Determining Invasion Depth in Superficial Pharyngeal Carcinoma by Transoral Ultrasonography.

OBJECTIVES: To examine the clinical usefulness of transoral ultrasonography (US) in determining the invasion depth of superficial pharyngeal carcinoma (SPC). Determining the invasion depth of SPC is crucial for transoral surgery including determining treatment strategy. This study aimed to examine the usefulness of transoral US in determining the invasion depth of SPC. METHODS: Forty-six patients with 51 lesions who underwent both magnifying endoscopy with narrow-band imaging (ME-NBI) and transoral US were included. The primary outcomes were the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of ME-NBI and transoral US findings for pathological tumor depth in SPCs. RESULTS: The accuracy (82.4%), sensitivity (85.2%), PPV (82.1%), and NPV (82.6%) rates of US for subepithelial propria (SEP) were higher than those of ME-NBI and macroscopic classification, indicating that transoral US is superior to ME-NBI in determining the invasion depth. All cases where the SEP was clearly invaded (SEP deep) could be diagnosed as SEP by transoral US. CONCLUSIONS: Transoral US may be useful in determining the invasion depth of SPCs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2192-2197, 2023.

A 14-year nationwide epidemiological analysis of delayed endolymphatic hydrops in Japan.

BACKGROUND: Delayed endolymphatic hydrops (DEH) is an inner ear disease that causes recurrent vertigo in the ipsilateral ear or fluctuating hearing in the contralateral ear due to endolymphatic hydrops secondary to preceding deafness. There are few reports of large, multicentre studies investigating the clinical-epidemiological characteristics of DEH. OBJECTIVE: This study aimed to clarify the characteristics of DEH in Japan. METHODS: Clinical data on 662 patients with DEH were analysed by nationwide, multicentre surveys conducted by the Peripheral Vestibular Disorders Research Group of Japan. RESULTS: The proportion of ipsilateral DEH (IDEH) was slightly higher than that of contralateral DEH (CDEH) at 55.4%. The time delay between onset of precedent deafness and onset of DEH was significantly longer for CDEH than for IDEH. The most common cause of precedent deafness was a disease of unknown cause with onset in early childhood (33.1%). Epidemiological characteristics were not significantly different between CDEH with and without vertigo. CONCLUSION: DEH appearing to be caused by viral labyrinthitis has a high rate of onset within 40 years of precedent deafness. Clinical and epidemiological characteristics of IDEH, CDEH with vertigo, and CDEH without vertigo were very similar. SIGNIFICANCE: The clinical-epidemiological characteristics of DEH in Japan were clarified.

Swallowing function after transoral surgery for laryngopharyngeal cancer.

Transoral surgery (TOS) has been widely used to treat laryngopharyngeal cancers. Although TOS is a minimally invasive procedure, postoperative complications, such as postoperative dysphagia, may occur, which can lead to a poor quality of life for patients undergoing TOS. This study aimed to investigate factors that may affect swallowing function in patients who underwent TOS for laryngopharyngeal cancers. Swallowing function of 84 patients who underwent endoscopic resection for oropharyngeal, hypopharyngeal, and supraglottic lesions was evaluated by the Functional Outcome Swallowing Scale, and predictors for postoperative dysphagia were identified. Multivariate analysis identified the following factors as independent predictors for postoperative dysphagia: Eastern Cooperative Oncology Group Performance Status (ECOG PS, p = 0.008), prior neck radiation therapy (p = 0.008), and operative time (p = 0.021). This study suggests that patients with poor ECOG PS or those who received prior neck radiation therapy should be fully assessed for preoperative swallowing function. In the future, we would like to clarify the criteria for preoperative swallowing evaluation to create a system that can identify patients suitable for TOS.

Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with clinical outcome in recurrent or metastatic head and neck cancer patients treated with nivolumab.

