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A comprehensive and correct understanding of epidemiologic finding about lower urinary tract symptoms (LUTS) is important for several reasons. First, LUTS are highly prevalent in both genders all around the world and are expected to be a major concern to physicians in the near future because of the rapid rise in the elderly population. Second, it is crucial to observe trends in prevalence when national health care policy is established. By using a Medline search with various terms related to LUTS and prevalence, a review of epidemiologic studies was undertaken with an emphasis on the status in Korea. Despite the suggestions made by the International Continence Society, the lack of uniform definitions and the lack of a unified threshold of symptoms are the biggest obstacles in epidemiologic study with regard to LUTS. Most Korean epidemiologic studies on LUTS have been reported since 2000 and reveal that the prevalences of specific clinical conditions, such as LUTS, benign prostatic hyperplasia, overactive bladder, and detrusor underactivity, are in line with prevalences in Western counties. However, the prevalence of nocturia is somewhat different from that in Western countries. Many epidemiologic studies of LUTS have provided us with valuable information and a better understanding of the clinical conditions. Given that the impact of these clinical conditions on quality of life and health care cost will be emphasized more in the near future, more studies on optimal management approaches to LUTS are needed on the basis of this knowledge.

To develop a Korean version of the Functional Assessment of Cancer Therapy (FACT)-Vanderbilt Cystectomy Index (VCI) from the original English version, with subsequent linguistic validation in Korean patients who underwent radical cystectomy with urinary diversion.Translation and linguistic validation were carried out between January and May of 2013, which consisted of the following stages:(1) permission for translation;(2) forward translation;(3) reconciliation;(4) backward translation;(5) cognitive debriefing and(6) final proof-reading.During the forward translation phases,word as such as "bother","spend time", "support", "coping" and "concern" were adjusted to be more comprehensible to the target population. There conciled Korean version was accepted without certain objections because the original version and the backward translation were almost congruent except for minor differences in a subset of questions. The translation was tested using 5 Korean-speaking subjects. The subjects took an average of 8.2 minutes to complete the questionnaire, without difficulty and found the questionnaire clear and easy to understand. The panel discussed each of the issues raised by subjects and most terms were judged by the panel as to not require further changes because the overall comprehension levels were relatively high and because the translated terms were accurately rendered in the target languages.This report has demonstrated that despite translation difficulties, the linguistic validation of the FACT-VCI in the Korean language was successful. The next step is to assess the psychometric properties of the Korean version of FACT-VCI.

Purpose We investigated the etiologies of lower urinary tract symptoms (LUTS) and compared urodynamic characteristics between different diagnostic groups in young men with chronic LUTS. Materials and Methods We reviewed the medical records of 308 men aged 18 to 50 years who had undergone a urodynamic study for chronic LUTS (≥6 months) without symptoms suggestive of chronic prostatitis. Results The men's mean age was 40.4 (±10.1) years and their mean duration of symptoms was 38.8 (±49.2) months. Urodynamic evaluation demonstrated voiding phase dysfunction in 62.1% of cases (primary bladder neck dysfunction [PBND] in 26.0%, dysfunctional voiding [DV] in 23.4%, and detrusor underactivity [DU]/acontractile detrusor [AD] in 12.7%) and a single storage phase dysfunction in 36.4% of cases (detrusor overactivity [DO] in 13.3%, small cystometric capacity in 17.9%, and reduced bladder sensation in 5.2%). Most of the demographic characteristics and clinical symptoms did not differ between these diagnostic groups. Whereas 53.9% of patients with voiding dysfunction had concomitant storage dysfunction, 69.6% of those with storage dysfunction had concomitant voiding dysfunction. Men with DV or DU/AD exhibited lower maximum cystometric capacity than did those with normal urodynamics. Low bladder compliance was most frequent among patients with PBND (10.0%, p=0.025). In storage dysfunctions, men with DO exhibited higher detrusor pressure during voiding than did those with other storage dysfunctions (p

Predictors Upgrading (N 105) Non-upgrading (N 93) Pvalue Mean age (y/o) 68 65 0.012 PSA (ng/ml) 14 11 0.280 Prostate volume (ml) 34 37 0.201 PSA density (ng/ml) 0.46 0.36 0.128 Mean max % Ca in any core 49 36 0.007 Mean days from Biopsy to RP 55 61 0.117 Number of biopsies 1.1 1.1 0.930 Mean No. of biopsy cores 9.2 8.9 0.504 Mean No. of positive cores 2.8 1.9 0.004 Bx Primary GS 3.0 3.2 0.031 Bx Secondary GS 3.0 3.1 0.967 Bx GS sum 6.0 6.3 0.678 T test & Mann-Whitney test

Objective: Recent studies have investigated a combination of two antimuscarinics for adult neurogenic bladder managed with clean intermittent catheterization or pediatric refractory overactive bladder (OAB). We assessed the efficacy and tolerability of this strategy in adults with idiopathic OAB.Methods: We reviewed 49 patients with idiopathic OAB whoreceived combined antimuscarinic medication. Patients had seriallyreceived different kinds of antimuscarinics as monotherapy, but wished to take combined medication due to a lack of sufficient subjective improvement in urgency, even with dosage escalation. Efficacy was measured by changes of episodes of urgency, daytime voiding, nocturia and mean voided volume before and after the addition of the second antimuscarinic.Results: The mean duration of combined medication was 9.3 months. After adding the second antimuscarinic, urgency per day decreased from 3.8 to 1.9 (p < 0.001) and daytime voiding decreased from 10.4 to 7.4 (p < 0.001). The number of nocturia episodes and the mean voided volume also improved, although therewas no statistical significance. Efficacy did not differ between the 29 cases, with non-selective and non-selective drugs and 20 cases with non-selective and M3 selective drugs. Thirty-three (67.3%) patients reported to have benefited from combined medication. Maximal flow rate and post-void residual volume did not change in either of the sexes. Eleven (22.4%) patients discontinued the combination due to continued ineffectiveness and dry mouth.Conclusion: This retrospective study suggests that combined medication can help adults with refractory idiopathic OAB. Combined medication was tolerated in most of our patients.

