[Impact of Microsurgical Exstirpation of Vestibular Schwannomas on the Sense of Taste]. / Effekt der mikrochirurgischen Entfernung von Vestibularisschwannomen auf das Schmeckvermögen.

Patients with single sided vestibular schwannoma may report about a taste dysfunction apart from the well known cardinal symptoms. Very few data are published so far on that topic. The aim of this study was to investigate the influence of microsurgery for vestibular schwannomas on taste perception prospectively using a well validated taste test. 25 patients could be included in the study. No ageusia was claimed by the patients. In average a decrease of the taste score postoperatively could be detected on the tumor as well as on the non treated side. The differences were not statistically significant. But a subgroup of » of the subjects revealed a new onset of side difference in the taste score that was not present before surgery. In all those cases the treated side showed a clinically significant reduced taste score of 6,2 in average. Within this subgroup the temporal access was overpresented in contrast to the whole group. This may indicate an influence of the choosen approach and that for the position of the tumor to the change of the taste score. The observations should be verified on a greater collective.

Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease.

BACKGROUND: Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. METHODS: After sinus surgery, 70 individuals with AERD were randomly allocated to a prospective double-blind placebo-controlled aspirin desensitization protocol with a maintenance dose of 100 mg daily. The primary outcome was polyp relapse after 36 months. Nasal endoscopy status, quality of life, and patients' symptom score as well as aspirin-related side-effects were monitored. RESULTS: Due to the high dropout rate, only 31 individuals were evaluated. After 36 months, nasal polyp relapse was less frequent (P = 0.0785) and the polyposis score was lower (P = 0.0702) in the therapy group. Quality of life obviously improved (P = 0.0324), clinical complaints (P = 0.0083) were significantly reduced, and no severe aspirin-related side-effects were observed. CONCLUSION: Aspirin desensitization with a maintenance dose of 100 mg daily has a positive impact on nasal polyp relapse and seems to be a safe and suitable therapy to improve clinical complaints and the quality of life of individuals with AERD.

17ß-Estradiol reduces nitric oxide production in the Guinea pig cochlea.

Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17ß-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17ß-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17ß-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17ß-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17ß-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection.

Lack of neurofibromatosis type 2 gene promoter methylation in sporadic vestibular schwannomas.

BACKGROUND: Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). In VS, losses of chromosomal material and mutations of the NF2 gene have been established to be causative. For a subset of VS without detectable gene alterations, promoter inactivation by hypermethylation has been suggested. However, published data are very limited and contradictory. METHODS: We analyzed NF2 gene promoter methylation in 35 sporadic VS by methylation-specific PCR. RESULTS: Twenty-three of the tumors were informative, showing no promoter methylation. In the remaining 12 tumors, promoter methylation could neither be verified nor excluded. CONCLUSIONS: Our study suggests that NF2 gene inactivation by promoter hypermethylation is a rare or very uncommon mechanism of NF2 gene inactivation in sporadic VS. Other mechanisms destabilizing the NF2 gene product, yet to be identified, might play a role in the genesis of VS apart from the loss or mutation of the NF2 gene.

The VEGF/VEGF-R axis in sporadic vestibular schwannomas correlates with irradiation and disease recurrence.

BACKGROUND/AIMS: The molecular mechanisms downstream of mutated neurofibromatosis type 2 (NF2) gene resulting in the growth and development of vestibular schwannoma (VS) are controversial. Several lines of evidence suggest the involvement of the vascular endothelial growth factor (VEGF) pathway in VS development. Given that recent studies of VEGF blockade in patients with NF2-associated VS showed positive effects on VS growth control, we initiated this comprehensive study of the VEGF pathway in sporadic VS. METHODS: A tissue microarray analysis of 182 sporadic VS was conducted. The expression of VEGF and its receptors as well as the proliferative activity of the tumors were quantified. The expression data were correlated to tumor volumes and diameters as well as to tumor recurrence and previous irradiation. RESULTS: All studied tumors expressed VEGF and its receptors. Proliferative activity was related to the growth characteristics of the tumors. Moreover, we found significantly higher VEGF levels in recurrent tumors (p = 0.0387) and in preoperatively irradiated tumors (p = 0.0213). CONCLUSION: Our data suggest a relevant role of the VEGF pathway in VS growth and therapy outcome. Therefore, targeting this pathway using antiangiogenic compounds might be beneficial for patients with sporadic VS, especially those with recurrent or irradiated tumors.