Background: Nivolumab has been approved for recurrent or metastatic head and neck cancer (R/M HNC) on March 2017 in Japan. Recently, many researchers have been actively studying the prognostic and predictive markers. However, they have not been clarified. In this study, we evaluate the prognostic and predictive markers of the anticancer effect of nivolumab.Objective: This study assessed baseline neutrophil-to-lymphocyte ratio (NLR) as a prognostic and predictive marker for nivolumab efficacy in patients with recurrent/metastatic head and neck cancer (R/M HNC).Material and methods: This retrospective cohort study used medical records of patients with R/M HNC treated with nivolumab from May 2017 to January 2018 at a university hospital in Japan.Results: Twenty-nine patients (median age, 64 years) were included. In univariate analyses, baseline NLR ≥5 was significantly associated with overall survival (HR 4.88; p = .045) and progressive disease (HR 5.0; p = .046). More patients with baseline NLR ≥5 changed from nivolumab to best supportive care, compared to patients with baseline NLR <5 (64.3% vs 26.7%, respectively).Conclusions and significance: Baseline NLR was associated with clinical benefit from nivolumab in patients with R/M HNC. We propose that baseline NLR be used as a predictive or prognostic marker for nivolumab efficacy in these patients.

Localization of melatonin and its receptors (melatonin 1a and 1b receptors) in the mouse inner ear.

Background: In the inner ear, evidence has been gathered indicating that melatonin plays important roles in inner ear physiology and pathophysiology. However, no attempt has been made previously to investigate the localization or expression of melatonin and its receptors in the whole inner ear. Aims/objectives: To analyze the presence of melatonin and its receptors in the normal mouse inner ear. Material and methods: C57BL6/J mice were used in this study. The localizations of melatonin, MT1a and MT1b in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion and endolymphatic sac (ES), were studied by immunohistochemistry. Results: The organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory cells, vestibular dark and transitional cells, and ES epithelial cells showed an immunofluorescence reaction to melatonin, MT1a and MT1b. Conclusion and significance: The present findings show that melatonin and its receptors (MT1a and MT1b) are present in the inner ear, thus supporting the hypothesis that melatonin plays a physiological role in the inner ear.

Low-dose dexamethasone with fosaprepitant and palonosetron to prevent cisplatin-induced nausea and vomiting in head and neck cancer patients.

OBJECTIVE: To determine if a lower dose of dexamethasone can be used in combination with fosaprepitant and palonosetron for cisplatin-induced nausea and vomiting in head and neck cancer patients, we conducted a single-center, two-arm, cross-over comparison study. METHODS: Patients were randomly assigned to either standard dose dexamethasone group: intravenous 9.9 mg on day 1 and 6.6 mg on days 2-4 or low-dose dexamethasone group: intravenous 3.3 mg on days 1-4 for the first course and crossed over to the other treatment for the second course. The primary endpoint was complete response (CR) in the overall period. RESULTS: Twenty-five patients were screened for the study and 22 were evaluable. Eleven patients were randomly assigned to the standard dose dexamethasone group and 12 patients to the low-dose dexamethasone group. The CR rate in the overall period was 86% in the standard dose group and 73% in the low-dose group, showing no significant difference (p = .61). CONCLUSION: The efficacy of low-dose dexamethasone with fosaprepitant and palonosetron was not inferior to that of the standard dose dexamethasone in the highly emetogenic cisplatin-based treatment for head and neck cancer patients.

Gastric-type H+,K+-ATPase in mouse vestibular end organs.

CONCLUSION: Gastric type H+,K+-ATPase in the vestibular end organs may be of importance for K+ circulation and may also be related to pH regulation in vestibular end organs and endolymphatic sac. OBJECTIVE: To analyze the expression of gastric-type H+,K+-ATPase in normal mouse vestibular end organs. METHODS: 8 weeks old CBA/J mice were used in this study. The presence of gastric-type H+,K+-ATPase α and ß in the vestibular end organs, viz. utricle, saccule, ampulla, vestibular ganglion, and endolymphatic sac, was investigated using immunohistochemistry. RESULTS: In the vestibular end organs, H+,K+-ATPase α and ß were almost identical. H+,K+-ATPase was expressed in sensory cells, the basolateral surface of dark cells, fibrocytes, in vestibular ganglion cells, and in the upper region of the endolymphatic sac epithelial cells.

