Jun Hyuk Hong

A Double-Blind Crossover Study Evaluating the Efficacy of Korean Red Ginseng in Patients With Erectile Dysfunction: A Preliminary Report

PURPOSE We investigated the efficacy of Korean red ginseng for erectile dysfunction using the International Index of Erectile Function, RigiScan (UroHealth Systems, Laguna Niguel, California), hormonal levels and penile duplex ultrasonography with audiovisual sexual stimulation. MATERIALS AND METHODS A total of 45 patients with clinically diagnosed erectile dysfunction were enrolled in a double-blind, placebo controlled, crossover study (8 weeks on treatment, 2 weeks of washout and 8 weeks on treatment) in which the effects of Korean red ginseng and a vehicle placebo were compared using multiple variables. The ginseng dose was 900 mg. 3 times daily. RESULTS Mean International Index of Erectile Function scores were significantly higher in patients treated with Korean red ginseng than in those who received placebo (baseline 28.0 +/- 16.7 and 38.1 +/- 16.6 versus 30.9 +/- 15.7, p <0.01). Scores on questions 3 (penetration) and 4 (maintenance) were significantly higher in the ginseng than in the placebo group (p <0.01). In response to the global efficacy question 60% of the patients answered that Korean red ginseng improved erection (p <0.01). Among other variables penile tip rigidity on RigiScan showed significant improvement for ginseng versus placebo. CONCLUSIONS Our data show that Korean red ginseng can be as effective alternative for treating male erectile dysfunction.

The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo.

Curcumin has become a focus of interest with regard to its antitumor effects in prostate cancer; however, the effects of this agent on invasion and metastasis remain less well understood. Matrix metalloproteinases (MMPs) are important prerequisite for tumor invasion and metastasis. In this study, we evaluated the effects of curcumin on prostate cancer cells (DU-145) invasion in both in vitro and in vivo. We utilized zymography and ELISA in order to determine the MMP-2 and MMP-9 activity. Matrigel invasion assay was performed to assess cellular invasion. We developed a xenograft model to examine tumorigenicity. Curcumin treatment resulted not only in a significant reduction in the expression of MMP-2 and MMP-9, but also effected the inhibition of invasive ability in vitro. Curcumin was shown to induce a marked reduction of tumor volume, MMP-2, and MMP-9 activity in the tumor-bearing site. The metastatic nodules in vivo were significantly fewer in the curcumin-treated group than untreated group. Curcumin appears to constitute a potential agent for the prevention of cancer progression, or at least of the initial phase of metastasis, in prostate cancer.

The Efficacy and Safety of Sunitinib in Korean Patients with Advanced Renal Cell Carcinoma: High Incidence of Toxicity Leads to Frequent Dose Reduction

OBJECTIVE The effects of sunitinib in a broad patient population, especially those of Asian ethnicity, have been rarely investigated. Here, we assessed the efficacy and safety of sunitinib in Korean patients with advanced renal cell carcinoma. METHODS Between April 2006 and August 2008, 77 Korean patients with advanced renal cell carcinoma were treated with sunitinib. We performed retrospective analysis for efficacy in terms of survival outcomes and response rate. Toxicity profiles were also assessed. RESULTS A total of 65 patients, including 39 (60%) patients without previous cytotoxic or immunotherapy, were eligible for the analysis. In 53 patients with measurable lesions, the objective response rate was 43% and disease control was achieved in 46 (86%) patients. The median time to treatment failure, time to progression and overall survival were 7.0, 11.8 and 22.8 months, respectively, with a median follow-up of 26.8 months in surviving patients. The most common treatment-related adverse events were fatigue (81%) and stomatitis (60%). The most common Grade 3 or 4 adverse events were hand-foot syndrome (16%), thrombocytopenia (16%) and stomatitis (10%). Dose reduction was required in 46% of patients. CONCLUSIONS The efficacy was similar to a previous Phase III trial and a safety profile of sunitinib was manageable in Korean patients with advanced renal cell carcinoma, although the incidence of dose reduction and Grade 3 or 4 adverse events were higher than those of western reports. Future studies should investigate the ethnic differences in toxicity profiles of sunitinib.

High-intensity focused ultrasound therapy for clinically localized prostate cancer

The efficacy of high-intensity focused ultrasound (HIFU) used for the treatment of localized prostate cancers has been demonstrated over the past decade. We present our early results after HIFU used as a single session in patients with clinically localized prostate cancer. A total of 58 patients were treated using the Ablatherm HIFU device with or without transurethral resection of the prostate (TURP). HIFU failure was defined as the presence of a cancer remnant on repeated biopsies or three consecutive increases in the prostate-specific antigen (PSA) ⩾1.0 ng/ml. The mean follow-up was 14 months (range, 6–21 months). After HIFU treatment, 78% of patients had a decreased PSA level to <0.5 ng/ml within 3 months. The median value of the last PSA was 0.6 ng/ml and the median nadir PSA was 0.2 ng/ml. The success rates of HIFU were 85, 77 and 47% in low-, intermediate- and high-risk groups, respectively. The HIFU failure rate was closely associated with clinical stage, presence of cancer on TURP chips and nadir PSA on univariate analysis. However, the only significant predictor for HIFU failure was the nadir PSA value by multivariate Cox regression analysis. The operation-related complications were minimal. Although both the period and number of patients were limited to evaluate the clinical efficacy, HIFU appears to be a safe and effective treatment option in selected patients with prostate cancer.

