Combined simultaneous endoscopic endonasal and transcranial surgery using high-definition three-dimensional exoscope for malignant tumors of the anterior skull base.

BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.

Adult T-Cell Leukemia/Lymphoma With Extranodal Involvement of the Hypopharynx.

Adult T-cell leukemia/lymphoma (ATLL) with extranodal lesions in the head and neck region is rare, with only a few cases reported so far. To our knowledge, this the first case reported involving the hypopharynx. The patient in this case was a 49-year-old woman who presented to an otolaryngology clinic complaining of an abnormal sensation in the throat and difficulty in swallowing. Endoscopic examination revealed an irregular mass with a smooth surface centered on the left piriform sinus and extending to the arytenoid and post-cricoid area. Imaging studies revealed lymphadenopathy in multiple cervical lymph nodes and in the hepatoduodenal mesentery. Examination of a peripheral blood smear revealed proliferation of atypical lymphocytes including flower cells. Further history-taking revealed that both the patient and her parents were positive for human T-cell lymphotropic virus type 1 (HTLV-1) antibodies and that her sister had developed ATLL. Lymph node biopsy was performed; hematoxylin-eosin staining of it showed a slight increase in atypical large lymphocytes, and flow cytometry of it showed CD4 and CD25 positivity in large lymphocytes. In peripheral blood samples, Southern blotting detected the monoclonal integration of the HTLV-1 provirus. Based on these findings, we diagnosed the patient with ATLL with extranodal involvement. ATLL should be included in the differential diagnosis for malignant lymphoma of the head and neck. A detailed medical interview and cooperation with the pathological department are key to a prompt diagnosis.

Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.

Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-κB subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-κB would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-κB-interacting inflammatory molecules, TNFα and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL.

A Multi-Institutional Study of Older Hearing Aids Beginners-A Prospective Single-Arm Observation on Executive Function and Social Interaction.

OBJECTIVES: To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment. DESIGN: Multi-institutional prospective single-arm observational study. SETTING AND PARTICIPANTS: Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan. METHODS: The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society-A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA). RESULTS: Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P = .0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P = .0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement. CONCLUSIONS AND IMPLICATIONS: HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family.

Immediate changes in transcription factors and synaptic transmission in the cochlea following acoustic trauma: A gene transcriptome study.

Pathologic mechanisms in cochleae immediately following the onset of noise-induced hearing loss (NIHL) remain unclear. In this study, mice were exposed to 120 dB of octave band noise for 2 h to induce NIHL. Three hours after noise exposure, expression levels of the whole mouse genome in cochleae were analyzed by RNA-seq and DNA microarray. Differentially expressed genes (DEGs) exhibiting >2-fold upregulation or downregulation in noise-exposed cochleae compared to controls without noise exposure were identified. RNA-seq and microarray analyses identified 273 DEGs regulated at 3 h post-noise (51 upregulated and 222 downregulated). Bioinformatic analysis revealed that these DEGs were associated with the functional gene pathway "neuroactive ligand-receptor interaction" and included 28 genes encoding receptors for neurotransmitters such as gamma-aminobutyric acid and glutamate. Other DEGs included 25 genes encoding transcription factors. Downregulation of 4 neurotransmitter receptors (Gabra3, Gabra5, Gabrb1, Grm1) and upregulations of 5 transcription factors (Atf3, Dbp, Helt, Maff, Nr1d1) were validated by RT-PCR. The differentially regulated transcription factor Atf3 immunolocalized to supporting cells and hair cells in the organ of Corti at 12-h post-noise. The present data serve as a basis for further studies aimed at developing medical treatments for acute sensorineural hearing loss.

Pathological evaluation of radiotherapy and concomitant intraarterial cisplatin for maxillary sinus cancer.

