[A case of metastatic salivary duct carcinoma successfully treated with trastuzumab-based targeted therapy].

Salivary duct carcinoma is a malignant salivary neoplasm with a poor prognosis. Effective treatment for remote metastases has not been recognized. We report herein on a case of this tumor overexpressing HER2 successfully treated with trastuzumab-based molecular targeted therapy. The patient was a 69-year-old man, who developed remote metastases into the liver and the thoracic vertebra six months after surgery and postoperative irradiation for the primary and nodal lesions. After targeted therapy including paclitaxel and trastuzumab, these metastatic lesions showed rapid and continued regression. After paclitaxel was discontinued due to peripheral neuropathy in the extremities, trastuzumab monotherapy followed without resulting in cardiotoxicity. After three years since development of remote metastases, the patient is doing well without re-progression of the disease.

[A study of salivary gland aspiration cytology reporting: guideline validity].

We retrospectively reviewed 44 cases of major salivary gland lesions surgically resected following preoperative fine-needle aspiration cytology (FNAC). Our objective was to determine the validity of the salivary gland FNAC reporting proposed in 2004 by the Japanese Society of Clinical Cytology. Of the 44 lesions, 33 were in the parotid gland and 11 in the submandibular gland. Of these, 8 lesions were malignant. Two from benign lesions could not be satisfactorily evaluated, and 4 from benign lesions and 1 from a malignant lesion were indeterminate. Results were 3 true positive, 30 true negative, and 4 false negative, with no false positive results. Calculated sensitivity was 42.9% (4/7), specificity 100% (30/ 30), and accuracy 89.2% (34/37). We concluded that using the new reporting decreases ambiguity in clinicians' interpretation of cytology reports, thus benefitting subjects.

Activation of JNK in the inner ear following impulse noise exposure.

Noise exposure is known to induce cell death signaling in the cochlea. Since c-Jun N-terminal kinase (JNK) signaling is known to induce both cell survival and apoptosis, the present study focused on early changes (within 24 h) after impulse noise exposure, inquiring whether cell death is always related to phosphorylation of JNK in the inner ear. Anesthetized adult albino rats were exposed to a single impulse noise exposure (194 kPa) and sacrificed 3 or 24 h later. Paraffin-embedded sections were examined for positive staining of phosphorylated JNK and the presence of cells with fragmented DNA (TUNEL staining). Positive TUNEL staining was observed at the spiral limbus and in the stria vascularis at 24 h following impulse noise exposure, but no correlation with JNK activation was found at these locations. In the hearing organ (organ of Corti) and in the lateral wall, TUNEL-reactive cells were observed at 24 h following trauma. This was preceded by p-JNK staining at 3 h, indicating JNK-activated cell death in these regions. Finally, p-JNK reactivity was observed in the spiral ganglion with no correlation to TUNEL staining within the time frame of this study. These results suggest that JNK activation following impulse noise exposure may not always be related to cell death, and conversely, some cells may die through JNK-independent signaling.

The relationship between cerebral T2 hyperintensity and fixation suppression of vestibulo-ocular reflex in elderly patients with dysequilibrium symptoms.

OBJECTIVES: To evaluate the relationship between cerebral T2 hyperintensity on MRI and visual suppression of vestibulo-ocular reflex (VOR) in elderly patients with dysequilibrium symptoms. METHODS: Eighty-nine elderly patients with no MRI abnormalities in the infratentorial region aged 60-89 years complaining dysequilibrium symptoms were studied. Cases with whom a definitive diagnosis of peripheral or central disease could be established were not included. T2 hyperintense lesions in the cerebrum: basal ganglia, subcortical white matter and periventricular white matter were evaluated. VOR in darkness and fixation-suppressed VOR using pseudo-sinusoidal rotation stimuli were recorded to calculate visual suppression rate. Correlation between visual suppression rate and semi-quantitative scores for severity of T2 hyperintensity in the cerebrum was investigated. RESULTS: Patients with T2 hyperintensity in the cerebrum exhibited significantly lower visual suppression rate than those without lesions in the cerebrum. Multiple regression analysis showed that visual suppression rate was significantly and negatively correlated with severity of lesions in the basal ganglia, but not with patient age, severity of subcortical white matter lesions, or that of periventricular white matter lesions. CONCLUSIONS: In elderly patients with dizziness with a non-specific history and otoneurological findings, fixation suppression of vestibular nystagmus was associated with T2 hyperintensities in the basal ganglia.

Bilateral epithelial-myoepithelial carcinoma of the parotid glands.

