Recurrence Rate and Risk Factors of Recurrence in Benign Paroxysmal Positional Vertigo: a Single-Center Long-Term Prospective Study With a Large Cohort.

OBJECTIVE: This study aimed to assess the long-term recurrence rate and correlations between recurrence and potential risk factors in patients with benign paroxysmal positional vertigo (BPPV). DESIGN: A total of 548 consecutive patients who demonstrated typical posterior or horizontal BPPV between January 2010 and December 2012 were included in this prospective study. All patients were contacted by phone every 6 months for 5 years and were asked to revisit the clinic when they experienced positional vertigo to be reexamined for recurrence. Recurrence of BPPV was defined as having positional vertigo and nystagmus confirmed following a symptom-free period of at least 7 days after complete resolution. We assessed the 5-year recurrence rate of BPPV, and the time point of recurrence in all patients as well as the risk factors of BPPV recurrence, including the clinical characteristics, therapeutic results of BPPV, and various comorbidities. RESULTS: Among the 548 patients, 121 (22.1 %) had at least one recurrence. Of these, 78 patients (54.5%) had only one recurrence within 5 years, while 43 (45.5%) patients experienced two or more recurrences. A recurrence occurred within 1 year in 82 patients (67.8%). The Cox proportional hazard ratio analysis found that head trauma (p = 0.015), Meniere's disease (p = 0.016), the number of canalith repositioning procedures performed (p = 0.037), and the number of previous vertigo attacks (p = 0.038) were significant risk factors of BPPV recurrence as opposed to hypertension or hyperlipidemia. CONCLUSIONS: The recurrence rate of BPPV was 22.1% at 5 years after the initial treatment. About 70% of recurred patients had a recurrence within 1 year. Head trauma, ipsilateral Meniere's disease, the number of canalith repositioning procedures performed, and the number of previous vertigo attacks were significant risk factors of BPPV recurrence.

Genetic Inheritance of Late-Onset, Down-Sloping Hearing Loss and Its Implications for Auditory Rehabilitation.

OBJECTIVES: Late-onset, down-sloping sensorineural hearing loss has many genetic and nongenetic etiologies, but the proportion of this commonly encountered type of hearing loss attributable to genetic causes is not well known. In this study, the authors performed genetic analysis using next-generation sequencing techniques in patients showing late-onset, down-sloping sensorineural hearing loss with preserved low-frequency hearing, and investigated the clinical implications of the variants identified. DESIGN: From a cohort of patients with hearing loss at a tertiary referral hospital, 18 unrelated probands with down-sloping sensorineural hearing loss of late onset were included in this study. Down-sloping hearing loss was defined as a mean low-frequency threshold at 250 Hz and 500 Hz less than or equal to 40 dB HL and a mean high-frequency threshold at 1, 2, and 4 kHz greater than 40 dB HL. The authors performed whole-exome sequencing and segregation analysis to identify the genetic causes and evaluated the outcomes of auditory rehabilitation in the patients. RESULTS: There were nine simplex and nine multiplex families included, in which the causative variants were found in six of 18 probands, demonstrating a detection rate of 33.3%. Various types of variants, including five novel and three known variants, were detected in the MYH14, MYH9, USH2A, COL11A2, and TMPRSS3 genes. The outcome of cochlear and middle ear implants in patients identified with pathogenic variants was satisfactory. There was no statistically significant difference between pathogenic variant-positive and pathogenic variant-negative groups in terms of onset age, family history of hearing loss, pure-tone threshold, or speech discrimination scores. CONCLUSIONS: The proportion of patients with late-onset, down-sloping hearing loss identified with potentially causative variants was unexpectedly high. Identification of the causative variants will offer insights on hearing loss progression and prognosis regarding various modes of auditory rehabilitation, as well as possible concomitant syndromic features.

Identification of a novel nonsynonymous mutation of EYA1 disrupting splice site in a Korean patient with BOR syndrome.

