Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.

A Case of Metastatic Submandibular Salivary Duct Carcinoma that Completely Responded to Pembrolizumab Monotherapy.

Salivary gland carcinoma is a rare cancer and has more than 20 histopathological types. Although chemotherapy has been the mainstay of treatment for unresectable carcinomas such as multiple recurrence and distant metastasis, no standard regimen is available. In this article, we report a case of poorly differentiated salivary duct carcinoma of the submandibular gland with distant metastases that was successfully treated with pembrolizumab monotherapy. A 66-year-old man became aware of a left submandibular mass 2 months before his first visit to our department. A needle biopsy at a previous hospital revealed carcinoma, not otherwise specified. The combined positive score on a programmed death ligand-1 immunohistochemistry test was 1-10%. The patient was referred to our department for further treatment. Computed tomography revealed left level II and IV neck lymphadenopathy, bilateral lung shadowing, and osteolytic changes in the 12th thoracic vertebra. Needle biopsy showed poorly differentiated carcinoma, positive human epidermal growth factor receptor 2, and positive androgen receptor, which suggested salivary duct carcinoma. These findings indicated a diagnosis of submandibular carcinoma T4aN2bM1 stage IVC. Pembrolizumab monotherapy was started, and tumor shrinkage was observed after three courses of treatment. At 1 year, complete response was achieved without adverse events, and treatment is ongoing. Despite a lack of evidence for the efficacy of immune checkpoint inhibitors in salivary gland carcinoma, the present case suggests that some patients might respond to this treatment. Hence, clinical trials are warranted.

Bilobed Flap for Reconstruction of Skin Defects after Excision of Parotid Carcinoma: A Case Report.

OBJECTIVES: Local flaps, pedicled flaps, and free flaps are used to reconstruct medium-sized skin defects after excision of parotid carcinoma. The bilobed flap is a local flap primarily used by plastic surgeons for small defects of nasal skin. We report a case of parotid carcinoma with skin infiltration successfully treated by skin reconstruction with a bilobed flap. METHODS: An 84-year-old man presented with a parotid mass he had noticed 2 months earlier. Parotid carcinoma with skin infiltration was diagnosed and he underwent radical surgery. The skin defect was round (diameter, 6 cm) and was resected and reconstructed with a bilobed flap designed to be caudal to the defect. RESULTS: Postoperative facial nerve palsy improved within 6 months. The postoperative course was otherwise uneventful, and the patient was discharged on postoperative day 7. Pathological examination revealed a sarcomatoid salivary duct carcinoma. CONCLUSIONS: Bilobed flaps are useful for reconstructing skin defects with a diameter of 6 cm or less.

Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.

Trapezius muscle branch of the spinal accessory nerve without penetrating the sternocleidomastoid muscle as a pitfall in neck dissection: prevalence in a Japanese institution and a protocol for the prevention of iatrogenic injury.

BACKGROUND: The spinal accessory nerve (SAN) has several anatomical variations, which may be a pitfall in neck dissection (ND). These include the trapezius muscle branch (TB), which stems from the common trunk before entering the sternocleidomastoid muscle (SCM). AIMS/OBJECTIVES: To investigate the prevalence of this variation and suggest a protocol for preventing unexpected injury of the TB in ND. MATERIALS AND METHODS: We conducted a retrospective cohort study for 93 patients who had undergone neck dissection (117 sides) without resection of the SCM nor SAN. We recorded the division of the TB after and before penetration of the SCM by the common trunk (penetrating type TB [PTB]) and non-penetrating type TB [NPTB], respectively). RESULTS: Among NDs, PTB and NPTB were observed in 61 (52%) and 56 (48%) sides, respectively. In the subgroup of 24 cases with bilateral ND, PTB/PTB, NPTB/NPTB, and NPTB/PTB were observed in eight (33%), nine (38%), and seven (29%) cases, respectively. The prevalence of PTB/NPTB did not differ according to age, sex, or laterality. CONCLUSIONS AND SIGNIFICANCE: NPTB is a common anatomical variation. The presence or absence of a branch from the common trunk must be initially checked to avoid unexpected damage to the TB.

