Faculty Bibliography

AIMS/OBJECTIVE:Our objective was to compare the efficacy and safety of imidafenacin over fesoterodine in patients with overactive bladder (OAB). METHODS:This study is a randomised, double-blind, parallel-group, fesoterodine-controlled study in patients with continuous OAB symptoms for ≥ 3 months, daily mean voiding frequency (DMVF) ≥ 8, and daily mean urgency or urgency incontinence frequency ≥ 2. A twice-daily 0.1 mg imidafenacin with placebo, or once-daily 4 mg fesoterodine with placebo were administered for 12 weeks. The primary efficacy end-point was the difference in DMVF at 12 weeks. The secondary efficacy end-points were differences in daily mean: (i) voiding frequency at 4 and 8 weeks; (ii) urgency frequency; (iii) urgency incontinence frequency; (iv) incontinence frequency; (v) nocturia frequency; and (vi) quality of life score. The variables for safety analysis were adverse events, vital signs, residual urine volume and clinical laboratory tests. An efficacy analysis was conducted in per-protocol patients and the safety analysis was conducted in all randomised patients. RESULTS:The differences in DMVF at 12 weeks were -3.38 ± 3.63 and -2.45 ± 3.73 in the imidafenacin and fesoterodine groups, respectively, and the difference was not significant between the two groups. Imidafenacin was non-inferior to fesoterodine, and the lower limit of 95% two-sided confidence intervals was -0.53. The other six secondary end-points and variables for safety analysis showed no difference between the two groups. CONCLUSIONS:Imidafenacin was non-inferior to fesoterodine in terms of efficacy, and showed no significant difference in terms of safety.

PURPOSE/OBJECTIVE:The use of laparoscopic radical cystectomy (LRC) for muscle-invasive bladder cancer is not yet widespread because of the technical difficulties of the procedure and the lengthy operating time. In this study, we report a single surgeon's experience with LRC. MATERIALS AND METHODS/METHODS:Thirty patients (25 men and 5 women) with bladder cancer underwent LRC and ileal conduit by a single surgeon between November 2007 and May 2011. An extracorporeal urinary diversion was performed through 5-6 cm midline incision for specimen extraction. RESULTS:The median operating time and estimated blood loss were 527.5 minutes and 275 mL, respectively. There was no conversion to open surgery. The median time to oral intake and postoperative hospital stay were 5 days and 12 days, respectively. The rates of immediate, early postoperative and late postoperative complication were 3.3%, 20% and 20%, respectively. With 16 months of median follow- up, the overall and recurrence-free survival rates were 70% and 56.7%, respectively. CONCLUSION/CONCLUSIONS:LRC is feasible for the management of invasive bladder cancer and, with appropriate patient selection, can be a good alternative to open or robot-assisted radical cystectomy in the era of robot-assisted surgery.

BACKGROUND AND PURPOSE/OBJECTIVE:Malignant ureteral obstruction (MUO) is a common condition and an intractable situation for patients with advanced cancer. There is currently no ideal ureteral stent to release the obstruction. Our purpose was to evaluate the clinical efficacy and safety of a novel, double-layered, coated, self-expandable metallic mesh stent (Uventa(™)) in MUO. PATIENTS AND METHODS/METHODS:In a retrospective design, a total of 71 ureter units (54 patients) were included from December 2009 to March 2012. Indications were those who had MUO with a polymeric Double-J stent malfunction, severe polymeric stent irritation, or severe pain during periodic stent change. Patients underwent Uventa placement using a retrograde approach. RESULTS:All stents were positioned at the proper site without procedure-related complications. The overall success (no obstruction and no additional intervention except supplementary Uventa placement) and primary success (no obstruction and no additional intervention) rates were 81.7% (58/71 ureter units) and 64.8% (46/71 ureter units) during the follow-up period, which had a median of 308 (35-802) days. The most common reason for primary failure was tumor progression beyond the stent segment (75.0%), followed by reactive hyperplasia at the stent tips (12.5%), bladder invasion of the primary tumor (8.0%), and stent-related pain (8.0%). Twelve patients had overall success after secondary Uventa placement. There were no severe complications. The complications included persistent flank pain (15.5%), lower urinary tract symptoms (7.0%), acute pyelonephritis (2.8%), stent migration (2.8%), and persistent hematuria (2.8%). CONCLUSIONS:These data show that Uventa can be an effective and safe option for palliative treatment of patients with MUO in a large series of patients.

