In Rae Cho

The Different Reduction Rate of Prostate-Specific Antigen in Dutasteride and Finasteride

Purpose To compare and analyze the therapeutic effects and changes in the prostate-specific antigen (PSA) level with treatment with finasteride or dutasteride for benign prostatic hyperplasia (BPH) for 1 year. Materials and Methods We retrospectively investigated patients who suffered from BPH for 1 year between January 2005 and December 2008. For treatment groups, we divided the patients into two groups: one was treated with alfuzosin and finasteride and the other was treated with alfuzosin and dutasteride. At the beginning of treatment, the patients underwent transrectal ultrasonography and measurement of urine flow rate, residual urine volume, PSA, and International Prostate Symptom Score (IPSS). Patients with diseases affecting urinary function were excluded. We not only analyzed the data at the time of initial treatment, but also after 1 year of treatment. A total of 219 patients were able to be evaluated for 1 year. Results Both finasteride and dutasteride reduced PSA and prostate volume significantly. The comparison between groups showed a more significant reduction of PSA (p=0.020) and prostate volume (p=0.052) in the dutasteride group. Other parameters did not differ significantly between the groups. Conclusions 5-α Reductase inhibitors for BPH treatment reduced PSA and prostate volume significantly when the patients were treated for 1 year. Administration of dutasteride is considered to be more effective in reducing PSA and prostate volume. Therefore, dutasteride should not be considered equivalent to finasteride in the reduction rate of PSA. The intensity of dutasteride must be reevaluated in comparison with finasteride.

A prospective study of reducing unnecessary prostate biopsy in patients with high serum prostate-specific antigen with consideration of prostatic inflammation.

Purpose We aimed to reduce unnecessary prostatic biopsy in patients with high prostate-specific antigen (PSA) by consideration of prostatic inflammation. Materials and Methods The investigation was conducted prospectively in 413 patients with a PSA level of 4 to 10 ng/ml from January 2004 to December 2009. All patients underwent the expressed prostatic secretion (EPS) or voided bladder urine 3 (VB3) test to be classified into two groups: positive group and negative group. Patients with a positive result on the EPS or VB3 test were treated with antibiotics for 2 months, and in cases in which the PSA level remained high, we performed prostate biopsy. In patients with a negative result on the VB3 test, we performed prostate biopsy directly. Results Of the 413 study patients, 215 (52%) patients had positive findings on the EPS or VB3 test. After 8 weeks of antibiotics therapy, 53 of the 215 men avoided prostate biopsy because their PSA level was normalized. The other patients (162 of 215) still had elevated PSA levels of more than 4 ng/ml, including 7 patients in whom the biopsy revealed cancer. Patients with negative findings (198 of 413) underwent prostate biopsy. Of the 198 patients, 41 were diagnosed with prostate cancer. The total prostate cancer detection rate was 11.6% in our subjects, where as it was 20.7% in the patients with negative findings on the EPS or VB3 and 3.3% in the patients with positive findings, respectively. Conclusions In cases in which the PSA level is increasing, if we first exclude prostatitis and carry out a serial diagnostic procedure, it may help to reduce unnecessary prostatic biopsy.

Virulence Characteristics and Phylogenetic Background of Ciprofloxacin Resistant Escherichia coli in the Urine Samples from Korean Women with Acute Uncomplicated Cystitis

To clarify the characteristics of the virulence factors (VFs) of ciprofloxacin resistant Escherichia coli (CFRE) with acute uncomplicated cystitis (AUC), we determined the VFs and the phylogenetic background of all 54 CFRE strains and the 55 randomly selected ciprofloxacin sensitive E. coli strains (CFSE) from patients with AUC in 22 Korean hospitals. The prevalence of the VFs was as follows: fimA, papEF, papGIII, sfaI, dafaBC, cnf1, and hlyA were presented in 96%, 54%, 68%, 91%, 49%, 72%, and 29% of the samples, respectively. The expressions of papEF, cnf1, and hlyA were significantly more prevalent in the CFSE. Moreover, the expressions of cnf, and papEF significantly reduced the risk of ciprofloxacin resistance. The CFSE was also marginally associated with the group B2 (P=0.05). Although the presence of pyuria and a previous cystitis history were not related with the phylotyping and the expressions of VFs, group B2, and fimA and papEF were more expressed in the younger age patients (P<0.05). In conclusion, the CFRE exhibits a selective loss of VFs and the non-B2 phylotype in Korean AUC patients. The group B2 and the presence of fimA and papEF are associated with a younger age of AUC patients.

