ß-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.

The mammalian cochlea is composed of sensory hair cells as well as multiple different types of non-sensory supporting cells. Pillar cells are one type of supporting cell that form the tunnel of Corti and include two morphologically and functionally distinct subtypes: inner pillar cells (IPCs) and outer pillar cells (OPCs). The processes of specification and differentiation of inner versus outer pillar cells are still unclear. Here, we show that ß-Catenin is required for establishing IPC identity in the mammalian cochlea. To differentiate the transcriptional and adhesion roles of ß-Catenin in establishing IPC identity, we examined two different models of ß-Catenin deletion; one that deletes both transcriptional and structural functions and one which retains cell adhesion function but lacks transcriptional function. Here, we show that cochleae lacking ß-Catenin transcriptional function lost IPCs and displayed extranumerary OPCs, indicating its requirement for establishing IPC identity. Overexpression of ß-Catenin induced proliferation within IPCs but not ectopic IPCs. Single-cell transcriptomes of supporting cells lacking ß-Catenin transcriptional function show a loss of the IPC and gain of OPC signatures. Finally, targeted deletion of ß-Catenin in IPCs also led to the loss of IPC identity, indicating a cell autonomous role of ß-Catenin in establishing IPC identity. As IPCs have the capacity to regenerate sensory hair cells in the postnatal cochlea, our results will aid in future IPC-based hair cell regeneration strategies.

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

Insulin-like growth factor 1 promotes the extension of Tracheal Epithelium in an in Vitro Tracheal organ culture model.

OBJECTIVE: Rapid epithelialization is crucial to maintain tracheal patency and prevent potential graft failure in tracheal reconstruction after tracheal resection for cancer with tracheal infiltration or tracheal stenosis. Insulin-like growth factor 1 is a liver-secreted endocrine molecule that controls cell proliferation, differentiation, and apoptosis and has been reported to promote epithelialization in several organs. Here, we utilized mouse tracheal organ cultures to examine the effect of insulin-like growth factor 1 on tracheal epithelialization. METHODS: The trachea was resected from thirteen-week-old female ICR mice, and cut into small plate-shaped tracheal sections. First, the expression of insulin-like growth factor 1 receptor was assessed by immunohistochemistry. Secondly, the tracheal sections were cultured for seven days in the culture medium, and the morphological change during the seven-day culture was assessed by immunohistochemistry, hematoxylin and eosin staining, and scanning electron microscopy. Moreover, the tracheal sections were cultured for 48 h with different concentration of insulin-like growth factor 1 (0, 0.1, 1 and 10 µg/mL) in the culture medium, and the extension length of the tracheal epithelium during culture was measured in order to assess the effect of topical IGF1 on tracheal epithelialization. RESULTS: Immunohistochemistry showed that insulin-like growth factor 1 receptor was expressed in tracheal epithelium. Immunohistochemistry, hematoxylin and eosin staining, and scanning electron microscopy showed that the tracheal organ cultures were stable for at least seven days without apparent morphological damage. The effect of insulin-like growth factor 1 on tracheal epithelialization was examined in plate-shaped tracheal sections cultured in medium supplemented with or without insulin-like growth factor 1 for 48 h. We also found that the epithelial edge of plate-shaped tracheal sections extended further along the surface of the tracheal section in culture medium containing insulin-like growth factor 1 compared with that in culture medium without insulin-like growth factor 1. CONCLUSION: The current study using an in vitro mouse tracheal organ culture model demonstrated that topical insulin-like growth factor 1 treatment promoted the extension of tracheal epithelium, suggesting the potential utility of insulin-like growth factor 1 in aiding rapid tracheal epithelialization in patients requiring tracheal reconstruction using tissue-engineered tracheas.

Csf1 Signaling Regulates Maintenance of Resident Macrophages and Bone Formation in the Mouse Cochlea.

