Assessing the usefulness of inner ear contrast-enhanced magnetic resonance imaging and pure-tone audiometry in estimating the prognostic value of hearing improvement in patients with definite Meniere's disease.

PURPOSE: Meniere's disease (MD) is characterized by combined cochlear and vestibular symptoms. However, its underlying cause remains unclear, with low-to-mid-tone hearing impairment being predominantly reported. Moreover, predicting hearing improvement after disease onset is not possible. This study aimed to assess whether hearing improvement in patients with definite MD (DMD) could be predicted using inner ear contrast magnetic resonance imaging (IEC-MRI) and pure-tone audiometry (PTA) at disease attack. MATERIALS AND METHODS: Between April 2020 and March 2022, seven outpatients with DMD were enrolled based on the Bárány Society DMD criteria. The patients were divided into two groups: low-tone hearing loss (LTL) group and low-to-mid-tone hearing loss (LMTL) group. Hearing improvement rates as well as the possible inter-relation between endolymphatic hydrops and hearing improvement were evaluated. RESULTS: Endolymphatic hydrops was found in two of four LTL cases. One of three LMTL cases had prominent lymphedema. All patients with LTL but only one patient with LMTL had hearing improvement. Endolymphatic hydrops was not found to be correlated with hearing improvement. CONCLUSIONS: Estimating hearing improvement in patients with DMD using IEC-MRI was not possible. However, PTA showed better hearing prognosis in LTL than in LMTL. Therefore, estimating hearing improvement using PTA was possible at disease attack.

Genetic background in late-onset sensorineural hearing loss patients.

Genetic testing for congenital or early-onset hearing loss patients has become a common diagnostic option in many countries. On the other hand, there are few late-onset hearing loss patients receiving genetic testing, as late-onset hearing loss is believed to be a complex disorder and the diagnostic rate for genetic testing in late-onset patients is lower than that for the congenital cases. To date, the etiology of late-onset hearing loss is largely unknown. In the present study, we recruited 48 unrelated Japanese patients with late-onset bilateral sensorineural hearing loss, and performed genetic analysis of 63 known deafness gene using massively parallel DNA sequencing. As a result, we identified 25 possibly causative variants in 29 patients (60.4%). The present results clearly indicated that various genes are involved in late-onset hearing loss and a significant portion of cases of late-onset hearing loss is due to genetic causes. In addition, we identified two interesting cases for whom we could expand the phenotypic description. One case with a novel MYO7A variant showed a milder phenotype with progressive hearing loss and late-onset retinitis pigmentosa. The other case presented with Stickler syndrome with a mild phenotype caused by a homozygous frameshift COL9A3 variant. In conclusion, comprehensive genetic testing for late-onset hearing loss patients is necessary to obtain accurate diagnosis and to provide more appropriate treatment for these patients.

Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF-CRT) for locally advanced squamous cell carcinoma of the external auditory canal.

PURPOSE: Chemoradiotherapy with docetaxel (DOC), cisplatin (CDDP), and 5-FU (TPF-CRT) for locally advanced external auditory canal cancer (EACC) has favorable oncological and functional outcomes. To establish TPF-CRT as a standard of care for advanced EACC, we conducted this study to determine the maximum tolerated (MTD) and recommended dose (RD) of DOC in TPF-CRT for locally advanced EACC. METHODS: To determine the recommended (RD) and maximum tolerated dose (MTD) of DOC in TPF-CRT for EACC, a phase I trial was conducted using the standard "3 + 3" design for maximum dose finding. DOC was administered twice every 4 weeks, CDDP at 70 mg/m2 and 5-FU at 700 mg/m2; patients were also receiving radiotherapy (66 Gy). Eight patients with T3 or T4 EACC were prospectively enrolled. RESULTS: Two patients treated with DOC, 50 mg/m2, and one out of six patients treated with DOC, 40 mg/m2, had dose-limiting toxicities. Prolonged febrile neutropenia was observed in three patients. Grade 3 non-hematological toxicities were observed in only three patients. At study completion, six patients survived, five of whom were disease free. CONCLUSION: The RD and MTD of DOC in TPF-CRT for locally advanced EACC are 40 mg/m2 when doses of CDDP and 5-FU are 70 mg/m2 and 700 mg/m2, respectively.

