Morphology studies of the human fetal cochlea in turner syndrome.

OBJECTIVES: Turner syndrome (TS) is the most frequent sex chromosome abnormality, and sensorineural hearing loss is common. We aimed to determine whether there are consistent morphologic cochlear abnormalities during gestational development that could be associated with TS. DESIGN: The histology of nine fetal temporal bones of TS autopsied after spontaneous abortion was studied. RESULTS: Gross morphologic examination of the TS cochleae failed to reveal a pattern of structural abnormalities that would explain the development of sensorineural hearing loss. Mondini-like cochlear dysplasia was observed in one 13-wk-old TS fetus. CONCLUSION: We could not demonstrate a consistent pattern of cochlear malformations.

Impact of tonsillectomy on quality of life in adults with chronic tonsillitis.

OBJECTIVES: Tonsillectomy is one of the most frequently performed surgical procedures. Nevertheless there is less known about the impact of this procedure on Health-Related Quality of life (HRQOL). The two different most common used surgical techniques are "cold" (CT) and "hot" (HT) tonsillectomy. The aim of this study was to measure patients' HRQOL-benefit after adult tonsillectomy with the indication of chronic tonsillitis and to compare HT and CT. METHODS: The Glasgow Benefit Inventory (GBI) was used to quantify the health benefit of CT and HT retrospectively in 600 patients aged 16 years and older. RESULTS: 227 of the patients returned the completed surveys. Mean total GBI score was 15.8 (18 SD, 13.2-18.4 CI) for CT and 11.6 (15 SD, 7-16.3 CI) for HT (p = 0.214). Patients reported an improvement in HRQOL in all GBI subscales. We could not find a significant difference in reported HRQOL benefit between HT and CT. CONCLUSION: Adult tonsillectomy, HT as well as CT, for the indication of chronic tonsillitis provides an improvement in HRQOL. This positive impact of tonsillectomy in patients with chronic tonsillitis should be considered in the clinical decision-making process for tonsillectomy.

Validation of the German Glasgow children's benefit inventory.

OBJECTIVE: The aim of this study was to validate the German Glasgow Children's Benefit Inventory (GCBI) in children with different surgical interventions. MATERIAL AND METHODS: The GCBI was translated by using accepted forward-backward translation techniques and mailed to 741 parents whose children underwent either an otorhinolaryngological (n = 641) or an urological intervention (n = 100). The assessment was performed in a retrospective manner at the Medical University Innsbruck, Austria between January and March 2006. An exploratory principal component factor analysis with varimax rotation using factor loadings of >or=0.40 to allocate items to a scale was performed. Frequencies, means and standard deviations were used to describe patient, clinical, sociodemographic, and scale characteristics. RESULTS: The questionnaire was completed and returned by 325 patients (43.9%). The GCBI showed a high internal consistency (alpha = 0.84). The four-factor solution, emotional, vitality, learning and physical health explained 55.7% of variance. CONCLUSION: The German version of the GCBI was proven to be valid and reliable. It is suitable for subjective outcome analysis of different paediatric interventions from infants to adolescents.

Modified radical neck dissection and minimal invasive tumor surgery in the middle of split course of concomitant chemoradiotherapy of advanced HNSCC.

OBJECTIVE: The effectiveness of modified radical neck dissection with concomitant chemoradiotherapy in patients with N2/3 advanced head and neck cancer was evaluated. STUDY DESIGN AND SETTING: Retrospective study of 35 patients treated at the University Hospital, Medical University, Innsbruck. The treatment consisted of a split course radiation up to 70 Gy with concomitant chemotherapy with Mytomicin C and 5-fluorouracil. Neck dissection and/or tumor resection was performed between the two cycles of radiation and chemotherapy. RESULTS: The 2-year progression-free survival was 64%, locoregional control 92% and overall survival 55. Observed toxicities included mucositis (grade 3, 35%; grade 4, 16%), neutropenia (grade 4, 28%), and thrombocytopenia (grade 4, 26%). No complications related to modified radical neck dissection were observed. CONCLUSION: Intermittent neck dissection was highly effective in controlling the neck disease. Mitomycin C-based chemoradiotherapy for treatment of locally advanced cancer seems to be an option to cisplatin-based regimens.

Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma.

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity to tyrosine kinase inhibitors (TKIs) and are present in 10-30% of non-small cell lung carcinoma depending on ethnic origin. EGFR protein is also overexpressed in about 90% of squamous cell carcinoma of head and neck (HNSCC), and treatment with TKIs has shown clinical benefit in a subgroup of these patients. Recently, EGFR mutations were described in three Asian patients with larynx cancer. We screened for EGFR tyrosine kinase mutations in tumour DNA of 100 patients of Caucasian origin with HNSCC by direct sequencing of the hotspot regions. Only one patient with larynx cancer displayed a novel, somatic EGFR missense mutation, K745R, affecting a highly conserved residue within the ATP cleft. Similar to reports in lung cancer, EGFR kinase domain mutations in HNSCC patients seem to show a lower incidence in patients of Caucasian origin.

Distant metastasis of parotid gland tumors.

The incidence of distant metastasis in head and neck cancer and especially in salivary gland cancer is relatively low in comparison to other malignancies. However, the presence of distant metastasis heralds a poor prognosis in head and neck cancer, with a median survival of 4.3-7.3 months. Treatment of these patients is usually performed in a palliative setting. Patients with malignant salivary gland tumors should have an X-ray or CT scan of the chest at their initial assessment to exclude the possibility of distant metastasis. The likelihood of developing distant metastasis is associated with high-grade tumors, such as adenoid cystic carcinoma, salivary duct carcinoma, high-grade mucoepidermoid carcinoma and tumors located in the submandibular gland, posterior tongue and pharyngeal tumors. A lower risk of developing distant metastasis is known for all other histological entities of salivary gland tumors. Nevertheless all patients who have a histologically confirmed malignant salivary gland tumor should have lifelong follow-up. On the basis of a clinical case regarding a patient with metastatic parotid gland cancer we present a review of the literature.

Does nasal septal surgery improve quality of life?

CONCLUSION: In addition to functional ameliorations we have shown that septoplasty creates a long-lasting improvement in quality of life in patients with nasal septal deviation. OBJECTIVES: The goal of this study was to evaluate whether nasal septal surgery alters patients' quality of life. PATIENTS AND METHODS: This 7-year retrospective study was undertaken in an otolaryngology center. A total of 600 patients who underwent septoplasty with or without turbinectomy in the past 7 years for the indication of septal deviation, were mailed a questionnaire to assess their quality of life after surgical intervention. The questionnaire with 24 items was summarized into 7 subscales (overall medical state, nasal symptoms, accompanying symptoms, sleep, practical problems, emotions and social life). A visual analog scale was provided to measure the patients' general feelings related to their nasal disease. RESULTS: In all, 285 patients (47.5%) responded. Analysis of the questionnaire showed an improvement in all disease-specific subgroups.

Maturation of dendritic cells in the presence of living, apoptotic and necrotic tumour cells derived from squamous cell carcinoma of head and neck.

Dendritic cells (DC) have been recently used as vaccines for stimulation of tumour-specific immunity in various types of cancer. Since data about interactions of DC with tumour cells derived from head and neck cancer are not available, in our study we investigated the effects of head and neck squamous cell carcinoma (HNSCC) cell lines on the maturation of DC. We found that immature DC efficiently internalise necrotic cells, but not living and apoptotic tumour cells. Although apoptotic cells induced a partial maturation of DC, they were not able to stimulate the secretion of IL-12. In contrast, necrotic tumour cell preparations from all three HNSCC cell lines induced the mature phenotype and IL-12 production by DC. Moreover, necrotic cells synergistically augmented stimulatory effects of monocyte-conditioned medium on the maturation of DC. Thus, DC-based vaccination utilizing necrotic tumour cells as a source of tumour antigens, even in combination with inflammatory stimulus, seems to be a suitable strategy for adjuvant immunotherapy in HNSCC.