In the mammalian cochlea, resident macrophages settle in the spiral ligament, spiral ganglion, and stria vascularis, even at the steady state. Resident macrophages in the cochlea are believed to maintain homeostasis in the inner ear and become active, as part of the front line defense, following inner ear damage. However, the exact roles of cochlear resident macrophages require further clarification. Colony stimulating factor-1 (Csf1) signaling regulates survival, proliferation, and differentiation of resident macrophages and appears to be essential for resident macrophages in the inner ear. To examine the roles of Csf1 signaling in auditory function, we examined the ossicles and inner ear of homozygous Csf1 mutant (Csf1 op/op ) mice. The ossicles including the incus and stapes of Csf1 op/op mice macroscopically demonstrated bone thickening, and the otic capsules of the inner ear were also thick and opaque. Histological analyses demonstrated that the otic capsules in Csf1 op/op mice were thickened and showed spongy bone degeneration. Measurements of the auditory brainstem response revealed significant elevation of thresholds in 4-week old Csf1 op/op mice compared with wild-type littermates, indicating that Csf1 op/op mice demonstrate hearing loss due to, at least in part, deformity of the ossicles and bone capsule of the inner ear. Furthermore, Csf1 op/op mice are deficient in the number of resident macrophages in the spiral ligament and stria vascularis, but not in the spiral ganglion. These data provide evidence that Csf1 signaling is important not only for bone formation in the inner ear, but also for the maintenance of resident macrophages in the spiral ligament and stria vascularis in the adult mouse cochlea.

Early Development of Resident Macrophages in the Mouse Cochlea Depends on Yolk Sac Hematopoiesis.

Resident macrophages reside in all tissues throughout the body and play a central role in both tissue homeostasis and inflammation. Although the inner ear was once believed to be "immune-privileged," recent studies have shown that macrophages are distributed in the cochlea and may play important roles in the immune system thereof. Resident macrophages have heterogeneous origins among tissues and throughout developmental stages. However, the origins of embryonic cochlear macrophages remain unknown. Here, we show that the early development of resident macrophages in the mouse cochlea depends on yolk sac hematopoiesis. Accordingly, our results found that macrophages emerging around the developing otocyst at E10.5 exhibited dynamic changes in distribution and in situ proliferative capacity during embryonic and neonatal stages. Cochlear examination in Csf1r-null mice revealed a substantial decrease in the number of Iba1-positive macrophages in the spiral ganglion and spiral ligament, whereas they were still observed in the cochlear mesenchyme or on the intraluminal surface of the perilymphatic space. Our results demonstrated that two subtypes of resident macrophages are present in the embryonic cochlea, one being Csf1r-dependent macrophages that originate from the yolk sac and the other being Csf1r-independent macrophages that appear to be derived from the fetal liver via systemic circulation. We consider the present study to be a starting point for elucidating the roles of embryonic cochlear resident macrophages. Furthermore, resident macrophages in the embryonic cochlea could be a novel target for the treatment of various inner ear disorders.

First Implant-Induced Changes in Rostral Brainstem Impair Second Implant Outcomes in Sequential Bilateral Cochlear Implant Children With Long Inter-Implant Delay.

