Effect of Early Sacral Neuromodulation on Bladder Function in a Rat Model of Incomplete Spinal Cord Injury Due to Focal Contusion.

OBJECTIVES: Incomplete spinal cord injury (SCI) accounts for two-thirds of all SCIs in clinical practice. Preclinical research on the effect of sacral neuromodulation (SNM) on bladder function, however, has been focused only on animal models of complete SCI. We aimed to evaluate the effect of early SNM on bladder responses in a rat model of incomplete SCI. MATERIALS AND METHODS: Altogether, 21 female Sprague-Dawley rats were equally assigned to control (CTR), SCI + sham stimulation (SHAM), and SCI + SNM (SNM) groups. In the SHAM and SNM groups, incomplete SCI was created by producing a moderate contusion with an NYU-MASCIS impactor at the T9-T10 level of the spine, with needle electrodes implanted bilaterally into the S2 or S3 sacral foramen. Only SNM group underwent electrical stimulation for 28 days, beginning on day 7 after SCI. Cystometry was performed 35 days after SCI. RESULTS: Although the interval between voiding contractions was significantly longer in the SHAM group than the CTR group (25.5 ± 1.4 vs. 12.5 ± 1.7 min; p < 0.05), there were no significant differences between the SNM group (16.5 ± 1.5 min) and the CTR group. Maximum voiding contraction pressure did not differ among the groups. The SNM group had a significantly lower frequency (3.5 ± 0.5 vs. 14.6 ± 2.0; p < 0.05) and maximum pressure (11.4 ± 6.2 vs. 21.3 ± 1.8 cmH2 O; p < 0.05) of nonvoiding contractions than the SHAM group. CONCLUSIONS: Our results provide experimental evidence that early SNM treatment may prevent or diminish bladder dysfunctions (e.g., detrusor overactivity, abnormal micturition reflex) in a clinical condition of incomplete SCI.

Prognostic Significance of the Proportion of Ductal Component in Ductal Adenocarcinoma of the Prostate.

PURPOSE: In prostate cancer ductal adenocarcinoma is mixed with the usual acinar adenocarcinoma. However, to our knowledge whether the proportion of the ductal component affects oncologic outcomes is currently unknown. We investigated whether the proportion of the ductal component predicts oncologic outcomes in ductal adenocarcinoma. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 3,038 patients with prostate cancer who underwent radical prostatectomy at our institution between 2005 and 2014. We excluded patients who received neoadjuvant or adjuvant treatment. Patients were stratified based on the proportion of the ductal component. We compared the probability of biochemical recurrence between groups and investigated how the proportion of the ductal component influences biochemical recurrence using Kaplan-Meier estimates and Cox regression models, respectively. RESULTS: Of 2,648 patients 101 (3.8%) had ductal adenocarcinoma and 2,547 (96.2%) had acinar adenocarcinoma. Freedom from biochemical recurrence in patients with ductal adenocarcinoma was significantly lower than in those with acinar adenocarcinoma (p <0.001). When ductal cases were stratified by the proportion of the ductal component, freedom from biochemical recurrence in the high ductal component group was significantly lower compared to that in the low ductal component group (30% or greater vs less than 30%, p = 0.023). On univariate and multivariate Cox regression analyses, a high ductal component was a significant predictor of biochemical recurrence (p <0.001). CONCLUSIONS: The prognosis for ductal adenocarcinoma can be stratified by the proportion of the ductal component. This marker could potentially be used as a surrogate for poor prognosis or as a determinant for adjuvant therapy.

Prognostic Significance of Vas Deferens Invasion After Radical Prostatectomy in Patients with Pathological Stage T3b Prostate Cancer.

