The current status of hormone treatment for prostate cancer patients in Korean real-world practice: a multi-institutional observational study.

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

PURPOSE: To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). MATERIALS AND METHODS: Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. RESULTS: Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). CONCLUSIONS: PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

Clinicopathologic differences between prostate cancers detected during initial and repeat transrectal ultrasound-guided biopsy in Korea.

PURPOSE: The aim of this study was to investigate clinicopathologic differences between prostate cancer (PCa) detected at initial and repeat transrectal ultrasound-guided prostate biopsy in a large Korean cohort. MATERIALS AND METHODS: From 2000 through 2012, a total of 7,001 patients underwent transrectal ultrasound-guided prostate biopsy at 6 centers in Daegu and Gyeongbuk provinces. Of these 7,001 patients, the initial biopsy was positive for PCa in 2,118 patients. Repeat biopsy was performed in 374 of the 4,883 patients with an initial negative finding and a persistently elevated prostate-specific antigen (PSA) level, nodules or asymmetry by digital rectal examination (DRE), high-grade prostatic intraepithelial neoplasia, or atypical small acinar proliferation. Numbers of biopsy cores varied from 6 to 12 according to center and biopsy date. RESULTS: Cancer was diagnosed in 2,118 of the 7,001 patients (30.3%) at initial biopsy and in 86 of the 374 patients (23.0%) at repeat biopsy. The repeat biopsy rate was 5.3%. Mean PSA values were 68.7±289.5 ng/mL at initial biopsy and 18.0±55.4 ng/mL at repeat biopsy (p<0.001). The mean number of cancer-positive cores per biopsy was 5.5±3.5 for initial biopsy and 3.0±2.9 for repeat biopsy (p<0.001). Mean Gleason score was 7.5±1.4 at initial biopsy and 6.6±1.3 at repeat biopsy (p<0.001). For detected cancers, the low-stage rate was higher for repeat biopsy than for initial biopsy (p=0.001). CONCLUSIONS: Cancers detected at repeat biopsy tend to have lower Gleason scores and stages than cancers detected at initial biopsy. The present study shows that repeat biopsy is needed in patients with a persistently high PSA or abnormal DRE findings.

Adolescent varicocele: are somatometric parameters a cause?

PURPOSE: It has been reported that varicocele is found less frequently in obese men. Accordingly, we evaluated varicocele patients and statistically analyzed the correlation between varicocele and somatometric parameters. MATERIALS AND METHODS: A total of 211 patients underwent surgery for varicoceles. All patients underwent history taking, physical examination, and scrotal ultrasound to determine the presence and severity of varicocele. An age-matched control group consisted of 102 patients who were found not to have varicocele according to physical examinations and scrotal ultrasound. The age, weight, height, and body mass index (BMI) of the two groups were compared. The statistical analyses were performed by use of PASW Statistics ver. 18.0. A p-value of less than 0.05 was used for statistical significance. RESULTS: In the varicocele group, the mean age, height, weight, and BMI were 29.42±14.01 years, 168.53±9.97 cm, 62.14±13.17 kg, and 21.66±3.21 kg/m(2), respectively. The distribution of varicocele grade was as follows: 103 (48.8%) grade III, 72 (34.1%) grade II, and 36 (17.1%) grade I. In the control group, the mean age, height, weight, and BMI were 30.83±17.31 years, 161.93±19.83 cm, 64.69±17.86 kg, and 24.04±3.64 kg/m(2), respectively. Analyzing these data specifically in adolescents, they showed significant differences in age, height, and BMI (p=0.000, p=0.000, and p=0.004, respectively) between two groups. There were no significant differences in somatometric parameters between patients with different grades of varicocele. CONCLUSIONS: Our results showed that patients with varicoceles were significantly taller and had a lower BMI than did patients without varicoceles, especially among adolescents. Carefully designed future studies may be needed.

Renal function following curative surgery for renal cell carcinoma: who is at risk for renal insufficiency?