OBJECTIVE: Since 2010, we have mainly performed surgical treatment following radiotherapy and concomitant intraarterial cisplatin (RADPLAT) for locally advanced maxillary sinus cancer (MSC). The present study investigated treatment results and pathological evaluations following RADPLAT for MSC. METHODS: Pathological response to RADPLAT was evaluated using surgical specimens. Pathological response was graded in accordance with the classification method that Shimosato reported in 1964, as grade V (no tumor cells remain in any of section), grade IV, III, II, I, and 0. Five-year overall and disease-specific survival rates were estimated using Kaplan-Meier methods. Univariate analyses of correlations between recurrence of MSC and other clinicopathological parameters were evaluated using the chi-square or Fisher's exact tests. RESULT: 19 patients were enrolled in this study, 5 patients showed T3 disease and 14 had T4 disease. One patient demonstrated local recurrence and 3 patients experienced distant metastasis. The 5-year overall survival rate was 67.1% (T3, 50.0%; T4, 69.6%), and the 5-year disease-specific survival rate was 81.9% (T3, 100%; T4, 76.0%). Histological response was categorized as grade V in 9 cases. No significant risk factors for residual cancer were identified. CONCLUSION: Our study suggested that RADPLAT not only has a low risk of side effects, but also could represent an effective procedure for locally advanced MSC by pathological evaluation. Increasing the therapeutic intensity of RADPLAT might provide an effective modality to avoid highly invasive surgery.

An Adult Case of Nasal Chondromesenchymal Hamartoma: Imaging Characteristics Including Diffusion-Weighted Images.

Nasal chondromesenchymal hamartoma (NCMH), a rare, benign, nasal cavity tumor, typically occurs in children. Differential diagnosis is difficult because NCMH often presents with non-specific findings, including cystic components and invasion of the surrounding area on T2-weighted magnetic resonance images. Here, we present a rare adult case of NCMH, with no clear hyperintensity on diffusion-weighted images (DWI), and bone remodeling on the tumor margins on computed tomography. To the best of our knowledge, this is the first report of DWI on NCMH, and these findings, which suggest benign disease, may be useful in diagnosing NCMH.

Progression of hearing loss and choice of hearing aids by patients in their 60s, 70s, and 80s and older: experience in the Japanese super-aged era.

Background: Demographic data of patients with sensorineural hearing loss (SNHL) in super-aged societies are still limited.Aims/objectives: To report audiometric statistics of SNHL and hearing aid (HA) use in patients in their 60s, 70s, and 80s and older during the super-aged era.Material and methods: Medical charts and audiograms of 2064 older patients with SNHL who visited a Japanese University Hospital in 2007-2018 were retrospectively reviewed. Among 270 patients referred to the HA service unit (HASU), the percentage of final decisions to continue using HAs was calculated.Results: The average pure tone thresholds on initial visit to the clinic were 56.9, 60.6, 69.4, and 82.4 dB HL in patients in their 60s, 70s, 80s, and 90s, respectively. The rates of progression were 0.25, 0.87, 1.19, and 1.37 dB/year in patients in their 50s, 60s, 70s, and 80s, respectively. The percentage of patients in HASU who chose to use HAs did not differ among the 60s (59.3%), 70s (51.2%), and 80s and older (58.2%).Conclusions and significance: The clinical picture of patients with SNHL in their 70s and 80s differs because progression accelerates exponentially through these ages. HAs can be recommended to older adult patients in all the age groups.

Clinical feasibility of auditory processing tests in Japanese older adults: a pilot study.

Background: Difficulty in listening comprehension is a major audiological complaint of older adults. Behavioural auditory processing tests (APTs) may evaluate it. Aims/Objectives: The aim was to assess the feasibility of administering Japanese APTs to older adults at otolaryngology clinics. Material and Methods: Using computer programs interfaced with an audiometer, APTs (dichotic listening test; fast speech test, FST; gap detection test, GDT; speech in noise test; rapidly alternating speech perception test) were administered to 20 older adults (65-84 years old; mean 75.3 years) and 20 young adults at the 40 dB sensation level. Monosyllable speech perception (MSP) and the Mini-Mental State Examination (MMSE) were evaluated. Results: APT results except for GDT were significantly correlated with MSP. The performance on each APT was worse in older adults than in young adults (p < .01). The older adults with good MSP ≥ 80% (n = 13) or excellent cognitive function (MMSE ≥ 28; n = 11) also did worse on APTs (p < .05). A ceiling effect was noted in the APT data, with FST showing a minimum ceiling effect and reflecting interindividual variations of data. Conclusions and Significance: It is feasible to administer APTs to older adults who visit otolaryngology clinics. Among our Japanese APTs, FST may be suitable for further large-scale clinical studies.