Localization of histamine (H1, H2, H3 and H4) receptors in mouse inner ear.

Conclusion The present findings show that all four types of histamine receptors (H1R, H2R, H3R, and H4R) are present in the inner ear, thus supporting the hypothesis that histamine plays a physiological role in the inner ear. Objective To analyse the presence of histamine receptors in the normal mouse inner ear. Methods CBA/J mice were used in this study. The localization of H1R, H2R, H3R, and H4R in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion, and endolymphatic sac, was studied by real-time PCR and immunohistochemistry. Results The mRNA for each receptor sub-type was detected in the inner ear. In the immunohistochemical study, the organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory epithelium, and endolymphatic sac cells showed an immunofluorescent reaction to all histamine receptors.

Localization of sirtuins (SIRT1-7) in the aged mouse inner ear.

CONCLUSION: The expression of sirtuin in vestibular end organs and cochlea responds differently to age-related changes. Down-regulation of SIRT1, 3, and 5 in the cochlea may weaken the protective activity regarding degeneration of the organ of Corti as well as of spiral ganglion cells, resulting in the development of age-related hearing loss. An increase in SIRT 1, 4, or 5 in vestibular tissue could indicate an increased need of detoxification of reactive oxygen species and an increased anti-ageing potential. OBJECTIVE: To analyse the expression of sirtuins (SIRT1-7) in the normal young and old mouse inner ears. METHODS: Young (8 weeks) and old (22 months) CBA/J mice were used in this study. Localization of SIRT1-7 in the inner ear, i.e. cochlea, vestibular end organs, and vestibular ganglion, was investigated using real-time PCR and immunohistochemistry. RESULTS: In the vestibular end organs, the expression of SIRT1, 2, 4, 5 (both mRNA and protein), SIRT6, and 7 (only mRNA) was found to be increased, while a slightly decreased immunoreactivity was observed in SIRT3. In the cochlea, the expression of SIRT1, 3, and 5 (both mRNA and protein) was decreased in the old mice, whereas no noticeable difference was observed regarding SIRT2, 4, 6, or 7.

Long-term administration of vasopressin can cause Ménière's disease in mice.

CONCLUSION: A new murine model of Ménière's disease has been developed, based on long-term administration of vasopressin. Induction of vestibular dysfunction in the present animal model can cause additional stress, by reducing inner ear blood flow. Latanoprost, a selective agonist for the FP prostanoid receptor, may become a new remedy for Ménière's disease. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, with a closer resemblance to the pathophysiological process in Ménière's disease. METHODS: Adult CBA/J or ICR mice were treated by subcutaneous injection of vasopressin for 5 days up to 8 weeks. Morphological analyses were performed of the cochlea, vestibular end organs and endolymphatic sac. The effect of latanoprost on the development of endolymphatic hydrops was also examined. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops, increasing in severity as the vasopressin treatment was prolonged. Animals treated with vasopressin for 8 weeks showed severe endolymphatic hydrops with partial loss of outer hair cells and spiral ganglion cells. These animals also had a reversible vestibular dysfunction following intratympanic injection of epinephrine. Latanoprost inhibited the development of endolymphatic hydrops caused by vasopressin.

Localization of sirtuins in the mouse inner ear.

CONCLUSION: It is suggested that SIRT1 and 3, and probably SIRT4 and 5, play an important role in the neuroprotection of the inner ear. SIRT2 may be related to neuroprotection and myelin sheath formation, while SIRT6 seems to have a significant role in maintaining the energy balance by metabolic regulation. OBJECTIVE: To analyze the expression of sirtuins (SIRT1-7) in the normal mouse inner ear. METHODS: CBA/J mice were used for this study. The localization of SIRT1-7 in the inner ear, i.e. cochlea, vestibular end organs, and endolymphatic sac, was investigated using real-time PCR and immunohistochemistry. RESULTS: We found high levels of mRNA of all seven sirtuins in the inner ear. In the immunohistochemical study, SIRT1-7 were abundant in many inner ear structures, i.e. stria vascularis, inner and outer hair cells, spiral ganglion cells, vestibular sensory and ganglion cells, vestibular dark and transitional cells, and the endolymphatic sac.

