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Highlights • Megalin and cubilin immunoreactivity (IR) was found in the human cochlea and vestibule. • Megalin-IR and cubilin-IR was seen in epithelial cells of the Reissner's membrane and spiral prominence. • Megalin-IR and cubilin-IR was seen in the transitional and dark cells of vestibular end organs. • Both megalin and cubilin may play an important role in inner ear endocytic transport. Abstract Megalin and cubilin are endocytic receptors expressed in many absorptive polarized epithelia. These receptors have been implicated in the transport of gentamicin in the inner ear as possible contributors to ototoxic damage. Megalin and cubilin have been characterized in detail in the mouse and rat inner ear, but not in the human inner ear. In this study, megalin and cubilin were localized by immunohistochemistry using affinity-purified antibodies in formalin fixed frozen cryostat and celloidin embedded sections of the human inner ear. In the cochlea megalin and cubilin were localized in marginal cells of the stria vascularis, epithelial cells of the spiral prominence and the Reissner's membrane. In the macula utricle and cristae ampullaris, megalin and cubilin were localized in transitional and dark cells, but not in vestibular hair cells and supporting cells. In the endolymphatic duct megalin and cubilin were localized in the epithelial cells. The localization of megalin and cubilin in the human inner ear is consistent with previous reports in the inner ear of animal models and suggest that these receptors may play an important role in the inner ear endocytic transport, and maybe potential targets for prevention of ototoxic damage or the delivery of medications. [ABSTRACT FROM AUTHOR]

Highlights • Nrf2-immunoreactivity (IR) was localized in the organ of Corti of the human cochlea. • Nrf2-IR was seen in the normal and pathological cochlea. • Nrf2-IR decreases significantly in the cochlea of older individuals. • Modulation of Nrf2 expression may protect from hearing loss due to noise and exposure to ototoxic drugs. Abstract Oxidative stress plays an important role in several inner ear diseases and normal aging. Nuclear (erythroid-derived 2)-like 2, also known as Nrf2, is a transcription factor encoded by the NFE2L2 gene that controls the expression of genes necessary to reduce oxidative stress. There are no studies to the date on the localization of Nrf2 in the human inner ear in normal or pathological conditions. Therefore, we investigated the immunohistochemical localization of Nrf2 in the human cochlea and vestibule using formalin-fixed celloidin-embedded human temporal bone sections. Nrf2 immunoreactivity (IR) was found in the inner and outer hair cells and supporting cells of the organ of Corti throughout the cochlea. Nfr2-IR was also found in hair cells and supporting cells of the maculae and cristae vestibular sensory epithelia. Nrf2-IR was decreased in the organ of Corti of older age individuals. The immunolocalization of Nrf2 in both auditory and vestibular sensory epithelia suggest that this transcription factor may play a relevant role in protecting sensory hair cells from oxidative stress. [ABSTRACT FROM AUTHOR]

Background Tracheotomy for pediatric patients is a surgical procedure with greater technical difficulty and higher rates of morbidity and mortality than that in adults. We report a new technique for pediatric tracheotomy that reduces the issue of granulation and recannulation after accidental decannulation. Methods Clinical data were retrospectively reviewed for 32 pediatric patients aged 3 weeks–32 months who underwent Quattro Flap Tracheotomy (QFT) at our hospital. The technique for the procedure is described and illustrated in detail. We analyzed the complications of surgery and the prognosis of patients. Results Twenty-seven out of 32 pediatric tracheotomy patients were aged < 12 months. Overall, one patient with subglottic stenosis developed granulation and required a resection. Three patients with granulation were cured using conservative treatment. Neither pneumothorax nor accidental decannulation and failure to reinsert the cannula occurred with QFT. No tracheotomy-related deaths occurred. The overall rate of postoperative complications was lower in the study group (4/32 cases, 12.5%) than in the control group (12/32 cases, 37.5%; p = 0.041). Conclusion QFT is a new method for pediatric tracheotomy that should be performed in younger infants. If performed appropriately, QFT may reduce the incidence of complications and death in many cases that involve persistent granulation. Levels of evidence IV. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the clinical factors associated with outcomes of head and neck small cell neuroendocrine carcinoma (SCNEC-HN).Materials and Methods: A retrospective review of clinical data was performed for 11 patients with SCNEC-HN treated at the Hamamatsu University Hospital (Hamamatsu, Japan). Clinical features, treatment methods, and outcomes were evaluated. The main outcome measurements were disease stage, patient age, primary tumor site, treatment procedures, and estimated survival rates. Survival rates were calculated using the Kaplan-Meier method.Results: Patients were followed for a mean of 40.0 months (range, 8 to 191 months). The 1-, 2-, and 5-year overall survival rates were 52.0, 20.8, and 10.4%, respectively. Rates did not differ significantly between the N2 and N0/1 groups, although the latter had a slightly better prognosis (P = .08).Conclusion: Chemoradiotherapy was a reasonable treatment for patients with SCNEC-HN. Those with N0/1 or maxillary sinus SCNEC-HN had a better prognosis than those with N2 disease or cancers at other sites, respectively. However, more aggressive treatment might not be warranted even for patients with limited disease. The outcomes continue to be suboptimal, and more effective therapies are needed because most patients had local or distant failure. [ABSTRACT FROM AUTHOR]