BACKGROUND: Seminal vesicle invasion (SVI) is associated with adverse clinical outcomes in prostate cancer (PCa) patients. Despite its anatomical similarity and close proximity to the seminal vesicle, the prognostic significance of vas deferens invasion (VDI) by PCa has not been elucidated. For these reasons, we investigated the impact of VDI on the oncological outcome of pT3b PCa in association with SVI. METHODS: We retrospectively reviewed the medical records of 3359 patients who had undergone a radical prostatectomy at our institution between January 2000 and December 2014 for PCa. Patients who received neoadjuvant or adjuvant treatment (radiation, androgen deprivation therapy, or both) and those without adequate medical records were excluded. A Kaplan-Meier analysis was performed to analyze biochemical recurrence-free survival (BCRFS), and a Cox regression model was used to test the influence of VDI on biochemical recurrence (BCR). RESULTS: Of 350 patients with pathologically confirmed SVI (pT3b), 87 (24.9%) had VDI, while the remaining 263 patients (75.1%) had isolated SVI. Compared with SVI patients without VDI, SVI patients with VDI were noted to have a significantly worse 5-year BCRFS (25.1 vs. 17.1%, respectively). VDI was a significant predictor of BCR in multivariate Cox regression analysis (hazard ratio 1.39, 95% confidence interval 1.02-1.90; p = 0.039). CONCLUSIONS: Our results shows that the prognosis of PCa with SVI might be further stratified by VDI status, thus suggesting the role of VDI either as a surrogate for poor prognosis or as a determinant for adjuvant therapy.

Impact of lymphovascular invasion on lymph node metastasis for patients undergoing radical prostatectomy with negative resection margin.

BACKGROUND: The association between lymphovascular invasion and lymphatic or hematogenous metastasis has been suspected, with conflicting evidence. We have investigated the association between the risk of biochemical recurrence and lymphovascular invasion in resection margin negative patients, as well as its association with lymph node metastasis. METHODS: One thousand six hundred thirty four patients who underwent radical prostatectomy from 2005 to 2014 were selected. Patients with bone or distant organ metastasis at the time of operation were excluded. Survival analysis was performed to assess biochemical recurrence, metastasis and mortality risks by Kaplan-Meier analysis and multivariate Cox proportional hazard regression. Odds of lymph node metastasis were evaluated by Logistic regression. RESULTS: LVI was detected in 118 (7.4%) patients. The median follow-up duration was 33.1 months. In the Kaplan-Meier analysis, lymphovascular invasion was associated with significantly increased 5-year and 10-year BCR rate (60.2% vs. 39.1%, 60.2% vs. 40.1%, respectively; p < 0.001), 10-year bone metastasis rate and cancer specific mortality (16.9% vs. 5.1%, p = 0.001; 6.8% vs. 2.7%, p = 0.034, respectively) compared to patients without LVI. When stratified by T stage and resection margin status, lymphovascular invasion resulted in significantly increased 10-year biochemical recurrence rate in T3 patients both with and without positive surgical margin (p = 0.008, 0.005, respectively). In the multivariate Cox regression model lymphovascular invasion resulted in 1.4-fold BCR risk and 1.7-fold metastasis risk increase (95% CI 1.045-1.749, 1.024-2.950; p = 0.022, 0.040, respectively). Lymphovascular invasion was revealed to be strongly associated with lymph node metastasis in the multivariate Logistic regression (OR 4.317, 95% CI 2.092-8.910, p < 0.001). CONCLUSION: Lymphovascular invasion increases the risk of recurrence in T3 patients regardless of margin status, by accelerating lymph node metastasis and distant organ metastasis.

Intermediate PSA half-life after neoadjuvant hormone therapy predicts reduced risk of castration-resistant prostate cancer development after radical prostatectomy.