Survival impact of local extension sites in surgically treated patients with temporal bone squamous cell carcinoma.

OBJECTIVES: Temporal bone squamous cell carcinoma (TSCC) is a rare malignancy. Due to its low incidence rate, studies involving TSCC treatment are limited. The aim of this study is to define the prognostic factors of surgery for TSCC by evaluating our clinical experience. METHODS: We reviewed the clinical charts of patients presenting at the University of Tokyo Hospital between 2001 and 2014 and identified 33 patients with TSCC who had been treated with surgery as initial curative treatment. RESULTS: Lateral and subtotal temporal bone resections were performed in 17 and 16 patients, respectively. The 5-year disease-specific and overall survival rate were 71 and 62%, respectively. The significant poor prognostic factors were pathological T4 (P = 0.03), dural invasion (P = 0.008), temporomandibular joint invasion (P = 0.04), and a positive surgical margin (P = 0.009). CONCLUSION: We demonstrated that the outcome of curative surgery for TSCC as initial treatment was favorable. However, because of the difficulty to ensure an adequate or clear surgical margin due to anatomical complexity, the surgical indication for T4 TSCC with temporomandibular joint invasion should be reconsidered.

Prognostic factors for long-term hearing preservation after canal-tympanoplasty for congenital aural atresia.

The present study aimed to determine favorable prognostic factors for long-term postoperative hearing outcome after canal-tympanoplasty for congenital aural atresia (CAA). We retrospectively reviewed pre and postoperative hearing results and image findings of 51 ears with CAA performed by canal-tympanoplasty for primary repair. Averages of the postoperative air and bone-conduction thresholds, and the air-bone gap (ABG) were calculated from the last pure-tone audiometry. Follow-up duration ranged from 16 to 139 months. A successful hearing result was defined as a postoperative ABG of ≤15 dB, or a postoperative pure-tone average of ≤30 dB. The influence of the following factors on the success of surgery was assessed by multivariate logistic regression analysis: total Jahrsdoerfer grading system score, age at surgery, and dimensions of middle ear including incudostapedial joint angulation, mesotympanic height, mesotympanic width, mesotympanic depth, mesotympanic area, mesotympanic volume, reconstructable external auditory canal (EAC) diameter, and reconstructable EAC height. Successful hearing outcomes were achieved in 24 of 51 ears (47.1%). A multivariate logistic regression analysis showed that an EAC area >72.3 mm(2) was the most significant favorable predictive factor (P = 0.006), followed by mesotympanic depth >5.5 mm (P = 0.013), mesotympanic height >4.6 mm (P = 0.016), and EAC diameter >9.5 mm (P = 0.029). In conclusion, the size of the reconstructable EAC and mesotympanum is important for predicting long-term favorable hearing outcome following canal-tympanoplasty for CAA.

The clinical manifestation and treatment of Meniere's Disease from the viewpoint of the water homeostasis of the inner ear.

Endolymphatic hydrops, a pathological feature of Ménière's disease, has been experimentally and clinically confirmed to be influenced by the blood circulation of vasopressin (VP). VP is a well-known hormonal regulator of water homeostasis. In addition, VP is influenced by various environmental changes, dehydration, fluctuation of atmospheric pressure, pregnancy, and other factors. Furthermore, VP is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is a major neuroendocrine system that controls reactions to emotional and physical stresses, as well as the sleep/wake cycle (circadian rhythm). Therefore, VP is susceptible to change via the HPA axis. This review considers possible mechanisms of the formation of endolymphatic hydrops from the perspective of the vasopressin-aquaporin 2 system.

Expression of AQP-10, -11 and -12 in the rat stria vascularis.

