Expanding the clinicopathologic and molecular spectrum of BCOR-associated sarcomas in adults.

AIMS: BCOR gene alteration is a genetic signature of rare subsets of sarcomas. Most BCOR-associated sarcomas thus far reported are in the pediatric population, except for uterine sarcomas. We studied seven cases of BCOR-associated non-uterine sarcomas in adult patients. METHODS AND RESULTS: The patients were four men and three women ranging from 26 to 71 years in age. Three tumors, two of which primarily affected the kidney, showed BCOR-CCNB3. One tumor with a ZC3H7B-BCOR occurred in the chest wall, and a tumor with a novel CIITA-BCOR was found in the sinonasal tract. Two tumors in the lung and breast harbored exon 15 internal tandem duplications of BCOR, a highly unexpected observation in this age group. All seven sarcomas consisted of dense proliferations of uniform round to spindle cells with fine chromatin within vascular stroma. BCOR-CCNB3 sarcomas showed swirling fascicular growth. The tumor with the ZC3H7B-BCOR fusion showed a multinodular growth of spindle cells, and the tumors with the CIITA-BCOR fusion showed palisading of oval cells. Both tumors with BCOR internal tandem duplication demonstrated nested to palisading growth of round cells within sclerotic non-myxoid stroma. All seven sarcomas diffusely expressed BCOR and SATB2 immunohistochemically, with all three BCOR-CCNB3 sarcomas being immunopositive for CCNB3. BCOR alterations were confirmed by RNA sequencing, polymerase chain reaction, Sanger sequencing, and/or fluorescence in situ hybridization. CONCLUSIONS: This study expands the clinicopathologic and molecular spectrum of BCOR-associated sarcomas, and emphasizes the importance of being aware of this entity in the differential diagnosis of adult non-uterine sarcomas.

Transient and Recurrent Pulmonary Infiltrations Associated with Familial Mediterranean Fever.

Chest symptoms and pleural effusion due to serositis in familial Mediterranean fever (FMF) are occasionally misdiagnosed as acute pneumonia. However, the actual pulmonary involvement of FMF is extremely rare. A 67-year-old man was referred to our hospital due to repeated and transient anterior chest pain. Chest images revealed a moderate amount of pericardial fluid, slight bilateral pleural effusion, and infiltrations in both lower lung lobes. Colchicine treatment without antibiotics rapidly improved these symptoms and findings. Pericarditis, pleurisy and the response to colchicine indicated FMF. FMF should be considered as a causative disease of pulmonary infiltrations, especially if it occurs repeatedly.

Development of receptive vocabulary and verbal intelligence in Japanese children with unilateral hearing loss.

OBJECTIVE: In the past, it was believed that unilateral hearing loss has a minimal impact on the speech and language development in children. However, several studies have suggested that some school-age children with unilateral hearing loss have learning impairments in language. In the present study, we first examined whether preschool-age children with unilateral severe-to-profound hearing loss (UHL) have delays in the development of receptive vocabulary and verbal intelligence. In the follow-up study, we tested the children again after school admission. The objective of the present study was to reveal the development of receptive vocabulary and verbal intelligence from preschool to school years in children with UHL. METHODS: Fifteen Japanese preschool-age children with UHL and a control group of 20 age-matched Japanese children with bilateral normal hearing (NH), who were examined because articulation disorder was suspected, were enrolled in this study. The development of receptive vocabulary and verbal intelligence was evaluated using the Picture Vocabulary Test-Revised (PVT-R) and the Wechsler Intelligence Scale, respectively. The present retrospective study was approved by the Committee for Medical Ethics of Tokushima University Hospital (#3801). RESULTS: The scaled score (SS) of the PVT-R and verbal intelligence quotient (VIQ)/verbal comprehension index (VCI), but not performance intelligence quotient/perceptual reasoning index in children with UHL were significantly lower than those in the control children with NH at preschool-age. The SS of the PVT-R and VIQ/VCI in children with UHL significantly improved after school admission. In the subgroup analysis, the SS of the PVT-R in the lower receptive vocabulary group of children with UHL at preschool-age was significantly increased after school admission, but the SS in the normal and higher receptive vocabulary group of children with UHL at preschool-age were still around the standardized mean of SS after school admission. CONCLUSION: These findings suggest that the development of receptive vocabulary and verbal intelligence was delayed in preschool-age children with UHL and that most of them caught up to exhibit normal language ability after school admission.

Differential cytokine profiles in pediatric patients with PFAPA syndrome and recurrent tonsillitis.

