Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis.

Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling.

Genetic polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and the risk for benign Warthin's tumors of the parotid gland.

Background: Warthin's tumors of the parotid gland are associated with smoking, whereas pleomorphic adenomas are not. Genetic polymorphisms in biotransformation enzymes, involved in detoxification of toxins and carcinogens in cigarette smoke, might modify the corresponding enzyme activity and influence detoxifying capacity. We hypothesize that these genetic polymorphisms may influence the individual risk for Warthin's tumor, but not for pleomorphic adenomas.

Chromosome instability predicts progression of premalignant lesions of the larynx.

The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7.

Combined effect of genetic polymorphisms in phase I and II biotransformation enzymes on head and neck cancer risk.

Background: Combinations of genetic polymorphisms in biotransformation enzymes might modify the individual risk for head and neck cancer.

Methods: Blood from 432 patients with head and neck cancer and 437 controls was investigated for genetic polymorphisms in 9 different phase I and II biotransformation enzymes. Analysis of the risk-modifying effect was performed according to predicted enzyme activities, based on genetic polymorphisms in the corresponding genes.

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls.

Genetic polymorphism in the conjugating enzyme UGT1A1 and the risk of head and neck cancer.

UDP-glucuronosyltransferase 1A1 (UGT1A1) is an enzyme which catalyses not only the glucuronidation of tobacco smoke carcinogens like benzopyrene, but also of the endogenous substrate bilirubin. Bilirubin for a long time was considered to be only a toxic waste product of hemoglobin degradation, but recent findings have shown that bilirubin is a potent antioxidant, which may play a protective role against cancer. We investigated whether a genetic polymorphism in UGT1A1 (UGT1A1*28), associated with a reduced UGT1A1 enzyme activity, may have a risk-modifying effect on head and neck carcinogenesis.

A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.

Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET.

Purpose: (18)F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves.

Shared care for hearing complaints: guideline effects on patient flow.

Rationale, Aims And Objectives: A national guideline was proposed to enable shared care in hearing complaints and therefore to change patient flows. In this study the effect of this guideline is evaluated.

Methods: From a total of 3500 patients with hearing complaints, consulting the Ear Nose and Throat Department of a large non-university hospital in the Netherlands in 2002, a random sample of 1000 patients was selected.

p16 INK4A overexpression is frequently detected in tumour-free tonsil tissue without association with HPV.

Aims: Oncogenic human papillomavirus (HPV) type 16 has been strongly associated with tonsillar squamous cell carcinoma (TSCC) and appears to be of prognostic significance. Because HPV+ TSCC also accumulates p16(INK4A), this cyclin-dependent kinase inhibitor has been proposed as a potential biomarker for HPV in clinical diagnosis. The aim of this study was to determine the prevalence of HPV in tumour-free tonsillar tissue and the value of p16(INK4A) overexpression in predicting its presence.

Genetic polymorphisms in the tobacco smoke carcinogens detoxifying enzyme UGT1A7 and the risk of head and neck cancer.

Background: UGT1A7 is an enzyme involved in the metabolism of (pre)carcinogens present in tobacco smoke. We investigated whether genetic polymorphisms in UGT1A7, with predicted altered enzyme activity, may have a risk-modifying effect on head and neck carcinogenesis.

Methods: Blood samples from 427 patients with oral, pharyngeal, and laryngeal carcinoma and 420 healthy control subjects were investigated for UGT1A7 polymorphisms.

Genetic polymorphisms of smoking-related carcinogen detoxifying enzymes and head and neck cancer susceptibility.

Smoking and the consumption of alcohol are the main risk factors for head and neck cancer. However, interindividual variation in the activity of enzymes involved in the detoxification of tobacco smoke (pro)carcinogens, such as microsomal epoxide hydrolase (mEH), glutathione-S-transferases (GSTs) and uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGTs), may influence the process of carcinogenesis. Genetic polymorphisms of these enzymes may alter their activity and may thus modulate the risk for squamous cell carcinomas of the head and neck (SCCHN).

P21 Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis.

Human papillomavirus is involved in the carcinogenesis of tonsillar squamous cell carcinomas. Here, we investigated the expression and the prognostic value of key cell cycle proteins in the pRb and p53 pathways in both human papillomavirus type 16-positive and -negative tonsillar squamous cell carcinomas. Using immunohistochemistry, 77 tonsillar squamous cell carcinomas with known human papillomavirus type 16 status and clinical outcome were analyzed for expression of Ki67, p16(INK4A,) cyclin D1, pRb, p14(ARF), MDM2, p53, p21(Cip1/WAF1), and p27(KIP1).

COX-2 polymorphisms and the risk for head and neck cancer in white patients.

Background: Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether functional genetic polymorphisms in COX-2 may have a risk-modifying effect on head and neck carcinogenesis.