HYPOTHESIS: Long-term unilateral use of a cochlear implant (CI) induces abnormal maturation of the rostral brainstem innervating the contralateral ear. BACKGROUND: In sequential bilateral CI children with long inter-implant delay, both sides of auditory cortices were dominantly activated by the first CI, but mechanisms of this abnormal development of the auditory system remain unclear. METHODS: Fifteen sequential bilateral CI children with long delay (mean ±â€ŠSD, 28.7 ±â€Š12.1 mo) underwent electrically evoked auditory brainstem response (EABR) testing using each of the first and second CI (CI1 and CI2, respectively), immediately after the second implantation. CI1 and CI2 were implanted at age of 23.7 ±â€Š9.6 and 53.1 ±â€Š12.1 months (mean ±â€ŠSD), respectively. Apical-to-basal difference in electrically evoked interwave III-V latencies (eIII-eV slope) which decreases with implant use was compared between the CI1 and CI2 sides. Their speech perception scores were evaluated 3 years after the second implantation. RESULTS: eIII-eV slopes evoked by the CI2 showed less mature pattern than those by the CI1. This CI2 versus CI1 difference in eIII-eV slopes, however, reduced as the inter-implant delay was prolonged, suggesting CI1-induced maturation of the rostral brainstem innervating the second ear before the second implantation. The smaller CI2 versus CI1 difference in eIII-eV slopes at the second implantation was correlated to poorer outcomes using the CI2 than the CI1. CONCLUSIONS: In this population, long-term unilateral CI use induced re-organization of the rostral brainstem innervating the second ear, which affected hearing outcomes using the CI2. Evaluation of eIII-eV slopes at the second implantation may be useful to predict hearing outcomes with CI2.

Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro.

In the context of acquired sensorineural hearing loss (SNHL), cochlear hair cells have long been thought to be among the most vulnerable elements in mammalian cochleae. However, recent studies have indicated that the synaptic connection between inner hair cells (IHC) and spiral ganglion neurons (SGN) can be an important target for the treatment of SNHL. Our previous studies in patients with sudden SNHL demonstrated delayed and gradual hearing recovery following topical application of insulin-like growth factor 1 (IGF-1), suggesting that not only protective but also regenerative mechanisms may account for hearing recovery after treatment with IGF-1. We then hypothesized that IGF-1 has the potential to drive the regeneration of IHC-SGN synapses. To test this hypothesis, we investigated the effects of IGF-1 on IHC-SGN synapses using cochlear explant cultures from postnatal day 2 mice that had been damaged by exposure to the excitatory amino acids N-methyl-d-aspartate and kainate. Cochlear explants that lost IHC-SGN synapses upon exposure to excitatory amino acids were cultured with exogenous IGF-1 for an additional 48 h. We observed increased numbers of IHC-SGN synapses after exogenous IGF-1 application. Pharmacological inhibition of the IGF-1 receptor attenuated the restoration of IHC-SGN synapses by exogenous IGF-1. These findings indicated that IGF-1 induces regeneration of IHC-SGN synapses in cochlear explant cultures from postnatal day 2 mice. Therefore, in a future study we will perform in vivo experiments using adult mice to ascertain the effects of IGF-1 on the regeneration of IHC-SGN synapses.

Orbital apex syndrome secondary to a fungal nasal septal abscess caused by Scedosporium apiospermum in a patient with uncontrolled diabetes: a case report.

BACKGROUND: Orbital apex syndrome is a localized type of orbital cellulitis, where mass lesions occur at the apex of the cranial nerves. Although nasal septal abscess is uncommon, the organism most likely to cause nasal septal abscess is Staphylococcus aureus, and fungal septal abscesses are rare. Here we present an extremely rare and serious case of orbital apex syndrome secondary to fungal nasal septal abscess caused by Scedosporium apiospermum in a patient with uncontrolled diabetes. CASE PRESENTATION: A 59-year-old man with a 1-month history of headache underwent consultation in an otolaryngological clinic of a general hospital. He was diagnosed with nasal septal abscess and was treated with incisional drainage and 1 month of an antibiotic drip; however, his symptoms persisted. The patient later complained of diplopia due to bilateral abducens nerve palsy, and was then referred to the department of Otolaryngology - Head and Neck Surgery, Kobe City Medical Center General Hospital. The septal lesion was biopsied under general anesthesia, and S. apiospermum was detected using polymerase chain reaction. The patient was treated with an antifungal drug and surgical resection of the lesion was performed. Although the patient survived, he lost his eyesight. CONCLUSIONS: This patient represents the second reported case of nasal septal abscess and orbital apex syndrome caused by S. apiospermum. If not treated properly, septal abscess can be life-threatening and cause severe complications, such as ablepsia.