The EYA1 gene is known as the causative gene of BOR (Branchio-oto-renal) syndrome which is a genetic disorder associated with branchial cleft cysts of fistulae, hearing loss, ear malformation, and renal anomalies. Although approximately 40% of patients with BOR syndrome have mutations in the EYA1 gene and over 130 disease-causing mutations in EYA1 have been reported in various populations, only a few mutations have been reported in Korean families. In this study, genetic analysis of the EYA1 gene was performed in a Korean patient diagnosed with BOR syndrome and his parents. A de novo novel missense mutation, c.418G>A, located at the end of exon 6, changed glycine to serine at amino acid position 140 (p.G140S) and was suspected to affect normal splicing. Our in vitro splicing assay demonstrated that this mutation causes exon 6 skipping leading to frameshift and truncation of the protein to result in the loss of eyaHR. To the best of our knowledge, this is the first report revealing that a missense mutation in the exon disturbs normal splicing as a result of a substitution of the last nucleotide of an exon in EYA1.

Novel Variant in CEP250 Causes Protein Mislocalization and Leads to Nonsyndromic Autosomal Recessive Type of Progressive Hearing Loss.

Genetic hearing loss is the most common hereditary sensorial disorder. Though more than 120 genes associated with deafness have been identified, unveiled causative genes and variants of diverse types of hearing loss remain. Herein, we identified a novel nonsense homozygous variant in CEP250 (c.3511C>T; p.Gln1171Ter) among the family members with progressive moderate sensorineural hearing loss in nonsyndromic autosomal recessive type but without retinal degeneration. CEP250 encodes C-Nap1 protein belonging to the CEP protein family, comprising 30 proteins that play roles in centrosome aggregation and cell cycle progression. The nonsense variant in CEP250 led to the early truncating protein of C-Nap1, which hindered centrosome localization; heterologous expression of CEP250 (c.3511C>T) in NIH3T3 cells within cilia expression condition revealed that the truncating C-Nap1 (p.Gln1171Ter) was not localized at the centrosome but was dispersed in the cytosol. In the murine adult cochlea, Cep250 was expressed in the inner and outer hair cells. Knockout mice of Cep250 showed significant hair cell degeneration and progressive hearing loss in auditory brainstem response. In conclusion, a nonsense variant in CEP250 results in a deficit of centrosome localization and hair cell degeneration in the cochlea, which is associated with the progression of hearing loss in humans and mice.

Pou3f4 deficiency causes defects in otic fibrocytes and stria vascularis by different mechanisms.

DFN3, the most prevalent X-linked hearing loss, is caused by mutations in the POU3F4 gene. Previous studies in Pou3f4 knockout mice suggest that defective otic fibrocytes in the spiral ligament of the cochlear lateral wall may underlie the hearing loss in DFN3. To better understand the pathological mechanisms of the DFN3 hearing loss, we analyzed inner ears of Pou3f4-deficient mice during development. Our results indicate that compartmentalization of the spiral ligament mesenchyme setting up boundaries for specific otic fibrocytes occurs normally in Pou3f4-deficient cochlea. However, differentiation of the compartmentalized mesenchyme into specific otic fibrocytes was blocked in the absence of Pou3f4 function. In addition, we found that stria vascularis in the cochlear lateral wall was also affected in Pou3f4-deficient cochlea. Unlike the otic fibrocytes, differentiation of stria vascularis was completed in the absence of Pou3f4 function, yet expression of Kir4.1 channels in the strial intermediate cells, essential for the sound transduction, was lost afterwards. These results suggest that Pou3f4 deficiency causes defects in both otic fibrocytes and stria vascularis at different developmental stages and by different pathological mechanisms, which may account for the progressive nature of DFN3 hearing loss.

Clinical Implications of Horizontal Beating Nystagmus Induced by Dix-Hallpike Test in the Diagnosis of Horizontal Canal Benign Paroxysmal Positional Vertigo.