Most of the cancer xenograft models are derived from tumor cell lines, but they do not sufficiently represent clinical cancer characteristics. Our objective was to develop xenograft models of bladder cancer derived from human tumor tissue and characterize them molecularly as well as histologically. A total of 65 bladder cancer tissues were transplanted to immunodeficient mice. Passagable six cases with clinico-pathologically heterogeneous bladder cancer were selected and their tumor tissues were collected (012T, 025T, 033T, 043T, 048T, and 052T). Xenografts were removed and processed for the following analyses: (i) histologic examination, (ii) short tandem repeat (STR) genotyping, (iii) mutational analysis, and (iv) array-based comparative genomic hybridization (array-CGH). The original tumor tissues (P 0) and xenografts of passage 2 or higher (≥P2) were analyzed and compared. As a result, hematoxylin and eosin staining revealed the same histologic architecture and degree of differentiation in the primary and xenograft tumors in all six cases. Xenograft models 043T_P2 and 048T_P2 had completely identical STR profiles to the original samples for all STR loci. The other models had nearly identical STR profiles. On mutational analysis, four out of six xenografts had mutations identical to the original samples for TP53, HRAS, BRAF, and CTNNB1. Array-CGH analysis revealed that all six xenograft models had genomic alterations similar to the original tumor samples. In conclusion, our xenograft bladder cancer model derived from patient tumor tissue is expected to be useful for studying the heterogeneity of the tumor populations in bladder cancer and for evaluating new treatments.

To analyze if clinically insignificant prostate cancer (CIPC) is more frequently detected with repeat prostate biopsies, we retrospectively analyzed the records of 2146 men diagnosed with prostate cancer after one or more prostate biopsies. The patients were divided into five groups according to the number of prostate biopsies obtained, e.g. group 1 had one biopsy, group 2 had two biopsies and group 3 had three biopsies. Of the 2146 patients diagnosed with prostate cancer, 1956 (91.1%), 142 (6.6%), 38 (1.8%), 9 (0.4%) and 1 (0.1%) men were in groups 1, 2, 3, 4 and 5, respectively. Groups 4 and 5 were excluded because of the small sample sizes. The remaining three groups (groups 1, 2 and 3) were statistically analyzed. There were no differences in age or prostate-specific antigen level among the three groups. CIPC was detected in 201 (10.3%), 28 (19.7%) and 9 (23.7%) patients in groups 1, 2 and 3, respectively (P<0.001). A multivariate analysis showed that the number of biopsies was an independent predictor to detect CIPC (OR=2.688 for group 2; OR=4.723 for group 3). In conclusion, patients undergoing multiple prostate biopsies are more likely to be diagnosed with CIPC than those who only undergo one biopsy. However, the risk still exists that the patient could have clinically significant prostate cancer. Therefore, when counseling patients with regard to serial repeat biopsies, the possibility of prostate cancer overdiagnosis and overtreatment must be balanced with the continued risk of clinically significant disease.

BACKGROUND:The 1997 international consensus conference on renal cell cancer (RCC) prognosis suggested erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and anaemia as prognostic biomarkers, but most studies reviewed were limited by small sample sizes. METHODS:The Cox proportional hazards model was used to evaluate whether ESR, ALP, haemoglobin (Hb), and haematocrit (Hct) could predict survival outcomes in 1307 patients with clear cell RCC (ccRCC) who underwent nephrectomy during 1994-2008. RESULTS:During a median follow-up of 43 months, we found that the patients with preoperative high levels of ESR, had a 2.10-fold (95% confidence interval (CI): 1.21-3.67) greater risk of dying from RCC compared with patients with low levels (normal range). Patients with preoperative anaemia, assessed by Hb and Hct, had a 3.11-fold (95% CI: 1.17-8.25) and 6.20-fold (95% CI: 2.30-16.72) greater risk of dying from other illnesses, respectively, compared with patients without anaemia. ALP levels were not associated with ccRCC patients' survival. These associations for ESR and anaemia were more pronounced in patients with body mass index (BMI) <25 compared with patients with BMI ≥ 25 kg m(-2). CONCLUSION/CONCLUSIONS:Preoperative high ESR, but not ALP, was a significant predictor for cancer-specific survival among ccRCC patients. Anaemia increases the risk of death from other illness.

