Yoshinobu Kidokoro

Deficiency of Transcription Factor Brn4 Disrupts Cochlear Gap Junction Plaques in a Model of DFN3 Non-Syndromic Deafness

Brn4, which encodes a POU transcription factor, is the gene responsible for DFN3, an X chromosome–linked, non-syndromic type of hearing loss. Brn4-deficient mice have a low endocochlear potential (EP), hearing loss, and ultrastructural alterations in spiral ligament fibrocytes, however the molecular pathology through which Brn4 deficiency causes low EP is still unclear. Mutations in the Gjb2 and Gjb6 genes encoding the gap junction proteins connexin26 (Cx26) and connexin30 (Cx30) genes, respectively, which encode gap junction proteins and are expressed in cochlear fibrocytes and non-sensory epithelial cells (i.e., cochlear supporting cells) to maintain the proper EP, are responsible for hereditary sensorineural deafness. It has been hypothesized that the gap junction in the cochlea provides an intercellular passage by which K+ is transported to maintain the EP at the high level necessary for sensory hair cell excitation. Here we analyzed the formation of gap junction plaques in cochlear supporting cells of Brn4-deficient mice at different stages by confocal microscopy and three-dimensional graphic reconstructions. Gap junctions from control mice, which are composed mainly of Cx26 and Cx30, formed linear plaques along the cell-cell junction sites with adjacent cells. These plaques formed pentagonal or hexagonal outlines of the normal inner sulcus cells and border cells. Gap junction plaques in Brn4-deficient mice did not, however, show the normal linear structure but instead formed small spots around the cell-cell junction sites. Gap junction lengths were significantly shorter, and the level of Cx26 and Cx30 was significantly reduced in Brn4-deficient mice compared with littermate controls. Thus the Brn4 mutation affected the assembly and localization of gap junction proteins at the cell borders of cochlear supporting cells, suggesting that Brn4 substantially contributes to cochlear gap junction properties to maintain the proper EP in cochleae, similar to connexin-related deafness.

Postoperative Management of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps: Impact of High-Dose Corticosteroid Nasal Spray

Introduction  Eosinophilic chronic rhinosinusitis (ECRS) is characterized by an eosinophilic inflammation driven by Th2-type cytokines. Glucocorticosteroids are the most common first-line treatment for ECRS with nasal polyps. Objective  We have evaluated the long-term treatment with double-dose intranasal corticosteroids in refractory ECRS nasal polyps resistant to the conventional dose and assessed the risk of adverse systemic effects Methods  Sixteen subjects were enrolled in this study. All subjects had ECRS after endoscopic sinus surgery that resulted in recurrent mild and moderate nasal polyps and were undergoing a postoperative follow-up application of mometasone furoate at a dose of 2 sprays (100 μg) in each nostril once a day (200 μg). All the patients were prescribed mometasone furoate, administered at a dose of 2 sprays (100 μg) in each nostril twice a day (400 μg) for 6 months. Results  The average scores of the symptoms during the regular dose of intranasal steroid treatment were 5.2 ± 2.2, but 6 months after the high-dose application, they had significantly decreased to 2.5 ± 1.4 ( p  < 0.05). The polyp size showed an average score of 1.38 during the regular dose which was significantly reduced to 0.43 ( p  < 0.01) by the double dose. Glycated hemoglobin (HbA1c) showed normal ranges in all the patients tested. The cortisol plasma concentration was also normal. Conclusion  Doubling the dose of the nasal topical spray mometasone furoate might be recommended for the treatment of recurrent nasal polyps in the postoperative follow-up of intractable ECRS.

Primary malignant lymphoma of the uvula

We experienced a very rare case of primary malignant lymphoma of the uvula. The patient was an 80-year-old Japanese woman with a one month history of oral discomfort. She had a uvular mass occupying the oropharyngeal space and received surgical treatment. Follicular lymphoma was diagnosed by immunohistochemical staining. In the general examination, PET-CT showed no abnormal accumulation in the body, and the marrow chromosome examination results were normal. From the above results, our case was considered stage IA (UICC) and we added postoperative radiotherapy (33.6Gy). At 3 years after the radiation therapy, no recurrence or metastasis was found. Correspondence to: Dr. Takeshi Kusunoki, Department of Otorhinolaryngology, Juntendo University of Medicine, Shizuoka Hospital, 1129 Nagaoka Izunokunishi, Shizuoka 410-2295, Japan; Fax: +81-55-948-5088; E-mail: ttkusunoki001@aol.com

Cervical fistula caused by submandibular sialolithiasis

In oto-rhino-laryngology, cases of submandibuillar sialolithiasis are common. Submandibular sialoadentis with sialolith may cause severe complications such as deep neck abscess and sepsis. We introduce a rare case of a cervical fistula with abscess caused by submandibular sialolith. The patient had diabetes. We performed drainage of the left submandibular gland that included a Wharton duct stone and abscess by an external skin incision approach. Submandibular sialoadentis due to sialolith would likely progress to neck abscess and the formation of a neck skin fistula; moreover, the condition can be worsen by the coexistence of diabetes. This neck abscess with skin fistula could have caused potentially fatal complications such a carotid artery rupture or sepsis. In such cases the infected source should be carefully removed as soon as possible.

