Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice.

Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of 'better-hearing ear' was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient's age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and -0.33, 95% confidence intervals [11.75-37.45] and [-0.58 to -0.09], respectively), but the CI surgery side did not (-6.76, [-14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing.

The add-on effect of an intranasal antihistamine with an intranasal corticosteroid in Japanese cedar pollinosis.

OBJECTIVE: Combination intranasal drugs with a corticosteroid and antihistamine are available in several countries with better effect than treatments with single agents. However, it remains unclear whether this effect is also seen in Japanese cedar pollinosis (JCP), the most prevalent seasonal allergic rhinitis in Japan. We investigated the effect of an add-on intranasal antihistamine with an intranasal corticosteroid in JCP during the pollen dispersal period. (UMIN000025508) METHODS: We performed a double-blinded, randomized, placebo-controlled trial from March 1 to 14, 2017. Patients (n = 20 per group) received either a mometasone furoate nasal spray (MFNS) plus a levocabastine nasal spray (levocabastine group) or MFNS plus a placebo nasal spray (placebo group). The primary endpoint was the difference in the total nasal symptom score (TNSS) after treatment between the two groups. Differences in the total ocular symptom score, total symptom score, total medication score, total symptom-medication score, and five individual symptoms as well as safety were the secondary endpoints. RESULTS: The change in the TNSS from baseline was significantly greater in the levocabastine group than in the placebo group. A significant reduction in the TNSS was observed more than 6 days earlier in the levocabastine group than in the placebo group. Such add-on effects were also seen in the secondary endpoints. Both treatments were well-tolerated. CONCLUSION: The intranasal antihistamine provided better control of not only nasal symptoms, but also of ocular symptoms, and decreased the need for rescue medications when added to intranasal corticosteroid treatment in JCP patients.

Midline involvement and perineural invasion predict contralateral neck metastasis that affects overall and disease-free survival in locally advanced oral tongue squamous cell carcinoma.

Introduction: Although patients with oral squamous cell carcinoma who develop contralateral neck metastasis (CLNM) have worse survival outcomes than those without CLNM, accurate prediction of occult CLNM in clinically negative contralateral neck (contralateral cN0) remains difficult. This study aimed to identify clinicopathological factors that could reliably predict CLNM in patients with locally advanced (clinical T3 and T4a) tongue squamous cell carcinoma (TSCC). Patients and methods: The medical data of 32 patients with cT3-4a TSCC who underwent curative surgery between 2010 and 2017 were retrospectively analyzed. The correlation of clinicopathological variables with CLNM was examined using logistic regression analysis. The diagnostic performance of significant variables was evaluated using the area under the receiver operating characteristic curves (AUC). Overall survival (OS) and disease-free survival (DFS) were assessed using a Cox proportional hazards model. Results: CLNM was eventually confirmed in 11 patients (34.4%). Multivariate logistic regression showed that midline involvement [odds ratio (OR) = 23.10, P = 0.017] and perineural invasion (PNI, OR = 14.96, P = 0.014) were independent predictors of CLNM. Notably, the prediction model comprising a combination of midline involvement and PNI exhibited superior diagnostic performance with an even higher OR of 80.00 (P < 0.001), accuracy of 90.3%, and AUC of 0.876. The multivariate Cox hazards model revealed independent significance of CLNM as an unfavorable prognostic factor for both OS [hazard ratio (HR) = 5.154, P = 0.031] and DFS (HR = 3.359, P = 0.038), as well as that of PNI for OS (HR = 5.623, P = 0.033). Conclusion: Our findings suggest that coexisting midline involvement and PNI of the primary tumor is highly predictive of CLNM development, which independently affects both OS and DFS in patients with locally advanced TSCC. Such reliable prediction enables efficient control of CLNM by optimizing management of the contralateral cN0 neck, which will likely contribute to improved prognosis of those patients without unnecessarily compromising their quality of life.

The fine-needle aspiration cytology and clinical findings of Kikuchi-Fujimoto disease in pediatric patients: a retrospective clinical study.

