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Background: Nivolumab, a programmed death-1 antibody, is an immune checkpoint inhibitor approved in Japan in March 2017 for the treatment of recurrent or metastatic head and neck cancers (RM-HNCs) after platinum drug administration. This study aimed to evaluate the effectiveness and safety of nivolumab and to determine the prognostic factors affecting the treatment outcome, in a real-world setting in Japanese RM-HNCs. Methods: Forty-six patients with RM-HNCs treated with nivolumab between April 2017 and April 2021 at Shinshu University Hospital were retrospectively assessed in this cohort study. Results: The overall response rate was 17.4%, and the disease control rate was 41.3%. The median first and second progression-free survival (PFS1 and PFS2) were 2.6 and 10.3 months, respectively. The median overall survival (OS) was 14.8 months. Multivariate analysis showed that performance status (PS) (p = 0.003) and a decrease in neutrophil-lymphocyte ratio (NLR) (p = 0.02) were significantly associated with a better OS, and a decrease in NLR (p = 0.035) was associated with a better PFS2. Conclusions: This study is the first report of PFS2 in RM-HNCs treated with nivolumab; the long PFS2 may contribute to prolonged OS. We propose that the PS and a decrease in NLR could be useful clinical prognostic markers of nivolumab therapy, which can easily be evaluated in the clinical setting.

Concurrent chemoradiotherapy (CCRT) is one of the standard treatment strategies for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Prophylactic percutaneous gastrostomy (pPEG) has been reported to be useful for nutritional intervention during CCRT. On the other hand, disadvantages such as complications of gastrostomy itself and long-term PEG dependence have also been reported. In the present study, we conducted a retrospective review of the data of HNSCC cases treated with CCRT and reevaluate the merit and demerit of pPEG. Patients with pharyngeal carcinoma treated by CCRT between 2015 and 2020 were enrolled for this analysis. In this study, we limited our analysis to those who received the following treatments: Radiation therapy was planned for a total dose of 70 Gy, and the concomitant chemotherapy regimen was high-dose (100 mg/m2) CDDP administered intravenously once every three weeks (three cycles). A total of 54 patients who underwent pPEG met the inclusion criteria. Fifteen patients who had received similar treatment without pPEG during the study period were used as a control group for comparison. The results revealed that in the pPEG group, there were fewer cases with a weight loss of 10% or more, nutritional intervention was started relatively early, and the hospitalization period after the end of CCRT was shorter as compared with the status in the non-PEG group. In regard to PEG tube dependence, the rate of PEG tube usage at 6 months after CCRT was relatively low, at approximately 13%. No significant factor was identified in this study regarding the need for nutritional intervention by routes, including PEG tube, nasogastric tube, and total parenteral nutrition, other than oral intake. In the review of the literature, it seemed difficult to make a simple comparison due to the lack of uniformity in the selection criteria for pPEG, patient background, and treatment intensity.

Introduction: Sarcopenia, characterized by low skeletal muscle mass, and the outcome of cancer therapy are closely related based on recent research. This study aimed to evaluate the correlation between skeletal muscle mass and prognosis in head and neck cancer (HNC) patients. Methods: In this study, 51 male patients with HNC treated nonsurgically between January 2016 and April 2018 at Shinshu University Hospital were evaluated. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and the skeletal mass index (SMI) was calculated to classify the patients. Results: The low-SMI group had a significantly worse overall survival (OS) than the normal-SMI group (3-year OS: 72.0% vs. 93.0%, p = 0.014), and there was a trend toward worse progression-free survival (PFS) in the low-SMI group (3-year PFS: 49.6% vs. 79.3%, p = 0.064). Multivariate analysis also showed that low SMI (p = 0.04) and severe N stage (p = 0.009) were significantly associated with poorer OS. Conclusion: The pretreatment assessment of SMI using bioelectrical impedance analysis is useful for identifying patients with poor prognoses. To improve the treatment outcome in HNC, we need to think of the intervention, such as cancer rehabilitation and nutritional support, during or before treatment, especially for patients with low SMI.

Thyroglossal duct cysts (TGDC) are the most common type of congenital neck masses, which generally present in young adults. We present a rare case of a giant TGDC in a 77-year-old patient who required atypical perioperative management. The patient presented with a large soft mass on his anterior neck. Computed tomography showed a lobulated cystic mass measuring 18 × 16 cm, extending from the tongue base to the inferior level of the clavicle. Because difficult intubation was expected, the cyst was punctured and most of the fluid was drained prior to surgery. The swelling of the tongue base was remarkably reduced, and intubation was performed safely. The cyst was extracted using the Sistrunk procedure and tracheotomy was performed. Histopathological examination confirmed the diagnosis of TGDC. Preoperative volume reduction of the cyst and tracheotomy should be considered for oral intubation and postoperative airway management, respectively, in patients with large TGDC.