Neuroglobin (Ngb) is an oxygen-binding protein with a demonstrated role in endogenous neuroprotective mechanisms. It has been shown to function as a scavenger for reactive oxidizing species thereby assisting in cellular defense against oxidative stress. In the present study, we characterized the presence of Ngb in the human cochlea. Immunohistochemical staining was performed on formalin fixed celloidin human cochlea sections obtained from human temporal bones, using affinity purified polyclonal antibodies against Ngb. Thirty-six temporal bones were analyzed, 15 with normal otologic histories and 21 diagnosed with different inner ear pathologies. Ngb immunoreactivity (Ngb-IR) was consistently expressed in the neurons of spiral ganglia (SG) and supporting cells of the organ of Corti. There was a significant decrease of Ngb-IR in SGNs from specimens with inner ear pathologies when compared to normal specimens. In contrast, Ngb-IR in the organ of Corti did not show significant changes between pathological and normal specimens. The differential pattern of Ngb expression in these cochlear structures suggests that Ngb may participate in defense mechanisms in inner ear pathologies where oxidative stress is involved. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a minimally invasive therapy used in the treatment of premalignant and malignant diseases, including head and neck carcinomas. It can be applied before or after chemotherapy, irradiation, or surgery. Unlike irradiation and surgery, it can be repeated many times at the same site, and it is also associated with better cosmetic and functional outcomes [ 1 ]. We have treated 10 patients with laryngeal carcinomas with PDT since 1998, and herein we describe two such patients who developed vocal cord adhesion due to PDT. To our knowledge, there are no previous reports of patients with glottis atresia due to PDT, thus the cases reported herein are rare, and educationally valuable. [ABSTRACT FROM AUTHOR]

Abstract: A 51-year-old man complained of left facial swelling and recurrent nasal bleeding. A giant solid tumor in the left maxillary sinus was detected on head CT and MRI, and this tumor was destroying the maxilla and extending into the orbit, pterygoid muscle and posterior paranasal sinuses. The resected specimen consisted of spindle cells containing necrotic material. Histological examination revealed immature tumor cells, and immunohistological study of the tumor showed staining was only positive for vimentin. We accordingly diagnosed undifferentiated sarcoma in the maxillary sinus. Combination chemotherapy with vincristine, doxorubicin, cyclophosphamide/ifosfamide with mesna and etoposide was administered; however, the tumor was unresponsive and the patient died after around 3 months. [Copyright &y& Elsevier]

A 74-year-old man was brought to the emergency department (ED) due to a 1-hour course of dyspnea and dysphonia. At arrival in the ED, his airway was managed by bag-valve-mask ventilation. The patient was intubated using a Macintosh laryngoscope with a gum elastic bougie guide. An indirect endoscopic examination revealed prominent epiglottal swelling. Simultaneously, we found a bilateral conjugate deviation to the right and a positive Barré sign for the left arm. Diffusion-weighted magnetic resonance imaging, magnetic resonance angiography, and computed tomography with contrast enhancement revealed a right cerebral hemisphere infarction and dissection of the brachiocephalic artery to the right internal carotid artery. After admission, the patient stated that the movement of his left arm was intact when he became aware of the dyspnea and that he noticed the paralysis of his left arm during transportation to the ED. We believed that these signs resulted from the right hemisphere brain infarction caused by dissection of the brachiocephalic artery to the right internal carotid artery, secondary to the acute epiglottitis. A decrease of intrathoracic pressure due to an upper airway obstruction may cause distention of the intrathoracic arteries and an afterload increase on the left ventricle. The patient was moved to another hospital for rehabilitation on the 20th day after admission. This is the first report of a brain infarction after a dissection of the intrathoracic arteries secondary to acute epiglottitis. Patients with acute epiglottitis should be closely monitored for both airway management and the pathology caused by decreasing intrathoracic pressure. [ABSTRACT FROM AUTHOR]

