Assessment of inner ear morphology and function in response to local positive pressure for Ménière's disease: a nonrandomized controlled trial.

Ménière's disease (MD) is an inner ear disorder in which the main pathological feature is endolymphatic hydrops (EH). Positive pressure therapy (PPT) using a portable device is now a second-line therapy for intractable MD when initial medical treatment fails. However, it remains unknown whether PPT causes the morphological and functional changes of inner ear in patients with active MD in accordance with reduction of vertigo attacks. In this nonrandomized controlled trial of 52 patients with MD, the volume of EH significantly decreased with reduction of vertigo attacks during 8 months of PPT combined with medications while the volume of that significantly increased with medications alone. There was no difference between Control group (n = 26) and PPT group (n = 26) regarding the vertigo control, however, PPT group achieved a significant functional improvement of vertical semicircular canals. The effect of volume reduction by PPT has been firstly demonstrated and the functional changes of all semicircular canals during PPT have been firstly examined. Morphological and functional changes in the inner ear by administrating local positive pressure are quite different from those caused by medications alone.Clinical trial registration: UMIN-CTR UMIN000041164 (registered on July 20, 2020).

Factors associated with spontaneous nystagmus changes in acute Ménière's disease.

BACKGROUND: Neuro-otological factors that influence changes in spontaneous nystagmus (SN) during vertigo attacks in Ménière's disease (MD) remain unclear. OBJECTIVE: To identify neuro-otological factors that might influence the initial direction of SN and the directional change of SN. METHODS: A prospective, observational study of 22 patients with definite MD to evaluate the initial direction and directional change of SN during vertigo attacks, endolymphatic hydrops (EH) volume, and the function of horizontal semicircular canal and hearing levels. RESULTS: SN consistently began as irritative in 17 of 22 cases, and 9 of 17 cases showed a definite change in direction after onset. SN consistently began as paralytic in 5 of 22 cases, and 3 of 5 cases showed a definite change in direction after onset. Subjects in the irritative initial SN group had less severe degrees of hearing loss, smaller cochlear and vestibular EH volume than the paralytic initial SN group (P = 0.017, < 0.001, and 0.009, respectively). Subjects in the SN direction change group had significantly smaller maximum slow phase velocity, percentage of caloric weakness and canal paresis than the no SN direction change group (P = 0.001, 0.006, and 0.001, respectively). Simple logistic regression analysis showed that smaller EH volume was significantly associated with initial irritative SN (OR = 0.867, 95% CI 0.762-0.988, P = 0.032) and that the degree of canal paresis was negatively associated with the presence of directional change of SN (OR = 0.022, 95% CI 0.002-0.289, P = 0.004). CONCLUSIONS: The morphology of EH and canal paresis may independently affect the characteristics of SN in patients with MD.

Antivertiginous Effect of Caloric Stimulation for Acute Peripheral Vertigo.

OBJECTIVE: To clarify therapeutic effect of caloric stimulation for acute peripheral vertigo. PATIENTS: Two patients with acute peripheral vertigo accompanied by spontaneous nystagmus. INTERVENTIONS: Therapeutic. MAIN OUTCOMES AND MEASURES: Changes in the maximum slow phase velocity of spontaneous nystagmus and subjective vertigo. RESULTS: Reduction in the maximum slow phase velocity of spontaneous nystagmus and mitigation of subjective vertigo was observed in both patients. CONCLUSION: Caloric stimulation could be one potential option as a suppressant for acute peripheral vertigo.

Rupture-Like Shrinkage and Regrowth of Endolymphatic Hydrops in Ménière's Disease During Remission.

OBJECTIVE: To clarify pathophysiological characteristics of Ménière's disease during the remission phase. PATIENTS: Two Ménière's disease patients with different disease durations, whose endolymphatic hydrops was longitudinally observed using 3-T magnetic resonance imaging. INTERVENTIONS: Diagnostic. MAIN OUTCOMES AND MEASURES: Morphological changes of endolymphatic hydrops visualized using 3-T magnetic resonance imaging. RESULTS: Rupture-like shrinkage and regrowth of endolymphatic hydrops during the remission phase was observed in both patients. CONCLUSION: The remission phase with hearing improvement could be as important as vertigo attacks in Ménière's disease.

Case Report: Positive Pressure Therapy Combined With Endolymphatic sac Surgery in a Patient With Ménière's Disease.