[Subglottic tracheal stenosis]. / Subglottische Trachealstenosen.

OBJECTIVES: To assess the results of endoscopic CO(2) laser resections combined with mitomycin-C and/or triamcinolone acetonide therapy in the treatment of patients with symptomatic subglottic tracheal stenosis. MATERIALS AND METHODS: Eleven patients (all female) with subglottic tracheal stenosis were divided into two groups: six patients with idiopathic subglottic tracheal stenosis and five with subglottic tracheal stenosis of known etiology (four with Wegener's disease and one with polychondritis of the trachea). Three patients showed signs of reflux. The primary outcome measure was improvement of the clinical symptoms and the secondary the postoperative reduction of airway resistance. RESULTS: All patients were treated with CO(2) laser resections combined with mitomycin-C and/or triamcinolone acetonide therapy. Postoperative examinations during a period of 7 to 72 months demonstrated a reduction of symptoms and of airway resistance in all patients. CONCLUSIONS: One or more endoscopic CO(2) laser resections combined with mitomycin-C and/or triamcinolone acetonide therapy are effective in the treatment of subglottic tracheal stenoses. Long-term oral steroid and immunosuppressive therapy as well as the use of proton pump inhibitors positively influences the postoperative outcome.

[Deficits in medical counseling in olfactory dysfunction]. / Defizite der ärztlichen Beratung bei Riechstörungen.

Olfactory dysfunctions are common with a prevalence of up to 20% in the population. An impaired sense of smell can lead to specific dangers, therefore, counseling and warning of hazardous situations to raise patient awareness is an important medical function. In this study 105 patients presenting to the University of Mainz Medical Centre with dysosmia were evaluated using a questionnaire. For quantification of the olfactory dysfunction a standardized olfactory test (Sniffin' Sticks) was used. Of the patients 46% were hyposmic and 40% were functionally anosmic. The median duration of the olfactory impairment was 10 months and the main causes of dysosmia were upper respiratory tract infections and idiopathic disorders. More than 90% of the patients consulted an otorhinolaryngologist and 60% a general practitioner before presenting to the University of Mainz Medical Center. More than two thirds of the patients conducted a professional activity, 95% of patients reported that they had not received any medical counseling and 6% of the subjects were forced to discontinue their profession because of olfactory dysfunction. In patients with olfactory dysfunctions appropriate diagnostics, including olfactometry should be performed. Furthermore, correct medical counseling concerning necessary additional arrangements (e.g. installation of smoke or gas detectors, precautions while cooking or for hygiene) has to be performed. For patients in a profession an analysis of the hazards at work is crucial.

Genomic changes in salivary gland pleomorphic adenomas detected by comparative genomic hybridization.

The aim of this study was to investigate whether so far unknown chromosomal alterations in pleomorphic adenoma (PA) exist. To this end, tissue samples from 18 patients with parotid gland PA were studied by comparative genomic hybridization (CGH) using Phi-29-DNA-polymerase for DNA amplification. The most common aberrations were losses of chromosomal material of 19p (6/18), 9q, 16p, and 19q (in 3 out of 18 patients each). Additional losses were observed on 4p, 5q, and 17q (2 / 18 each). Gains involved chromosomes 2p, 4p, 6p, 17q, and 21q (2 / 18 each). Losses of 19p have been associated with inactivation of tumor-suppressor genes in carcinomas previously. As a result, pleomorphic adenomas show a considerable diversity of chromosomal gains and losses detected by CGH. The 19p arm, and particularly its 19p13 region, need be further studied to elucidate the potential impact of associated lost tumor suppressor genes on PA development.