BACKGROUND: Histological evaluation of lymph node is crucial for the definitive diagnosis of Kikuchi-Fujimoto disease (KFD). However, lymph node biopsy under local anesthesia is often difficult in pediatric patients. OBJECTIVES: We evaluated cytological findings for pediatric patients with prolonged cervical lymphadenitis clinically suggestive of KFD and investigated the clinical characteristics of patients diagnosed with KFD by fine-needle aspiration cytology (FNAC). METHODS: This retrospective clinical study included 58 Japanese pediatric patients with cervical lymphadenitis who underwent FNAC. RESULTS: Cytological diagnosis was KFD for 22 and suspicion of KFD for 11 patients. The remaining 25 patients were diagnosed with non-specific lymphadenitis (NSL). Tenderness was independently associated with a higher frequency of both KFD in narrow and broad senses, compared with NSL (p = .009; p = .038). The percentage of patients who underwent FNAC within 28 days from symptom onset tended to be higher among patients with KFD in a narrow sense than those with NSL (p = .052). CONCLUSION: This study indicated that the period from symptom onset to FNAC (<28 days) and the symptom of tenderness were associated with the cytological diagnosis of KFD.

Application of Lip Biopsy for the Histological Diagnosis of Immunoglobulin G4-Related Disease.

We describe the case of a 51-year-old woman with immunoglobulin G4-related disease (IgG4-RD) diagnosed using lip biopsy. She reported having bilateral submandibular nodules for a month. Magnetic resonance imaging showed diffuse swelling in the bilateral submandibular glands (SMGs), suggesting inflammatory changes. Laboratory data revealed an elevated level of serum IgG4. Fine needle aspiration cytology of the SMG showed a considerable number of lymphocytes with degeneration but did not demonstrate specific findings for a definitive diagnosis of IgG4-RD. Lip biopsy was performed, and a biopsy specimen from the labial salivary gland showed abundant lymphoplasmacytic infiltration with a large number of IgG4-positive cells. The patient was diagnosed with IgG4-RD based on histological and laboratory findings. Findings of further examinations revealed that the patient had autoimmune pancreatitis, confirming our diagnosis. Four months after prednisolone administration, improvement of the submandibular and pancreatic lesions was observed. One year after the initial presentation, the serum IgG4 level was normalized. In cases of IgG4-RD with salivary gland involvement, lip biopsy might be one of the options for the histological diagnosis of IgG4-RD.

Methotrexate-Associated Lymphoproliferative Disorders Mimicking Granulomatosis With Polyangiitis: A Radiological Diagnostic Challenge.

Methotrexate-associated lymphoproliferative disorders (MTX-LPD) frequently involve the extranodal organs throughout the body. Among the extranodal occurrences of MTX-LPD, pulmonary involvement is most frequent. In contrast, there are only a few reports of MTX-LPD in the nasal cavity or paranasal sinuses. Moreover, there are no previous reports of MTX-LPD mimicking granulomatosis with polyangiitis (GPA) in imaging examinations. We describe a case of a 53-year-old woman with MTX-LPD mimicking GPA in the nasal cavity and lungs. She complained of left nasal obstruction and discharge, general fatigue, and continual fever for 2 months. The patient had been diagnosed with rheumatoid arthritis and received methotrexate (MTX) for over 10 years. Contrast-enhanced computed tomography revealed unenhanced masses in the nasal cavity and multiple masses with cavitary changes in the bilateral lungs, suggesting GPA. However, histological examination of the nasal lesion and a history of MTX treatment indicated a diffuse large B-cell lymphoma type MTX-LPD. Two weeks after MTX withdrawal, prominent improvements in both lesions were observed. Complete regression of the nasal lesion was observed 3 months after discontinuation of MTX. Thus, MTX-LPD may mimic GPA in imaging examinations.

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.

Otorhinolaryngologists/head and neck surgeons' knowledge, attitudes, and practices regarding fertility preservation in young cancer patients treated with chemotherapy: an anonymous questionnaire survey.

BACKGROUND: It is well known that chemotherapy for adolescent and young adult (AYA) patients with cancer can reduce fertility regardless of the regimen. A decline in fertility greatly affects the quality of life of cancer survivors in the AYA age group; however, few patients are thought to be receiving fertility preservation measures. METHODS: A questionnaire survey was conducted to assess the current understanding and consideration of fertility among otorhinolaryngologists/head and neck surgeons who treat AYA patients with cancer, and to inform them of the guidelines for fertility preservation. A total of 275 otorhinolaryngologists/head and neck surgeons working at our hospital in Ehime, Japan, six neighboring universities, and their affiliated facilities were included in this study. The questionnaire was mailed and requested to be returned by fax. Twenty questions were asked about respondents' years of experience as physicians, specialties, experience in medical care and chemotherapy for AYA patients with cancer, and knowledge and experience in fertility reduction measures. RESULTS: Although 58.7% of the physicians were aware that cryopreservation of eggs and sperm prior to chemotherapy was recommended, only 7 out of 40 physicians (17.5%) had referred AYA patients with cancer to an appropriate medical facility (department) after obtaining informed consent for chemotherapy. CONCLUSIONS: Although fertility preservation has been discussed at professional conferences and seminars, consideration and actions in the field of otorhinolaryngology/head and neck surgery have not been sufficient. We hope that the results of this survey will help raise awareness of fertility preservation.

