Parotid Gland Tumors: A Multicenter Analysis of 1020 Cases. Increasing Incidence of Warthin's Tumor.

We assessed the frequency of the parotid gland tumor entities and correlated sex and age in different tumor types. Retrospective data were obtained from three major otorhinolaryngology clinics in Karlsruhe and Pforzheim, Germany within a 10-year period. In total, 1020 cases of parotidectomy for benign and malignant lesions were identified. We found 864 (84.7%) and 156 (15.3%) patients with benign and malignant tumors of the parotid gland, respectively. The most common benign parotid tumor was Warthin's tumor, followed by pleomorphic adenoma. The most common primary malignant tumor types were acinic cell carcinoma and mucoepidermoid carcinoma. Secondary malignant tumors of the parotid gland included lymphoma and metastatic, cutaneous squamous cell carcinoma. The frequency of Warthin's tumors was higher than that of pleomorphic adenomas. A large proportion of the malignant parotid tumors represent metastases from squamous cell carcinoma of the skin of the head and neck.

Diagnostic value of computed tomography in Eustachian tube dysfunction.

OBJECTIVE: Investigate radiological findings on temporal bone computed tomography, which are associated with obstructive Eustachian tube dysfunction and determine its diagnostic validity. METHODS: The present study was conducted as a prospective, cross-sectional case series study in a tertiary referral center. Forty patients with clinically diagnosed unilateral Eustachian tube dysfunction and older than 16 years old underwent pre interventional radiological assessment by temporal bone computed tomography while performing a Valsalva-maneuvre to enhance visualization of Eustachian tube lumen. The Eustachian tubes were assessed for intersite morphological differences, presence of mucus in the lumen or middle ear cleft and secretion retention or mucosal swelling in the adjacent sinuses. Image analyses and radiological statements about the side of pathology were delivered blinded to the clinical diagnoses. RESULTS: The radiologic detection of mucus/mucosal edema in Eustachian tube or adjacent middle ear cleft structures was associated with the pathological side (t (1, N = 40) = 3.60, p = 0.001 < 0.05). On the contrary, there is no association between radiological findings of sinonasal disease and side of Eustachian tube dysfunction (x2 (1, N = 40) = .00, p = 1.00 > 0.05). The diagnostic value of radiologic assessment in Eustachian tube dysfunction has a sensitivity and specificity of 52,5 and 97,5% respectively. CONCLUSION: The sensitivity of radiologic assessment is rather low, and hence it is inappropriate as a screening tool for Eustachian tube dysfunction in routine clinical practice. In the case of present CT-scans of the temporal bone, the focus should be laid on the detection of mucus in the Eustachian tube or adjacent structures, as a predictor of disease.

Inflammatory Pseudotumor in the Parapharyngeal Space: Is It Possible to Diagnose by Exclusion?

Inflammatory pseudotumor (IP) is a rare pathologic condition that easily can be confounded with malignancy. The clinical presentation depends on the site of occurrence and the radiological or laboratory findings are not specific. Diagnosis can be established only with histology. We report a case of a 64-year-old woman with IP in an uncommon localization, the parapharyngeal space extending to skull base. Although the diagnosis was not certain after histopathological examination, broad diagnostic workup helped to exclude malignancy or bacterial infection and led to diagnosis of an IP by exclusion. We observed a good clinical and radiological regression of symptoms after administration of oral immunosuppressants, confirming the immunological mechanism of the disease.

Morphologic measurements of 3D Eustachian tube model and their diagnostic value regarding Eustachian tube dysfunction - A cross-sectional observational study.