No evidence for a correlation of glutathione S-tranferase polymorphisms and chronic rhinosinusitis.

OBJECTIVE: Cellular detoxification mechanisms are mandatory for cellular protection against oxidative stress and reactive oxygen species. One major group of antioxidative active enzymes involved in cellular detoxification are the Glutathione S-Transferases (GST). Multiple subtypes like GSTM1, GSTP1, and GSTT1 and variants of them are known, arising from allelic variations of the GST loci. Moreover, functional variants occur in high percentages and have been associated with diseases like bronchial asthma and bronchial hyperresponsiveness. The interplay of oxidative stress, detoxifying genes like GSTs and the genesis of respiratory tract illness is under contradictory debate. In this study, we analysed the potential association of GST-polymorphisms and chronic rhinosinusitis (CRS). METHODS: In total 170 nasal tissue samples, 49 tissue samples from patients with CRS without nasal polyps, 69 tissue samples from CRS with nasal polyps and 52 healthy tissue controls of the inferior turbinate were analysed for their individual GST-status. Genotypes for GSTM1 (null versus present), GSTT1 (null versus present), and GSTP1 (Ile105Val) were determined by Polymerase Chain Reaction. The respective genotypes were correlated to the incidence of CRS with and without nasal polyps in aspirin-tolerant and intolerant patients and to the individual health status concerning asthma and allergies. RESULTS: No correlation between any GST-polymorphism and CRS with and without nasal polyps or allergies or asthma or aspirin-intolerance was observed. CONCLUSION: Our results do not suggest that there is a relevant genetic predisposition considering the individual GST-status for the susceptibility of nasal respiratory epithelia leading to CRS.

Evaluation of the efficacy of the 'nasal airflow-inducing manoeuvre' for smell rehabilitation in laryngectomees by means of the Sniffin' Sticks test.

OBJECTIVE: To determine the efficacy of the nasal airflow-inducing manoeuvre (NAIM) as a method for olfactory rehabilitation in laryngectomees by the means of the Sniffin' Sticks test. STUDY DESIGN: Prospective open interventional trial. SETTING: Tertiary academic hospital. PARTICIPANTS: Thirty-seven patients after laryngectomy have been screened and 25 patients have been included into the study. The participant's sense of smell was tested with the Sniffin' Sticks test before and after learning the nasal airflow inducing manoeuvre. The individual level of threshold, discrimination and identification (TDI) was determined and the individual threshold, discrimination and identification score was used to classify the patients as being anosmic, hyposmic or normosmic. MAIN OUTCOME MEASURES: The primary endpoint was the change of the threshold, discrimination and identification score before and after learning the nasal airflow inducing manoeuvre. The secondary endpoint was a change in the diagnostic group (normosmic, hyposmic and anosmic) after learning of the nasal airflow inducing manoeuvre. RESULTS: There was a statistically significant increase in the total threshold, discrimination and identification score (P < 0.001) and the three sub-scores (P ≤ 0.02) before and after the learning of the nasal airflow inducing manoeuvre. Patients gained seven points on average in the threshold, discrimination and identification score. Twenty of 25 patients showed an increase of five or more point in the threshold, discrimination and identification score. In the classification of the smell ability, 15 of 25 patients showed a change to a higher class (hyposmic to normosmic or from anosmic to hyposmic or normosmic). CONCLUSION: The nasal airflow inducing manoeuvre is a method for the successful rehabilitation of the sense of smell in laryngectomees. The evaluation with the Sniffin' Sticks tests showed a clinically relevant increase of olfaction in 80% of patients. The teaching of the nasal airflow inducing manoeuvre should be included in post-laryngectomy rehabilitation programmes.

