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To describe oncological outcomes after progressive site-directed therapy (PSDT) in genuine and induced oligometasatic (OM)-castration-resistant prostate cancer (CRPC).Thirty-seven patients with OM-CRPC treated with PSDT were retrospectively analyzed, and oncological outcomes and recurrence patterns on whole-body diffusion-weighted MRI (WB-DWI) were evaluated.Twenty-two (59%) were classified as genuine OM-CRPC and 15 (41%) as induced OM-CRPC. A 50% decline in PSA after PSDT was observed in 21 (95%) genuine OM-CRPCs and 7 (47%) induced OM-CRPCs (p = 0.0005). At a median observation period of 7.3 months, median PSA progression-free survival were 10.9 months in the genuine OM-CRPCs and 4.8 months in the induced OM-CRPCs (p = 0.015). Among the patients who developed PSA progression after PSDT, 11 of 15 in the genuine OM-CRPCs (73%) and 11 of 14 in the induced OM-CRPCs (79%) underwent WB-DWI at PSA progression. The median numbers of newly detected metastases were 2 (range: 1-5) in the genuine OM-CRPCs and 4 (range: 1-40) in the induced OM-CRPCs (p = 0.049). Only one new metastasis appeared in 5 patients from the genuine OM-CRPCs (46%) and 1 from the induced OM-CRPCs (9.1%, p = 0.048). In 7 of 9 patients from the genuine OM-CRPCs (78%) and 7 of 8 patients from the induced OM-CRPCs (88%) who had bone metastases alone, the newly detected metastasis limited to the bone.Genuine OM-CRPC had better oncological outcomes after PSDT than induced OM-CRPC, and the number of lesions detected at recurrence was limited. Induced OM-CRPC might be a disseminated condition with micrometastases at OM diagnosis.

Prostate cancer localization is reportedly associated with the laterality of lymph node metastasis. Thus, it may be feasible to predict side-specific lymph node metastasis (LNM) at radical prostatectomy (RP). To investigate whether multiparametric magnetic resonance imaging and biopsy findings can predict side-specific negative LNM and to explore the feasibility of unilateral lymph node dissection (LND) at RP.A total of 500 patients who were diagnosed with prostate cancer with prebiopsy multiparametric magnetic resonance imaging of the prostate and subsequent prostate biopsy and who underwent RP and extended LND without neoadjuvant treatment were enrolled. Multiparametric magnetic resonance imaging, biopsy findings, and LNM were assessed for each side. The negative predictive value (NPV) of multiparametric magnetic resonance imaging or biopsy or both for ipsilateral LNM was examined.LNM was found in 9.2% (46/500) and 15.6% (28/180) of patients in the overall and high-risk cohorts, respectively. Magnetic resonance imaging and biopsy findings were negative in 408 and 262 sides, respectively, in the overall cohort and 144 and 100 sides, respectively, in the high-risk cohort. The NPVs of magnetic resonance imaging, biopsy, and both for ipsilateral LNM were 98.3%, 98.5%, and 99.1%, respectively, in the overall cohort, and 95.8%, 97.1%, and 97.6%, respectively, in the high-risk cohort.Unilateral LND may be indicated based on side-specific LNM risk as assessed by prebiopsy multiparametric magnetic resonance imaging and biopsy.

BACKGROUND Whole-body diffusion-weighted MRI (WB-DWI) is useful for assessing disease activity in castration-resistant prostate cancer (CRPC). MET-RADS-P is a subjective assessment-based reporting system proposed to standardize the interpretation of WB-DWI. However, a quantitative evaluation of WB-DWI has not been fully investigated. PURPOSE To investigate the validity, and analyze the prognostic value, of quantitative evaluation of WB-DWI based on apparent diffusion coefficient (ADC) values for CRPC. STUDY TYPE Retrospective. POPULATION Sixty-six patients with CRPC. The median age was 75 years. During the median follow-up period of 25.2 months, 23 of 66 patients (34.8%) died of prostate cancer. FIELD STRENGTH/SEQUENCE A 1.5 T WB-DWI was used with two b-values (0 s/mm2 -1000 s/mm2 ). A single-shot echo-planar imaging sequence was used. ASSESSMENT WB-DWI were evaluated by three readers according to MET-RADS-P scoring system. Using imaging software, Attractive BDScore, tumor diffusion volume (mDV) and ADC value of metastatic lesion (mADC) was calculated by two readers. The mDV was calculated with ADC values (×10-3 mm2 /sec) of 0.4-0.9 (mDV0.4-0.9 ), 0.9-1.4 (mDV0.9-1.4 ), and 1.4-1.8 (mDV1.4-1.8 ), respectively. STATISTICAL TESTS Spearman's rank correlation coefficient was used to assess the correlation. The relationships between the variables with cancer-specific survival (CSS) were evaluated. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS mDVs showed a strong positive correlation with MET-RADS-P scores (r = 0.90/0.87, P