Auricular reconstruction with porous polyethylene frameworks: outcome and patient benefit in 65 children and adults.

BACKGROUND: This study evaluates outcome and patient benefit after plastic auricular reconstruction using a porous polyethylene framework and a temporoparietal fascia flap in both pediatric and adult patient collectives. METHODS: Seventy-eight patients were asked to answer validated questionnaires determining the effects of the reconstruction on the patients' health-related quality of life (Glasgow Benefit Inventory or Glasgow Children's Benefit Inventory); Glasgow Benefit Inventory and Glasgow Children's Benefit Inventory scores can range from -100 (maximal adverse effect), through 0 (no effect), to 100 (maximal positive effect). Furthermore, patients were questioned regarding satisfaction, complaints, and complications with the reconstructed ear. RESULTS: Sixty-five patients (83.3 percent) returned a valid questionnaire. In the adult collective (n = 45), the mean total Glasgow Benefit Inventory score was 21.2 (p < 0.001); 72.7 percent were satisfied with the aesthetic result, and 86.7 percent would again decide in favor of the operation. In the pediatric collective (n = 20), the mean total Glasgow Children's Benefit Inventory score was 27.7 (p < 0.001); 70.0 percent of the parents and 85.0 percent of the children were satisfied with the aesthetic result; 95.0 percent of the parents and 90.0 percent of the children would again decide in favor of the operation. The health-related quality of life was raised in 75.6 percent of the adults and 100 percent of the children. Scars and feel of the reconstructed ear were the main complaints in both collectives. Patients with acquired auricular defects were approximately two times as likely not to be satisfied with the result compared with patients with congenital defects. CONCLUSIONS: Auricular reconstruction using a porous polyethylene framework can significantly increase patients' health-related quality of life, and leads to a high rate of patient satisfaction.

Does perinatal asphyxia induce apoptosis in the inner ear?

Pre- and perinatal asphyxia is known to be an important risk factor in the development of neonatal hearing impairment. This study aims to evaluate the role of apoptosis, which is known to play an essential role in the development of the inner ear structures, in the development of neonatal hearing loss caused by pre- and perinatal asphyxia. Eight temporal bones of six different newborns were included. We performed a morphologic analysis by both light microscopy, and transmission electron microscopy, as well as immunohistochemical staining to detect the cleaved form of caspase 3 as apoptosis marker and Bcl 2 as anti-apoptotic marker. Early and late phases of apoptosis were evidenced by condensation of chromatin (electron-dense, black structure along nuclear membrane) and fragmentation of the nucleus, respectively. Changes in nuclear morphology during apoptosis correlate with cleavage by caspase 3 located downstream of Bcl 2 action. The immunohistochemistry for cleaved caspase 3 showed a particular predilection for the inner and outer hair cells, spiral ganglion cells and the marginal cells of the stria vascularis. The brain of all examined cases did not show signs of apoptosis. In summary, this investigation suggests that apoptosis takes place before brain tissue apoptosis and is probably an earlier event than thought. Apoptosis of the cochlea is known to play an essential role in the development of the inner ear. Additionally, this study shows that apoptosis may play an important role in the development of hearing impairment, caused by pre- and perinatal asphyxia.

Epidermal growth factor receptor expression in human fetal cochlea with Turner syndrome.

HYPOTHESIS: Growth hormones have beneficial effects on increasing height in adults with Turner syndrome (TS) and may also affect auditory function. BACKGROUND: Turner syndrome is the most common sex-linked chromosomal abnormality in female conceptions. Epidermal growth factor and its receptor (EGFR) affect differentiation, proliferation, and migration of epithelial cells and function as survival factors. The expression of EGFR is found in the developing and juvenile inner ear of experimental animals but is absent in adults. METHODS: To determine whether EGFR plays a role in TS, its expression was analyzed in the cochlea of healthy fetus and fetus with TS and in healthy adults. RESULTS: In healthy fetuses, EGFR protein expression was localized to the inner and outer hair cells and the Reissner membrane. The fetuses with TS on the 13th gestational week (GW) showed a similar pattern of immunoreactivity as the normal 16th and 20th GW cochlea. By the 23rd GW, EGFR immunoreactivity was not detectable in the TS hair cells or the Reissner membrane, and less intensive staining was found in the surrounding fibrocytes of the spiral ganglion. CONCLUSION: This is the first demonstration of EGFR immunoreactivity in the human cochlea and illustrates how EGFR expression is altered during development in TS. These findings indicate the importance of growth hormone receptors for inner ear development in humans.

