Dong-Il Sun

Fractionated stereotactic radiotherapy as reirradiation for locally recurrent head and neck cancer.

PURPOSE We report early preliminary experience with CyberKnife radiosurgery (RS) as salvage treatment for locally recurrent head and neck cancer (HNC). METHODS AND MATERIALS Between March 2004 and August 2006, 36 patients (44 sites) were treated with CyberKnife RS as reirradiation for locally recurrent HNC. Treatment sites were as follows: nasopharynx (8), maxillary sinus (8), neck lymph nodes (8), skull base (7), nasal cavity (4), retropharyngeal lymph nodes (3), orbit (2), and others (4). Total doses administered were 18-40 Gy (median, 30 Gy) in 3 to 5 fractions to the 65%-85% isodose line for 3-5 consecutive days. Previous external radiation dose ranged from 39.6 to 134.4 Gy (median, 70.2 Gy). Gross tumor volume ranged from 0.2 to 114.9 cm(3) (median, 22.6 cm(3)). Median follow-up was 17.3 months. RESULTS Thirty-five of 44 sites were evaluated for response. Fifteen (42.9%) sites achieved complete response, 13 sites (37.1%) achieved a partial response, 3 (8.6%) sites maintained stable disease, and 4 sites (11.4%) showed tumor progression. Grade III acute complications were noted in 13 patients. Late complications were observed in three patients (1 bone necrosis, 2 soft tissue necrosis) during follow-up. CONCLUSION These preliminary results suggest that fractionated stereotactic radiosurgery is an effective treatment modality as a salvage treatment with good short-term local control. The early overall response rate is encouraging. However, more experience and a longer follow-up are necessary to determine the role of fractionated stereotactic radiosurgery as a salvage treatment of locally recurrent HNC and to define long-term complications.

Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma

Purpose: In this study, we tested the ability of a panel of hypermethylation markers to improve the sensitivity of histologic prostate cancer detection in sextant needle biopsies. Experimental Design: We obtained fresh-frozen sextant biopsies from 72 excised prostates and directly compared blinded histologic review and quantitative real-time methylation-specific PCR for hypermethylation of four genes, Tazarotene-induced gene 1 (TIG1), adenomatous polyposis coli (APC), retinoic acid receptor β2 (RARβ2), and glutathione S-transferase π (GSTP1) to detect the presence of prostate cancer. Results were compared with the final surgical pathological review of the resected prostates as the gold standard. Results: Histologic review alone detected carcinoma with a sensitivity of 64% (39 of 61 cases) and 100% specificity. Quantitative real-time methylation-specific PCR for TIG1, APC, RARβ2, and GSTP1 detected carcinoma with a sensitivity of 70%, 79%, 89%, and 75%, respectively, with 100% specificity for all of the genes. Using this panel of methylation markers in combination with histology resulted in the detection of 59 of 61 (97%) cases of prostate with 100% specificity, a 33% improvement over histology alone. Conclusion: The use of a panel of methylation markers as an adjunct to histologic review may substantially augment prostate cancer diagnosis from needle biopsies.

High-risk human papillomavirus and cervical lymph node metastasis in patients with oropharyngeal cancer.

The purpose of this study was to determine the role of high‐risk human papillomavirus (HPV) in lymph node metastasis and the depth of invasion in oropharyngeal cancer.

Relationship between vascular endothelial growth factor and Notch1 expression and lymphatic metastasis in tongue cancer.

Objective: To determine the role of angiogenesis in lymph node metastasis and the depth of invasion in early tongue cancer. Study Design: Retrospective analysis. Subjects and Methods: The study included 51 subjects with tongue cancer. Immunohistochemical staining for vascular endothelial growth factor, Notch1, and Notch3 was performed. Microvessel density was evaluated by counting the number of CD34-stained microvessels in each pathologic specimen. Results: Significant correlations were found between vascular endothelial growth factor and Notch1 expression and cervical lymph node metastasis (P = 0.020 and P < 0.009, respectively), tumor depth of invasion (P = 0.001 and P < 0.001, respectively), and microvessel density indicated by CD34 staining (P = 0.001 and P < 0.001, respectively). Nodal metastasis (P = 0.022), T stage (P = 0.002), and positive VEGF expression (P = 0.044) were statistically significant prognostic factors for disease-specific survival. Conclusion: Vascular endothelial growth factor and Notch1 expression are significantly related to cervical lymph node metastasis and depth of invasion in tongue cancer patients.

