Effect of head position on cochlear implant MRI artifact.

PURPOSE: A new generation of cochlear implant (CI) magnets and specific surgical techniques (e.g., implant positioning) has changed the relationship between a CI and magnet resonance imaging (MRI). MRI allows a pain free in vivo evaluation of the inner ear fluid state and internal auditory canal after the insertion of an electrode. The aim of this study is to evaluate how the patient's head position in the MRI scanner influences the CI magnet-related artefact. METHODS: We performed in vivo measurement of MRI artefacts at 3 T with a CI system containing a bipolar diametrical magnet. The implant magnet was positioned with a head bandage at different positions from the nasion and external auditory canal in three volunteers. We used a turbo spin echo (TSE) T2w sequence on the axial and coronal planes and observed three positions: (1) regular position, (2) chin to chest (anteflexion), and (3) hyperextension (retroflexion). RESULTS: By comparing the positions, anteflexion of the cervical spine in a chin-to-chest position allowed us to place the artefact in a more apical position from the IAC in the coronal plane. The hyperextension of the cervical spine position shifts the artefact father towards the cochlea's direction. CONCLUSION: The head's position can influence the location of MRI artefacts. In cases where the artefact diminished the IAC or cochlea, anteflexion of the cervical spine in the chin-to-chest position of the head in the MRI scanner should be attempted to allow a visualization of the IAC.

[A rare pathology of the petrous part of the temporal bone: adenoma of the middle ear]. / Eine seltene Pathologie des Felsenbeins: Das Adenom des Mittelohres.

Adenomas are very rare tumors of the middle ear. They are benign neoplasms originating from the glandular components of the mucous membrane of the middle ear. The middle ear adenoma was first described by Hyams and Michaels in 1976, which was named an adenomatous tumor. This article reports the case of a 50-year-old female patient, who presented with recurrent right-sided dull otalgia and pulse synchronous tinnitis, which began 1 year prior to presentation, with the suspected diagnosis of a glomus tympanicum tumor. Following the otorhinolaryngological examination and imaging an unclear mesotympanal space-occupying lesion was detected. A transmeatal endoscopic complete removal of the tumor was carried out. The histopathological investigations enabled the diagnosis of an adenoma of the middle ear. Adenomas are a rare differential diagnosis of tumors of the middle ear. In cases with a suitable localization an adequate exposure and removal of this rare tumor can be achieved by a transmeatal endoscopic access.

[Ectopic thyroid tissue after total thyroidectomy]. / Ektopes Schilddrüsengewebe nach erfolgter Thyreoidektomie.

Ectopic thyroid gland tissue can occur either as the only detectable thyroid gland tissue or in addition to a normotopic thyroid gland. After a total thyroidectomy thyroid-stimulating hormone (TSH) can induce a compensatory volume increase of previously asymptomatic ectopic tissue. This hyperplastic ectopic tissue can occur as an unclear cervical space-occupying lesion. Prior to surgical exploration of an unclear cervical mass the possibility of ectopic thyroid tissue should be included in the differential diagnostic considerations.

Immunotherapeutics for head and neck squamous cell carcinoma stem cells.

Cancer stem cell (CSC)-related therapy resistance has become a new obstacle to the successful application of cancer treatment and head and neck squamous cell carcinoma (HNSCC) is no exception to this finding. Head and neck squamous cell carcinoma is highly immune-suppressive, and recently the immune suppression and invasion of HNSCC-CSCs have been characterized. These characteristics have received research and clinical attention because they would enable the stratification of patients into specific cancer subtypes and, consequently, the establishment of new therapeutic approaches with improved efficacy. This review discusses the feasibility of CSC-targeted strategies and their incorporation with nanotechnology to improve the efficacy of cancer immunotherapy.

[Perspectives of genome editing in otorhinolaryngology]. / Perspektiven der Genomeditierung in der Hals-Nasen-Ohren-Heilkunde.

