Characteristic Video Laryngeal Endoscopic "Pharyngeal Rotation" in Unilateral Pharyngeal Constrictor Muscle Paresis: A Case of Herpes Zoster Pharyngitis.

Herpes zoster pharyngitis (HZP) is a rare condition that should be considered as a differential diagnosis of acute dysphagia secondary to unilateral glossopharyngeal and/or vagal nerve palsy. Although early treatment is important to avoid adverse sequelae, serological diagnosis of varicella zoster virus (VZV) takes over a few days. Therefore, it is important to actively suspect VZV infection based on physical findings. Mucocutaneous lesions, curtain signs, and laryngeal palsy are well-known characteristic physical findings. In addition to these findings, the video laryngeal endoscopic finding that the pharyngeal constrictor muscles contract on only one side during swallowing, showing an appearance of "pharyngeal rotation", is one of the characteristic findings of glossopharyngeal/vagal nerve palsy and can support the diagnosis. We report the case of an 82-year-old Asian female who presented with acute dysphagia, sore throat, left ear pain, and fever that persisted for several days. Initial video laryngeal endoscopy revealed a markedly decreased pharyngeal reflex and significant salivary retention without mucosal vesicular lesions. Repeat videoendoscopic evaluation of swallowing revealed characteristic pharyngeal rotation, which was helpful in diagnosing unilateral pharyngeal constrictor muscle paresis, thus suggesting unilateral glossopharyngeal/vagal nerve palsy. An increase in serum antibody titers (IgG and IgM) against VZV was observed. Bilateral differences and rotation of the pharynx during pharyngeal contraction can be detected endoscopically in pharyngeal constrictor muscle paresis caused by glossopharyngeal/vagal nerve palsy and should be evaluated during video laryngeal endoscopy in patients with dysphagia.

Blast-Induced Central Auditory Neurodegeneration Affects Tinnitus Development Regardless of Peripheral Cochlear Damage.

Blast exposure causes serious complications, the most common of which are ear-related symptoms such as hearing loss and tinnitus. The blast shock waves can cause neurodegeneration of the auditory pathway in the brainstem, as well as the cochlea, which is the primary receptor for hearing, leading to blast-induced tinnitus. However, it is still unclear which lesion is more dominant in triggering tinnitus, the peripheral cochlea or the brainstem lesion owing to the complex pathophysiology and the difficulty in objectively measuring tinnitus. Recently, gap detection tests have been developed and are potentially well-suited for determining the presence of tinnitus. In this study, we investigated whether the peripheral cochlea or the central nervous system has a dominant effect on the generation of tinnitus using a blast-exposed mouse model with or without earplugs, which prevent cochlear damage from a blast transmitted via the external auditory canal. The results showed that the earplug (+) group, in which the cochlea was neither physiologically nor histologically damaged, showed a similar extent of tinnitus behavior in a gap prepulse inhibition of acoustic startle reflex test as the earplug (-) group, in which the explosion caused a cochlear synaptic loss in the inner hair cells and demyelination of auditory neurons. In contrast, both excitatory synapses labeled with VGLUT-1 and inhibitory synapses labeled with GAD65 were reduced in the ventral cochlear nucleus, and demyelination in the medial nucleus of the trapezoid body was observed in both groups. These disruptions significantly correlated with the presence of tinnitus behavior regardless of cochlear damage. These results indicate that the lesion in the brainstem could be dominant to the cochlear lesion in the development of tinnitus following blast exposure.

Predictive factors for dissection-free sentinel node micrometastases in early oral squamous cell carcinoma.

This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of < 3.0 mm in one-positive SN group, there were 18 (33%) negative-NSN and no positive-NSN. Regarding prognosis, 3-year overall survival rate of this group (n = 18) and other (n = 37) were 94% and 73% (p = 0.04), and 3-year recurrence free survival rate of this group and other were 94% and 51% (p = 0.03), respectively. Absolutely a further prospective clinical trial would be needed, micrometastases may be defined as solitary SN metastasis with < 3.0 mm of metastatic focus, and approximately 33% of neck dissections could be avoided using these criteria.

The efficacy of thoracoscopic surgery for descending necrotizing mediastinitis.

