53.3%) Indians, 23 (38.3%) Chinese, 4 (6.7%) Malays and one (1.7%) Nepalese. All had histopathological confirmation of their primary existing PMEL as inclusion criteria. A total of 70 primary lesions were detected. The most common PMEL found was oral lichen planus. Of these, 28 (46.7%) patients exhibited bilateral ‘mirror-image’ lesions (n = 42) either synchronously (n = 32/42) or metachronously (n = 10/42). The remaining 32 (53.3%) patients had normal-looking contralateral mucosa. Present findings suggest that patients presenting with oral PMELs are at greater risk of developing a second lesion, most probably in the contralateral ‘mirror-image’ site.     

The assessment of the impact of anorexia nervosa on the vocal apparatus in adolescent girls – A preliminary report

BackgroundChronic undernourishment in the course of anorexia nervosa leads to various metabolic and hormonal changes, which translates to the impaired functioning of the majority of systems and internal organs. The impact of eating disorders on the condition of the vocal apparatus has been described in the literature; nevertheless, it concerns mainly bulimia nervosa.Objectivesassessment of the vocal apparatus in adolescent girls diagnosed with anorexia nervosa from the point of view of possible influence on the function and structure of the larynx, low body mass accompanying anorexia, as well as energy deficiency, hormonal and emotional disturbances.Materials and methodsThe research included 41 girls aged 12–19 years, diagnosed with anorexia, who were assessed for the condition of the vocal apparatus, using the perceptual assessment of voice according to GRBAS scale, videolarynostroboscopy, acoustic assessment, and voice self-assessment in Jacobson's VHI scale (voice handicap index).ResultsThe perceptual assessment of voice using the GRBAS scale revealed that changes in voice were mainly weak, asthenic in nature (70.73%) and there was also the feature of puffing perceived in voice (41.46%). In voice self-assessment with the use of VHI, most subjects seemed to point to changes of voice self-perception in emotional subscale (68%). Videolaryngostroboscopy revealed some features of functional disturbances of voice in more than half of subjects, mainly in the form of hyperfunctional dysphonia (31.78%). The maximal phonation time was significantly shorter, in proportion to duration of the primary disease. In the acoustic analysis, the decrease in the basic frequency F0 and narrowing of the voice scale were observed. 55% of older, post-adolescent patients presented with the structure of the larynx that was inappropriate for their age.ConclusionsThese results might indicate that anorexia nervosa could have led to the structural and functional changes in the vocal apparatus. Such disturbances may be explained by the hormonal dysfunctions as well as starvation. Hormonal substitution at the appropriate time might be beneficial for the structure and phonation function of the larynx in girls with AN.     

Acquired stenosis of the external auditory canal – long-term results and patient satisfaction

Background: The surgical treatment of acquired post-inflammatory atresia of the external auditory canal (EAC) is challenging. Based on the long-term surgical experience, a modified split skin graft technique has been established at our clinic.

Aims/Objectives: The aim was to evaluate the clinical and audiological data and patient satisfaction after performing meatoplasty.

Material and methods: In total, 16 patients were included who underwent intraoperative enlargement of the bony EAC, resection of the fibrotic scar tissue, reconstruction with split skin grafts and splinting of the anterior tympanomeatal angle in the period of 2004–2016. Patients presented at a long-term follow-up appointment for reevaluation.

Results: The mean follow-up time was 52 months after surgery. The pure-tone average (52?dB vs. 31?dB) and the air-bone gap (27?dB vs. 11?dB) decreased significantly compared to the preoperative status. The grade of stenosis also showed a significant improvement during the follow-up visit. Complete re-atresia was observed only in two patients (10.5%).

Conclusion: The applied surgical technique is a safe and successful treatment option for acquired atresia of the EAC.

Significance: The study provides important data for the surgical treatment of acquired atresia of the EAC and corroborates the significance of intensive aftercare.     