The Value of Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy

PURPOSE We evaluated the value of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma in the targeted therapy era. MATERIALS AND METHODS We reviewed the records of 78 patients treated with targeted therapy for metastatic renal cell carcinoma between 2006 and 2009. A total of 45 patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 33 were treated with targeted therapy alone (noncytoreductive nephrectomy group). We estimated progression-free and overall survival using Kaplan-Meier curves. The prognostic significance of each variable was estimated with a Cox proportional hazards regression model. RESULTS Clinicopathological variables did not differ in the 2 groups except for Karnofsky performance status and sarcomatoid feature. The treatment response rate did not differ in the 2 groups (23.1% vs 30.3%, p = 0.488). Median progression-free survival was 11.7 and 9.0 months in the cytoreductive and noncytoreductive nephrectomy groups (p = 0.270), and median overall survival was 21.6 and 13.9 months, respectively (p = 0.128). On multivariate analysis Karnofsky performance status (HR 2.9, 95% CI 1.4-5.7, p = 0.003) and sarcomatoid features (HR 2.9, 95% 1.3-6.7, p = 0.013) were independent predictors of progression-free survival. Karnofsky performance status (HR 3.3, 95% 1.7-6.5, p = 0.001), sarcomatoid features (HR 2.7, 95% 1.2-6.2, p = 0.021) and liver metastasis (HR 2.7, 95% 1.0-7.1, p = 0.045) were independent predictors of overall survival. CONCLUSIONS We found no significant differences in tumor response or survival between the 2 groups. Prospective trials are needed to confirm our results.

Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells

Recently, studies have investigated the significance of the Wnt/β-catenin pathway in prostate cancer. The transcriptional activity of the androgen receptor (AR) is modulated by interaction with coregulators, one of which is β-catenin. Curcumin, a dietary yellow pigment of Curcuma longa, has emerged as having a chemopreventive role. Although curcumin has been shown to inhibit AR expression, its molecular mechanism has not been fully elucidated. In this study, whether curcumin mediates the Wnt/β-catenin signaling pathway with regard to AR/β-catenin interactions was studied. Curcumin was shown to induce significant inhibition of AR expression in a dose-dependent manner. Marked curcumin-induced suppression of β-catenin was shown in the nuclear and cytoplasmic extracts as well as whole cell lysates. Further analysis revealed that phosphorylation of Akt and glycogen synthase kinase-3β were attenuated, but phosphorylated β-catenin was increased after curcumin treatment. Finally, cyclin D1 and c-myc, the target gene of the β-catenin/T-cell factor transcriptional complex, were also decreased. These findings suggest that curcumin modulates the Wnt/β-catenin signaling pathway and might have a significant role in mediating inhibitory effects on LNCaP prostate cancer cells.

The Protective Role of Renal Parenchyma as a Barrier to Local Tumor Spread of Upper Tract Transitional Cell Carcinoma and its Impact on Patient Survival

PURPOSE We investigated whether tumor location has independent prognostic significance in upper tract transitional cell carcinoma cases and which factor determines it. MATERIALS AND METHODS We reviewed data on 122 renal pelvis and 102 ureteral tumor cases, including the recurrence pattern. Tumor location and other clinicopathological variables were evaluated regarding cancer specific and recurrence-free survival. Stage pT3 tumors were stratified into those invading renal parenchyma or peripelvic/periureteral fat. RESULTS Overall 5-year cancer specific survival and recurrence-free survival rates were 77.0% and 71.6%, respectively, at a mean followup of 60.7 months. Of the clinicopathological parameters T stage was the most significant prognosticator of the survival rate, while nodal involvement, high grade and ureteral tumor location were also significant for lower survival rates. Stratification analysis for matching pathological stage revealed that, while survival rates were similar in the renal pelvis and ureteral tumor groups at stage pT2 or less, renal pelvic tumors were associated with significantly higher survival rates than ureteral tumors for stage pT3. Specifically renal pelvic tumors invading the renal parenchyma were associated with a lower local failure rate, and higher cancer specific and recurrence-free survival rates than tumors invading peripelvic or periureteral fat, ie 77.5% vs 49.7% 5-year cancer specific survival and 75.6% vs 32.0% 5-year recurrence-free survival (p = 0.014 and 0.003, respectively). CONCLUSIONS Tumor location is an independent prognostic factor for pT3 upper tract transitional cell carcinoma. The overall better prognosis of renal pelvic tumors was mainly attributable to pT3 tumor outcomes, specifically lesions invading the renal parenchyma. These findings may be due to the protective role of thick renal parenchyma against local tumor spread.