OBJECTIVES: The purpose of this study was to identify the diverse patterns of nystagmus during the Dix-Hallpike test (DHT) and analyze their clinical significance in horizontal canal benign paroxysmal positional vertigo (HC-BPPV). STUDY DESIGN: Retrospective medical records review. PATIENTS: Two hundred ninety-five patients diagnosed with HC-BPPV. METHODS: Various nystagmus patterns identified during the DHT in patients with HC-BPPV were analyzed. The correlation between the affected side of HC-BPPV and the direction of the horizontal beating nystagmus (HBN) during the DHT was also analyzed. RESULTS: The nystagmus pattern during the DHT in 128 patients with geotropic HC-BPPV demonstrated, direction-changing positional nystagmus on both sides in 48 (37.5%) patients, HBN toward one side in 25 (19.6%) patients, and no nystagmus in 55 (42.9%) patients. In 144 patients with apogeotropic HC-BPPV, 54 (37.5%) patients presented with direction-changing positional nystagmus on both sides, 27 (18.8%) patients presented with HBN toward one side, and 63 (43.7%) patients did not show nystagmus during the DHT. The direction of HBN provoked by the DHT was significantly correlated with the affected side in each subtype of HC-BPPV (geotropic type, p = 0.049; apogeotropic type, p = 0.040; respectively). CONCLUSION: More than half of the patients with HC-BPPV (56.6%) showed HBN during the DHT. When HBN was present during the DHT, it may provide a clue for determining the subtype and affected side in diagnosis of HC-BPPV before performing the supine roll test.

Therapeutic efficacy of super-high-dose steroid therapy in patients with profound sudden sensorineural hearing loss: a comparison with conventional steroid therapy.

BACKGROUND: In patients with sudden sensorineural hearing loss (SSNHL), steroid therapy is an optional treatment method, but there is controversy about its dose. OBJECTIVE: We aimed to compare the efficacy of super-high-dose steroid therapy with that of conventional steroid therapy in patients with profound SSNHL (pSSNHL). MATERIAL AND METHODS: Fifty-two patients diagnosed with pSSNHL between March 2010 and May 2017 were divided into the following groups based on their steroid regimen: a conventional steroid regimen (prednisolone at 1.0 mg/kg/day for 10 days) was applied in Group 1, and a super-high-dose steroid regimen (prednisolone at 1.5 mg/kg/day for 14 days) was applied in Group 2. The treatment outcomes were compared between the groups at 2 and 4 weeks after the initial treatment by use of Siegel's criteria. RESULTS: Of the 52 patients, 31 were classified into Group 1 and 21 into Group 2. When comparing the proportion of patients in complete or partial recovery by Siegel's criteria, the recovery rate was significantly higher in Group 2 than in Group 1 (19% vs 0%, p = .022 at 2 weeks; 35.7% vs 7.4%, p = 0.035 at 4 weeks). CONCLUSIONS AND SIGNIFICANCE: Patients with pSSNHL treated using the super-high-dose steroid regimen demonstrated better recovery rates to serviceable hearing than did those treated using the conventional steroid regimen without significant complications.

Optimal reassessment time for treatment response in posterior canal benign paroxysmal positional vertigo.

OBJECTIVES/HYPOTHESIS: The present study aimed to evaluate the optimal reassessment time for treatment response in posterior canal benign paroxysmal positional vertigo (PC-BPPV) following the initial Epley maneuver. STUDY DESIGN: Prospective, single-blinded, randomized study. METHODS: One hundred eight patients with PC-BPPV agreed to participate. These patients received a single modified Epley maneuver (recommended by the 2008 American Academy of Otolaryngology-Head and Neck Surgery guidelines) daily until positional nystagmus disappeared during the Dix-Hallpike maneuver 24 hours after the treatment. Repeated Dix-Hallpike testing to reassess the treatment response was performed at 1 hour (post-1 hour), every 24 hours (post-24 hours) until the positional nystagmus resolved, 1 week (post-1 week), and 1 month (post-1 month) following the therapeutic maneuver. The difference in the resolution rates at post-1 hour and post-24 hours reassessment was analyzed, and the recurrence rates at post-1 week and post-1 month were evaluated. RESULTS: The resolution rate was 67.6% at post-1 hour, which increased to 79.6% at post-24 hours reassessment. There was a statistically significant difference in the results of the Dix-Hallpike test between post-1 hour and post-24 hours follow-up. After complete resolution, nine out of 108 patients (8.3%) demonstrated recurrence within 1 month. CONCLUSIONS: Reassessment after 24 hours following the initial Epley maneuver is more advantageous than a 1-hour follow-up in patients with PC-BPPV. This information may be helpful for clinicians in deciding the appropriate follow-up period after treatment for PC-BPPV. LEVEL OF EVIDENCE: 1b Laryngoscope, 130:496-499, 2020.

Double-blind randomized controlled trial on efficacy of cupulolith repositioning maneuver for treatment of apogeotropic horizontal canal benign paroxysmal positional vertigo.