• Head and neck squamous cell carcinoma patients received photodynamic therapy (PDT). • The efficacy and 5-year overall survival rates were 97.6 % and 57.8 %, respectively. • Sex, tumor stage, and tumor location were associated with overall survival. • Light dose was not significantly associated with local control or survival. • Photofrin-mediated PDT is a useful therapy in head and neck squamous cell carcinoma. Photodynamic therapy is a less invasive therapeutic procedure for carcinomas. The goal of this study was to evaluate the utility of Photofrin (porfimer sodium)-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma. Forty-two head and neck squamous cell carcinoma patients who underwent Photofrin-mediated photodynamic therapy were treated by intraoperative light activation at 630 nm via a fiber optic microlens, 48 h after injection. We evaluated the impact of age, sex, tumor stage, primary site, light dose, and cancer history on overall survival using a Cox proportional hazards model. Information on the survival status of patients was obtained after a mean follow-up period of 51 months (range, 6–180 months). The 5-year overall survival for all patients was 57.8 % (95 % confidence interval of the survival rate: 39.8 %–72.1 %). The complete response rate was 69.0 %, and the efficacy (complete response + partial response) was 97.6 %. Earlier tumor stage was associated with increased survival (p = 0.012). Diseases of the respiratory tract also showed significant association with survival as compared to those of the alimentary tract (p = 0.01). Photofrin-mediated photodynamic therapy is useful for treating head and neck squamous cell carcinomas, and provides an improved quality of life in patients with recurrent or residual disease. [ABSTRACT FROM AUTHOR]

Purpose: Methods for cytologic diagnosis, such as fine-needle aspiration (FNA) and touch smear (TS) cytology, have been frequently used for malignant tumor screening; however, false-negative cases often result in misdiagnosis. The purpose of this study was to investigate the causes of false-negative cases and methods to decrease the false-negative rate in salivary gland tumor TS cytology.Materials and Methods: In this cross-sectional study, the authors examined pathologically confirmed salivary gland tumors in 127 cases in which FNA and TS cytology were performed before the operation or open biopsy at Numazu City Hospital (Numazu, Japan) from 2002 to 2016. The authors evaluated the false-negative rates of TS and FNA cytology separately and when used in combination and other variables, such as age, gender, sensitivity, accuracy, specificity, and overall pathologic diagnosis by resection.Results: The overall false-negative rate of postoperative pathologic diagnosis was lower when TS and FNA were combined (1 of 127 cases; 0.8%) compared with FNA cytology alone (10 of 127 cases; 7.9%; P = .034). Suggested causes of a false-negative FNA (or TS) result include cytologic difficulties present in certain malignancies, such as mucoepidermoid carcinoma, adenoid cystic carcinoma, and others.Conclusion: False-negative cases were decreased when a combination of preoperative FNA and intraoperative TS cytology was performed. TS cytology appears to be a useful method to avoid misdiagnosis in salivary gland diseases. [ABSTRACT FROM AUTHOR]

Small cell neuroendocrine carcinoma (SNEC) of the paranasal sinuses is an extremely rare and distinctive tumor with aggressive clinical behavior. Moreover, SNECs originating in the head and neck region have been reported to be highly aggressive and to have a poor prognosis. This report describes a patient with a maxillary sinus SNEC who was successfully treated with induction chemotherapy using cisplatin and etoposide followed by concurrent chemoradiation therapy with cisplatin and etoposide as radiosensitizers. The patient has remained free of recurrence during 7 years of follow-up. To the authors' knowledge, this is the first case report describing long-term survival in a patient with a resolved primary SNEC of the maxilla that was successfully treated with neoadjuvant chemotherapy and concurrent chemoradiotherapy. The clinical and pathologic features of the tumor and the optimal treatment of this patient are discussed. [ABSTRACT FROM AUTHOR]

Gaucher disease is a lysosomal storage disorder that is caused by congenital defective function of the enzyme glucocerebrosidase. Glucocerebroside that is not hydrolyzed by glucocerebrosidase mainly accumulates in the reticular tissue. We describe a Japanese boy with Gaucher disease type 1 who developed bilateral profound sensorineural hearing loss within approximately 4years. We performed cochlear implantation initially on his right ear and again on his left ear 5 months later. The cochlear implants were successfully utilized with a speech discrimination score of 95% on a Japanese sentence recognition test. There are many reports of central hearing loss in Gaucher disease type 2 or 3. However, to the best of our knowledge, this is the first report of profound inner ear hearing loss with Gaucher disease. It also appears to be the first record of cochlear implantation for Gaucher disease. Cochlear implants may be useful for sensorineural hearing loss in patients with Gaucher disease without neurological symptoms other than hearing loss. [ABSTRACT FROM AUTHOR]

