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Reports of multiple primary cancers are increasing, but simultaneous primary cancers are not frequently reported especially originated in the same organ. We encountered a 71-year-old female who had two simultaneous carcinomas at both edges of the tongue. Histologically, the carcinoma of the right edge was a well-differentiated squamous cell carcinoma, while that on the left edge was a moderately-differentiated squamous cell carcinoma. No other tumors were detected on other examinations, including gallium-67 scintigraphy, CT scan of the chest, upper gastrointestinal fiberscopy and so on. She underwent surgical treatment without other induction treatments such as radiotherapy and chemotherapy. Her postoperative radiotherapy and chemotherapy were also uneventful because of her age. Fourteen-month follow-up revealed neither recurrence nor metastasis.

Objective: We present the response rate and adverse effects of our regimen of concurrent chemoradiotherapy with pirarubicin (THP) and 5-fluorouracil (5-FU) for oral and maxillary carcinoma., Patients and Methods: Fifteen patients with oral (10 cases) or maxillary (5 cases) squamous cell carcinoma who underwent our concurrent chemoradiotherapy with the combination of intraarterial pirarubicin, intravenous continuous 5-fluorouracil, and radiation between March 2001 and February 2003 in our department were entered in this study. THP (5 mg/day) was infused into the lingual or maxillary artery one hour before radiation on days 1-5 and 8-12, while intravenous 5-FU (150 mg/m2/day) was instilled continuously on days 1-5, 8-12, 15-19, and 22-26 in accordance with the radiation schedule (2 Gy/day). Consequently, total doses of THP, 5-FU, and radiation were 50 mg, 3000 mg/m2 and 40 Gy, respectively. After the treatment series, response rate and adverse effects were evaluated., Results: Response rate achieved 100% (12 cases exhibited a complete response and the remaining 3 a partial response). Notably, all 10 patients with oral carcinoma exhibited complete response. The main adverse effects were leucopenia (6/15) and mucositis (6/15), both of which were acceptable., Conclusions: This concurrent chemoradiotherapy is very useful for oral and maxillary carcinoma as a preoperative modality with remarkably high response rate and acceptable adverse events.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hyponatremia and the plasma hypoosmolality induced by water retention attributable to persistent antidiuretic hormone (ADH) release. It has been reported that SIADH may occur due to various factors in patients with malignant tumor. We report a case of hypopharyngeal cancer complicated by SIADH following chemotherapy. A 72-year-old woman with hypopharyngeal cancer was treated by oral administration of S-1 and intravenous administration of low-dose cisplatin following radiation therapy. General fatigue and coma occurred during the third course of this chemotherapy, using S-1 and low-dose cisplatin. We believed that she had SIADH because of the results of examinations including hyponatremia, serum hypoosmolality and increasing serum ADH level. We treated her by fluid restriction and intravenous administration of hypertonic saline and furosemide, and she recovered. Unfortunately, her hypopharyngeal cancer gradually progressed and she died of acute pneumonia three months later.

Objective: Nitric oxide (NO) has a toxic effect on neuronal cells related to glutamate receptors. NO released from post-synaptic cells with glutamate receptors can induce nearby cell death. In this experiment, we examined the effect of NO on cochlear hair cells., Methods: Two concentrations, 0.5 and 0.1 molar concentration (MC) of 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5), which is a NO donor, were placed on the round window of the guinea pig cochlea and its morphological changes were investigated at 12, 28, 72 h after the treatment., Results: By the trypan blue dye extrusion method, the cell death was recognized in the outer hair cells at the percentage 0, 36.0+/-6.6, 4.9+/-1.2% at 12, 28, 72 h after treatment respectively in the group 0.5 MC NOC-5, but no inner hair cell death was recognized. In the group of 0.1 MC NOC-5 and control any cell death was not detected. Transmission electron microscopy revealed this cell death was characteristic of apoptosis., Conclusion: The findings that apoptosis was induced in the outer hair cells of the organ of Corti by NO suggests the possibility that the cochlea is affected when extra NO release occurs there, leading to cochlear dysfunction.

