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Objectives: 18 F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG-PET/CT) is a diagnostic imaging method that is based on the Warburg effect, which is the increased uptake of glucose through aerobic glycolysis in cancer cells. The diagnostic value of 18 F-FDG-PET/CT for thyroid cancer is controversial. However, uptake of 18 F-FDG and the corresponding maximum standardized uptake value (SUVmax) is expected to reflect the metabolic status of cancer cells. In the present study, we sought to determine the relationship between 18 F-FDG uptake and tumor metabolism- associated factors., Methods: This was a single-center retrospective study. In the present study, SUVmax was compared with the expression of hexokinase 2 (HK2), glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF), and glutaminase 1 (GLS1) in 41 patients with thyroid cancer., Results: GLS1 expression was found to be moderately correlated with SUVmax (p < 0.001, r = 0.51), whereas HK2 and VEGF expression were weakly correlated (p = 0.011, r = 0.28, p = 0.008, r = 0.29, respectively) and GLUT1 did not correlate with SUVmax (p = 0.62, r = 0.06)., Conclusion: Our findings suggest 18 F-FDG PET/CT reflects GLS1 expression in thyroid cancer and could be used to select suitable candidates for GLS1 inhibitor treatment., Competing Interests: Declaration of competing interest No conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC)., Methods: This prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin. All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0., Results: SN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis. After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC., Conclusion: SLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III)., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study examined olfactory dysfunction in LATY136F knock-in mice and its pathogenic mechanism., Methods: The olfactory function of LATY136F knock-in mice was assessed by a behavioral test using cycloheximide solution, which has been used as a mice repellant because of its peculiar smell and unpleasant taste. The tests were administered to each group of LATY136F knock-in mice and WT mice at 8, 12, 16, 20, and 24 weeks of age. After the behavioral tests to evaluate olfactory function, the mice were sacrificed for evaluations by immunohistochemistry., Results: Behavioral tests to evaluate olfactory function showed that the LATY136F knock-in mice had a statistically significant level of olfactory dysfunction (P < 0.05). Histological analysis showed that the thickness of the olfactory epithelium in these mice was thinner than that in the age-matched wild type mice. There was no IgG4-RD like lesion in the olfactory epithelium of LATY136F knock-in mice. Olfactory marker protein and growth-associated protein 43 expressions in the olfactory epithelium of the LATY136F knock-in mice were markedly lesser than those in the wild type mice (P < 0.05)., Conclusion: The present study demonstrated that olfactory disturbances occurred in LATY136F knock-in mice. Furthermore, the mechanism was suggested to be reduced regeneration of the olfactory epithelium., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Silicosis is caused by inhalation of silica dust and is the most common type of pneumoconiosis. The characteristics of silicosis are inflammation of lung tissue and calcified lymphadenopathy of pulmonary hilum, mediastinum and paratrachea. We present a papillary thyroid carcinoma (PTC) case with paratracheal and superior mediastinal calcified lymphadenopathy caused by silicosis. The patient did not exhibit any respiratory symptoms or abnormal chest x-ray findings due to early phase silicosis. The lymph nodes were thought to be metastasis of PTC before surgery. Patient underwent total thyroidectomy with neck and superior mediastinum dissection. Post-surgery pathological examination exhibited coexistence of silica nodules and micrometastasis of PTC in paratracheal lymph nodes, but only silica nodules were observed in superior mediastinum lymph nodes. Patient's occupation was office worker but had worked as a stonemason for several decades prior. This is a first observed case of superior mediastinal lymphadenopathy by silicosis mimicking metastasis of PTC. Benign calcified lymphadenopathy may mimic metastasis of PTC in the evaluation of neck or mediastinal lesions., Competing Interests: Declaration of Competing Interest There was no conflict of interest with regard to this work., (Copyright © 2019. Published by Elsevier B.V.)