Clinical implication of serum C-reactive protein in patients with uncomplicated acute pyelonephritis as marker of prolonged hospitalization and recurrence.

OBJECTIVES To analyze the clinical value of C-reactive protein (CRP) as a marker of prolonged hospitalization and a predictor of recurrence in patients after uncomplicated acute pyelonephritis (APN). METHODS A total of 202 consecutive adult patients with APN were prospectively enrolled from September 2005 to June 2007. APN was defined as the concomitant presence of 4 major and >/=2 minor clinical or laboratory signs or symptoms suggestive of APN. All patients were treated with parenteral antibiotics. The patients were discharged after normalization of body temperature, serum white blood cell counts, and urinalysis. Correlations among the recurrence of APN and various factors, including CRP, were investigated. RESULTS Of the 202 patients, 13 were excluded because of the presence of complicating factors or insufficient data. APN recurrence developed in 4 patients (2.1%). The CRP level at discharge correlated significantly with the recurrence of APN on univariate and multivariate analysis. Irrespective of the normalization of body temperature, serum white blood cell counts, and urinalysis, the recurrence of APN was significantly greater in the patients with CRP >4 mg/dL than in those with <4 mg/dL at discharge. Patients with a maximal CRP of >15 mg/dL during admission had a longer hospitalization and required more intravenous antibiotic therapy than did the patients with a maximal CRP of <15 mg/dL. CONCLUSIONS As a marker of prolonged hospitalization and recurrence, CRP can complement the present clinical and laboratory parameters used as guides in the proper treatment of patients with uncomplicated APN.

Preoperative Clinical Factors for Diagnosis of Incidental Prostate Cancer in the Era of Tissue-Ablative Surgery for Benign Prostatic Hyperplasia: A Korean Multi-Center Review

Purpose To identify potential predictive factors of incidental prostate cancer (IPca) in patients considering tissue-ablation treatment for benign prostatic hyperplasia (BPH). Materials and Methods From the 11 centers, 1,613 men who underwent transurethral resection of the prostate (TURP) or open prostatectomy were included. Before surgery, prostate biopsy was performed in all patients with prostate-specific antigen (PSA) ≥4.0 ng/ml or with abnormal digital rectal examination (DRE) findings. The patients with prostate cancer preoperatively or with PSA >20 ng/ml were excluded. As predictive factors of IPca, age, body mass index, PSA, DRE, and transrectal ultrasonography (TRUS) findings, including total prostate volume (TPV), transition zone volume (TZV), and the presence of hypoechoic lesions, were reviewed. PSA density (PSAD) and PSAD in the transition zone (PSAD-TZV) were calculated. Results IPca was diagnosed in 78 patients (4.8%). DRE findings, PSA, and TZV were independent predictive factors in the multivariate analysis. In the receiver operating characteristic curve analysis of PSA, PSAD, and PSAD-TZV, the area under the curve (AUC) was the largest for PSAD-TZV (AUC, 0.685). Conclusions IPca was detected in 4.8% of the population studied. In addition to DRE findings, the combination of TZV and PSA can be useful predictive factors of IPca in patients considering tissue-ablation treatment as well as TURP.

Prostate-specific antigen velocity in healthy Korean men with initial PSA levels of 4.0 ng/mL or less.

