Does intensity-modulated radiation therapy by helical tomotherapy for prostate cancer increase the subsequent risk of bladder cancer? A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the risk of bladder cancer after intensity-modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk post-radical prostatectomy (RP) using propensity score-matched analysis and to assess the risk factors for bladder cancer. METHODS: This retrospective study included 2067 patients with non-metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow-up time as matched covariates. A propensity score-matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared. RESULTS: In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score-matched analysis, the 5-year bladder cancer-free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436-18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000-1.001, p = 0.010, respectively). CONCLUSIONS: IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.

Efficacy of a cultured conditioned medium of exfoliated deciduous dental pulp stem cells in erectile dysfunction patients.

Majority of current treatment strategies against erectile dysfunction (ED) has been consisted of only a supportive care to sustain enough erection during a sexual intercourse. In this study, we investigated whether the cultured conditioned medium of human exfoliated deciduous dental pulp stem cells (SHED-CM) had an ability to treat ED through fundamentally repairing the pathological damage of vascular endothelial cells of the corpus cavernosum. An open-label pilot study was performed from April 2016 to October 2020. SHED-CM was injected directly into the corpus cavernosum of penis of 38 ED patients who visited our clinic and fulfilled the inclusion criteria. Efficacy was assessed using the simplified International Index of Erectile Function (IIEF-5) questionnaire. The average age and initial IIEF-5 score of the patients enrolled in this study was 56 (31-79) years old and 13.1 (5-20) points, respectively. Medical history revealed 7 patients with diabetes, 7 patients with hypertension and 1 patient with priapism undergone shunt operation. Of these, 37 patients (97.4%) showed an improvement in IIEF-5 of an average of 19.3 (7-25) points or 64.4 (10-300) % increase after three injections of SHED-CM. Eighteen patients (47.4%) achieved more than 21 points (no ED) in IIEF-5. No adverse events were encountered. This is the first clinical report of ED treatment in the literatures evaluating the efficacy of SHED-CM. Treatment with SHED-CM is expected to repair vascular damages of the corpus cavernosum, which are the main cause of ED, and to be widely spread as a fundamental clinical application for ED.

Clinical significance of preoperative renal function and gross hematuria for intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To investigate the predictive values of perioperative factors and to develop a nomogram for intravesical recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. METHODS: A retrospective analysis of 144 patients who underwent radical nephroureterectomy from 1996 to 2014 was carried out. The actuarial probabilities of the intravesical recurrence-free survival rate were calculated using the Kaplan-Meier method. Prognostic indicators for intravesical recurrence were identified using competing-risks regression analyses. RESULTS: Intravesical recurrence occurred in 63 patients during the follow-up period. The intravesical recurrence-free survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In univariate analysis, the presence of gross hematuria (P = 0.028) and the preoperative serum creatinine level (P = 0.033) were significantly associated with intravesical recurrence. In multivariate analysis, the presence of gross hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145-3.496; P = 0.013) and the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95% CI 1.161-3.534; P = 0.021) were independent predictors for intravesical recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the model was developed. The concordance index of this model was 0.632. CONCLUSION: The presence of gross hematuria and preoperative serum creatinine levels seem to be independent predictors for intravesical recurrence after radical nephroureterectomy. Our nomogram developed based on these factors might aid in appropriate patient selection for clinical trials of novel therapeutic interventions, including administration of intravesical chemotherapy.

Sarcopenia as a Novel Preoperative Prognostic Predictor for Survival in Patients with Bladder Cancer Undergoing Radical Cystectomy.