Growing evidence suggests that obesity, an established cause of renal cell cancer (RCC), may also be associated with a better prognosis. To evaluate the association between RCC survival and obesity, we analyzed a large cohort of patients with RCC and undertook a meta-analysis of the published evidence. We collected clinical and pathologic data from 1,543 patients who underwent nephrectomy for RCC between 1994 and 2008 with complete follow-up through 2008. Patients were grouped according to BMI (kg/m(2) ): underweight <18.5, normal weight 18.5 to <23, overweight 23 to <25 and obese ≥25. We estimated survival using the Kaplan-Meier method and Cox proportional hazard models to examine the impact of BMI on overall survival (OS) and cancer-specific survival (CSS) with adjustment for covariates. We performed a meta-analysis of BMI and OS, CSS and recurrence-free survival (RFS) from all relevant studies using a random-effects model. The 5-year CSS increased from 76.1% in the lowest to 92.7% in the highest BMI category. A multivariate analysis showed higher OS [hazard ratio (HR) = 0.45; 95% CI: 0.29-0.68) and CSS (HR = 0.47; 95% CI: 0.29-0.77] in obese patients than in normal weight patients. The meta-analysis further corroborated that high BMI significantly improved OS (HR = 0.57; 95% CI: 0.43-0.76), CSS (HR = 0.59; 95% CI: 0.48-0.74) and RFS (HR = 0.49; 95% CI: 0.30-0.81). Our study shows that preoperative BMI is an independent prognostic indicator for survival among patients with RCC.

The association of body mass index, smoking, and blood pressure, which are related to the three well-established risk factors of renal cell carcinoma, and survival in patients with renal cell carcinoma is not much studied. Our objective was to evaluate this association. A cohort of 1,036 patients with low stage (pT1 and pT2) renal cell carcinoma who underwent radical or partial nephrectomy were enrolled. We retrospectively reviewed medical records and collected survival data. The body mass index, smoking status, and blood pressure at the time of surgery were recorded. Patients were grouped according to their obesity grade, smoking status, and hypertension stage. Survival analysis showed a significant decrease in overall (P = 0.001) and cancer-specific survival (P < 0.001) with being underweight, with no differences of smoking status or perioperative blood pressure. On multivariate analysis, perioperative blood pressure ≥ 160/100 mmHg (HR, 2.642; 95% CI, 1.221-5.720) and being underweight (HR, 4.320; 95% CI, 1.557-11.984) were independent predictors of overall and cancer-specific mortality, respectively. Therefore, it is concluded that being underweight and perioperative blood pressure ≥ 160/100 mmHg negatively affect cancer-specific and overall survival, respectively, while smoking status does not influence survivals in patients with renal cell carcinoma.

OBJECTIVE:The aim of this study was to compare oncological and functional outcomes of pure laparoscopic radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALRP) performed by a single surgeon. MATERIAL AND METHODS/METHODS:In total, 327 consecutive patients with prostate cancer who underwent radical prostatectomy (144 with LRP and 183 with RALRP) were enrolled. No significant differences were found in prostate-specific antigen level, biopsy Gleason score, clinical T stage or D'Amico risk stratification between the two groups. The operating time was longer in the LRP group (p < 0.001). The RALRP group patients had significantly lower postoperative pain numerical rating scale (NRS) (p = 0.016) and catheter duration (p < 0.001). There were no differences in pathological Gleason score, pathological T stage or positive surgical margin rate. No differences were found in biochemical recurrence-free survival. Postoperative pad-free continence rates revealed a more rapid recovery in the RALRP group, but rates at 12 months were not significantly different. Multivariate analysis showed that the type of surgery was a strong independent factor to predict early postoperative pad use. Postoperative potency rates were not significantly different at 3, 6 and 12 months in patients who underwent nerve-sparing procedures. CONCLUSIONS:LRP and RALRP performed by a single surgeon yielded similar results in terms of safety and oncological outcomes. More favorable outcomes were noted in operating time, pain NRS and catheter duration, as well as urinary continence recovery time. Therefore, RALRP showed more favorable components in terms of postoperative quality of life than LRP.