Tonsillectomy Combined With Steroid Pulse Therapy Prevents the Progression of Chronic Kidney Disease in Patients With Immunoglobulin A (IgA) Nephropathy in a Single Japanese Institution.

Background Despite the abundant experience of tonsillectomy with steroid pulse therapy (TSP) for patients with immunoglobulin A (IgA) nephropathy, the therapeutic efficacy of TSP on renal prognosis remains controversial. The purpose of this study was to evaluate the efficacy of whether TSP effectively prevents chronic kidney disease (CKD) progression. Methods This was a single-center, retrospective observational study. A total of 149 patients were enrolled in the current study who were confirmed with IgA nephropathy by renal biopsy between February 2011 and August 2019. The impact of TSP on CKD progression was compared with conservative treatment during a follow-up period of 3 years. Results In total, 110 patients received TSP and 39 patients received conservative treatment. There were no differences between the two groups in the initial CKD stages: 65.1% of patients had CKD G1-2, 32.2% had CKD G3, and 2.7% had CKD G4-5. The initial urine protein was 0.7 g/gCr, which was not different between the two groups. Kaplan-Meier analysis showed that patients with TSP had a significantly better renal prognosis than those in the conservative treatment group after one and a half years (p = 0.007). Multivariable analysis revealed that TSP had a significant impact on the prevention of CKD progression, with an adjusted odds ratio of 0.07 (95% confidence interval, 0.01-0.87; p=0.039). However, we could not confirm the predictive value of the Oxford Classification on TSP efficacy. Additionally, the initial urinary protein level was a risk factor for CKD progression. Conclusions TSP was associated with a lower risk of CKD progression. In this regard, our study supports that TSP may be a reasonable treatment option for patients with IgA nephropathy. In the featured study, it needs to be elucidated which histopathological classifications benefit from TSP treatment.

Syndrome of Inappropriate Secretion of Antidiuretic Hormone Caused by Very Short-term Use of Proton Pump Inhibitor.

Proton pump inhibitors (PPIs) are widely used medicines worldwide. However, a rare etiology of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) related to PPI was recently reported. Therefore, the putative role of PPIs in SIADH cannot be underestimated. A 78-year-old Japanese woman was admitted to our hospital for treatment of left Bell's palsy. On admission, the patient was oriented with normal laboratory data, including a serum Na level of 135 mEq/L. Oral glucocorticoids and a proton pump inhibitor were initiated in combination with oral valaciclovir. Six days later, the patient's consciousness became impaired. Laboratory data showed a serum Na level of 103 mEq/L, a urine Na level of 64.8 mEq/L, a urine K level of 43.6 mEq/L, and a urine osmolality of 450 mOsm/kg H2O. The patient met the criteria for SIADH. The initial treatment included water restriction and 3% hypertonic saline administration. The cessation of PPI significantly improved the urine diluting capacity and concomitantly increased serum Na, which indicated that the use of PPI had been responsible for the etiology of SIADH. The present case illustrates that physicians need to be aware of the uncommon adverse effects of PPI, such as SIADH.

Clinical characteristics, the diagnostic criteria and management recommendation of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) proposed by Japan Otological Society.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a form of necrotizing vasculitis with few or no immune deposits. It primarily affects small and medium blood vessels. AAV is classified into three categories, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangitis (EGPA), and two major ANCAs, proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA are involved in their pathogenesis. Intractable otitis media frequently occurs in patients with GPA, MPA or EGPA, although all patients show similar clinical features, regardless of the type of AAV. Furthermore, approximately 15% patients with otitis media caused by AAV do not show ANCA positivity, histopathological evidence, or any other AAV-related lesions at the initial visit; therefore, these patients do not fulfill the ordinary diagnostic criteria for systemic AAV. Thus, we first proposed that this condition could be categorized as "otitis media with AAV (OMAAV)". Subsequently, the Japanese Otological Society (JOS) conducted a nationwide survey between December 2013 and February 2014 and identified 297 patients with OMAAV. The survey revealed that OMAAV is a disease that initially occurs in the middle ear and subsequently spreads to other organs such as the lungs and kidneys, with eventual involvement of all body organs. Severe sequelae such as facial palsy, hypertrophic pachymeningitis, complete deafness, and subarachnoid hemorrhage resulting in death can also occur. In this review, we introduce the clinical features, diagnostic criteria, and treatment strategies recommended by JOS for early diagnosis and treatment of OMAAV.

