研究者詳細 - 小川　郁

論文 - 小川　郁

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GFAP aggregates in the cochlear nerve increase the noise vulnerability of sensory cells in the organ of Corti in the murine model of Alexander disease

Masuda Masatsugu, Tanaka Kenji F., Kanzaki Sho, Wakabayashi Kenichiro, Oishi Naoki, Suzuki Takafumi, Ikenaka Kazuhiro, Ogawa Kaoru

Neuroscience Research 62 （ 1 ） 15 - 24 2008年09月

ISSN 0168-0102

Outer hair cell (OHC) loss in the auditory sensory epithelium is a primary cause of noise-induced sensory-neural hearing loss (SNHL). To clarify the participation of glial cells in SNHL, we used an Alexander disease (AxD) mouse model. These transgenic mice harbor the AxD causal mutant of the human glial fibrillary acidic protein (GFAP) under the control of the mouse GFAP promoter. It is thought that GFAP aggregates compromise the function of astrocytes. In the auditory pathway, the formation of GFAP aggregates was observed only in GFAP-positive cells of the cochlear nerve. The presence of GFAP aggregates did not change auditory function at the threshold level. To assess the change in vulnerability to auditory excitotoxicity, both transgenic and control mice were treated with intense noise exposure. Auditory threshold shifts were assessed by auditory brainstem responses (ABR) at 1 and 4 weeks after noise exposure, and OHC damage was analyzed by quantitative histology at 4 weeks after exposure. Transgenic mice showed more severe ABR deficits and OHC damage, suggesting that cochlear nerve glial cells with GFAP aggregates play a role in noise susceptibility. Thus, we should focus more on the roles of cochlear nerve glial cells in SNHL.

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Sentinel node concept in clinically N0 laryngeal and hypopharyngeal cancer

Tomifuji Masayuki, Shiotani Akihiro, Fujii Hirofumi, Araki Koji, Saito Koichiro, Inagaki Koji, Mukai Makio, Kitagawa Yuko, Ogawa Kaoru

Annals of Surgical Oncology 15 （ 9 ） 2568 - 2575 2008年09月

ISSN 1068-9265

Background: Sentinel nodes (SNs) are the lymph nodes that directly receive lymphatic flow from a primary cancer lesion. The SN concept implies that lymphatic metastasis initially occurs at SNs. SN navigation surgery can be introduced for cancers in which the SN concept is established. In SN navigation surgery, lymph node dissection beyond SNs can be omitted if SNs are metastasis free. Although the SN concept has been investigated frequently for oral and oropharyngeal cancer, it has so far been investigated less for laryngeal and hypopharyngeal cancer. In this study, we investigated whether the SN concept is applicable for laryngeal and hypopharyngeal cancer. Methods: Twenty patients with T2-T4 and clinically N0 laryngeal and hypopharyngeal cancer were recruited. ^99mTc-phytate was injected into several sites surrounding the tumor on the day before surgery. Lymphoscintigrams were acquired from at least two different viewpoints. SNs were surveyed intraoperatively, and neck dissections including at least levels II, III, and IV were performed. Results: SNs had occult metastases in five cases. In the remaining 15 cases, neither SNs nor other lymph nodes contained metastases, consistent with the SN concept. There was one false-negative case showing delayed nodal metastasis 2 years after initial surgery. The overall accuracy of the SN concept was 95%. Conclusion: Our study shows that SN biopsy is a reliable strategy to determine correct lymph node status in N0 laryngeal and hypopharyngeal cancer. SN detection was valuable in evaluating the need for neck dissection, whether ipsilaterally or bilaterally.