Targeted PCR Array Analysis of Genes in Innate Immunity and Glucocorticoid Signaling Pathways in Mice Cochleae Following Acoustic Trauma.

AIM: To comprehensively analyze cochlear gene expressions related to innate immunity and glucocorticoid signaling at onset of acute noise-induced hearing loss (NIHL). BACKGROUND: Recent studies suggested innate immunity is involved in the cochlear pathology of NIHL. Glucocorticoids may modulate immune actions in cochleae. METHODS: Mice were exposed to 120 dB-octave band noise for 2 hours. Twelve hours later, a targeted PCR array analyzed cochlear expressions of 84 key genes in inflammation and immune pathways and 84 genes in the glucocorticoid signaling pathway. Real-time RT-PCR was used to analyze expression of two immune-related genes, Ccl12 and Glycam1, in noise-exposed cochleae with or without dexamethasone. RESULT: In inflammatory and immune gene pathways, 31.0% (26/84 genes) were significantly upregulated (>2-fold change) or downregulated (<0.5-fold change) (p < 0.05) in noise-exposed cochleae compared with controls. Sixteen of these differentially expressed genes (DEGs) encoded chemokines. DEGs included Ccl12, Ccl2, Ccl4, Ccl7, Cxcl1, Cxcl10, and Ptgs2 (upregulated genes), and Ccr7, Cxcr2, Kng1, Ltb, and Tnfsf14 (downregulated genes). In the glucocorticoid signaling pathway, 92.9% (78/84 genes) were unchanged in noise-exposed cochleae without dexamethasone administration. Cochlear expressions of Ccl12 and Glycam1 were significantly upregulated by noise and downregulated by dexamethasone. CONCLUSION: The targeted PCR array demonstrated that several dozen genes involved in innate immunity are actively regulated in cochleae with NIHL. The glucocorticoid signaling pathway was not endogenously regulated at 12 hours post-noise trauma. Systemic dexamethasone downregulated Ccl12 and Glycam1, which are upregulated in noise-exposed cochleae. These data may provide a basis for genomic medicine treatment of acute sensorineural hearing loss.

A novel mutation of the GAA gene in a patient with adult-onset Pompe disease lacking a disease-specific pathology.

We herein report a novel compound heterozygous mutation of the acid α-glucosidase (GAA) gene in a 23-year-old man with adult-onset Pompe disease. The patient was admitted for respiratory failure and a highly elevated serum level of creatine kinase (CK). His muscle pathology did not show typical vacuolated fibers; however, globular inclusion bodies with acid phosphatase (ACP) activity was observed. A molecular genetic analysis of the GAA gene revealed a novel compound heterozygous mutation, c.1544 T>A (M515K), combined with a previously reported mutation, c.1309 C>T (R437C). The presence of ACP-positive globular inclusion bodies is a useful diagnostic marker for adult-onset Pompe disease, even when typical vacuolated fibers are absent.

Synthesis of chiral and modifiable hexahydroxydiphenoyl compounds.

A reliable method for synthesizing each enantiomer of the hexahydroxydiphenoyl (HHDP) compounds has been developed. The synthesis involved atropselective construction of the aryl-aryl bond of the HHDP compounds. This construction relied on the CuCl(2)·n-BuNH(2)-mediated intramolecular coupling of bis(4-O-benzylgallate) on two simple chiral auxiliaries, both of which were derived from l-(+)-tartaric acid. The coupling reaction realized complete or near-perfect atropselectivity. The two auxiliaries induced opposite axial chirality despite their identical origin. The diastereoselectivities of these couplings were probably controlled kinetically. Modifications of the free phenolic hydroxy groups and the carbonyl groups in the resulting HHDP compounds demonstrated the potential derivatization of a wide variety of HHDP analogues.