BACKGROUND: Recent advances in DNA sequencing technology have enabled researchers to identify the genetic background underlying human illness. In addition, the latest genome editing technology, CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9), provides great potential to edit genomic DNA sequences precisely with high efficiency. This technology has been evaluated for treatment of genetic diseases in recently published preclinical studies. Since many such genetic disorders can affect functional structures in the head and neck area, the technology bears high therapeutic potential in otorhinolaryngology. OBJECTIVE: In this article, we summarize the concept of CRISPR-Cas9-based therapies, recent achievements in preclinical applications, and future challenges for the implementation of this technology in otolaryngology. MATERIALS AND METHODS: Genetic targeting strategies were analyzed or established using genome sequencing data derived from online databases and literature. RESULTS: Recent research on animal models has shown that genome editing can be used to treat genetic diseases by specifically targeting mutant genomic loci. For example, one preclinical study in the field of otolaryngology has demonstrated that inherited autosomal dominant deafness in mice can be treated using CRISPR-Cas9. Moreover, the same strategies can be used to establish applications for the treatment of head and neck cancer. The greatest challenge appears to be establishment of a system for the safe and efficient delivery of therapeutic nucleotides in clinics. CONCLUSIONS: In theory, genome editing could be used in otolaryngology to target disease-causing genomic loci specifically. However, various challenges have to be overcome until applications can be used clinically.

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1).

BACKGROUND: Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for locally advanced head and neck cancer. This phase II study investigated the effectivity of a split-dose TPF ICT before surgery for locally advanced resectable (stage III/IVA) oral and oropharyngeal cancer. PATIENTS AND METHODS: Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2 docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders (reduction tumor volume ≥30% after first cycle) received three 3-week cycles and non-responders only one cycle before surgery and postoperative radio(chemo)therapy (RCT). The primary endpoint was progression-free survival rate after 24 months. Secondary endpoints were amongst others overall survival, histopathological response to ICT, toxicity, quality of life and swallowing function. RESULTS: Fifty-four patients (91% stage IVA, 87% male, 72% oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis. The progression-free survival rate after 24 months was 88.5% for responders and 60.6% for non-responders (P = 0.005). The overall survival rate after 24 months was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of histopathological complete remission of the primary tumor was higher in responders (P = 0.015). High-risk classification for postoperative RCT was lower in responders (P < 0.0001). The most common grade 3+ adverse event was neutropenia in 26% of patients during ICT and mucositis in 13% during postoperative RCT. During treatment and follow-up quality of life and swallowing function was not different between responders and non-responders. CONCLUSION: Patients with oral and oropharyngeal cancer responding to split-dose TPF before surgery and postoperative RCT show good oncological results. The tri-modal treatment regime was well tolerated. ICT using tumor response as criterion for duration of ICT before surgery of oral and oropharyngeal cancer merits additional investigation in a phase III study. CLINICAL TRIAL NUMBER: NCT01108042.

Balloon Eustachian tuboplasty: a retrospective cohort study.

BACKGROUND: Eustachian tube dysfunction is regarded as a 'black box' term, reflecting a spectrum of dysfunction. The key to its diagnosis and management is in identifying the aetiology and exact pathophysiology of the dysfunction. DESIGN: We present our retrospective 5-year results for the technique of transnasal endoscopic balloon dilatation of the cartilaginous part of the Eustachian tube, balloon Eustachian tuboplasty (BET). The indication for treatment is chronic obstructive Eustachian tube dysfunction. MAIN OUTCOME MEASURES: Preoperatively, the Eustachian tube score (ETS) was obtained by a clinico-objective assessment involving tubomanometry (TMM) and reported patient symptom. The measurements were repeated 1, 2, 3, 4 and 5 years postoperatively. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 622 patients (1076 ears) were treated with BET. RESULTS: One year after treatment, the Eustachian tube score improved from 3.13 (± 2.47 SD) to 5.75 (± 2.76 SD). The Eustachian tube score improved significantly in 73% of ears. The average Eustachian tube score 2 years after treatment improved from 2.65 (± 2.89 SD) to 6.26 (± 3.07 SD). In 82% of patients, the Eustachian tube score improved significantly at 5 years. The subjective satisfaction of the patients was approximately 80%. CONCLUSIONS: Our long-term results suggest that BET is a safe and feasible treatment for chronic obstructive Eustachian tube dysfunction with a success rate of more than 70%. This study has important implications for other Eustachian tube-related clinical entities, such as glue ear management (adults and children), continued grommet insertion and tympanomastoid surgery outcomes.

Evaluation of tubomanometry as a routine diagnostic tool for chronic obstructive Eustachian tube dysfunction.