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Mucoepidermoid carcinoma of the head and neck

Ozawa Hiroyuki, Tomita Toshiki, Sakamoto Koji, Tagawa Takamasa, Fujii Ryoichi, Kanzaki Sho, Ogawa Kaoru, Kameyama Kaori, Fujii Masato

Japanese Journal of Clinical Oncology 38 （ 6 ） 414 - 418 2008年06月

ISSN 0368-2811

Objective: It is well known that mucoepidermoid carcinoma (MEC) displays a variety of biological behaviors. While the high-grade type is a highly aggressive tumor, its low-grade counterpart usually demonstrates a more benign nature and several systems have, therefore, been proposed to grade this neoplasm. Methods: This report analyzes 43 patients suffering from head and neck MEC, who were treated in our department during the period from 1989 to 2005. The relationship between clinical and pathologic characteristics and survival rate was investigated. Results: The 5-year overall and disease-free survival rate was 62.3 and 57.2%. Multivariate analysis demonstrated that the parameters that significantly affected survival were the patient's age (P = 0.040) and treatment method (P = 0.011). Conclusions: The patient's age and treatment method is the prognostic parameter in this study. Although complete surgical resection is the standard treatment for MEC, we should aggressively consider adjunctive radiotherapy in those cases that have a high risk of recurrence and poor prognosis.

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An anatomical study of the three-dimensional structure of the nasal septum in patients with alveolar clefts and alveolar-palatal clefts

Nagasao Tomohisa, Miyamoto Junpei, Yasuda Shohei, Ogata Hisao, Imanishi Yorihisa, Zhu Xiaohai, Jiang Hua, Ogawa Kaoru, Nakajima Tatsuo

Plastic and Reconstructive Surgery 121 （ 6 ） 2074 - 2083 2008年06月

ISSN 0032-1052

BACKGROUND: The present study was performed to quantitatively analyze the three-dimensional morphology of the nasal septa of patients with alveolar and alveolopalatal clefts. METHODS: Twenty-five unilateral complete cleft lip patients with alveolar clefts only (alveolar cleft group) and 35 unilateral complete cleft lip patients with alveolar and palatal clefts (alveolar and palatal cleft group) were included in the study. Although no patient in either group had undergone alveoloplasty, all patients had undergone palatoplasty. The degree of nasal septum deviation was studied for each patient at three different depths along the anteroposterior axis using three-dimensional computed tomographic data; the data were compared between the two groups to elucidate whether the difference in cleft type affects the morphologic patterns of the nasal septum. RESULTS: The nasal septa of the alveolar and palatal cleft group patients presented more uneven morphologic patterns than those of the alveolar cleft group patients. In the alveolar cleft group, the nasal septa did not present significantly different degrees of deviation at their anterior and posterior parts. In the alveolar and palatal cleft group, however, the posterior parts of the nasal septa presented greater deviation than the anterior parts. In the alveolar and palatal cleft group, furthermore, a significant correlation was observed between the severity of the cleft and the degree of the nasal septum deviation. CONCLUSIONS: The nasal septa present different three-dimensional morphologic patterns between the patients with alveolar clefts only and those with alveolopalatal clefts. This difference should be considered when performing surgical treatments for these patients.

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Migraine associated dizziness and treatment

Goto Fumiyuki, Yabe Haruna, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 67 （ 3 ） 205 - 210 2008年06月

ISSN 0385-5716

Introduction: The importance of the relationship between vertigo and headache, especially migraine, has been recognized. Vertigo has been found to be three times more common in patients with migraine than in controls, and migraine is found at a prevalence of 30%-50% in patients presenting with vertigo. Several authors have proposed different diagnostic criteria for defining migrainous vertigo and vestibular migraine. In this study, we attempted to clarify the current situation of migraine-related dizziness at our institute. Subjects and Methods: A retrospective review of 9 patients with migraine-related vertigo who visited our institute was conducted. We used the diagnostic criteria proposed by Neuhauser (2001). Results: Of the 9 patients, 1 was male and 8 were female; 6 patients had visited a neurosurgeon once, 3 patients had been diagnosed once as having Meniere's disease, although they had normal hearing. Calcium channel blockers, antidepressants, SSRIs (Selective Serotonin Reuptake Inhibitors) and anxiolytics had been prescribed as prophylactic agents. Of the 9 patients, 5 improved with the prophylactic treatment, 2 improved slightly, and 2 showed no change. The patients who showed improvement in the migraine with the prophylactic treatment also showed improvement of their vertigo at the same time. As acute-phase treatment NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and triptans were prescribed. Three patients had a past history of BPPV (benign paroxysmal positional vertigo). Conclusion: The importance of diagnosis of migrane-associated vertigo was confirmed, since both prophylactic and acute-phase treatment were effective against both migraine and vertigo in these patients. To obtain further evidence for the treatment of migraine-associated vertigo, a more organized study should be conducted. The relationship between BPPV and migraine-associated vertigo should also be investigated in a future study.