Positive pressure therapy (PPT) is applied for medically-intractable vertigo in Ménière's disease (MD); however, it remains unknown whether PPT affects in vivo endolymphatic hydrops (EH). In this case report, we describe a 5-year course of MD in a patient in which EH was repeatedly observed. As the patient experienced recurrent vertigo attacks after endolymphatic sac surgery, he began to use the PPT device additionally and vertiginous episodes decreased in accordance with a decrease in the EH volume. The mechanism of PPT is suggested that the pressure increase in the middle ear inhibits EH development. PPT, if added after surgery, might be more effective to reduce EH volume compared with surgery alone. A larger study group size is required to test these preliminary data concerning EH changes.

Assessment of the Progression of Vertical Semicircular Canal Dysfunction and Increased Vestibular Endolymphatic Hydrops in Patients With Early-Stage Ménière Disease.

Importance: Vertical semicircular canals and endolymphatic hydrops play important roles in the pathophysiological mechanisms of Ménière disease. However, their characteristics and associations with disease progression during medical treatment have not been determined. Objective: To examine the function of both the horizontal and vertical semicircular canals in patients with Ménière disease and to evaluate the change in endolymphatic hydrops volume during medical treatment, including treatment with diuretic therapy, over a 2-year period. Design, Setting, and Participants: This prospective longitudinal observational cohort study included 55 patients with definite unilateral Ménière disease and was performed in a tertiary care hospital in Japan. Participants were enrolled between April 1, 2017, and January 31, 2018, and those with vestibular migraine were excluded. All participants received education regarding diet and lifestyle modifications and treatment with betahistine mesylate (36 mg daily) and/or an osmotic diuretic (42-63 mg daily). Patients were followed up for vertigo and hearing evaluations at least once per month for more than 12 months and were instructed to record episodes of vertigo in a self-check diary. Audiometry was performed monthly, video head impulse testing and caloric testing were performed every 4 months, and magnetic resonance imaging was conducted annually. Data were analyzed from May 15, 2017, to January 31, 2020. Main Outcomes and Measures: Neurootological testing to evaluate vestibuloocular reflex gain over time, magnetic resonance imaging to evaluate the change in endolymphatic hydrops volume over time, and monthly vertigo and hearing evaluations for more than 12 months. Results: Among 55 participants with definite Ménière disease, 32 patients (58.2%) were female, and the mean (SD) age was 59.0 (15.1) years. The median disease duration was 2 years (interquartile range, 0-4 years), with 43 patients (78.2%) having an early stage (ie, disease duration ≤4 years) of Ménière disease. Over the 2-year study period, the vestibuloocular reflex gain decreased from 0.76 to 0.56 in the superior semicircular canals, for a difference of 0.20 (95% CI, 0.14-0.26) and from 0.68 to 0.50 in the posterior semicircular canals, for a difference of 0.18 (95% CI, 0.14-0.22). The maximum slow-phase velocity and vestibuloocular reflex gain in the horizontal semicircular canals were maintained. The volume ratio of vestibular endolymphatic hydrops increased from 19.7% to 23.3%, for a difference of 3.6% (95% CI, 1.4%-5.8%). The frequency of vertiginous episodes decreased, and the hearing level over the study period worsened from 40.9 dB to 44.5 dB, for a difference of 3.5 dB (95% CI, 0.7-6.4 dB). Conclusions and Relevance: In this study, during a 2-year period of medical treatment among patients with Ménière disease, vestibuloocular reflex gain decreased in the vertical semicircular canals but was maintained in the horizontal semicircular canals; the endolymphatic hydrops volume ratio increased, and the frequency of vertiginous episodes decreased. These findings describe the pathological progression of chronic Ménière disease and expand the understanding of its pathophysiological characteristics during the early stage of disease.

Vertical head impulse and caloric are complementary but react opposite to Meniere's disease hydrops.

OBJECTIVES/HYPOTHESIS: Meniere's disease (MD) patients can show normal head impulses despite poor caloric test results. This study aimed to investigate the discrepancy in the vestibulo-ocular reflex (VOR) in MD patients and whether endolymphatic hydrops (EH) influence the VOR. STUDY DESIGN: Prospective, cross-sectional observational study. METHODS: Ninety MD patients were enrolled. Neuro-otological testing, including a video head impulse test (vHIT) of all semicircular canals (SCs), and gadolinium-enhanced inner ear magnetic resonance imaging were performed. The vestibular EH volume was quantitatively evaluated by processing magnetic resonance images. RESULTS: Abnormal vHIT results in MD patients were found most frequently in the posterior (44.4%) SCs, followed by the horizontal (13.3%) and anterior (10%) SCs. Canal paresis (CP) was assessed using the vHIT and the caloric test, and results were not significant when vHIT responses were assessed as CP only using the horizontal SC. The difference in the vestibular EH between the presence and absence of CP was not significant if assessed using the vHIT (P = .5591), but it was statistically different if assessed using the caloric test (P = .0467). CONCLUSIONS: The contradictory reaction of VOR in MD patients may result from the high specificity but low sensitivity of CP in the horizontal vHIT. EH volume in the vestibule affects the caloric response but does not affect the vHIT response. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:1660-1666, 2019.