PURPOSE: To investigate the incidence and predictive factors associated with the development of chronic kidney disease (CKD) in patients undergoing curative surgery for renal cell carcinoma. MATERIALS AND METHODS: From 2003 to 2010, we retrospectively investigated 108 patients undergoing partial nephrectomy or radical nephrectomy (RN) for renal tumors with a preoperative glomerular filtration rate (GFR)≥60. The GFR was calculated by use of the four-variable modification of diet in renal disease (MDRD) formula. CKD was defined as an estimated GFR (eGFR) less than 60 mL/min per 1.73 m(2). Demographic and clinicopathologic parameters were evaluated by using the chi-square and Student t-tests and multivariate regression analysis to determine the variables independently associated with the development of postoperative CKD. RESULTS: Of the 108 patients without preoperative CKD, CKD developed in 43 patients (39.8%). In the analysis of clinical factors between patients with and those without CKD development, gender, body mass index, diabetes mellitus, hypertension, and tumor size were not significant clinical factors. Statistical significance for CKD development was found for age of 60 years or greater (p=0.013), decreased preoperative eGFR (p<0.001), and RN group (p<0.001). In the multivariate analysis, decreased preoperative eGFR (p=0.001) and RN group (p=0.002) were significant independent predictors. CONCLUSIONS: The results of our study show that decreased preoperative renal function and RN were significant independent predictors of postoperative CKD. In patients who had a relatively decreased preoperative eGFR, especially when estimated by use of the MDRD formula, nephron-sparing surgery should be considered for the treatment of small renal tumors.

Evaluation of bladder capacity in Korean children younger than 24 months: a nationwide multicenter study.

PURPOSE: Bladder capacity is an important factor in the diagnosis and treatment of children with voiding dysfunction. The purpose of this study was to define the normal maximal voided volume formula in Korean children younger than 2 years. METHODS: We measured the bladder capacities of 151 Korean children between 0 and 24 months of age (83 boys and 68 girls) who did not have clinical voiding dysfunction. The maximal voided volume was determined in all subjects using a 2-day frequency volume chart with a four-hour voiding observation. The largest voided volume for each patient was considered to be the maximal voided volume. Statistical analyses were carried out using linear regression analysis. RESULTS: The maximal voided volume increased with age and weight (P = 0.0001). There was no significant difference between males and females (P = 0.771). A formula that approximates bladder capacity with respect to age is the following: bladder capacity (ml) = [1.6 × age (months)] + 45 (t = 8.757, P = 0.0001). A formula that approximates bladder capacity with respect to weight is the following: bladder capacity (ml) = [4.1 × weight (kg)] + 28 (t = 10.152, P = 0.0001). CONCLUSIONS: These formulas may be useful for the diagnosis of abnormal bladder capacity and the evaluation of voiding dysfunction in Korean children younger than 24 months.

The inhibitory effect of chimeric decoy oligodeoxynucleotide against NF-κB and Sp1 in renal interstitial fibrosis.

The pathophysiology of chronic renal disease is characterized by a progressive loss of renal function and deposition of the extracellular matrix, leading to widespread tissue fibrosis. Much of the matrix in chronic renal disease is synthesized by interstitial myofibroblasts, recruited from resident fibroblasts and circulating precursors. These changes are believed to be derived from epithelial-mesenchymal transition (EMT) of tubuloepithelial cells. To develop a novel therapeutic approach for treating renal fibrosis, we examined the simultaneous inhibition of the transcription factors NF-κB and Sp1 in a mouse model of unilateral ureteral obstruction (UUO). To simultaneously inhibit both NF-κB and Sp1, we developed chimeric (Chi) decoy oligodeoxynucleotide (ODN) which contained binding sequences for both NF-κB and Sp1 in a single decoy molecule to enhance the effective use of decoy ODN strategy. Chi decoy ODN significantly attenuated tubulointerstitial fibrosis in a mouse model of UUO compared to scrambled decoy ODN, as demonstrated by the reduced interstitial volume, macrophage infiltration, and fibrosis-related gene expression. Interestingly, Chi decoy ODN also regulated EMT-related gene expression, leading to the inhibition of renal fibrotic changes in vivo and in vitro. The present study demonstrates the feasibility of Chi decoy ODN treatment for preventing renal fibrosis and EMT processes. This strategy might be useful to improve the clinical outcome after chronic renal disease.