PURPOSE: To investigate the prognostic significance of sarcopenia on long-term outcomes in patients with bladder cancer after radical cystectomy (RC). METHODS: We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma at our institution. Prognostic impact of the preoperative clinical, laboratory, and radiologic parameters were evaluated by Cox proportional hazard model analyses, and a nomogram was developed to predict cancer-specific survival (CSS) after RC. RESULTS: The mean follow-up was 46.7 months. Patients with sarcopenia had a significantly shorter CSS than those without sarcopenia. On univariate Cox analysis, clinical T stage, histology of transurethral resection of bladder tumor (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum albumin level, presence of hydronephrosis, and presence of sarcopenia were associated with significantly worse CSS. On multivariate Cox stepwise analysis, sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3; p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant independent predictors of an unfavorable prognosis Based on the results of the multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS after RC. CONCLUSIONS: Sarcopenia, clinical T stage, presence of hydronephrosis, histology of TURBT specimen, and NLR are novel preoperative prognostic factors even after adjustment for other known preoperative predictors in patients undergoing RC for bladder cancer.

Prediction of renal function after nephroureterectomy in patients with upper tract urothelial carcinoma.

OBJECTIVE: The estimated glomerular filtration rate is significantly decreased after nephroureterectomy. Deteriorating renal function likely affects the eligibility for cisplatin-based chemotherapy in patients with upper tract urothelial carcinoma. The present study was undertaken to identify preoperative factors for the prediction of postoperative renal function and develop a prediction model. METHODS: Between June 1996 and January 2014, 110 patients who underwent radical nephroureterectomy at our institution were analyzed in this study. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. Univariate linear regression analyses were performed to investigate the correlation between postoperative estimated glomerular filtration rate and preoperative variables. A stepwise multivariate linear regression analysis was performed to identify independent predictors of postoperative estimated glomerular filtration rate. RESULTS: Comparison of preoperative and postoperative estimated glomerular filtration rate for each patient showed a median difference of 13.1 ml/min/1.73 m(2). The postoperative estimated glomerular filtration rate was significantly lower than the preoperative estimated glomerular filtration rate (P < 0.001). On univariate analysis, age and preoperative estimated glomerular filtration rate were significantly correlated with postoperative estimated glomerular filtration rate. On multivariate analysis, age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictive factors of postoperative estimated glomerular filtration rate. The predicted postoperative estimated glomerular filtration rate, which was calculated using these independent factors, showed a significant correlation with the observed postoperative estimated glomerular filtration rate (correlation coefficient = 0.7533). CONCLUSIONS: Age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictors of postoperative estimated glomerular filtration rate in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. The predicted postoperative estimated glomerular filtration rate based on these factors may be useful for choosing alternative management strategies such as neoadjuvant chemotherapy for patients with upper tract urothelial carcinoma.

Prediction of biochemical recurrence after robot-assisted radical prostatectomy: analysis of 784 Japanese patients.

OBJECTIVES: To examine biochemical recurrence after robot-assisted radical prostatectomy in Japanese patients, and to develop a risk stratification model for biochemical recurrence. METHODS: The study cohort consisted of 784 patients with localized prostate cancer who underwent robot-assisted radical prostatectomy without neoadjuvant or adjuvant endocrine therapy. The relationships of biochemical recurrence with perioperative findings were evaluated. The prognostic factors for biochemical recurrence-free survival were evaluated using Cox proportional hazard model analyses. RESULTS: During the follow-up period, 80 patients showed biochemical recurrence. The biochemical recurrence-free survival rates at 1, 3, and 5 years were 92.2%, 85.2% and 80.1%, respectively. In univariate analysis, the prostate-specific antigen level, prostate-specific antigen density, biopsy Gleason score, percent positive core, pathological T stage, pathological Gleason score, lymphovascular invasion, perineural invasion and positive surgical margin were significantly associated with biochemical recurrence. In multivariate analysis, prostate-specific antigen density ≥0.4 (P = 0.0011), pathological T stage ≥3a (P = 0.002), pathological Gleason score ≥8 (P = 0.007) and positive surgical margin (P < 0.0001) were independent predictors of biochemical recurrence. The patients were stratified into three risk groups according to these factors. The 5-year biochemical recurrence-free survival rate was 89.4% in the low-risk group, 65.6% in the intermediate-risk group and 30.3% in the high-risk group. CONCLUSIONS: The prostate-specific antigen density, pathological T stage, pathological Gleason score and positive surgical margin were independent prognostic factors for biochemical recurrence. The risk stratification model developed using these four factors could help clinicians identify patients with a poor prognosis who might be good candidates for clinical trials of alternative management strategies.