BACKGROUND: Water homeostasis is essential for inner ear function. Several aquaporins (AQPs), which are water transport proteins in the cell or plasma membrane, have been reported in the lateral wall of the rat inner ear (cochlea). However, the presence of AQP-10, -11 and -12 has not been reported in the rat stria vascularis (SV) to date. AIMS/OBJECTIVES: We have aimed to clarify the expression of AQP-10, -11 and -12 in the cochlea lateral wall. MATERIALS AND METHODS: Using Wistar rats, we examined the expression of AQP-10, -11 and -12 in the cochlea lateral wall using molecular approaches and immunohistochemistry. RESULTS: AQP-11 was molecular biologically expressed, but the expression of AQP-10 and -12 was not observed. Immunohistochemically, AQP-11 was diffusely localized in the basal cells and marginal cells of the rat SV but was not expressed at the apical site of marginal cells with double staining. The expression of AQP-10 and -12 was not observed. CONCLUSIONS AND SIGNIFICANCE: Only AQP-11 was expressed in the basal cells and marginal cells, but it was not expressed at the apical site of marginal cells. Based on this study, AQP-11 may not have an important role in water flux between the perilymph and endolymph.

Expression of EGFR and p16 in Squamous Cell Carcinoma of External Auditory Canal.

The expression of EGFR and p16 in the external auditory canal squamous cell carcinoma (EACSCC) and their impacts on oncological outcomes were not well studied. Seventeen-one consecutive patients who were treated for EACSCC at Kobe University Hospital from 1995 to 2018 were enrolled in this study. The expression of EGFR, and p16 were evaluated and their impacts on oncological outcomes were statistically analyzed. Positive expression of EGFR was observed in 62 patients (87%). Strong positive expression of p16 were observed in 18 patients (32.4%), and weakly positive expression in 30 patients (42.3%), respectively. While the number of the patients with negative EGFR expression were limited, all the surgically treated patients with negative EGFR expression have been alive without disease. In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.

Morphological and functional changes in a new animal model of Ménière's disease.

The purpose of this study was to clarify the underlying mechanism of vertiginous attacks in Ménière's disease (MD) while obtaining insight into water homeostasis in the inner ear using a new animal model. We conducted both histopathological and functional assessment of the vestibular system in the guinea-pig. In the first experiment, all animals were maintained 1 or 4 weeks after electrocauterization of the endolymphatic sac of the left ear and were given either saline or desmopressin (vasopressin type 2 receptor agonist). The temporal bones from both ears were harvested and the extent of endolymphatic hydrops was quantitatively assessed. In the second experiment, either 1 or 4 weeks after surgery, animals were assessed for balance disorders and nystagmus after the administration of saline or desmopressin. In the first experiment, the proportion of endolymphatic space in the cochlea and the saccule was significantly greater in ears that survived for 4 weeks after surgery and were given desmopressin compared with other groups. In the second experiment, all animals that underwent surgery and were given desmopressin showed spontaneous nystagmus and balance disorder, whereas all animals that had surgery but without desmopressin administration were asymptomatic. Our animal model induced severe endolymphatic hydrops in the cochlea and the saccule, and showed episodes of balance disorder along with spontaneous nystagmus. These findings suggest that administration of desmopressin can exacerbate endolymphatic hydrops because of acute V2 (vasopressin type 2 receptor)-mediated effects, and, when combined with endolymphathic sac dysfunction, can cause temporary vestibular abnormalities that are similar to the vertiginous attacks in patients with MD.

Evaluation of the internal structure of normal and pathological Guinea pig cochleae using optical coherence tomography.

Optical coherence tomography (OCT) makes it possible to visualize the internal structures of several organs, such as the eye, in vivo. Although visualization of the internal structures of the inner ear has been used to try and identify certain pathological conditions, attempts have failed mainly due to the thick bony capsule surrounding this end organ. After decalcifying the bony wall of the cochlea with ethylenediamine tetraacetic acid, we could clearly visualize its internal structures by using OCT. We identified endolymphatic hydrops, strial atrophy and damage to the organ of Corti, evident as a distention of Reissner's membrane, thinning of the lateral wall and flattening of the organ of Corti, respectively. When specimens embedded in paraffin, sliced and stained with hematoxylin and eosin (HE) were examined under a light microscope, the OCT images of normal and pathological cochleae were virtually identical with those of the HE specimens, except that the HE specimens exhibited several artifacts unrecognized in OCT images, which were considered to be induced during the preparation process. Since OCT enables one to obtain arbitrary plane images by manipulating the slice axis of the specimens and avoids any misinterpretation due to artifacts induced during histological preparation, our technique would be useful for examining cochlear pathologies without or prior to histological evaluations.