Contralateral type of delayed endolymphatic hydrops may consist of two phenotypes based on a magnetic resonance imaging preliminary study.

OBJECTIVE: This study was performed to determine the volume distribution of EH in contralateral DEH. PATIENTS AND METHODS: Five contralateral DEH patients (age range = 21-77 years) and one ipsilateral DEH patient. Visualization of in vivo EH using 3T magnetic resonance (MR) imaging was performed by intravenous administration of gadolinium. The EH volume was determined quantitatively by adding the area of EH in consecutive MR images. RESULTS: The total EH volume of the patients with contralateral DEH varied from 24.2 to 56.6 µL in the first ear and 20.2 to 35.7 µL in the contralateral ear. EH was dominantly developed in the first ear for Patient no. 3 and 4, and not dominantly developed in the first ear for Patient no. 1, 2, and 5. CONCLUSIONS: The volume distribution of endolymphatic hydrops (EH) in contralateral delayed endolymphatic hydrops (DEH) was classified into two phenotypes. This suggests that contralateral DEH may consist of two etiologies.

Longitudinal up-regulation of endolymphatic hydrops in patients with Meniere's disease during medical treatment.

Objective/Hypothesis: Meniere's disease (MD) is a common inner ear disease characterized by repeated episodic vertigo, fluctuating sensorineural hearing loss, and tinnitus. Its pathology is defined as endolymphatic hydrops (EH) in the inner ear and EH has been hypothesized to correlate with the clinical symptoms of MD. We presented the dynamics of in vivo EH in MD patients during medical treatments. Study Design: Prospective, single-arm repeated measures. Methods: Eleven MD patients were enrolled. All subjects prospectively underwent gadolinium-enhanced inner ear magnetic resonance (MR) imaging and neuro-otological testing before and after medical treatment. The volume of EH was quantitatively evaluated by processing MR images. All MD patients were administered continuous medication and followed up for more than 12 months. Results: The frequency of vertigo episodes decreased in all patients and vestibular function decreased to 13-91% of the pre-treatment level. The volume ratio of post-treatment EH-to-pre-treatment EH ranged from 1.01-3.22. The total volume of pre-treatment EH was significantly correlated with cochlear symptom disease duration and the affected ear's hearing level. Conclusion: EH in MD patients developed longitudinally with deterioration of inner ear function during medical treatment. The natural course of MD may progress with development of EH at least for a certain period. Level of Evidence: 2b.

Preceding profound deafness and co-factors promote development of endolymphatic hydrops in preliminary patients with delayed endolymphatic hydrops.

CONCLUSION: Profound deafness (PD) is unlikely to be the only cause of endolymphatic hydrops (EH) in patients with delayed endolymphatic hydrops (DEH). Further studies in large patient cohorts are required to determine the etiologic co-factors involved in the development of EH in patients with PD and DEH. OBJECTIVES: DEH usually occurs in patients with sustained unilateral PD who then develop episodic vertigo or fluctuating hearing loss. The latency can vary markedly between PD and development of DEH, but the factors affecting inner ear homeostasis and causing EH during this latency period remain unclear. The study aimed to assess the differences in EH and functional status of the inner ear between patients with PD only and those with DEH. METHOD: Two PD and 10 DEH patients who had developed PD in early childhood were enrolled. Gadolinium-enhanced magnetic resonance imaging of the inner ear was performed in all patients to assess the degree of EH in the vestibule and cochlea. RESULTS: There was no evidence of EH in the affected ears of patients with PD alone. DEH patients, however, showed significant EH in either the cochlea or vestibule, suggesting that EH development and DEH onset were strongly correlated.

[Significant factors for surgical site infection: analysis of 203 head and neck surgeries].