Visual effects on the subjective visual vertical and subjective postural head vertical during static roll-tilt.

OBJECTIVES: Tilt perception is part of the perception of spatial orientation. It is determined not only by the allocentric gravity axis, but also by a second allocentric axis induced by visual information as well as by the egocentric body (head) axis induced by somatosensory information. The aim of this study was to quantify roll-tilt perception using the subjective visual vertical (SVV) and the newly developed subjective postural head vertical (SPHV) and to investigate the visual effects on both during static roll-tilt. STUDY DESIGN: Basic science. METHODS: Nine male volunteers participated in this study. A flight simulator was used to create several roll-tilt environments that were then combined with visual information. SVV and SPHV were evaluated in healthy participants during static roll-tilt. RESULTS: The SVV evaluation revealed significant differences between the dark condition (control) and other visual conditions with respect to some of the body roll-tilt environments, and between a body roll-tilt of 0° and ≥ 20°. The SPHV evaluation revealed a significant difference between the dark condition and the visual condition that was always roll-tilted 20° to the right of the body axis. However, there were no significant differences in SPHV error between a body roll-tilt of 0° and other tilt angles for every visual condition, unlike SVV error. CONCLUSIONS: Our data indicate that human susceptibility to spatial disorientation is dependent on roll-tilt angle and visual information. They also suggest that the SPHV is not affected by roll-tilt angle, and thus differs from SVV. LEVEL OF EVIDENCE: NA.

Protein transduction therapy into cochleae via the round window niche in guinea pigs.

Cell-penetrating peptides (CPPs) are short sequences of amino acids that facilitate the penetration of conjugated cargoes across mammalian cell membranes, and as such, they may provide a safe and effective method for drug delivery to the inner ear. Simple polyarginine peptides have been shown to induce significantly higher cell penetration rates among CPPs. Herein, we show that a peptide consisting of nine arginines ("9R") effectively delivered enhanced green fluorescent protein (EGFP) into guinea pig cochleae via the round window niche without causing any deterioration in auditory function. A second application, 24 hours after the first, prolonged the presence of EGFP. To assess the feasibility of protein transduction using 9R-CPPs via the round window, we used "X-linked inhibitor of apoptosis protein" (XIAP) bonded to a 9R peptide (XIAP-9R). XIAP-9R treatment prior to acoustic trauma significantly reduced putative hearing loss and the number of apoptotic hair cells loss in the cochleae. Thus, the topical application of molecules fused to 9R-CPPs may be a simple and promising strategy for treating inner ear diseases.

Pathophysiology of the inner ear after blast injury caused by laser-induced shock wave.

The ear is the organ that is most sensitive to blast overpressure, and ear damage is most frequently seen after blast exposure. Blast overpressure to the ear results in sensorineural hearing loss, which is untreatable and is often associated with a decline in the quality of life. In this study, we used a rat model to demonstrate the pathophysiological and structural changes in the inner ear that replicate pure sensorineural hearing loss associated with blast injury using laser-induced shock wave (LISW) without any conductive hearing loss. Our results indicate that threshold elevation of the auditory brainstem response (ABR) after blast exposure was primarily caused by outer hair cell dysfunction induced by stereociliary bundle disruption. The bundle disruption pattern was unique; disturbed stereocilia were mostly observed in the outermost row, whereas those in the inner and middle rows stereocilia remained intact. In addition, the ABR examination showed a reduction in wave I amplitude without elevation of the threshold in the lower energy exposure group. This phenomenon was caused by loss of the synaptic ribbon. This type of hearing dysfunction has recently been described as hidden hearing loss caused by cochlear neuropathy, which is associated with tinnitus or hyperacusis.