Localization of aquaporins in the mouse vestibular end organs.

CONCLUSION: We found that aquaporins (AQPs) in the fluid transporting cells, such as vestibular dark cells and endolymphatic sac epithelial cells, seem to be of importance in fluid transport in the inner ear, while those in the sensory and ganglion cells may play a functional role in sensory cell transduction. OBJECTIVE: Expression of AQPs (0-12) was analyzed in normal mouse vestibular end organs. METHODS: CBA/J mice were used in this study. Localization of AQPs 0-12 in the vestibular end organs and endolymphatic sac was investigated by immunohistochemistry. RESULTS: The AQPs were found abundantly distributed in many structures in the vestibular end organs, i.e. vestibular sensory and supporting cells, vestibular dark cells, vestibular ganglion cells, and the endolymphatic sac.

Expression of prostanoid receptors (EP1, 2, 3, and 4) in normal and methimazole-treated mouse olfactory epithelium.

CONCLUSION: Prostanoid receptors (EP1, EP2, EP3, and EP4) are expressed in the olfactory epithelium (OE), and the EP4 prostanoid receptor may play an important role in the OE. OBJECTIVE: The purpose of the present study was to investigate the expression and localization of the four types of prostanoid receptors (EP1, EP2, EP3, and EP4) in the OE of normal and methimazole-treated mice to gain more complete knowledge about the functional significance of the prostanoid receptors in OE. METHODS: CBA/J mice were used in this study. The localization of the prostanoid receptors (EP1, EP2, EP3, and EP4) in the OE was investigated by immunohistochemistry. The changes in expression of prostanoid receptors were studied in methimazole-treated mice. Furthermore, the effect of EP agonists on the methimazole-induced degeneration of OE was assessed by morphological analysis and by assessment of apoptosis. RESULTS: All four types of EP receptors were recognized in mouse OE. Expression of EP4 in the OE was significantly reduced after methimazole treatment. In the methimazole-treated mice, an EP4 agonist reduced OE damage and apoptosis.

Expression of Trefoil factor family peptides in the nasal allergic mucosa.

OBJECTIVE: Trefoil factor family peptides (TFFs) are the secretory products of mucous cells and are closely associated with mucins. TFFs appear to be important in mucosal healing processes. Although TFF1/3 are expressed in the human respiratory tract, their role in the nasal mucosa is not thoroughly understood. We investigated the association between TFFs and mucins and the role TFFs in the human nasal mucosa. MATERIAL AND METHODS: Patients undergoing turbinectomy were included and it was determined whether patients had nasal allergies or not. The localization of TFF1/3, MUC5AC/5B expression was investigated using immunohistochemistry. The levels of the mRNA transcripts were examined using quantitative real-time PCR. RESULTS: TFF1/3 had a similar pattern of localization in epithelial goblet cells and submucosal glandular cells. TFF1/3 co-localized with MUC5AC in the epithelium, and co-localized with MUC5B in the epithelium and the submucosal glandular cells. The levels of TFF1/3 and MUC5B mRNA in allergic patients were significantly increased. CONCLUSION: Our results suggest that TFF1/3 may associate with MUC5AC and MUC5B in the nasal mucosa, and that up-regulation of TFF1/3 and MUC5B may play an important role in the clinical condition of the nasal allergic mucosa.

Localization of aquaporins 1, 2, and 3 and vasopressin type 2 receptor in the mouse inner ear.