Objective: Microglia are highly specialized tissue macrophages in the central nervous system. Their activation in the auditory system has been reported in adult hearing loss models, but their status in the developing auditory system is less understood. Therefore, we investigated microglial status in the cochlear nucleus (CN) during normal developing periods and after exposing rats to amikacin, a potent ototoxin, around the time of hearing onset., Methods: To develop the deafness model, rats were administered with a daily intraperitoneal injection of amikacin (500 mg/kg) from postnatal day 7 (P7) to P15. To evaluate the expression of ionized calcium binding adaptor molecule 1 (Iba1), we performed immunohistochemical analysis using rat brains from P10-60. To compare the expression of microglia-related gene, reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis were performed., Results: Immunohistochemical analysis revealed that, under normal conditions, microglia had relatively large cell bodies with several extended processes that surrounded other cells at P10, while the sizes and number of these cells gradually decreased afterward. In contrast, when amikacin was administered from P7 to P15, microglia maintained large cell bodies with relatively shorter processes at both P15 and P21. Furthermore, RT-qPCR analysis revealed upregulation of genes including phagocytotic and anti-inflammatory markers after amikacin administration., Conclusion: These results suggest that microglia are activated in the CN, and they may contribute to tissue remodeling after early hearing loss in the developing auditory system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Cancer-related fatigue impairs daily functioning and negatively impacts health-related quality of life (HRQoL). Our previous study revealed that cisplatin-based chemoradiotherapy (CRT) impairs the carnitine system and carnitine deficiency leads to poor physical functioning. This open label, randomized, controlled prospective study investigated the effects of l-carnitine administration on plasma carnitine concentration, CRT-induced fatigue, and decline in HRQoL in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: Patients were divided into experimental group (received 1000mg of oral liquid l-carnitine once daily for 8 weeks) and control group. The primary and secondary endpoints were the change in HRQoL scores and the change in carnitine levels, respectively, from baseline (pre-CRT) to after CRT., Results: The mean total plasma carnitine concentration in the control group decreased significantly, 2 weeks after the end of chemotherapy, while no significant differences were seen in the l-carnitine group. l-carnitine administration, therefore, kept the physical functioning score unchanged., Conclusion: Our study shows that patients who receive CRT experience chemotherapy-induced damage of carnitine homeostasis leading to deficiency of carnitine and impairment of HRQoL. l-carnitine administration is beneficial in improving the HRQoL in patients with HNSCC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: A combination of platinum-based chemotherapy and radiotherapy is the standard treatment for nasopharyngeal carcinoma (NPC). However, the efficacy of chemotherapy has reached a plateau. Many autophagy studies suggest that autophagy can either promote or suppress to cancer progression. Thus, a role of autophagy in the acquisition of chemoradioresistance has recently been a notable event. Therefore, we examined the relationship between autophagy and chemotherapy in NPC., Methods: The expression of Beclin 1 and microtubule-associated protein light chain 3 (LC3), a marker of autophagy, was determined by immunohistochemistry in the biopsy samples of patients with NPC before and after the first course of chemotherapy. Additionally, to investigate in the effect of autophagy suppression in chemotherapy, NPC cell line C666-1 cells were treated with cisplatin and/or chloroquine, an inhibitor of autophagy., Results: The expression of Beclin 1 increased after chemotherapy in all patients. In NPC cell line C666-1, compared to cisplatin alone, combination therapy (cisplatin and chloroquine) reduced cell viability, and promoted cell apoptosis., Conclusions: These results suggest that autophagy, represented by Beclin 1, is upregulated after chemotherapy in both in vitro and in vivo NPC studies. Inhibition of autophagy could therefore be new strategy for NPC treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Unilateral cochlear damage has profound effects on the central auditory pathways in the brain., Methods: We examined the effects of unilateral cochlear ablation on VGLUT1 expression in the cochlear nucleus (CN) and the superior olivary complex (SOC) in neonatal rats., Results: VGLUT1 expression in the CN subdivisions (the AVCN, the PVCN and the DCN-deep layers) and the SOC (the MnTB, the LSO and the MSO) ipsilateral to the ablated side was significantly suppressed by unilateral cochlear ablation. Interestingly, VGLUT1 expression in the PVCN and the DCN-deep layers contralateral to the ablated side was also reduced., Conclusion: Our findings indicate that unilateral cochlear ablation affects VGLUT1 expression in the central auditory pathways not only ipsilateral but also contralateral to the ablated side., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Recurrent acute otitis media (AOM) in young children is rapidly increasing worldwide. Repeated antibiotic use leads to antibiotic-resistant pathogen development. Complementary and alternative medicine approaches have been suggested as a supplemental treatment option to conventional antimicrobial medicine. This randomized, parallel-group, open-label, non-herbal medicine controlled trial assessed the efficacy of a traditional Japanese herbal medicine, juzen-taiho-to (JTT) for AOM prevention in otitis-prone children., Methods: Children prone to recurrent AOM aged 6-48 months were recruited from 26 otolaryngology clinics in Japan and received conventional AOM treatment based on Japanese guidelines with or without 2 daily oral doses of JTT (0.10-0.25g/kg/day). The mean number of AOM episodes, coryza episodes, and duration of total antibiotic administration per month were compared during 3-month intervention., Results: At least one episode of AOM was diagnosed in 71% of JTT-group and 92% of control participants during follow-up. JTT administration reduced the frequency of AOM episodes by 57% compared with children who received conventional treatment alone (0.61±0.54 vs. 1.07±0.72 AOM instances/month; P=0.005) and also significantly decreased number of coryza episodes (P=0.015) and total antibiotic administration (P=0.024)., Conclusions: This is the first report of recurrent AOM prevention by herbal medication. JTT appears to effectively prevent recurrent AOM in children. Subsequent double-blind studies are needed to confirm the beneficial effects of JTT on recurrent AOM and upper respiratory tract infections., (Copyright © 2016. Published by Elsevier B.V.)

