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We reported on transcanal endoscopic myringoplasty in 25 cases preliminarily in 2014. Now our number of transcanal endoscopic myringoplasty reached to 209 ears and allowed us to adequately investigate the visibility, necessity of canalplasty, treatment results, and multivariate analysis.A prospective case series.Tertiary referral center.Transcanal endoscopic myringoplasty was performed on 209 ears in 201 patients between 2011 and 2019 and followed up over 1 year.Preoperative endoscopic and microscopic views for the same patient were compared. We examined success rates at 1 year after surgery according to operation type, perforation size, operation side, gender, cause of perforation, and age, and also examined hearing results. Logistic regression analysis was performed to investigate the basic demographic and clinical characteristics of the patients associated with perforation closure.The anterior edge of the preoperative perforation was not visible under microscopy in 14.4% of patients. In contrast, endoscopic views revealed the entire tympanic membrane in one field. However, canalplasty was required in 2.4% of tympanic procedures due to difficulty of manipulation. The overall closure rate for perforations was 90.4%. Logistic regression analysis revealed that age11 was the only significant factor associated with perforation closure. The average reduction in air-bone gap was 12.1 dB.The endoscopic myringoplasty produced better visualization, the same or better closure rates, and the same or lower complication rates as compared with traditional microscopic techniques.

Objective Facial nerve schwannomas (FNSs) and chorda tympani schwannomas are very rare. Diagnosis of these tumors is sometimes difficult, and treatment consensus has not yet been reached. We report here a series of cases of FNS and chorda tympani schwannoma and highlight the usefulness of our newly developed technique of non-rigid registration of post-enhanced 3D-T1 Turbo Field Echo and CT images (TURFECT) in their diagnosis and treatment. Methods MRI images were adjusted with the corresponding CT images in terms of angle and position in order to index the anatomical structures. The well-enhanced T1-Gd+ lesions of tumors having good blood flow show up as bright red after color mapping. Results Between 2014 and 2018, five patients were diagnosed with schwannomas in the temporal bone: three with FNS and two with chorda tympani schwannoma. Gd-enhanced MRI showed only a high-intensity mass, and we could not detect the relationship between tumor-like mass and bone (including the ossicles) by MRI only. In contrast, TURFECT was very useful for diagnosing the precise location, allowing us to decide on an endoscopic surgical plan in some of our cases. An endoscope enabled visualization of the medial wall of the tympanic cavity and the status of the tumors, thus we could successfully perform transcanal endoscopic biopsy and resections. Conclusion TURFECT can be very useful for diagnosis of FNSs and chorda tympani schwannomas and for deciding surgical treatments such as a transcanal endoscopic approach.

Objective To demonstrate the efficacy of transcanal endoscopic ear surgery (TEES) for congenital middle ear anomalies. Study design Retrospective case review. Setting Tertiary referral center. Patients Twenty-one patients ranging in age from 4 to 62 years old (median: 15 yr) who underwent TEES between 2011 and 2017 were compared with 19 patients ranging in age from 3 to 49 years old (median: 11 yr) who underwent microscopic ear surgery (MES) between 2000 and 2011. Intervention Ossiculoplasty or stapes surgeries were performed with TEES or MES. TEES was performed using a rigid endoscope with an outer diameter of 2.7-mm coupled with a full high-definition video system. MES was performed via a transcanal approach with a retroauricular incision. Main outcome measure Middle ear anomaly classification, operating time, and hearing outcomes based on the American Academy of Otolaryngology and Head and Neck Surgery criteria were evaluated and compared between the TEES and MES groups. Results For Teunissen and Cremers class III anomalies, defined as ossicular chain malformations with a mobile stapes footplate, postoperative air-bone gap closure to 10 dB or less was achieved in 50% of the TEES group and 47% of the MES group. Postoperative air-bone gap closure to 20 dB or less was achieved in 86% of the TEES group and 100% of the MES group. No significant difference was found in the operating time between the two groups. All MES procedures required a retroauricular incision. Conclusion Our results indicate that TEES has similar auditory outcomes compared with MES while avoiding a retroauricular incision.