Surgical site infection (SSI) is a common complication in head and neck surgeries. The aim of this study was to assess the rate of, and risk factors for SSI following surgical procedures of the head and neck. The study population comprised 206 patients who underwent surgery of head and neck region in NTT West Osaka Hospital between 2009 and 2011. The incidence rate and risk factors were estimated by the chi-square test and a logistic regression analysis. SSI occurred in 22 cases (10.8%) of 203 patients. A broad range of putative risk factors was recorded in each patient and statistically analyzed to elucidate SSI related factors. Univariate analysis indicated that low BMI, diabetes mellitus, anemia, hypoalbuminemia, surgical wound classification, duration of operation, blood loss, left implants and preoperative radiotherapy were risk factors associated with SSI. Multivariate statistics revealed four independent risk factors: surgical wound classification (odds ratio (OR) 5.88, p = 0.02), hypoalbuminemia (OR 11.48, p < 0.01), duration of operation (OR 18.66, p < 0.01) and left implants (OR 20.24, p < 0.01). Thus, to achieve a reduction in SSI, we need to take care of not only the factors related with surgical technique such as the duration of the operation or left implants, but the preoperative nutrition status.

The role of fine-needle aspiration cytology and magnetic resonance imaging in the management of parotid mass lesions.

CONCLUSION: Fine-needle aspiration cytology (FNAC) is the diagnostic modality of first choice for characterization of parotid mass lesions, while magnetic resonance imaging (MRI) should not be requested routinely. MRI can be reserved until FNAC shows the indication for surgical intervention. OBJECTIVES: Although both FNAC and MRI are useful preoperative diagnostic modalities for parotid mass lesions, it is not well established which modality is more effective. In the present study we sought to address the relative value of FNAC and MRI in relation to the differential diagnosis of benign and malignant parotid mass lesions. SUBJECTS AND METHODS: Eighty-one patients with parotid mass lesions (60 benign and 21 malignant) who had preoperatively undergone FNAC and MRI were reviewed retrospectively. RESULTS: Unsharp margin and infiltration into adjacent tissues on MRI significantly correlated with a malignant histology. The sensitivity/specificity/accuracy of FNAC and MRI were 90%/95%/94% and 81%/92%/89%, respectively. Either FNAC or MRI served equally to predict the malignant nature of parotid mass lesions. Furthermore, the combination of FNAC and MRI yielded no diagnostic advantage over either modality alone. Accurate histological typing rates by FNAC were 80% and 62% for benign and malignant lesions, respectively.

[Clinical analysis of cervical lymph node metastasis from an unknown primary carcinoma].

We retrospectively evaluated the efficacy of neck dissection followed by radiotherapy by using the clinical outcome in 15 patients (median age: 60 years) with upper cervical lymph node (level II) metastasis from unknown primary carcinoma undergoing curative treatment from 1999 to 2007. The male-to-female ratio was 4 : 1, and the histopathological diagnosis in 11 patients (73.3%) was squamous cell carcinoma. Clinical N status was distributed as follows: N1, 1; N2a, 4; N2b, 8; and N2c, 2. Of the 15 patients, 13 patients (86.7%) underwent neck dissection and 11 (84.6%), including 2 unresectable cases undergoing concurrent chemoradiotherapy using DOC and CDDP making their condition resectable, underwent neck dissection combined with radiotherapy. Follow-up was from 5 to 72 months (median: 39 months). In 2 of 6 patients, we detected the primary site at the ipsilateral tonsil through tonsillectomy conducted concurrently with neck dissection. Overall 5-year survival determined by the Kaplan-Meier method was 88.9%, and only 1 patient died of metastasis without achieving complete response 29 months after initial treatment. None of the 15 was observed to have local regional recurrence or distant metastasis after initial treatment. These results indicate that neck dissection followed by radiotherapy is recommended for improving the outcome of patients with cervical lymph node metastasis from an unknown primary carcinoma.

Synchronous squamous cell carcinoma and malignant lymphoma in the head and neck region.

Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the head and neck region is extremely rare. Here, we report the case of a 57-year-old man with a right-sided neck mass; he was referred to our hospital in September 2001. A series of staging work-ups revealed that he was simultaneously affected by oropharyngeal SCC and nasopharyngeal ML. He underwent conventional radiotherapy, and both the primary tumors showed complete remission. The metastatic lymph nodes showed poor response to the radiotherapy, and the patient was surgically salvaged by modified radical neck dissection. Although systemic chemotherapy against ML was scheduled, he refused the treatment and died of disseminated ML. It is essential to determine the lesion that should be given priority treatment in case of double primary malignancies; this can be facilitated by determining the prognosis of each malignancy.

Concurrent chemoradiotherapy with cisplatin and docetaxel for advanced head and neck cancer. A phase I study.