A case of desmoid tumor co-existing with recurrent squamous cell carcinoma in the larynx.

Extra-abdominal desmoid tumor, also known as aggressive fibromatosis, has aggressive behavior with local infiltration and tendency for recurrence. Though head and neck is reported to be one of the most common sites, a desmoid tumor in the larynx is extremely rare. A 67-year-old male visited our hospital with prolonged hoarseness and received laryngo-microsurgery with the diagnosis of laryngeal polyp. After the operation, he eventually developed a laryngeal squamous cell carcinoma with papilloma, confirmed by second laryngo-microsurgery and received radiation therapy. After the third laryngo-microsurgery to remove residual papilloma, white irregular mass appeared on the right vocal cord and grew rapidly beneath the glottis, causing dyspnea. After 2 additional laryngo-microsurgeries, he was diagnosed having the dermoid tumor co-existing with recurrent squamous cell carcinoma. He underwent near-total laryngectomy and is currently alive without disease, speaking using a vocal shunt. Only five cases of the desmoid tumors arising in the adult larynx have been reported in the English literature. In this case, repeated surgery and radiation were suspected as the causes. Also, the present report is the first to describe desmoid tumor co-existing with recurrent squamous cell carcinoma in the larynx.

Detection of subclinical recurrence or second primary cancer using (18) F-FDG PET/CT in patients treated curatively for head and neck squamous cell carcinoma.

BACKGROUND: The efficacy of posttreatment surveillance (18) F-fluorodeoxyglucose positron emission tomography ((18) F-FDG PET)/CT was evaluated in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The subjects were 158 patients with HNSCC who underwent PET/CT after definitive treatment. PET/CT detection of subclinical recurrence or a second primary cancer and the effect of timing of PET/CT scans on survival were analyzed. RESULTS: Recurrence or a second primary cancer occurred in 70 patients, and 67% of these cases were detected by PET/CT. Detection rates were 17%, 9%, 5%, and 5% in the first, second, third, and fourth scans at 4, 9, 15, and 21 months, respectively. In multivariate analysis, patients who underwent early first scans had significantly better disease-specific (hazard ratio [HR] = 0.37; p = .031) and overall (HR = 0.45; p = .040) survival compared with those who underwent late first scans. CONCLUSION: Earlier detection of subclinical lesions by surveillance PET/CT within 4 months after treatment may improve survival in patients with HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E511-E518, 2016.

Bilateral duplication of the internal auditory canal: a case with successful cochlear implantation.

We report a case of bilateral duplication of the internal auditory canal (IAC). An 11-month-old girl with congenital profound hearing loss was referred to our hospital. Imaging evaluations revealed bilateral IAC duplication, which contained the facial and cochleovestibular nerves in one canal, but no nerves in the other. She underwent cochlear implantation. At 5 months after surgery her hearing thresholds with the cochlear implant are 40 and 45dB at 2000 and 4000Hz, respectively. Bilateral duplicated IAC is extremely rare, with seven cases reported in the literature. This case represents a previously unreported type of IAC duplication, and is the first case in which cochlear implantation was successfully performed.

Characteristics and prognosis of patients with thyroglobulin-positive and radioactive iodine whole-body scan-negative differentiated thyroid carcinoma.