Preoperative prognostic factors for biochemical recurrence after robot-assisted radical prostatectomy in Japan.

PURPOSE: We investigated oncological outcomes in Japanese patients who underwent robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: This study included 389 patients who underwent RARP at a single institution with a follow-up period of at least 1 year. Preoperative findings were compared with biochemical recurrence (BCR). Predictors of BCR-free survival (BCRFS) were evaluated by univariate and multivariate Cox proportional hazard model analyses, and a risk stratification model based on the relative risks of BCR was established. RESULTS: Fifty incidences of BCR were noted during a median follow-up period of 28.7 months (range, 12.1-80.0 months). The BCRFS rate for the entire cohort at the median follow-up time was 85.9 %; the 1-, 3-, and 5-year estimates were 91.0, 85.1, and 81.1 %, respectively. From univariate analyses, prostate-specific antigen (PSA), PSA density, biopsy Gleason score, and percent positive core were significantly associated with BCR. Multivariate analysis showed that PSA [hazard ratio (HR), 2.75; p = 0.001], percent positive core (HR, 2.22; p = 0.001), and biopsy Gleason score (HR, 2.61; p = 0.007) were independent predictors of BCR. CONCLUSION: This study at a single Japanese center demonstrates that RARP provides a satisfactory BCRFS rate. This report provides a framework with which to estimate oncological outcomes in patients who underwent RARP for localized prostate cancer. Our results support the increased use of RARP for the treatment of localized prostate cancer in Japan.

Robotic-assisted laparoscopic radical prostatectomy for treatment of a newly identified lesion revealed no viable cells in the previously treated area with microwave focal therapy.

Introduction: Histological outcome of the targeted focal therapy is in principle confirmed by targeted needle biopsy from the treated area in clinical trial. Herein, we report a rare case in which the MFT was followed by RARP. Case presentation: A 68-year-old man with PSA 9.6 ng/mL and PI-RADS 4 lesion in the right transition zone on multi-parametric MRI underwent MR/ultrasound fusion-guided targeted biopsy, which revealed grade-group 1 cancer. Targeted focal therapy with microwave ablation was performed, resulting in disappearance of the PI-RADS 4 lesion at post-operative 4 months. However, PSA rose to 11.5 ng/mL, and a new PI-RADS 4 lesion, was identified in the left peripheral zone. RARP was performed to reveal new grade-group 3 cancer, and no viable cells in the previously treated area with MFT. Conclusion: RARP was safely performed even after MFT and proved the pathological complete response of microwave ablation.

Hiding in plain view: genetic profiling reveals decades old cross contamination of bladder cancer cell line KU7 with HeLa.

PURPOSE: KU7 is a popular urothelial carcinoma cell line that was isolated from the bladder of a patient at Keio University in 1980. It has subsequently been widely used in laboratories around the world. We describe how routine cell line authentication revealed that KU7 was cross contaminated almost 30 years ago with HeLa, a cervical carcinoma cell line. MATERIALS AND METHODS: Presumed KU7 clones dating from 1984 to 1999 were provided by M.D. Anderson Cancer Center, Vancouver Prostate Centre, Kyoto University, Tokyo Medical University and Keio University. HeLa was obtained from ATCC. Genomic DNA was isolated and short tandem repeat analysis was performed at the M.D. Anderson Cancer Center Characterized Cell Line Core Facility, Johns Hopkins University Fragment Analysis Facility and RIKEN BioResource Center, Ibaraki, Japan. Comparative genomic hybridization was performed on a platform (Agilent Technologies, Santa Clara, California) at Vancouver Prostate Centre. RESULTS: The short tandem repeat profile of all KU7 clones was an exact match with that of HeLa. Comparative genomic hybridization of all samples revealed an abundance of shared chromosomal aberrations. Slight differences in some genomic areas were explained by genomic drift in different KU7 clones separated by many years. CONCLUSIONS: Our analysis identified that cross contamination of KU7 with HeLa occurred before 1984 at the source institution. All KU7 clones in the urological literature should be considered HeLa and experimental results should be viewed in this light. Our results emphasize the need to authenticate cell lines in oncological research.