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Neuroprotective effects of T-817MA against noise-induced hearing loss

Yamashita Daisuke, Shiotani Akihiro, Kanzaki Sho, Nakagawa Masaya, Ogawa Kaoru

Neuroscience Research 61 （ 1 ） 38 - 42 2008年05月

ISSN 0168-0102

Oxidative stress, including reactive oxygen species and other free radicals, is thought to play an important role in neuronal cell death, including noise-induced hearing loss. 1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate (T-817MA), a novel neurotrophic agent, protects against oxidative stress-induced neurotoxicity. This study examines the effects of T-817MA in noise-induced ototoxicity in the cochlea. Guinea pigs received treatment with T-817MA-enhanced water (0.2, 0.7 mg/ml) or untreated water (control) beginning 10 days prior to noise exposure and continuing through this study. All subjects were exposed to 4-kHz octave-band noise at 120-dB SPL for 5 h. Auditory thresholds were assessed by sound-evoked auditory brainstem response at 4, 8, and 16 kHz, prior to and 10 days following noise exposure. Hair cell damage was analyzed by quantitative histology. T-817MA significantly reduced threshold deficits and hair cell death. These results suggest T-817MA reduces noise-induced hearing loss and cochlear damage, suggesting functional and morphological protection.

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Noninvasive in vivo delivery of transgene via adeno-associated virus into supporting cells of the neonatal mouse cochlea

Iizuka Takashi, Kanzaki Sho, Mochizuki Hideki, Inoshita Ayako, Narui Yuya, Furukawa Masayuki, Kusunoki Takeshi, Saji Makoto, Ogawa Kaoru, Ikeda Katsuhisa

Human Gene Therapy 19 （ 4 ） 384 - 390 2008年04月

ISSN 1043-0342

There are a number of genetic diseases that affect the cochlea early in life, which require normal gene transfer in the early developmental stage to prevent deafness. The delivery of adenovirus (AdV) and adeno-associated virus (AAV) was investigated to elucidate the efficiency and cellular specificity of transgene expression in the neonatal mouse cochlea. The extent of AdV transfection is comparable to that obtained with adult mice. AAV-directed gene transfer after injection into the scala media through a cochleostomy showed transgene expression in the supporting cells, inner hair cells (IHCs), and lateral wall with resulting hearing loss. On the other hand, gene expression was observed in Deiters cells, IHCs, and lateral wall without hearing loss after the application of AAV into the scala tympani through the round window. These findings indicate that injection of AAV into the scala tympani of the neonatal mouse cochlea therefore has the potential to efficiently and noninvasively introduce transgenes to the cochlear supporting cells, and this modality is thus considered to be a promising strategy to prevent hereditary prelingual deafness.

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Bcl-2 genes regulate noise-induced hearing loss

Yamashita Daisuke, Minami Shujiro B., Kanzaki Sho, Ogawa Kaoru, Miller Josef M.

Journal of Neuroscience Research 86 （ 4 ） 920 - 928 2008年03月

ISSN 0360-4012

Proteins of the Bcl-2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise-induced hearing loss. In this study, we assessed the expressions of anti- and proapoptotic Bcl-2 genes, represented by Bcl-xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4-kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL-xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl-2 family proteins in regulating sensory cell survival or death following intense noise. Bcl-xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death.