Objective : An attempt was made to identify characteristic cytokine profiles to distinguish periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPAS) from recurrent tonsillitis, of which clinical manifestations are similar to those of PFAPAS in children. Methods : Serum concentrations of IL-6, IL-4 and IFN-γ were measured during febrile episodes in pediatric patients. Results : The levels of IL-6 during febrile episodes were markedly increased above the upper limit of normal ranges in patients with both PFAPAS and recurrent tonsillitis, but there were no significant differences between groups. The levels of IL-4 during febrile episodes in PFAPAS patients were significantly lower than those in recurrent tonsillitis patients. The levels of IFN-γ during febrile episodes in PFAPAS patients were significantly higher than those in recurrent tonsillitis patients. Conclusion : In pediatric patients with PFAPAS, despite an increase of IL-6, IL-4 was suppressed with a marked increase of IFN-γ during febrile episodes. On the contrary, in febrile pediatric patients with recurrent tonsillitis, both IL-6 and IL-4, but not IFN-γ were increased. The characteristic cytokine profiles of IL-6, IL-4 and IFN-γ can be used for differential diagnosis of PFAPAS from recurrent tonsillitis in children in clinical ear, nose and throat (ENT) settings. J. Med. Invest. 68 : 38-41, February, 2021.

Effects of vocal nodules on acoustic characteristics of voice in children†:†an acoustic analysis of voice.

Objective : In the present study, an attempt was made to evaluate the acoustic characteristics of voice in pediatric patients with vocal nodules using acoustic analysis of voice. Methods : Thirty-five pediatric patients with vocal nodules and 32 control children without dysphonia were enrolled in this study. Their voice samples were analyzed using the Multi-Dimensional Voice Program. Acoustic parameters of voice, such as pitch period perturbation quotient (PPQ), amplitude perturbation quotient (APQ), and noise-to-harmonic ratio (NHR), were measured. Results : In phonation at a loudness of over 80 dBA, the PPQ, APQ, and NHR values of the voice significantly increased in children with vocal nodules than in the control children without dysphonia. The sensitivities and specificities of PPQ, APQ, and NHR for prediction of vocal nodules in children were 62.86% and 84.38%, 74.29% and 75.00%, and 31.43% and 93.75%, respectively. Discussion : The present findings suggest that vocal nodules affect vocal fold vibration, resulting in impaired control of pitch and loudness leading to increased noise components. NHR could be used to evaluate the efficacy of treatment, such as voice rehabilitation, in pediatric patients with vocal nodules because of its high specificity for prediction of vocal nodules in children. J. Med. Invest. 68 : 276-279, August, 2021.

Effects of FM system fitted into the normal hearing ear orcartilage conduction hearing aid fitted into the affected ear on speech-in-noise recognition in Japanese children with unilateral congenital aural atresia.

The effects of FM system fitted into the normal hearing ear (NHE) or a cartilage conduction hearing aid (CCHA) fitted into the affected ear (AE) on the speech recognition ability in noise were examined in children with unilateral congenital aural atresia (UCAA). In children with bilateral normal hearing (BNH), speech recognition score (SRS) was significantly decreased in the noisy environment of -5 dB signal-to-noise ratio (SNR), compared with those in quiet. In children with UCAA, SRS was significantly decreased in noisy environments of 0 and -5 dB SNR, compared with those in quiet. In noisy environments of 0 and -5 dB SNR, SRS in children with UCAA was significantly decreased, compared those in children with BNH. In the noisy environment of -5 dB SNR, SRS in UCAA children aided by FM system fitted into NHE was significantly better than those in unaided children in the same group. In the noisy environment of 0 dB SNR, SRS in UCAA children aided by CCHA into AE tended to be higher than those in unaided children in the same group. FM system and CCHA can be recommended as an audiological management for the improvement of speech recognition in children with UCHL in classrooms. J. Med. Invest. 67 : 134-138, February, 2020.

Effects of FM system fitted into normal hearing ear on speech-in-noise recognition in Japanese school-aged children with unilateral severe-to-profound hearing loss.

OBJECTIVES: We examined speech recognition ability of elementary school-aged Japanese children with unilateral hearing loss under noisy environments and then examined the effects of the FM system fitted into their normal hearing ear on their speech recognition ability. METHODS: Twelve children with severe-to-profound sensorineural hearing loss and ten age-matched children with bilateral normal hearing received speech recognition test in quiet and noisy environments. Other nine children with severe-to-profound sensorineural hearing loss received speech recognition test with or without the FM receiver fitted to the normal hearing ear in quiet and noisy environments. RESULTS: Signal-to-noise ratio (SNR) in Japanese elementary school classrooms was estimated to be -6.9 dB at a preferential seat. In noisy environment of -5 dB SNR similar to working classrooms, the correct rates of speech recognition test in children with unilateral hearing loss were significantly lower, compared with those in children with bilateral normal hearing. In the noisy environment, the correct rates in children aided by the FM system with unilateral hearing loss were significantly better, compared with unaided ones. CONCLUSION: The results suggested that the FM system is recommended as an audiological management for improvement of speech recognition of children with unilateral hearing loss in noisy classrooms. J. Med. Invest. 65:216-220, August, 2018.

Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: a randomized, placebo-controlled, double-blind, comparative study.

OBJECTIVE: The aim of this study was to assess whether aural stimulation with ointment containing capsaicin improves swallowing function in elderly patients with dysphagia. STUDY DESIGN: A randomized, placebo-controlled, double-blind, comparative study. SETTINGS: Secondary hospital. PATIENTS AND METHODS: Twenty elderly dysphagic patients with a history of cerebrovascular disorder or Parkinson's disease were randomly divided into two groups: 10 receiving aural stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The ointments were applied to the external auditory canal with a cotton swab. Then, swallowing of a bolus of blue-dyed water was recorded using transnasal videoendoscopy, and the swallowing function was evaluated according to both endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale. RESULTS: The sum of endoscopic swallowing scores was significantly decreased 30 and 60 min after a single administration in patients treated with capsaicin, but not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of the SMRC scale was significantly increased 5, 30 and 60 min after single administration in patients treated with capsaicin, but not with placebo. No patient showed signs of adverse effects. CONCLUSION: As capsaicin is an agonist of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest that improvement of the swallowing function, especially glottal closure and cough reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific mechanical stimulation with a cotton swab.

Efficacy of proton pump inhibitor in combination with rikkunshito in patients complaining of globus pharyngeus.

OBJECTIVE: Globus pharyngeus (GP) is a common symptom of laryngopharyngeal reflux disease (LPRD), and proton pump inhibitor (PPI) and rikkunshito, a traditional Japanese medicine having prokinetic effect improve LPRD symptoms. In the present study, we examined the efficacy of high-dose PPI in combination with rikkunshito in patients complaining of GP. METHODS: 106 patients complaining of GP without any organic endoscopic findings were enrolled. RESULTS: Patients were first administrated with high-dose PPI alone for 4 to 8 weeks and the symptom was improved in 65 patients. Among 41 patients with PPI-refractory GP, 22 patients were administrated with high-dose PPI in combination with rikkunshito, and the symptom was improved in 14 of 22 patients 4 weeks later. The average value of a modified reflux symptom index of the responders was similar to that of non-responders. Only a few patients had positive values in reflux finding scores in both groups. CONCLUSION: The present findings suggest the existence of a high prevalence of LPRD in patients complaining of GP. The data also suggest that gastroesophageal dysmotility is involved in GP, in addition to excessive acid reflux. The pre-therapeutic laryngopharyngeal symptoms and endoscopic findings could not predict the efficacy of the treatment for GP. J. Med. Invest. 63: 227-229, August, 2016.

Effects of aural stimulation with capsaicin ointment on swallowing function in elderly patients with non-obstructive dysphagia.

OBJECTIVE: In the present study, an attempt was made to examine the effects of aural stimulation with ointment containing capsaicin on swallowing function in order to develop a novel and safe treatment for non-obstructive dysphagia in elderly patients. DESIGN: A prospective pilot, non-blinded, non-controlled study with case series evaluating a new treatment. SETTING: Secondary hospitals. PATIENTS AND METHODS: The present study included 26 elderly patients with non-obstructive dysphagia. Ointment containing 0.025% capsaicin (0.5 g) was applied to the external auditory canal with a cotton swab under otoscope only once or once a day for 7 days before swallowing of a bolus of colored water (3 mL), which was recorded by transnasal videoendoscopy and evaluated according to the endoscopic swallowing score. RESULTS: After a single application of 0.025% capsaicin ointment to the right external auditory canal, the endoscopic swallowing score was significantly decreased, and this effect lasted for 60 minutes. After repeated applications of the ointment to each external auditory canal alternatively once a day for 7 days, the endoscopic swallowing score decreased significantly in patients with more severe non-obstructive dysphagia. Of the eight tube-fed patients of this group, three began direct swallowing exercises using jelly, which subsequently restored their oral food intake. CONCLUSION: These findings suggest that stimulation of the external auditory canal with ointment containing capsaicin improves swallowing function in elderly patients with non-obstructive dysphagia. By the same mechanism used by angiotensin-converting enzyme inhibitors to induce cough reflex, which has been shown to prevent aspiration pneumonia, aural stimulation with capsaicin may reduce the incidence of aspiration pneumonia in dysphagia patients via Arnold's ear-cough reflex stimulation.