OBJECTIVE: The objective of this study was to demonstrate the reliability of tubomanometry (TMM) described by Estéve in the diagnosis of chronic obstructive Eustachian tube (ET) dysfunction. STUDY DESIGN: Combined prospective and retrospective clinical study. SETTING: Tertiary referral centre, affiliated to university. METHODS: Two hundred and fifteen healthy subjects were examined once, 25 healthy subjects underwent TMM weekly for 6 weeks, and six healthy subjects were tested three times a day on at least three different days. The results of tubomanometry in healthy subjects were compared to data obtained from 171 patients with chronic obstructive ET dysfunction. RESULTS: In healthy subjects, there was an immediate opening of the ET at 30-50 mbar with an R-value ≤ 1 in at least 94% of the cases. In patients with chronic ET dysfunction, an opening of the ET could be registered in only 42% of patients at 30 mbar and in 58% at 50 mbar. The average of the R-value in these subjects always indicated towards a delayed opening (R > 1). When measurements are repeated in the same subject with a weekly interval, the intraclass correlation (ICC) was 0.49 for the TMM with 30 mbar, 0.51 for the TMM with 40 mbar and 0.52 for the TMM with 50 mbar in healthy people. For the patients with symptoms of ET dysfunction, the ICC for up to four repeated measures was 0.50 for the TMM with 30 mbar, 0.53 for the TMM with 40 mbar and 0.54 for the TMM with 50 mbar. A complete agreement of the results in repeated measurements within seconds was present in 86% for 30 and 40 mbar and in 79% for 50 mbar. The ICC was 0.61 for the TMM with 50 mbar, 0.62 for the TMM with 40 mbar and 0.68 for the TMM with 30 mbar. CONCLUSIONS: Tubomanometry can support the diagnosis of ET dysfunction. An R-value ≤ 1 indicates a regular function of the ET, an R-value >1 indicates a delayed opening of the ET, and no definable R-value means no detectable opening of the ET. TMM is a reliable and valid instrument to support the diagnosis of chronic obstructive ET dysfunction.

[Bacteriologic investigation of the Eustachian tube and the implications of perioperative antibiotics before balloon dilation]. / Bakteriologische Untersuchungen der Tuba auditiva und die Implikation einer perioperativen Antibiotikagabe vor Ballondilatation.

BACKGROUND: Balloon Eustachian Tuboplasty (BET) is a new minimally invasive treatment for chronic Eustachian tube dysfunction (ETD). Initially, perioperative prophylactic antibiotic therapy with ciprofloxacin 2 × 500 mg p.o. for 5 days was administered. This study aimed to characterize the bacterial flora in the ET, nose, and pharynx in patients with chronic obstructive ETD. Additionally, we investigated the necessity of perioperative antibiotic prophylaxis in BET patients. PATIENTS AND METHODS: We examined 40 patients undergoing BET: 20 patients with and 20 patients without perioperative antibiotic prophylaxis. All patients were followed-up for clinical signs and symptoms of local infection for at least 2 weeks after surgery. Following BET, the tips of 35 balloon catheters, as well as swabs from the nose and pharynx were sent for microbiologic analysis. RESULTS: None of these 40 patients had postoperative signs of infection. Of the swabs of the balloon catheters, 46% were sterile and 23% showed standard flora. The remaining 31% of swaps revealed specific bacteria. However, none of the nasal or nasopharyngeal swaps were sterile. CONCLUSION: Due to the lack of signs of postoperative infection in either investigated group, the authors no longer favor use of perioperative antibiotic prophylaxis in patients undergoing BET. The relevance of biofilms and pathogen colonization to ET function has recently been intensively discussed, and should be further investigated in future studies.

[Assessment of chronic obstructive eustachian tube dysfunction : Evaluation of the German version of the Eustachian Tube Dysfunction Questionnaire]. / Beurteilung der chronisch-obstruktiven Tubenfunktionsstörung : Evaluation des "Eustachian Tube Dysfunction Questionnaire" in der deutschen Übersetzung.

BACKGROUND: Eustachian tube dysfunction can cause middle ear diseases and impair quality of life. Sufficient diagnostic tools for chronic obstructive eustachian tube dysfunction are lacking and not reliable enough. PATIENTS AND METHODS: The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was published by McCoul et al. in 2012 as an instrument to evaluate eustachian tube function. They demonstrated the reliability und validity of their questionnaire. The cut-off point for the diagnosis of eustachian tube dysfunction is ≥ 14.5 at 100 % sensitivity and 100 % specificity. We translated the ETDQ-7 into German and used it on 100 healthy subjects and 43 patients with chronic obstructive eustachian tube dysfunction. RESULTS: The results in the English questionnaire were confirmed by our examinations with the German version of the questionnaire. The mean ETDQ-7 score was 8.67 in the healthy subjects and 24.7 in the patients with chronic obstructive eustachian tube dysfunction. The area under the curve in ROC analysis was 98.8 % (p < 0.0001). CONCLUSION: We recommend the ETDQ-7 as an addition to patient history in the examination of eustachian tube dysfunction. It may as well be valuable in follow-up examinations to monitor treatment success.

