Comprehensive analysis of syndromic hearing loss patients in Japan.

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

Clinical features and treatment outcomes of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV): A retrospective analysis of 235 patients from a nationwide survey in Japan.

OBJECTIVE: We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV). METHODS: This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text. RESULTS: Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and older (median age: 68 years); (3) predominantly myeloperoxidase (MPO)-ANCA-positive (60%), followed by proteinase 3 (PR3)-ANCA-positive (19%) and both ANCAs-negative (16%); (4) frequently observed accompanying facial palsy (36%) and hypertrophic pachymeningitis (28%); and (5) disease often involving lung (35%) and kidney (26%) lesions. Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse. The occurrence of hypertrophic pachymeningitis was associated with facial palsy (p < 0.05), both ANCAs-negative phenotype (p < 0.001), and headache (p < 0.001). The administration of corticosteroid together with an immunosuppressant was an independent predicting factor for lack of disease relapse (odds ratio [OR] = 1.90, p = 0.03) and an improvement in hearing loss (OR =2.58, p = 0.0002). CONCLUSION: Since OMAAV has novel clinical features, the disease may be categorized as a subentity for the classification of AAV.

[Assessment of Cachexia in Head and Neck Cancer Patients Based on a Modified Glasgow Prognostic Score].

We retrospectively analyzed 54 patients who died of head and neck squamous cell caricinoma regarding the process and duration of cachexia using the modified Glasgow Prognostic Score (mGPS). The patients were classified as having cachexia when the serum albumin level was less than 3.5 mg/dL and the C-reactive protein (CRP) level was more than 0.5 mg/dL. The number of patients with cachexia was eight (8%) at the first visit and 50 (93%) at the time of death. In the 50 patients, the median and average time of having cachexia was 59 and 95 days, respectively. Thirty-two of the 50 patients (64%) died within three months after the presence of cachexia was confirmed. In this study, the time of having cachexia was so short, then the policy of care should be converted from aggressive into supportive in patients classified as having cachexia. mGPS would be an accurate assessment tool for cachexia and ascertain the end stage of head and neck cancer patients.

Chemoselection combined with alternating chemoradiotherapy or surgery for hypopharyngeal cancer.

OBJECTIVES/HYPOTHESIS: In order to make possible organ preservation, since 2007 our hospital has performed induction chemotherapy (ICT) with cisplatin and 5-fluorouracil (PF) for hypopharyngeal cancer as chemoselection, followed by alternating chemoradiotherapy (ACRT) with docetaxel, cisplatin, and 5-fluorouracil in (TPF) good responders and curative surgery was used in poor responders. METHODS: Twenty-six patients with stage III to stage IVB hypopharyngeal cancer received ICT. Eleven of the patients were classified as poor responders and received curative surgery. The remaining 15 patients were classified as good responders. Three of these patients underwent curative surgery, and the remaining 12 underwent ACRT. RESULTS: The primary lesions in the 12 ACRT patients responded completely to treatment without severe late toxicities. The estimated 3-year laryngectomy-free rate for all 26 patients was 23%. The estimated 3-year overall survival rates for all 26 patients, 12 patients treated with ACRT, and 14 patients who underwent curative surgery, were 79%, 75%, and 84%, respectively. CONCLUSION: The patients who underwent ACRT showed no significant difference in overall survival compared with the patients who underwent curative surgery. All the patients were able to proceed with this series of therapy, indicating that ICT with PF could be a feasible tool for choosing good responders. Because ACRT with TPF had a high response rate and fewer severe toxicities, this treatment could be safe and have enough impact to control hypopharyngeal cancer in good responders. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1349-1353, 2016.

Presence of cytomegalovirus in the perilymphatic fluid of patients with profound sensorineural hearing loss caused by congenital cytomegalovirus infection.

CONCLUSION: Not all patients diagnosed with congenital infection using umbilical cord assay were found to be positive for CMV-DNA by perilymphatic fluid assay. In addition, a CMV-DNA-positive result was observed in one patient who had not been diagnosed with congenital infection. Sampling of perilymphatic fluid from a large population of patients with congenital SNHL caused by congenital CMV infection or of unknown etiology is required to determine the prevalence of CMV-related profound HL. OBJECTIVES: Sensorineural hearing loss (SNHL) is one of the most frequent manifestations in patients with congenital cytomegalovirus (CMV) infection. Using dried umbilical cord, a PCR-based assay was recently developed for the retrospective detection of congenital CMV infection. This study analyzed the presence of CMV in the perilymphatic fluid and evaluated differences in the effect of cochlear implantation between CMV-positive and -negative groups. METHOD: Perilymphatic fluid was collected from each patient at the time of cochlear implantation and analyzed for the presence of CMV using a PCR method. RESULTS: The perilymphatic fluid in two of the five patients suffering from congenital CMV infection and in one of the 17 patients without congenital CMV infection was found to be positive for CMV.