Objective: Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan., Methods: Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status., Results: Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111)., Conclusion: In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: A recent study identified a survival benefit with prophylactic neck dissection (ND) at the time of primary surgery as compared with watchful waiting followed by therapeutic neck dissection for nodal relapse, in patients with cN0 oral squamous cell carcinoma (OSCC). Alternative management of cN0 neck cancer is recommended to minimize the adverse effects of ND, indicating the need for sentinel node biopsy (SNB) and limited neck dissection. We conducted a multicenter Phase II study to examine the feasibility of SNB for clinically N0 OSCC., Methods: Previously untreated N0 OSCC patients (n=57) with clinical late-T2 or T3 tumors were enrolled across 10 institutions. SNB navigated with multislice frozen section analysis of sentinel nodes (SNs) and SNB supported sentinel node lymphatic basin dissection (SN basin dissection) were performed in a one-stage procedure. The endpoint was to investigate the rate of false-negative metastases after SN basin dissection and SNB alone., Results: Most tumors were late-T2 lesions (n=50; 87.7%). SNs were identified in all patients. A total of 196 SNs were detected. Among these SNs, 35 (17.8%) were positive for metastasis (9 in level I, 12 in level II, 12 in level III, 1 in level V and 2 in the contralateral region of the neck). The false-negative rate of SNB supported by SN basin dissection and SNB alone was 4.5% and 9.1%, respectively. The concordance of the SN status in intraoperative frozen sections with the permanent histopathology was 97.4% (191/196). The sensitivity and specificity of intraoperative pathological evaluation were 85.7% (30/35) and 100% (30/30), respectively. The 3-year overall survival (OS) and disease-free survival was 89.5% and 82.5%, respectively. The OS of SN-negative patients was significantly longer than that of SN-positive patients (P=0.047)., Conclusion: The current study verified that SN basin dissection was a useful back-up procedure for SNB performed as a one-stage procedure, showing a low false-negative rate. SNB alone is an appropriate staging method for patients with clinical N0 staging, and a reliable procedure to determine the appropriate levels for neck dissection., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of the HIF-1α and HIF-1β subunits. HIF-1 is a central regulator of responses to hypoxia; it enhances metastasis-related factors such as matrix metalloproteinases and vascular endothelial growth factor (VEGF). We have reported critical roles for HIF-1α in tumor microenvironments, and oncogenic properties of HIF-1α have been suggested in malignancies. Seven in absentia homologue (Siah) appeared to upregulate HIF-1 production, which prompted us to investigate the Siah association with HIF-1α expression in oral squamous cell carcinoma (OSCC)., Methods: Samples from fifty-five patients with OSCC were evaluated by immunohistochemistry for the protein expressions of Siah-1 and -2, HIF-1α, and VEGF. The expression levels of each protein and clinicopathological data were statistically analyzed., Results: Siah-1 and, Siah-2, HIF-1α, and VEGF were immunolocalized on the cell membranes and cytoplasm of the tumor cells. The expression of Siah-1 showed a linear dependence on the expression of HIF-1α (r=0.627, p<0.001). In 17 cases of the large tumor size category (T3 and 4), the mean Siah-1 expression score was significantly higher than in 41 cases of the small tumor size category (T1 and 2; p=0.001). In addition, in 16 cases of the lymph node metastasis-positive category (N1-3), the mean Siah-1 expression score was significantly higher than that in 42 cases of the lymph node metastasis-negative category (N0, p=0.001)., Conclusion: These results suggested that the expressions of Siah-1 and HIF-1α were clearly correlated in OSCC. Moreover, Siah-1 appears to be correlated with clinicopathological data, particularly tumor size., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: The treatment of recurrent respiratory papillomatosis (RRP) continues to be difficult. Adjuvant pharmacological treatment is increasingly being used, and intralesional cidofovir injection remains the leading option. Almost all papers regarding the treatment come from the United States and Europe. The present study demonstrated it for the first time from Asia., Methods: Ten patients with RRP were treated with intralesional cidofovir injection. The severity of papillomatosis and adverse events including blood leukocytes, blood neutrophils, and serum creatinine were evaluated before and after the completion of treatment., Results: Human papillomavirus (HPV) type 6 was detected in nine patients, and no types of HPV were detected in a remaining patient. Severity scores significantly improved after treatment (p=0.005). However, complete resolution was achieved in only one patient. No significant differences were observed between before and after treatment with respect to adverse events (p=0.866 for blood leukocytes, p=0.866 for blood neutrophils, and p=0.933 for serum creatinine). Squamous cell carcinoma occurred three and half years after the completion of treatment in a patient without HPV detection. However, the link between cidofovir and the occurrence of carcinoma in the case remains questionable., Conclusion: This initial report of intralesional cidofovir injection for RRP from Asia demonstrated acceptable efficacy without