Vestibular function after simultaneous bilateral cochlear implantation in adults.

Introduction: Binaural hearing enhances speech intelligibility, source localization, and speech comprehension in noisy environments. Although bilateral cochlear implantation (CI) offers several benefits, concerns arise regarding the risk of bilateral postoperative vestibular dysfunction with simultaneous CI. This study aimed to longitudinally evaluate changes in vestibular function in adult patients who underwent simultaneous bilateral CI using minimally invasive electrodes and surgical techniques. Methods: A retrospective review was conducted on 10 patients who underwent simultaneous bilateral CI at our hospital. Vertigo symptoms and vestibular function test results were examined preoperatively, 1-6 months postoperatively, and 1 year postoperatively. Nystagmus tests, caloric reflex tests, vestibular evoked myogenic potentials (VEMP) measurements, and static stabilometry were performed as vestibular function tests. Results: Although an initial transient decline in vestibular function was observed, no significant long-term decline was observed in the caloric reflex test, ocular VEMP (oVEMP), or cervical VEMP (cVEMP). Moreover, regardless of the presence or absence of abnormalities in caloric reflex, oVEMP, or cVEMP, no significant deterioration was detected in the static stabilometer test. While two patients reported preoperative dizziness, all patients were symptom-free 1 year postoperatively. Discussion: The findings suggest that using current minimally invasive electrodes and surgical techniques in simultaneous bilateral CI leads to temporary vestibular function decline postoperatively. However, most patients experience a recovery in function over time, highlighting the potential safety and efficacy of the procedure. Simultaneous bilateral CI surgery is viable, depending on the patient's auditory needs and burden.

Live Imaging of the Dehydration Effect of Isosorbide on the Normal and Hydropic Guinea Pig Cochleae Using Optical Coherence Tomography.

OBJECTIVE: To investigate the isosorbide-induced dehydration effect on the endolymphatic space by intratympanic administration of isosorbide. BACKGROUND: Isosorbide, an osmotic diuretic, is used orally as a typical conservative therapy for Menière's disease (MD) in Japan. The dehydration effect occurs 6 hours after isosorbide ingestion. Intratympanic administration of isosorbide resolves endolymphatic hydrops faster than oral ingestion. In addition, the dehydration effect has never been shown directly. Therefore, we investigated the dehydration effect of intratympanic administration of isosorbide on endolymphatic hydrops using optical coherence tomography. METHODS: We used eight Hartley guinea pigs, divided into normal and hydrops groups. In the hydrops group, the animals underwent endolymphatic sac obliteration to create endolymphatic hydrops. We obtained midmodiolar section images of the cochleae using optical coherence tomography. Then, 50 to 70% isosorbide was sequentially administered intratympanically for 5 minutes, and the apical turn of the cochlea was observed. The relative midmodiolar cross-sectional area of the scala media was calculated for quantitative assessment of the endolymphatic space. RESULTS: In the normal group, 50% isosorbide had a slight but significant dehydration effect on the scala media; at 55 to 70%, Reissner's membrane became flat. In the hydrops group, 50% isosorbide slightly reduced endolymphatic hydrops; 65% flattened Reissner's membrane, and 70% slightly concaved it toward the basilar membrane. CONCLUSION: The results suggest that we could select the concentration of isosorbide according to the stage or severity of MD and relief from acute attack. Intratympanic administration of isosorbide may be a promising treatment for patients with MD.

Oncological outcomes of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for locally advanced squamous cell carcinoma of the external auditory canal: A single-center study.

