[Measuring the cochlea using a tablet-based software package: influence of imaging modality and rater background]. / Vermessung der Cochlea mittels eines Tablet-basierten Softwarepakets: Einfluss der Bildgebungsmodalität und des Untersucherhintergrunds.

BACKGROUND: Cochlear duct length (CDL) is subject to significant individual variation. In the context of cochlear implantation, adapting the electrode array length to the CDL is of potential interest, as it has been associated with improvements in both speech recognition and sound quality. Using a tablet-based software package, it is possible to measure CDL at the level of the organ of Corti (CDLOC) to select appropriate electrode array lengths based on individual cochlear anatomy. OBJECTIVE: To identify effects of imaging modality and rater background on CDL estimates. METHODS: Magnetic resonance imaging (MRI) and flat-panel volume CT (fpVCT) scans of 10 patients (20 cochleae) were analyzed using the OTOPLAN software package (MED-EL, Innsbruck, Austria). Raters were an otorhinolaryngology (ORL) specialist, an ORL resident, and an audiologist. To analyze effects of rater background and imaging modality on CDL measurements, linear mixed models were constructed. RESULTS: Measurements showed mean CDLOC(fpVCT) = 36.69 ± 1.78 mm and CDLOC(MRI) = 36.81 ± 1.87 mm. Analyses indicated no significant effect of rater background (F(2, 105) = 0.84; p = 0.437) on CDL estimates. Imaging modality, on the other hand, significantly affected CDL (F (1, 105) = 20.70; p < 0.001), whereby estimates obtained using MRI were 0.89 mm larger than those obtained using fpVCT. CONCLUSION: No effect of rater background on CDL estimates could be identified, suggesting that comparable measurements could be obtained by personnel other than specially trained neurootologists. While imaging modality (fpVCT vs. MRI) did impact CDL results, the difference was small and of questionable clinical significance.

A clinical comparison of DPOAE fine structure reduction methods.

OBJECTIVE: To evaluate two real-time methods for reducing distortion product otoacoustic emission (DPOAE) fine structure in terms of DPOAE amplitude and fine structure depth. DESIGN: A prospective, repeated-measures design was used to assess DPOAE characteristics in response to a conventional stimulation method (Conv.), as well as for methods implementing either a generic suppressor tone (Supp.) or frequency modulation of the f2 primary tone (FM). STUDY SAMPLE: Eighty-three young adults (58 females) between the ages of 20 and 34 years with normal hearing completed testing for this study. RESULTS: Use of the Conv. and FM methods resulted in consistently higher DPOAE levels relative to the Supp. method, with average advantages of 6 and 5 dB, respectively. For all methods, increased fine structure depth was observed for stimulation with lower level (25-45 dB SPL) and lower frequency (1000-3000 Hz) primary tones. Finally, use of the Supp. and FM methods resulted in significantly decreased fine structure depth relative to the Conv. method. CONCLUSION: Through frequency modulation of the f2 primary tone, it was possible to reduce the depth of fine structure across a clinically meaningful range of stimulation levels and frequencies without concomitant reduction in DPOAE amplitude.

From Acute to Chronic Tinnitus: Pilot Data on Predictors and Progression.

Little is known about the transition from acute tinnitus to chronic tinnitus. By means of this study, we are attempting to close this gap by presenting prospective pilot data of patients with acute tinnitus, followed by tracking their condition's trajectory over a period of 6 months. Forty-nine patients presenting with acute tinnitus (duration < 28 days) were recruited in two clinics. We recorded demographic and clinical tinnitus-related data as well as data on personality, health, treatments, and life-style, during patients' first appearance in the clinic and again three and 6 months thereafter. Standard audiograms were performed at the first and the second visit. Nine (18.4%) patients showed full remission of their tinnitus. These patients differed from patients with a chronic course of tinnitus by shorter tinnitus duration, lower fear-related hyperacusis, higher proportion of female gender, increased ear pressure, and lower levels of alcohol consumption. Among the patients with a chronification of tinnitus, there was no change in tinnitus characteristics. However, their tinnitus distress improved moderately over time. These preliminary data are in line with earlier studies that have shown that only a small proportion of those patients presenting in the clinic with acute tinnitus experience a full remission. The results of this study can be of service in deducing hypotheses for the transition from acute to chronic tinnitus and in developing designs for interventional studies.