Tracheal stenosis due to huge adenomatous goiter

Background: Some thyroid anaplastic carcinoma and lymphoma have been reported to cause tracheal stenosis or choking. Begin thyroid tumors with dyspnea due to tracheal stenosis are exceedingly rare. Case presentation: We experienced a huge adenomatous goiter (resected specimen weight: 520g). Total thyroidectomy resolved the dyspnea and there was no tracheomalacia. Postoperative CT confirmed a normal tracheal lumen free from stenosis. Conclusions: We reviewed the CT findings of thyroid benign tumors with dyspnea and found that tumors occupied the space between the posterior wall of trachea and esophagus leading to tracheal stenosis as in our case. Such tracheal findings would actually lead to dyspnea. Correspondence to: Dr. Takeshi Kusunoki, Department of Otorhinolaryngology, Juntendo University of Medicine, Shizuoka Hospital 1129 Nagaoka Izunokunishi, Shizuoka 410-2295, Japan; Fax: +81-55-948-5088; E-mail: ttkusunoki001@aol.com

Two Cases of the Laryngeal Cystic Lesions

We experienced two rare cases with laryngeal cystic lesions (laryngocele and laryngeal cyst). In the first case, the laryngocele case was removed by laryngomicrosurgery using an oral approach under general anesthesia. In the second case, the magnetic resonance imaging demonstrated a dumbbell-type cyst with mucus widely extending from the laryngeal lumen to the neck through the thyroid cartilage. The patient had undergone chemotherapy for renal carcinoma with multiple lung and bone metastases. Therefore, we performed only fine needle aspiration rather than aggressive surgery for extirpation of the cyst using an external approach. This fine needle aspiration could improve the quality of life by decreasing both the left laryngeal swelling and the resulting pain, which were the chief complaints.

A case of a very elongated styloid process 8 cm in length with frequent throat pain for 10 years

We experienced a case of an elongated styloid process that was 8 cm in length. The patient was a 68-year-old Japanese man with frequent episodes of left-sided throat pain for 10 years. The elongated styloid process could be diagnosed by 3D-computed tomography (left and right length: 7.8 cm and 8.0 cm, respectively) and successfully treated with surgery, since the anatomic relationships could be fully visualized. Surgical methods for shortening an elongated styloid process involve an intraoral or external approach. The external approach to the styloid process involves a trans-cervical approach to the parapharyngeal space, which enables wider visualization in the operative field than an intraoral approach. In the present case, the styloid process reached the parapharyngal space. Therefore, we selected the external approach and shortened only the left-sided styloid process (the same side as the throat pain). The chief complaint disappeared immediately after the operation.

A Case of Maxillary Bone Metastasis from Lung Cancer.

We experienced a very rare case of maxillary bone metastasis from lung cancer. The patient was a 77-year-old Japanese man with 1-month history of right alar swelling with hard pain as his chief complaint. Computed tomography scan showed a 1 cm length round lesion in the right nasal vestibule close to the pyriform fossa edge of the right maxillary bone. He had severe pulmonary dysfunction due to recurrent end stage lung cancer and diabetes. The expected remainder of his life would be half a year. Therefore, his very poor condition precluded general anesthesia. To relieve the nasal pain, shorten the stay in the hospital and improve the quality of life (QOL), we performed minimally invasive surgery under local anesthesia. Our minimally invasive surgery could improve QOL by relieving the hard nasal pain until the recurrence of cancer and enable the patient to live at home.

A case of laryngeal cancer associated with dermatomyositis

We experienced a rare case of laryngeal cancer associated with dermatomyositis. The patient was a 63-year-old male and Japanese. He was admitted to our department of Otorhinolaryngology with dysphagia for a day as a chief complaint. He became aware of hoarseness with bloody sputum and then face edema with redness a half year before. At first physical examination, he had bilateral eyelid edema with erythema, finger edema with keratinizing erythema and limb extensor erythema. Serous creatine phosphokinase was 850 IU/mL (normal range: 40-200 IU/mL). Later, he was referred to the rheumatology department and was diagnosed as having dermatomyositis. Fiberscopic examination revealed laryngeal cancer with left laryngeal palsy. We gave priority to the laryngeal treatment. As a result, the symptoms of dermatomyositis were improved.