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Case report

Goto Fumiyuki, Nakai Kimiko, Kunihiro Takanobu, Ogawa Kaoru

2008年01月

Background: Psychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT), which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease. Case presentation: A 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs) failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT), he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no additional treatment. He is now free from drugs, including tranquilizers, and has continued AT. No additional treatment was performed. When we examined him six and nine months later for follow-up, he was free of vertigo and insomnia. Conclusion: AT together with CBT can be a viable and palatable treatment option for Meniere's disease patients who are not responsive to other therapies.

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Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction

Mizutari Kunio, Matsunaga Tatsuo, Kamiya Kazusaku, Fujinami Yoshiaki, Fujii Masato, Ogawa Kaoru

Journal of Neuroscience Research 86 （ 1 ） 215 - 222 2008年01月

ISSN 0360-4012

We recently showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) causes hearing loss mainly due to degeneration of cochlear lateral-wall fibrocytes. In the present study, we analyzed the effect of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-VAD-FMK) on 3-NP-induced hearing loss in a model showing temporary threshold shifts at low frequencies and permanent threshold shifts at high frequencies. The model rats received an intraperitoneal injection of either Z-VAD-FMK or vehicle for 3 days starting 1 day prior to 3-NP treatment. One day after the administration of 3-NP, the auditory brain-stem response (ABR) threshold at 20 kHz was elevated to 70 dB in the Z-VAD-FMK group and to 85 dB in controls. The Z-VAD-FMK group completely recovered to the preoperative level within 14 days, whereas in the controls, the ABR threshold remained elevated at 50 dB even 28 days after the administration of 3-NP. Treatment with Z-VAD-FMK also improved recovery of hearing at 8 kHz but did not change recovery at 40 kHz. Histological examination demonstrated that treatment with Z-VAD-FMK inhibited progressive degeneration of the lateral-wall fibrocytes in the cochlear basal turn, as well as apoptosis of these fibrocytes. These results clearly indicate that caspase-dependent apoptosis of fibrocytes in the cochlear lateral wall plays an important role in hearing loss in the present animal model. Moreover, the results of the present study suggest that systemic administration of a caspase inhibitor may be an effective therapy for sensorineural hearing loss caused by acute energy failure such as that observed in cochlear ischemia.

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Cost-Effectiveness of different treatment modalities for seasonal allergic rhinitis in japan — comparison of laser treatment with subcutaneous immunotherapy and oral medication —

Taniguchi Yuki, Fujii Shunji, Ohshiro Takafumi, Sasaki Katsumi, Ohshiro Toshio, Suzuki Takafumi, Kanzaki Sho, Ogawa Kaoru

Laser Therapy 17 （ 4 ） 193 - 197 2008年

ISSN 0898-5901

Allergic rhinitis is a condition which shows a high prevalence throughout the world. Once a person is sensitized to a specific allergen, spontaneous resolution of the allergy occurs only very rarely and this results in a steady accumulation of patient population. Worldwide attention to this affliction is being paid from both the medical and the economic perspectives. In Japan, the most typical seasonal allergic rhinitis is caused by cedar pollen during the spring months of late February to early May. Rough estimates of a 15 to 20% prevalence rate have been reported and hence Japanese cedar pollinosis is deemed as a national disease. The efficacy and cost-effectiveness of the treatment are of great concern to the social medical system of Japan. Previously there have been several reports regarding the cost-effectiveness of new medications and desensitization immunotherapy. The authors have previously reported their experience of treating allergic rhinitis with the Nd:YAG laser and its efficacy. However there are no reports, as of yet, on the cost-effectiveness of this procedure. The authors compared the costs of three typical treatment protocols for cedar pollenosis: Nd:YAG laser treatment, anti-histamine prescription and desensitization immunotherapy. The results revealed that the direct costs associated with the Nd:YAG laser treatment were less compared to the two other treatment protocols. The authors also believe that the indirect economical losses associated with allergic rhinitis such as loss of work force for hospital visits was also lessened with the Nd:YAG laser treatment.