Different Materials for Plugging a Dehiscent Superior Semicircular Canal: A Comparative Histologic Study Using a Gerbil Model.

HYPOTHESIS: The choice of the material for plugging a dehiscence of the superior semicircular canal is based on the ease of use and the success of the procedure to permanently relieve symptoms without adverse side effects. BACKGROUND: Dehiscence of the superior semicircular canal can lead to autophony, conductive hearing loss, and vertigo. Surgical treatment by plugging the canal is a highly effective treatment of the symptoms in many patients, although, the procedure can be associated with some degree of hearing loss in more than or equal to 25% of the patients. The available data indicate that adverse effects may be more frequently observed with bone wax as compared with other materials. METHODS: In the present study we compare the tissue reactions induced by plugging the superior semicircular canal with autologous bone pate/bone chips, muscle, fat, artificial bone wax, and teflon in the gerbil model in an attempt to identify the material leading to successful plugging with the least adverse tissue reactions. RESULTS: Our data show that successful plugging was achieved in 100% of the ears by bone pate/bone chips, teflon, and bone wax while the success rate was significantly lower (<50%) following muscle and fat. The proportion of adverse tissue reactions was significantly more pronounced using bone wax as compared with teflon and bone pate/bone chips. CONCLUSION: The use of teflon or autologous bone as a material for plugging a dehiscent superior semicircular canal should be favored over bone wax, muscle, and fat.

How to Avoid a Learning Curve in Stapedotomy: A Standardized Surgical Technique.

OBJECTIVE: To evaluate, whether a learning curve for beginners in stapedotomy can be avoided by using a prosthesis with thermal memory-shape attachment in combination with a standardized laser-assisted surgical technique. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Fifty-eight ears were operated by three experienced surgeons and compared with a group of 12 cases operated by a beginner in stapedotomy. INTERVENTION: Stapedotomy. MAIN OUTCOME MEASURES: Difference of pure-tone audiometry thresholds measured before and after surgery. RESULTS: The average postoperative gain for air conduction in the frequencies below 2 kHz was 20 to 25 dB and decreased for the higher frequencies. Using the Mann-Whitney-U test for comparing mean gain between experienced and inexperienced surgeons showed no significant difference (p = 0.281 at 4 kHz and p > 0.7 for the other frequencies). A Spearman rank correlation of the postoperative gain for air- and bone-conduction thresholds was obtained at each test frequency for the first 12 patients consecutively treated with a thermal memory-shape attachment prosthesis by two experienced and one inexperienced surgeon. This analysis does not support the hypothesis of a "learning effect" that should be associated with an improved outcome for successively treated patients. CONCLUSION: It is possible to avoid a learning curve in stapes surgery by applying a thermal memory-shape prosthesis in a standardized laser-assisted surgical procedure.

Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.

IMPORTANCE: Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE: To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS: This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES: Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS: Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P < .001). CONCLUSIONS AND RELEVANCE: The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.

Localization of gentamicin uptake in the acutely isolated inner ear of the rat.

The quantitative analysis of fluorescence in frozen sections of rat inner ears exposed to Texas Red conjugated gentamicin revealed distinct gradients of gentamicin fluorescence. At 500 µg/ml gentamicin fluorescence occurred in inner and outer hair cells, the interdental cell region, the spiral limbus below the interdental cells, the nerve fiber bundle in the spiral lamina, the inner sulcus cells and the dorsal region of the spiral ligament. No gentamicin fluorescence was observed in the Hensen / Claudius cells, the ventral region of the spiral ligament, the stria vascularis and the spiral ganglion. In the vestibule only the hair cell epithelium and the transitional cells of the saccule showed gentamicin fluorescence while no gentamicin fluorescence was found in hair cell epithelia and transitional cells of utricle and ampule, nerve fibers below hair cell epithelia of saccule, utricle and ampule and in dark cells. The gentamicin flurescence increased at higher concentrations. Gentamicin exposure led to more pronounced gentamicin fluorescence in the cochlea compared to the vestibule. Based on the predominant gentamicin fluorescence in the hair cell - limbus region of the cochlea at a low dose we propose that gentamicin may interact with the K(+)-flow from the inner hair cells back to the scala media.

A micro-computed tomographic study: determination of the angle between the tympanic membrane and stapes footplate in a total ossicular reconstruction prosthesis reconstruction.