Predicting factors of breakthrough infection in children with primary vesicoureteral reflux.

PURPOSE: Many pediatric urologists still favor using prophylactic antibiotics to treat children with vesicoureteral reflux (VUR). However, breakthrough infection sometimes occurs, leading to significant increases in morbidity as a result of renal scarring. Therefore, we tested whether abnormal renal scan and other factors are predictive of breakthrough infection using univariate analyses. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 163 consecutive children who were diagnosed with vesicoureteral reflux between November 1997 and June 2010. Clinical parameters for the statistical analysis included form of presentation, gender, age, VUR grade, laterality, presence of intrarenal reflux, class of antibiotic drug, and presence of abnormal renal scan by Dimercapto-succinic acid. Clinical parameters used for prognostic factors were established by univariate analyses. Fisher's exact test and unpaired t-test were done using SPSS software [SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA)]. RESULTS: Breakthrough infection developed in 61 children (48.0%). A total of 58 children (45.7%) had abnormal renal scans. Time to development of breakthrough infection was significantly longer in girls (9.0±8.2 months) than in boys (5.8±4.8 months, p<0.05). On univariate analysis, though statistically not significant, the most predictive factor of breakthrough infection was abnormal renal scan (p=0.062). In patients with abnormal renal scans, breakthrough infection was not associated with mode of presentation, gender, grade or prophylactic antibiotics. However, there was a significant difference between patients younger than 1 year and those 1 year old or older. Mean±SD age at diagnosis of VUR in patients with breakthrough infection (1.14±3.14) was significantly younger than in those without breakthrough infection (5.05±3.31, p=0.009). There was also a significant difference between patients with bilateral or unilateral reflux (p=0.028). CONCLUSION: Our data showed that abnormal renal scan was the most predictive factor of breakthrough infection and demonstrated statistical significance in patients under the age of 1 year. Parents and physicians should remain aware that these patients are at high risk of breakthrough urinary tract infection, which may potentially lead to renal damage.

Is increased prostatic urethral angle related to lower urinary tract symptoms in males with benign prostatic hyperplasia/lower urinary tract symptoms?

PURPOSE: The prostatic urethra is a bent tube, and the clinical significance of the prostatic urethral angle (PUA) was recently reported. We investigated the statistical significance of an increased PUA on the International Prostate Symptom Score (IPSS) in men with benign prostatic hyperplasia (BPH)/lower urinary tract symptom (LUTS). MATERIALS AND METHODS: A retrospective analysis was done of 270 men with BPH/LUTS from July 2009 to June 2011. Prostate volume, PUA, and intravesical prostatic protrusion (IPP) were measured by transrectal ultrasonography (TRUS). The IPSS was analyzed separately as storage and voiding symptom score. In order to minimize the effect of prostate size on voiding, patients with prostate size over 40 ml were excluded. RESULTS: The mean age was 62.0±9.3 years. The mean prostate volume was 29.0±5.5 ml (range, 20 to 40 ml), and median PUA and IPP were 34° (range, 12 to 52°) and 1.7 mm (range, 0 to 5.3 mm), respectively. The mean IPSS, mean IPSS-ss, and mean IPSS-vs were 19.0±8.2, 7.3±4.0, and 11.6±5.5, respectively. The prostate volume had no statistically significant correlation with IPSS, IPSS-ss, or IPSS-vs. IPP had a statistically significant correlation with IPSS (p<0.001), IPSS-ss (p<0.001), and IPSS-vs (p<0.001). PUA had no statistically significant correlation with IPSS or IPSS-ss. However, PUA had a significant correlation with IPSS-vs (p=0.047). Comparing a higher PUA (≥34°) with a lower PUA (<34°), patients with a higher PUA had a higher IPSS (p=0.001) and a higher IPSS-vs (p=0.001). There was no significant difference in IPSS-ss, prostate volume, or PSA between the two groups. CONCLUSIONS: IPP showed significantly correlated with the IPSS and voiding symptom score was affected by the PUA but not by the prostate volume. As the PUA increased, the patients' voiding symptoms worsened. Further study may be needed.