[Possible molecular mechanisms of spontaneous remission in sudden idiopathic hearing loss]. / Mögliche molekulare Mechanismen einer Spontanremission nach Hörsturz.

According to current knowledge, it must be assumed that temporary idiopathic hearing loss and its spontaneous remission are based on mechanical and/or pathological alterations in the inner ear. The causal mechanisms might be based on inter-individual variations. Induced by dose-dependent activators, temporary as well as permanent damage might occur. Sudden hearing loss may be initiated by an increase in the local nitric oxide (NO) concentration. Spontaneous remission, i.e. functional restoration, can be explained by a local decrease in the NO concentration. In this context, regulatory systems such as the gap-junction system, blood vessels or synapses might be affected. In addition, alterations in the hormone level of estrogen and mineralocorticoids, as well as cellular glutathione and vitamin levels, might lead to temporary alterations in the inner ear. Recent experimental findings indicate a role for the shuttle protein Survivin in the spontaneous remission of sudden hearing loss.

[Malignant thyroid neoplasms: a diagnostic challenge for ENT specialists]. / Das Schilddrüsenmalignom: Eine diagnostische Herausforderung für den HNO-Arzt.

BACKGROUND: Thyroid carcinoma is frequently diagnosed incidentally during routine ENT examinations. METHODS: Symptoms and clinical findings of 40 patients with thyroid malignancies presenting in our department were analysed retrospectively. The aim was to define characteristics indicative for the final diagnosis of thyroid malignancy. RESULTS: In 48% the initial presentation was not because of thyroid-specific complaints, however during the course of the general ENT examination, unspecific thyroid pathology was detected and further evaluated using sonography, scintigraphy and fine needle biopsy (FNB). The results of scintigraphy were suspicious in 67% and FNB was positive in 30%, inconclusive in 30% and false negative in 40%. For suspected malignancies a rapid frozen section examination was carried out which was positive only in 60% and false negative or inconclusive in 20% each. CONCLUSION: Thyroid lesions incidentally found during ENT examination should undergo ultrasound examination, FNB and scintigraphy with the clear understanding that there is no single diagnostic feature leading to the correct diagnosis and that only the synopsis of various findings and sometimes only final histology leads to the correct diagnosis.

[Protection of the cochlea by ascorbic acid in noise trauma]. / Protektion der Kochlea durch Vitamin C bei Lärmexposition.

BACKGROUND: The protective effect of ascorbic acid against noise-induced hearing loss and increased nitric oxide (NO) formation after noise exposure have already been demonstrated in animal models. However, the influence of ascorbic acid on noise-induced NO production within the cochlea is still unclear. METHODS: Guinea pigs (n=48) were fed for 7 days with low [25 mg/kg bodyweight (bw)/day] and high (525 mg/kg bw/day) doses of ascorbic acid. Then half of the animals were exposed to noise (90 dB for 1 h). The hearing levels were recorded beforehand, on the 3rd and 7th days after feeding, and directly after noise exposure. Finally, the organ of Corti and the lateral wall were removed from the inner ear and incubated separately for 6 h in culture medium, and the nitrite content was determined in the supernatant. RESULTS: Compared with low-dose feeding, feeding of high doses of ascorbic acid resulted in a reduction of hearing impairment of about 8 dB after noise exposure. A correlation between hearing improvement and decreased NO production was detectable for both cochlea regions but was more pronounced in the lateral wall. CONCLUSION: A high dose of ascorbic acid lowers NO production in the inner ear, reduces hearing loss, and protects the cochlea from nitroactive stress.

Multifocal adult rhabdomyoma of the head and neck: a case report and literature review.

Adult rhabdomyoma is a rare, usually solitary, primary tumour of striated muscle origin that almost exclusively presents in the head and neck region with predilection for male. We herein present a rare case of a multifocal adult rhabdomyoma in a 72-year-old woman. The lesions were located, the first one in the area of the left aryepiglottic fold and the second one right cervical arising from oesophagus. The diagnosis of the cervical mass was obtained prior to resection through cytological examination (FNAC). We discuss the clinical, cytological and histological findings and we provide a brief review of the literature on this entity.