Pelizaeus Merzbacher disease: morphological analysis of the vestibulo-cochlear system.

CONCLUSION: In agreement with previously published findings, our results demonstrate that Pelizaeus Merzbacher disease (PMD) does not affect the development and morphology of the peripheral vestibulo-cochlear system. OBJECTIVE: PMD is a consequence of X-linked mutation of the main central nervous system (CNS) myelin protein resulting in a complex neurological syndrome. Otorhinolaryngological symptoms include nystagmus and alterations of auditory-evoked brainstem responses. To date no histopathological analysis of the inner ear has been performed. MATERIALS AND METHODS: The temporal bone morphology of an affected fetus was examined with light microscopy and synchrotron radiation-based micro computed tomography. RESULTS: The regular structure of the vestibulo-cochlear system was shown in this multi-modular analysis.

The cochlea in fetuses with neural tube defects.

In this study different malformations of the cochlea could be demonstrated. Nevertheless, we could not delineate a distinct malformation of the inner ear, that can be linked to a neural tube defect. Neural tube defects are a frequent and heterogeneous group of malformations, ranging from the survivable spina bifida to fatal anencephaly. In multiple animal models an involvement of the vestibulocochlear system has been demonstrated. In this article human fetal temporal bones of neural tube defects were analysed in a multimodular work-up. The morphologic study was performed with light microscopy, transmission electron microscopy and synchrotron radiation-based microcomputed tomography. Immunohistochemistry for different neuronal markers such as peripherin, beta-III-tubulin and vimentin helped to evaluate ontogenetic tissue development. Eight fetal temporal bones with neural tube defects and five control temporal bones were included into the morphologic study. The morphologic results of the neural tube defect temporal bones showed six regularly developed cochleas and two with only a single cochlear turn. Three of the neural tube defect temporal bones were further examined with immunohistochemical analysis. No differences in the staining pattern for peripherin, beta-III-tubulin and vimentin were detected.

EGFR inhibition as a therapy for head and neck squamous cell carcinoma.

BACKGROUND: Improved understanding of disease biology of head and neck squamous cell carcinoma (HNSCC) with nearly universal expression of EGFR has led to the introduction of targeted therapies to interrupt signalling of this negative prognostic marker. OBJECTIVE: We performed a literature review on the mechanisms and efficacy of anti-EGFR antibodies and EGFR tyrosine kinase inhibitors in patients with locally advanced or recurrent/metastatic HNSCC. RESULTS/CONCLUSION: Clinical trials in HNSCC have administered EGFR directed drugs as single agents, in combination with chemotherapy or radiotherapy and demonstrated a good safety profile with antitumour activity in a subgroup of patients. The biology of responsiveness is still unclear, although there is growing evidence of an association of skin toxicity or presence of shorter EGFR intron 1 cytosine-adenine repeats with positive outcome.

Pilot study: volatile organic compounds as a diagnostic marker for head and neck tumors.

BACKGROUND: In the last decade, the analysis of volatile organic compounds (VOC) has undergone a rapid development. In this pilot study, patients with HNSCC were tested with a proton transfer reaction-mass spectrometry in order to establish a minimal invasive screening method. METHODS: Overall in a period of 2 years, 22 carcinoma patients were recruited for the study. All patients had a newly diagnosed histologically secured squamous cell carcinoma of the upper aerodigestive tract. These results were statistically compared with 3 control groups: healthy controls, high-risk, and posttherapy patients. RESULTS: Two hundred nine different masses were measured; 188 of these were evaluated. The statistical workup of the 4 study groups produced 42 different masses, which showed a statistically significant difference from the carcinoma group compared with the control groups. CONCLUSION: A screening method for HNSCC using VOC seems to be possible, but further investigation is necessary.