OBJECTIVES: To examine the anatomical relationship of the angles between tympanic membrane and stapes footplate and the variation of these angles among different temporal bones in order to characterize the optimal shape of total ossicular reconstruction prostheses (TORPs). METHODS: Ten specimens of human temporal bones were prepared for examination with micro-computed tomography. Five of the 10 temporal bones were implanted with 3 types of TORPs before subjecting them to micro-computed tomography. The angles between tympanic membrane and stapes footplate were determined. The contact of the TORPs to these structures was assessed. RESULTS: The angle between the stapes footplate and the tympanic membrane was, on average, 25.9 degrees in a plane along the transverse axis of the stapes footplate and 24.6 degrees in a plane along the longitudinal axis of the stapes footplate. Consideration of these angles in TORPs resulted in an optimal contact with the tympanic membrane and stapes footplate, especially for prostheses with a large foot. CONCLUSION: TORPs should be adjusted in shape before insertion into the middle ear. Further developments should consider prostheses with preadjusted angles or appliances for the exact modification of the prostheses during surgery.

Influence of Surface Processing on the Biocompatibility of Titanium.

Surface conditioning of titanium middle ear implants results in an improved biocompatibility, which can be characterized by the properties of fibroblasts cultured on conditioned surfaces. Titanium has been established as a favorable biomaterial in ossicular chain reconstruction. The epithelization of the surface of the implants is important for their integration and stable positioning in the middle ear. Mouse fibroblast cells were cultured on platelets made from pure Grade 2 titanium. Platelets that had been etched along their production process were compared to unetched platelets. The DNA in the cell nuclei was stained with DAPI and the actin filaments of the cytoskeleton were stained with FITC-conjugated phalloidin in order to analyze the cells grown on etched and unetched platelets by fluorescence microscopy. SEM (scanning electron microscopic) images were used to compare the surface structure of etched and unetched titanium platelets. There was a statistically significant increase of the area covered by the cytoplasm and increased actin expression by fibroblasts grown on the etched titanium platelets. In addition, the area of the platelets covered by nuclei on the etched platelets exceeded on average the one on unetched platelets, although this difference was not significant. The SEM pictures comparing unetched and etched titanium platelets showed a clear difference in surface structure. Surface conditioning of titanium implants improved the epithelization by fibroblasts and consequently etched titanium should be the preferred biomaterial for reconstructive middle ear surgery.

Prognostic importance of "clear versus revised margins" in oral and pharyngeal cancer.

BACKGROUND: Opinions differ regarding the usefulness of accurate, but costly, frozen sections. Most physicians believe that negative margins are essential for the prognosis of patients with oral and pharyngeal cancer. We examined whether immediate repeated resections in patients with positive margins, based on findings from frozen sections, resulted in improved patient survival. METHODS: Data from 417 patients identified with cancer of the pharynx and floor of the mouth were analyzed retrospectively. RESULTS: The 5-year survival rate for R0 and R1-R0 groups was 72% to 76% and was significantly better (p ≤ .034) than that for R1 and R2 groups (58%, 40%). Despite clear margins, large tumors had a poorer prognosis than that of small tumors. CONCLUSIONS: Patients receiving repeated resection had the same survival rate as patients who had the tumor resected immediately with negative margins. The use of frozen sections yields a benefit for 15.6% of the operated patients and increases the overall 5-year survival rate by 2% to 3%.

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs approximately US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age

Morphology of the malleus handle and the comparison of different prostheses for malleostapedotomy.

OBJECTIVES: To assess malleus morphology to characterize optimal sites for prosthesis attachment in malleostapedotomy and to examine attachment, position, and depth of penetration in the vestibule of the 3 most used prostheses. METHODS: Ten mallei were processed for histologic examination with the light microscope. Using digitized video images of the histologic slices, the diameters, circumference, and shape of the specimen were determined. Implantation of 3 prostheses (Gyrus Nitinol piston, Storz titanium stapes piston, and Kurz malleovestibulopexy piston), was performed in 3 temporal bones for a total of 27 implantations. RESULTS: The cross-section of the malleus just distal to the lateral process shows an inclined oval shape with a mean minimum diameter of 0.84 +/- 0.10 mm, a mean maximum diameter of 1.02 +/- 0.23 mm, and a mean circumference of 3.23 +/- 0.49 mm. The quality of attachment to the malleus, the position of the prosthesis piston, and the depth of penetration were reliable for the Storz titanium stapes piston, satisfactory though variable for the Gyrus Nitinol piston and poor for the Kurz malleovestibulopexy piston as judged by contact with the malleus surface and predictability of insertion depth into the vestibule. CONCLUSION: The oval and inferoanteriorly inclined shape of the malleus distal to the lateral process requires the use of a prosthesis capable of molding itself to its surface for reliable attachment. To achieve the correct perpendicular position of the piston as it relates to the stapedotomy opening, individualized adaptation of the prosthesis shaft and loop to the anterior position of the malleus should be made in situ.