OBJECTIVES: Thoracotomy is a reliable approach for descending necrotizing mediastinitis (DNM), and the use of video-assisted thoracic surgery (VATS), a minimally invasive procedure, has been increasing. However, which approach is more effective for DNM treatment is controversial. METHODS: We analysed patients who underwent mediastinal drainage via VATS or thoracotomy, using a database with DNM from 2012 to 2016 in Japan, which was constructed by the Japanese Association for Chest Surgery and the Japan Broncho-esophagological Society. The primary outcome was 90-day mortality, and the adjusted risk difference between the VATS and thoracotomy groups using a regression model, which incorporated the propensity score, was estimated. RESULTS: VATS was performed on 83 patients and thoracotomy on 58 patients. Patients with a poor performance status commonly underwent VATS. Meanwhile, patients with infection extending to both the anterior and posterior lower mediastinum frequently underwent thoracotomy. Although the postoperative 90-day mortality was different between the VATS and thoracotomy groups (4.8% vs 8.6%), the adjusted risk difference was almost the same, -0.0077 with 95% confidence interval of -0.0959 to 0.0805 (P = 0.8649). Moreover, we could not find any clinical and statistical differences between the 2 groups in terms of postoperative 30-day and 1-year mortality. Although patients who underwent VATS had higher postoperative complication (53.0% vs 24.1%) and reoperation (37.9% vs 15.5%) rates than those who underwent thoracotomy, the complications were not serious and most could be treated with reoperation and intensive care. CONCLUSIONS: The outcome of DNM treatment does not depend on thoracotomy or VATS.

Primary tracheobronchial necrosis after esophagectomy: A nationwide multicenter retrospective study in Japan.

Background: The clinical features of postoperative primary tracheobronchial necrosis (P-TBN; the necrosis without anastomotic leakage or other cervical and mediastinal abscess) remains unclear. This nationwide multicenter retrospective study first investigated the clinical features of P-TBN after esophagectomy for upper aerodigestive tract cancer with a large cohort. Methods: As a study of the Japan Broncho-Esophagological Society, a nationwide questionnaire survey was conducted in 67 institutions. The clinical data of 6370 patients who underwent esophagectomy for laryngeal, pharyngeal, and esophageal cancer between 2010 and 2019 were collected. Grades of P-TBN were defined as follows: Grade 1, mucosal necrosis; Grade 2, transmural bronchial wall necrosis without fistula or perforation; Grade 3, transmural bronchial wall necrosis with fistula or perforation. Results: P-TBN was observed in 48 (0.75%) of 6370 patients. The incidences of P-TBN for pharyngo-laryngo-cervical esophagectomy (PLCE; n = 1650), total pharyngo-laryngo-esophagectomy (TPLE; n = 205), and subtotal esophagectomy (SE; n = 4515) were 2.0%, 5.4%, and 0.1%, respectively. The upper mediastinal LN dissection (P = 0.016) and the higher level of the tracheal resection (P = 0.039) were significantly associated with a higher grade of necrosis in PLCE and TPLE. Overall survival rates were significantly lower in patients with Grade 2 (P = 0.009) and Grade 3 (P = 0.004) than in those with Grade 1. Conclusion: The incidence of TBN restricted to P-TBN was lower than previously reported. Maintaining the tracheal blood flow is essential to prevent worsening P-TBN, especially in PLCE and TPLE. Our new P-TBN severity grade may predict the outcome of patients with P-TBN.

Effects of Unilateral Vagotomy on LPS-Induced Aspiration Pneumonia in Mice.