Purpose To identify the prevalence and clinical features of detrusor underactivity (DU) in elderly men and women presenting with lower urinary tract symptoms (LUTS). Materials and Methods We reviewed 1,179 patients aged over 65 years who had undergone a urodynamic study for LUTS with no neurological or anatomical conditions. DU was defined as a bladder contractility index

To investigate the longitudinal changes in lower urinary tract symptoms (LUTS) after robot-assisted radical prostatectomy (RARP).Data on 127 patients who underwent RARP and completed the American Urological Association Symptom Score (AUASS) preoperatively and at 3, 6, and 12 months after surgery were collected prospectively and reviewed retrospectively. Based on the preoperative AUASS, the patients were divided into 2 groups: mild vs moderate to severe.In patients with moderate to severe LUTS, the AUASS gradually decreased after RARP. However, in patients with mild LUTS, the AUASS increased significantly at 3 months postoperatively; although LUTS began to improve at 6 months postoperatively. In multivariate logistic regression analysis, higher body mass index (BMI) was associated with an exacerbation of LUTS at 3 months postoperatively (odds ratio [OR] = 1.148, P .05). Within the moderate to severe LUTS group, urinary continence at 3 months after RARP was independently associated with the symptom improvement of LUTS at 1 year after surgery (OR = 4.772, P .05). In a subgroup analysis, lower BMI and urinary continence at 3 months after RARP predicted a significant improvement in storage symptoms at 12 months postoperatively (OR = 0.856, P .05, and OR = 3.828, P .05, respectively).After RARP, LUTS significantly improved over a 1-year period in patients with moderate to severe LUTS. However, in the immediate postoperative setting, LUTS was exacerbated in patients with mild LUTS. Increased BMI was associated with a lack of improvement in LUTS, whereas early recovery of urinary continence after surgery predicted better symptomatic improvement in LUTS, especially storage symptoms.

To evaluate the clinical prognosis of incontinence and to determine the predictors for further recovery of urinary continence in patients not achieving urinary continence within 1 year after radical prostatectomy.A total of 708 patients were evaluated regarding urinary continence status at 1 year after surgery from a prospectively maintained radical prostatectomy database. Of these, 73 (10.3%) did not recover urinary continence within 1 year after surgery. For these patients, incontinence status and the number of pads for urinary control were assessed serially.In 708 patients, factors associated with the recovery of urinary continence within 1 year after radical prostatectomy were membranous urethral length, prostatic apex shape and patient age. Among 73 patients with urinary incontinence, 41 (56.2%) achieved urinary continence with a mean time of 15.4 months subsequent to the first year after radical prostatectomy (baseline). A younger age at surgery (P = 0.027) and one pad being required (vs ≥2 pads) at baseline (P = 0.046) were identified as independent factors for achievement of urinary continence within a further 2 years. Only the number of pads was a significant factor for further recovery of urinary continence in the longer follow up (hazard ratio 0.36, P = 0.029).Compared with factors related to the prostate or membranous urethra, patient age and severity of incontinence at 1 year after radical prostatectomy are more strongly related to the recovery of urinary continence later than 1 year after surgery. These findings might help to decide whether a definite treatment is required for persistent incontinence beyond 1 year after radical prostatectomy.

Previously, the authors demonstrated the feasibility of a pure transvesical natural orifice translumenal endoscopic surgery (NOTES) for uterine horn resection (UHR) using a rigid ureteroscope in swine as an appendectomy model. However, visualization was poor, and there was room for improvement. The authors have assessed the feasibility and safety of a revised technique that uses a 5-mm rigid laparoscope. Eight operations on four female pigs (35–40 kg) were performed as a proof of concept study. Four right-side operations were performed in a survival model. The surgical procedure was similar to the original technique. However, the rigid ureteroscope was replaced by a 5-mm laparoscope after modification of the access system. In addition, the clipped metal threads used for bladder closure were easily placed with a long 13-gauge needle. In the survival model, a Foley catheter was placed for 1 day. The new technique provided considerably better visualization and operability than the original technique. The mean total operative time was 96.6 ± 18.2 min, and the mean estimated blood loss was 15.0 ± 13.5 ml. On postoperative day 3, pig 2 in the survival study died of peritonitis resulting from a small bowel injury. The lab results for the other pigs demonstrated no adverse events and tolerable immune responses. Necropsy showed complete healing of the vesicotomy. The revised transvesical NOTES UHR technique improved the outcomes and feasibility of the original technique. This approach may be translatable to human appendectomy procedures in the future.