Management of severe congenital laryngeal webs – a 12 year review

ObjectiveThe aim of this study was to investigate respiratory and voice outcomes after open surgery for severe congenital laryngeal web.MethodsIncluded were all patients treated for severe congenital glottic web (Cohen type 3 and 4) between 2002 and 2014. Demographic data, symptoms, endoscopic findings, type of operation, outcome and complications were analyzed. Open surgery was performed with division of the web and enlargement of the subglottis by a laryngotracheal reconstruction or an extended partial cricotracheal resection.ResultsFourteen patients were included. Information on the pre-operative voice was available in 11 patients. Aphonia was present in 6 patients (55%), dysphonia was severe in 1 (9%), moderate in 2 (18%) and mild in 2 (18%). Median age at operation was 19.3 months. As a first line treatment, laryngotracheal reconstruction was performed in 12 patients, and an extended partial cricotracheal resection in 2. Median follow-up was 9.5 months. All patients were successfully decannulated in a median time of 4 months after first surgery. Voice was improved in 10/11 (91%). Post-operatively, 3 patients (27%) had good voice. Dysphonia was severe in 2 (18%), moderate in 3 (27%) and mild in 3 patients (27%).ConclusionOpen surgery for Cohen type 3 and 4 glottic web allowed establishing a patent airway with successful decannulation in all cases. Quality of voice was improved in 91%, however, voice results were variable. In our opinion a delicate operative technique described in the paper is important for optimal voice results.     

What is the evidence that gastroesophageal reflux is involved in the etiology of laryngeal cancer?

PURPOSE OF REVIEW: To review recent literature on the possible mechanisms and role of gastroesophageal reflux in the etiology of laryngeal cancer, in patients with and without the accepted risk factors of smoking and alcohol consumption. RECENT FINDINGS: A recent systematic review was not conclusive. The issue remains a popular one for small-scale clinical surveys, when different inclusion criteria and a range of diagnostic tests are used. SUMMARY: After three decades of interest, there is still no unequivocal evidence for the role of reflux in the etiology of laryngeal cancer, whether in smokers or in nonsmokers.     

Effects of Japanese herbal medicine,Juzen-taiho-to,in otitis-prone children – a preliminary study

Conclusion: Juzen-taiho-to (JTT, TJ-48), a Japanese herbal medicine that improves immune function, was found to be effective in otitis-prone in children. Objective: To evaluate the efficacy of JTT against intractable and recurrent infections in immature immune systems, we administered JTT to otitis-prone infants and investigated clinical changes before and during JTT administration. Subjects and methods: Twenty-four otitis-prone infants were administered JTT at 0.10–0.14 g/kg/day twice a day for 3 months. We compared clinical course, such as frequency of acute otitis media (AOM), duration of fever and antibiotics administration, and hospital visits for the periods before and during JTT administration. Results: Medication compliance rate was 87.5%, and administration of JTT led to remission in 95.2% patients. No apparent side effects were observed. The frequency of AOM decreased significantly (Wilcoxon signed rank test, p=0.000) with JTT. The duration of fever (p=0.000) and administration of antibiotics (p=0.001), as well as the number of hospital visits (p=0.001) and emergent hospital visits (p=0.000) showed significant decreases after JTT administration. After the end of the JTT period, 14 of 21 (66.7%) patients started to take it again, as they experienced purulent otitis media and/or other infections after discontinuation. The frequency of AOM increased significantly after stopping JTT (p=0.004) and decreased again with JTT resumption (p=0.005).     

Prognostic value of the inmunohïstochemical expression of protein p27KIP1 in laryngeal cancer

In this paper we carried out an immunohistochemical study of protein p27KIP1 expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain). In the cases with lymph node metastasis we also studied p27KIP1 expression at this level. Furthermore we have analysed the value of protein p27KIP1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between p27KIP1 expression and other clinic and pathologic parameters.     

Thyroid spindle epithelial tumor with thymus-like differentiation (the “settle” tumor)

An intrathyroid primary epithelial spindle-cell tumor with mucous cysts is described in a 9-year-old child. Histologically, this well-circumscribed tumor exhibited a nodular pattern, a prominent spindle cell component with minimal pleomorphism, and well-differentiated mucinous glands within fibrous bands. The spindle cells demonstrated diffuse immunopositivity for cytokeratin and vimentin. Electron microscopy of tissue sections demonstrated that cells contained bundles of cytoplasmic tonofilaments and numerous desmosomes. The light and electron microscopic features and immunohistochemical profile of this tumor were similar to those of recently described thyroid tumors that have been called SETTLE tumors (i.e., spindle epithelial tumor with thymus-like differentiation). These uncommon tumors can be considered intrathyroid thymoblastomas and must be regarded as potentially malignant lesions.