Myung Jin Ban

Endoscopic supraomohyoid neck dissection via a retroauricular or modified facelift approach: Preliminary results

Based on our previous experiences with endoscopic or robotic neck surgery utilizing the retroauricular (RA) or modified facelift (MFL) approach, we realized the value of verifying the feasibility of endoscopic supraomohyoid neck dissection (SOND). Therefore, the purpose of this study was to evaluate the potential role of endoscopic SOND.

Hypoxia Induces Epithelial-Mesenchymal Transition in Follicular Thyroid Cancer: Involvement of Regulation of Twist by Hypoxia Inducible Factor-1α.

Purpose Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poor prognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroid cancer. We showed that hypoxia inducible factor-1α (HIF-1α) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1α-induced invasive characteristics. Materials and Methods Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on HIF-1α, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-time PCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functional character of EMT. The involvement of HIF-1α and Twist in EMT were studied using gene overexpression or silencing. After orthotopic nude mouse model was established using the cells transfected with lentiviral shHIF-1α, tissue analysis was done. Results Hypoxia induces HIF-1α expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentin expression. We showed that overexpression of HIF-1α via transfection resulted in the aforementioned changes without hypoxia, and repression of HIF-1α with RNA interference suppressed hypoxia-induced HIF-1α and EMT. Furthermore, we also observed that Twist expression was regulated by HIF-1α. These were confirmed in the orthotopic FTC model. Conclusion Hypoxia induced HIF-1α, which in turn induced EMT, resulting in the increased capacity for invasion and migration of cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategy to prevent invasive and metastatic FTC.

Comprehensive application of robotic retroauricular thyroidectomy: The evolution of robotic thyroidectomy.

As an evolvement of the robotic application to the thyroidectomy, we sought to seek the potential role of robotic thyroidectomy with the retroauricular (RA) approach prior to future comparative study between RA and transaxillary thyroidectomy. This study aims to verify the surgical feasibility of robotic RA thyroidectomy.

c-Met-mediated reactivation of PI3K/AKT signaling contributes to insensitivity of BRAF(V600E) mutant thyroid cancer to BRAF inhibition.

BRAF (V600E) mutation is the most commonly detected genetic alteration in thyroid cancer. Unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response in thyroid cancer is reported to be low. The purpose of this study is to investigate the resistance mechanism responsible for this low treatment response to BRAF inhibitor in order to maximize the effect of targeted therapy. We examined the expression of feedback regulation mechanisms and alterations in the upper signal transduction pathway in thyroid cancer cell lines harboring BRAF mutation. Also, we investigated the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C (anaplastic thyroid cancer) and BCPAP (papillary thyroid cancer) were selected and treated with PLX4032 and its drug sensitivity were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on orthotopic xenograft mouse models. Unlike BCPAP cells, 8505C cells presented drug resistance to PLX4032 treatment and this was mainly due to increased expression of c‐Met. Effective inhibitions of c‐Met, p‐AKT, and p‐ERK were achieved after dual treatment with BRAF inhibitor (PLX4032) and c‐Met inhibitor (PHA665752). Similar results were confirmed by in vivo study with orthotopic xenograft mouse model. c‐Met‐mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF (V600E) mutant anaplastic thyroid cancer cells to PLX4032. Dual inhibition of BRAF and c‐Met leads to sustained treatment response.

The Efficacy of Fibroblast Growth Factor for the Treatment of Chronic Vocal Fold Scarring: From Animal Model to Clinical Application

Objectives This study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition. Methods FGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post-injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection. Results FGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (P<0.05). In the clinical trial, significant improvements in the majority of the subjective and objective voice parameters were registered 3 months after FGF injection and were maintained at 12 months. Complications associated with the FGF injections, such as granuloma, were not observed during the follow-up period. Conclusion Based on the animal model and the prospective clinical trial, vocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring.

The effects of single‐dose dexamethasone on inflammatory response and pain after uterine artery embolisation for symptomatic fibroids or adenomyosis: a randomised controlled study

To investigate the effects of single‐dose intravenous dexamethasone on inflammatory responses, pain, nausea, and vomiting after uterine artery embolisation (UAE).

Learning Curve for Robot-Assisted Neck Dissection in Head and Neck Cancer A 3-Year Prospective Case Study and Analysis

IMPORTANCE Robot-assisted neck dissection (RAND) for the management of regional metastases is a recently developed technique in the field of head and neck cancer that uses a robotic surgical system. This is the first report that estimates the learning curve for RAND. OBJECTIVES To evaluate a learning curve for RAND according to the types of neck dissection and report clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS Prospective case study of 90 patients undergoing neck dissection between May 2010 and April 2013 at a university tertiary referral center. INTERVENTIONS Fifty modified radical neck dissections (MRNDs) and 40 supraomohyoid neck dissections (SONDs) were performed by a single surgeon using a robotic surgical system to treat head and neck cancer. The MRND and the SOND groups were subdivided into 5 and 4 consecutive subgroups of 10 patients each, respectively. MAIN OUTCOMES AND MEASURES Perioperative parameters were compared, including mean operation time, duration and amount of drainage, length of hospital stay, and postoperative complications. RESULTS Significant decreases in mean operation time were observed as experience performing RAND increased in both the MRND and the SOND groups. The mean operation time for the MRND group decreased by 29% over the course of our study (initial subgroup, 298.1 minutes; last subgroup, 212.4 minutes). The mean operation time for the SOND group decreased by 53% over the course of our study (initial subgroup, 226.5 minutes; last subgroup, 106.1 minutes). There were no significant differences between subgroups for the other perioperative parameters. CONCLUSIONS AND RELEVANCE We explored the RAND learning curve in a single institution over a 3-year period. This study can be used as a timeline reference for institutions where the RAND procedure will be adopted as an alternative procedure.