Purpose: Using meta-analysis, the study’s aim was to evaluate the efficacy of tamsulosin, an alpha-blocker, in the treatment of ureteral stones with or without shockwave lithotripsy (SWL) in Korean patients. Materials and Methods: Relevant randomized controlled studies published through June 2011 were identified in a search of MEDLINE, KoreaMed, and the Korean Medical Database. No language restriction was applied. Only randomized controlled trials conducted with Korean patients were eligible for the analysis. The primary outcome assessed was the stone clearance rate. Two reviewers independently assessed the quality of the study and extracted the data. Meta-analysis was conducted by using R, version 2.13.0. Results: A total of 6 articles were selected as being suitable for evaluation. Pooling of the trials demonstrated a 43% higher expulsion rate for tamsulosin treatment compared to a control group (risk ratio [RR], 1.43; 95% confidence interval [CI]: 1.24 to 1.65). Similar results were obtained in all subgroup analyses according to stone location (upper: RR, 1.31; 95% CI, 1.02 to 1.68, lower: RR, 1.50; 95% CI, 1.20 to 1.88) or concomitant SWL (yes: RR, 1.38; 95% CI, 1.14 to 1.68, no: RR, 1.48; 95% CI, 1.21 to 1.83). Conclusions: This meta-analysis of randomized controlled studies provides a high level of evidence supporting the suggestion that treatment with tamsulosin augments the stone expulsion rate for ureter stones with or without SWL in a Korean population. However, a high-quality, large-scale, multicenter, randomized controlled trial is warranted to fully support this hypothesis.

dations: 2 of 3 UA with 3 rbc/hpf. Upper tract imaging consisted of multiphase CT or IVP plus renal ultrasound. All patients underwent cystoscopy. Urologists reported: 1. Hx of gross hematuria in past 6 months; 2. Result of imaging; 3. Cystoscopy findings; 4. Cause of hematuria. UA results, stratified as 0-3, 4-10, 11-25, 26-50, 50 rbc/hpf. Smoking history, and patient demographics were abstracted. Statistical Analysis Multivariable logistic regression models were used to build a predictive risk model. Patient age, sex, degree of hematuria on UA, recent hx of gross hematuria and smoking history were included. The model’s predictive ability was assessed using the area under the receiver operating characteristic (ROC) curve. The resulting risk score was applied to an independent validation cohort and the area under the ROC curve was estimated. RESULTS: The overall CA detection rate was 2.1% in a cohort of 4414. Patients with a recent hx of gross hematuria and age over 50 were at greatest risk of being diagnosed with a urinary tract CA. Smoking hx and male sex were less predictive. Degree of hematuria ( 25rbc/hpf) was least predictive. The areas under the receiver operating characteristic curves were 0.849 and 0.842 for the original and validation cohorts, respectively. CONCLUSIONS: These data suggest that patients under age 50, with no hx of gross hematuria, approximately 1/3 of pts evaluated, may safely avoid unnecessary and potentially hazardous testing for AMH. Microscopic hematuria of any degree should not be the basis to determine diagnostic evaluation.

at interval follow-up visits by the physician. Successful continence was defined as using zero pads at the time of visit. Statistical analyses were performed using the Shapiro-Wilk, t, Mann-Whitney, and 2 tests as well as multivariate regression with SPSS v15.0 (IBM Corporation, Armonk, NY). RESULTS: Of the 66 men who underwent pre-RALP UDS, 42 (64%) had successful return of continence. The median time to continence was 19 weeks. Baseline characteristics and pathologic stages were similar between the two groups, although mean preoperative IPSS was higher in the continent group (14.1 vs. 8.6, p 0.02, See Table 1). Time to continence was analyzed as a function of baseline characteristics, tumor stage and UDS parameters. The flow at maximum pressure was positively and significantly associated with time to continence (p 0.038, adjusted R2 0.62, See Table 2). CONCLUSIONS: Flow at maximum pressure can be a predictor of time to continence in men undergoing RALP. It is easily measured and can be used to help counsel men regarding recovery of postoperative continence. Larger and prospective studies are needed to further define the role of preoperative UDS in predicting continence outcomes following robotic prostatectomy.

To assess whether the severity of lower urinary tract symptoms (LUTS) is associated with the risk of prostate cancer (PCa) detection via a multi (≥12)-core prostate biopsy.From January 2004 to May 2011, 3,107 patients underwent transrectal ultrasound (TRUS) prostate biopsies due to elevated PSA levels ranging between 3 and 20 ng/ml or abnormal digital rectal exams (DREs). Multivariate logistic analysis was used to assess the potential association of LUTS and PCa detection via biopsy. The predictive accuracy of the multivariate model was assessed based on the receiver operating characteristics-derived area under the curve.The median International Prostate Symptom Score (IPSS) was 11, and the mean PSA was 6.81 ng/ml. Of the total subjects, PCa was detected from biopsy in 931 (30.0%) patients. In a comparison of 1,465 patients with IPSS ≥ 11 and 1,642 patients with IPSS11, those with a higher IPSS were older, had higher PSA and had a larger prostate, but there were no significant differences in the PCa detection rates. However, in multivariate analysis incorporating other associated variables, a higher IPSS was significantly associated with lower odds of PCa detection (P = 0.016). Nevertheless, addition of the IPSS did not significantly increase the accuracy of the multivariate model devised for the detection of PCa (P = 0.098).Although PCa was detected less commonly among men with higher LUTS, LUTS may not provide additional prognostic information beyond that which can be obtained via previously established prognostic factors.

The aim of the present study was to assess the impact of a novel posterior reconstruction technique during robot-assisted laparoscopic prostatectomy on continence recovery. A total of 116 consecutive patients who received the novel posterior reconstruction (case group) were retrospectively compared with a cohort of 126 patients who did not receive posterior reconstruction (control group). The primary end-point was the duration of continence recovery (no pad use) after robot-assisted laparoscopic prostatectomy. The posterior reconstruction was obtained by opposing the median dorsal fibrous raphe to the posterior counterpart of the detrusor apron, rather than the Denonvilliers' fascia. The case group showed higher continence rates at all points of evaluation, which were 2 weeks (30.1% vs 19.8%), 1 month (58.4% vs 45.7%), 3 months (82.7% vs 70.5%) and 6 months postoperatively (95.3% vs 86.4%) (P = 0.007). Application of the novel posterior reconstruction technique, age and length of membranous urethra were significant variables for the complete recovery of continence on multivariable analysis. This study shows that the application of this novel PR technique significantly improves the recovery of continence in patients undergoing robot-assisted laparoscopic prostatectomy.