Stiffness of salivary gland and tumor measured by new ultrasonic techniques: Virtual touch quantification and IQ.

OBJECTIVE: To evaluate normal salivary gland stiffness and compare the diagnostic performance of virtual touch quantification (VTQ) and virtual touch imaging quantification (VTIQ) for head and neck tumor. METHODS: A total of 92 measurements were examined, comprising 77 normal salivary glands, 11 benign tumors and four malignant tumors. Examinations were made to evaluate normal salivary gland stiffness and compare the diagnostic performances of new ultrasonic techniques regarding head and neck tumor. RESULTS: The mean values of VTQ and VTIQ for the normal salivary group (NSG) were 1.92 and 2.06m/s, respectively. The VTQ and VTIQ values were correlative, and there were no statistical differences in each mean value between the normal parotid glands and submandibular glands. For the benign tumor group (BTG), four of the 11 values were non-numeric and were considered above the measurable range. The mean VTIQ value for the BTG was 4.24m/s. For the malignant tumor group (MTG), all four VTQ values were non-numeric. The mean VTIQ value for the MTG was 6.52m/s. For the mean VTIQ values, significant differences were observed among the three groups. The optimum VTQ cutoff value to detect malignant tumors was above the measurable range, and that of VTIQ was 4.83m/s. CONCLUSION: The VTQ and VTIQ values were correlative for the salivary glands, and the stiffnesses of normal parotid glands were almost same as those of submandibular glands. VTQ and VTIQ values could be applied for the preoperative diagnosis in salivary gland lesions.

Usefulness of sentinel node navigation surgery in the management of early tongue cancer.

OBJECTIVE: To determine the validity of sentinel node navigation surgery (SNNS) in early stage tongue cancer, the occurrence rate of postoperative cervical metastasis (POCM) after lead plate technique (LPT) introduction and survival rates in patients who underwent SNNS were analyzed. METHODS: SNNS was performed in 29 patients (stage I: 14, stage II: 15) from 2000 to 2007. Tc-labeled phytate was prepared as a radiotracer a day before SNNS. The sentinel node (SN) was then examined pathologically during surgery. For cases where metastasis in SN was positive, neck dissection was performed. Occurrence of POCM after LPT introduction was compared with that before LPT introduction. 'Wait and see' policy was performed in 52 patients (stage I: 27, stage II: 25) from 1987 to 1999 as a historical control. The observation period of SNNS cases and 'wait and see' policy cases ranged from 10 months to 165 months (median: 91 months) and from 7 months to 268 months (median: 87 months), respectively. RESULTS: Six of the 29 SNNS cases (21%) were proven metastatic SNs. Before LPT introduction, POCM occurred in 2 of the 15 cases, while we had no occurrences after LPT introduction. The 5-year overall survival rate of the 29 patients who underwent SNNS and the 52 patients with 'wait and see' policy were 96% and 84%, respectively, and there was statistical significance in the two groups (p<0.05). CONCLUSIONS: As the survival rate of the patients with the SNNS tended to be better than that with the 'wait and see' policy in our cases, SNNS could avoid unnecessary neck dissection. SNNS provides useful information regarding decision-making for neck dissection in early stage tongue cancer.

[A case of hereditary angioedema defined by gene analysis].

Hereditary angioedema (HAE) is a disease that is characterized by localized edema that can occur anywhere in the body, and is caused by a mutation of the C1-inhibitor gene. In the oto-rhino-laryngological region, it occurs in the mouth, pharynx, larynx, and on the face. Occasionally, laryngopharyngeal edema can in particular sometimes be fatal. We report herein on a case of a 59-year-old female who was admitted to our hospital for further evaluation and treatment of laryngopharyngeal edema. She had a history of subcutaneous edema during pregnancy and ascites of unknown origin without a definitive diagnosis. On admission, there were low C1 inhibitor and complement C4 levels, and normal C1q levels. As the patient had no family history of HAE, we performed gene analysis, which revealed mutation of the C 1-inhibitor gene in Exon7. In cases of HAE without family history, gene analysis is required for accurate diagnosis.