Backgrounds: Although various therapeutic maneuvers have been proposed, it is still unclear which maneuver is better to treat apogeotropic horizontal canal benign paroxysmal positional vertigo (HC-BPPV).Objectives: This study aimed to assess the therapeutic efficacy of the cupulolith repositioning maneuver (CuRM) in apogeotropic HC-BPPV in comparison with the therapeutic head-shaking maneuver and modified Lempert maneuver.Materials and Method: This is double-blind randomized prospective study. Forty-nine consecutive patients diagnosed with apogeotropic HC-BPPV were allocated randomly to CuRM (n = 18), therapeutic head-shaking (n = 16), or modified Lempert maneuver (n = 15). The presence of nystagmus and vertigo on positional testing were evaluated at 30 min, on 1 day, and 1 week after treatment.Results: There were no significant differences in any clinical characteristics between the three groups at randomization. After a single trial of therapeutic maneuvers on the initial visit day, the CuRM (38.9%) and therapeutic head shaking maneuver (12.5%) did not show differences compared to modified Lempert maneuver (33.3%). The therapeutic effects on the 2nd day and at 1 week after treatment also did not differ between the three groups.Conclusions: Although the CuRM is theoretically considered to be a better therapeutic method, the therapeutic efficacy of CuRM was not statistically different compared to the other two maneuvers.

Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein.

X-linked deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations in the POU3F4 locus, which encodes a member of the POU family of transcription factors. Despite numerous reports on clinical evaluations and genetic analyses describing novel POU3F4 mutations, little is known about how such mutations affect normal functions of the POU3F4 protein and cause inner ear malformations and deafness. Here we describe three novel mutations of the POU3F4 gene and their clinical characterizations in three Korean families carrying deafness segregating at the DFN3 locus. The three mutations cause a substitution (p.Arg329Pro) or a deletion (p.Ser310del) of highly conserved amino acid residues in the POU homeodomain or a truncation that eliminates both DNA-binding domains (p.Ala116fs). In an attempt to better understand the molecular mechanisms underlying their inner ear defects, we examined the behavior of the normal and mutant forms of the POU3F4 protein in C3H/10T1/2 mesodermal cells. Protein modeling as well as in vitro assays demonstrated that these mutations are detrimental to the tertiary structure of the POU3F4 protein and severely affect its ability to bind DNA. All three mutated POU3F4 proteins failed to transactivate expression of a reporter gene. In addition, all three failed to inhibit the transcriptional activity of wild-type proteins when both wild-type and mutant proteins were coexpressed. Since most of the mutations reported for DFN3 thus far are associated with regions that encode the DNA binding domains of POU3F4, our results strongly suggest that the deafness in DFN3 patients is largely due to the null function of POU3F4.

Outcomes and Predictive Factors of Electroacoustic Stimulation Rehabilitation in Children With Limited Low-Frequency Hearing.

OBJECTIVE: To evaluate the clinical feasibility and auditory benefits of hearing rehabilitation using electroacoustic stimulation (EAS) after cochlear implantation (CI) and to identify the predictive factors for successful EAS rehabilitation in children with limited low-frequency hearing. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Seventeen children (21 ears) under the age of 15 years with residual low-frequency hearing who underwent CI using hearing preservation techniques. INTERVENTION: Patients underwent CI using hearing preservation techniques, and the postoperative audiograms were obtained to evaluate the hearing preservation rate. EAS rehabilitation was applied in patients with successful low-frequency hearing preservation. OUTCOME MEASURES: Improvements in speech perception in both quiet and noise conditions were compared between the EAS mode and the CI-only mode. The predictive factors for successful EAS rehabilitation in children were analyzed. RESULTS: Functional low-frequency residual hearing less than or equal to 85 dB at 250 and 500 Hz was achieved postoperatively in six of 21 ears, and successful EAS rehabilitation was possible in nine of 21 ears. Better speech perception scores were observed in quiet conditions using the EAS mode compared with the CI-only mode, although the difference did not reach statistical significance. Significantly, better scores were observed in noise conditions with the EAS mode compared with the CI-only mode. Postoperative low-frequency pure-tone average was the only significant predictive factor of successful EAS rehabilitation. CONCLUSION: CI surgery using hearing preservation techniques with EAS rehabilitation should be performed in children, even in patients with limited residual hearing, to improve auditory outcomes.