CONCLUSION: It is suggested that aquaporins (AQPs) 1, 2, and 3, and vasopressin type 2 receptors (V2Rs) in the fluid transporting cells, such as stria vascularis, vestibular dark and transitional cells, and endolymphatic sac epithelial cells, have an important role in fluid transport in the inner ear, while those in the sensory and ganglion cells may play a functional role in the sensory cell transduction system. OBJECTIVE: To analyze expression of AQP1, AQP2, and AQP3 as well as V2Rs in the normal mouse inner ear. METHODS: CBA/J mice were used in this study. Localization of AQP1, AQP2, AQP3, and V2Rs in the inner ear, i.e. cochlea, vestibular end organs, and endolymphatic sac, was investigated by immunohistochemistry. RESULTS: The results show that AQP1, AQP2, AQP3, and V2Rs are abundantly distributed in many inner ear structures, i.e. stria vascularis, inner and outer hair cells, spiral ganglion cells, vestibular sensory and ganglion cells, vestibular dark and transitional cells, and the endolymphatic sac.

Localization of prostanoid receptors in the mouse inner ear.

CONCLUSION: EP4, EP2, and IP prostanoid receptors exert an otoprotective function and FP may be important for fluid homeostasis in the inner ear. OBJECTIVE: To investigate the expression of prostanoid receptors in the normal mouse inner ear. METHODS: CBA/J mice were used in this study. The localization of prostanoid receptors, i.e. DP, EP1, EP2, EP3, EP4, FP, IP, and TP, in the inner ear, i.e. the cochlea, vestibular end organs, endolymphatic sac, was studied by immunohistochemical techniques. RESULTS: The EP4, IP, and FP prostanoid receptors were found to be abundantly distributed in many inner ear structures, i.e. stria vascularis, inner and outer hair cells, spiral ganglion cells, vestibular sensory and ganglion cells, and the endolymphatic sac. EP2 and EP3 are also localized in the inner ear whereas DP, EP1, and TP are only weakly expressed.

Expression of transient receptor potential channel vanilloid (TRPV) 1–4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazole-treated mouse olfactory epithelium.

CONCLUSION: It is suggested that TRPV1, 2, 3, and 4, TRPM5 and 8, and TRPA1 may play several roles in the olfactory epithelium (OE), contributing to olfactory chemosensation, olfactory adaptation, olfactory­trigeminal interaction, and OE fluid homeostasis. In patients with olfactory disturbance, TRPV1 and TRPM8 may be closely related to a high rate of recognition of curry and menthol odors, while TRPV2 may also play a crucial role in the regeneration of olfactory receptor neurons. OBJECTIVE: Expression of TRPV1­4, TRPM5 and 8, and TRPA1 in the normal and methimazole-treated mouse OE was analyzed. METHODS: The localization of TRPV1­4, TRPM5 and 8, and TRPA1 in the OE of normal and methimazole-treated CBA/J mice was investigated by immunohistochemistry. RESULTS: Normal OE showed a positive immunofluorescent reaction to TRPV1­4, TRPM5 and 8, and TRPA1. In lamina propria, the nerve fibers displayed TRPV 1, 2, and 3, TRPM8 and TRPA1. In the pathological condition, the expression of TRPV3, TRPV4, TRPM5, and TRPA1 was markedly reduced and took a long time to recover. In contrast, expression of TRPM8 was scarcely affected, even in the pathological condition, while TRPV1 and TRPV2 showed early recovery following methimazole treatment.

Effect of intravitreal bevacizumab on iris vessels in neovascular glaucoma patients.

