[Local recurrence of iodine refractory thyroid cancers. Surgical therapy options for larynx and trachea infiltration]. / Lokalrezidive von jodrefraktären Schilddrüsenkarzinomen ­ chirurgische Therapieoption bei Infiltration des Kehlkopfs.

AIM: Local recurrence of thyroid carcinomas can result in tumor infiltration in the lower region of the larynx. Since these tumors typically no longer store iodine, treatment options are greatly limited. The present study describes our experience with laryngo-tracheal resection of such cases of local recurrence. MATERIALS AND METHODS: From July 2019 to November 2020, we treated five patients with malignant infiltration of the trachea and larynx due to local recurrence of a thyroid carcinoma. We performed laryngo-tracheal resection with end-to-end anastomosis in four patients and frontolateral partial laryngectomy in one patient. RESULTS: The median length of hospital stay was 6 days (5-14). An R0 resection was performed in two patients. Problems with the anastomosis or bilateral recurrent laryngeal nerve paralysis was not seen in any of the patients. One patient had to be reintubated on the second postoperative day due to lung failure. He was able to be extubated after five days. CONCLUSION: High tracheal resection with partial resection of the larynx was able to be performed with minimal risk. Although radical resections are rare, they expand oncological treatment options in the case of local recurrence of thyroid carcinomas that are iodine-refractory. High tracheal resection could be part of the oncological treatment spectrum in the case of local recurrence of thyroid carcinomas that no longer store iodine.

[Imaging of the Inner Ear Before Cochlear Implantation]. / Bildgebende Diagnostik des Innenohrs vor Cochleaimplantation.

If sufficient speech understanding can no longer be achieved with conventional hearing aids, the indication for a cochlear implant is very often present. Imaging plays an important preoperative role, as it is the only way to decide whether a cochlear implant is possible or not. The preoperative evaluation of the temporal bone for the precise selection of the candidates for cochlear implant is including CT (Computed Tomography) and MRI (Magnetic Resonance Imaging).

Characteristics and Spontaneous Recovery of Tinnitus Related to Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: To evaluate the characteristics and spontaneous recovery of tinnitus related to idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Retrospective analysis from two randomized placebo-controlled clinical trials for treatment of ISSNHL within 48 hours from onset (Study A), or of tinnitus related to ISSNHL within 3 months from onset (Study B). SETTING: Forty-eight European sites (academic tertiary referral centers, private ENT practices). PATIENTS: One hundred thirteen adult patients of which 65 with hearing loss ≥30 dB (Study A) and 48 with persistent acute tinnitus (Study B) at baseline. INTERVENTIONS: Intratympanic (i.t.) injection of placebo gel in single dose or in triple dose during 3 consecutive days. MAIN OUTCOME MEASURES: Frequency of tinnitus, subjective tinnitus loudness, rates of complete tinnitus remission, and complete hearing recovery during 3 months follow-up. RESULTS: In acute ISSNHL, tinnitus loudness decreased rapidly in cases of mild-moderate hearing loss, and tinnitus had completely resolved in two-thirds of patients after 3 months. Hearing recovery preceded tinnitus resolution. When associated with severe-profound hearing loss, tinnitus improved significantly less. Complete hearing recovery and full tinnitus remission were both about three times more frequent in mild-moderate hearing loss patients than in severe-profound cases. Improvement in tinnitus loudness over time can be approximated by a negative exponential function. CONCLUSIONS: Prognosis for ISSNHL-related tinnitus is relatively poor in case of severe-profound hearing loss and the longer it has persisted. Alleviation or management of tinnitus should be a key therapeutic objective especially in pronounced ISSNHL cases.

Common cavity and custom-made electrodes: speech perception and audiological performance of children with common cavity implanted with a custom-made MED-EL electrode.