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Phobic postural vertigo treated with autogenic training

Goto Fumiyuki, Nakai Kimiko, Kunihiro Takanobu, Ogawa Kaoru

Cases Journal 1 （ 1 ） 2008年

ISSN 1757-1626

Case presentation: We present a case of a patient who suffered from phobic postural vertigo. A 37-year-old female complained of dizziness. She had started experiencing dizziness almost 3 years She was intractable to many sort of conventional therapy. In the end, her symptom disappeared after introduction of autogenic training.Conclusion: Autogenic training can be a viable and acceptable treatment option for phobic postural vertigo patients who fail to respond to other therapies. This case emphasizes the importance of autogenic training as a method to control symptom of phobic postural vertigo.Background: Patients suffering from dizziness due to vertigo are commonly encountered in the department of otolaryngology. If various clinical examinations do not reveal any objective findings, then the patients are referred to the department of internal medicine or psychiatry. In many cases, the diagnosis is psychological dizziness. Phobic postural vertigo, which was first reported by Brandt T et al in 1994, is supposed to be a type of psychological dizziness. The diagnosis is based on 6 characteristics proposed by Brandt et al. Patients are usually treated with conventional medical therapy, but some cases may be refractory to such a therapy. Psychotherapy is recommended in some cases; however, psychotherapy including autogenic training, which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of autogenic training in a patient suffering from phobic postural vertigo.

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A multidisciplinary approach to carotid body tumors. Report of five cases

Tomita Toshiki, Ozawa Hiroyuki, Tagawa Takamasa, Sakamoto Koji, Ogawa Kaoru

Journal of Otolaryngology of Japan 110 （ 12 ） 743 - 751 2007年12月

ISSN 0030-6622

We performed a retrospective review of five patients with carotid body tumors at our institution between 1997 and 2005. Out of the five patients, three patients were treated by surgical resection of the tumor, and 2 patients were observed. It would seem that it is difficult to suspect this disease based only on the clinical findings, because the disease was suspected in only one patient at the first medical examination. Imaging tests are important for establishment of the diagnosis. Color Doppler sonography and MR angiography in addition to MRI are useful. Angiography and balloon Matas test are important for selection of candidates for the operation. The resected tumors were all classified in Shamblin's group II. Delayed cerebral infarction was caused in one patient postoperatively, although the carotid artery was preserved. The dissection in a tumor-adventitial plane using the bipolar coagulation technique under the microscope was performed in the other two cases. Histological examination of the specimen revealed no tumor cells in the excision stump. Dissection in the tumor-adventitial plane using bipolar coagulation under the microscope is important for carotid artery preservation and radical resection of Shamblin's group I and II tumors. It is necessary to compare the risk of the operation with the problems of observation in the process of decision making and to achieve reliable informed consent. Moreover, it is necessary to examine the indications for operation in individual cases referring to the age, past history, expected Shamblin's classification, and result of the balloon Matas test. A multidisciplinary approach should be used, involving the fields of otolaryngology, radiology, neurosurgery and vascular surgery to treat these patients.

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"Ear popper®", new device to treat otitis media with effusion

Goto Fumiyuki, Yabe Haruna, Goto Kazuyoshi, Ogawa Kaoru

Oto-Rhino-Laryngology Tokyo 50 （ 5 ） 330 - 332 2007年10月

ISSN 0386-9687

Otitis media with effusion is a common disease and is the most common cause of hearing impairment among children. It is important to treat this condition in children to provide them a better quality of life. "Ear popper®" is a new device distributed in the US for non-surgical treatment of middle ear effusion. The device allows easy insufflation of the eustachian tube. We used the "Ear popper®" for the treatment of middle ear effusion in 18 patients. The patients ranged in age from 2 to 9 years old, and were composed of 8 males and 10 females. Successful insufflation without any problems was achieved in 17 out of the 18 patients at our hospital. This was confirmed by visual observation of the tympanic membrane, impedance audiometry and pure-tone audiometry. The new device is portable and easy to use. Although in this clinical trial, the use of this device was restricted only to doctors at the hospital, we are currently attempting to introduce the use of this device at home by the patients by themselves, just as in the U.S.A. We consider that the home treatment of persistent otitis media with effusion in children with "Ear popper®" is highly efficacious.