Multimodality treatment for poorly differentiated neuroendocrine head and neck carcinomas--a single institution experience.

Poorly differentiated head and neck neuroendocrine neoplasms are very rare. Surgical resection alone is insufficient to control the disease because of the high incidence of metastases. However, due to the lack of randomised clinical trials, treatment recommendations for this cancer vary considerably and are based on a limited number of small retrospective studies. We performed a retrospective analysis of all patients treated at our institution between 2003 and 2011. We assessed the stage of disease, type of therapy, toxicity, treatment response, time to progression and overall survival for all cases. Ten patients received combined modality treatment with chemotherapy in addition to surgery or radiation or both. According to Response Evaluation Criteria In Solid Tumours (RECIST) criteria, six of nine evaluable patients achieved complete remission and three patients had a partial remission. The mean duration of response was 358 days, with a range from 141 to 1080 days. The overall 1-year survival rate was 88%; however, only approximately 50% of patients were alive after 2 years. Multimodality treatment concepts induce high initial remission rates in poorly differentiated neuroendocrine head and neck carcinomas. However, the time to relapse is usually short, and therefore long-term prognosis of this rare head and neck tumour remains poor.

[Tympanotomy and sealing of the round window membrane in sudden sensorineural hearing loss: a retrospective analysis]. / Tympanoskopie mit Abschottung der Rundfenstermembran beim idiopathischen Hörsturz: Eine retrospektive Analyse.

BACKGROUND: The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) still remains unclear. This retrospective study was performed to evaluate the effectiveness of tympanotomy and sealing of the round window membrane after unilateral idiopathic sudden sensorineural hearing loss. METHODS: A total of 74 patients with idiopathic sudden sensorineural hearing loss were treated with antiphlogistic-rheologic infusion therapy according to Stennert (steroids and pentoxyphylline). In addition, all patients underwent exploratory tympanotomy and sealing of the round window membrane. Pure tone audiometry was performed pre- and postinterventionally. RESULTS: The average hearing loss (four pure tone average) of all patients was 58.9 dB pre-, and 46 dB postinterventionally, which is an average improvement of 12.9 dB. Patients with hearing loss of more than 60% improved significantly compared to patients with hearing loss less than 60% (33.9% vs. +3.3%). Sealing of the round window membrane was found to be more effective when performed within 8 days after ISSHL. A membrane rupture did not lead to better therapy results. No significant correlation was found between therapy outcome and other clinical symptoms. CONCLUSION: Sealing of the window membrane shows equal results to conservative methods. If patients with hearing loss of more than 60% have more benefit in tympanotomy with sealing of the window membrane than patients with less hearing loss--as shown as in this study--has to be proved in randomized examinations. Intraoperatively found ruptures of the round window membrane had no significant effect on the therapy outcome.

[The patulous eustachian tube-novel surgical approaches]. / Das Syndrom der klaffenden Tube - neue chirurgische Therapieansätze.

A patulous eustachian tube (tuba aperta) may lead to an enormous reduction in quality of life. A patulous eustachian tube can cause symptoms such as autophony, breath synchronous tinnitus, pressure sensation in the ear, and hearing loss. In combination with so-called "sniffing", it can trigger the development of cholesteatoma. Due to the diffuse symptoms the correct diagnosis of this disease can be challenging. A patulous eustachian tube can be best diagnosed through a well-structured examination including patient history, physical examination with thorough observation of movements of the tympanic membrane, and tympanometry with reflex decay. This publication reviews recent literature on the patulous eustachian tube. We focused on the evaluation of the different surgical strategies such as the patulous eustachian tube reconstruction, the Kobayashi plug or the injection of Vox® implants into the torus tubarius.

[Therapy of chronic obstructive eustachian tube dysfunction: evolution of applied therapies]. / Therapie chronisch obstruktiver Funktionsstörungen der Tuba Eustachii: Konzepte im Wandel der Zeit.