OBJECTIVE: Few studies exist on children with common cavity, fewer still on their long-term audiological development after having received a cochlear implant. Our goal was to observe and report the long-term audiological progress of children with common cavity who were implanted with a custom-made electrode. METHODS: In this longitudinal, multi-center study, 19 children were implanted with a MED-EL custom-made electrode via either single slit cochleostomy or double posterior labyrinthotomy. We observed their audiological development with a test battery consisting of Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), and Ling 6-Sounds tests. We tested the children 1 month prior to the surgery; at first fitting; at 1, 3, 6, 12, and 18 months post first-fitting; at 2 years after first-fitting; and, whenever possible, at 3, 4, and 5 years after first-fitting. RESULTS: Children with common cavity tend to steadily and significantly improve their audiological skills over time. This development may, however, be highly individual; probably in part due to relatively high levels of additional needs. Parents should be counseled to establish realistic post-implantation expectations. Surgically, contrary to our expectations, we cannot confirm that double posterior labyrinthotomy reduces intracochlear electrode movement or that the MED-EL custom electrode leads to fewer incidences of intra- or post-implantation complications. CONCLUSIONS: Cochlear implantation is a safe and effective treatment option in children with common cavity. The majority of children with CC derive significant audiological benefit from implantation. Intra- and post-surgical complications, while serious, and be dealt with effectively in most cases.

Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics.

OBJECTIVES: Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. DESIGN: Prospective analysis. PATIENTS: 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype-phenotype analyses. SETTING: All analyses were performed in a large German laboratory specialised in genetic diagnostics. RESULTS: 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p.Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. CONCLUSIONS: On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype-phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum that is influenced by MITF mutation type and position.

Assessment of tinnitus-related impairments and disabilities using the German THI-12: sensitivity and stability of the scale over time.

OBJECTIVE: To evaluate the reliability, dimensionality, predictive validity, construct validity, and sensitivity to change of the THI-12 total and sub-scales as diagnostic aids to describe and quantify tinnitus-evoked reactions and evaluate treatment efficacy. DESIGN: Explorative analysis of the German tinnitus handicap inventory (THI-12) to assess potential sensitivity to tinnitus therapy in placebo-controlled randomized studies. Correlation analysis, including Cronbach's coefficient α and explorative common factor analysis (EFA), was conducted within and between assessments to demonstrate the construct validity, dimensionality, and factorial structure of the THI-12. STUDY SAMPLE: N = 618 patients suffering from subjective tinnitus who were to be screened to participate in a randomized, placebo-controlled, 16-week, longitudinal study. RESULTS: The THI-12 can reliably diagnose tinnitus-related impairments and disabilities and assess changes over time. The test-retest coefficient for neighboured visits was r > 0.69, the internal consistency of the THI-12 total score was α ≤ 0.79 and α ≤ 0.89 at subsequent visits. Predictability of THI-12 total score and overall variance increased with successive measurements. The three-factorial structure allowed for evaluation of factors that affect aspects of patients' health-related quality of life. CONCLUSIONS: The THI-12, with its three-factorial structure, is a simple, reliable, and valid instrument for the diagnosis and assessment of tinnitus and associated impairment over time.

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus.

BACKGROUND: Neramexane is a new substance that exhibits antagonistic properties at α9α10 cholinergic nicotinic receptors and N-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus. METHODS: A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12). RESULTS: Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (p = 0.098 for 50 mg/d; p = 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with p values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence. CONCLUSIONS: This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00405886.

Simvastatin and Ginkgo biloba in the treatment of subacute tinnitus: a retrospective study of 94 patients.

OBJECTIVES: Studies suggest that hypercholesterolemia promotes the development of inner ear disorders such as tinnitus. However, the underlying pathomechanisms are still not clearly defined. METHODS: A retrospective study was performed to assess whether a reduction of serum cholesterol by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may result in a relief of subacute tinnitus. Remission rates of 58 patients were investigated after 4 months of treatment with simvastatin (40 mg). Results were compared to treatment with Ginkgo biloba (120 mg; n = 36) as control group. Differences between tinnitus score at the day of first treatment and after 4 months were used as main outcome measure. RESULTS: After treatment with simvastatin or G biloba, tinnitus score decreased from 41.3 ± 10.4 to 37.4 ± 17.3 and from 44.7 ± 11.2 to 41.2 ± 8.7, respectively. However, independently of the treatment regimen, differences of tinnitus scores were considered not significant. CONCLUSIONS: After administration of simvastatin over 4 months, this retrospective study has shown no significant efficacy in treatment of subacute tinnitus. For a more conclusive answer, further prospective, double-blind, and placebo-controlled studies with a larger number of patients are needed.