obvious adverse events. However, the uncontrolled spread of this treatment should be avoided, and eighteen statements approved by the task force of the United States should be referred to while planning this treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Recurrent respiratory papillomatosis (RRP) has historically been and still continues to be a difficult disease to treat. The present study aimed to characterize current practices in the treatment of RRP in Japan., Methods: A questionnaire was posted to the Department of Otolaryngology of all 80 central university hospitals in Japan., Results: A total of 56 universities responded to the survey. Regarding the use of surgical instruments, a trend toward a preference for lasers (50 hospitals) rather than a microdebrider (16 hospitals) or cold instruments (20 hospitals) was observed. Among the 50 hospitals frequently performing laser surgery, a carbon dioxide (CO2) laser was most commonly used, followed by a potassium-titanyl-phosphate (KTP) laser. The most favored adjuvant therapy was traditional Chinese medicine. Eight of the 56 university hospitals had an experience of using cidofovir, involving a total of 28 patients., Conclusion: The present study demonstrated the current trends in the management of RRP based on a questionnaire survey in a geographical area other than the US and UK for the first time. Treatment trends were generally similar in all three areas except for the least popular use of cidofovir in Japan., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Hypothyroidism is a late side effect after curative radiotherapy in the head and neck region. Superselective intra-arterial chemotherapy (SSIAC), when combined with radiation (SSIAC-R), shows higher control potential for locally advanced head and neck cancers, which is attributable to a delivery of higher concentrations of chemotherapeutic agents. However, it could enhance damages in the normal tissues. Hypothyroidism is a late adverse effect after curative radiotherapy in the head and neck region. This study focuses on the toxic effect of treatment modality for thyroid function., Methods: A retrospective analysis was performed to examine patients' thyroid function after SSIAC-R for laryngeal and hypopharyngeal cancer., Results: Hypothyroidism was observed in 21 (77.8%) of 27 patients receiving SSIAC-R, 4 (33.3%) of 12 patients treated with radiation alone, and 7 (41.1%) of 17 who underwent systemic chemoradiotherapy. The number of administered vessels significantly correlated with the incidence of developing hypothyroidism among SSIAC-R treated patients (P=0.03)., Conclusion: Concurrent setting of SSIAC with radiation significantly raises the possibility of hypothyroidism. Therefore, monitoring late complications of therapeutic procedures is essential during follow-up visits., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Dysphagia eventually occurs in amyotrophic lateral sclerosis (ALS). Swallowing in patients with ALS at their initial diagnosis was evaluated using videofluoroscopy (VF)., Methods: Nineteen consecutive patients with ALS, 14 with bulbar symptoms, and 5 without them, underwent VF. Fourteen physiologic components, 6 oral and 8 pharyngeal components, were assessed during the examination., Results: Significantly poorer scores were observed in three of the 6 oral components and 3 of the 8 pharyngeal components in patients with bulbar symptoms. Furthermore, bolus transport from the oral cavity to pharynx, pharyngeal constriction, oral residue and pharyngeal residue were impaired in patients even without bulbar symptoms. On the other hand, pharyngoesophageal segment opening was preserved in patients even with bulbar symptoms. Bolus transport and initiation of pharyngeal swallow were correlated with the swallowing category of the ALS severity scale., Conclusion: Defining types of impairment in patients with or without bulbar symptoms is useful for evaluating dysphagia in this disease. Although VF showed impairment of oral and pharyngeal phases of swallowing, the oral phase affected the eating habit in ALS at the initial diagnosis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The persistent stapedial artery (PSA) is a very rare, congenital, vascular anomaly. It presents as a pulsatile middle ear mass and sometimes causes conductive hearing loss. The diagnosis of the presence of a PSA is always accidental, because it is so rare and difficult to predict. CT findings include the absence of the foramen spinosum and a soft-tissue prominence in the region of the tympanic segment of the facial nerve. The risks of surgery include facial palsy, hemiplegia caused by coagulation of the PSA, and bleeding due to injury of the carotid artery during surgery in cases of aberrant internal carotid. In this article we report a case of PSA with stapes ankylosis for which we performed malleus-stapedotomy using a Teflon wire piston. We did not coagulate the PSA. Nevertheless the PSA attached to the prosthesis, the patient presented significant improvement in hearing level and had no complaint of pulsating tinnitus. Thus, we have shown that attachment of the prosthesis to the PSA does not necessarily disturb improvement of hearing level after malleus-stapedotomy for otosclerosis with PSA. Based on our experience, many cases can be treated by stapedotomy using a prosthesis and without coagulating the PSA., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to clarify the role of IL-33 in tumor progression., Methods: Surgical specimens from 81 patients with squamous cell carcinoma of the tongue were studied using