Objectives The aim of this study was to investigate the effects of induction and knocking down of hypoxia-inducible factor (HIF)-1α and/or -2α on tumor biology in androgen insensitive prostate cancer cell lines. Materials and methods The induction patterns of HIF-1α and -2α after treatment with ZnSO 4 were evaluated in PC3 and DU145 cells. Both cell lines were transfected with siRNA targeted against HIF-1α and/or -2α, and the expression patterns of these 2 HIF isoforms were examined. We next performed cell counting Kit-8 (CCK-8) assays and matrigel invasion assays. Potential additive effects of HIF blockade to chemotherapy (docetaxel) or target agents (sunitinib and sorafenib) were examined. In addition, gene expression changes were determined in ZnSO 4 -treated DU145 cells using Western blotting. Results ZnSO 4 affected the expression of HIF in a dose-dependent manner. HIF expression was increased within the first 3 hours but then decreased. Cells in which HIF-1α and/or -2α had been knocked down using siRNA showed decreased cell viability. Invasion abilities were increased by ZnSO 4 treatment in both cell lines overexpressing HIF. However, invasion potencies were decreased in response to treatment with HIF siRNAs. Blocking HIF prominently augmented the antitumor effects of target agents. The underlying mechanism could be associated with p21, cMET, IGF-1, and GLUT-1. Conclusions Our results demonstrate that HIF-1α and -2α are important for cell proliferation and invasion ability in prostate cancer. Together, our results indicate that combinations of target agents with HIF knockdown may represent a promising strategy for the treatment of prostate cancer.

We tried to determine whether clinical and urodynamic differences exist between women with and without detrusor overactivity (DO) using a large database of overactive bladder (OAB) patients. We reviewed the medical records of 513 women who underwent urodynamic studies for OAB symptoms without neurogenic or anatomical conditions that affect micturition function. Clinical symptoms were evaluated using a 3-day frequency-volume chart (FVC) including the Urinary Sensation Scale and American Urological Association Symptom Index (AUA-SI). All clinical and urodynamic findings were compared between women with and without DO. The patients’ mean age was 58.9 years. DO was identified urodynamically in 167 (32.6 %) women. Those with DO were older (62.9 vs 57.0 years, p

detrusor, greater post-micturition residue and lower compliance. The group A presented TEAC levels greater than to the group B. Comparative analysis of group A, B and C demonstrated significantly greater malondialdehyde levels in group B in relation to groups A and C. The group B presented smaller contraction amplitudes than did groups A and C, in electrically stimulated contractions. Conclusions: That oxidative stress is implicated in the damage to the detrusor musculature following a period of chronic intravesical obstruction. We show, for the first time, that administration of an antioxidant prior to and following the start of chronic obstruction makes it possible to avoid the cellular lesions that cause detrusor dysfunction. Editorial Comment: Release of free radicals and subsequent oxidative stress is one of the most plausible theories about what causes the aging process in humans and other living organisms. Although there are limited available clinical data, many people choose to take antioxidant supplements or eat food rich in antioxidants in an attempt to slow this process. With the exception of some studies showing a potential relationship between oxidative stress and some genitourinary malignancies, there have been few data on this topic regarding other urological conditions. This experimental study demonstrated an increase in oxidative stress in bladder tissue in animals with partial outlet obstruction compared to controls. This finding appeared to lead to worsening urodynamic alterations in this group. Dietary supplementation with the antioxidant flavonoid galangin appeared to be protective of these effects. The authors noted that this compound is highly lipophilic and also has some smooth muscle relaxant properties. They postulate that this compound might have additional usefulness for intravesical as well as oral administration. It will be interesting to see if similar findings are observed in humans.

The significance of preoperative urodynamic studies in women with a "clinically-defined pure stress urinary incontinence (SUI) symptom" has been debated in recent years. We evaluated changes of reliability of pure SUI symptoms for prediction of pure urodynamic SUI (USUI) when the assessment of post-void residual (PVR) volume and a stress test, designated as the initial standard evaluation in the NICE and AUA guidelines, were added to the process for the diagnosis of pure SUI symptoms.We reviewed records of 1,019 women aged 30-80 who underwent urodynamic study for incontinence. Criteria for pure SUI symptoms were defined as absence of overactive bladder symptoms and voiding difficulties based on a frequency-volume chart and AUA Symptom Index. We then added assessment of PVR volume and a stress test to the process for clinical diagnosis.Of subjects, 211 (20.7%) could be classified as having a pure SUI symptom. Of these, only 167 (79.1%) had pure USUI and 33 (15.7%) had detrusor overactivity. Eight (3.8%) had detrusor underactivity/bladder outlet obstruction. Sensitivity and specificity of pure SUI symptoms for pure USUI were 28.6% and 89.9%. Addition of assessment of PVR volume and a stress test resulted in an increase of predictive accuracy of only 3.6%.As one-fifth of women with pure SUI symptoms exhibit the pathophysiologies that could affect the surgical outcomes despite additional use of PVR assessment and a stress test in the clinical diagnostic process, urodynamic evaluation is considered necessary before anti-incontinence surgery in this population.