Preoperative prediction of malignant involvement of resected ureters in patients undergoing radical cystectomy for bladder cancer.

OBJECTIVE: To investigate preoperative predictors of ureteral involvement of bladder malignancy and to develop a novel preoperative model for the prediction of ureteral involvement in bladder cancer patients undergoing radical cystectomy. METHODS: This study included 197 consecutive bladder cancer patients treated with radical cystectomy. The correlations of preoperative factors with ureteral involvement were analyzed by univariate analysis with Pearson's χ(2-) test and multivariate logistic regression analysis with a stepwise selection procedure. RESULTS: Positive ureteral involvement was observed in 38 (19.3%) patients. Tumor location (involvement of the vesical trigone), clinical T stage (≥ cT3) and the number of tumors (≥ 3), but not sex, tumor grade and histological features determined by transurethral resection of bladder tumor, tumor size, shape of tumor, concomitant presence of carcinoma in situ, preoperative intravesical therapy, number of transurethral resection of bladder tumor procedures or the presence of hydronephrosis were significantly associated with ureteral involvement in the univariate analysis. Multivariate logistic regression analysis confirmed that the aforementioned three significant factors identified in the univariate analysis were significant independent predictors of ureteral involvement. The probability of ureteral involvement estimated by a combination of these three parameters was well correlated with the real incidence (R = 0.904, P = 0.0021). CONCLUSIONS: Tumor location (involvement of vesical trigone), clinical T stage (≥ cT3) and the number of tumors (≥ 3) are significant independent preoperative predictors of ureteral involvement of malignancy in bladder cancer patients undergoing radical cystectomy. Our predictive model might be useful for preoperative prediction of ureteral tumor involvement.

Robotic versus open radical cystectomy: prospective comparison of perioperative and pathologic outcomes in Japan.

OBJECTIVE: In Japan, no study has compared the perioperative outcomes observed between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). This study aimed at a prospective comparison of the perioperative outcomes between RARC and ORC performed by a single surgeon. METHODS: Between 2008 and 2011, 26 bladder cancer patients underwent radical cystectomy by one surgeon, 11 robotically and 15 by open procedure. We prospectively collected perioperative and pathological data for these 26 patients, and retrospectively compared these two different surgical procedures. RESULTS: The RARC cohort had a significant decrease in both estimated blood loss (656.9 vs. 1788.7 ml, P=0.0015) and allogeneic transfusion requirement (0 vs. 40%, P=0.0237). The total operative time was almost the same (P=0.2306) but increased duration of bladder removal and lymphadenectomy was observed in the RARC cohort (P=0.0049). Surgery-related complication rates within 30 days were not significantly different (P=0.4185). Positive surgical margin was observed in three patients in the ORC cohort and in one patient in the RARC cohort (P=0.4664). The RARC cohort had a larger number of removed lymph nodes than the ORC cohort, and the difference was statistically significant (20.7 vs. 13.8, P=0.0421). CONCLUSIONS: We confirmed that RARC is safe and yields acceptable outcomes in comparison with ORC for the treatment of bladder cancer if it is performed by a surgeon who has experience of over 60 cases of robot-assisted radical prostatectomy. It is hoped that RARC will gain acceptance in Japan as a minimally invasive surgery for muscle-invasive bladder cancer.

Risk stratification of survival by lymphovascular invasion, pathological stage, and surgical margin in patients with bladder cancer treated with radical cystectomy.