immunohistochemistry. Primary tumor sections were analyzed for IL-33 and ST2 expression. To examine the influence of IL-33 on the microenvironment of the tumor, we determined the mast cell density (MCD) and microvessel density of the stroma., Results: Patients with high IL-33 expression had a significantly worse prognosis (p=0.004). IL-33 expression was significantly elevated in patients with local and nodal recurrence (p=0.014 and p=0.019). ST2 expression was also associated with a worse prognosis (p=0.024) and was significantly elevated in patients with nodal recurrence (p=0.004). MCD was associated with worse prognosis (p=0.038) and correlated significantly with IL-33 expression (r=0.626, p<0.001). Micovessels in the stroma were significantly increased in the high IL-33 group (p<0.001)., Conclusion: These data suggest that the IL-33/ST2 axis contributes to tumor aggressiveness and affects the tumor microenvironment. Immunohistochemical evaluation of IL-33 and ST2 is useful for identifying patients at a high risk for poor prognosis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory condition associated with elevated serum IgG4 levels and tissue infiltration by IgG4-expressing plasma cells. Several inflammatory conditions associated with IgG4-RD have been reported. Warthin's tumor is a benign parotid gland tumor consisting of oncocytic epithelial cells and lymphoid stroma containing lymphoid follicles with reactive germinal centers. This is the first report describing a case of Warthin's tumor with possible involvement of IgG4-RD. The patient was a 71-year-old man presenting with swollen right parotid and bilateral submandibular glands. He had a history of a Warthin's tumor of the left parotid gland, autoimmune pancreatitis, and an inflammatory abdominal aortic aneurysm. Laboratory tests revealed a high serum IgG4 level. Histological examination of the resected parotid gland showed a Warthin's tumor and a nodule showing severe lymphocytic infiltration containing many IgG4-positive plasma cells. This case shows the possible involvement of Warthin's tumor with IgG4-RD., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Superficial siderosis is a rare disease characterized by accumulation of hemosiderin in the leptomeninges, subpial tissue, spinal cord, and cranial nerves. The first clinicopathological description was reported in 1908. Most patients (95%) experience progressive bilateral hearing loss that begins early in the course of disease. The initial management of a patient with hearing loss secondary to superficial siderosis involves sound amplification using hearing aids. However, cochlear implants can be considered in cases where the patient can no longer gain significant benefit from hearing aids. Only 10 studies have described the use of cochlear implants in superficial siderosis and results have been variable. We report the case of a 65-year-old woman with bilateral progressive sensorineural hearing loss caused by superficial siderosis who benefited significantly from cochlear implantation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine the efficacy and safety of garenoxacin, a new generation of quinolone antimicrobial agent, in the treatment of adult upper respiratory tract infections., Methods: A total of 113 subjects were enrolled in this study. Garenoxacin (400mg/day) was administered to patients with pharyngolaryngitis, tonsillitis, and otitis media for 5-7 days and to those with sinusitis for 7-10 days. Clinical symptoms and findings were examined and quantitatively evaluated using a scoring system., Results: We found 80 to 100% improvement rate in symptoms and findings for each infection. In addition, we found significant improvement in subjective evaluations from patient questionnaires even in the early stage of the treatment. X-ray examination for acute sinusitis demonstrated that the clinical efficacy was 84% (27/32) and 76% (19/25) patients were already improved within seven days. Among the detected 84 bacteria, 75 (89%) were identified as the major pathogenic bacteria of respiratory tract infections such as Streptococcus pneumoniae (27 strains) and Haemophillus influenzae (14 strains). Garenoxacin administration completely eradicated bacteria in 53 out of 54 cases (98%). There were 8 adverse events (8.3%) including 3 diarrhea cases (3.1%)., Conclusion: These results suggest that garenoxacin is a highly effective and safe antimicrobial agent in the treatment of community-acquired upper respiratory infections. Additionally, garenoxacin did not induce the growth of resistant bacteria because of its strong antimicrobial activity., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Nasopharyngeal carcinoma (NPC) is a kind of rare head and neck cancer in Japan. However, NPC has some unique features. It is one of the most popular cancers in southern China, Southeast Asia, the Arctic, and the middle East/north Africa. This distinctive racial, ethnical, and geographic predisposition to NPC implies that both genetic susceptibility and environmental factors contribute to the development of this tumor. NPC is an Epstein-Barr virus - associated tumor. Consistent elevation of EBV antibody titers is a well-established risk factor of development of NPC. Not only pathophysiological relationship, but also molecular mechanism of EBV-mediated carcinogenesis has been enthusiastically investigated. LMP1, an EBV primary oncogene, upregulates each step of metastasis, and contribute to highly metastatic feature of NPC. A tumor suppressor gene p53 is mostly intact and overexpressed in NPC whereas expression of p16, a cyclin-dependent