Cochlear hair cells are essential for the mechanotransduction of hearing. Sensorineural hearing loss can be irreversible because hair cells have a minimal ability to repair or regenerate themselves once damaged. In order to develop therapeutic interventions to prevent hair cell loss, it is necessary to understand the signaling pathway operating in cochlear hair cells and its alteration upon damage. Diacylglycerol kinase (DGK) regulates intracellular signal transduction through phosphorylation of lipidic second messenger diacylglycerol. We have previously reported characteristic expression and localization patterns of DGKs in various organs under pathophysiological conditions. Nevertheless, little is known about morphological and functional aspects of this enzyme family in the cochlea. First RT-PCR analysis reveals predominant mRNA expression of DGKα, DGKε and DGKζ. Immunohistochemical analysis shows that DGKζ localizes to the nuclei of inner hair cells (IHCs), outer hair cells (OHCs), supporting cells and spiral ganglion neurons in guinea pig cochlea under normal conditions. It is well known that loud noise exposure induces cochlear damage, thereby resulting in hair cell loss. In particular, OHCs are highly vulnerable to noise exposure than IHCs. We found that after 1 week of noise exposure DGKζ translocates from the nucleus to the cytoplasm in damage-sensitive OHCs and gradually disappears thereafter. In sharp contrast, DGKζ remains to the nucleus in damage-resistant IHCs. These results suggest that DGKζ cytoplasmic translocation is well correlated with cellular damage under noise-exposure stress conditions and is involved in delayed cell death in cochlear outer hair cells.

Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab’s efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.

The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese patients with hearing loss. Furthermore, the clinical features of OTOA-associated hearing loss have not yet been clarified. In this study, we performed CNV analyses of a large Japanese hearing loss cohort, and identified CNVs in 234 of 2262 (10.3%, 234/2262) patients with autosomal recessive hearing loss. Among the identified CNVs, OTOA gene-related CNVs were the second most frequent (0.6%, 14/2262). Among the 14 cases, 2 individuals carried OTOA homozygous deletions, 4 carried heterozygous deletions with single nucleotide variants (SNVs) in another allele. Additionally, 1 individual with homozygous SNVs in the OTOA gene was also identified. Finally, we identified 7 probands with OTOA-associated hearing loss, so that its prevalence in Japanese patients with autosomal recessive hearing loss was calculated to be 0.3% (7/2262). As novel clinical features identified in this study, the audiometric configurations of patients with OTOA-associated hearing loss were found to be mid-frequency. This is the first study focused on the detailed clinical features of hearing loss caused by this gene mutation and/or gene deletion.

Ear surgery in many ways lagged behind other surgical fields because of the delicate anatomical structures within the ear which leave surgeons with little room for error. Thus, while surgical instruments have long been available, their use in the ear would most often do more damage than good. This state of affairs remained the status quo well into the first half of the 20th century. However, the introduction of powered surgical instruments, specifically the electric drill used in conventional microscopic ear surgery (MES) and the ultrasonic aspirator, the Sonopet® Omni, in transcanal endoscopic ear surgery (TEES) marked major turning points. Yet, these breakthroughs have also raised concerns about whether the use of these powered surgical instruments within the confines of the ear generated so much noise and vibrations that patients could suffer sensorineural hearing loss as a result of the surgery itself. This paper reviews the intersection between the noise and vibrations generated during surgery; the history of surgical instruments, particularly powered surgical instruments, used in ear surgeries and the two main types of surgical procedures to determine whether these powered surgical instruments may pose a threat to postoperative hearing.

Orotate phosphoribosyltransferase (OPRT) is engaged in de novo pyrimidine synthesis. It catalyzes oronitine to uridine monophosphate (UMP), which is used for RNA synthesis. De novo pyrimidine synthesis has long been known to play an important role in providing DNA/RNA precursors for rapid proliferative activity of cancer cells. Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase. These 5-FU metabolites are misincorporated into DNA/RNA, thereby producing dysfunction of these information processing. However, it remains unclear how the subcellular localization of OPRT and how its variable expression levels affect the response to 5-FU at the cellular level. In this study, immunocytochemical analysis reveals that OPRT localizes to the Golgi complex. Results also show that not only overexpression but also downregulation of OPRT render cells susceptible to 5-FU exposure, but it has no effect on DNA damaging agent doxorubicin. This study provides clues to elucidate the cellular response to 5-FU chemotherapy in relation to the OPRT expression level.

Orotate phosphoribosyltransferase (OPRT) is engaged in de novo pyrimidine synthesis. It catalyzes oronitine to uridine monophosphate (UMP), which is used for RNA synthesis. De novo pyrimidine synthesis has long been known to play an important role in providing DNA/RNA precursors for rapid proliferative activity of cancer cells. Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase. These 5-FU metabolites are misincorporated into DNA/RNA, thereby producing dysfunction of these information processing. However, it remains unclear how the subcellular localization of OPRT and how its variable expression levels affect the response to 5-FU at the cellular level. In this study, immunocytochemical analysis reveals that OPRT localizes to the Golgi complex. Results also show that not only overexpression but also downregulation of OPRT render cells susceptible to 5-FU exposure, but it has no effect on DNA damaging agent doxorubicin. This study provides clues to elucidate the cellular response to 5-FU chemotherapy in relation to the OPRT expression level.