BACKGROUND: The aim of this study was to investigate prognostic factors and develop a prognostic factor-based risk stratification model for disease-specific survival (DSS) in a radical cystectomy (RC) series. METHODS: The patient cohort comprised 194 consecutive patients with bladder cancer treated with RC. Univariate and multivariate Cox proportional hazard model analyses were performed to identify significant prognostic factors for DSS. A risk stratification model was developed based on the relative risks (RRs) of DSS. RESULTS: Median follow-up period was 26.8 months. The 1-, 3-, and 5-year DSS were 88.0, 74.0, and 64.9%, respectively. In the univariate analysis, pathological T (pT) (≥ pT2), lymphovascular invasion (LVI), non-urothelial carcinoma component, surgical margin (SM), and lymph node metastases (pN) were significantly associated with poor prognosis. In the multivariate analysis, pT (≥ pT2), LVI, and SM were independent factors for predicting poor prognosis. Based on these results, patients were stratified into three risk groups: low (RR = 1.00-3.626), intermediate (5.860-9.826), and high (21.24). The 1-, 3-, and 5-year survival rates were 96.9, 85.1, and 85.1% in the low-risk group, 83.0, 63.4, and 43.8% in the intermediate group, and 51.0, 19.4, and 19.4% in the high-risk group, respectively. The differences among these groups were significant. CONCLUSIONS: In our RC series, pT (≥ pT2), LVI, and SM were independent prognostic factors. This information may be useful to identify patients with poor prognosis, who might be good candidates for innovative treatment.

The Long-Term Effect of Intensity Modulated Radiation Therapy for Prostate Cancer on Testosterone Levels.

Purpose: Concern about a long-term effect of the delivery of intensity modulated radiation therapy (IMRT) for prostate cancer on serum testosterone levels remains unelucidated. We evaluated how IMRT for localized prostate cancer affects serum testosterone levels during a follow-up period of up to 10 years. Methods and Materials: We retrospectively evaluated data from 182 patients with localized prostate cancer who underwent definitive IMRT alone between 2007 and 2014. Serum total testosterone (TT) levels were measured by blood draws between 6 AM and 11 AM before treatment and at every posttreatment follow-up for 10 years. Pretreatment values and each posttreatment testosterone value were compared using a Wilcoxon signed rank test. The data set was stratified into 4 groups based on the pretreatment testosterone (pre-TT) values using quartiles. Results: The median absolute or relative changes in TT levels from pretreatment were -0.42 ng/mL or -12.0% at 3 months after radiation therapy (P < .0001). Subsequently, TT levels gradually recovered to nearly the pretreatment levels 24 to 36 months after IMRT. When analyzed according to the pre-TT quartile, median TT levels initially decreased at the 3- to 12-month period in all the quartiles; however, median TT levels increased from the 18-month period in the first and second quartile groups, whereas they were maintained at less than the pretreatment levels in the third and the fourth quartile groups throughout the entire decade after radiation therapy. The proportion of patients with hypogonadal status, defined as TT levels <3.00 ng/mL, did not increase over time. Conclusions: A transient and modest decrease of TT levels after IMRT spontaneously recovered to the pretreatment levels at the 24- to 36-month period except in patients in the higher quartile of pre-TT. This might have been partly owing to a variable sensitivity of individual testicular function to scattered radiation. Patients with lower pre-TT did not demonstrate a progressive overall rate of hypogonadism until 10 years after radiation therapy.

Comparison of CT urography and excretory urography in the detection and localization of urothelial carcinoma of the upper urinary tract.