Opioid peptides and their receptors have been localized to the inner ear of the rat and guinea pig mammalian models. The expression of mu opioid receptor (MOR) in the human and mouse cochlea is not yet known. We present MOR protein localization by immunohistochemistry and mRNA expression by in situ hybridization in the human and mouse spiral ganglia (SG) and organ of Corti. In the human most of the (SG) neurons were immunoreactive; a subset was non-immunoreactive. In situ hybridization revealed a similar labeling pattern across the neurons of the SG. A similar distribution MOR pattern was demonstrated in the mouse SG. In the mouse organ of Corti MOR was expressed in inner and outer hair cells. Fibers underneath the inner hair cells were also MOR immunoreactive. These results are consistent with a role of MOR in neuromodulation of the auditory periphery. The present results show that the expression of MORs is well-conserved across multiple mammalian species, indicative of an important role in auditory processing. [ABSTRACT FROM AUTHOR]

Abstract: Glutamate plays an important role in the central nervous system as an excitatory neurotransmitter. However, its abundance can lead to excitotoxicity which necessitates the proper function of active glutamate transporters. The glutamate-aspartate transporter (GLAST) has been shown to exist and function within non-human cochlear specimens regulating the inner ear glutamate concentration. In this study, we examined human cochleas from formalin-fixed celloidin-embedded temporal bone specimens of three different types of patients (Meniere's disease, normal controls, and other otopathologic conditions) and examined the differential expression of GLAST in the spiral ligament of the basal, middle, and apical turns of the cochlea. Immunohistochemical staining was performed with polyclonal antibodies against GLAST and image analysis was carried out with the Image J analysis software. In contrast to other studies with non-human specimens, GLAST was expressed in the spiral ligament fibrocytes but was not detected in the satellite cells of the spiral ganglia or supporting cells of the Organ of Corti in the human cochlea. Our data also showed that GLAST expression significantly differs in the basal and apical turns of the cochlea. Lastly, post-hoc analysis showed a difference in the GLAST immunoreactive area of patients with Meniere's disease when compared to that of patients with other otopathologic conditions—such as presbycusis or ototoxicity. These results may potentially lead to further understanding of different disease states that affect hearing. [Copyright &y& Elsevier]

Abstract: 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 105 population per year was 0.29. For the period of 1986–1995, the age-standardized incidence of NPC was 0.28 per 105 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 105 persons per year, being relatively low and stable. [Copyright &y& Elsevier]

• This study uses Na,K-ATPase α1 subunit-immunoreactivity to identify cellular structures in the human cochlea. • Na,K-ATPase α1-IR was present in the cochlea of patients with hearing loss of different etiologies. • Na,K-ATPase α1-IR area did not appear to change in the stria vascularis with age. • These results suggest an important role of Na,K-ATPase in the function of the human cochlea and in the presence of inner ear pathology. Na+, K+-ATPase (Na,K-ATPase) is an ubiquitous enzyme in the inner ear and a key factor in the maintenance of the osmotic gradient of the endolymph. This study uses Na,K-ATPase α1 subunit immunoreactivity (IR) to identify cellular structures in the normal and disease human cochlea. Formalin-fixed celloidin-embedded (FFCE) human temporal bone sections were immunoreacted with mouse monoclonal antibodies against Na,K-ATPase α1 subunit. Na,K-ATPase α1 IR was examined in the cochlea of 30 patients: four with normal hearing, 5 with Meniere's disease, and 21 with other inner ear diseases: 11 male, 19 female; ages 42 to 96 years-old (yo), average age of 77 yo. Na,K-ATPase α1 IR area was quantified using the ImageJ software program. Na,K-ATPase α1 IR was located in the stria vascularis, and in type I, II and IV fibrocytes of the spiral ligament in the cochlea from patients with normal hearing. Na,K-ATPase α1 IR was seen in Deiters's cells and inner phalangeal cells of the organ of Corti. Na,K-ATPase α1 IR was present in satellite cells that surround the neurons of the spiral ganglia. In the inner ear of pathological specimens, Na,K-ATPase IR area was decreased (compared to the normal) in the stria vascularis, supporting cells in the organ of Corti and satellite cells of the spiral ganglia. These results show that Na,K-ATPase α1 IR is a good marker to identify cellular structures of the human inner ear and may be used to study cellular changes in the cochlea associated with aging and disease. The ubiquitous localization of Na,K-ATPase α1 in the human cochlea is consistent with the Na,K-ATPase role in ionic homeostasis and osmolarity, similar to that seen in animal models. [ABSTRACT FROM AUTHOR]