Purpose: Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a key enzyme in the androgen biosynthesis pathway. CYP17A1 has been focused on because of the promising results of a potent CYP17A1 inhibitor in the treatment of castration-resistant prostate cancer (CRPC). A hypothesis that intratumoral androgenesis may play a role in the progression of CRPC has recently been postulated. Thus, we evaluated whether commonly used prostate cancer cell lines express CYP17A1. Materials and Methods: Androgen-sensitive LNCaP and androgen-insensitive PC-3 and DU145 cells were used. To evaluate the expression of CYP17A1 protein and RNA, we performed Western blotting and RT-PCR, respectively. Results: We were unable to detect either CYP17A1 protein or RNA in any of the cell lines tested. We failed to detect any expression of CYP17A1, despite several repetitions of these techniques under different conditions. Conclusions: The expression of CYP17A1 protein and RNA in LNCaP, PC-3, and DU145 cells appears to be either absent or too low for detection. The mechanism of action of abiraterone acetate, a CYP17A1 inhibitor, may be related more to adrenal androgen blockade than to intratumoral androgenesis.

Objective We aimed to investigate significance of smoking regarding pathologic and biochemical outcomes following radical prostatectomy (RP).

Previously we reported that the histone deacetylase inhibitor trichostatin A (Sigma®) synergistically potentiates the antitumor effects of cisplatin in human bladder cancer cells. In the current study we explored the synergistic interaction between trichostatin A and gemcitabine (Novartis Korea, Seoul, Korea), the other mainstay chemotherapeutic regimen for advanced bladder cancer.The bladder cancer cell lines HTB5, HTB9, T24, J82, UMUC14 and SW1710 (ATCC®) were exposed to gemcitabine and/or trichostatin A. Synergism between the 2 drugs was determined by the combination index based on the Cell Counting Kit-8 assay (Dojindo Molecular Technologies, Rockville, Maryland) and by a clonogenic assay. Flow cytometry was used to evaluate cell cycle distribution and apoptosis. The expression of cell cycle (p21(WAF1/CIP1), cyclin A, B1 and D1, p-CDC2C, CDC2C, p-CDC25C, CDC25C and pRb), apoptosis (caspase-3, 8 and 9, PARP, Bcl-2, Bad and Bax), NF-κB (NF-κB, p-IκBα, IκBα, p-IKKα, IKKα, cIAP1, cIAP2 and XIAP) and survival (p-Akt, Akt, p-mTOR, mTOR and PTEN) related proteins was analyzed by Western blot.Isobolic analysis of the Cell Counting Kit-8 assay revealed strong synergism between gemcitabine and trichostatin A, which caused a 4.6 to 25.4-fold gemcitabine dose reduction and a 1.9 to 41.4-fold trichostatin A dose reduction while killing an estimated 90% of bladder cancer cells. The underlying mechanisms could be synergistic cell cycle arrest, induction of caspase mediated apoptosis, and down-regulation of the antiapoptotic NF-κB and Akt signaling pathways.Results show that trichostatin A may synergistically enhance gemcitabine mediated cell cycle arrest and apoptosis, suggesting the potential of using histone deacetylase inhibitors as combination agents to enhance the antitumor effect of gemcitabine for advanced bladder cancer.

Purpose: Sunitinib malate (Sutent; Pfizer, New York, NY, USA) is a highly selective multi-targeted agent and has been reported to have potent anti-tumor effects against various tumors, including renal cell carcinoma and gastrointestinal stromal tumors. In this study, we explored in vitro the anti-tumor effect and related molecular mechanisms of sunitinib malate against human bladder cancer cell lines. We also determined the synergistic anti-tumor effect between sunitinib and conventional cytotoxic drugs, cisplatin and gemcitabine, in bladder cancer cells. Materials and Methods: Six human cancer cell lines (HTB5, HTB9, T24, UMUC14, SW1710, and J82) were exposed to an escalating dose of sunitinib alone or in combination with cisplatin/gemcitabine, and the cytotoxic effect of the drugs was examined by CCK-8 assay. The synergistic effect between sunitinib and cisplatin/gemcitabine was determined by the combination index (CI) and clonogenic assay. Alterations in cell cycle (cyclin D, B1), survival (p-Akt, t-Akt), and apoptosis (Bax, Bad) regulator expression were analyzed by Western blotting. Results: Like cisplatin and gemcitabine, sunitinib exerted a dose- and time-dependent anti-tumor effect in bladder cancer cells. However, sunitinib exhibited entirely different sensitivity profiles from cisplatin and gemcitabine. Sunitinib suppressed the expression of cyclin B1, p-Akt, and t-Akt while augmenting the expression of cyclin D and pro-apoptotic Bax and Bad in HTB5 cells. Analysis of the drug combination by the isobolic method and clonogenic assay revealed that sunitinib acts in synergy with gemcitabine in HTB5 cells. Conclusions: These results indicate that sunitinib malate has a potent anti-tumor effect and may synergistically enhance the anti-tumor effect of gemcitabine in human bladder cancer cells.

This article reviews neurogenic bladder related to traumatic injury as well as vascular lesion of brain/spinal cord. Because urological manifestations of traumatic or vascular brain/spinal cord injury are highly diversified and complex, the approaches to achieve accurate diagnosis and administer proper treatment can be complicated. The goal of primary treatment is preservation of renal function and attainment of social continence. Maintaining low intravesical pressure and adequate bladder emptying are central to the treatment strategy. Diagnosis and appropriate urological management of these disease entities should depend on urodynamic studies because of poor correlation between clinical symptoms or somatic neurologic signs and urodynamic findings.