BACKGROUND: Squamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. However, a standard treatment has not yet been established. We retrospectively evaluated the efficacy, adverse events, and feasibility of TPF-CCRT (concomitant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil) in patients with advanced EACSCC. METHODS: Thirty-five consecutive patients with advanced EACSCC (T3, T4) initially treated with TPF-CCRT at Kobe University Hospital were included. T4 diseases with invasion of the brain, internal carotid artery, or internal jugular vein were classified as T4b, and those without these features were classified as T4a. RESULTS: Five-year overall survival rates for T3 and T4 were 100% and 64.2%, respectively. A significant difference was observed between T4a and T4b (82.4% vs. 30%, p = 0.007). Five-year progression-free survival rates of T3, T4a, and T4b were 100%, 68%, and 20% (p = 0.022), respectively. CONCLUSIONS: TPF-CCRT should be considered as a plausible treatment option for advanced EACSCC.

A 14-year nationwide epidemiological analysis of delayed endolymphatic hydrops in Japan.

BACKGROUND: Delayed endolymphatic hydrops (DEH) is an inner ear disease that causes recurrent vertigo in the ipsilateral ear or fluctuating hearing in the contralateral ear due to endolymphatic hydrops secondary to preceding deafness. There are few reports of large, multicentre studies investigating the clinical-epidemiological characteristics of DEH. OBJECTIVE: This study aimed to clarify the characteristics of DEH in Japan. METHODS: Clinical data on 662 patients with DEH were analysed by nationwide, multicentre surveys conducted by the Peripheral Vestibular Disorders Research Group of Japan. RESULTS: The proportion of ipsilateral DEH (IDEH) was slightly higher than that of contralateral DEH (CDEH) at 55.4%. The time delay between onset of precedent deafness and onset of DEH was significantly longer for CDEH than for IDEH. The most common cause of precedent deafness was a disease of unknown cause with onset in early childhood (33.1%). Epidemiological characteristics were not significantly different between CDEH with and without vertigo. CONCLUSION: DEH appearing to be caused by viral labyrinthitis has a high rate of onset within 40 years of precedent deafness. Clinical and epidemiological characteristics of IDEH, CDEH with vertigo, and CDEH without vertigo were very similar. SIGNIFICANCE: The clinical-epidemiological characteristics of DEH in Japan were clarified.

Evaluation of the Carhart effect in congenital middle ear malformation with both an intact external ear canal and a mobile stapes footplate.

The medical charts of 41 ears with congenital middle ear malformation with both an intact external ear canal and a mobile stapes footplate were reviewed retrospectively to study the Carhart effect. The operations were categorized as successful or unsuccessful according to the extent of decrease in the average air-bone gap. Statistically significant differences were observed between the 2 groups with respect to the changes in pure-tone average and the changes in the bone conduction (BC) threshold at 1 and 2 kHz. Linear regression analysis revealed weak correlations between the change in the BC threshold and the postoperative BC threshold at an overall level and at the 4 frequencies tested. Stapes ankylosis is a main cause of the Carhart effect. The present study showed that in congenital middle ear malformation, the Carhart effect was caused not only by stapes ankylosis but also by other types of disruption in the ossicular chain.

Endocytosis of microperoxidase in marginal cells is mainly regulated by RhoA signaling cascade, but not by Rho-associated protein kinase, myosin light-chain kinase and myosin phosphatase.

Endocytosis plays an important role in cell function and the activation and propagation of signaling pathways. Signaling occurs on endocytic pathways and signaling endosomes, and endocytosis is subjected to high-order regulation by cellular signaling mechanisms. Marginal cells showed active endocytosis of microperoxidase (MPO) via the clathrin-independent pathway. We examined the signaling pathway that regulates MPO endocytosis in marginal cells using specific inhibitors and activators of signaling molecules. The results showed that pertussis toxin - which inhibits the ribosylation of G-protein-coupled receptor - did not affect MPO endocytosis, but Clostridium botulinum C3 toxin - which induces RhoA inactivation resulting in extracellular-signal-related kinase inactivation - inhibited MPO endocytosis. The main endocytotic pathway of MPO did not depend on the Rho-associated protein kinase molecular switch or actin/myosin motor system, but was mainly regulated by the RhoA signaling cascade.

Classification of the Chorda Tympani: An Endoscopic Study.