Jugular foramen schwannoma: analysis on its origin and location.

OBJECTIVE: To examine the microsurgical anatomy of the jugular foramen and correlate anatomical findings to clinical manifestations of jugular foramen schwannomas concerning tumor origin and location. STUDY DESIGN: Anatomical analysis of jugular foramen was performed by dissection of 25 cadavers (50 sides). By retrospective review of 9 cases of jugular foramen schwannomas surgically treated, the origin and location of tumor were studied. SETTING: Tertiary referral center. MAIN OUTCOME MEASURES: The anatomical characteristics of jugular foramen, lower cranial nerves, and inferior petrosal sinus were correlated with the origin and growth pattern of jugular foramen schwannomas. RESULTS: The superior and inferior ganglions of the glossopharyngeal nerve and the superior ganglion of the vagus nerve were located within the jugular foramen. The superior ganglions of the glossopharyngeal and vagus nerves were located superiorly, whereas the inferior ganglion of the glossopharyngeal nerve was found inferiorly in relation to the inferior petrosal sinus orifice. In our series of 9 cases of jugular foramen schwannoma, the most common nerve of origin was the vagus nerve, followed by the glossopharyngeal nerve. CONCLUSION: The reason for the predilection of the jugular foramen schwannoma for the glossopharyngeal and vagus nerves may be associated with the presence of their ganglions within the jugular foramen. Also, the inferior petrosal sinus may act as a barrier to tumor growth, and the location of the ganglion of tumor origination within the jugular foramen in relation to the inferior petrosal sinus may be correlated to the predominant direction of tumor extension.

Clinical significance of quantitative analysis of facial nerve enhancement on MRI in Bell's palsy.

CONCLUSIONS: Quantitative analysis of the facial nerve on the lesion side as well as the normal side, which allowed for more accurate measurement of facial nerve enhancement in patients with facial palsy, showed statistically significant correlation with the initial severity of facial nerve inflammation, although little prognostic significance was shown. OBJECTIVES: This study investigated the clinical significance of quantitative measurement of facial nerve enhancement in patients with Bell's palsy by analyzing the enhancement pattern and correlating MRI findings with initial severity of facial palsy and clinical outcome. SUBJECTS AND METHODS: Facial nerve enhancement was measured quantitatively by using the region of interest on pre- and postcontrast T1-weighted images in 44 patients diagnosed with Bell's palsy. The signal intensity increase on the lesion side was first compared with that of the contralateral side and then correlated with the initial degree of facial palsy and prognosis. RESULTS: The lesion side showed significantly higher signal intensity increase compared with the normal side in all of the segments except for the mastoid segment. Signal intensity increase at the internal auditory canal and labyrinthine segments showed correlation with the initial degree of facial palsy but no significant difference was found between different prognostic groups.

Typical sensory organization test findings and clinical implication in acute vestibular neuritis.

OBJECTIVE: Sensory organization test (SOT) is used to evaluate postural instability. We wanted to characterize the SOT findings in patients with acute vestibular neuritis (VN). METHODS: Eighty-seven patients with VN were enrolled. The bithermal caloric and SOT were performed, and the results were compared with those from the dizziness handicap inventory (DHI). Abnormal SOT patterns were classified: severe, visual vestibular, vestibular, inconsistent, or normal patterns. The results were also analyzed by sensory analysis (somatosensory, visual, vestibular, and visual preference) and composite scores. RESULTS: Sixty-one patients (70%) showed abnormal findings for conditions 5 and/or 6 (vestibular pattern), and half (30 of 61, 49%) of them showed additional abnormal results in more than conditions 5 and 6. In pattern analysis, the vestibular pattern (abnormal in conditions 5 and 6) was the most common pattern (36%), and the visual vestibular pattern (abnormal in conditions 4, 5, and 6) was the second most common (24%). In sensory analysis, vestibular dysfunction was observed in 59 patients (68%), visual dysfunction in 37 (43%), visual preference in 17 (20%), and somatosensory dysfunction in 5 (6%). Composite scores of SOT showed a significant correlation with the DHI scores, though no correlation was observed between DHI and caloric results (p<0.05). CONCLUSION: VN can adversely influence on postural instability, with more severe patterns as well as classical vestibular patterns, indicating that abnormal vestibular inputs can influence postural stability in all SOT conditions and subjective symptom in patients with acute VN is more closely associated with the postural instability rather than canal dysfunction.