Photobiomodulation rescues the cochlea from noise-induced hearing loss via upregulating nuclear factor κB expression in rats.

Photobiomodulation (PBM) is a noninvasive treatment that can be neuroprotective, although the underlying mechanisms remain unclear. In the present study, we assessed the mechanism of PBM as a novel treatment for noise-induced hearing loss, focusing on the nuclear factor (NF)-κB signaling pathway. Sprague-Dawley rats were exposed to 1-octave band noise centered at 4kHz for 5h (121dB). After noise exposure, their right ears were irradiated with an 808nm diode laser beam at an output power density of 165mW/cm(2) for 30min a day for 5 consecutive days. Measurement of the auditory brainstem response revealed an accelerated recovery of auditory function in the groups treated with PBM compared with the non-treatment group at 4, 7, and 14 days after noise exposure. Immunofluorescent image analysis for inducible nitric oxide synthase and cleaved caspase-3 showed lesser immunoreactivities in outer hair cells in the PBM group compared with the non-treatment group. However, immunofluorescent image analysis for NF-κB, an upstream protein of inducible nitric oxide synthase, revealed greater activation in the PBM group compared with the naïve and non-treatment groups. Western blot analysis for NF-κB also showed stronger activation in the cochlear tissues in the PBM group compared with the naïve and non-treatment groups (p<0.01, each). These data suggest that PBM activates NF-κB to induce protection against inducible nitric oxide synthase-triggered oxidative stress and caspase-3-mediated apoptosis that occur following noise-induced hearing loss.

The beneficial effect of Hangesha-shin-to (TJ-014) in gentamicin-induced hair cell loss in the rat cochlea.

OBJECTIVE: Ototoxic damage caused by aminoglycosides (AG) leads to the loss of cochlear hair cells (HCs). In mammals, mature cochlear HCs are unable to regenerate, and their loss results in permanent hearing deficits. Our objective was to protect the inner ear from damage after an AG challenge. The generation of reactive oxygen species (ROS), one of the earliest events in the process of AG ototoxicity, is considered to play a key role in the initiation of HC death. We examined whether Hangesha-shin-to (TJ-014), a traditional Japanese Kampo medicine considered to be a potent antioxidant, protects HCs from gentamicin (GM)-induced damage. METHODS: Organ of Corti explants removed from postnatal day 3-5 rats were maintained in tissue culture and exposed to 50µM GM for up to 48h. The effects of TJ-014 on GM-induced ototoxicity were assessed by HC counts and immunohistochemistry against cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and a probe reacting to mitochondrial function changes. RESULTS: TJ-014 treatments significantly reduced GM-induced HC loss and immunoreactivities for cleaved caspase-3 and 8-OHdG; these effects were correlated with increasing TJ-014 concentrations. Moreover, TJ-014 protected the mitochondrial membrane potential from GM ototoxicity. CONCLUSION: These findings indicate the potential of TJ-014 to prevent GM-induced cochlear damage involving ROS.

A case of nasal septal abscess caused by medication related osteonecrosis in breast cancer patient.

Antiresorptive drugs have been widely used to treat patients with hypercalcemia caused by malignancy, bone metastasis, multiple myeloma, and osteoporosis. However, it is well known that antiresorptive drugs can cause osteonecrosis of the jaw (ONJ). Herein, we report a rare case of nasal septal abscess caused by medication related osteonecrosis of the jaw (MRONJ) in a breast cancer patient. A 69-year-old woman was referred to our clinic for evaluation of nasal obstruction. Physical examination revealed a cherry-like swelling of the nasal mucosa emanating from the septum that obstructed both nasal cavities and a fistulous tract showing pus discharge after extraction of the bilateral maxillary central incisors (MCI) and the right maxillary lateral incisor (MLI). Computed tomography and panoramic radiography revealed extensive osteonecrosis of the maxilla and swelling of the nasal mucosa. The clinical diagnosis was nasal septal abscess caused by osteonecrosis of the maxilla. Surgical procedure was undertaken for this case. An indwelling drain was placed in the oral cavity, and sequestrectomy was performed with incision and drainage of the anterior portion of left nasal septum. The patient was doing well at the 7-month follow-up. The patient had a medical history of breast cancer with bone, lung, liver metastases, and had received intravenous bisphosphonate, which is one of the antiresorptive medicines, over the past 4 years. We suspect that this history played an important role in MRONJ induced nasal septal abscess.