OBJECTIVE: The prognosis of differentiated thyroid carcinoma is generally favorable. However, some patients have negative radioiodine whole-body scans and detectable serum thyroglobulin with biochemical radioiodine-refractory carcinoma and are candidates for treatment with a multikinase inhibitor, such as sorafenib. The purpose of this study is to investigate the characteristics and prognosis of differentiated thyroid carcinoma patients who are thyroglobulin positive and scan negative. METHODS: We retrospectively classified 153 patients treated for 15 years by serum thyroglobulin level and radioiodine scan results and examined the relationship between clinical characteristics and prognosis. RESULTS: Overall, 27% of the patients were classified as thyroglobulin positive/scan negative (positive/negative) while 61% were thyroglobulin negative/scan negative (double negative). Compared with double-negative patients, positive/negative patients were significantly older, predominantly male, had a higher pT and pN, stage, and had higher pre-operative thyroglobulin values. Positive/negative patients showed worse prognosis in terms of overall survival, disease-specific survival and disease-free survival than double-negative patients (10-year overall survival, 85 vs. 93%, P = 0.001; 10-year disease-specific survival, 94 vs. 100%, P = 0.03, 10-year disease-free survival, 77 vs. 93%, P < 0.001). Multivariate analysis revealed that positive/negative status was the only factor associated with disease-free survival, including age and TNM stage (hazard ratio: 6.37, 95% confidence interval: 1.22-33.3). However, the median duration of disease-free period for positive/negative patients was 14.2 years. CONCLUSIONS: Few patients among thyroglobulin-positive/scan-negative patients are candidates for sorafenib, despite the significant survival differences from double-negative patients.

A case of angiosarcoma arising from internal jugular vein.

Primary angiosarcoma is a rare disease with a poor prognosis. It most commonly arises in the head and neck region; localization in the deep soft tissue of the neck is extremely rare. We herein present a case of angiosarcoma derived from the right internal jugular vein. A 79-year-old man presented with a 1-month history of a growing right neck mass. Computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography, and fine-needle aspiration cytology revealed a malignant tumor of unknown origin. Right neck dissection was performed for both diagnosis and therapy. Immunostaining of the resected tumor cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2-40, which allowed for a definitive diagnosis of angiosarcoma. Postoperative radiotherapy (66Gy) was performed on the right neck, including the surgical bed and upper mediastinum. The patient was followed up for 10 months with no recurrence. Only six cases of angiosarcoma arising in the deep soft tissue of the neck have been reported in the English-language literature. The present report is the first to describe angiosarcoma arising from the internal jugular vein.

Prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography/CT volume-based parameters in patients with oropharyngeal squamous cell carcinoma with known p16 and p53 status.

BACKGROUND: The purpose of this study was to determine whether pretreatment 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) volume-based parameters, such as metabolic tumor volume and total lesion glycolysis, add more prognostic information in patients with oropharyngeal squamous cell carcinoma (SCC). METHODS: The subjects were 47 patients with oropharyngeal SCC who underwent 18F-FDG PET/CT before any treatment and followed by definitive therapy. PET parameters (metabolic tumor volume and total lesion glycolysis) and tumor p16/p53 status were evaluated retrospectively. Univariate and multivariate analyses were performed for disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). RESULTS: All volume-based PET parameters were found to be significant prognostic factors for DFS, DSS, and OS in univariate analysis. In multivariate analysis, only metabolic tumor volume for total tumor lesions (cutoff 65) retained an independent association with DFS, DSS, and OS. CONCLUSION: Metabolic tumor volume for total tumor lesions may be a predictive marker for survival outcomes in patients with oropharyngeal SCC with known p16/p53 status.

Is 18F-fluorodeoxyglucose positron emission tomography/computed tomography helpful in the decision-making process for neck dissection in patients with T1-T2 lingual cancer?

CONCLUSION: The usefulness of addition of positron emission tomography/computed tomography (PET/CT) in decisions as to whether to perform neck dissection in patients with T1-T2 lingual squamous cell carcinoma (SCC) might be limited, but adding the condition of lymph nodes with a maximum standardized uptake value (SUVmax) >4.5 to existing criteria would be helpful. OBJECTIVES: The purpose of this study was to investigate the usefulness of PET/CT for performing neck dissection in patients with T1-T2 lingual SCC. METHODS: This retrospective review surveyed 19 patients with T1-T2 lingual SCC who underwent neck dissection after meeting one or more of the following criteria: (1) clinically positive nodes; (2) >4 mm thickness; (3) ≥ 3 cm longest diameter of the primary tumor. Focal 18F-fluorodeoxyglucose (FDG) uptake was considered to indicate PET-positive nodes (PET + Ns). The relation between pathologically positive nodes (p + Ns) and PET + Ns was estimated. RESULTS: There were 14 PET + Ns at 12 of 66 levels (18%) in 8 of the 19 (42%) patients. There were also 6 p + Ns (1%) among 412 nodes at 5 cervical lymph node levels (8%) in 5 patients (26%). The sensitivity and specificity for PET/CT were 80% and 64%, respectively. The SUVmax was measured, and receiver operating characteristic (ROC) analysis was undertaken to obtain better accuracy. The sensitivity and specificity were 60% and 100% when the SUVmax cut-off value was set at 4.5.

