Published papers

Objective: Systemic steroid injections are used to treat idiopathic sudden-onset sensorineural hearing loss (ISSHL) and some inner ear disorders. Recent studies show that transtympanic (TT) steroid injections are effective for treating ISSHL. As in vivo monitoring of drug delivery dynamics for inner ear is lacking, its time course and dispersion of drugs is unknown. Here, we used a new in vivo imaging system to monitor drug delivery in live mice and to compare drug concentrations over time after TT and systemic injections. Methods: Luciferin delivered into the inner ears of GFAP-Luc transgenic mice reacted with luciferase in GFAP-expressing cells in the cochlear spiral ganglion, resulting in photon bioluminescence. We used the Xenogen IVIS® imaging system to measure how long photons continued to be emitted in the inner ear after TT or systemic injections of luciferin, and then compared the associated drug dynamics. Results: The response to TT and IP injections differed significantly. Photons were detected five minutes after TT injection, peaking at ~20 minutes. By contrast, photons were first detected 30 minutes after i.p. injection. TT and i.p. drug delivery time differed considerably. With TT injections, photons were detected earlier than with IP injections. Photon bioluminescence also disappeared sooner. Delivery time varied with TT injections. Conclusions: We speculate that the drug might enter the Eustachian tube from the middle ear. We conclude that inner-ear drug concentration can be maintained longer if the two injection routes are combined. As the size of luciferin differs from that of therapeutics like dexamethasone, combining drugs with luciferin may advance our understanding of in vivo drug delivery dynamics in the inner ear.

Objective: Transoral approach from the anterior direction is necessary if an upper spinal tumor is too big to extirpate via the posterior approach alone. To obtain a good anterior view of the surgical field, the mandible, tongue, and soft palate have to be split, and we developed a criterion to select the surgical strategy. Study Design: We indicated a decision-making process of splitting techniques and indications with actual cases and review of literatures. Result: Tumors were located from the level of C1 to the lower part of C3. Computerized tomography and magnetic resonance imaging were important to decide approaches. The orthopedic surgical team invited oral and maxillofacial surgeons team to assist in all transoral anterior approach cases. Conclusions: Vertical splitting of the mandible, incising the skin of the mental region, and splitting the middle of the tongue were combined according to the position of the spinal tumor.

Conclusion: Increase in the average value of bilateral neck muscle tension (ANT) indicates the increase in neck muscle tension to stabilize static posture resulting from vestibular compensation. Asymmetry of neck muscle tension was closely related to postural imbalance. Objective: Patients with dizziness often complain of neck symptoms with stiff neck. This study was conducted to clarify the pathophysiological mechanism of neck symptoms in patients with dizziness. Methods: We objectively measured bilateral trapezius muscle tension in patients with chronic dizziness and determined its relationship with static postural perturbation. The study included 26 patients with chronic dizziness caused by unilateral vestibular deficit and 24 healthy controls. The tension of bilateral trapezius muscles was objectively measured using a neck muscle tension meter. ANT and the ratio (right/left) of the bilateral neck muscle tension (RNT) were calculated. Static posturography was performed to measure total length of path (LNG). Results: ANT was negatively correlated to LNG under the eyes closed (EC) condition only in the case of the patients (r 0.44, p < 0.05). In the case of both the controls and the patients with a unilateral vestibular deficit, RNT was positively correlated to LNG under the EC condition.

A 72-year-old man with positional vertigo and tinnitus was referred to us. He did not want to perform provoking test except once due to his fear. No positional nystagmus was provoked. He found that his attacks usually occurred when he lay on his right ear. From his clinical history, benign paroxysmal positional vertigo was suspected. Conventional pharmacotherapy as well as non-specific physical therapy did not have significant effect. His feeling of positional vertigo with pyrosis was actually presyncope. We suspected cardiovascular disorders, and referred him to a cardiologist. Portable cardiogram monitoring revealed paroxysmal bradycardia. He was diagnosed with neurally mediated syncope, and a pacemaker was implanted. His paroxysmal dizziness soon disappeared. It is important to study the clinical history of the patients in detail, as they are not always able to accurately explain their symptoms. We should carefully rule out cardiovascular disorders, especially when we see the patients with suspected BPPV without the characteristic positional nystagmus.