Cisplatin is the mainstay of treatment for advanced bladder cancer. However, intrinsic or acquired resistance to cisplatin is common, which severely limits its therapeutic potential. We determined the synergistic antitumor effect of cisplatin and the histone deacetylase inhibitor trichostatin A in cisplatin resistant human bladder cancer cells.The cisplatin resistant human bladder cancer cell line T24R2 was exposed to cisplatin and/or trichostatin A. Tumor cell proliferation was examined by cell counting kit assay. Synergism between 2 drugs was examined by the combination index. Changes in cell cycle and apoptosis were determined by flow cytometry. We analyzed the expression of caspase-3, 8 and 9, poly(adenosine diphosphate-ribose) polymerase, p21WAF1/CIP1, cyclin A, B1 and D1, Cdc2c, p-Cdc2c, Cdc25c, p-Cdc25c, cytochrome c, p-Akt, t-Akt, Bcl-2, Bax, Bad, vascular endothelial growth factor and fetal liver kinase-1 by Western blot and colorimetric assay.Based on the combination index and isobole analysis of the Cell Counting Kit-8 assay we observed a strong synergistic antitumor effect between cisplatin and trichostatin A, allowing a 3.5 and 4.9-fold dose reduction in cisplatin and trichostatin A, respectively, while achieving an estimated 90% kill of T24R2 cells. The underlying mechanism could be synergistic cell cycle arrest, induction of caspase mediated apoptosis or up-regulated expression of pro-apoptotic Bad and Bax.Results indicate that trichostatin A may synergistically enhance the antitumor effect of cisplatin and resensitize cisplatin resistant bladder cancer cells. These findings suggest the potential use of histone deacetylase inhibitor as a combination agent to enhance the antitumor effect of cisplatin in patients with advanced bladder cancer.

OBJECTIVES To investigate the prognostic significance of undetectable ultrasensitive prostate-specific antigen (PSA) nadir in patients who received radical prostatectomy (RP) for prostate cancer. METHODS We reviewed records of 384 patients who received RP for prostate cancer and were followed for at least 2 years with ultrasensitive PSA testing. Undetectable ultrasensitive PSA level was defined as

Due to lack of tactile feedback, dissection of surgical planes during delicate procedures of nerve-sparing robot-assisted laparoscopic radical prostatectomy (RALRP) can be hampered more by postbiopsy hematomas or adhesions compared with open surgery. Thus, we investigated association between extent of postbiopsy hemorrhage observed via preoperative magnetic resonance (MR) imaging with surgical difficulty of RALRP.We reviewed records of 154 men who received prostate biopsy, MR imaging, and subsequently, nerve-sparing RALRP for clinically localized prostate cancer within 2 weeks of MR imaging. We scored degree of postbiopsy hemorrhage as shown on T1-weighted MR imaging (hemorrhage score) and analyzed potential association of hemorrhage score with variables representative of surgical difficulty (operative time, estimated blood loss, and margin positivity) and functional outcomes (urinary continence and erectile function).Among our subjects, total hemorrhage score demonstrated no significant associations with interval from biopsy to MR imaging (p = 0.210). In multivariate analyses, prostate volume and total hemorrhage score were observed to be significantly associated with operative time (p = 0.004 and 0.039, respectively) and estimated blood loss (p = 0.009 and 0.023, respectively). Patients' age and total hemorrhage score was observed to be independent predictor of the return of erectile function sufficient for vaginal intercourse at 6 months following RALRP (p = 0.003 and 0.036, respectively).Degree of postbiopsy hemorrhage observed in preoperative MR imaging may be predictive of surgical difficulty for RALRP. Such findings provide concrete evidences that aftereffects of prostate biopsy have significant impact on performing RALRP.

We compared the preventive effects of cyclosporine A combined with prednisolone and melatonin (Sigma-Aldrich) on damage to the contralateral testis after ipsilateral testicular torsion-detorsion between pubertal and adult rats.We divided pubertal and adult Sprague-Dawley rats into groups 1-sham operation, 2-detorsion, 3-detorsion plus cyclosporine A with prednisolone and 4-detorsion plus melatonin. After 4 hours of ipsilateral testicular torsion we treated the rats with detorsion only or with detorsion plus drug depending on the group.Seminiferous tubule diameter and germ cell layer thickness were greater in pubertal group 3 and adult group 4 than at each age in group 2 (each p0.05). The number of spermatids per tubule was greater in pubertal groups 3 and 4, and in adult group 4 than at each age in group 2 (each p0.05). Of pubertal rats those in groups 3 and 4 had fewer TUNEL positive cells than group 2 (p = 0.061 and 0.057, respectively). Of adult rats the number of TUNEL positive cells was greater in group 3 and significantly lower in group 4 vs that in group 2 (p0.05).The preventive effects of cyclosporine A combined with prednisolone on contralateral testicular damage were noted only in pubertal rats while the preventive effects of melatonin were noted in pubertal and adult rats. Results suggest that damage to the contralateral testis induced by an immunological mechanism may be more significant during puberty than during adulthood.