OBJECTIVES To assess the longitudinal changes in serial prostate-specific antigen (PSA) levels in healthy Korean men with initial PSA levels of 4.0 ng/mL. METHODS The rate of PSA change or PSA velocity (PSAV) in 24 869 healthy men with an initial PSA level of 4.0 ng/mL or less who were clinically free of genitourinary disease was analyzed at intervals of at least 12 months. The influence of age, initial PSA level, and the interval between measurements was assessed. RESULTS The mean age, initial PSA level, interval between measurements, and change in PSA and PSAV was 46.2 years, 0.86 ng/mL, 21.9 months, and 0.03 ng/mL and 0.02 ng/mL/y, respectively. A cumulative frequency plot of PSAV demonstrated that 50%, 95%, and 97% of subjects had a PSAV of 0.01, 0.40, and 0.52 ng/mL/y or less, respectively. The PSAV correlated with age, initial PSA level, and interval between measurements. The percentage of men with a PSAV greater than 0.75 ng/mL/y was 0.61% (151 of 24 869) and was 0.51% (92 of 17 985) for those with an initial PSA level of less than 1.0 ng/mL, 0.86% (50 of 5807) for those with a PSA level of 1.1-2.0 ng/mL, and 0.84% (9 of 1077) for those with an initial PSA level of 2.1-4.0 ng/mL. CONCLUSIONS In healthy Korean men with an initial PSA level of 4.0 ng/mL or less, most will have a PSAV of less than 0.75 ng/mL/y. Thus, traditional PSAV cutoff values are not applicable in this population. We propose that a lower PSAV cutoff value should be used to indicate biopsy. Additional large-scale prospective studies, including biopsy data, are required to assess the cutoff value of PSAV for healthy Korean men with a PSA level of 4.0 ng/mL or less.

A multi-institutional study on histopathological characteristics of surgically treated renal tumors: The importance of tumor size

Purpose The incidence of accidentally detected small renal tumors is increasing throughout the world. In this multi-institutional study performed in Korea, histopathological characteristics of contemporarily surgically removed renal tumors were reviewed with emphasis on tumor size. Materials and Methods Between January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent surgical treatment at 14 training hospitals in Korea for radiologically suspected malignant renal tumors. Clinicopathological factors and patient survival were analyzed. Results Of the 1,702 tumors, 91.7% were malignant and 8.3% were benign. The percentage of benign tumors was significantly greater among those ≤ 4 cm (13.2%) than those > 4 cm (4.5%) (p < 0.001). Among renal cell carcinoma patients, the percentage of tumors ≤ classed as stage ≥ T3 was significantly less among tumors 4 cm (5.2%) than those > 4 cm (26.8%) (p < 0.001). The percentage of tumors classed as Fuhrmans nuclear grades ≥ 3 was also significantly less among tumors ≤ 4 cm (27.3%) than tumors > 4 cm (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrmans nuclear (p < 0.001) grade were the only independent predictors of cancer-specific survival. Conclusion In renal tumors, small tumor size is prognostic for favorable postsurgical histopathologies such as benign tumors, low T stages, and low Fuhrmans nuclear grades. Our observations are expected to facilitate urologists to adopt function-preserving approach in the planning of surgery for small renal tumors with favorable predicted outcomes.

Relationship between Prostate-Specific Antigen and Body Mass Index according to Age: Lower Prostate-Specific Antigen in Middle-Aged Overweight and Obese Korean Men

Objective: To analyze the relationship between serum prostate-specific antigen (PSA) and body mass index (BMI) according to age in a population of ostensibly healthy Korean men. Patients and Methods: Between 2002 and 2006, data from 13,025 men who visited health promotion centers were evaluated. All men underwent anthropometric measurements and serum PSA determination. The relationship between serum PSA and BMI according to age was analyzed. Results: The median age was 50.0 years and the median serum PSA level was 0.69 ng/ml. There was no relationship between serum PSA and BMI in the group whose BMI was <23 kg/m2. The serum PSA showed a significant inverse relationship in those with BMI of ≧23 kg/m2. However, this finding was only true among 40- to 59-year-old middle aged men and no such relationship between serum PSA and BMI was seen in the older groups (60–79 years of age). Conclusion: Our study revealed serum PSA had a significant inverse relationship with BMI in overweight and obese men aged between 40 and 59 years; however, there was no relationship between serum PSA and BMI in men whose age was older than 60 years.