Prognostic Significance of Perinephric Fat Infiltration and Tumor Size in Renal Cell Carcinoma

PURPOSES It is controversial that perinephric fat infiltration has an impact on survival in patients with renal cell carcinoma. Therefore, we evaluated the influence of perinephric fat infiltration and tumor size on patient survival. MATERIALS AND METHODS We retrospectively reviewed the medical records of 783 and 77 patients with pT1-2 (cN0M0) and pT3a (cN0M0) renal cell carcinoma, respectively. Sporadic unilocular noncystic renal cell carcinoma was included. Univariate and multivariate analyses of prognostic factors, including perinephric fat infiltration, on cancer specific and disease-free survival were performed. Median followup was 56.0 months after surgery. RESULTS Patients with pT1-2 and pT3a tumors had a 5-year cancer specific survival rate of 96.1% and 84.9%, and a 5-year disease-free survival rate of 93.4% and 74.7%, respectively (each p <0.01). Age, tumor size and Fuhrman nuclear grade were independent prognostic factors for cancer specific and disease-free survival, whereas perinephric fat infiltration was significant only for disease-free survival. However, perinephric fat infiltration had a significant effect on cancer specific survival in patients with pT3a tumors more than 7 cm (p = 0.001). In contrast, patients with pT3a tumors 7 cm or less had cancer specific and disease-free survival similar to that of patients with pT2 tumors. Recurrence of pT3a tumors greater than 7 cm was observed in 44% of patients but in only 14.6% of those with pT3a tumors 7 cm or less (p = 0.029). In contrast to the recurrence of tumors 7 cm or less, recurrence of pT3a tumors more than 7 cm usually developed at multiple sites with a large tumor burden and it progressed rapidly. Consequently 85% of patients with recurrence of pT3a tumors larger than 7 cm died of renal cell carcinoma compared with 33% of those with recurrence of pT3a tumors 7 cm or less (p = 0.001). CONCLUSIONS In pT3a renal cell carcinoma tumor size was the strongest prognostic factor of disease-free and cancer specific survival. Perinephric fat infiltration was an independent prognostic factor for disease-free survival but not for cancer specific survival due to the less aggressive behavior of small (7 cm or less) pT3a tumors after recurrence. Tumor size and perinephric fat infiltration should be included in T3a renal cell carcinoma staging.

Urodynamic interpretation of changing bladder function and voiding pattern after radical prostatectomy: a long-term follow-up

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

Do molecular biomarkers have prognostic value in primary T1G3 bladder cancer treated with bacillus Calmette-Guerin intravesical therapy?

OBJECTIVES We examined whether altered protein expression for 7 potential biomarkers, including p53, pRb, PTEN, Ki-67, p27, FGFR3, and CD9, could predict tumor recurrence and progression in patients treated with bacillus Calmette-Guerin (BCG) therapy for primary stage T1 grade 3 (T1G3) bladder cancer (BC). MATERIALS AND METHODS The study included 61 patients with primary T1G3 BC who were treated with 6 weekly intravesical BCG instillations after clinically complete transurethral resection of bladder tumor between 1990 and 2007. All patients had proper muscle tissue in their specimen. Protein expression for 7 molecular biomarkers before BCG therapy was analyzed by immunohistochemistry based on tissue microarray methodology, and the percentage of positive cells was determined quantitatively in a blind fashion. Survival analysis was performed using Kaplan-Meier curves and Cox regression to determine the effect of each marker on recurrence-free survival (RFS) and progression-free survival (PFS) after BCG therapy. RESULTS Overall 5-year RFS and PFS rates were 56.0% and 84.5%, respectively, with a median follow-up of 60.0 months (range 6-217). The altered expression for each marker were noted in 53.3% for p53, 73.3% for pRb, 63.8% for PTEN, 40.0% for Ki-67, 66.1% for p27, 37.3% for FGFR3, and 47.5% for CD9, respectively. No significant association was found between altered marker status and clinicopathologic characteristics. While increased p53 expression was associated with progression after BCG therapy (5-year PFS rates: 90.7% in p53 < 10% vs. 78.7% in p53 ≥ 10%, P = 0.0495), no single marker was associated with RFS and PFS after BCG therapy in univariate and multivariate Cox regression analysis. Similarly, in subgroup analysis according to tumor size, multiplicity, and morphology, no single marker was associated with RFS and PFS. No difference was noted in molecular marker status between BCG responders and nonresponders. CONCLUSIONS Our findings indicate that immunohistochemical analysis for 7 potential molecular markers has no predictive value for recurrence and progression in primary T1G3 BC treated with BCG therapy. Large prospective studies are needed to validate the prognostic molecular markers in primary T1G3 BC.