PURPOSE: To investigate the diagnostic value of three-dimensional morphologic measurements of the Eustachian tube on computed tomography in Eustachian tube dysfunction. METHOD: This prospective cross-sectional observational study includes forty patients with unilateral Eustachian tube dysfunction. The clinical diagnosis is verified using the Eustachian tube score - 7 and the Eustachian tube dysfunction questionnaire - 7. Computed tomography scans of the temporal bone are acquired while performing a Valsalva manoeuvre to improve the visualization of the air-filled Eustachian tube lumen. The Eustachian tubes are delineated on curved planar reconstructions, and three-dimensional models are constructed. Seven morphological parameters are measured for each Eustachian tube: the cross-sectional size of the tympanic and pharyngeal orifice; the visualization length; the inclination angles, and the curvature angles. Morphological measurements and Eustachian tube scores are correlated. RESULTS: The mean value of the visualization length of the complete Eustachian tube and in its bony segment is significantly higher in healthy sides than in pathological sides (p = 0.034 and p = 0.029, respectively). There is a significant correlation between the Eustachian tube score - 7 and the cross-sectional size of the tympanic orifice (rP = 0.361; p = 0.022). The Eustachian tube score - 7 correlates significantly with the visualization length of complete Eustachian tube (rP = 0.436; p = 0.005) and its bony segment (rS = 0.598; p < 0.0001), respectively. CONCLUSIONS: The cross-sectional size of the tympanic orifice may be a specific imaging feature indicating the obstructive Eustachian tube. However, 3D morphologic measurements of the Eustachian tube are insufficient to yield useful data about its function.

Balloon Eustachian Tuboplasty (BET) in Children: A Retrospective Multicenter Analysis.

OBJECTIVE: Generation of pilot data for planning of prospective BET-studies for treatment of dilatory Eustachian tube (ET) dysfunction in children. STUDY DESIGN: Retrospective multicenter analysis. SETTING: Nine ENT departments at tertiary care teaching hospitals. PATIENTS: 4-12-year-old children with chronic otitis media with effusion (COME) for more than 3 months or more than 3 episodes of acute otitis media during the last year, having failed standard surgical therapy at least once. INTERVENTION: BET with or without paracentesis, ventilation tube insertion, or tympanoplasty. MAIN OUTCOME MEASURES: Tympanic membrane appearance, tympanometry, and hearing threshold. RESULTS: Two hundred ninety-nine ETs of 167 children were treated. Mean age was 9.1 years (95% confidence interval [95% CI]: 8.7-9.4 yr). In 249 ears (83.3%), COME and/or retraction of the tympanic membrane were the indication for BET. Median hearing threshold was 20 dB HL (95% CI: 0-46 dB). One hundred fifty-five ears (51.8%, 95% CI: 46.1-57.4%) showed a tympanogram type B. Treatment consisted of BET without other interventions ("BET-only") in 70 children, 128 ears. Median length of follow-up for 158 (94.6%) children was 2.6 months (95% CI: 0.3-16.1 mo). After treatment, the tympanic membrane appeared normal in 196 ears (65.6%, 95% CI: 60.0-70.8%, p < 0.001). Median hearing threshold improved to 10 dB HL (95% CI: 0-45 dB, p < 0.001). Tympanograms shifted toward type A and C (type A: 39.1%, 95% CI: 33.7-44.7, p < 0.001). These improvements were also observed in subgroup analyses of "BET-only" treatment and the indication of "COME" respectively. CONCLUSION: BET is improving a variety of dilatory ET dysfunction-related ear diseases in children. This study provides detailed data for design and planning of prospective studies on BET in children.

Randomized, double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy.