OBJECTIVE: The purpose of this study was to compare the accuracy of CT urography and excretory urography for the detection and localization of upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: Of 128 patients at high risk for upper tract urothelial carcinoma who were examined with both CT urography and excretory urography between 2002 and 2007, 24 were undiagnosed and excluded. CT urography and excretory urography results of the remaining 104 patients and 552 urinary tract segments were compared with histopathologic examination or follow-up imaging at 1 year. Two readers independently scored the confidence levels for the presence or absence of upper urinary tract urothelial carcinoma in each of six upper urinary tract segments on both CT urography and excretory urography; differences were resolved by consensus. RESULTS: Upper urinary tract urothelial carcinoma was diagnosed in 77 (14%) segments of 46 (44%) patients. Per-patient sensitivity, specificity, overall accuracy, and area under the receiver operating characteristic curves for detecting carcinomas with CT urography (93.5% [43/46], 94.8% [55/58], 94.2% [98/104], and 0.963, respectively) were significantly greater than those for excretory urography (80.4% [37/46], 81.0% [47/58], 80.8% [84/104], and 0.831, respectively) (p = 0.041, p = 0.027, p = 0.001, and p < 0.001, respectively). Per-segment sensitivity and overall accuracy for the localization of upper urinary tract urothelial carcinoma were significantly greater with CT urography (87.0% [67/77] and 97.8% [540/552]) than with excretory urography (41.6% [32/77] and 91.5% [505/552]) (p < 0.0001). CONCLUSION: CT urography was more accurate than excretory urography in the detection and localization of upper urinary tract urothelial carcinoma and should be considered as the initial examination for the evaluation of patients at high risk for upper urinary tract urothelial carcinoma.

Maintenance intravesical bacillus Calmette-Guérin instillation for Ta, T1 cancer and carcinoma in situ of the bladder: randomized controlled trial by the BCG Tokyo Strain Study Group.

OBJECTIVES: We carried out a prospective, randomized, controlled trial to investigate the efficacy and safety of both induction and maintenance therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) for high-risk non-muscle invasive bladder cancer (NMIBC). METHODS: Intravesical instillation of 80 mg Tokyo strain was given to patients with high-risk NMIBC, including carcinoma in situ (CIS), once weekly for eight consecutive weeks as induction therapy. Patients who achieved complete response (CR) were randomly assigned to either the maintenance group or the observation group. RESULTS: A total of 90 patients were enrolled. After induction therapy, 75% of the patients achieved CR and 53 of them were enrolled in the randomized comparative phase. A total of four maintenance instillations were given. Median follow-up was 26.5 and 28.7 months after randomization in the maintenance and the observation group, respectively. Although it was not statistically significant, the 2-year recurrence-free survival rate in the maintenance group (95.8%) was higher than that in the observation group (74.1%, P = 0.078). Univariate analysis identified maintenance therapy as a significant factor influencing recurrence. During induction therapy, 82.2% of patients experienced urination-related adverse drug reactions, but most events were not serious. There were fewer adverse drug reactions with maintenance therapy than with induction therapy. Neither induction therapy nor maintenance therapy reduced patients' quality of life (QOL). CONCLUSIONS: These findings show high levels of efficacy and safety of BCG induction treatment for high-risk NMIBC, and suggest that the number of maintenance instillations could probably be reduced without reducing treatment efficacy or influencing QOL.

Radical retropubic prostatectomy with running vesicourethral anastomosis and early catheter removal: our experience.

OBJECTIVES: To assess the outcomes of patients undergoing radical retropubic prostatectomy (RRP) with a running vesicourethral anastomosis and catheter removal on postoperative day 3 or 5. METHODS: From February 2006 through December 2007, 55 patients underwent RRP at our institution. All procedures were performed by a single surgeon using a running suture for the vesicourethral anastomosis. A cystogram was carried out before catheter removal in all patients. The initial 23 of 55 patients (Group 1; n = 23) had the cystogram on postoperative day 5, the other 32 patients (Group 2; n = 32) had the cystogram on postoperative day 3. Removal of the catheter was only carried out if there was no anastomotic extravasation. RESULTS: The success rate of catheter removal in group 1 and 2 was 100% and 96.9%, respectively. Overall continence rates were 83.3%, 87% and 90.7% at 24, 48 and 72 h after removal of the catheter, respectively. There was no significant difference in terms of continence rate between groups 1 and 2. None of the patients had acute urinary retention and/or anastomotic stricture after catheter removal. CONCLUSIONS: These findings suggest that an advanced running vesicourethral anastomosis during RRP is technically feasible, allowing safe early catheter removal in most patients.