Perspectives on the pathophysiology and treatment of sudden idiopathic sensorineural hearing loss.

BACKGROUND: Sudden, idiopathic sensorineural hearing loss is an acute dysfunction of the inner ear whose cause cannot be determined with the currently available methods of clinical diagnosis. METHODS: This continuous medical education article is based on a selective review of the literature and on the revised S2 guidelines for acute sensorineural hearing loss of the Association of the Scientific Medical Societies in Germany (AWMF), which were issued on 28 January 2009. RESULTS: Recent surveys in Germany suggest that the incidence of sudden, idiopathic sensorineural hearing loss may be as high as 300 per 100,000 persons per year. To distinguish this entity from acute hearing loss of other causes, special tests are necessary, including ear microscopy, pure-tone audiometry, and acoustic evoked response audiometry. No clinical trial of the highest evidence level has yet been published to document the efficacy of any type of treatment for sudden, idiopathic sensorineural hearing loss. Nonetheless, there is evidence from trials with lower levels of evidence, post-hoc analyses, and assessments of secondary endpoints of clinical trials indicating that plasma-expander therapy, the systemic and local (intratympanic) administration of cortisone, and the reduction of acutely elevated plasma fibrinogen levels may be beneficial. CONCLUSION: Further clinical trials are needed to validate these preliminary results. Until clear data are available, the predicted benefit and risk of any proposed treatment for sudden, idiopathic sensorineural hearing loss should be discussed in detail with the patient before the treatment is begun.

Effect of atorvastatin on progression of sensorineural hearing loss and tinnitus in the elderly: results of a prospective, randomized, double-blind clinical trial.

OBJECTIVE: To test whether the 3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitor atorvastatin can slow down the progression of presbycusis. PATIENTS: Fifty patients 60- to 75-years-old with presbycusis and moderately elevated serum cholesterol. INTERVENTION(S): In a double-blind design, patients were randomly assigned to treatment with either atorvastatin (40 mg/d orally) or placebo. MAIN OUTCOME MEASURE(S): Pure-tone audiometry and tinnitus evaluation at enrolment and after 7 and 13 months. RESULTS: Development of hearing thresholds after 7 and 13 months showed no significant differences between the groups. Tinnitus score continuously improved in the atorvastatin group (34.8 at 7 and 27.6 at 13 mo), whereas it slightly deteriorated in the placebo group (24.8 at 7 and 26.8 at 13 mo). The effect on tinnitus was a tendency without statistic significance (p = 0.0833). CONCLUSION: Atorvastatin had no effect on the development of hearing thresholds, but resulted in a trend toward a relief of tinnitus.

Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity.

HYPOTHESIS: In this study we tested the effect of local administration of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 on cisplatin ototoxicity in guinea pigs to the round window membrane. BACKGROUND: Cisplatin is an important antineoplastic agent in the therapy of many malignancies. Its clinical utility is limited by severe side effects, including ototoxicity. Recent studies have shown protection against cisplatin ototoxicity in animal experiments by the systemic administration of D-methionine and sodium thiosulfate. Growth factors such as brain-derived neurotrophic factor and fibroblast growth factor-2 also have shown otoprotective effects in in vitro studies. METHODS: Osmotic pumps (Alzet) were implanted unilaterally in 30 guinea pigs. Five groups of six animals received either D-methionine, sodium thiosulfate, fibroblast growth factor-2, brain-derived neurotrophic factor, or saline 0.9%. Cisplatin was administered intraperitoneally for 5 consecutive days. Distortion product otoacoustic emissions were recorded every day. The animals were killed on day 6, and their cochleae were removed and analyzed by transmission electron microscopy. RESULTS: Compared with control animals, guinea pigs treated with D-methionine showed better otoacoustic emissions on days 3 and 4 (Mann-Whitney test, p < 0.05). The differences were not evident on days 5 and 6. Sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 showed no significant protective effect. CONCLUSION: Local application to the round window membrane can be used as an effective treatment in the prevention of cisplatin toxicity. Local application may avoid systemic side effects and reduce the antineoplastic effects of cisplatin.