Bisacurone inhibits adhesion of inflammatory monocytes or cancer cells to endothelial cells through down-regulation of VCAM-1 expression.

Bisacurone, one of the active compounds of the traditionally used indigenous herb Curcuma longa Linne (Zingiberaceae), has anti-oxidant, anti-inflammatory, and anti-metastatic activities. We studied how the level of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules in the development of atherosclerosis as well as carcinogenesis and metastasis, might be affected by bisacurone in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Bisacurone dose-dependently inhibited TNF-alpha-mediated expression of VCAM-1. It showed significant suppressive effect on ROS generation in response to TNF-alpha stimulation and it blocked nuclear factor-kappa B (NF-kappaB) p65 translocation into the nucleus and phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also inhibited phosphorylation of Akt and PKC, which are upstream in the regulation of VCAM-1 by TNF-alpha. Furthermore, bisacurone decreased U937 monocyte and human oral cancer cell (Hep-2, QLL-I, SCC-15) adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of these cells by regulating the expression of critical adhesion molecules by TNF-alpha. Thus, bisacurone may be beneficial in the treatment of inflammatory diseases, such as atherosclerosis, where inflammatory monocytes are involved in their pathology, and, moreover, in the development of tumors.

Difference in expression of EGFR, pAkt, and PTEN between oropharyngeal and oral cavity squamous cell carcinoma.

OBJECTIVES The aims of this study were to evaluate the expression of EGFR, PI3K, Akt, mTOR, and PTEN in the oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. MATERIALS AND METHODS One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Marys Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used to detect the existence of human papillomavirus (HPV). RESULTS Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and two of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression was significantly higher in oral cavity cancers than in oropharyngeal cancers. Loss of PTEN occurred significantly more frequently in oral cavity cancers than in oropharyngeal cancers. The expression levels of PIK3CA, mTOR, and p53 did not differ significantly between the two cancers. Overexpression of EGFR and pAkt and loss of PTEN were observed more frequently in HPV-negative tumors. Multivariate Cox regression analysis showed that pAkt expression had a significantly unfavorable impact on relapse-free survival in oropharyngeal cancer. CONCLUSION We conclude that the expression levels of EGFR, pAkt, and PTEN differ between oropharyngeal and oral cavity cancer and it may be attributed to HPV-related molecular pathogenesis. The expression of pAkt might be an unfavorable prognostic marker for relapse-free survival in oropharyngeal cancer.

Combination of Voice Therapy and Antireflux Therapy Rapidly Recovers Voice-Related Symptoms in Laryngopharyngeal Reflux Patients

Objective. Patients with laryngopharyngeal reflux frequently experience voice-related symptoms. This study was designed to investigate the effectiveness of combined voice and medical therapy in comparison with medical therapy alone in the improvement of voice-related symptoms and parameters in patients with laryngopharyngeal reflux. Study Design. Concurrent nonrandomized comparative trial. Setting. Otolaryngology department at a university hospital. Subjects and Methods. In this prospective study, 100 patients diagnosed with laryngopharyngeal reflux with voice symptoms were divided into 2 groups: 50 patients were treated with medication alone, and 50 were treated with medication plus voice therapy. The following data were recorded before treatment and at 1, 2, and 3 months posttreatment: reflux symptom index (RSI), reflux finding score (RFS), voice handicap index (VHI), perceptual analysis, and acoustic analysis. The numbers of patients showing clinically significant reductions in these parameters were compared between groups using the following cutoff values: change in RSI ≥5, change in RFS ≥3, change in VHI ≥15, and change in grade, roughness, breathiness, asthenia, and strain scale (GRBAS) ≥1. Results. Significantly more patients in the study group showed a clinically significant change in RSI, VHI, and GRBAS score at the 1-, 2-, and 3-month follow-up evaluations. No clinically significant change in RFS was achieved in either group at 1 or 2 months, but a significantly greater change was achieved in the study group at 3 months. Conclusions. Voice therapy may help to restore reversible mucosal change secondary to acidic reflux, inducing rapid resolution of symptoms and shortening of the treatment period.