BACKGROUND: We aimed to investigate the effects of a single 1-mg injection of intravitreal bevacizumab on iris vessels in neovascular glaucoma (NVG) patients. METHODS: Twenty-two surgically resected irises from glaucoma patients were obtained during trabeculectomy. Eight were from patients with NVG who received a 1-mg injection of intravitreal bevacizumab (IVB) before glaucoma surgery, eight were from patients with primary open-angle glaucoma (POAG), and six were from patients with NVG who were not administered IVB. The collected iris specimens were compared after immunohistochemical staining with anti-CD34 monoclonal antibodies and anti-VEGF monoclonal antibody, and the percentage of CD34-positive and VEGF-positive regions in the total area of the specimens from the three groups was compared. RESULTS: The difference in the CD34-positive area between all groups was statistically significant (p = 0.0061, Kruskal-Wallis test). There was no significant difference in the CD34-positive area between the NVG with IVB group and the POAG group (p = 0.3017, Mann-Whitney U test with Bonferroni correction). The POAG group had significantly fewer CD34-positive regions than the NVG without IVB group (p = 0.0019, Mann-Whitney U test with Bonferroni correction). Many vessels remained in the iris stroma, and there was no significant difference in the CD34-positive area between the NVG with IVB and NVG without IVB groups (p = 0.0357, Mann-Whitney U test with Bonferroni correction). The ratio of the length of CD34 expression on the iris surface in the NVG without IVB group was significantly longer than that in the NVG with IVB group (p = 0.0002, Mann-Whitney U test). The difference in VEGF expression between all groups was statistically significant (p = 0.04, Kruskal-Wallis test). There was no significant difference between the NVG with IVB group and the NVG without IVB group (p = 0.7963 Mann-Whitney U test with Bonferroni correction). The frequency of hyphema and fibrin formation in the anterior chamber 1 day after surgery between the two NVG groups was not statistically significant. CONCLUSION: A single intravitreal dose of IVB at 1 mg/0.04 ml to eyes with rubeotic glaucoma reduced the neovascularization in the human iris surface, but could not eliminate completely neovascularization in iris stroma. This finding implies that the prevention of hyphema and fibrin formation based on the slit-lamp examination can not be predicted, even if neovascularization in iris surface seems to be eliminated by a single dose of IVB.

Clinical characteristics of delayed endolymphatic hydrops in Japan: A nationwide survey by the Peripheral Vestibular Disorder Research Committee of Japan.

CONCLUSION: Similarly to almost all delayed endolymphatic hydrops (DEH) cases with both precedent sudden deafness and mumps deafness, two-thirds of DEH cases with precedent deafness of unknown cause with onset in early childhood developed DEH symptoms within 40 years after the precedent deafness. In spite of the diagnosis of precedent deafness, viral labyrinthitis may build up the late endolymphatic hydrops in most DEH cases up to four decades. OBJECTIVE: To clarify the characteristics of DEH in Japan. METHODS: Clinical information on 198 DEH cases was collected by nationwide, multicenter surveys conducted by the Peripheral Vestibular Disorders Research Committee of Japan. RESULTS: The incidence of the ipsilateral type of DEH was 47.5%, which was almost equal to that of the contralateral type. In both types of DEH, the most common diagnosis of precedent deafness was deafness of unknown cause with onset in early childhood: 43.9% in both types of DEH. Sudden deafness and mumps deafness were the subsequent diagnoses of precedent deafness. The distribution of time delay of the onset between precedent deafness of unknown cause with onset in early childhood and DEH was different from that between precedent sudden and mumps deafness and DEH.

Expression of transient receptor potential channel mucolipin (TRPML) and polycystine (TRPP) in the mouse inner ear.

CONCLUSIONS: TRPML3 may play distinct roles in the inner ear, such as stereociliar organization, sensory cell transduction, and inner ear fluid homeostasis, and TRPP3 may be important for fluid homeostasis in the inner ear. OBJECTIVE: To study the expression of TRPML1-3 and TRPP2, 3, and 5 in the mouse inner ear. MATERIALS AND METHODS: Localization of TRPML1-3 and TRPP2, 3, and 5 in the inner ear of CBA/J mice was investigated by immunohistochemistry. RESULTS: TRPML1-3 immunoreactivity was evident in the stria vascularis, spiral prominence, and spiral ligament. TRPML immunoreactivity was also observed in outer and inner hair cells, supporting cells, and spiral ganglion cells. The vestibular end organs, vestibular sensory cells, dark cells, and ganglion cells all showed immunoreactivity to TRPML. TRPP2 immunoreactivity was evident in the outer lining of the lateral wall of the cochlea, spiral ganglion cells, vestibular sensory cells, and ganglion cells. TRPP3 immunoreactivity was present in stria vascularis, spiral ganglion cells, vestibular sensory cells, dark cells, and ganglion cells. Faint TRPP5 immunoreactivity was observed in the spiral ganglion cells and vestibular ganglion cells.