OBJECTIVES To assess the prognostic value of the width of a healthy surgical margin in the enucleoresection of small renal cell carcinoma, in which 68% of cases had a margin width of 3.0 mm or less. METHODS We retrospectively reviewed 98 consecutive enucleoresections regarding the width of healthy margin and tumor recurrence in 96 patients followed up for more than 3 years after surgery. The mean follow-up was 70.8 months. RESULTS The mean tumor size was 2.8 cm (range, 1.0-6.1). Three cases had a positive surgical margin, and 2 of them had positive frozen biopsy results with additional negative biopsies. The other case did not have a frozen biopsy and did not show any evidence of recurrence during follow-up. The mean width of the surgical margin of the remaining 95 enucleoresections was 2.9 mm (0.5-15.0): 26.3% were 1 mm or less, 42.1% were 1.1-3.0 mm, 23.2% were 3.1-5.0 mm, and 8.4% were 5.1 mm or more. Only 1 patient developed tumor recurrence during follow-up, excluding a patient with von Hippel Lindau disease. This patient with a 2-mm width healthy margin but capsular invasion had enlarged abdominal lymph nodes at 38 months of follow-up. CONCLUSIONS The width of the surgical margin was not associated with the oncological prognosis in our enucleoresection series of small renal cell carcinoma, in which the width of the margin was 3.0 mm or less in more than two-thirds of the cases.

Central vein catheterization is a common procedure for monitoring the central venous pressure, securing vascular access, administrating vasoactive drugs and removing air embolisms. However, many complications can occur, such as vessel injury, pneumothorax, hydrothorax, nerve injury, arrhythmia and infection at the insertion site. We encountered an unusual complication of a localized right hydrothorax that was initially misinterpreted as an atelectasis after left internal jugular vein catheterization and right lateral positioning for a left lower lobectomy.

We prospectively investigated whether postoperative statin use would contribute to earlier recovery of erectile function in men who underwent bilateral nerve sparing radical retropubic prostatectomy for clinically localized prostate cancer.A total of 50 potent men without hypercholesterolemia undergoing bilateral nerve sparing radical retropubic prostatectomy for clinically localized prostate cancer were prospectively randomized into 2 equal groups. Group 1 patients were instructed to ingest only 50 mg sildenafil per day if needed following hospital discharge after radical retropubic prostatectomy. Group 2 patients were prescribed atorvastatin at a dose of 10 mg daily from postoperative days 1 to 90 and they were also instructed to ingest sildenafil, as in group 1. Patient status regarding potency and adverse events were assessed 6 months after surgery.The 2 groups demonstrated no significant differences regarding various baseline factors, including International Index of Erectile Function-5 scores. Group 2 had a significantly higher postoperative International Index of Erectile Function-5 score than group 1 at 6 months postoperatively (p = 0.003). Meanwhile, as judged by a preset definition, the incidence of potent patients 6 months after prostatectomy was 26.1% in group 1 and 55% in group 2 (p = 0.068). Also, 17.4% and 40% of the men reported achieving intercourse by vaginal penetration without a phosphodiesterase 5 inhibitor in groups 1 and 2, respectively (p = 0.172). No serious adverse events associated with medication were reported.Postoperative treatment with atorvastatin in men who report normal erectile function preoperatively may contribute to earlier recovery of erectile function after nerve sparing radical retropubic prostatectomy.

INTRODUCTION AND OBJECTIVES: We analyzed whether expansion of existing active surveillance (AS) protocols to include men with biopsy Gleason score (GS) 3þ4 prostate cancer (PCa) would significantly alter pathologic and biochemical outcomes of potential candidates of AS. METHODS: Among patients who underwent radical prostatectomy at our center between 2006 and 2013, we identified 577 patients (group A) who preoperatively fulfilled at least one of 6 different AS criteria. Also, we identified 217 patients (group B) with biopsy GS 3þ4 but fulfilled non-GS criteria from at least one of 6 AS criteria. Designating group C as expanded group incorporating all patients in group A and B, we compared risk of unfavorable disease (pathologic GS 4þ3 and/or pathologic T stage pT3a) and biochemical recurrence (BCR)free survival between groups. RESULTS: Rates of unfavorable disease were not significantly different between patients of group A and C who met AS criteria from 5 institutions (all p> 0.05), not including University of Toronto (p 0.05). Among group B, PSAD >0.15 ng/mL/cm3 (p1⁄4 0.011) and tumor length of biopsy GS 3þ4 core > 4 mm (p1⁄4 0.007) were significant predictors of unfavorable disease. When these two criteria were newly applied in defining group B, rates of unfavorable disease in group A and B was 15.6% and 14.7%, respectively (p1⁄4 0.886). CONCLUSIONS: Overall rate of pathologically aggressive PCa harbored by potential candidates for AS may not be increased significantly with expansion of criteria to biopsy GS 3þ4 under most contemporary AS protocols. PSAD and tumor length of biopsy GS 3þ4 core may be useful predictors of more aggressive disease among potential candidates for AS with biopsy GS 3þ4.

Purpose: Few data are available concerning the clinical outcome of abiraterone acetate treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) in terms of the duration of androgen deprivation therapy (ADT) before diagnosis of CRPC. We investigated the clinical efficacy of abiraterone acetate according to the duration of ADT. Materials and Methods: We reviewed the medical records of 20 patients with mCRPC who received abiraterone acetate after failure of docetaxel chemotherapy from May 2012 to March 2014 at Seoul National University Bundang Hospital. Clinical factors including prostate-specific antigen (PSA) nadir level, time to PSA nadir, PSA doubling time, PSA response, and modes of progres sion (PSA, radiologic, clinical) were analyzed. Disease progression was classified according to the Prostate Cancer Working Group 2 criteria. Results: The mean age and PSA value of the entire cohort were 76.0±7.2 years and 158.8±237.9 ng/mL, respectively. The median follow-up duration was 13.4±6.7 months. There were no statistically significant differences in clinical characteristics between pa tients who received abiraterone acetate with ADT duration