Respiratory-related dysphagia and aspiration pneumonia can be attributed to multiple causes. However, reproduction of multiple factor-related respiratory distress and aspiration pneumonia in a single animal model is challenging. To validate animals with vagal nerve palsy as novel models for severe aspiration pneumonia associated with respiratory distress, we investigated the effects of unilateral vagotomy on the swallowing function and severity of pneumonia after forced aspiration in mice. Unilateral vagotomy was performed in C57BL6 male mice that subsequently underwent evaluation of swallowing function by videofluoroscopic swallow study (VFSS) and histological assessments for aspiration pneumonia induced by lipopolysaccharide (LPS). VFSS examinations demonstrated that unilateral vagotomy did not cause apparent aspiration in mice, but it resulted in a significant loss of body weight (BW) due to decreased oral intake. In addition, when aspiration pneumonia was induced by forced administration of LPS, significantly prolonged BW loss and severe infiltration of inflammatory cells associated with aspiration pneumonia were observed in the mice that underwent unilateral vagotomy. In conclusion, the vagotomized mice showed appropriate characteristics as a model of aspiration pneumonia caused by multiple factors, including the paralysis of vocal fold movement and respiratory distress. This model can help elucidate the pathogenesis of aspiration pneumonia and the treatment methods for the respiration-compromised model.

The value of serum p53 antibody as a biomarker in oral and pharyngeal squamous cell carcinoma.

BACKGROUND: The development of more sensitive biomarkers for the detection of early-stage head and neck squamous cell carcinoma is needed. AIMS/OBJECTIVES: This study was performed to assess the value of serum p53 antibody (s-p53-Ab) as a biomarker for oral and pharyngeal carcinoma. MATERIAL AND METHODS: Pre-treatment serum was collected for 71 patients with oral and pharyngeal carcinoma and 117 healthy volunteers as controls and analyzed s-p53-Ab using enzyme-linked immunosorbent assay (ELISA). RESULTS: Using 1.3 U/mL as the cut-off value, 14 of 71 patients (sensitivity 19.7%), and 12 of 117 control cases were positive for s-p53-Ab (specificity 89.7%). Excluding 12 cases of p16-positive oropharyngeal and nasopharyngeal cancer which were all negative for s-p53-Ab, the sensitivity in early-stage 1-2 cases was 30.0%, which was higher than conventional tumor markers. CONCLUSIONS AND SIGNIFICANCE: The s-p53-Ab was not detected in any cases of virus-related cancer in which p53 gene mutations were not involved in carcinogenesis. Since the s-p53-Ab sensitivity was high even in early-stage disease, s-p53-Ab measurement may be useful as an early diagnostic biomarker in patients with oral, p16- oropharyngeal, and hypopharyngeal cancer.

Evaluation of chronological changes in videofluorographic findings after transoral videolaryngoscopic surgery to reveal mechanism of dysphagia.

OBJECTIVES: Transoral surgery preserves good swallowing function in most cases, however, postoperative dysphagia sometimes leads to fatal complication such as aspiration pneumonia. We investigated the chronological changes in swallowing function have not been revealed relationship with dysphagia. The primary aim of this study was to reveal the mechanism of dysphagia following transoral surgery by analyzing chronological videofluorography (VF) findings. Moreover, the secondary aim of this study was to evaluate the relationship between mechanism of dysphagia and risk factors of patients to clarify the risk for dysphagia lead to prevention of postoperative complications. METHODS: 22 patients who underwent transoral videolaryngoscopic surgery (TOVS) for either supraglottic or hypopharyngeal cancer were evaluated swallowing function. We performed VF during the preoperative, postoperative acute, and stable phases and investigated the chronological changes in the VF findings. The following parameters were evaluated by VF: horizontal distance of laryngeal movement, vertical distance of laryngeal elevation, laryngeal elevation delay time (LEDT), Bolus Residue Scale (BRS) scores, and Penetration Aspiration Scale (PAS) scores. Additionally, we evaluated risk factors for postoperative aspiration by investigating relationships between preoperative VF parameters, age of patients, history of radiation therapy, resection area, tumor (T) stage, postoperative Numeric Rating Scale (NRS), and PAS and BRS scores. RESULTS: The median time at which oral feeding was resumed in this study was 9 (2-200) days. The patients who had postoperative acute PAS scores of 4 and above exhibited delays in resuming oral ingestion after surgery. TOVS did not impair laryngeal elevation and LEDT; however, the BRS and PAS scores temporarily worsened in the acute phase compared to the preoperative scores. These scores almost recovered to their preoperative states in the stable phase, and both the BRS and PAS scores worsened and recovered concurrently. Patients who exhibited poor vertical distance in laryngeal elevation as observed via preoperative VF or who had histories of radiation therapy had worse PAS scores in postoperative acute phase VF. Patients with broad resection areas had worse BRS scores in postoperative acute phase VF. CONCLUSION: TOVS didn't impair the function of laryngeal elevation and elicitation of the swallowing reflex whereas pharyngeal bolus clearance, laryngeal penetration, and aspiration temporarily deteriorated concurrently but eventually almost recovered to their baseline values. Patients with histories of radiotherapy, poor laryngeal elevation, and broad resection areas are at the risk of postoperative dysphagia after TOVS. Patients with these risk factors need appropriate evaluation before resuming postoperative oral intake.