Progressive hearing loss in vitamin A-deficient mice which may be protected by the activation of cochlear melanocyte.

Vitamin A deficiency (VAD) produces various pathologic phenotypes in humans and animals. However, evidence regarding the effect of VAD on hearing function has been inconsistent. In this study, we evaluated the effect of VAD on hearing function in two mouse models of VAD. Hearing ability was evaluated on the basis of auditory brainstem response from 3 to 20 weeks after birth in C57BL/6 (pigmented) and imprinting control region (albino) mice. The two mice strains were divided into the VAD (purified vitamin A-free diet from 7 days after pregnancy) and control (normal diet) groups. Albino VAD mice exhibited hearing loss after 6 weeks and became deaf at 18 weeks. Histological findings revealed degenerative changes in outer hair cells and neuronal loss in the spiral ganglion in albino VAD mice. In contrast, pigmented VAD mice, except those with middle-ear infection, showed no significant hearing loss. Interestingly, pigmented VAD mice exhibited melanocyte activation in the stria vascularis and upregulation of tyrosinase. Recovery of hearing after noise exposure was poorer in pigmented VAD mice than in control mice. In conclusion, complete VAD might be related to age-related or noise-induced hearing loss in mice, protection against which might involve melanocyte activation.

Management of facial nerve schwannoma in patients with favorable facial function.

OBJECTIVE: We report six cases of facial nerve schwannomas in which surgical management allowed the preservation of facial nerve function. Specifically, this paper reports that a stripping surgery may provide favorable functional outcomes. STUDY DESIGN: A retrospective review of preoperative and postoperative data for six patients with facial nerve schwannoma that had normal facial nerve function or a House-Brackmann grade II facial palsy before the surgery. METHODS: Stripping surgery, which removed the schwannoma from the remaining nerve fascicle, was attempted on the six patients. Postoperative facial nerve function and imaging (magnetic resonance imaging) were evaluated. RESULTS: Stripping surgery with gross total tumor removal of the mass was performed in four cases. In the two remaining cases, the stripping surgery was not possible, and decompression alone was performed. Favorable preservation of facial function was achieved in all six cases. CONCLUSION: It was possible to preserve facial function after surgery to remove facial nerve schwannoma. We suggest that stripping surgery, focused on the preservation of continuity of the facial nerve, may be attempted for facial nerve schwannoma in which favorable facial function has been preserved.

Hearing results after ossiculoplasty using Polycel prosthesis.

CONCLUSIONS: Polycel is an effective material to use in ossiculoplasty. Good prognostic factors for hearing improvement after ossiculoplasty were healthy middle ear mucosa and the presence of stapes superstructure. OBJECTIVE: During the last decade, the surgical use of alloplasts has become increasingly widespread among otologists. This study aimed to evaluate the hearing results after ossiculoplasty using Polycel prosthesis. MATERIALS AND METHODS: We retrospectively reviewed 188 patients who underwent ossicular chain reconstruction using Polycel prosthesis and were followed up postoperatively for more than 12 months at Severance Eye-ENT Hospital from 1998 to 2002. Postoperative hearing results were assessed by measuring the postoperative air-bone gap (ABG) and closure of the ABG. Successful postoperative ABG criteria were defined as the following three measurements: ABG of

Growth inhibition and apoptosis by (-)-epicatechin gallate are mediated by cyclin D1 suppression in head and neck squamous carcinoma cells.

In recent studies, green tea components have been shown to induce cell growth arrest and apoptosis in head and neck squamous cell carcinoma (HNSCC) cells. In this report, we have investigated the effects of epicatechin gallate (ECG), one of the catechins in green tea, on anti-cancer activity in vitro. We found that cyclin D1 was highly expressed in HNSCC cells, and ECG suppressed 90% of cyclin D1 expression in SCC7 cells. We have also evaluated the effect of ECG on cell growth and apoptosis, showing that ECG (50 microM) exhibited a significant inhibition (50%) on the growth of SCC7 cells via G1 cell cycle arrest. ECG suppressed cyclin D1 in SCC7 cells in a dose- and time-dependent manner, and the suppression of the beta-catenin pathway by ECG is one of the mechanism to facilitate ECG-induced cell growth arrest. These results suggest that ECG has a potential usage as a chemopreventive agent in HNSCC.