Risk factors for retropharyngeal cellulitis in Kawasaki disease.

OBJECTIVE: Kawasaki disease (KD) is an acute multisystemic vasculitis of unknown etiology that occurs in infants and children. Retropharyngeal cellulitis has been reported as a rare manifestation of KD. This study investigated the frequency and characteristics of patients with KD manifesting as retropharyngeal soft-tissue swelling. METHODS: We retrospectively reviewed 277 patients, with a mean age of 1 year and an age range of 7 months to 12 years, in whom KD had been diagnosed between 2005 and 2011. RESULTS: In 10 patients (3.6%), contrast-enhanced computed tomography (CECT) showed low-density lesions without ring enhancement in the retropharyngeal spaces. These patients presented initially with fever and cervical lymphadenopathy, and were initially treated by their pediatricians for suppurative lymphadenitis (seven patients) or retropharyngeal abscess (three patients). KD was finally diagnosed either after antibiotics had been ineffective or when other symptoms characteristic of KD emerged. CONCLUSION: Low-density lesions in the retropharyngeal space were identified by CECT in 3.6% of the KD patients. Early diagnosis of KD is essential because coronary artery lesions develop in 50% of untreated patients. If a child presents with fever, cervical lymphadenopathy, and swelling of the retropharyngeal space, KD should be included in the differential diagnoses.

Prognostic impact of p16 and p53 expression in oropharyngeal squamous cell carcinomas.

BACKGROUNDS: A p16 protein is known to be overexpressed in human papillomavirus-positive head and neck squamous cell carcinoma specimens. p53 is a tumor suppressor protein detectable by immunohistochemistry in carcinogen-associated head and neck squamous cell carcinoma as a result of gene mutations. The purpose of this study is to investigate the prognostic impact of p16 and p53 expression in oropharyngeal squamous cell carcinomas. METHODS: We retrospectively examined the relationship between prognosis, and p16 and p53 expression levels of oropharyngeal squamous cell carcinoma specimens in 53 patients using immunohistochemistry. RESULTS: Overall, 55% of patients were p16 positive and 45% p16 negative, while 28% were p53 positive and 72% p53 negative. The p16 status showed an inverse relationship with the p53 status. A survival analysis by p16 status, p53 status, Union for International Cancer Control stage and main treatment modality demonstrated that only p16 status was related to better prognosis in terms of overall survival and disease-specific survival (3-year overall survival, 87 vs. 62%, P = 0.02; 3-year disease-specific survival, 90 vs. 62%, P = 0.02). To evaluate the practical prognostic factors in oropharyngeal squamous cell carcinoma patients, we classified patients as either p16-positive or p53-negative oropharyngeal squamous cell carcinomas, representing human papillomavirus-related oropharyngeal squamous cell carcinoma with wild-type p53 or the remaining patients with p16-negative or p53-positive OPSCCs, respectively. The former group showed survival advantages in terms of overall survival and disease-specific survival by log-tank test compared with the latter group (3-year overall survival, 96 vs. 58%, P = 0.005; 3-year disease-specific survival, 96 vs. 63%, P = 0.02). CONCLUSIONS: A group of patients who were p16 positive/p53 negative had better prognoses in terms of overall survival and disease-specific survival than that who were p16-positive alone.