Proangiogenic effects of ionizing irradiation on squamous cell carcinoma of the hypopharynx.

OBJECTIVE: There is experimental evidence that ionizing irradiation affects a proangiogenic response. However, the relevance of this effect on tumour growth in vivo is not in detail investigated yet. The present objectives were to examine the influence of ionizing radiation on the expression of the vascular endothelial growth factor (VEGF) and its receptors (flt-1 and flk-1), the microvessel density and the tumour proliferation, in head and neck squamous cell carcinoma (HNSCC). METHODS: We used a HNSCC-cell line, derived from a hypopharyngeal tumour, for subcutaneous injection in 16 athymic nude mice. After reaching an average diameter of 12-14 mm the xenografts were randomised and 8 out of the 16 animals (therapy group) were irradiated with a single fraction of 6 Gy while the control group remained without any intervention. The irradiated and the respective control tumours were prepared after 7 (T7) and 70 days (T70) for immunohistochemical analysis. The expression of VEGF, its receptors flk-1 and flt-1, the vessel density (CD31) and the proliferation rate (Ki67) were quantified. RESULTS: At the point of time T7 we observed a reduction of the tumour growth rate, of the proliferative activity and of the VEGF- as well as of the VEGF-R-expression. At the point of time T70 we found increased values for proliferation, microvessel density, VEGF- and flk-1 expression in the therapy group compared to the therapy group at T7 as well as to the control group at T70. CONCLUSION: These changes might suggest a long-term proangiogenic effect of irradiation, which might result in growth promotion of the remaining tumour after the end of therapy.

[No correlation between reflux of gastric contents and obstructive sleep apnea]. / Besteht ein Zusammenhang zwischen der Refluxerkrankung und dem obstruktiven Schlafapnoesyndrom?

Reflux of gastric contents can be associated with many ENT disorders. Some authors describe an association with obstructive sleep apnea, but it is not clear whether the reflux causes the apnea or vice versa. Furthermore, authors did not distinguish between gastroesophageal reflux and extraesophageal reflux, which is essential to understand a connection with obstructive sleep apnea. Therefore, we performed polysomnography and two-channel pH testing simultaneously in patients with obstructive sleep apnea syndrome (OSAS) and compared the findings with data of healthy volunteers. After exclusion of a changed sleep architecture due to the pH testing system, the results show that patients with OSAS do not suffer more often from reflux than healthy volunteers. This is true for gastroesophageal as well as for extraesophageal reflux. Furthermore, an increasing number of reflux events during the night is not correlated with the number of apnea events. Thus, in summary our data cannot support the postulation that there is a connection between obstructive sleep apnea syndrome and reflux disease.

[Determination of normal values of extraesophageal reflux in 24-h two-channel pH testing]. / Normalwertbestimmung des extraösophagealen Reflux (EER) in der 24-h-2-Kanal-pH-Metrie.

Extraesophageal reflux (EER) causes multiple diseases of the upper aerodigestive tract. EER is diagnosed by two-channel pH testing. However, little data exist about normal values. Therefore, we performed ambulatory two-channel pH testing in healthy volunteers and determined normal values for the number of reflux episodes, fraction, and reflux area index. These values were determined for pH 14.72 were excluded from the evaluation. In the other patients, the mean number of reflux episodes was 2.6+/-0.9 (95(th) percentile 4.4), the fraction of pH

Incidence of childhood cancer of the head and neck in Germany.