Prognostic implications of hemoglobin levels before and after surgery as well as before and after radiochemotherapy for head and neck tumors.

Several studies have shown that tumor cells may develop resistance to radiotherapy, proliferating under hypoxic conditions. Following surgery, patients may develop low hemoglobin levels, which may cause low oxygen conditions. This retrospective analysis was undertaken to determine the impact of low hemoglobin levels in patients with head and neck tumors treated with combined-modality therapy (surgery and postoperative radiochemotherapy). We studied 120 patients with mostly advanced head and neck tumors (88% stage III/IV) who had undergone macroscopically complete resections of their primary tumors and lymph node metastases. At 20-277 days after surgery (median: 51.3 days), these patients received postoperative chemoradiotherapy (56.7 Gy of radiation over 28-49 days and cisplatin 6 mg/m(2) body surface area on radiation treatment days with a cumulative dose of 96 mg/m(2)). Normal hemoglobin levels were considered to be 12 g/dl for females and 13 g/dl for males. Decreased hemoglobin levels before or after surgery and before or after chemoradiotherapy were correlated with the prognosis. Preoperatively, 99 of 114 patients (87%) had normal levels of hemoglobin compared with only 20 of 107 patients (19%) postoperatively. At the onset of radiochemotherapy, the hemoglobin levels of 82 of 116 patients (71%) were within the normal range. After radiochemotherapy, however, 62 of 114 patients (54%) had normal hemoglobin levels. Univariate analysis (Kaplan-Meier method and log-rank test) showed that patients with decreased pre- or postoperative hemoglobin levels had significantly worse locoregional control ( P=0.032 and P=0.0001, respectively) and lower overall survival ( P=0.0013 and P=0.0002, respectively) than patients with normal hemoglobin levels. The 3-year locoregional control rates in patients with preoperative hemoglobin levels that were normal, were reduced by 1-2 g/dl or were reduced by more than 3 g/dl, respectively, were 78%, 55% and 50%. Correlated with normal and diminished postoperative hemoglobin levels, the 3-year locoregional control rates were 90%, 84% and 50%, respectively. There was no correlation between prognosis and hemoglobin level at the onset or after radiochemotherapy. On multivariate analysis, only the postoperative hemoglobin level remained a prognostic factor for locoregional control ( P=0.0241) and overall survival ( P=0.0080). We conclude that low postoperative hemoglobin levels resulting from blood loss may influence the efficacy of postoperative radiochemotherapy in patients with head and neck cancer. Early intervention to raise the postoperative hemoglobin level may result in better tumor control and overall survival after combined-modality therapy.

Hyperfibrinogenemia as a risk factor for sudden hearing loss.

OBJECTIVE: To clarify predisposing conditions for vascular events. SETTING: Vascular events, immunologic processes, and viral infections have to be considered as pathomechanisms for most cases of sudden hearing loss. STUDY DESIGN: Hemorrheologic parameters were studied in 53 patients with sudden hearing loss within 5 days of the onset. PATIENTS: A control group of 53 normal-hearing people was matched pairwise according to age and gender. RESULTS: Fibrinogen levels were significantly higher in patients with sudden hearing loss (343 +/- 98 mg/dl) than in control subjects (303 +/- 69 mg/dl). Erythrocyte aggregation (27.3 +/- 5.6 a.u. versus 20.9 +/- 8.5 a.u.) and plasma viscosity (1.31 +/- 0.13 mPa/s versus 1.26 +/- 0.08 mPa/s) in patients with SHL were also significantly higher than in control subjects. No significant difference could be found in the parameters of clinical chemistry, hematology, and hemostasias investigated. CONCLUSION: Because elevated plasma fibrinogen plays a major role in cardiovascular diseases such as myocardial infarction and stroke, it is possible that this plasma protein is also involved in the pathogenesis of sudden hearing loss of vascular origin. More research is still required to determine the value of measuring plasma fibrinogen levels in clinical practice and identifying hyperfibrinogenemia in sudden hearing loss.