Clinical features of rapidly progressive bilateral sensorineural hearing loss.

CONCLUSION: Rapidly progressive bilateral sensorineural hearing loss (SNHL) often develops as a symptom of intracranial diseases or systemic vasculitis. For early diagnosis and treatment of these potentially fatal diseases, a history of hearing deterioration within 2 months and associated symptoms may be important. OBJECTIVES: To reveal clinical features and causative diseases for rapidly progressive bilateral SNHL. METHODS: The inclusion criterion was patients with bilateral progressive SNHL, who had experienced difficulty in daily conversation within 4 days to 1 year after the onset of hearing loss awareness. This study was a retrospective evaluation of 12 patients with rapidly progressive bilateral SNHL who visited our hospital between 2007 and 2011. RESULTS: The causative disease for hearing loss was identified in 11 of 12 patients; intracranial lesions including nonbacterial meningitis, meningeal metastasis of lymphoma, and superficial siderosis in 4 patients, systemic vasculitis in 2, auditory neuropathy spectrum disorder in 1, and an isolated inner ear disorder in 4. Relatively rapid hearing deterioration within 2 months showed a significant association in six patients with an intracranial lesion or systemic vasculitis. Moreover, all these six patients complained of dizziness and/or non-cochleovestibular symptoms such as fever, headache, and/or altered mental state in addition to hearing loss.

Predictive value of middle ear aeration before second-stage operation in staged tympanoplasty with soft-wall reconstruction.

CONCLUSION: The extent of middle ear aeration before second-stage canal wall-down (CWD) tympanoplasty was correlated with postoperative middle ear stability. OBJECTIVE: To evaluate middle ear aeration before second-stage CWD tympanoplasty as a predictor of postoperative re-aeration potential and external auditory canal (EAC) stability in staged CWD tympanoplasty with soft-wall reconstruction (SWR). METHODS: Middle ear aeration was evaluated before and at 1 year after the second-stage operation in patients who underwent staged CWD tympanoplasty with SWR for middle ear cholesteatoma. Based on the computed tomography (CT) findings, middle ear aeration was graded as A when the mastoid and tympanic cavities were aerated, B when only the tympanic cavity was aerated, and C in cases with no aeration in the tympanic cavity. We also examined postoperative EAC stability. RESULTS: Forty-one ears were included. In all, 17 of 19 ears (89.5%) with grade A aeration preoperatively maintained grade A aeration postoperatively, while 5 of 18 ears (27.8%) with grade B aeration had grade A aeration, and no ear with grade C aeration had recovered grade A aeration. All ears with grade A aeration preoperatively maintained smooth EACs. EAC retraction requiring additional treatment occurred in five ears with grade B aeration and all ears with grade C aeration.

[A case of intraorbital solitary fibrous tumor resected successfully with preoperative arterial embolization].

The solitary fibrous tumor (SFT) is a rare spindle cell neoplasm derived from mesenchymal cells. It sometimes recurs clinically, and is categorized as an 'intermediate malignancy' tumor under the WHO (World Health Organization) classification of soft tissue tumors. Several studies have reported on intraorbital SFTs, but none of them has pointed out the utility of preoperative arterial embolization in the case of an intraorbital SFT. A 75-year-old man, who had received a dacryocystectomy for a benign tumor in the right lacrimal sac 30 years previously, visited our hospital complaining of lower eyelid swelling and lachrymation that had persisted for a year. CT and MRI revealed an intraorbital lesion, and the open biopsy specimen showed dense growth of spindle cells, which turned out to be an SFT by immunohistochemistry based on the findings. After preoperative embolization of the infraorbital artery, we removed the tumor with a skin incision on the lower rim of the orbit with little bleeding. The surgical specimen revealed that the tumor was close to a lacrimal canaliculus, which suggested the tumor originated from the lacrimal apparatus considering the patient's past history. He was followed up for three months without recurrences.