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.

Subjective Evaluation of Balance by the Dizziness Handicap Inventory Does Not Predict Fall Risk in Older Adults Visiting Otolaryngology Clinics.

OBJECTIVES: Subjective symptoms of dizziness in older adults are affected not only by objective data such as postural balance, but also by complex psychological factors. Published data analyzing how simultaneous evaluations of both objective and subjective assessments of balance can predict fall risk remain lacking. This study examined how fall risk can be predicted based on both objective data for balance and hearing and subjective symptoms of dizziness among older adults visiting otolaryngology clinics. METHODS: Medical charts of 76 patients ≥65 years old with dizziness/vertigo who visited the otolaryngology clinic were reviewed. Objective data were evaluated by postural balance (posturographic data with eyes open and closed, and one-leg standing test), spontaneous nystagmus, and mean hearing levels. Subjective handicap associated with dizziness/vertigo was assessed using the Dizziness Handicap Inventory (DHI). Subjective mental status of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Information on history (cardiovascular diseases) and fall accidents within the preceding year was collected using an in-house interview sheet. RESULTS: Objective data on postural balance did not correlate with subjective symptoms on DHI or HADS (P > .05, Pearson's correlation coefficient). Adjusted logistic regression modeling with the outcome of incident falls revealed that poor postural balance significantly predicted fall risk (P < .05; 4.9 [1.4-16.8] per 10-cm2 increment). Nystagmus tended to be associated with fall risk. In contrast, DHI score did not predict fall risk (P = .43; 1.0 [0.9-1.03]). Receiver operating characteristic analysis proposed a cut-off for postural sway with eyes closed >6.1 cm2 as optimal to predict falls in patients with nystagmus (AUC, 0.74; 95% confidence interval, 0.48-0.997). CONCLUSION: Poor postural balance is associated with increased fall risk after adjusting for subjective symptoms in older adults at otolaryngology clinics. Conversely, the self-perceived dizziness handicap of DHI score is an insufficient tool to evaluate their fall risk.

Cochlear implants in Japan: Results of cochlear implant reporting system over more than 30 years.

OBJECTIVE: To conduct a longitudinal national survey of cochlear implantation (CI) in Japan from 1985 through 2017. METHODS: A retrospective analysis of adult and pediatric CI cases from 1985 to 2017 using the Oto-Rhino-Laryngological Society of Japan CI registration database was conducted. Surgical statistics were obtained, including number of surgeries, age, implanted side, facilities, and preoperative threshold levels for CI. RESULTS: Since 1985, more than 11,100 CI surgeries have been conducted in Japan. The number exceeded 500 in 2005 and 1,000 in 2015. Since 2007, pediatric cases consistently surpassed adult cases until 2016. More facilities meet criteria for conducting CI as determined by Ministry of Health, Labor and Welfare and have now reached more than 100. Adult patients over 70 years old have become proportionally higher. Age at implantation steadily reduced in accordance with modifications of Japanese CI guidelines for children but is still not comparable to that in other developed countries. Although the number of CI surgeries for patients with moderate to severe hearing loss increased in the past ten years, the proportion was small. CONCLUSIONS: The CI database in Japan is quite unique in that it documents almost all the CI surgeries in Japan, allowing us to summarize the present situation as follows: fewer CI surgeries occur than are necessary, and children receiving implants are older than those in other developed countries. Continuous improvement of CI awareness is needed in Japan.

PD-L1 expression in tongue squamous cell carcinoma.