Boettcher cells lie on the basilar membrane beneath Claudius cells. The cells are considered supporting cells for the organ of Corti, and present only in the lower turn of the cochlea, which responds to high-frequency sound. Boettcher cells interdigitate with each other, and project microvilli into the intercellular space. Their structural specialization suggests that Boettcher cells may play a significant role in the function of the cochlea. Nitric oxide synthase (NOS) has previously been detected in substructures of the cochlea. In the cochlea, it is believed that nitric oxide plays an important role in neurotransmission, blood flow regulation, and induction of cytotoxicity under pathological conditions. Findings concerning detection of NOS on Boettcher cells are rare. We demonstrated here the localization of NOS on Boettcher cells of the rat by immunohistochemistry using polyclonal antibody to NOS. On observation with the light microscope using DAB staining, positive immunostaining to NOS was observed in Boettcher cells. In immunoelectron micrographs, NOS was detected abundantly in the cytoplasm of the interdigitations. This suggests that the interdigitations may play significant roles by using NOS. It follows from this that the nitric oxide (NO) on Boettcher cells may influences neighboring Boettcher cells. The ultrastructure of Boettcher cells suggests that they may be active cells, which perform both secretory and absorptive functions.

Objective: To present our surgical technique for congenital atresia of the external ear canal with middle ear infection., Methods: A modified transmastoid approach to congenital atresia of the external ear canal with middle ear infection was applied. Our method is to visualize the landmarks of the mastoid cavity such as the antrum, sinodural angle and digastric ridge by the canal-open method to avoid facial nerve injury and then prepare a relatively large external ear canal with reconstruction of the posterior wall of the external ear canal., Results and Conclusion: This method is suitable not only for treating congenital atresia of the external ear canal with middle ear infection, but also for avoiding facial nerve injury and postoperative complications such as re-stenosis of the new ear canal and postoperative middle ear infection.

Pulmonary lymphangitic carcinomatosis (PLC) is an uncommon type of pulmonary metastasis from laryngeal carcinoma. We encountered a case of fatal respiratory failure after surgery for supraglottic laryngeal carcinoma with multiple cervical lymph node metastases. On day 25 postoperatively, the patient suddenly developed fever and noted slowly progressive difficulty in breathing. Laboratory data, radiological findings, and the clinical course of this patient were strongly suggestive of PLC. The patient refused fiberoptic bronchoscopy and glucocorticoid therapy, leading to rapid deterioration due to increasing respiratory distress, and died of respiratory failure on postoperative day 32. PLC should be considered a possible presentation of pulmonary metastasis associated with head and neck carcinoma. Chest CT may be needed to detect subclinical PLC, especially in cases of advanced head and neck carcinomas.

Objective: This study was conducted to evaluate the efficacy and feasibility of our accelerated hyperfractionation with concomitant boost for stage II laryngeal cancer and stages III-IVb locally advanced head and neck cancer., Patients and Methods: From January 2000 to October 2001, eight patients with AJCC 1998 stage II laryngeal cancer and 11 patients with AJCC 1998 stages III-IVb locally advanced head and neck cancer underwent accelerated hyperfractionated radiation therapy. For the stage II laryngeal cancer, radiation was delivered at a 2.0 Gy fraction a day, 5 fractions per week for the first 3 weeks, then 2 fractions (1.8 and 1.2 Gy) a day, 5 times a week for 2.5 weeks, with total dose of 69 Gy. For stages III-IVb head and neck cancer, radiation was given at a 1.8 Gy fraction a day, 5 fractions per week for 6 weeks and a boost was added up to 70.5 Gy with 1.5 Gy as a second daily fraction during the last 2.2 weeks. Among the patients, 16 (84%) received concomitant chemotherapy, mainly with low-dose carboplatin. Acute toxicity based on RTOG criteria and tumor response at 1 month post-treatment were estimated as initial effects., Results: The overall response rate was 100% in patients with stage II laryngeal cancer and 91% in patients with stages III and IVb head and neck cancer. The incidence of grade 3 or worse acute effects was 47%. Eighteen patients (95%) completed radiation therapy without interruption related to acute side effects, while one had prolongation of the treatment for more than 1 week because of neutropenia., Conclusions: Our results demonstrated that accelerated hyperfractionation, mostly combined with concomitant chemotherapy, had a good overall response rate with acceptable toxicity in stage II laryngeal cancers and stages III-IVb head and neck tumors.