We report a case of primary small cell carcinoma (SCC) of the paranasal sinus, which is a rare clinical entity, originating in the right ethmoid sinus. A 45-year-old woman seen for right nasal obstruction was found in anterior rhinoscopy to have a hemorrhagic tumor in the right nasal cavity. Computed tomography (CT) showed swelling of the right ethmoidal mucosa. Nasal tumor biopsy yielded a diagnosis of SCC. She was treated with irradiation and four courses of chemotherapy using cisplatin and etoposide. To evaluate the therapeutic effect, she underwent endoscopic sinus surgery, judged to be Grade 3. No recurrence has been seen in the 15 months since initial treatment.

The number of tonsillectomies, involving children has decreased and those involving adult dense peritonsillar adhesions has increased. Tonsil surgery is generally the first basic procedure an otolaryngologist learns and conducts alone. Since tonsil operations are numerous, the postoperative course is fairly constant, and the clinical path is easily applicable, otolaryngologists must master this basic procedure as a minimum for general hospital surgery and otolaryngology department management. While serious complications rare, we report the case of an 18-year-old woman who developed a pulmonary embolism the morning after bilateral tonsillectomy. We conducted an aggregate analysis of tonsil surgeries by otolaryngologists and the incidence of postoperative complications.

Sialolithiasis refers to calculi forming where saliva is produced, with over 90% occuring in the submandibular gland. When saliva stagnates due to sialolithiasis, swelling develops and eating becomes painful. Symptoms are severe in the acute stage, but an asymptomatic state may persist. A 19-year-old woman with right submandibular sialolithiasis detected while she was in primary school developed an abscess that was not ameliorated in conservative treatment. An intraoral attempt to remove calculi released only pus. Despite temporary improvement, Wharton's duct was obstructed 2 months postoperatively, with impaired saliva outflow causing acute submandibular swelling. Computed tomography (CT) showed a huge mucosal cyst in the oral floor. The mandibular gland and cyst were removed by external incision.

The endoplasmic reticulum (ER), comprised of an interconnected membrane network, is a site of phospholipid and protein synthesis. The diacylglycerol kinase (DGK) enzyme family catalyzes phosphorylation of diacylglycerol to phosphatidic acid. Both of these lipids are known not only to serve as second messengers but also to represent intermediate precursors of lipids of various kinds. The DGK family is targeted to distinct subcellular sites in cDNA-transfected and native cells. Of DGKs, DGKe localizes primarily to the ER, suggesting that this isozyme plays a role in this organelle. Using experiments with various deletion and substitution mutants, this study examined the molecular mechanism of how DGKe is targeted to the ER. Results demonstrate that the N-terminal hydrophobic sequence 20-40 plays a necessary role in targeting of DGKe to the ER. This hydrophobic amino acid segment is predicted to adopt an α-helix structure, in which Leu22, L25, and L29 are present in mutual proximity, forming a hydrophobic patch. When these hydrophobic Leu residues were replaced with hydrophilic amino acid Gln, the mutant fragment designated DGKe (20-40/L22Q,L25Q,L29Q) exhibits diffuse distribution in the cytoplasm. Moreover, full-length DGKe containing these substitutions, DGKe (L22Q,L25Q,L29Q), is shown to distribute diffusely in the cytoplasm. These results indicate that the N-terminal hydrophobic residues play a key role in DGKe targeting to the ER membrane. Functionally, knockdown or deletion of DGKe affects the unfolding protein response pathways, thereby rendering the cells susceptible to apoptosis, to some degree, under ER stress conditions.

Recent studies have revealed that phosphoinositide (PI) signaling molecules are expressed in mammalian retinas, suggesting their importance in its signal transduction. We previously showed that diacylglycerol kinase (DGK) isozymes are expressed in distinct patterns in rat retina at the mRNA level. However, little is known about the nature and morphological aspects of DGKs in the retina. For this study, we performed immunohistochemical analyses to investigate in the retina the expression and localization of DGK isozymes at the protein level. Here, we show that both DGKβ and DGKι localize in the outer plexiform layer, within which photoreceptor cells make contact with bipolar and horizontal cells. These isozymes exhibit distinct subcellular localization patterns: DGKι localizes to the synaptic area of bipolar cells in a punctate manner, whereas DGKβ distributes diffusely in the subsynaptic and dendritic regions of bipolar and horizontal cells. However, punctate labeling for DGKϵ is evident in the outer limiting membrane. DGKζ and DGKα localize predominantly to the nucleus of ganglion cells. These findings show distinct expression and localization of DGK isozymes in the retina, suggesting a different role of each isozyme.