Outcome of cochlear implantation in children with congenital cytomegalovirus infection or GJB2 mutation.

CONCLUSIONS: Outcomes following cochlear implantation in children with congenital cytomegalovirus (CMV) infection were almost equivalent to those of children with GJB2 mutation-related sensorineural hearing loss (SNHL). Although our patients with developmental disorder showed poor auditory performance and speech and language skills after cochlear implantation, SNHL with developmental disorder should not be a contraindication for the procedure. OBJECTIVE: Congenital CMV infection accounts for approximately 20% of all cases of neonatal hearing loss, while the GJB2 mutation accounts for 30-50% of all cases of profound nonsyndromic hearing loss. Here, outcomes for auditory behavior and speech and language skills were compared in children with congenital CMV infection or GJB2 mutation who received cochlear implantation for profound SNHL. METHODS: Five children with asymptomatic congenital CMV infection and seven children with GJB2 mutation-related SNHL, with and without developmental disorder, underwent cochlear implantation. Hearing level and speech and language development were evaluated post-implantation using IT-MAIS, MUSS, and S-S method. RESULTS: The IT-MAIS and MUSS scores of the congenital CMV infection group and the GJB2 mutation group continued to increase for 4 years after implantation. The S-S method score in both groups gradually increased, although the scores for children with mental retardation were low.

Sentinel node mapping for node positive oral cancer: potential to predict multiple metastasis.

OBJECTIVE: The objective of this study is to evaluate lymph node mapping for clinically positive neck metastasis using a sentinel node navigation technique. METHODS: 99mTc-labeled rhenium sulfide was injected as a radiotracer in 10 patients with squamous cell carcinoma of the tongue. After surgery, lymph nodes were classified into two categories according to the radioactive accumulation: nodes with radioactivity and nodes without radioactivity. The ratio of the metastatic area (RMA) of pathologically metastatic lymph nodes was measured. RESULTS: In 5 of 10 cases, all of the metastatic nodes had radioactive accumulation. In one case with three metastatic nodes, radioactivity was not detected in one metastatic node, although it was detected in the other two nodes. In the other four cases, there were no radioactivities in any of the metastatic nodes. RMA of lymph nodes in which radioactivity was not detected was higher than that of lymph nodes in which radioactivity was detected. None of the nodes in which radioactivity was detected was fully occupied by metastatic carcinoma cells. In each case, in comparing the clinically positive lymph nodes, RMA of the nodes in which no radioactivity was detected was higher than that of the nodes in which radioactivity was detected. CONCLUSION: The principle behind the sentinel node technique is detection of the node that has the most lymph flow from the tumor through injection of the tracer into the circumference of the tumor. When no radioactive accumulation is found in clinically positive metastatic lymph nodes, the possibility of metastasis to other lymph nodes should be highly suspected.

[Pharmacodynamics of tongue tissue and plasma after intraarterial infusion of cis-diammine glycolato platinum (CDGP)].

We measured total Pt concentration in serum and tongue tissue in CDGP intraarterial infusion with male rats. Subjects were 40 male rats sorted into intraarterial infusion (n=20), intravenous infusion (n=20), and CDGP infusion groups at a dose of 10 mg/kg. Total Pt concentration was measured every 30 minutes for 120 minutes after CDGP infusion was completed. Total Pt concentration in tongue tissue was measured on the dosage and nondosage side. Total Pt concentration on the dosage side of tongue tissue of the intraarterial infusion group was higher than in the intravenous infusion group for 120 minutes. Total Pt concentration in intraarterial infusion group tongue tissue on the dosage side was higher than on the nondosage side for 120 minutes. Serum total Pt concentration, total Pt concentration in nondosage side tongue tissue, AUC of total Pt in serum, elimination half-life (t1/2) did not show a difference in the intraarterial or intravenous infusion groups. Total Pt AUC in tongue tissue on the intraarterial infusion group dosage side was greater than in others. In intraarterial infusion of CDGP, Pt concentration in tongue tissue is higher than in intravenous infusion. Serum Pt concentration, did not differ by group. This study showed that intraarterial infusion of CDGP has the potency to become a chemotherapy indication the same as intravenous infusion, in addition to the target organ.