BACKGROUND: The magnitude and rapidity of the tumor response to androgen deprivation is known to predict the durability of the therapy. We have investigated the predictive value of categorizing patients by the half-life of PSA under neoadjuvant androgen deprivation therapy in patients with biochemical recurrence after radical prostatectomy. METHODS: Medical records of 317 patients who received neoadjuvant androgen deprivation therapy before radical prostatectomy and developed biochemical recurrence were analyzed. The patients were categorized into five groups according to PSA half-life. Risk of developing castration resistance was evaluated by Kaplan-Meier analysis and by Cox proportional risk regression analysis. RESULTS: The median follow-up duration was 50.1 months (IQR 31.8-68.7) and median PSA half-life was 22.1 days (IQR 12.7-38.4). Comparison of survival curves revealed that patients in the intermediate response group showed significantly lower 5-year castration-resistant prostate cancer rate (37.5%) compared to non-response and ultra-rapid response groups (63.6%, p = 0.007; 56.1%, p = 0.031; respectively). In the multivariate regression model, intermediate response compared to non-response was associated with significantly reduced risk of castration resistance development (hazard ratio 0.397, 95% confidence interval 0.191-0.823, p = 0.013) and overall mortality (hazard ratio 0.138, 95% confidence interval 0.033-0.584, p = 0.007). When subcategorized by Gleason score, Kaplan-Meier curve revealed that, in the high Gleason score stratum, 5-year castration-resistant prostate cancer rate for intermediate response group (44.0%) was exceptionally lower than that in non-response group (66.7%, p = 0.047), while castration resistance increased in other groups. CONCLUSION: Short PSA half-life as well as no response after androgen deprivation is associated with increased risk of treatment failure compared to intermediate PSA half-life.

Nocturnal polyuria and decreased serum testosterone: is there an association in men with lower urinary tract symptoms?

OBJECTIVES: To investigate the putative association between nocturia and decreased serum testosterone in men with lower urinary tract symptoms. METHODS: Frequency volume charts and serum testosterone levels of patients visiting the outpatient clinic for lower urinary tract symptoms were collected and analyzed. Age, prostate volume, body mass index and the presence of comorbidities were accounted for. Frequency volume charts were analyzed for pathophysiological components of nocturnal polyuria, global polyuria, decreased nocturnal bladder capacity and increased frequency to identify associated risks. Frequency volume charts were also used to chart 8-h changes of volume, frequency and capacity to identify time diurnal interactions with risk factors based on serum testosterone levels. RESULTS: A total of 2180 patients were enrolled in the study. Multivariate analysis showed testosterone decreased 0.142 ng/mL for every increase in nocturia, independent of other factors. Logistic regression analysis showed a significant difference between pathophysiological components. Decreased testosterone was shown to carry a significant independent risk for overall nocturia (odds ratio 1.60, 95% confidence interval 1.013-2.527, P = 0.044), and particularly nocturnal polyuria (odds ratio 1.934, 95% confidence interval 1.001-3.737, P = 0.027). Repeated measurement models showed patients with serum testosterone below 2.50 ng/mL to have a paradoxical increase in nocturnal urine volume at night. CONCLUSIONS: Nocturia, especially nocturnal polyuria, is associated with decreased serum testosterone. Patients with low serum testosterone show increased nocturnal urine output.

Transurethral resection of fibrotic scar tissue combined with temporary urethral stent placement for patients with in anterior urethral stricture.

INTRODUCTION: Fibrotic scar formation is a main cause of recurrent urethral stricture after initial management with direct vision internal urethrotomy (DVIU). In the present study, we devised a new technique of combined the transurethral resection of fibrotic scar tissue and temporary urethral stenting, using a thermo-expandable urethral stent (Memokath(TM) 044TW) in patients with anterior urethral stricture. MATERIALS AND METHODS: As a first step, multiple incisions were made around stricture site with cold-utting knife and Collins knife electrode to release a stricture band. Fibrotic tissue was then resected with a 13Fr pediatric resectoscope before deployment of a MemokathTM 044TW stent (40 - 60mm) on a pre-mounted sheath using 0° cystoscopy. Stents were removed within12 months after initial placement. RESULTS: We performed this technique on 11 consecutive patients with initial (n = 4) and recurrent (n = 7) anterior urethral stricture (April 2009 ­ February 2013). At 18.9 months of mean follow-up (12-34 months), mean Qmax (7.8±3.9ml/sec vs 16.8 ± 4.8ml/sec, p < 0.001), IPSS (20.7 vs 12.5, p = 0.001 ), and QoL score (4.7 vs 2.2, p < 0.001) were significantly improved. There were no significant procedure-related complications except two cases of tissue ingrowth at the edge of stent, which were amenable by transurethral resection. In 7 patients, an average 1.4 times (1-5 times) of palliative urethral dilatation was carried out and no patients underwent open surgical urethroplasty during the follow-up period. CONCLUSION: Combined transurethral resection and temporary urethral stenting is a effective therapeutic option for anterior urethral stricture. Further investigations to determine the long-term effects, and safety profile of this new technique are warranted.