OBJECTIVES: To determine the ability of preoperative computed tomography (CT) to predict the variable surgical anatomy of the chorda tympani nerve (CTN) based on endoscopic tympanotomy. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: We identified 192 ears of 162 patients who underwent transcanal endoscopic ear surgery from August 2013 to June 2018. Patients with middle ear malformations, revision surgeries, myringoplasty, and cholesteatoma involving the CTN were excluded. INTERVENTIONS: An intraoperative endoscopic image depicting the chorda tympani was selected for each patient and classified into one of five types. Preoperative CT images were analyzed to match the pictorial classification. MAIN OUTCOME MEASURES: The visible tympanic segment of the chorda tympani was classified into the following five types: external auditory canal (EAC), detached, attached long, attached short, and ultrashort. RESULTS: A total of 128 ears from 101 patients ranging in age from 2 to 81 years were enrolled. The EAC, detached, attached long, attached short, and ultrashort types of CTN were found in 7 (5.5%), 6 (4.7%), 84 (65.6%), 18 (14.0%), and 13 (10.2%) patients, respectively. The presence of the EAC type could be predicted by preoperative CT while the other four types could be predicted by binning into two groups, with a sensitivity of 0.61 and specificity of 0.72. CONCLUSION: The variable anatomy of the chorda tympani nerve can be classified into five major groups based on endoscopic tympanotomy.

Reconstruction of the external auditory canal using full-thickness rolled-up skin graft after lateral temporal bone resection for T1 and T2 external auditory canal cancer.

OBJECTIVE: To present our results of the external auditory canal (EAC) reconstruction procedure using rolled-up full-thickness skin graft with tympanoplasty after lateral temporal bone resection (LTBR) for early-stage EAC carcinoma. PATIENTS AND METHODS: A retrospective review of 15 patients who had undergone LTBR with reconstruction of the EAC for T1 and T2 EAC cancer between 2016 and 2020. RESULTS: Postoperative mean air-bone gap was 30.7 decibel hearing level. Although a few patients experienced chronic granulation, persistent otorrhea, and/or laterization of the tympanic membrane, most patients showed no serious complications related to the EAC reconstruction. CONCLUSION: EAC reconstruction using a full-thickness skin graft in combination with tympanoplasty is useful for minimizing the hearing loss, maintaining the cosmetic appearance, and facilitating the observation into the ear cavity.

The clinical value of extratympanic electrocochleography in the diagnosis of Ménière's disease.

OBJECTIVE: To evaluate the clinical conditions causing an elevation in the click-evoked summation potential (SP)/action potential (AP) amplitude ratio (SP/AP ratio), the cause of the SP enhancement in Ménière's disease (MD) and the diagnostic efficacy of electrocochleography (ECoG) were discussed. STUDY DESIGN: Retrospective case review. SETTING: An outpatient clinic of the Otolaryngology Department of Kochi Medical School. PATIENTS: ECoG testing was performed in 632 patients (727 ears) with vertigo/dizziness and/or deafness over a 10-year period (1995-2005). Among them, 334 patients had diagnoses of definite MD, including 95 cases of bilateral involvement. MAIN OUTCOME MEASURES: Audiological thresholds and SP/AP ratio. RESULTS: An enhanced SP was observed in 56.3% of patients with MD. The incidence of an enhanced SP was low in patients for whom the disease duration was 2 years or less and the frequency of attacks was once a year or less, but was significantly higher in cases where the disease duration was 2 years or longer and/or the frequency of attacks was several times a year (Games-Howell test, p < 0.05). The incidence of an enhanced SP was significantly elevated in cases with pure-tone average exceeding 31 dB (Kendall's rank correlation test, p < 0.001). However, the enhanced SP, once it appeared, did not always disappear in spite of hearing improvement. Hearing improvement induced by the glycerol test also produced no alteration in an SP/AP ratio, and there was no significant difference between the glycerol test results and the incidence of an enhanced SP (chi2 goodness-of-fit test). CONCLUSIONS: The longer the patients were symptomatic or the severer the ear symptoms, the more likely the ECoG was to be positive. The abnormally elevated SP, once it had appeared, persisted for long periods. Spontaneous and glycerol-induced hearing gains did not result in a decrease in SP/AP ratio. These clinical characteristics of ECoG seem to indicate that the enhanced SP in MD might be caused by the malfunction of hair cells, not by the displacement of the basilar membrane toward the scala tympani.