The treatment of a man with six metachronous primary cancers is described. The primary lesions were in the soft palate, both edges of the tongue, the hard palate, the esophagus, and the right ureter. Pathologically, all of the first five tumors in the head and neck and esophagus were proven to be squamous cell carcinoma with various grades of differentiation, and the last one was transitional cell carcinoma. The cancers were found in the early clinical stage, and were completely controlled one by one except for the ureteral tumor under treatment. His characteristic medical history and physical findings, i.e. bilateral cataracts, short stature, baldness, diabetes mellitus, high-pitched voice, and multiple malignancies, met the clinical criteria for possible Werner syndrome, a genetic premature aging disorder, though the possibility of phenocopy of this syndrome has not been ruled out. We have followed him carefully because he might be vulnerable to malignant tumor formation.

Objective: The eye-focused video camera as sensitive to infrared light is very useful for detecting nystagmus with open eyes in the dark. The existence of physiological nystagmus has been reported. We investigated how frequently physiological positional and positioning nystagmus is seen in healthy individuals under infrared video goggles., Materials and Methods: Eighty-nine healthy individuals were examined in this study. Positional and positioning nystagmus was examined with infrared video goggles., Results: Positional nystagmus could be detected in 65 of the 89 subjects under infrared video goggles. The majority of nystagmus was horizontal nystagmus, and vertical nystagmus was also seen in four subjects. Nystagmus was most frequently recognized in right or left shoulder down position. Positioning nystagmus was detected in 40 subjects., Conclusions: Positional and positioning nystagmus frequently exist in healthy subjects. This finding means that the existence of physiological nystagmus must be considered when diagnosing dizzy patients using this equipment.

We examined the usefulness of the dye extrusion method for assessing cochlear hair cell death in guinea pigs. Unilateral temporal bones were incubated in sterile Dulbecco modified Eagle's medium for 1-6 h and then perfused with PBS/0.3% trypan blue to determine hair cell viability. Cells with nuclei stained with trypan blue were assumed to have died. The contralateral temporal bones of each animal were incubated with the same medium for 1-6 h and examined by transmission electron microscopy (TEM). This method revealed that hair cell viability under these conditions was maintained for at most 3 h. After incubation for more than 3 h, hair cell injury began and increased. After 6 h incubation, TEM revealed apoptotic death of outer hair cells. The results with this method agreed with the TEM findings. The dye extrusion method is simple, easy and useful for screening hair cell death in the cochlea under pathological conditions.

Glutamate is an excitatory neurotransmitter in the cochlea and has toxic effects on the organ of Corti in various pathological conditions. The toxic effects of glutamate have not been determined in detail. In this study, we examined morphological changes in the organ of Corti of guinea pigs following local application of glutamate. Morphological changes were noted in outer hair cells. Degeneration of outer hair cells was found 24 h after glutamate treatment. The extent of degeneration depended on exposure time. Inner hair cells did not exhibit any degeneration. In addition, no degenerative changes were detected in nerve endings attached to hair cells. These findings suggest that outer hair cells are the initial site of degeneration caused by application of excess glutamate to the inner ear.

OK432, a heat- and penicillin-treated lyophilized powder of a low virulent Su strain of Streptococcus pyogenes, was injected into the perilymphatic space of guinea pigs in order to determine the kinetics of exudation of inflammatory cells into the cochlea over a 7-day period. OK432 induced exudation of many neutrophils and Asialo GM1-positive cells into the scala tympani. The numbers of these cells peaked on the first day after OK432 treatment, and then gradually decreased. Four days after treatment very few of either of these types of cells were observed in the scala tympani. Asialo GM1-positive cells were confirmed to be activated macrophages. In ears treated with physiological saline or with the additive included in OK432 in control studies, no notable changes in the inner ear were recognized. These findings suggest that the inner ear can undergo induction of macrophage rapidly exudation by OK432 treatment as has previously been observed for other organs.