Factors affecting the incidence of chorda tympani nerve transection in middle ear surgery.

Objective: To reveal the factors affecting the incidence of chorda tympani nerve (CTN) transection during middle ear surgery. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: We analyzed 232 ears (117 ears with cholesteatoma, 101 ears with chronic otitis media, and 14 ears with otosclerosis) that underwent tympanoplasty or stapes surgery during 2017-2020. Intervention: Eighty-four ears underwent transcanal endoscopic ear surgery (TEES), 103 ears underwent microscopic ear surgery (MES), and 45 ears underwent surgery using both endoscopy and microscopy (Dual). Main Outcome Measure: To confirm CTN transection, intraoperative endoscopic/microscopic video images were evaluated. We used the same video images to determine the anatomical variation of the CTN course in the middle ear. Results: In 18 ears (7.8%: 6/84 TEES ears [7.1%], 6/103 MES ears [5.8%], and 6/45 Dual ears [13.3%]), the CTN was cut during middle ear surgery. There was no significant difference in CTN transection among groups. In cholesteatoma patients, stapes involvement resulted in a significantly higher CTN transection incidence. CTN anatomical variants such as the "Attached Short type" and "Ultrashort type" showed a significantly higher CTN transection incidence. Conclusion: Although endoscopic surgery did not reduce the incidence of CTN transection during middle ear surgery, pathological involvement of the stapes and CTN anatomical variants, such as the "Attached Short type" and "Ultrashort type," may increase this incidence. Preoperative evaluation of stapes involvement and anatomical location of the CTN course could help identify patients at greater risk for iatrogenic CTN transection. Level of Evidence: 4.

A Case of Pancreatic Metastasis From Small Cell Neuroendocrine Carcinoma of the Oropharynx.

Small cell neuroendocrine carcinoma (SNEC) rarely occurs in the head and neck and usually occurs in the lungs. We report the case of a 55-year-old Asian male with SNEC in the oropharynx and jaundice due to pancreatic metastasis, which was successfully palliated by amrubicin (AMR), radiotherapy, and an endoscopic biliary stent. Although pancreatic metastases are known to occur at the end stage of small cell lung cancer, there are limited data on the treatment protocols for pancreatic metastases from SNEC. The main complication of SNEC for pancreatic lesions is obstructive jaundice. Palliative radiotherapy and biliary drainage may have life-prolonging effects in patients with extrahepatic biliary obstruction. It may also be a worthwhile risk to use anticancer drugs, such as AMR that are metabolized in the liver, if the obstructive jaundice is caused by tumor growth.

Real-world treatment patterns and outcomes in Japanese patients with cervical esophageal cancer.

BACKGROUND: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method. PATIENTS AND METHODS: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities. RESULTS: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%. CONCLUSION: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.

Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.

Correlation of Blast-Induced Tympanic Membrane Perforation with Peripheral Cochlear Synaptopathy.

The auditory organs, including the tympanic membrane, cochlea, and central auditory pathway, are the most fragile components of the human body when exposed to blast overpressure. Tympanic membrane perforation (TMP) is the most frequent symptom in blast-exposed patients. The impact of TMP on the inner ear and central auditory system, however, is not fully understood. We aimed to analyze the effect of blast-induced TMP on the auditory pathophysiological changes in mice after blast exposure. Mice aged seven weeks were exposed to blast overpressure to induce TMP and allowed to survive for two months. All TMP cases had spontaneously healed by week three after the blast exposure. Compared with controls, blast-exposed mice exhibited a significant elevation in hearing thresholds and an apparent disruption of stereocilia in the outer hair cells, regardless of the occurrence or absence of TMP. The reduction in synapses in the inner hair cells, which is known as the most frequent pathology in blast-exposed cochleae, was significantly more severe in mice without TMP. A decrease in the number of excitatory central synapses labeled by VGLUT-1 in the cochlear nucleus was observed, however, regardless of the absence or presence of TMP. Our findings suggest that blast-induced TMP mitigates peripheral cochlear synaptic disruption but leaves the central auditory synapses unaffected, indicating that central synaptic disruption is independent of TMP and peripheral cochlear synaptic disruption. Synaptic deterioration in the peripheral and central auditory systems can contribute to the promotion of blast-induced hearing impairment, including abnormal auditory perception.