Dexamethasone increases fluid absorption via Na+/H+ exchanger (NHE) 3 activation in normal human middle ear epithelial cells.

The proper homeostasis of the liquid lining the surface of the middle ear cavity is vitally important for maintaining a fluid-free middle ear cavity. Disruption of this homeostasis leads to fluid collection in the middle ear cavity and results in otitis media with effusion. We demonstrated the molecular and functional expression of the Na+/H+ exchanger (NHE)s in normal human middle ear epithelial (NHMEE) cells. We also evaluated the role of NHEs in fluid absorption and the effect of dexamethasone on NHE function and NHE-dependent fluid absorption in NHMEE cells. Western blot analysis was performed for NHE1, -2, and -3 in NHMEE cells. The fluid absorption rate was measured after liquid application on the luminal surface of the cells. Intracellular pH (pHi) was measured using the pH-sensitive fluorescent probe bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-AM. NHE activity was determined as Na+-induced pHi recovery from an acid load achieved by luminal exposure to 40 mmol/l NH4Cl. NHE1, -2 and -3 were all expressed in the NHMEE cells. The pHi recovery rate was suppressed by inhibition of NHE2 and -3 with HOE694 at concentrations greater than 50 microM. Inhibition of NHE3 with 650 microM of HOE694 or S3226 significantly decreased the fluid absorption rate. Dexamethasone increased the Na+-induced pHi recovery rate which was reversed by the inhibition of NHE3 with 650 microM of HOE694. Dexamethasone treatment up-regulated NHE3 expression in a dose-dependent manner. The fluid absorption rate was increased by treatment with dexamethasone (10(-7) M) and reversed by the inhibition of NHE3. In summary, we have shown that NHE3 are involved in the regulation of both pHi and fluid absorption on the luminal surface of NHMEE cells. Dexamethasone stimulates NHE3 expression and NHE3-dependent fluid absorption in NHMEE cells. These findings provide a new insight into mechanisms that regulate periciliary fluid and the therapeutic mechanisms behind steroid treatment of otitis media with effusion.

Is dissection of level IV absolutely necessary in elective lateral neck dissection for clinically N0 laryngeal carcinoma?

A prospective study of 73 previous untreated consecutive patients with clinically N0 laryngeal squamous cell carcinoma (SCC) from January 1997 to October 2002 was undertaken to determine whether level IV lymph nodes can be saved in elective lateral neck dissection (LND) performed as a treatment for the N0 neck. The incidence of pathological metastases to level IV lymph nodes was evaluated, as were the incidence of regional recurrence after elective LND, and postoperative complications such as chylous leakage and phrenic nerve paralysis. A total of 142 LNDs were enrolled in this prospective study. The mean number of harvested lymph nodes by level was as follows; 13.1 in level II, 7.1 in level III, and 9.2 in level IV. Pathologic examination revealed nodal involvement in 25 neck specimens (17.6%, 25 of 142). Five necks had lymph nodes which were positive for microscopic metastasis in level IV (3.5%, 5 of 142). These necks were all ipsilateral (6.8%, 5 of 73) and none of the 69 contralateral neck specimens had level IV lymph node metastasis (0%, 0 of 69). With regard to T stage, 3.3% (1 of 30) of ipsilateral necks of T2 tumors exhibited occult metastasis in level IV lymph nodes, 5.9% (2 of 34) for T3 tumors, and 33.3% (2 of 6) for T4 tumors. There were no cases of T1 (n = 3). Separate skip metastasis in level IV lymph nodes was observed in two necks (1.4%, 2 of 142). Four cases of regional recurrence (5.5%, 4 of 73) were observed. Postoperative chylous leakage and phrenic nerve paralysis occurred in four cases (5.5%, 4 of 73) and two cases (2.7%, 2 of 73), respectively. The results of the present study demonstrate the rare incidence of level IV occult lymph node metastasis, as well as infrequent nodal recurrence after elective LND in the treatment of clinically N0 laryngeal SCC. Therefore, dissection of level IV lymph node pads, especially in the ipsilateral neck of early T staged tumors or the contralateral neck, may be unnecessary for the treatment of laryngeal SCC patients with a clinically N0 neck.