MP98-18 INHIBITION OF HSP90 SYNERGISTICALLY POTENTIATES ANTITUMOR EFFECT OF NVP-BEZ235 AND SATRAPLATIN COMBINATION THERAPY IN CISPLATIN-RESISTANT HUMAN BLADDER CANCER CELLS THROUGH THE DOWN-REGULATION OF AKT AND ERK SIGNALING

INTRODUCTION AND OBJECTIVES: Chemoresistance to cisplatin is a principal cause of treatment failure and disease progression of advanced bladder cancer. In the present study we explore the novel relationship between cisplatin resistance and pyruvate kinase 2 (PKM2) e a rate-limiting enzyme responsible for Warburg effect in cancer cells, and whether down-regulating PKM2 by RNAi or small molecules reduces chemoresistance and enhances chemosensitivity of bladder cancer cells to cisplatin. METHODS: Cell lines from mouse and human bladder cancer and their derivatives expressing RNAi of PKM2 were assessed for their chemosensitivity to cisplatin or shikonin a chemical inhibitor of PKM2, or both. The effects and mechanisms of PKM2 inhibition on cisplatinresistance were examined. Cisplatin and shikonin as single or dual agents for inhibiting bladder cancer proliferation and metastasis were further tested in syngeneic mice. RESULTS: Shikonin binds PKM2 and inhibits bladder cancer cell proliferation in a dose-dependent but pyruvate kinase activity-independent manner. Down-regulation of PKM2 by shRNA blunts cellular responses to shikonin but enhances the responses to cisplatin. Shikonin and cisplatin together exhibit significantly greater growth inhibition and apoptosis than when used alone. Experimentally induced cisplatinresistance is strongly associated with PKM2 overexpression, and cisplatin-resistant cells respond sensitively to shikonin. In syngeneic mice, shikonin and cisplatin together, but not as single-agents, markedly reduces bladder cancer growth and lung metastases. CONCLUSIONS: PKM2 overexpression is a key mechanism of natural and acquired chemoresistance of bladder cancer to cisplatin. Inhibition of PKM2 via RNAi or chemical inhibitors may be a highly effective approach to overcome chemoresistance and improve the outcome of advanced bladder cancer.

MP40-20 RELATIONSHIP BETWEEN NON-TUMOR PROSTATE VOLUME AND RISK OF POSITIVE SURGICAL MARGIN IN ORGAN CONFINED PROSTATE CANCER

7 academic centers and included. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate risk PCa with a primary Gleason pattern of 4, a percentage of positive biopsy cores (PPBC) >50%, or >1 intermediate risk factors (IRFs) (cT2bec, PSA 10e20 or Gleason score 7) according to Zumsteg et al. (ref). Remaining PCa cases were classified as favorable. Pathological results were compared using Fisher’s exact test. Univariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS). RESULTS: Median follow up was 44.4 months (IC95%1⁄442.1; 47.0). Patients with UIR disease had poorer PSA-RFS (68.8vs 83.5%, HR: 2.05 (1.78; 2.36); p1⁄40.0193) compared with those with favorable disease. The need for adjuvant therapy was significantly higher in the UIR group. Primary Gleason pattern 4(HR: 2.38 [1.92;2.96], p1⁄40.00001), PPBC >50% (HR:1.28 [1.10 ;1.48], p1⁄40.0011), and >1 IRFs were significant predictors of increased PSA-RCF in multivariate analyses. CONCLUSIONS: Intermediate risk PCa is a heterogeneous group that can be easily and pre-operatively dichotomized into two separate risk groups demonstrating significant oncologic outcomes. This easy-to-use stratification could help physician in decision making and patient counseling.