OBJECTIVES To investigate the impact of variations in bony pelvic dimensions observed from preoperative magnetic resonance imaging on operative time, intraoperative blood loss, and surgical margin status on performing open radical retropubic prostatectomy. METHODS A prospective study was undertaken in which preoperative magnetic resonance imaging was performed in 190 patients who were diagnosed with clinically localized prostate cancer before radical retropubic prostatectomy. Using the magnetic resonance image findings, various bony pelvic dimensions were measured. The associations of the measured pelvic dimensions and various clinicopathologic factors with the operative time, estimated blood loss, and surgical margin status were analyzed on multivariate analyses. RESULTS For operative time, none of the individual pelvic dimensions measured demonstrated significant associations on univariate analysis. In contrast, only the newly developed parameter, the pelvic dimension index, approached significance (P = 0.095). Only body mass index (BMI) proved to be independently associated with the operative time on multivariate analysis (P = 0.030). Also, only the prostate volume (P = 0.015) was independently associated with the estimated blood loss. For the surgical margin status, the preoperative PSA level (P = 0.041), pathologic Gleason score (P = 0.015), and BMI (P = 0.020), along with the pelvic dimension index (P = 0.048), demonstrated significant associations on univariate analyses. However, only the PSA level (P = 0.071) and BMI (P = 0.059) approached significance on multivariate analysis. CONCLUSIONS Our results have demonstrated that variations in the bony pelvic dimensions might have some impact, but not significantly so, on open radical retropubic prostatectomy compared with other patient-related baseline factors such as the BMI or prostate volume.

Lung resection surgery in patients with a previous internal mammary artery (IMA) graft to coronary arteries is challenging, because the arterial graft may be injured during dissection of adhesions between the graft and the lung [1-3]. A 68-year-old male patient, diagnosed with a squamous cell carcinoma in the left lower lobe of the lung, required a left lower lobectomy. The patient (height, 160.4 cm; weight, 73.5 kg) was on the following medications: Aspirin, clopidogrel, losartan, amlodipine, and atorvastatin. Three years previously the patient had a coronary artery bypass graft surgery including a left IMA graft to the left anterior descending (LAD) artery. An electrocardiogram (ECG) showed normal sinus rhythm, occasional premature ventricular contractions (PVCs), and left ventricular hypertrophy. A preoperative transthoracic echocardio gram showed mild inferior wall hypokinesia. Preoperative coronary angiography revealed a patent left IMA to LAD artery flow. After the patient arrived in the operating room, catheteri zation was performed on the patient's right radial artery. The patient was induced with 1-3.5 vol% sevoflurane after receiving 100 mg of propofol and 60 mg of lidocaine by intravenous injection. Tracheal intubation using a double lumen endotracheal tube (37 Fr) was performed for one-lung ventilation 3 minutes after the patient received 50 mg of rocuronium by intravenous injection. A central venous catheter was inserted into the right internal jugular vein due to the fear of graft pedicle injury and because we prefer the right internal jugular vein due to its straight course. At the start of the surgery, the patient’s blood pressure was stable (mean systolic pressure, 100-120 mmHg; diastolic pressure, 40-60 mmHg). After the thoracotomy, a severe adhesion between the upper lobe and the surrounding parietal pleura was noticed. The operator compressed the pericardium to control the bleeding using a sponge stick without considering the left internal mammary artery (LIMA) pedicle. During this period, ST-segment depression occurred, a series of PVCs appeared in about 5-6 seconds, and blood pressure decreased on the direct arterial pressure monitor (systolic pressure, 60 mmHg; diastolic pressure, 30 mmHg). Phenylephrine (20 μg/cc from a micro solution set) was dripped to increase blood pressure. The operator was notified immediately, the sponge stick compression was stopped, and the ECG and the blood pressure recovered to the previous state. Subsequent

Objectives We developed a mobile application-based Seoul National University Prostate Cancer Risk Calculator (SNUPC-RC) that predicts the probability of prostate cancer (PC) at the initial prostate biopsy in a Korean cohort. Additionally, the application was validated and subjected to head-to-head comparisons with internet-based Western risk calculators in a validation cohort. Here, we describe its development and validation. Patients and Methods As a retrospective study, consecutive men who underwent initial prostate biopsy with more than 12 cores at a tertiary center were included. In the development stage, 3,482 cases from May 2003 through November 2010 were analyzed. Clinical variables were evaluated, and the final prediction model was developed using the logistic regression model. In the validation stage, 1,112 cases from December 2010 through June 2012 were used. SNUPC-RC was compared with the European Randomized Study of Screening for PC Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC). The clinical value was evaluated using decision curve analysis. Results PC was diagnosed in 1,240 (35.6%) and 417 (37.5%) men in the development and validation cohorts, respectively. Age, prostate-specific antigen level, prostate size, and abnormality on digital rectal examination or transrectal ultrasonography were significant factors of PC and were included in the final model. The predictive accuracy in the development cohort was 0.786. In the validation cohort, AUC was significantly higher for the SNUPC-RC (0.811) than for ERSPC-RC (0.768, p

We report a case of simultaneous contralateral renal transitional cell carcinoma and renal cell carcinoma. A 63-yr-old male presented with hematuria. He was diagnosed with left renal pelvis tumor and contralateral renal cell carcinoma. Subsequently, the patient received left nephrectomy and paraaortic lymphadenectomy (transitional cell carcinoma, pT3N2M0). Post-operatively, chemotherapy of renal pelvis tumor and angioinfarction of contralateral renal cell carcinoma are being considered. We believe that management planning should be individualized in such cases.