The role of c-FLIP in cisplatin resistance of human bladder cancer cells.

PURPOSE: We investigated the mechanisms underlying cisplatin resistance in human bladder cancer cells to provide novel molecular targets for the treatment of cisplatin resistant bladder cancer. MATERIALS AND METHODS: The differential gene expression of cisplatin sensitive (T24) and resistant (T24R2) human bladder cancer cell lines was analyzed and validated by microarray and Western blot analysis. Changes in cisplatin sensitivity by c-FLIP knockdown and related mechanisms in T24R2 cells were assessed using the Cell Counting Kit-8 assay (Dojindo Molecular Technologies, Gaithersburg, Maryland) and Western blot. siRNA oligonucleotides that specifically target c-FLIP were prepared and siRNA transfection was done. RESULTS: Microarray analysis revealed that the expression of 1,086 and 322 genes showed more than twofold and fourfold changes in the T24R2 and T24 cell lines, respectively. Especially genes involved in the c-FLIP related death receptor apoptosis pathway, including caspase 2 and 9, NF-kB, BID, c-FLIP, XIAP, and cIAP1 and 2, showed differential expression in the 2 cell lines. Western blot demonstrated complete cisplatin mediated suppression of c-FLIP expression in T24 cells but no change in c-FLIP expression was observed in T24R2 cells after cisplatin treatment in the same dose range. Suppression of c-FLIP expression in T24R2 cells by siRNA transfection rendered these cells significantly more sensitive to cisplatin treatment than untransfected T24R2 cells (p <0.05). CONCLUSIONS: Results reveal that c-FLIP has an important role in the cisplatin resistance of human bladder cancer cells and c-FLIP modulation may at least partially reverse cisplatin resistance in bladder cancer cells.

Women with pure stress urinary incontinence symptoms assessed by the initial standard evaluation including measurement of post-void residual volume and a stress test: are urodynamic studies still needed?

AIMS: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Bladder stone due to accidentally intravesically inserted intrauterine device.

Bladder stones occasionally develop due to foreign body in the bladder. A 45-year-old woman, who had had an intrauterine contraceptive device inserted 10 years earlier, presented with dysuria, frequency and voiding difficulty with suprapubic pain. The intrauterine device was found in the bladder with stone formation and was removed by cystoscopic procedure.

Urinary continence after radical prostatectomy: predictive factors of recovery after 1 year of surgery.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Induction of caspase mediated apoptosis and down-regulation of nuclear factor-κB and Akt signaling are involved in the synergistic antitumor effect of gemcitabine and the histone deacetylase inhibitor trichostatin A in human bladder cancer cells.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The histone deacetylase inhibitor trichostatin A synergistically resensitizes a cisplatin resistant human bladder cancer cell line.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Is body mass index associated with pathological outcomes after radical prostatectomy in Korean men?