Factors That Predict Postoperative Pulmonary Complications After Supracricoid Partial Laryngectomy

OBJECTIVE To determine the risk factors related to postoperative pulmonary complications in patients who undergo supracricoid partial laryngectomy. DESIGN Retrospective analysis of medical records. SETTING Tertiary care referral center. PATIENTS One hundred eleven patients who underwent supracricoid partial laryngectomy from January 1, 1993, through December 31, 2008. MAIN OUTCOME MEASURES Relationship between postoperative pulmonary complications and perioperative risk factors, such as age, sex, chronic lung disease, smoking status, tumor site, tumor stage, preoperative irradiation, extent of surgery, reconstruction method, and pulmonary function tests. RESULTS Thirty-six patients (32.4%) developed postoperative pulmonary complications. Significant correlations were found among age (P = .002), chronic lung disease (P = .005), smoking status (P = .02), and postoperative pulmonary complications. Cricohyoidopexy (P = .008) and ipsilateral arytenoidectomy (P = .03) were associated with postoperative pulmonary complications. The multivariate analysis showed a significant association of the postoperative pulmonary complications with age (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.2-11.7 in patients 60 to 69 years old; and OR, 7.1; 95% CI, 1.3-37.6 in patients 70 to 79 years old) and cricohyoidopexy (OR, 4.4; 95% CI, 1.1-18.1). CONCLUSION Patients 60 years or older and patients with cricohyoidopexy are at high risk of having postoperative pulmonary complications after supracricoid partial laryngectomy.

Radiation Therapy Combined with (or without) Cisplatin-based Chemotherapy for Patients with Nasopharyngeal Cancer: 15-years Experience of a Single Institution in Korea

PURPOSE This retrospective study was carried out to evaluate the efficacy and toxicity of radiation therapy (RT) with/without cisplatin-based chemotherapy in nasopharyngeal cancer (NPC). MATERIALS AND METHODS One hundred forty six patients with NPC received curative RT and/or cisplatin-based chemotherapy. Thirty-nine patients were treated with induction chemotherapy (IC), including cisplatin and 5-fluorouracil followed by RT. Another 63 patients were treated with concurrent chemoradiotherapy (CCRT) using cisplatin, and 22 patients were treated with IC followed by CCRT. The remaining 22 patients were treated with RT alone. RESULTS One hundred four (80.0%) patients achieved complete response (CR), and 23 (17.7%) patients achieved partial response (PR). The patterns of failure were: locoregional recurrences in 21.2% and distant metastases in 17.1%. Five-year overall survival (OS) and progression free survival (PFS) were 50.7% and 45.0%, respectively. Multivariate Cox stepwise regression analysis revealed CR to chemoradiotherapy to be a powerful prognostic factor for OS. CR to chemoradiotherapy and completion of radiation according to the time schedule were favorable prognostic factors for PFS. A comparison of each treatment group (IC --> RT vs. CCRT vs. IC --> CCRT vs. RT alone) revealed no significant differences in the OS or PFS. However, subgroup analysis showed significant differences in both OS and DFS in favor of the combined chemoradiotherapy group compared with RT alone, for stage IV and T3-4 tumors. Grade 3-4 toxicities were more common in the combined chemoradiotherapy arm, particularly in the CCRT group. CONCLUSIONS This study was limited in that it was a retrospective study, much time was required to collect patients, and there were imbalances in the number of patients in each treatment group. Combined chemoradiotherapy remarkably prolonged the OS and PFS in subgroup patients with stage IV or T3-4 NPC.

Cell growth inhibition and down-regulation of survivin by silibinin in a laryngeal squamous cell carcinoma cell line.

Objectives: Abnormalities in the regulation of apoptotic cell death have been shown to have an important effect on the pathogenesis and progression of cancer. Survivin, which is identified in most cancers and has recently been identified as an inhibitor of apoptosis, is a potential therapeutic target for cancer management. We investigated cell growth, apoptosis, and expression of survivin in laryngeal squamous cell carcinoma cell lines after treatment with the bioactive compound silibinin. Methods: Cultured human laryngeal squamous cell carcinoma SNU-46 cells were treated with different concentrations of silibinin, and the degree of cell growth and apoptosis was analyzed. Additionally, survivin protein and messenger RNA were analyzed by Western immunoblotting and reverse transcription–polymerase chain reaction. Results: Silibinin inhibited the growth of SNU-46 cells in a both dose- and time-dependent manner (p < 0.01). Upon fluorescence-activated cell sorter analysis, silibinin (200 μmol/L) treatment increased the proportion of apoptotic cells from 7% to 40%. At high concentrations (more than 150 μmol/L), silibinin greatly reduced messenger RNA and protein expression of survivin. Conclusions: Our findings demonstrate that silibinin induced apoptosis of laryngeal squamous carcinoma cells by a mechanism involving decreased survivin expression, which suggests the possibility that silibinin may be an effective treatment of laryngeal cancers.