Methods: Blood from 431 white patients with oral, pharyngeal, or laryngeal carcinoma and 438 white healthy controls was investigated for the presence of 2 functional promoter region polymorphisms (-1195A-->G and -765G-->C) in COX-2.

Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications.

Purpose: Patients with human papillomavirus (HPV)-containing oropharyngeal squamous cell carcinomas (OSCC) have a better prognosis than patients with HPV-negative OSCC. This may be attributed to different genetic pathways promoting cancer.

Experimental Design: We used comparative genomic hybridization to identify critical genetic changes in 60 selected OSCC, 28 of which were associated with HPV-16 as determined by HPV-specific PCR and fluorescence in situ hybridization analysis and positive p16(INK4A) immunostaining.

Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review.

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.

Microsomal epoxide hydrolase genotypes and the risk for head and neck cancer.

Background: Microsomal epoxide hydrolase (mEH) is an enzyme involved in the metabolism of (pre)carcinogens in tobacco smoke. We investigated whether functional genetic polymorphisms in mEH may have a risk-modifying effect on head and neck carcinogenesis.

Methods: Blood from 429 patients with oral, pharyngeal, and laryngeal carcinoma and 419 healthy subjects was investigated for mEH polymorphisms.

The effects of neuromuscular electrical stimulation for dysphagia in opercular syndrome: a case study.

A 76-year-old man with opercular syndrome characterized by complete bilateral loss of voluntary control of facial, lingual, pharyngeal and masticatory muscles is presented with focus on the severe dysphagia. Three years earlier the patient had experienced two strokes resulting in opercular syndrome with severe dysphagia. Despite initial logopedic dysphagia treatment, swallowing did not improve.

Stapedius muscle fibre characterization in the noise exposed and auditory deprived rat.

In skeletal muscle, interventions that unload the muscle cause slow-to-fast myosin heavy chain (MHC) conversions, whereas fast-to-slow conversions are seen when the muscles are engaged in resistance training and endurance exercise. The stapedius muscle (SM) is reported to prevent cochlear damage by noise. This theory may be supported by showing comparable changes of muscle fibre composition when ears are exposed to longstanding noise (SM training).

Rejection of injectable silicone "Bioplastique" used for vocal fold augmentation.

A rare case of repeated granulomatous inflammation after silicone injection laryngoplasty for vocal fold immobility as well as its treatment by endoscopic approach is reported. The patient presented a right-sided vocal fold immobility after laryngeal trauma and remained dysphonic despite of logopedic voice therapy because of severe glottal insufficiency. An endoscopic transoral intrafold silicone injection was applied to improve the vocal function.

Paraneoplastic syndromes in patients with primary head and neck cancer.

Paraneoplastic syndromes represent the clinical manifestations of the indirect and remote effects produced by tumor metabolites or other products. The clinical spectrum of the various paraneoplastic syndromes related to primary malignancies of the head and neck region is presented. A review of the literature on paraneoplastic syndromes in patients with primary head and neck cancer was carried out.

Predictive value of lymph node metastases and extracapsular extension for the risk of distant metastases in laryngeal carcinoma.

Objective: The objective of this retrospective chart analysis was to determine the prognostic value of the lymph node status and extracapsular lymph node extension (ECE) of the neck for the development of distant metastases in squamous cell carcinoma of the larynx.

Methods: One hundred sixty-five patients treated for laryngeal carcinoma with a neck dissection with histologic evaluation were included. Primary study end point was distant metastasis-free survival.

Stapedius muscle fiber characterization during postnatal development in the rat.

The stapedius muscle (SM) is reported to prevent cochlear damage by noise. Functional demands are then the ability of fast contraction with long endurance. At the end of the third postnatal week, the middle ear of the rat is completely pneumatized and according to electrophysiological data, the auditory function starts to match the adult.

Lipoma of the deep lobe of the parotid gland: report of 3 cases.

Since lipomas are common soft-tissue neoplasms in other regions of the body, they are found only rarely in the parotid gland and are, therefore, often not considered in the initial differential diagnosis of parotid gland tumours. Even rarer are lipomas arising in the deep lobe of the parotid gland with only 6 cases presented in the literature. Lipomas originating in the parapharyngeal space are also extremely rare.

Compliance and efficiency before and after implementation of a clinical practice guideline for laryngeal carcinomas.

We evaluated whether the implementation of a nationwide clinical practice guideline for diagnosis, treatment and follow-up of laryngeal carcinomas led to changes in hospital costs, balanced against clinical changes observed following the guideline's implementation. Charts of 822 patients with larynx carcinoma (459 treated before the introduction of the guideline and 363 thereafter) in five hospitals were retrospectively investigated. In all phases, no differences in total hospital costs were observed after the guideline's implementation.