ERK2 mediates inner hair cell survival and decreases susceptibility to noise-induced hearing loss.

Extracellular signal-regulated kinase (ERK) is a member of the family of mitogen-activated protein kinases (MAPKs) and coordinately regulates a multitude of cellular processes. In response to a variety of extracellular stimuli, phosphorylation of both threonine and tyrosine residues activates ERK. Recent evidence indicates that ERK is activated in response to cellular stress such as acoustic trauma. However, the specific role of ERK isoforms in auditory function is not fully understood. Here, we show that the isoform ERK2 plays an important role in regulating hair cell (HC) survival and noise-induced hearing loss (NIHL) in mice (C57BL/6J). We found that conditional knockout mice deficient for Erk2 in the inner ear HCs had hearing comparable to control mice and exhibited no HC loss under normal conditions. However, we found that these knockout mice were more vulnerable to noise and had blunted recovery from NIHL compared to control mice. Furthermore, we observed a significantly lower survival rate of inner hair cells in these mice compared to control mice. Our results indicate that ERK2 plays important roles in the survival of HC in NIHL.

Low-level laser therapy for prevention of noise-induced hearing loss in rats.

Noninvasive low-level laser therapy (LLLT) is neuroprotective, but the mechanism of this effect is not fully understood. In this study, the use of LLLT as a novel treatment for noise-induced hearing loss (NIHL) is investigated. Sprague-Dawley rats were exposed to intense noise and their right ears were irradiated with an 808nm diode laser at an output power density of 110 or 165mW/cm(2) for a 30min period for 5 consecutive days. Measurement of the auditory brainstem response revealed an accelerated recovery of auditory function in the groups treated with LLLT compared with the non-treatment group at days 2, 4, 7 and 14 after noise exposure. Morphological observations also revealed a significantly higher outer hair cell survival rate in the LLLT groups. Immunohistochemical analyses for inducible nitric oxide synthase (iNOS) and cleaved caspase-3 were used to examine oxidative stress and apoptosis. Strong immunoreactivities were observed in the inner ear tissues of the non-treatment group, whereas these signals were decreased in the LLLT group at 165mW/cm(2) power density. Our findings suggest that LLLT has cytoprotective effects against NIHL via the inhibition of iNOS expression and apoptosis.

Characteristics of laser-induced shock wave injury to the inner ear of rats.

Recently, the number of blast injuries of the inner ear has increased in the general population. In blast-induced inner ear injury, a shock wave (SW) component in the blast wave is considered to play an important role in sensorineural hearing loss. However, the mechanisms by which an SW affects inner ear tissue remain largely unknown. We aimed to establish a new animal model for SW-induced inner ear injury by using laser-induced SWs (LISWs) on rats. The LISWs were generated by irradiating an elastic laser target with 694-nm nanosecond pulses of a ruby laser. After LISW application to the cochlea through bone conduction, auditory measurements revealed the presence of inner ear dysfunction, the extent of which depended on LISW overpressure. A significantly lower survival rate of hair cells and spiral ganglion neurons, as well as severe oxidative damage, were observed in the inner ear exposed to an LISW. Although considerable differences in the pressure characteristics exist between LISWs and SWs in real blast waves, the functional and morphological changes shown by the present LISW-based model were similar to those observed in real blast-induced injury. Thus, our animal model is expected to be useful for laboratory-based research of blast-induced inner ear injury.

Inhaled hydrogen gas therapy for prevention of noise-induced hearing loss through reducing reactive oxygen species.