Development of solitary plasmacytoma in the internal auditory canal and inner ear after allogeneic hematopoietic stem cell transplantation for plasma cell leukemia

Masuda Masatsugu, Inoue Yasuhiro, Tanosaki Ryuji, Kanzaki Sho, Ogawa Kaoru

Japanese Journal of Clinical Oncology 37 （ 9 ） 701 - 703 2007年09月

ISSN 0368-2811

Here we report the first case of the development of intracranial solitary plasmacytoma in the inner ear after allogeneic stem cell transplantation (allo-SCT) in a 39-year-old Japanese female with primary plasma cell leukemia (PCL). A point to note is that this is not a case on multiple myeloma but on PCL. She was successfully treated with local irradiation and survived more than 6 years from the time of diagnosis and transplantation. This case elucidates the biology of PCL and stresses the need for an individual approach to the clinical management of patients with plasma cell neoplasm undergoing allo-SCT.

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Liposarcoma of the retropharyngeal space

Ozawa Hiroyuki, Soma Keiko, Ito Mari, Ogawa Kaoru

Auris Nasus Larynx 34 （ 3 ） 417 - 421 2007年09月

ISSN 0385-8146

Liposarcoma is a soft tissue malignant tumor that is common in adults, though the incidence of this type of tumor in the head and neck region is extremely low. Herein, we report a case of myxoid liposarcoma occurring in the retropharyngeal space. We were unable to make a proper diagnosis of this tumor prior to surgery because of the radiographic findings and the anatomical location resembled those of neurogenic tumor. Myxoid liposarcoma often recurs. So its excision must be carried out carefully and radical dissection is recommended. In the past, liposarcomas arising in the retropharyngeal space were not radically resected because the extent of resection in the head and neck area risked poor functional outcome. In the present case, functional resection and radiotherapy were performed and proved to be efficacious in that no recurrence was observed for 2 years.

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Clinical study of 28 cases of cervical lymph node metastasis from an unknown primary carcinoma

Tagawa Takamasa, Tomita Toshiki, Yamaguchi Hiroshi, Ozawa Hiroyuki, Sakamoto Koji, Ogawa Kaoru, Fujii Masato

Nippon Jibiinkoka Gakkai kaiho 110 （ 7 ） 506 - 512 2007年07月

ISSN 0030-6622

From 1989 to 2005, 28 patients--20 men and 8 women--with cervical lymph node metastasis from an unknown primary carcinoma were treated and studied retrospectively. In histological diagnosis, open biopsy was conducted in 11 patients and non-open biopsy (FNA or frozen section diagnosis during surgery) in 17. Blind biopsy under general anesthesia was conducted in 10 patients, showing one primary tumor in the nasopharynx. Tonsillectomy for diagnosis was not done. In region of maximum-size lymph node metastasis, the upper cervical region accounted for 22 cases (79%). The N stage of cervical lymph nodes was as follows: N2a in 4, N2b in 14, N2c in 3, and N3 in 7. The histopathological diagnosis of cervical lymph node was as follows: squamous cell carcinoma in 21, adenocarcinoma in 3, mucoepidermoid carcinoma in 2, and others in 2. Therapy was as follows: only neck dissection in 7, neck dissection with postoperative radiation therapy in 13, and irradiation and chemotherapy in 8. All patients treated with irradiation and chemotherapy had been judged to be inoperable. Seven patients were found to have a subsequent primary tumor. Primary tumor sites were as follows: tonsils in 3 and upper gingiva, base of tongue, lung, and nasopharynx in 1 each. FDG-PET was conducted in 7 patients but revealed no primary tumor. Overall 5-year survival in this study was 46%. We should pay particular attention to the tonsils for detecting primary tumors in patients with cervical metastasis from an unknown primary carcinoma.