Effects of a KiSS-1 peptide, a metastasis suppressor gene, on the invasive ability of renal cell carcinoma cells through a modulation of a matrix metalloproteinase 2 expression.

Although effects of a metastasis suppressor gene, KiSS-1, have been postulated to be mediated by its receptor, hOT7T175, the mechanism of such effects remains unknown. This study was designed to evaluate the mechanism of how KiSS-1 works and to assess effects of a synthesized truncated KiSS-1 protein on the invasive ability of renal cell carcinoma (RCC) cells. Four RCC cell lines, Caki-1, KU19-20, RSP and RSM, were investigated to determine mRNA expressions of KiSS-1, its receptor, hOT7T175, matrix metalloproteinases (MMPs) and MMP inhibitors. While all cell lines demonstrated hOT7T175 mRNA expressions, only Caki-1 had KiSS-1 transcripts. A synthesized truncated KiSS-1 peptide, metastin (45-54), produced a marked suppression of the invasive ability in KU19-20 cells, which were deficient for KiSS-1 transcripts, but not in Caki-1 cells. Metastin (45-54) also increased the ability of KU19-20 cells to attach to collagen 4. Both MMP-2 mRNA levels and protein production were significantly decreased only in KU19-20 cells by metastin (45-54). In conclusion, metastin (45-54) may have potential therapeutic use by suppressing the motility and invasive ability of RCC cells which possess hOT7T175 with either a negative expression or very low expression level of KiSS-1 through, at least in part, the down-regulation of MMP-2.

The novel NF-kappaB activation inhibitor dehydroxymethyl-epoxyquinomicin suppresses anti-Thy1.1-induced glomerulonephritis in rats.

BACKGROUND: NF-kappaB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-kappaB in inflammatory renal diseases. Therefore, NF-kappaB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl-epoxyquinomicin (DHMEQ), a novel NF-kappaB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). METHODS: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-kappaB activation was analyzed by a fluorescent electrophoretic mobility shift assay. RESULTS: On day 7, DHMEQ treatment resulted in marked inhibition of NF-kappaB, decreased proteinuria (223.2 +/- 42.3 vs. 434.8 +/- 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 +/- 0.38 vs. 1.07 +/- 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 +/- 1.2 vs. 31.2 +/- 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. CONCLUSION: DHMEQ inhibited NF-kappaB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.

Establishment of orthotopic mouse superficial bladder tumor model for studies on intravesical treatments.

Various animal models of bladder tumor have been developed for the preclinical evaluation of therapeutic modalities for the treatment of bladder cancers. The ideal model for the investigation of therapeutic effects of proposed novel intravesical treatments requires the mass of the implanted tumor to be confined to the urothelium of the bladder at least for the initial phase. However, previously reported bladder tumor models are not suitable for the evaluation of intravesical therapies for the treatment of superficial bladder cancer, since the muscle invasive tumors have developed from the beginnings of the experiments. These models are too aggressive to study local treatment effects. In the current study, we demonstrated that careful instillation of MBT-2 mouse bladder cancer cells into the bladder of a syngenic C3H/HeJ mouse could establish a superficial bladder tumor with an incidence of 100%. The procedure and technique for handling animals are simple for standard animal investigators. Maintenance of the in vitro conditions of MBT-2 cells without contamination of Mycoplasma and careful selection of the substrain of C3H mouse seem to be essential for stable tumor establishment. This bladder tumor model appeared to be easy to reproduce among several investigators in different institutions. The orthotopic bladder tumor model, which was confined to urothelium, lets us evaluate various intravesical treatment strategies.

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer.

OBJECTIVE: The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated. METHODS: TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis. RESULTS: Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without (P < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers. CONCLUSIONS: Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.