Identification of the rare EGFR mutation p.G796S as somatic and germline mutation in white patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are involved in tumorigenesis and response to targeted therapies in distinct cancer types. Squamous cell carcinomas of the head and neck (HNSCC) show an incidence of EGFR mutations varying from 7% in Asians to 0% to 4% in white patients. Mutational screening predominantly focuses on the analysis of hotspot regions of EGFR (exons 19 and 21). METHODS: In a follow-up study, we screened for mutations in exons 18 to 21 of the EGFR gene in 127 patients. RESULTS: In this cohort, a mutation frequency of 2.4% (3/127) was detected. In addition to the previously reported mutation p.K745R, the otherwise rare EGFR mutation p.G796S occurred in 2 patients with HNSCC (2/127). CONCLUSION: EGFR kinase mutations are rare in white patients with HNSCC. Extension of mutational screening to exon 20 may clarify the frequency and impact of the mutation p.G796S.

Resection of accessory parotid gland tumors through a peroral approach with facial nerve monitoring.

Accessory parotid glands are an anatomic variation. Pathologic alterations, which occur in these tissues, are related to those found in the parotid gland. At this time, first-line therapy consists of total resection. In consideration of the delicate anatomy in this region, a careful approach through a lateral parotidectomy or a facelift incision is recommended. In this report, we give an account of a minimally invasive surgical alternative through a peroral approach with facial nerve monitoring. The histologically secured pleomorphic adenoma was completely removed. During surgery, a branch of the facial nerve was detected and secured with active nerve monitoring. We are confident that the peroral resection, supported by active and passive facial nerve monitoring, is a discussable alternative for well-selected tumors of accessory parotid glands.

Health-related quality of life outcome of adult patients after otoplasty.

Prominent ears are relatively frequent. Decreased self-esteem, increased anxiety, behavioral problems and social avoidance may result from disfigurement. In modern medicine it is becoming increasingly important to measure the benefit of surgical intervention by its impact on the patient's Quality of Life (QOL). Our study was performed in a retrospective manner at our institution including 40 adult patients with prominent ears. The Glasgow Benefit Inventory (GBI), a reproducible, valid and responsive questionnaire, was the basis of the used inquiry for detecting the changes in HRQOL after otoplasty. We showed an improvement in GBI subscores after intervention. There was no difference in GBI subscores between men and women. The follow-up time as well as critical life event and chronic concomitant disease have no influence on the GBI results. Otoplasty has a positive impact on the HRQOL of adult patients with prominent ears. The importance of this benefit is not only of individual nature. In times of healthcare economization, an amelioration of QOL followed by increased productivity at work of the individual is an important argument to justify health care expenditures. We believe that otoplasty is an appropriate therapy for selected adult patients burdened by prominent ears.

Pharmacodiagnostic value of the HER family in head and neck squamous cell carcinoma.

Two protooncogene products, EGFR (Her-1, c-erbB-1) and HER2 (Her-2/neu, c-erbB-2), have been reported to be frequently overexpressed in head and neck squamous cell carcinoma (HNSCC). In order to identify patients who may benefit from targeted cancer treatment for these two molecules, we determined the expression status of EGFR and HER2 in 129 HNSCC tumor specimens. Two pharmacodiagnostic kits (EGFR pharmDx and HercepTest) were used to identify HNSCC tumors that overexpress EGFR or HER2. Overexpression of EGFR was detected in 42.6% of the tumor specimens, while HER2 was only rarely expressed (overexpression was observed in just 3.1% of all cases). Given the necessity of new therapeutic modalities for patients suffering from HNSCC, treatment EGFR signaling inhibitors appears to be warranted, whereas therapeutic intervention with HER2 inhibitors seems to be inappropriate in this tumor type.