OBJECTIVES: To study the safety and efficacy of continuous intratympanic dexamethasone-phosphate (Dex-P) for severe to profound sudden idiopathic sensorineural hearing (ISSHL) or sudden idiopathic anacusis after failure of systemic therapy. STUDY DESIGN: Randomized, double-blind, placebo controlled multicenter trial. METHODS: Patients with ISSHL and insufficient recovery (mean 4PTA = 97 dB HL) after systemic high dose glucocorticoid therapy received either Dex-P (4 mg/ml) or placebo (NaCl 0.9%) continuously applied for 14 days into the round window niche via a temporarily implanted catheter. For ethical reasons, intratympanic treatment was continued with Dex-P in all patients for another 14 days after the placebo-controlled study period. According to a two-step adaptive study design an interim analysis was performed after inclusion of 23 patients. RESULTS: Intention-to-treat analysis for the primary outcome criterion (4PTA: 0.5-3 kHz) during the placebo controlled study period (14 days) showed an average hearing improvement in the treatment group of 13.9 dB (SD: 21.3) and in the placebo group of 5.4 dB (SD: 10.4). This difference in hearing improvement between the two groups (mean: 8.4 dB, SD: 17.0, 95% CI: -7.1-24.1) was statistically not significant (p = .26). Of the secondary outcome parameters, the largest benefit of local salvage therapy was found for maximum speech discrimination with an improvement of 24.4% (SD: 32.0) in the treatment and 4.5% (SD: 7.6) in the placebo group (p = 0.07). After a 3 month follow-up period (i.e. after all patients received intratympanic Dex-P) hearing improvement in the two groups was very similar. No serious adverse events were observed. Sample size calculation after the interim analysis resulted in stopping of the trial. CONCLUSIONS: The tendency toward better hearing improvement in the treatment group, the rather conservative inclusion criteria, the limited placebo-controlled observation period and the absence of serious adverse events supports further investigation local inner ear drug delivery as a first or second line treatment option for ISSHL.

Outcomes research analysis of continuous intratympanic glucocorticoid delivery in patients with acute severe to profound hearing loss: basis for planning randomized controlled trials.

CONCLUSIONS: The data presented herein form the basis for conducting randomized placebo-controlled clinical trials evaluating the safety and efficacy of salvage treatment in patients with idiopathic sudden severe sensorineural hearing loss (but not anacusis) refractory to initial systemic therapy. Comparison of different application protocols and drug delivery systems will allow assessment of the value of continuous versus intermittent intratympanic glucocorticoid drug delivery. OBJECTIVES: To describe and critically evaluate the results of continuous intratympanic glucocorticoid delivery in patients with acute unilateral severe and profound sensorineural hearing loss refractory to initial systemic therapy and to compare the outcome with a historical control group. MATERIAL AND METHODS: In a retrospective chart review, treatment results were analyzed in 23 patients with acute severe and profound hearing loss and failure of systemic standard therapy who received a continuous intratympanic delivery of glucocorticoids as a salvage treatment. Audiological results were compared within the local therapy group and with the results of an historical control group who did not receive salvage treatment. The study and control groups were matched with respect to hearing loss after initial systemic treatment failure. RESULTS: The average pure-tone threshold after intratympanic salvage treatment showed a statistically significant improvement of 15 dB (95% CI 7-24 dB; p<0.001). After exclusion of patients with complete anacusis, i.e. a non-measurable hearing threshold, the local therapy group showed a significantly better improvement (mean 19 dB; 95% CI 6-32 dB) than the historical control group (mean 5 dB; 95% CI -2-11 dB; p<0.05).

Tonic mechanosensitivity of outer hair cells after loss of tip links.

Tip links - the extracellular connectors between the distal ends of adjacent stereocilia - are essential for the fast mechanical gating of hair-cell transducer channels. Transduction in the absence of tip links was investigated for outer hair cells of the adult guinea-pig cochlea by patch-clamp recordings of the whole-cell current during mechanical stimulation of the hair bundle. Loss of tip links induced by application of BAPTA led to permanently opened transducer channels, as evidenced by a constant inward current, loss of response to sinusoidal mechanical deflection of the hair bundle and block by the open-channel blocker dihydrostreptomycin (100 microM). Step deflection of the hair bundle (200-500 nm) in the inhibitory direction exponentially reduced this current to a constant value with time constant, tau(on), of the order of seconds. The current returned exponentially to the pre-stimulus level with time-constant, tau(off), also of the order of seconds. tau(on) was dependent on the inter-stimulus interval, Deltat, such that reducing this interval below about 40 s resulted in an exponentially faster response. tau(off) was independent of Deltat. Application of the calcium ionophore, ionomycin (10 microM), showed that tau(on) became independent of Deltat after saturating elevation of the intracellular Ca(2+) concentration. Flash-photolytic release of intracellular caged calcium (25-microM NP-EGTA/AM) showed that tau(on) is dependent on intracellular Ca(2+) concentration. These experiments imply an intracellular, calcium-dependent gating mechanism for hair-cell transducer channels.