A Nationwide Survey on Digestive Reconstruction Following Pharyngolaryngectomy With Total Esophagectomy: A Multicenter Retrospective Study in Japan.

AIM: Digestive reconstruction after pharyngolaryngectomy with total esophagectomy (PLTE) remains challenging, with the optimal method remaining unclear. The current study aimed to clarify the short-term outcomes after PLTE and determine the optimal digestive reconstruction method. METHODS: Based on a nationwide survey of 151 patients who underwent PLTE, outcomes of digestive reconstruction methods are described. RESULTS: Among digestive reconstruction methods, a simple gastric tube was most frequently used (37.1%), followed by gastric tube combined with free graft transfer (FGT) (35.1%), gastric tube with microvascular anastomosis (22.5%), and other procedures (5.3%). Intraoperative evaluation of microcirculation (IOEM) was utilized in 29 patients (19.2%). Among the included patients, 66.9% developed any-grade complications, 41.0% developed severe complications, and 23.8% developed digestive reconstruction-related complications (DRRCs; leakage or necrosis). Reoperation within 30 days for any complications and DRRCs was required in 13.9% and 8.6% of the patients, respectively. Mortality within 90 days was observed in 4.6%. Among the three major methods, gastric tube combined with FGT promoted the least DRRCs in the gastric tube (P = .005), although the overall incidence of DRRCs was comparable. The use of IOEM was significantly associated with a reduction of severe DRRCs (P = .005). CONCLUSIONS: Pharyngolaryngectomy with total esophagectomy is a high-risk surgery significantly associated with the occurrence of postoperative morbidity and mortality. Nonetheless, the addition of FGT can help prevent gastric tip complications, while IOEM can be an effective method for improving outcomes.

Distribution pattern and pathologic analysis of metastatic sentinel and non-sentinel lymph nodes in lymphatic basin dissection for clinical T2/T3 oral cancer with clinical N0 status.

OBJECTIVE: The localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC). METHODS: This prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin. All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0. RESULTS: SN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis. After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC. CONCLUSION: SLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III).

Inhibition of extracellular signal-regulated kinase pathway suppresses tracheal stenosis in a novel mouse model.

Tracheal stenosis is a refractory and recurrent disease induced by excessive cell proliferation within the restricted tracheal space. We investigated the role of extracellular signal-regulated kinase (ERK), which mediates a broad range of intracellular signal transduction processes in tracheal stenosis and the therapeutic effect of the MEK inhibitor which is the upstream kinase of ERK. We histologically analyzed cauterized tracheas to evaluate stenosis using a tracheal stenosis mouse model. Using Western blot, we analyzed the phosphorylation rate of ERK1/2 after cauterization with or without MEK inhibitor. MEK inhibitor was intraperitoneally injected 30 min prior to cauterization (single treatment) or 30 min prior to and 24, 48, 72, and 96 hours after cauterization (daily treatment). We compared the stenosis of non-inhibitor treatment, single treatment, and daily treatment group. We successfully established a novel mouse model of tracheal stenosis. The cauterized trachea increased the rate of stenosis compared with the normal control trachea. The phosphorylation rate of ERK1 and ERK2 was significantly increased at 5 min after the cauterization compared with the normal controls. After 5 min, the rates decreased over time. The daily treatment group had suppressed stenosis compared with the non-inhibitor treatment group. p-ERK1/2 activation after cauterization could play an important role in the tracheal wound healing process. Consecutive inhibition of ERK phosphorylation is a potentially useful therapeutic strategy for tracheal stenosis.

Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice.

Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.