HYPOTHESIS: We investigated whether inflammatory biomarkers and stress are involved in the pathophysiology of idiopathic sensorineural hearing loss (ISHL). STUDY DESIGN: Individual cohort study. SETTING: Two tertiary centers. PATIENTS: Forty-three ISHL and 10 non-ISHL patients seen in our ENT departments from 2004 to 2010 within a week from the onset of new symptoms and without steroid administration before visiting our departments. INTERVENTION: Multiple audiologic evaluations, blood tests including leukocyte counts, natural killer cell activity (NKCA), interleukin 6 (IL-6), tumor necrosis factor, high-sensitivity CRP (hCRP), and the General Health Questionnaire were used to evaluate the systemic stress and inflammatory response. MAIN OUTCOME MEASURES: Correlations between biomarkers and ISHL severity and prognosis were evaluated by statistical analysis. RESULTS: In the ISHL patients, a neutrophil count above the reference range was associated with severe hearing loss and poor prognosis, and was accompanied by low NKCA and high IL-6. In the non-ISHL patients, these associations were not present. The abnormal neutrophil count was independent of preexisting vascular diseases. The abnormal counts responded to treatment and decreased into the reference range. CONCLUSION: Neutrophil counts above the reference range of a facility will be a useful indicator of poor prognosis of ISHL. Synchronism of different types of NF-κB activation pathways could be required to cause severe ISHL. An NKCA decrease, an acute neutrophil count increase, and an IL-6 increase can induce NF-κB activation in the cochlea and cause severe ISHL. Further epidemiologic surveys should be conducted to evaluate whether stressful life events increase the risk of severe ISHL onset.

Of the transsellar transsphenoidalmeningoencephaloceles (TTSMEs), the true type presents with the hernial sac extending from the intracranium to the epipharynx through the sellar floor. The true type is the most serious and difficult to manage, especially when the hernial sac contains vital structures, such as the anterior cerebral artery, pituitary gland, optic nerve, hypothalamus, and third ventricle. Surgical outcome for true type TTSME is reported to be poor. We describe a successful case of endoscopic repair for a 36-year-old man with true type TTSME. Our success with endoscopic repair for true type TTSME in an adult is the first reported case. We believe that the endoscopic transsphenoidal approach allows less invasive surgery and provides an acceptable operative outcome in comparison with other microsurgical approaches.

In order to assess the clinical outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) who were initially treated in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1997 and 2006, statistical analyses were performed based on the patient medical records. Cause-specific survival (CSS) and disease-free survival (DFS) in all cases (stage I to IV, n = 32) and advanced cases (stage III and IV, n = 22) were estimated using the Kaplan-Meier method. The independent prognostic values of the clinical and therapeutic factors were determined using multivariate Cox proportional hazards models. Results: The 5-year CSS/DFS were 43.4%/34.8% in all cases and 34.596/29.8% in advanced cases. Multivariate analysis revealed that, in all cases, the independent prognostic factors for CSS were age ≥ 61 vs. ≤60, risk ratio (RR) =5.717, p = 0.006), T-stage (3/4 vs. 1/2, RR = 6.957, p = 0.004), and the use of platinum agents (unused vs. used, RR = 3.911, p = 0.012), whereas those for DFS were T-stage (3/4 vs. 1/2, RR=3.499, p = 0.019) and the use of platinum agents (unused vs. used, RR=2.947, p = 0.028). In advanced cases, the use of platinum agents alone was significant for both CSS (RR = 4.503, p = 0.023)and DFS (RR=4.218, p = 0.014). The patients who received neoadjuvant chemotherapy (NAC) showed better CSS and DFS than the patients who did not (p = 0.066 and p = 0.025, respectively) in a univariate analysis (Log-rank test), although no significant difference was seen between these groups in the multivariate analysis. Conclusion: The advantage of the administration of platinum agents in the treatment of NPC was statistically corroborated even in our study with its small sample size. As agents combined with chemoradiotherapy, the efficacy of do-cetaxel alone did not seem comparable to that of platinum agents. The docetaxel-CDDP-5-FU regimen applied as NAC was suggested to be possibly beneficial for advanced cases of NPC.

