Myung Woul Han

Therapeutic effectiveness over time of intratympanic dexamethasone as salvage treatment of sudden deafness

Conclusion. Intratympanic dexamethasone (ITD) within 1 month after initial treatment failure should be utilized as salvage treatment for refractory sudden sensorineural hearing loss (SSNHL). Objective. To investigate the therapeutic efficacy over time of ITD as salvage treatment in SSNHL. Materials and methods. We retrospectively reviewed the medical records and audiograms of 99 SSNHL patients who were refractory to 2 weeks of oral steroid treatment, from August 2003 to October 2006. Patients were divided into those receiving no further treatment (control group) and those receiving ITD within 2 weeks (early-ITD), between 2 weeks and 1 month (mid-ITD), and between 1 and 2 months (late-ITD) after initial treatment failure. ITD was performed in the supine position on four separate occasions over the course of 2 weeks. Final assessment of hearing was carried out 3 months after outbreak of SSNHL. Hearing improvement was defined as a >15 dB decrease in four-tone average (FTA). Results. Overall hearing improvement was observed in 8 of 50 (16.0%) control patients, 7 of 16 (43.8%) early ITD patients, 6 of 20 (30.0%) mid ITD patients, and 2 of 13 (15.4%) late ITD patients.CONCLUSION Intratympanic dexamethasone (ITD) within 1 month after initial treatment failure should be utilized as salvage treatment for refractory sudden sensorineural hearing loss (SSNHL). OBJECTIVE To investigate the therapeutic efficacy over time of ITD as salvage treatment in SSNHL. MATERIALS AND METHODS We retrospectively reviewed the medical records and audiograms of 99 SSNHL patients who were refractory to 2 weeks of oral steroid treatment, from August 2003 to October 2006. Patients were divided into those receiving no further treatment (control group) and those receiving ITD within 2 weeks (early-ITD), between 2 weeks and 1 month (mid-ITD), and between 1 and 2 months (late-ITD) after initial treatment failure. ITD was performed in the supine position on four separate occasions over the course of 2 weeks. Final assessment of hearing was carried out 3 months after outbreak of SSNHL. Hearing improvement was defined as a > 15 dB decrease in four-tone average (FTA). RESULTS Overall hearing improvement was observed in 8 of 50 (16.0%) control patients, 7 of 16 (43.8%) early ITD patients, 6 of 20 (30.0%) mid ITD patients, and 2 of 13 (15.4%) late ITD patients.

Zinc deficiency may be a cause of burning mouth syndrome as zinc replacement therapy has therapeutic effects

BACKGROUND Zinc is known to play an important role for growth and development, the immune response, neurological function, and reproduction. Although the etiology of burning mouth syndrome (BMS) is unknown, zinc deficiency may be implicated in the pathogenesis of BMS. The aim of this study was to demonstrate a causal relationship between zinc deficiency and BMS and to assess whether zinc replacement is an effective therapy for BMS. METHODS Serum zinc level was evaluated in 276 patients with BMS. To assess the therapeutic effect of zinc replacement, patients with zinc deficiency were administered a zinc supplement (14.1 mg/day). Pain intensity 6 months after zinc replacement was evaluated using an 11-point numerical scale. We also developed an animal model of zinc deficiency to assess the effects of zinc deficiency on the oral mucosa. RESULTS Of the 276 patients with BMS, 74 (26.8%) had low serum zinc levels. Zinc replacement therapy lowered the mean numerical pain scale in these patients from 8.1 to 4.1, compared with a mean decrease from 7.7 to 6.7 in a control group (P = 0.004). In our animal model of zinc deficiency, the main pathologic findings were hyperkeratinization and increased mitosis on the dorsum of the tongue, although there were no gross oral mucosal lesions. CONCLUSIONS Zinc deficiency might play a role in some patients with BMS. In such patients, appropriate zinc replacement therapy is effective in relieving symptoms.

Radioresistant Cancer Cells Can Be Conditioned to Enter Senescence by mTOR Inhibition

Autophagy is frequently activated in radioresistant cancer cells where it provides a cell survival strategy. The mTOR inhibitor rapamycin activates autophagy but paradoxically it also enhances radiosensitivity. In this study, we investigated the mechanisms of these opposing actions in radiation-resistant glioma or parotid carcinoma cells. Radiation treatment transiently enhanced autophagic flux for a period of 72 hours in these cells and treatment with rapamycin or the mTOR inhibitor PP242 potentiated this effect. However, these treatments also increased heterochromatin formation, irreversible growth arrest, and premature senescence, as defined by expression of senescence-associated β-galactosidase activity. This augmentation in radiosensitivity seemed to result from a restoration in the activity of the tumor suppressor RB and a suppression of RB-mediated E2F target genes. In tumor xenografts, we showed that administering rapamycin delayed tumor regrowth after irradiation and increased senescence-associated β-galactosidase staining in the tumor. Our findings suggest that a potent and persistent activation of autophagy by mTOR inhibitors, even in cancer cells where autophagy is occurring, can trigger premature senescence as a method to restore radiosensitivity.

Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence

Radiotherapy is one of the well-established therapeutic modalities for cancer treatment. However, the emergence of cells refractory to radiation is a major obstacle to successful treatment with radiotherapy. Many reports suggest that inhibitors targeting the mechanistic target of rapamycin (MTOR) can sensitize cancer cells to the effect of radiation, although by which mechanism MTOR inhibitors enhance the efficacy of radiation toward cancer cells remains to be elucidated. Our studies indicate that a potent and persistent activation of autophagy via inhibition of the MTOR pathway, even in cancer cells where autophagy is occurring, can trigger premature senescence, cellular proliferation arrest. Combined treatment of MTOR inhibitor and radiation induce heterochromatin formation, an irreversible growth arrest and an increase of senescence-associated GLB1 (β-galactosidase) activity, which appear to result from a constant activation of TP53 and a restoration in the activity of retinoblastoma 1 protein (RB1)-E2F1. Thus, this study provides evidence that promoting cellular senescence via inhibition of the MTOR pathway may serve as an avenue to augment radiosensitivity in cancer cells that initiate an autophagy-survival mode to radiotherapy.

p16 immunohistochemistry alone is a better prognosticator in tonsil cancer than human papillomavirus in situ hybridization with or without p16 immunohistochemistry.

Abstract Conclusions: p16 immunohistochemistry (IHC) status correlated with less exposure to smoking and/or alcohol in Korean patients with locally advanced tonsillar squamous cell carcinoma (TSCC), and was an independent prognostic factor for survival. Objective: TSCC is more likely to be human papillomavirus (HPV)-positive than other head and neck squamous cell carcinoma (HNSCC) subtypes. The objective of this study was to ascertain the HPV status of TSCC in Korean patients and to determine its relationship with clinical parameters and prognosis. Methods: The locally advanced TSCCs of 79 patients who were treated between 2000 and 2008 were tested by p16 IHC and HPV in situ hybridization (ISH) with a tissue microarray. Results: Sixty-three patients (80%) were positive for p16 IHC, while 54 (68%) were positive by HPV ISH. p16 IHC status correlated significantly with lower exposure to smoking and alcohol (p < 0.05) but did not correlate with T and N stage classification, histological differentiation, age, or gender. The p16-positive group had a significantly higher 5-year overall survival rate in comparison with the p16-negative group (78% vs 63%, hazard ratio (HR) = 0.347, 95% CI = 0.14, 95% Cp = 0.025). p16 IHC was a favorable independent prognostic factor for overall survival, even after adjustment for age and T stage (HR = 0.283, 95% CI = 0.103, 95% p = 0.015).

Lipo-prostaglandin E1 in combination with steroid therapy is effective for treatment of sudden sensorineural hearing loss in Korean patients with Type 2 diabetes

Background  Diabetes mellitus is a risk factor for sudden sensorineural hearing loss (SSNHL), possibly as a result of microvascular damage, increased blood viscosity and embolic and thrombotic episodes.

Detection of the primary lesion in patients with cervical metastases from unknown primary tumors with narrow band imaging endoscopy: Preliminary report

We investigated whether the addition of narrow band imaging (NBI) to standard diagnostic workups could enhance the detection of primary lesions in patients with carcinoma of unknown primary (CUP).

Patterns of lymph node metastasis and their influence on outcomes in patients with submandibular gland carcinoma.

Little is known about lymph node metastasis and the extent of neck dissection (ND) in patients with submandibular gland (SMG) carcinoma. We therefore evaluated the metastatic topography of neck lymph nodes in patients with SMG carcinoma and the influence of metastases on tumor recurrence and patient survival.

Impact of adenotonsillectomy on nocturnal enuresis in children with sleep-disordered breathing: A prospective study.

To investigate the relationship between sleep‐disordered breathing (SDB) and nocturnal enuresis (NE) in children and to prospectively evaluate the effectiveness of adenotonsillectomy on resolving enuresis in indicated SDB patients with NE.

Epithelial-Mesenchymal Transition Clinical Implications for Nodal Metastasis and Prognosis of Tongue Cancer

Objective The development of biomarkers for the prediction of lymph node metastasis and prognosis is critical for deciding the treatment modality of tongue cancer. The purpose of our study is to investigate the clinical implications of epithelial-mesenchymal transition (EMT) expression in tongue cancer. Study Design Historical cohort study Setting Tertiary-care hospital. Subjects and Methods The study included 95 subjects with tongue cancer who underwent wide excision and neck dissection. According to characteristics of immunohistochemical staining for E-cadherin and vimentin, we classified the tumors as complete EMT phenotype, incomplete EMT phenotype, or epithelial phenotype. The correlation between risk factors and nodal metastasis was assessed, and disease-free survival (DFS) was analyzed. Results Positive lymph nodes were detected in 46 (48.4%) patients and was found to correlate significantly with depth of invasion ≥4 mm and EMT expression on multivariate analysis (P = .030, P = .022, respectively). The mean follow-up period of all patients was 96.3 months (range, 6-149 months). Overall 5-year DFS was 61.7%. On multivariate analysis, the only factors affecting DFS were nodal stage and EMT expression (P = .033, P = .021, respectively). Conclusions Our study reveals that EMT expression is a significant biomarker for predicting lymph node metastasis and tumor recurrence in tongue cancer. Evaluation of EMT expression in tongue cancer can allow therapy to be offered accordingly.