The pathogenesis of Kikuchi's disease (Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis) remains unclear. However, some previous studies have suggested that a disorder in cellular immunity is responsible for this disease, and apoptotic cell death appears to be the principal finding in the histogenesis of this disease. In the present study, a lymph node from a female patient with Kikuchi's disease was examined by transmission electron microscopy (TEM). TEM revealed specific morphological features of apoptotic cells, such as nuclear chromatin condensation and fragmentation along the nuclear membrane with intact organelles, and the presence of histiocytes phagocytosing karyorrhectic debris (apoptotic bodies) in areas affected by Kikuchi's disease. Although neither the role nor the trigger of apoptosis in Kikuchi's disease has been clearly determined, our findings show that apoptotic cell death clearly plays a role in the pathogenesis of Kikuchi's disease.

Redox regulation reportedly plays a role in maintaining cochlear homeostasis. However, little is known about the roles of oxidation-reduction systems in the cochlea. We examined the role of the cystine/cysteine oxidation-reduction system in survival of cochlea hair cells in vitro. The survival of hair cells was evaluated in cochlea specimens following incubation with the medium supplemented with various concentrations of cystine. Dying hair cells were detected by the trypan blue extrusion method. The rates of cell death for both outer and inner hair cells increased significantly with a decrease in the concentration of cystine. In addition, the rate of cell death of IHCs tended to be higher than that of OHCs. These findings suggest that the cystine/cysteine system might be required for maintenance of homeostasis in cochlear hair cells, especially in IHCs.

Nitric oxide (NO) is a neurotoxic gas which causes neuronal cell death. NO ototoxicity has also been reported, 1-Hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5), NO donor, was used for studying NO. In this in vitro study, we examined whether NOC-5 and the cleavage products arising from it after production of No have ototoxic effects on the cochlea. The temporal bones of 55 guinea pigs were dissected and incubated in Dulbecco Modified Eagle's Medium (DMEM) with low glucose and 10% foetal bovine serum (FBS) perfused with various concentrations (100, 50, 10, 1 mM, 100 microM) of NOC-5 (pH 7.4) or the same concentrations of N-isopropyl 1-3 propanildiamine (R-NH2). Hair cell death was assessed using trypan blue staining. With NOC-5, percentages of outer hair cell death were 99.2, 98.0, 45.2, 40.5, and 20%, respectively, and percentages of inner hair cell death were 69.3, 70.2, 22.5. 11.1 and 0%, respectively. With R-NH2, percentages of outer hair cell death were 90.3, 81.1, 29.8, 21.0 and 19.3%, respectively, and percentages of inner hair cell death were 61.4, 48.1, 10.2, 5.4 and 0%, respectively. Ultramicroscopic examination showed that hair cell death was necrotic. Although NOC-5 is useful for study of NO, its cleavage products are also ototoxic.

Cancer extending from the retromolar fossa to the masticator space with neck metastasis (T4N2M0, Stage IV) was surgically removed en bloc by maxillectomy using a mandibular swing technique. This approach allowed a wide surgical view and was useful as handling the external and internal pterygoid muscles and upper neck dissection could be combined. Though there have been several surgical approaches to the masticator space, in the case of tumors which are commonly malignant there, this approach is useful and satisfactory.

Over the 10 years from 1988 to 1997, a total of 18 cases of tuberculosis of the head and neck (8 of the cervical lymph node, 5 of the larynx, 2 of the salivary glands, and 1 each of the hypopharynx, tongue and middle ear) were diagnosed in our department. Four cases were diagnosed in 1996 and 8 in 1997, indicating a rapid increase over these 2 years. Definitive diagnosis was based on histopathological examination in 14 cases, detection of M. tuberculosis in 1 case and exclusion diagnosis, mainly using the tuberculin skin test, in 3 cases. The length of time from the first examination to obtaining a definitive diagnosis was 14.2 +/- 6.5 days in five subjects in whom tuberculosis was suspected from the beginning or in whom tuberculosis was suggested by the physician in making a differential diagnosis, 25.3 +/- 17.2 days in the group in whom malignant tumour was suspected and 64.3 +/- 57.3 days in other cases. Although no significant difference was found (p = 0.077), the length of time until diagnosis tended to be shorter in the cases that were suspected of having tuberculosis from the beginning. Family history and past history of tuberculosis, contact with a tuberculous patient and abnormal findings at chest X-ray were examined as background factors, and some of these were present in nine out of the 18 cases. In the five cases diagnosed in the early stage, some of the background factors were found in four cases. However, no significant difference in the time until definitive diagnosis was found between the groups with or without background factors in all cases (p = 0.675). These results suggest the importance of considering tuberculosis when performing differential diagnoses.