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Today, controversies continue with regards to the potential impact of obesity or increased body mass index (BMI) on actual pathological features of prostate cancer and/or clinical outcome after radical prostatectomy (RP). Moreover, a paucity of relevant data exist in the literature regarding Asian or Korean men. For the first time to our knowledge, the study demonstrated that although higher BMI was significantly associated with extracapsular extension of tumour, BMI did not significantly enhance ability to preoperatively predict extracapsular extension of tumour and was not significantly associated with PSA outcome as well as other objective pathological outcomes in Korean men undergoing RP, who are generally leaner than Western counterparts. OBJECTIVE: • To investigate the impact of increased body mass index (BMI) on pathological features after radical prostatectomy (RP) in Korean patients. PATIENTS AND METHODS: • We reviewed the records of 1000 Korean patients who underwent RP for prostate cancer and assessed the differences in pathological outcomes and biochemical recurrence-free survival after RP according to BMI of subjects via univariate and multivariate analyses. • A multivariate logistics regression model, the performance of which was analysed from a receiver operator characteristics curve, was applied to assess the predictive capacity of variables shown to be significant predictors of adverse pathological outcome. RESULTS: • Among our subjects, only 17 (1.7%) men had BMI ≥30 kg/m(2). After adjusting for various clinical variables, BMI (highest quartile vs others) was shown to be significantly associated with extracapsular extension of tumour (P= 0.014) and positive surgical margin (P= 0.019), but not with high pathological Gleason score (P= 0.912) and seminal vesicle invasion (P= 0.191). • Meanwhile, the addition of BMI to a multivariate model devised for preoperatively predicting extracapsular extension of tumour did not significantly increase predictive accuracy of the model (P= 0.319). On multivariate analysis, BMI was not shown to be a significant predictor of biochemical recurrence-free survival (P= 0.201). CONCLUSION: • Although higher BMI was significantly associated with extracapsular extension of tumour, BMI did not significantly enhance the ability to preoperatively predict extracapsular extension of tumour and was not significantly associated with PSA outcome or with other objective pathological outcomes in Korean men undergoing RP, who are generally leaner than their western counterparts.

Early recovery of urinary continence after radical prostatectomy: correlation with vesico-urethral anastomosis location in the pelvic cavity measured by postoperative cystography.

OBJECTIVES: To determine the association of vesico-urethral anastomosis location (VUAL) with early recovery of urinary continence (UC) after radical prostatectomy (RP). METHODS: A retrospective analysis of 678 patients who underwent RP was carried out. Patients were divided into three groups based on the VUAL as determined by postoperative cystography: group I - VUAL above the upper margin of the symphysis pubis (SP), group II - between the upper margin and the middle of the SP, and group III - below the middle of the SP. Early recovery of UC was defined as using no pads or an occasional security pad within 3 months. Recovery rates were compared between the groups and factors predicting an early recovery of UC were investigated. RESULTS: Among all patients, 62.2% achieved an early recovery of UC. Patients in group I were younger, with a longer membranous urethra, greater percent of nerve sparing and shorter time to continence than those in groups II or III. Early recovery rates were 89.5%, 69.8% and 40.7% in group I, II and III, respectively (P < 0.001). VUAL remained an independent predictor of early recovery of UC (OR 3.2 for group I vs II and 10.8 for group I vs III [P < 0.001]) when adjusted for age, operative time, membranous urethral length and operation by surgeon with high surgical volume. CONCLUSION: VUAL represents an independent predictor of recovery of UC after RP. A higher VUAL is associated with a higher rate of early recovery of UC.

Effect of the dual 5alpha-reductase inhibitor, dutasteride, on serum testosterone and body mass index in men with benign prostatic hyperplasia.

OBJECTIVE: To investigate the effects of dutasteride on serum testosterone level and body mass index (BMI) in men who received medical therapy for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 120 patients with BPH were randomized to three treatment groups: tamsulosin 0.2 mg/day (alpha-blocker group), dutasteride 0.5 mg/day (dutasteride group), or tamsulosin 0.2 mg plus dutasteride 0.5 mg/day (combination group) for 1 year. For all patients the BMI and serum testosterone levels were checked at baseline and after 1 year of treatment. RESULTS: Among the evaluable 107 patients, the dutasteride (33) and combination groups (37) had significantly greater increases in serum testosterone level (16.3% and 15%, respectively) than the alpha-blocker group (37; 0.3%) after 1 year of treatment (both P < 0.001). When analysed by baseline serum testosterone tertile, the increases in serum testosterone level among the dutasteride and combination group were greatest in the lowest tertile. For BMI, the dutasteride and combination group had mean decreases of 0.17 and 0.20 kg/m(2), respectively, at 1 year, whereas the alpha-blocker group had a mean increase of 0.04 kg/m(2). The decreases in BMI for the dutasteride and combination group were statistically significant only in the lowest tertile (P = 0.048 and 0.010, respectively). CONCLUSION: Our results show that dutasteride treatment in men with BPH led to a significant increase in serum testosterone level and a significant decrease in BMI among those with relatively lower baseline serum testosterone levels.