kinase inhibitory protein, is downregulated in 2/3 of NPC. Intention modulated radiotherapy (IMRT) is now getting prevalent for the treatment of NPC because of complicated structure and location of nasopharynx. A good therapeutic result can be achieved by distributing a high dose to the tumor while keeping down normal tissue complications by reducing radiation dose to normal tissues. Chemotherapy is important to control distant metastasis of chemoradiosensitive NPC, and thus, should play an important role. However, most effective combination of anti-tumor drugs, protocol of chemoradiotherapy has not well-established. Finally, molecular targeting therapy, including targeting EBV gene product, has been developing and on the way to the clinical use., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: It has become clear through epidemiological analysis that the incidence of cancers of the lung, liver, colon, and rectum are increasing in Japan every year. However, there have been few epidemiological analyses of nasopharyngeal carcinoma (NPC) in Japan. The aim of this study was to analyze the epidemiology and current incidence of NPC in the Chubu region of Japan during the period from 1996 to 2005., Methods: Takeshita et al. conducted a similar investigation in the Chubu region 10 years ago, and, as a result, this is a comparative study. The Chubu region is the central region of Japanese main island. We researched NPC patients treated in hospitals in each prefecture over a 10-year period (1996-2005) using a questionnaire., Results: A total of 525 cases (male:385, female:134, unknown:6) were analyzed epidemiologically, histologically, serologically, and clinically in this study. The incidence per 10(5) population per year was 0.29. For the period of 1986-1995, the age-standardized incidence of NPC was 0.28 per 10(5) persons per year in Takeshita's report. There was no significant difference between the two periods. The ages of the patients ranged from 13 to 90 years. The mean age of was 55.2 years. On the basis of the World Health Organization (WHO) histological criteria, 36% of the patients were classified as WHO I, 27% as WHO II, and 37% as WHO III. Carcinoma was located in the posterosuperior region in 56%, lateral in 41%, and inferior in 3%. Tumor staging showed that 6% to belonged to stage I, 25% to stage II, 31% to stage III, and 38% to stage IV. A neck mass was present in 52% of the patients, ear symptoms in 48%, nasal symptoms in 27%, headaches in 10%, pharyngeal symptoms in 9%, ophthalmologic symptoms in 9%, and cranial neurological symptoms in 9%. The positive rates of serum titers of the antibodies to Epstein-Barr virus (EBV)-related antigens were calculated. The positive rate of anti-EBV-viral capsid antigen (VCA) immunoglobulin (Ig) G titers was 58.6%, that of anti-EBV-VCA IgA titers was 53.6%, and that of EBNA was 81%. The five-year survival rate for all patients was 67.6%, and that for those in stage I, II, III, and IV was 75%, 84%, 69%, and 53%, respectively. The five-year survival rate for stage IV was significantly lower than those for the other stages (P<0.05)., Conclusion: The age-standardized annual incidence of NPC in our survey was 0.29 per 10(5) persons per year, being relatively low and stable., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Although it appears very uncommon in adult COM, Mycobacterium abscessus should be considered as a possible cause of a chronically draining ear. Multi-antibiotic chemotherapy including high-dose clarithromycin can effectively treat adult COM cased by M. abscessus. The first case report of adult chronic otitis media (COM) caused by M. abscessus is described here. A 61-year-old woman presented persistent otorrhea for 2 months, despite treatment with standard antimicrobial drugs. Physical examination revealed a small perforation of the tympanic membrane and edematous middle ear mucosa. Mycobacterial cultures and PCR yielded non-tuberculous mycobacteria (NTM); M. abscessus. Intravenous panipenem/betamipron and amikacin and oral clarithromycin were administered for 36 days. Computed tomography of the temporal bone showed improved aeration in the tympanic cavity, but soft tissue shadow remained unchanged in the mastoid 31 days after starting medication. She therefore underwent tympano-mastoidectomy at 36 days. At surgery, inflammation remained in the middle ear, and edematous pale mucosal tissue was noted around the stapes and ossicular chain. Histopathologic examination showed inflammation and granulation tissue, but no caseating necrosis or acid-fast bacilli. After surgery the symptoms resolved and remained well without evidence of infection recurrence 12 months after the operation., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To present an extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer., Materials and Methods: A 74-year-old male who noted a mass on the lower anterior neck and consulted our department immediately. The mass rapidly grew to 6cm from 2cm in diameter within 2 months after the initial presentation., Results: Fiberoptic laryngoscopy was unremarkable. Surgical excision of the lesion showed well differentiated squamous cell carcinoma with invasion into the surrounding tissues. Postoperative radiotherapy was added. During follow-up after those treatments, thickening of the right vocal cord was observed, which gradually became more apparent. Total laryngectomy was performed 13 months after the initial operation., Conclusion: Delphian node metastasis is included in the differential diagnosis in a case of rapidly increasing mass in the anterior neck.