PURPOSE: Immune checkpoint proteins programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important therapeutic targets for head and neck cancer. This large-scale case study aimed to analyze tongue squamous cell carcinomas (SCCs) and evaluate the correlation between PD-L1 expression and clinical prognosis. So far, this study is the largest case study on PD-L1 expression in tongue SCCs. METHODS: This is a case-control study that analyzed 121 tongue SCCs. Paraffin-embedded sections and clinical data were obtained retrospectively and immunohistochemistry with PD-L1 was performed. RESULTS: 11.6% contained ≥ 50% of PD-L1-positive cells, 57.1% of these cases had a poor prognosis with nodal metastasis. Among cases of T1/2 primary lesions with nodal metastasis, cases of high PD-L1 expression had a significantly shorter disease-free survival than cases of no PD-L1 expression (p = 0.018). The hazard ratio for high PD-L1 expression was 3.21 (95 per cent CI, 1.26-8.72) compared with no PD-L1 expression after adjusting for other factors. CONCLUSIONS: These data indicate that PD-L1 upregulation in tongue SCCs is associated with a more advanced stage and shorter disease-free survival. PD-1/PD-L1 inhibitors might hence constitute potential adjuvant therapy for tongue SCCs with PD-L1 upregulation.

Supraglottic subepithelial benign mass lesions: Focus on clinical features of sialolipoma-like lesion.

OBJECTIVES: Sialolipoma has been classified as a benign soft tissue lesion in the 2017 World Health Organization classification of head and neck tumors. To our knowledge, only one case of laryngeal sialolipoma has been reported in the English literature. We conducted a retrospective study to identify clinical characteristics of supraglottic sialolipoma-like lesion and differentiate it from other supraglottic subepithelial masses. METHODS: Medical records of 16 patients with supraglottic subepithelial benign mass lesions who underwent histological evaluation between 2003 and 2019 were retrospectively analyzed. Sialolipoma-like lesion was defined as a local finding of a well-circumscribed gross mass with pathological presence of salivary gland-like parenchymal lobules with evenly interspersed adipose tissue. RESULTS: Eight patients showed histological positivity for sialolipoma-like lesion, 3 for amyloidosis, 2 for hemangioma, and 1 each for cyst, lymphoid hyperplasia, and chondrometaplasia. Sialolipoma-like lesion tended to be predominant among men; those affected had a mean age of 52.8 (range, 39-74) years. By contrast, among patients with amyloidosis, the ratio of men to women was 1:2 (100% vs. 33%; p = 0.055). Fiberscopic examination of all patients with sialolipoma-like lesions identified well-circumscribed, yellowish masses, closely resembling local amyloidosis findings. Sialolipoma-like lesion was associated with a significantly higher body-mass index (BMI; 27.4 ± 2.8 kg/m2) than amyloidosis (21.6 ± 1.4 kg/m2; p = 0.014). The transoral approach was used for lesion resection in all patients with sialolipoma-like lesion. No patient experienced postoperative recurrence. CONCLUSION: Laryngeal sialolipoma-like lesion might be more prevalent than was previously reported, and histological examination is important to differentiate it from amyloidosis. Supraglottic sialolipoma-like lesion must be differentially diagnosed in patients with high BMI presenting with well-circumscribed, yellowish supraglottic masses.

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.

Effect of Prostaglandin D2 on mRNA Expression of Three Isoforms of Hyaluronic Acid Synthase in Nasal Polyp Fibroblasts.

BACKGROUND: Hyaluronan is one of the major extracellular matrixes in chronic rhinosinusitis (CRS) associated with tissue remodeling. Prostaglandin D2 (PGD2) is also associated with the pathogenesis of CRS. However, little is known about whether PGD2 regulates hyaluronan production by human airway fibroblasts. OBJECTIVE: We sought to determine the effect of PGD2 on the mRNA expression of three isoforms of membrane-bound hyaluronic acid synthase (HAS1, HAS2 and HAS3) in fibroblasts, the major source of hyaluronan production, derived from CRS patients. METHODS: Nasal polyp-derived fibroblasts (NPDF) and uncinate tissue-derived fibroblasts (UTDF) were established from CRS patients with nasal polyps and those without, respectively. These fibroblasts were stimulated with PGD2 or PGD2 receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. mRNA levels for HAS1, HAS2 and HAS3 were determined by real-time quantitative PCR. RESULTS: PGD2 (1 µM) significantly enhanced HAS1 but not HAS2 or HAS3 mRNA expression by NPDF. Enhanced HAS1 mRNA expression was also obtained by stimulation with a DP receptor-selective agonist, but not with a CRTH2 receptor-selective agonist. In addition, PGD2-induced HAS1 mRNA expression was significantly inhibited by pre-treatment with DP receptor-selective antagonists. Similar induction of PGD2-induced HAS1 mRNA expression was seen in UTDF. CONCLUSION: PGD2 selectively stimulates HAS1 mRNA expression in local fibroblasts in CRS via DP, but not CRTH2, receptors.

A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery.

A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.