Comparison of radiographic and pathologic sizes of renal tumors.

PURPOSE: We investigated the difference between tumor sizes measured via preoperative computed tomography (CT) images and in surgical specimens during pathologic examinations in a contemporary cohort of patients who received extirpative surgery for renal tumors. METHODS: We reviewed records of 467 patients who received radical or partial nephrectomy for renal lesions suspicious for malignancy. For our study, only patients who underwent preoperative CT within 4 weeks of surgery were included. In all patients, radiographic tumor size, defined as the largest diameter of tumor measured via CT images, and pathologic tumor size, the largest diameter of tumor measured in surgical specimen, were compared and analyzed by various factors. RESULTS: Among total subjects, mean radiographic and pathologic tumor size were 4.56 +/- 2.99 and 4.49 +/- 3.23 cm, respectively (P = 0.399). When subjects were categorized according to radiographic tumor size (1-cm range), statistically significant difference (average of 2 mm) between radiographic and pathologic tumor size was observed only in the 4 to <5 cm range (P = 0.046). Among those with clear cell renal cell carcinoma, mean radiographic tumor size was significantly larger than pathologic size, but by only 1.4 mm (P = 0.012). Factors such as age, gender, body mass index, tumor stage, tumor grade, and tumor location were observed to have no significant impact on differences observed between radiographic and pathologic tumor size. CONCLUSIONS: Although actual size of renal mass can be generally overestimated by CT images, difference may be minimal and clinically insignificant in most cases.

Significance of postbiopsy hemorrhage observed on preoperative magnetic resonance imaging in performing robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Synergistic Antitumor Effects of Combined Treatment with HSP90 Inhibitor and PI3K/mTOR Dual Inhibitor in Cisplatin-Resistant Human Bladder Cancer Cells.

PURPOSE: The current study aimed to investigate the synergistic antitumor effect of combined treatment with 17-DMAG (HSP90 inhibitor) and NVP-BEZ235 (PI3K/mTOR dual inhibitor) on cisplatin-resistant human bladder cancer cells. MATERIALS AND METHODS: Human bladder cancer cells exhibiting cisplatin resistance (T24R2) were exposed to escalating doses of 17-DMAG (2.5-20 nM) with or without NVP-BEZ236 (0.5-4 µM) in combination with cisplatin. Antitumor effects were assessed by CCK-8 analysis. Based on the dose-response study, synergistic interactions between the two regimens were evaluated using clonogenic assay and combination index values. Flow cytometry and Western blot were conducted to analyze mechanisms of synergism. RESULTS: Dose- and time-dependent antitumor effects for 17-DMAG were observed in both cisplatin-sensitive (T24) and cisplatin-resistant cells (T24R2). The antitumor effect of NVP-BEZ235, however, was found to be self-limiting. The combination of 17-DMAG and NVP-BEZ235 in a 1:200 fixed ratio showed a significant antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range, and clonogenic assay showed compatible results with synergy tests. Three-dimensional analysis revealed strong synergy between the two drugs with a synergy volume of 201.84 µM/mL²%. The combination therapy resulted in G1-phase cell cycle arrest and caspase-dependent apoptosis confirmed by the Western blot. CONCLUSION: HSP90 inhibitor monotherapy and in combination with the PI3K/mTOR survival pathway inhibitor NVP-BEZ235 shows a synergistic antitumor effect in cisplatin-resistant bladder cancers, eliciting cell cycle arrest at the G1 phase and induction of caspase-dependent apoptotic pathway.

Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis.

Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based on their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simian virus 40 T/t-antigens that is associated with the biological behavior and prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair, and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb, or BRCA1 expression but not in tumors initiated through the overexpression of myc, ras, her2/neu, or polyoma middle T oncogenes. Importantly, human breast, lung, and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Because this class of epithelial tumors is generally intractable to currently existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Because these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in preclinical testing of therapies focused on these biologically important targets.