BACKGROUND: Only very limited data are available in the literature on the incidence of childhood cancer of the head and neck worldwide. METHODS: Based on data obtained from the national German Childhood Cancer Registry, a total of 370 malignancies of the head and neck in children under the age of 15 (199 boys and 171 girls), which were reported to this institution between 1994 and 2003, were analysed in this study. RESULTS: The overall incidence of malignancies of specific sites of the head and neck in Germany is 4.48 per 100000 children. The most frequently observed entities, representing primary tumours, are soft tissue sarcomas (0.39/100000), lymphomas (0.09/100000) and thyroid carcinoma (0.07/100000). The most commonly affected organs are the thyroid (1.21/100000), orbita (0.91/100000), nasopharynx (0.66/100000), tonsils (0.43/100000) and paranasal sinuses (0.14/100000). Overall, boys are more frequently affected than girls; however, incidence increases in girls with age and exceeds that of boys in the age group between 10 and 14 years. CONCLUSIONS: This is a first statistical evaluation detailing cumulative incidences of various histologic types of malignancies of the head and neck including age and gender distribution as well as organ-specific localization in children below the age of 15 in Germany.

[Extraesophageal reflux in patients suffering from Zenker's diverticulum]. / Extraösophagealer Reflux und Zenker-Divertikel.

INTRODUCTION: Patients with Zenker's diverticulum often present with a hiatal hernia. Theoretically, the gastric acid fluid could rise up to the hypopharynx producing an injury to the mucosa of Killian's triangle and hypertrophy of the cricopharyngeal muscle. We performed dual-channel pH monitoring in healthy people as a control group and in patients with a Zenker's diverticulum to elucidate the relationship between Zenker's diverticulum and gastroesophageal reflux disease (GERD) as well as extraesophageal reflux (EER). METHODS: Patients with Zenker's diverticulum underwent dual-channel 24-h pH monitoring to exclude the possibility of an EER or a GERD. The measurements were performed in 4 patients preoperatively and postoperatively as well as in 14 patients only postoperatively. The control group consisted of healthy volunteers who did not suffer from a reflux disease (n=20). In each group we determined the number of refluxes, the fraction time, the RAI (reflux area index), and the DeMeester Score Index. In addition we classified the severity of the EER with a grading system which was developed in an earlier study in our department. RESULTS: Patients with a Zenker's diverticulum suffered significantly from EER (p<0.01). The difference between the patients measured preoperatively and the patients postoperatively was minor. More than 72% of the patients suffered from a severe EER. CONCLUSIONS: Patients with a Zenker's diverticulum have a high possibility of suffering from EER and GERD. The pathophysiology of this relationship can only be speculated. In addition to a cricopharyngeal myotomy, long-term therapy with a PPI (proton pump inhibitor) seems indicated.

[Practicability of a surgical multilevel therapy in patients with obstructive sleep apnea]. / Anwendung eines chirurgischen Multi-Level-Konzepts bei obstruktiver Schlafapnoe.

BACKGROUND: Obstructive sleep apnea syndrome is a "systemic disease" of the upper airways and the upper digestive tract. The concept of multilevel surgery takes account of the fact that the location of the obstruction frequently cannot be identified precisely. PATIENTS AND METHODS: In this retrospective study over 4 years, data on 25 patients (median age 49.9 years) with moderate to severe OSAS treated with a surgical multilevel therapy were statistically evaluated. The treatment carried out consisted in reduction of the inferior turbinate, if necessary combined with septum plasty, and conventional uvulopalatopharyngoplasty (UPPP), combined with tonsillectomy and radiofrequency therapy of the base of the tongue if appropriate. Pre- and postoperative clinical and polysomnographical checks were performed. RESULTS: The mean apnea-hypopnea index (AHI) was 39.2+/-19.7/h before surgery. Postoperatively a highly significant reduction of AHI to 16.5+/-9.9/h (p<0.0001) was seen. In 13 out of 25 patients (52%) the disease was cured (AHI<20 and 50% reduction). In 23 patients the AHI improved. In 15 patients AHI was reduced by more than 50%. CONCLUSION: Multilevel surgery should be considered as an alternative for patients suffering from OSAS, especially in view of the poor long-term results in patients who receive CPAP therapy or are intolerant to CPAP.