Primary Vesico-Ureteral Reflux: Comparison of Factors between Infants and Children.

PURPOSE: The association of age, sex and renal parenchymal damage (RPD) in vesicoureteral reflux (VUR) is well known. We compared various factors between infants and children in a cohort of patients with primary VUR. MATERIALS AND METHODS: Medical records of 147 patients diagnosed as VUR between 1997 and 2010 were reviewed. Of these children 91 (61.9%) were boys and 56 (38.1%) were girls. 99 (67.3%) of the 147 patients were younger (Group 1), and 48 (32.7%) were older than 1 year (Group 2). The impact of patient's gender and age as well as VUR grade on RPD were analyzed in each patient. The Fisher's exact test and chi square test was done with SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA). RESULTS: VUR was unilateral in 88 patients (59.9%) and bilateral in 59 patients (40.1%). Abnormal renal scan was found in 78 (37.7%) renal units. The incidence of VUR was significantly higher in male in group 1 (p<0.01) and in female in group 2 (p<0.01). The incidence of abnormal renal scan was significantly higher in intermediate and high grade VUR comparing low grade VUR in group 1 (p=0.042). In both group, abnormal renal scan didn't show any difference between male and female statistically (p>0.05). CONCLUSIONS: Our data showed that VUR in infant was significantly higher in male than in female, whereas VUR in children was significantly higher in female. This may be due to that characteristic of a population where neonatal circumcision is not a common procedure in infant and urinary tract infections are more common in female children. Further study may be needed to identify gender difference in RPD in infant with high grade reflux.

Malignant mesothelioma of the spermatic cord.

Primary tumors arising from the spermatic cord are very rare. Mesothelioma derives from the mesothelial cells lining the serous membrane, such as the pleura, peritoneum, and tunica vaginalis of testis. Paratesticular malignant mesothelioma (MM), which usually presents as a hydrocele or intrascrotal mass, accounts for 0.3% to 1.4% of MMs. MMs of the spermatic cord account for less than 10% of paratesticular MMs. We report a case of MM of the spermatic cord in a 65-year-old man who primarily presented to the hospital with a left inguinal mass. Following the diagnosis after surgery, he was found to have a contralateral right inguinal mass and died in 6 months. Despite their rare occurrence in the spermatic cord, MMs need to be suspected, especially in patients with a history of asbestos exposure.

Transcriptional regulation of NF-kappaB by ring type decoy oligodeoxynucleotide in an animal model of nephropathy.

Inflammation of the tubulointerstitial compartment, leading to fibrosis, is a major factor in the progressive loss of renal function in a wide variety of kidney diseases. In order to develop a therapeutic approach for nephropathy, we examined the simultaneous inhibition of transcription factor nuclear factor-kappaB (NF-kappaB), which is responsible for a wide range of cellular processes, especially inflammation, in a mouse model of unilateral ureteral obstruction. In this study, we employed a ring-type NF-kappaB (R-NF-kappaB) decoy oligodeoxynucleotide (ODN), containing consensus promoter sequences of NF-kappaB. This R-NF-kappaB decoy ODN is more highly resistant to degradation by nucleases than is the current phosphothiolated double stranded NF-kappaB decoy ODN. The inhibitory effect of R-NF-kappaB decoy ODN on nephropathy was confirmed by molecular and histological examinations. In addition, treatment with R-NF-kappaB decoy ODN reduced the activities of inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-1beta. Interestingly, the treatment with R-NF-kappaB decoy ODN also suppressed the gene expression of transforming growth factor-beta1 and fibronectin, resulting in the inhibition of fibrotic changes. These results suggest that the inhibition of NF-kappaB using R-NF-kappaB decoy ODN has potential therapeutic application in the prevention of renal fibrosis.