Reactive oxygen species (ROS) that form in the inner ear play an important role in noise-induced hearing loss (NIHL). Recent studies have revealed that molecular hydrogen (H2) has great potential for reducing ROS. In this study, we examined the potential of hydrogen gas to protect against NIHL. We tested this hypothesis in guinea pigs with 0.5%, 1.0% and 1.5% H2 inhalation in air for 5h a day after noise exposure, for five consecutive days. All animals underwent measurements for auditory brainstem response after the noise exposure; the results revealed that there was a better improvement in the threshold shift for the 1.0% and 1.5% H2-treated groups than the non-treated group. Furthermore, outer hair cell (OHC) loss was examined 7 days after noise exposure. A significantly higher survival rate of OHCs was observed in the 1.0% and 1.5% H2-treated group as compared to that of the non-treated group in the basal turn. Immunohistochemical analyses for 8-hydroxy-2'-deoxyguanosine (8-OHdG) were performed to examine the amount of oxidative DNA damage. While strong immunoreactivities against 8-OHdG were observed of the non-treated group, the H2-treated group showed decreased immunoreactivity for 8-OHdG. These findings strongly suggest that inhaled hydrogen gas protects against NIHL.

Activated protein C rescues the cochlea from noise-induced hearing loss.

Activated protein C (APC) is a serine/threonine protease and a physiological anticoagulant that exerts anti-inflammatory and anti-apoptotic effects. Although recent studies have revealed that APC has the potential to protect endothelial cells from apoptosis, the mechanisms of its cytoprotective effect are not fully understood. We examined the potential of APC to protect against noise-induced hearing loss (NIHL) and investigated phosphorylation of serine-threonine kinase (Akt) and inhibition of apoptosis as possible cytoprotective mechanisms. We administered intraperitoneal injections of APC (150, 300 U/kg) or normal saline to rats 30 min before exposure to a sound pressure level (SPL) of 126 dB and 4-kHz octave band noise for 5h. The auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were measured before and after exposure. ABR and DPOAE measurements revealed greater improvement in the APC group than in the control group 28 days after exposure. Our examination of outer hair cells (OHCs) at 28 days after noise exposure revealed a significantly higher OHC survival rate in the APC group than in the control group. Immunohistochemical analyses for cleaved-caspase 3, phospho-p38 (p-p38), TUNEL, and phospho-Akt (p-Akt) revealed strong immunoreactivities against cleaved-caspase 3, p-p38, and TUNEL in the inner ear tissues of the control group; however, these signals were decreased in the APC group. Moreover, APC significantly induced activation of p-Akt in the cochlea. These findings suggest that APC has a novel protective effect on the cochlea against NIHL that is mediated by p-Akt and the anti-apoptotic signaling pathway.

Minimally invasive surgery of sialolithiasis using sialendoscopy.

OBJECTIVE: The introduction of minimally invasive surgical procedures using sialendoscopy has significantly reduced the rate of major salivary gland removal due to sialolithiasis. The present study assessed the utility of sialendoscopy and identified potential factors influencing successful sialendoscopic salivary stone retrieval. METHODS: Medical records of sialendoscopic procedures performed at the Department of Otolaryngology of the National Defense Medical College in Japan from November 2007 to January 2014 were retrospectively reviewed. We identified 78 patients diagnosed with sialolithiasis and treated with sialendoscopy (SE). Factors analyzed included stone location, size, symptom duration, surgical methods, and complications. RESULTS: The mean age at presentation was 41 years (range, 11-76 years) with a male-to-female gender ratio of 1:1.89. In total, 73 submandibular and 5 parotid endoscopies were performed. Stone size ranged from 2 to 20mm in diameter. Submandibular stones were removed either by SE alone (9.6%), by transoral stone removal (19.2%), or a combined approach (57.5%). Only 13.7% (10/73) of the cases required submandibular gland removal. Stone size and shape were significant predictors for successful endoscopic stone removal, and stone size and location were significant predictors for submandibular gland removal. CONCLUSION: Sialendoscopy is a reasonable, minimally invasive treatment option for sialolithiasis that avoids salivary gland removal. The present results indicate that sialendoscopy is the first treatment of choice for submandibular gland sialolithiasis. Complete surgical excision is becoming uncommon as a first-line treatment, but it remains indispensable in certain cases.