Nodular fasciitis has been generally considered as a benign and probably reactive fibroblastic growth originating from the subcutaneous fascia. In the present paper, we report a case with nodular fasciitis arising in the retroauricular region. The patient was a 23-year-old woman who had noticed a mass about 5 mm in diameter in the left retroauricular region. She was referred to our hospital because the mass was gradually growing and was tender to touch. At the initial examination, a pigmented mass about 1 cm in size was found in the left retroauricular region. The surface was smooth and the mass was freely mobile. Computed tomography (CT) revealed a mass-like tension which showed the same enhancement as a venous intensity. At operation, we found a white solid mass which had no capsule. The mass was easily removed, because it was not adherent to the surrounding tissues. The pathological diagnosis was nodular fasciitis which showed positive immunostaining for vimentin, HHF 35 (muscle actin), type III collagen and lysozyme, but negative immunostaining for desmin, S-100 protein and CD 34. This rare condition can be diagnosed only by pathological examination, however, it must be kept in mind in the differential diagnosis of retroauricular mass lesions.

Two patients presented with hypoglossal neurinoma extending both intra- and extracranially. A 63-year-old male presented with right trigeminal neuralgia and hypoglossal nerve paresis. The intracranial part of the tumor was removed totally via a suboccipital craniectomy. Over-coagulation of the venous collaterals, particularly the emissary veins, resulted in dural venous sinus thrombosis and cerebellar infarction. Unfortunately this patient died. A 48-year-old male presented with pareses of the VII, IX, X, XI, and XII cranial nerves and cerebellar sign. The tumor extended both extra- and intracranially, and was completely removed by opening the hypoglossal canal and the jugular foramen without over-coagulation of the venous collaterals. Preservation of the venous collaterals is very important for the prevention of postoperative venous complications.

Objective: The aim of this study is to describe the long-term outcome of preserved hearing after vestibular schwannoma surgery.Methods: Subjects are 20 unilateral vestibular schwannoma patients whose class A hearing of the AAO-HNS classification was preserved successfully after tumor removal. Hearing preservation surgery was attempted via the middle cranial fossa (MCF) or the extended MCF approach. The follow-up periods ranged from 2 to 16 years. The outcome measures included the pure tone average (PTA) and speech discrimination score (SDS).Results: PTA was maintained in less than 30 dB in 11 out of 20 patients within 2 years follow-up, six out of 13 patients within 4 years follow-up, and two out of five patients within 6 years follow-up, respectively. SDS was maintained in more than 70% in 17 out of 20 patients within 2 years follow-up, ten out of 13 patients within 4 years follow-up, and three out of five patients within 6 years follow-up, respectively.Conclusions: The preserved hearing maintained about more than 40% of the patients with the class A hearing in every 2 years follow-up. From this result, we can conclude that the hearing preservation surgery could be one of the best treatments for vestibular schwannoma patients with class A hearing. However, further study will be needed to clarify the mechanism of the deterioration in hearing after hearing preservation surgery. Copyright (C) 2000 Elsevier Science Ireland Ltd.

In this study, we analysed the clinical and audiological features of 24 vestibular schwannoma patients presenting with sudden deafness who visited our hospital within 10 days after its onset. The relationships between the prognosis of hearing loss and the clinical and audiological features including the pure-tone average (PTA), the presence of dizziness and/or vertigo, the tumour size and the auditory brain stem response (ABR) findings were evaluated. Hearing recovery depended on the PTA and tumour size, but even a small tumour induced sudden deafness. Impaired hearing completely recovered in five our of 24 patients. ABR findings indicated that the aetiology of sudden deafness in the vestibular schwannowa patients might vary in each patient.