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Decreased expression of connexin-30 and aberrant expression of connexin-26 in human head and neck cancer

Ozawa Hiroyuki, Matsunaga Tatsuo, Kamiya Kazusaku, Tokumaru Yutaka, Fujii Masato, Tomita Toshiki, Ogawa Kaoru

Anticancer Research 27 （ 4 B ） 2189 - 2195 2007年07月

ISSN 0250-7005

Background: The relation of connexins and carcinogenesis has been studied in various organs and cell lines, with connexins currently being considered tumor suppressors. Materials and Methods: The expression of connexin-26 (Cx26) and connexin-30 (Cx30) in human head and neck carcinomas, as well as in adjacent normal mucosa, was evaluated by immunohistochemistry. Furthermore, the expression of these connexins with regard to apoptosis and cell differentiation was investigated. Results: In the cancer tissues, Cx30 expression was drastically reduced compared to apparently normal mucosa while Cx26 expression was almost the same. The intracellular distribution patterns of Cx26 and Cx30 in cancer cells differed between cancer locations. In the cancer tissues, expression of Cx26 and Cx30 was not related to apoptosis assessed by TdT-mediated dUTP-biotin nick end labeling (TUNEL) reaction or to cell differentiation assessed by immunoreaction to involucrin. Conclusion: The present results suggest that connexins may play a role in the carcinogenesis of head and neck cancer.

Clinical study of 28 cases of cervical lymph node metastasis from an unknown primary carcinoma

Tagawa Takamasa, Tomita Toshiki, Yamaguchi Hiroshi, Ozawa Hiroyuki, Sakamoto Koji, Ogawa Kaoru, Fujii Masato

Journal of Otolaryngology of Japan 110 （ 7 ） 503 - 505 2007年07月

ISSN 0030-6622

From 1989 to 2005, 28 patients-20 men and 8 women-with cervical lymph node metastasis from an unknown primary carcinoma were treated and studied retrospectively. In histological diagnosis, open biopsy was conducted in 11 patients and non-open biopsy (FNA or frozen section diagnosis during surgery) in 17. Blind biopsy under general anesthesia was conducted in 10 patients, showing one primary tumor in the nasopharynx. Tonsillectomy for diagnosis was not done. In region of maximum-size lymph node metastasis, the upper cervical region accounted for 22 cases (79%). The N stage of cervical lymph nodes was as follows : N2a in 4, N2b in 14, N2c in 3, and N3 in 7. The histopathological diagnosis of cervical lymph node was as follows : squamous cell carcinoma in 21, adenocarcinoma in 3, mucoepidermoid carcinoma in 2, and others in 2. Therapy was as follows : only neck dissection in 7, neck dissection with postoperative radiation therapy in 13, and irradiation and chemotherapy in 8. All patients treated with irradiation and chemotherapy had been judged to be inoperable, Seven patients were found to have a subsequent primary tumor. Primary tumor sites were as follows : tonsils in 3 and upper gingiva, base of tongue, lung, and nasopharynx in 1 each. FDG-PET was conducted in 7 patients but revealed no primary tumor. Overall 5-year survival in this study was 46%. We should pay particular attention to the tonsils for detecting primary tumors in patients with cervical metastasis from an unknown primary carcinoma.

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A novel drug therapy for recurrent laryngeal nerve injury using T-588

Mori Yuko, Shiotani Akihiro, Saito Koichiro, Araki Koji, Ikeda Ken, Nakagawa Masaya, Watabe Kazuhiko, Ogawa Kaoru

Laryngoscope 117 （ 7 ） 1313 - 1318 2007年07月

ISSN 0023-852X

OBJECTIVES/HYPOTHESIS: We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy.R(-)-1- (benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models. STUDY DESIGN: Animal study. METHODS: Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold. RESULTS: T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls. CONCLUSION: These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.

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