BACKGROUND: The most common histological diagnosis of bilateral parotid gland neoplasm is Warthin tumor. Bilateral malignant tumors of the parotid gland are extremely rare. METHODS: A 60-year-old man presented with a painless mass in the right preauricular area and an MRI scan showed multiple masses in the parotid glands, bilaterally. A standard superficial parotidectomy was performed on the right parotid gland followed by subtotal parotidectomy on the left. The diagnosis was synchronous bilateral epithelial-myoepithelial carcinoma arising in the parotid glands. RESULTS: Histopathology of the tumor on both sides indicated epithelial-myoepithelial carcinoma. There was no evidence of locoregional or remote disease during a 5-year follow-up period. CONCLUSION: Malignant tumors should be included in the differential diagnosis of bilateral parotid gland tumors. Management of unilateral malignant parotid tumors should involve careful observation of the contralateral parotid gland.

Validity and limitation of manual rotational test to detect impaired visual-vestibular interaction due to cerebellar disorders.

The aim of this study was to investigate validity and limitation of the novel infrared system to record and analyze horizontal visual-vestibular interaction using whole-body rotation rapidly and conveniently in the routine vestibular clinic. We examined 11 patients with cerebellar dysequilibrium and 25 patients with peripheral dysequilibrium for vestibulo-ocular reflex in darkness (DVOR), visually-enhanced vestibulo-ocular reflex (VEVOR), and fixation suppression of vestibulo-ocular reflex (FSVOR), and compared the results with those of examination for head-fixed smooth pursuit and fixation suppression during caloric stimulation. The manual rotation stimuli were 0.5-0.75 Hz in frequency and 60-90 degrees /s in maximal angular velocity. Gain of vestibulo-ocular reflex in darkness was not significantly correlated with maximal slow phase velocity (MSPV) of caloric-induced nystagmus at that stimulus condition either in patients with peripheral dysequilibrium or in those with cerebellar dysequilibrium. An index for fixation suppression of vestibulo-ocular reflex during rotation stimulus was significantly lower in patients with cerebellar dysequilibrium than in normal control subjects and those with peripheral dysequilibrium. On the other hand, there was no significant difference among the two disease groups and the normal control group in gain of visually-enhanced vestibulo-ocular reflex. In about a half of patients with cerebellar dysequilibrium, measured smooth pursuit gain was lower than estimated smooth pursuit gain calculated based on a simple superposition theory of vestibulo-ocular reflex and smooth pursuit. Testing fixation suppression using the present system is an unusually convenient tool for detection of cerebellar dysequilibrium.

Neck and superior mediastinal granular cell tumor excised via a combined approach.

Granular cell tumor (GCT) is an uncommon tumor of Schwann cell origin. GCT occurs in various sites throughout the body, but mediastinal GCT is very rare. We present an extremely rare case of GCT of the neck and superior mediastinum. A 36-year-old man with a 3-month history of cough was investigated at our hospital. CT and MRI revealed a spindle-shaped mass in the left neck and superior mediastinum, with features suggesting a neurogenic tumor. The tumor was successfully excised via combined neck incision and video-assisted thoracoscopic surgery. Histopathological examination showed proliferation of polygonal and spindled cells with eosinophilic granule-rich cytoplasm. These cells were S-100 protein positive, and the cytoplasmic granules were periodic acid-Schiff positive. Based on these histopathological and immunohistochemical findings, a diagnosis of GCT was established. The patient developed hoarseness immediately after the operation, and laryngoscopy revealed the left vocal cord palsy in the paramedian position, which resolved after about 3 months. The tumor did not recur during the following 10 months.

Alteration of E-cadherin and beta-catenin in mouse vestibular epithelia during induction of apoptosis.

The aim of this study was to examine if adhesion molecules had relation with degeneration and regeneration processes of mammalian vestibular epithelia. The distribution of E-cadherin and beta-catenin was immunohistochemically examined in normal and aminoglycoside-treated utricles of mice. E-cadherin and beta-catenin linearly expressed between epithelial cells in normal specimens. Aminoglycoside injury resulted in temporal alteration in distribution of these molecules with induction of apoptosis in hair cells. Degradation of both molecules was widely observed in vestibular epithelia, while some supporting cells exhibited accumulation of beta-catenin. After completion of induction of apoptosis, expression of these adhesion molecules was normal in distribution. These findings suggest that the E-cadherin-beta-catenin complex plays roles in degeneration and subsequent repair processes in vestibular epithelia affected by aminoglycosides.

A novel technique for inducing local inner ear damage.

With significant development of mouse genomics and the availability of transgenic and knockout mice, the mouse will be the preferred animal model for inner ear research. However, few studies have used mice as experimental animals for examination of hair cell degeneration, because of their relative resistance to ototoxic agents and difficulties in surgical treatment. This study presents a model for induction of apoptotic cell death in sensory epithelia of the mouse inner ear using injection of neomycin into the posterior semicircular canal. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay revealed that local application of neomycin produced sufficient induction of apoptotic cell death in both auditory and vestibular epithelia over a definite time course. Supplementation of the general caspase-inhibitor significantly reduced induction of TUNEL-positive cells, indicating caspase-dependency of apoptotic cell death observed in the present model. In addition, the approach to the posterior semicircular canal was an easy technique, and sham-operation induced no significant induction of TUNEL-positive cells. This model, hence, enables the use of various genetic tools in studies for mechanisms of hair cell apoptosis.