Sensorineural hearing loss is a common deficit and mainly occurs due to genetic factors. Recently, copy number variants (CNVs) in the STRC gene have also been recognized as a major cause of genetic hearing loss. We investigated the frequency of STRC deletions in the Japanese population and the characteristics of associated hearing loss. For CNV analysis, we employed a specialized method of Ion AmpliSeqTM sequencing, and confirmed the CNV results via custom array comparative genomic hybridization. We identified 17 probands with STRC homozygous deletions. The prevalence of STRC homozygous deletions was 1.7% in the hearing loss population overall, and 4.3% among mild-to-moderate hearing loss patients. A 2.63% carrier deletion rate was identified in both the hearing loss and the control population with normal hearing. In conclusion, our results show that STRC deletions are the second most common cause of mild-to-moderate hearing loss after the GJB2 gene, which accounts for the majority of genetic hearing loss. The phenotype of hearing loss is congenital and appears to be moderate, and is most likely to be stable without deterioration even after the age of 50. The present study highlights the importance of the STRC gene as a major cause of mild-to-moderate hearing loss.

GJB2 gene mutations are known to be the most common cause of hereditary hearing loss worldwide. Therefore, genetic testing for GJB2 mutations is one of the most important screening processes for the molecular diagnosis of deafness. However, some caution is due in the diagnosis of hearing loss based on GJB2 screening as several types of large deletions have been reported. Here, we report a novel deletion (copy number variation: CNV) in the GJB2 gene observed in a Japanese patient presenting with profound hearing loss. This deletion was observed in trans to a GJB2‐mutated allele carrying the GJB2:{"type":"entrez-nucleotide","attrs":{"text":"NM_004004.5","term_id":"195539329","term_text":"NM_004004.5"}}NM_004004.5:c.427C>T:p.R143W mutation by PCR fragment analysis. It should be noted that this deletion was identified as homozygosity of c.427C>T:p.R143W by Sanger sequencing. Array‐CGH analysis showed the deleted segment started in the middle of the GJB2 coding region and extended for at least eight thousand base pairs, although the GJB6 gene remained intact. The distal breakpoint downstream of the GJB6 gene differed from the breakpoints of the known DFNB1 locus deletions. This partial deletion in the GJB2 gene highlights the need for further improvements in GJB2 screening. Inherited sensorineural hearing loss (HL) is an extremely heterogeneous group of sensory disorders in humans. The overall incidence is estimated to be one in approximately 1000 newborns.1, 2 The GJB2 gene (MIM# 121011), which encodes the gap junction protein connexin 26 (Cx26), is the most common genetic etiology associated with congenital HL worldwide, with the mutation spectrums known to vary among different ethnic groups.3, 4, 5 The GJB2 gene is a small gene composed of two exons, one of which possesses a 678‐bp coding sequence. As screening of the GJB2 gene is considered a standard, first‐step approach in the diagnosis of genetic hereditary HL, it is not surprising that more than 300 mutations in the GJB2 gene sequence have been described (The Human Gene Mutation Database). In general terms, GJB2‐related congenital HL develops through a biallelic mutation. Among patients with a single GJB2 heterozygous status, some caution is due in the diagnosis of hearing loss based on GJB2 screening as a large deletion located in the 13q12 region encompassing the GJB2 and GJB6 genes (the so‐called DFNB1 locus) is sometimes seen in trans with GJB2‐coding region variants. Therefore, the potential for such deletions to be present should be kept in mind. To date, six large deletions contributing to HL have been identified in the DFNB1 region.6, 7, 8, 9, 10, 11 Here, we report for the first time a novel large deletion in the GJB2 gene in one Japanese family with nonsyndromic HL. The present work highlighted the diagnostic pitfalls of GJB2‐related hearing loss and could expand the pathogenic spectrum and strengthen our understanding of the complicated mechanisms by which GJB2 gives rise to HL.

The present study revealed that various etiologies are involved in single-sided deafness (SSD), and that the cause of SSD and asymmetrical hearing loss (AHL) differed greatly between congenital/early-onset cases and adult cases. Clarification of the etiology is the first step toward providing appropriate intervention.The study aimed to clarify the etiology of SSD and AHL patients.The etiology of a total of 527 SSD or AHL patients who visited Shinshu University Hospital between 2006 and 2016 were analyzed by imaging as well as serological tests for mumps virus, and CMV DNA testing.In our cohort of congenital/early-onset SSD (n = 210), the most prevalent cause in children was cochlear nerve deficiency (43.7%; 87 of 199 patients undergoing CT and/or MRI), followed by CMV infection, mumps infection, anomalies of the inner ear, ANSD, and other rare etiologies. In contrast, half of the adult SSD patients presented with idiopathic sensorineural hearing loss, followed by various types of otitis media, cerebellopontine angle tumor and other rare etiologies.