The crimping problem in stapes surgery.

AIM OF THE STUDY: The goal of this study was to compare the attachment of stapes prostheses with differently shaped loops to the long process of the incus. METHOD: Gold, steel/Teflon, platinum/Teflon, and two different titanium stapes prostheses were inserted in 30 specially prepared temporal bones by three experienced surgeons using the Fisch technique with the McGee crimper and straight alligator forceps for the crimping of the loops. RESULTS: In all prostheses, a sufficiently firm attachment of the long process of the incus was achieved. The band-shaped loops showed a better contact with the incus than did the wire loops. However, the broad spiral-shaped loops led to a loss of the perpendicular axis of the piston to the long incus process. CONCLUSION: The geometry of the loop affects the final length of the piston in the vestibule and its angle to the long process of the incus.

Stapes surgery: the diameter of the long process of the incus.

HYPOTHESIS: The aim of this study was to examine the long process of the incus in respect of its shape and its dimensions at the site of the attachment of a stapes prosthesis. BACKGROUND: One of the complications in stapes surgery is the erosion of the long process of the incus at the site of the attachment of the prosthesis, resulting in a fluctuating conductive hearing loss. Knowing the dimensions of the attachment site of the prosthesis at the long process of the incus will make it possible to optimize the size of the prosthesis loop. METHODS: The incus was obtained from 11 patients who had undergone middle ear surgery for hearing improvement or cholesteatoma removal. The ossicles were kept in 4% paraformaldehyde and were processed for histological examination after decalcification in ethylenediamine tetra-acetic acid. The 5-microm slices were stained with toluidine blue and examined in the light microscope. Using digitized video images of the histological slices, the diameters, circumference, and surface of the specimens were determined. RESULTS: The diameter of the long process of the incus at 1.4+/-0.28 mm from the tip, which is the average site of prosthesis attachment, showed an oval shape with a minimum diameter of 0.66+/-0.05 mm, a maximum diameter of 0.81+/-0.1 mm, and a circumference of 2.46+/-0.23 mm. CONCLUSION: The loop of a stapes prosthesis should have the following dimensions: diameter 0.9 mm, loop length of 2.2 mm, and opening of loop 0.7 mm. However, the material of the prosthesis and its malleability are also important factors.

Stapes surgery: how precisely do different prostheses attach to the long process of the incus with different instruments and different surgeons?

HYPOTHESIS: The goal of this study was to compare the attachment of stapes prostheses with differently shaped loops to the long process of the incus. BACKGROUND: In stapes surgery, the attachment of the prosthesis to the long process of the incus plays an important role concerning the gain in hearing and the development of late complications such as incus erosion and necrosis. Band-shaped and spiral loops have been developed to achieve a broad, firm attachment to the long process of the incus. During stapes surgery, the view at the prosthesis is restricted, making it impossible to evaluate the effects of the differently shaped loops. METHODS: Gold, steel/Teflon, platinum/Teflon, and two different titanium stapes prostheses were inserted in 30 specially prepared temporal bones by three experienced surgeons using the Fisch technique with the McGee and straight alligator forceps for the crimping of the loops. Photographs were taken with 0- and 70-degree rod lens telescopes at defined views. RESULTS: In all prostheses, a sufficiently firm attachment to the long process of the incus was achieved. The attachment of band-shaped loops proved to be better with the straight alligator forceps. The band-shaped loops showed a better contact with the incus than did the wire loops. However, the broad spiral-shaped loops led to a loss of the perpendicular axis of the piston to the long incus process. CONCLUSION: The geometry of the loop affects the final length of the piston in the vestibule and its angle to the long process of the incus.