This paper reviews the past and present developments in the treatment of chronic obstructive eustachian tube dysfunction. Alongside tube catheterization and bougie insertion, modern approaches such as laser eustachian tuboplasty and balloon eustachian tuboplasty (BET) are described. In BET, transnasal endoscopic insertion via the pharyngeal ostium places a balloon catheter in the cartilaginous portion of the eustachian tube. This is then dilated to a pressure of 10 bar for 2 min. Up until January 2013, 351 chronic obstructive eustachian tube dysfunction patients had been treated in our department using BET. The average preoperative eustachian tube score was 2.1 (± 1.8 standard deviation, SD); 12 months postoperatively it was 6.1 (± 2.6 SD). Of these patients, 87% expressed satisfaction with the improvement in chronic obstructive dysfunction. These results demonstrate that BET is a safe and effective treatment for improving eustachian tube function and ear ventilation.

[Chronic obstructive eustachian tube dysfunction in adults: long-term results of balloon eustachian tuboplasty]. / Chronisch obstruktive Tubenfunktionsstörung des Erwachsenen: Langzeitergebnisse der Ballondilatation der Tuba Eustachii.

BACKGROUND: Sufficient diagnostic tools and effective therapies for chronic obstructive eustachian tube dysfunction are lacking. PATIENTS AND METHODS: A total of 120 patients (209 ears) with chronic obstructive eustachian tube dysfunction were treated over a 2-year period using transnasal endoscopic balloon dilatation of the cartilaginous part of the eustachian tube (balloon eustachian tuboplasty, BET). A balloon catheter is inserted into the eustachian tube via the pharyngeal opening and dilated with a pressure of 10 bar for 2 min. RESULTS: The first 12 patients (20 dilatations) had a pretreatment average tube score of 1.25 (± 1.83 SD), and 1 year after treatment, the score improved to 6.2 (± 2.61 SD). Furthermore, the pretreatment and 2-month posttreatment data of 66 additional patients (115 dilatations) were analyzed. In these patients, the tube score improved significantly from 2.21 (± 2.02 SD) to 5.4 (± 2.53 SD). CONCLUSION: The initial long-term results suggest that BET is feasible and safe for the treatment of chronic obstructive eustachian tube dysfunction.

Perilymph Fistula as a Complication of Eustachian Tube Dilation and Tympanoplasty.

Eustachian tube dilation (ETD) is an established, minimally invasive therapeutic approach for chronic eustachian tube dysfunction. The complications associated with performing a ETD are rare. A 22-year-old female patient presented with chronic otitis media on the right side and chronic obstructive tube dilation disorder on both sides. A type I tympanoplasty was performed on the right side because of a tympanic membrane perforation after a ETD on both sides without apparent complications. On the 5th postoperative day, she presented with headache, dizziness and hearing loss on the right side. There was a decrease of hearing threshold on the right side in the pure-tone audiogram and vHIT, cVEMP, and SVV were irregular. The ß-2-transferrin test was positive. Since a right-sided perilymph fistula was suspected, an emergency tympanotomy was performed with a round window membrane cover with fascia on the right side. Intraoperatively, a regular, intact ossicular chain was found with a slightly moist middle ear mucosa. The round window membrane was covered by the promontorial lip. Under these measures, the patient's dizziness regressed. The right ear pure-tone threshold vHIT, cVEMP, and SVV normalized.

Ipsilateral Vestibular Schwannoma after Cochlear Implantation.

OBJECTIVE: The vestibular schwannoma incidence rate is approximately 4.2 per 100,000/year. Thus far, about 700,000 cochlear implantations have been performed worldwide; therefore, the occurrence of vestibular schwannoma postcochlear implantations can be assumed to be infrequent. Recent developments allow safe observation and surveillance of the implanted-side internal auditory canal (IAC) and cochlea by magnetic resonance imaging (MRI), even after cochlear implantation. Patients. A 71-year-old woman with sudden hearing loss and a contralateral vestibular schwannoma without clinical and genetic signs of neurofibromatosis type II. Intervention(s). Ipsilateral cochlear implantation and contralateral vestibular schwannoma extirpation with regular tumor follow-up. Main Outcome Measure(s). Comparison of ipsilateral pre and postcochlear implantation 3T MRI T1 GAD. RESULTS: We observed a tumor growing at the fundus of the internal auditory canal 1 year after cochlear implantation on the ipsilateral side. Although first detected after cochlear implantation beside a known vestibular schwannoma on the contralateral side, a scan slice thickness of 2 mm cannot fully exclude the preoperative persistence of a small tumor. Based on the clinical findings and after genetic exclusion of NFII, the patient was classified as a NFII mosaic type. CONCLUSION: Even after cochlear implantation, tumors in the IAC causing vertigo, facial palsy, and affecting the audiologic outcome can be detected by MRI. The MRI slice thickness used before cochlear implantation should be under 2 mm.

Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics.

Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs) harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs) within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.