We report the first case of three delayed complications following irradiation for laryngeal carcinoma: bilateral vocal cord immobility, obstruction of esophagus and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial fixation of bilateral vocal cords and stenosis of cervical esophagus were noted at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging into the hypopharynx and obstruction of the esophagus occurred at 35 years after irradiation. The life-threatening hemorrhage was successfully treated by microcoil embolization of the common carotid artery. The relationship between these complications and irradiation is also discussed.

We present the imaging and pathological features of a 38-year-old man in whom a large parapharyngeal solitary fibrous tumor (SFT) on the left side was found. On MRI, the tumor showed a nodule-in-nodule appearance. The inner nodule revealed high signal intensities both on T1- and T2-weighted MR images. The entire tumor showed heterogeneous enhancement on gadolinium-enhanced T1-weighted images. (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identified heterogeneous radiotracer uptake of FDG in the inner nodule of the tumor. Histologic examinations revealed an admixture of growth patterns, including a "patternless pattern" and "haemangiopericytoma-like pattern". The tumor was positive for CD34. Imaging features of SFT arising in the parapharyngeal space are discussed with a review of literatures. This is the first report of FDG-PET finding of SFT arising in the head and neck. More cases are needed to achieve diagnostic significance from FDG-PET findings of parapharyngeal SFTs.

The majority of the oncogenic osteomalacia-associated mesenchymal tumors are considered to belong to the category of phosphaturic mesenchymal tumors, mixed connective tissue (PMTMCT) variant, of which malignant cases are very rare. Here we report a case of a recurrent malignant PMTMCT variant which arose in the tongue. The patient was treated with surgery at an initial treatment and the first recurrence. In accordance with the tumor recurrence and resection, the hypophosphatemia progressed and improved. However, hypophosphatemia did not progress after receiving radiation therapy at the second recurrence even though the recurrent tumor gradually increased its size. These results suggest clinical feature of malignant PMTMCT could be changed by radiation therapy. Thus, this report could add an insight to the nature of PMTMCT.

Objective: Matrix metalloproteinase-1 (MMP-1) and interleukin-8 (IL-8) play an important role in cancer development and metastasis. There is a single nucleotide polymorphism (SNP) located in the promoter region of MMP-1 and IL-8 that regulates gene expression. MMP-1 -1607 2G/2G and IL-8 -251 A/A genotypes enhance transcriptional activity and may be associated with increased risk in malignant tumors. We therefore evaluated the impact of these SNPs in tongue squamous cell carcinoma (SCC)., Methods: In this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry., Results: We found a significant difference in IL-8 A/A genotypes with nodal recurrence (P=0.0068). An analysis of disease-free survival rates showed that the presence of both MMP-1 2G/2G and IL-8 A/A genotypes was associated with a particularly poor prognosis (P=0.0032) and was an independent prognostic factor (P=0.001). The expression of MMP-1 was significantly correlated with the frequency of MMP-1 2G/2G genotypes (P=0.049)., Conclusion: These results suggest that SNP in the promoter region of MMP-1 and IL-8 plays an important role in tumor progression and recurrence through its expression in tongue SCC.

Objectives: Although organ-preserving radiotherapy or chemoradiotherapy has offered good locoregional control, many patients still experience recurrent disease requiring salvage laryngectomy. The pharyngocutaneous fistula (PCF) is a common and troublesome complication in the early post-operative period after laryngectomy. Here, we evaluated the cause of PCF after laryngectomy, with special emphasis on radiotherapy and/or chemotherapy., Patients and Methods: A total of 63 consecutive patients undergoing salvage total laryngectomy for squamous cell carcinoma of the larynx at Kanazawa University Hospital from 1990 to 2005 were reviewed. Forty of the 63 had received primary total laryngectomy (PL). Ten patients underwent radiotherapy alone (SL-RT) and 13 patients underwent concurrent chemoradiotherapy (SL-CRT) followed by salvage laryngectomy., Results: Overall, 17 of the 63 patients (27.0%) developed PCF after laryngectomy. Fisher's exact test showed a significant increase of PCF formation in SL-CRT (7/13, 53.8%) compared with PL (7/40, 17.5%) (p=0.0252). There were non-significant increases of PCF formation both in SL-CRT (7/13, 53.8%) compared with SL-RT (3/10, 30.0%) (p=0.4015), and also in SL-RT (3/10, 30.0%) compared with PL (7/40, 17.5%) (p=0.3969). The Mann-Whitney U-test showed that the duration of PCF was significantly longer for SL-CRT PCF (121.2+/-95.0 days) compared with those for PL (39.0+/-55.3 days) (p=0.0298) or SL-RT (28.0+/-16.2 days) (p=0.0325). However, we did not find a significant difference in the duration of PCF with respect to PL (39.0+/-55.3 days) and SL-RT (28.0+/-16.2 days) (p=0.4367)., Conclusions: Although radiotherapy or chemotherapy has only a limited impact on PCF formation, concurrent chemoradiotherapy significantly increases PCF formation. The addition of chemotherapy to irradiation delays PCF closure.