Adult dermatomyositis with bleeding ulcer in the pharynx.

Dermatomyositis (DM) is one of the idiopathic inflammatory myopathies caused by complement-mediated vasculopathy or vasculitis in the muscle. Although the gastrointestinal (GI) mucosa has been reported to be involved as a result of vasculitis or vasculopathy, ulceration in the pharynx is a rare manifestation of DM. A 54-year-old woman complaining of muscle weakness in the extremities, low-grade fever, and dysphagia was diagnosed as having DM. Despite medical treatment with corticosteroids and immunosuppressive agents, her DM progressed rapidly, leading to exacerbation of the dysphagia. About 3 weeks after undergoing tracheostomy as a preventive measure against aspiration, the patient developed intractable respiratory tract hemorrhage. Repeated laryngoendoscopy revealed a bleeding ulceration in the pharynx that required hemostasis with electric cautery under general anesthesia. No bleeding recurred thereafter. Histopathologically, the pharynx exhibited nonspecific inflammatory cell infiltration in the muscle tissue. This rare manifestation may be considered in cases of DM with unexplainable airway bleeding.

c-Fos expression in the mouse brainstem after unilateral labyrinthectomy.

CONCLUSION: The results indicated that the vestibular, prepositus hypoglossal, and inferior olive nuclei were activated after unilateral labyrinthectomy in mice like in other species. It is expected that the application of the present procedure to appropriate gene-deficient mice will elucidate the mechanism of the process of vestibular compensation. OBJECTIVE: Vestibular compensation is attributed to functional and structural reorganization of neural networks in the central vestibular system, but its precise mechanism is still not clear. c-Fos protein is used as a marker of neuronal activation, because of its very limited expression in the normal state and rapid appearance after external stimulation. Previous reports, investigating c-Fos expression after unilateral labyrinthectomy were made in rats and guinea pigs, but not in the mouse brainstem. MATERIALS AND METHODS: For future application to the gene knockout mouse, we examined c-Fos expression in the mouse after unilateral labyrinthectomy. RESULTS: Twenty-four hours after surgery, significantly increased c-Fos positive cells were observed in the bilateral medial vestibular nucleus (MVe), bilateral spinal vestibular nucleus (SpVe), contralateral prepositus hypoglossal nucleus (PrH), and contralateral inferior olive nucleus (IO).

Vestibular compensation in glutamate receptor delta-2 subunit knockout mice: dynamic property of vestibulo-ocular reflex.

The delta-2 subunit of the glutamate receptor delta subfamily is selectively localised in cerebellar Purkinje cells. Delta-2 knock-out mice have defects in Purkinje cell synapse formation, as well as cerebellar long- term depression. In order to elucidate the roles of neural transmission around Purkinje cells in vestibular compensation, the gain and phase of the vestibulo-ocular reflex were measured before and after unilateral vestibular differentiation in delta-2 knock-out mice. After unilateral injury of the inner ear, gain decreased and then recovered in both knock-out mice and wild-type mice. However, recovery of VOR gain after unilateral vestibular differentiation was slower in knock-out mice than in wild-type mice. The knock-out mice displayed lower VOR gain than wild-type mice during the period between the 1st and the 2nd postoperative weeks. The results suggest that the cerebellum is necessary for augmentation of vestibulo-ocular reflex gain during the partially compensated stage of vestibular compensation after unilateral vestibular differentiation.

Signaling pathway for apoptosis of vestibular hair cells of mice due to aminoglycosides.

Previous studies on regeneration of mammalian vestibular hair cells have indicated the potential for self-repair of damaged hair cells. The rescue of damaged hair cells from cell death may therefore increase regenerated hair cells in affected vestibular epithelia. The role of apoptosis in the degradation of vestibular hair cells following aminoglycoside treatment has been elucidated. To seek a method of protecting vestibular hair cells from aminoglycoside toxicity, we examined the apoptosis signaling pathway of vestibular hair cells due to aminoglycoside toxicity. Induction of apoptosis in hair cells of mouse ampullar cristae damaged by local application of neomycin was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method and transmission electron microscopy (TEM). Immunohistochemistry for apoptosis-related proteins was employed to determine the signaling pathway of apoptosis of hair cells. The occurrence of apoptosis in hair cells was demonstrated by TUNEL staining and TEM. In apoptotic hair cells, activation of caspase-3 and -9, and redistribution of cytochrome c was identified, while there was no expression of activated caspase-8 or apoptosis-inducing factor. In conclusion, these findings indicate that the mitochondria-mediated pathway of apoptosis may play a role in inducing the apoptosis of vestibular hair cells due to aminoglycoside toxicity. Stabilization of the mitochondrial membrane may therefore rescue vestibular hair cells from apoptosis, leading to an increase in self-repaired hair cells in affected vestibular epithelia.