The regulation of cochlear lateral wall blood flow was investigated in rats using histochemistry, immunohistochemistry and transmission electron microscopy. The contractile protein, tropomyosin (TM) was localized in the pericyte around the vessels of spiral ligament but little was seen around strial capillaries. Prostaglandin I2 (PGI2) is a vasodilatory substance produced by PGI2 synthase (PGI2S), which is present in the endothelium of the vessels of spiral ligament but not much is present around strial capillaries. Endothelial nitric oxide synthase (eNOS) was present in the endothelium of both the vessels of spiral ligament and strial capillaries. These findings indicate that the blood flow of the cochlear lateral wall is regulated mainly in the spiral ligament by locally produced substances and that strial blood flow is not significantly regulated by pericytes responsible for enlargement or constriction of capillaries.

Free radicals are known to cause damage to biological tissues. We used histochemical methods to examine the emergence of free radicals in kanamycin (KM)-treated guinea pig cochlea. As a preliminary in vitro study, the emergence of free radicals was observed in guinea pig cochlea incubated with KM. In an in vivo study, KM was placed on the guinea pig round window membrane and the emergence of free radicals was observed over time. The emergence of free radicals was observed along the luminal membrane and hair bundles of outer hair cells. The appearance and disappearance of free radicals in the cochlea coincided with the transport of KM into the inner ear. These findings suggest that the emergence of free radicals could be attributed to the administration of KM.

The presence of ganglio-N-tetraosylceramide (asialo GM1)-positive cells in mouse cochlea was tested for using an immunohistochemical method with an anti-asialo GM1 antibody which reacts with natural killer cells and macrophages in mouse. Only a few asialo GM1-positive cells were present on the surface of the scala tympani of the basal turn near the collecting venules. Transmission electron microscopic study showed the internal structure of these cells to be that of macrophages. These findings suggest that asialo GM1-positive cells function as resident type macrophages against invasion by pathogens of the mouse cochlea.

The effect of acoustic trauma on cochlear strial circulation was investigated immunohistologically in the guinea pig. Kanamycin was used as a tracer of blood flow. Moreover, histochemical examinations were made to reveal the emergence of free radicals in the cochlea following acoustic trauma. At 5 min (5 min after intense sound exposure 120-125 dB SPL, 3 h) the blood flow in the stria vascularis was greatly diminished. At 2 h the strial blood flow started to recirculate and at 6 h it appeared to have returned to normal. Superoxide anion radicals (O2-) emerged along the luminal membrane of the marginal cells of the stria vascularis at 5 min. O2- disappeared at 30 min, but reappeared at 2 h. The cause of its emergence at 5 min was obscure. However, the strange phenomenon that O2- emerged again at 2 h seemed ascribable to the re-circulation of strial blood flow after sound exposure.

Recent studies have shown that inner ear sensory cells may regenerate in mammals as well as in birds. In this in vivo study we investigated the regeneration of vestibular hair cells in guinea pigs after gentamycin intoxication, and found that the vestibular sensory epithelia reproduced new hair cells 30 days after degeneration, due to 30 consecutive days of gentamycin treatment. From the regeneration pattern of sensory epithelia, the supporting cells were identified as the progenitors of hair cells.

The present immunohistologic study demonstrates that cochlear strial blood circulation is markedly damaged in guinea pigs subjected to intense acoustic stimulation. In contrast, autonomic unbalance of the inner ear induced by resection or electric stimulation of the superior cervical ganglion has no appreciable effect on cochlear strial blood flow. In consequence, although strial blood circulation in the cochlea is susceptible to pathological change in some conditions, it does not appear to be affected by autonomic unbalance alone.

Transplacental distribution of kanamycin (KM) to 35-60 day embryonal or fetal inner ear of the guinea pig following maternal treatment was investigated by an immunohistological technique. KM, administered at any stage of pregnancy, migrated through the placenta and entered into the cochlea. The drug pathway to the organ of Corti seemed to consist of two routes: the spiral vessels and the capillaries of the spiral limbus. However, at an early stage of pregnancy, KM was detected only slightly in the area corresponding to the stria vascularis, probably due to immaturation of strial capillaries.