The p38 SAPK pathway is required for Ha-ras induced in vitro invasion of NIH3T3 cells.

Constitutive activation of the ras oncoprotein plays a critical role in cancer invasion and metastasis. Particularly, ras-related protease expression such as the serine protease urokinase plasminogen activator (u-PA) has been implicated in mediating cancer cell invasion. Previous studies have shown that ras-mediated u-PA expression is regulated through the mitogen- (MAPK) and stress-activated protein kinase (SAPK) signal transduction pathways extracellular signal-regulated kinase (ERK) and c-Jun-activating kinase (JNK). We therefore asked the question, if ras-related cell invasion might additionally require the third MAPK/SAPK signal transduction cascade, p38. Indeed, we found that ras induces invasion based on the activation of certain p38 protein kinase isoforms, in particular, p38alpha. Moreover, ras activation through transient or stable expression of a Ha-rasEJ mutant induced the expression of u-PA. This was found to be a consequence of an increase of u-PA m-RNA, which was paralleled by only a modest activation of the u-PA promoter. In conclusion, we provide evidence for the requirement of a novel ras-p38alpha-u-PA pathway for ras-dependent cellular invasion.

[Acute otitis media and its life-threatening complications]. / Die akute Mittelohrentzündung und ihre lebensbedrohlichen Komplikationen.

Acute otitis media is a widespread disease affecting all ages. The introduction of antibiotics has led to a reduction in the incidence of complications from approx. 17% to 1%. Nevertheless, life-threatening complications still occur. The present paper describes the course and treatment of mastoiditis, petrositis and sepsis, as well as intracranial complications, i.e. meningitis, sigmoid sinus thrombosis, extradural abscess, subdural empyema, brain abscess and otitic hydrocephalus. The importance of antibiotic treatment for acute otitis media and the need to assess treatment outcomes are emphasised.

Chromosome 11 monosomy in conjunction with a mutated SDHD initiation codon in nonfamilial paraganglioma cases.

Paragangliomas of the head and neck region are a group of rare, usually benign, slow-growing tumors developing from paraganglionic chemoreceptors in most patients. Mutations in a subunit of the mitochondrial enzyme II complex (succinate dehydrogenase [SDHD]) were shown to be responsible for the formation of paragangliomas. In addition, loss of heterozygosity (LOH) on chromosome 11, mainly in 11q23 (PGL1), was observed recently. We analyzed DNA derived from tumor sections of three unrelated paraganglioma patients (one case with multiple paragangliomas, two cases with single tumors; all of them sporadic cases) for mutations in the SDHD gene by direct sequencing. Microsatellite-based LOH was performed, and events of chromosomal loss were validated by fluorescence in situ hybridization (FISH) on paraffin-embedded tumor and normal tissue by using centromeric satellite DNA. Sequence analysis revealed mutations in SDHD exon 1 in all patients, affecting the initiation codon (M1V). Another alteration was detected in exon 2 but was lacking in tumor DNA and therefore classified as polymorphism (H50R). LOH and FISH analyses demonstrated partial/total monosomy for chromosome 11 in the tumor samples tested. A common genetic mechanism appears to be the pathophysiologic basis for sporadic tumor development because the proposed two-hit model comprising both LOH and point mutation is manifest in our patients. Loss of chromosome 11 regions, including the deletion of PGL1 and PGL2 loci, may result in a more severe phenotype, as exemplified by the development of multiple tumors in one of the patients.

Mechanical transduction in outer hair cells.

The outer hair cells are responsible for the exquisite sensitivity, frequency selectivity and dynamic range of the cochlea. These cells are part of a mechanical feedback system involving the basilar membrane and tectorial membrane. Transverse displacement of the basilar membrane results in relative motion between the tectorial membrane and the reticular lamina, causing deflection of the stereocilia and modulation of the open probability of their transduction channels. The resulting current causes a change of membrane potential, which in turn produces mechanical force, that is fed back into the motion of the basilar membrane. Experiments were conducted to address mechanical transduction mechanisms in both the stereocilia and the basolateral cell membrane, as well as modes of coupling of the outer hair cell force to the organ of Corti.