Objective: Epstein-Barr virus (EBV) is a causative agent of nasopharyngeal carcinoma (NPC), and EBV gene expression is considered to be closely associated with the pathogenesis of NPC. Among EBV genes expressed in NPC, EBV-encoded non-polyadenylated RNAs, termed EBERs, are the most abundant transcripts of EBV in NPC. However, the role of EBERs still remains unclear. This study was designed to investigate the relevance of EBERs to the oncogenesis of NPC., Methods: Two types of EBERs expression vectors (EBERs-high-expression vector and EBERs-low-expression vector) were constructed and transfected into EBV-negative cells, MDCK or EBV-negative clones of NPC-KT cells. Then, malignant transformation, represented by anchor independent growth, was evaluated between the EBERs-transfected cells and EBERs-negative cells using a soft agar colony formation assay. Apoptosis was induced by serum deprivation (0.1% concentration of fetal bovine serum) and interferon-alpha (IFN-alpha) (500 U/ml) treatment. Cell viability was evaluated with a trypan blue exclusion test. The activation of cellular transcriptional factor NF-kappaB was studied with the IL-8 promoter sequence using a luciferase reporter assay., Results: EBERs-high-expression vector-transfected MDCK cells showed enhanced growth ability in soft agar compared with either EBERs-low-expression vector-transfected MDCK cells or EBERs-untransfected MDCK cells. However, they did not show the acquisition of any anti-apoptotic potential against either IFN-alpha or serum deprivation. Introduction of EBERs-low-expression vector into MDCK cells did not show anchor independent growth characteristics. Neither EBV-negative NPC-KT cells nor MDCK cells transfected with EBERs-high-expression vector showed any difference from EBERs-untransfected EBV-negative NPC-KT cells. Introduction of EBERs into MDCK cells did not transactivate the IL-8 promoter, indicating that neither NF-kappaB nor AP-1 was activated by EBERs., Conclusion: EBERs are believed to induce the initial transformation of epithelial cells, thus contributing to the oncogenesis of NPC. Expression of abundant EBERs is considered to be critical for this transforming property of EBERs.

Outside the nasopharynx, undifferentiated carcinomas occur only rarely at other head and neck locations. Although the association between undifferentiated nasopharyngeal carcinoma and Epstein-Barr virus (EBV) is consistent, there is conflicting evidence as to the association of EBV with undifferentiated carcinomas outside the nasopharynx. Here, we report on a case of undifferentiated carcinoma of the tongue base. A 71-year-old male, who had been treated with irradiation for primary unknown right neck metastatic EBV-positive undifferentiated carcinoma 9 years previously, was referred to our clinic with masses at the tongue base and right neck. The lesion at the tongue base was revealed to be an EBV-positive undifferentiated carcinoma. He was treated with resection of tongue base tumor and bilateral-neck dissection, and the defect at the tongue base was reconstructed with a free rectus abdominis myocutaneous flap. Re-irradiation was added post-operatively because of a positive surgical margin at the tongue base. The patient is presently alive without recurrence or distant metastasis 20 months after treatment. Although it is unclear whether our case is recurrent or newly developed EBV-latently infected undifferentiated carcinoma, we propose that EBV-associated tumors should be carefully observed after treatment at least for more than 10 years.

Malignant myoepitheliomas of the salivary gland are very rare tumors which may either arise de novo or develop in a pre-existing pleomorphic adenoma. We report a case of malignant myoepithelioma of the minor salivary gland that progressed from benign pleomorphic adenoma. The original pleomorphic adenoma was resected in 1979 (the '79 tumor). The first recurrent tumor was operated in 1995 (the '95 tumor). The '95 tumor was diagnosed as pleomorphic adenoma. Although the myoepithelial tumor component was more prevalent in the '95 tumor, histological features of the first recurrent tumor were similar to the '79 tumor. The second recurrent tumor showed more aggressive clinical features (the '98 tumor). It also showed massive growth of myoepithelial tumor cells with bone invasion, which led to the diagnosis of the '98 tumor as malignant myoepithelioma. With adequate surgical margin, the patient has been free from tumor recurrence for 20 months.