BACKGROUND: This phase I study of weekly low-dose administration of cisplatin (CDDP) and docetaxel (DOC) combined with concurrent conventionally fractionated radiotherapy was designed for locoregionally advanced head and neck cancer. PATIENTS AND METHODS: Twelve patients were treated at varying levels of DOC (level 1: 5 mg/m2/week, level 2: 7.5 mg/m2/week, level 3: 10 mg/m2/week) with CDDP constant at 20 mg/m2/week in four cohorts of three patients. Radiation was given at 1.8-2.0 Gy/fraction to a total dose of 60-70.2 Gy. RESULTS: Hematological toxicities, except lymphocytopenia, were minimal. Mucosal toxicities, especially grade 3 mucositis, were common. Dose-limiting toxicity was grade 3 pain, although level 3 did not reach a maximum tolerated dose. No grade 4 toxicities were observed. Complete response rate ranged from 33% to 67% in the various dose levels. CONCLUSION: This concurrent chemoradiotherapy seems to be a promising treatment modality, in which level 3 is the recommended dose for a phase II study.

Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses.

CD100/Sema4D belongs to the semaphorin family, factors known to act as repulsive cues for axons during neuronal development. Mouse CD100 plays a crucial role in both humoral and cellular immunity through ligation of the lymphocyte receptor, CD72. It remains controversial, however, whether human CD100 can function through human CD72 in a manner similar to mouse CD100. To determine the function of human CD100, we generated a recombinant soluble human CD100 protein comprised of the extracellular region of human CD100 fused to the human IgG1 Fc region (hCD100-Fc). hCD100-Fc specifically binds to cells expressing human CD72. As observed previously in the mouse, hCD100-Fc induces the tyrosine dephosphorylation of human CD72, leading to the dissociation of SHP-1 from the CD72 cytoplasmic tail. Consistent with findings for mouse CD100, hCD100-Fc exerts a co-stimulatory effect on B cells and dendritic cells that are stimulated with anti-CD40 mAb. Furthermore, both hCD100-Fc and anti-human CD72 agonistic mAb induce the production of the pro-inflammatory cytokines tumor necrosis factor-alpha, IL-6 and IL-8, even in the absence of anti-CD40 mAb. Collectively, our findings not only demonstrate that human CD100, interacting with human CD72, can function as a ligand in a manner similar to mouse CD100, but also suggest the involvement of human CD100 in inflammatory responses.

Overexpression of the Wilms' tumor gene WT1 in head and neck squamous cell carcinoma.

The expression levels of the Wilms' tumor gene WT1 were examined in 56 cases of head and neck squamous cell carcinoma (HNSCC) using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). They included 4 cases of floor of mouth, 9 of gingiva, 25 of tongue, 10 of oropharynx, 3 of hypopharynx, and 5 larynx squamous cell carcinoma (SCC). All (100%) of 4 cases of floor of mouth, 5 (56%) of 9 gingiva, 17 (68%) of 25 tongue, 8 (80%) of 10 oropharynx, all (100%) of 3 hypopharynx, and all (100%) of 5 larynx SCC overexpressed the WT1 gene in the range of 3.07 x 10(-4)-8.60 x 10(-1) levels (the WT1 expression level in K562 leukemic cells was defined as 1.0). Thus, 42 (75%) out of 56 cases of HNSCC overexpressed the WT1 gene. The high expression level of the WT1 gene significantly correlated with poor histological tumor differentiation and high tumor stage of HNSCC. Immunohistochemical analysis confirmed the expression of WT1 protein in 6 cases (one floor of mouth, 2 tongue, 2 oropharynx, and one larynx SCC) with overexpression of the WT1 gene. The direct sequencing analysis of the WT1 genomic DNA showed no mutations in any of 10 exons of the WT1 gene in 5 different HNSCC. These findings suggest an important role of the wild-type WT1 gene in the tumorigenesis of HNSCC.

Malignant transformation of thyroid follicular cells by galectin-3.

Galectin-3, a beta-galactoside binding lectin, is highly expressed in thyroid carcinomas of follicular cell origin, whereas neither benign thyroid adenomas nor normal thyroid tissues express galectin-3. We previously showed that antisense inhibition of galectin-3 expression markedly reduced the malignant phenotype of thyroid papillary carcinoma cells. In the present study we transfected galectin-3 cDNA into TAD-2 normal thyroid follicular cells. Stable transfectants expressing galectin-3 acquired the phenotype of serum-independent growth, clonogenicity in soft agar, as well as loss of contact inhibition. We also compared the gene expression profile of the galectin-3 transfectants to that of the vehicle control, which revealed that a series of genes were differentially expressed between the two. They include proliferating cell nuclear antigen, replication factor C, and retinoblastoma genes that participate in G1-S transition. These results indicate the transformation of thyroid follicular cells by galectin-3 and possible involvement of galectin-3 in cell cycle.