Therapeutic Effects of Carbogen Inhalation and Lipo-Prostaglandin E1 in Sudden Hearing Loss

Purpose Vascular disorders and viral infections are considered the main causes of sudden hearing loss (SHL), although its pathogenesis remain unclear. Treatments include carbogen inhalation and lipo-prostaglandin E1 (lipo-PGE1), both of which have circulation-enhancing effects. We investigated the effectiveness of carbogen inhalation and lipo-PGE1 in SHL. Materials and Methods This retrospective review included 202 patients with idiopathic SHL who visited our clinic within 14 days of symptom onset between January 2006 and June 2010. All patients received oral prednisolone for 10 days. Of the 202 patients, 44 received no additional treatment, 106 received additional carbogen inhalation, and 52 received additional lipo-PGE1. Hearing improvement was measured using Siegels criteria. Results Overall recovery rates were 67.9% in the carbogen group, 53.8% in the lipo-PGE1 group, and 52.3% in the steroid-only control group (p=0.097). Limited to type 1 and type 2 categories of Sigelss criteria, the carbogen group had a significantly higher recovery rate (53.8%) than the lipo-PGE1 group (26.9%) and the steroid-only control group (38.6%) (p=0.005). Conclusion Carbogen inhalation added to steroid was a more effective treatment than lipo-PGE1 added to steroid or steroid alone in patients with SHL.

Acquired resistance to BRAF inhibition induces epithelial-to-mesenchymal transition in BRAF (V600E) mutant thyroid cancer by c-Met-mediated AKT activation

Previously, the authors have identified that c-Met mediates reactivation of the PI3K/AKT pathway following BRAF inhibitor treatment in BRAF (V600E) mutant anaplastic thyroid cancer, thereby contributing to the acquired drug resistance. Therefore dual inhibition of BRAF and c-Met led to sustained treatment response, thereby maximizing the specific anti-tumor effect of targeted therapy. The present study goes one step further and aims to investigate the effect of acquired resistance of BRAF inhibitor on epithelial-to-mesenchymal transition (EMT) in BRAF mutant thyroid cancer cells and the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C and BCPAP were selected and treated with BRAF inhibitor, PLX4032 and its effect on EMT were examined and compared. Further investigation was carried out in orthotopic xenograft mouse models. Unlike BCPAP cells, the BRAF inhibitor resistant 8505C cells showed increased expressions of EMT related markers such as vimentin, β-catenin, and CD44. The combinatorial treatment of PLX4032 and PHA665752, a c-Met inhibitor reversed EMT. Similar results were confirmed in vivo. c-Met-mediated reactivation of the PI3K/AKT pathway contributes to the drug resistance to PLX4032 in BRAF (V600E) mutant anaplastic thyroid cancer cells and further promotes tumor cell migration and invasion by upregulated EMT mechanism. Dual inhibition of BRAF and c-Met leads to reversal of EMT, suggesting a maximal therapeutic response.

Prognostic Factors and Treatment Outcomes of Parotid Gland Cancer: A 10-Year Single-Center Experience.

Objective To investigate the treatment outcomes of parotid gland cancer at a single center over a 10-year period and to evaluate the prognostic significance of maximum standardized uptake value. Study Design Retrospective case series with chart review. Setting Academic care center. Subjects and Methods Ninety-eight patients with primary parotid gland cancer who were surgically treated at Yonsei University Head & Neck Cancer Clinic between January 1999 and December 2008 were analyzed. Patient data were collected retrospectively from medical charts. The investigators analyzed the association of clinicopathological factors and maximum standardized uptake value on 18F-fluorodeoxyglucose positron emission tomography–computed tomography scan with disease-specific survival. Results Mean patient age was 49.7 years. Mean follow-up was 48.8 months. Thirty-three, 40, 30, and 23 patients had stage I, II, III, and IVA disease, respectively. Mucoepidermoid carcinoma was the most common histologic type (34.7%), followed by acinic cell carcinoma (27.6%). Eighteen patients (18.4%) experienced recurrences (mean recurrence gap, 20.6 months; range, 2-87 months). Five- and 10-year disease-specific survival rates were 93.6% and 81.8%, respectively. In the univariate analysis, pathologic T stage, pathologic lymph node status, resection margin, external parenchymal extension, and maximum standardized uptake value were significantly associated with disease-specific survival. Pathologic lymph node status and maximum standardized uptake value were independent prognostic factors in the multivariate analysis. Conclusion Our single-center experience with parotid gland cancer treatment is consistent with the literature. Cervical lymph node metastasis and high maximum standardized uptake value are associated with poor survival in parotid gland cancer.