Objectives To investigate the outcomes and feasibilities of gasless laparoendoscopic single-port clampless sutureless partial nephrectomy. Methods We reviewed 356 consecutive patients with primary unilateral non-metastatic renal masses who underwent gasless laparoendoscopic single-port partial nephrectomy (2011-2018), which was performed retroperitoneally using a three-dimensional flexible endoscope, without vascular clamping or renorrhaphy in principle. Results The median tumor size was 2.5 cm, and 213 (60%), 105 (29%), and 38 (11%) patients had peripheral, central, and hilar tumors, respectively. Clampless and sutureless partial nephrectomy was accomplished in 337 patients (95%), while eight (2%) and 16 (4%) patients required vascular clamping and renorrhaphy, respectively. The median operative time and blood loss were 220 min and 266 mL, respectively; eight patients (2%) received blood transfusion. Clavien-Dindo grade 3a complications occurred in 27 patients (8%); all these patients had urinary leakage treated with ureteral stent placement, one of whom also developed a postoperative pseudoaneurysm. Among 324 patients diagnosed with renal cell carcinoma, six (2%) had positive surgical margins, and one (0.3%) and seven (2%) developed metastatic and local recurrences, respectively. During a median follow-up of 54 months, no patient died from kidney cancer. The median percent decrease in estimated glomerular filtration rate at 3 months after surgery was 5.7%. No patient experienced postoperative acute renal failure, while one patient with preexisting renal impairment started dialysis at 70 months after surgery. Conclusions Clampless and sutureless partial nephrectomy can be safely accomplished in most patients undergoing gasless laparoendoscopic single-port surgery, yielding favorable oncological and functional outcomes.

OBJECTIVE To evaluate the time course of lower urinary tract symptoms (LUTS) after artificial urinary sphincter (AUS) implantation based on individual longitudinal changes of patient-reported outcomes. METHODS This retrospective study included 66 male patients with severe urinary incontinence who were treated with primary AUS implantation between 2009 and 2019. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and International Prostate Symptom Score (IPSS) questionnaires were used to evaluate continence status and LUTS preoperatively, 1, 3, and 12 months after activation, and then annually. The annual changes in scores were calculated with a linear mixed model. RESULTS Of the 66 patients, 63 (95%) achieved complete or social continence (number of pads used ≤1/d) at 1 month after activation. Mean preoperative ICIQ-SF, IPSS, and IPSS-quality of life (QOL) score were 18.9, 14.9, and 5.4, respectively; the corresponding scores at 1 month after activation were 4.5, 9.0, and 1.7 (all P

OBJECTIVE To assess the feasibility and functional/oncological outcomes of selective tetramodal bladder-preservation therapy in elderly patients with muscle-invasive bladder cancer. METHODS This study analyzed 154 patients with non-metastatic muscle-invasive bladder cancer who were enrolled into the protocol. After maximal transurethral resection and induction chemoradiotherapy, patients with clinical complete response were offered consolidative partial cystectomy to achieve bladder preservation; otherwise, radical cystectomy was recommended. Postoperative complications, preserved bladder function, and oncological outcomes were compared between elderly (aged ≥75 years) and younger patients (aged

Objectives To evaluate the oncological and functional outcomes associated with selective tetramodal bladder-sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND). Materials and methods In the present study, 154 patients with non-metastatic muscle-invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder-preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC-recurrence-free survival (RFS); cancer-specific survival (CSS); overall survival (OS), and cross-sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36-item Short-Form Health Survey (SF-36) score. Results The median follow-up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder-preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5-year MIBC-RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post-void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF-36, patients had favourable scores, equivalent to the age-matched references in all the QoL scales. Conclusion Selective tetramodal bladder-preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

Objective To estimate postoperative residual renal function after radical nephroureterectomy for upper tract urothelial carcinoma using the preoperative dynamic computed tomography renal cortex enhancement ratio in comparison with the split kidney glomerular filtration rate measured by 99m Tc-diethylenetriaminopentacetic acid renography. Methods A total of 47 patients who received radical nephroureterectomy and underwent both preoperative dynamic computed tomography and renography were the model-development cohort; and 109 patients who underwent dynamic computed tomography alone were the validation cohort. Postoperative renal function of the unremoved kidney was estimated using the following formulas: preoperative estimated glomerular filtration rate × the percentage of total renal cortex radiodensity for the intact kidney in Hounsfield units obtained from corticomedullary phase images in the computed tomography-based model, or the percentage of the total glomerular filtration rate measured by renography in the nuclear model. The correlation between observed and estimated postoperative renal function was determined. The computed tomography-based prediction model derived from linear regression analysis was validated externally. Results The correlation of computed tomography-based split renal function with the observed postoperative estimated glomerular filtration rate (r = 0.80) was equivalent to that of nuclear split renal function (r = 0.78). In the validation cohort, the computed tomography-based prediction model showed an equivalently strong correlation (r = 0.78). Conclusions The present study showed that the percentage of total renal cortex radiodensity for the intact kidney is a useful tool for predicting unremoved kidney function in upper tract urothelial carcinoma patients, thereby allowing appropriate patient selection for perioperative cisplatin-based combination chemotherapy.

Objectives To evaluate the incidence and predictors of acute kidney injury after clampless partial nephrectomy, and its impact on intermediate-term renal function. Methods The incidence and severity of acute kidney injury were assessed for 262 patients undergoing clampless partial nephrectomy between 2010 and 2015. The association between perioperative covariates and acute kidney injury was evaluated using multivariate logistic regression analysis. An annual change in estimated glomerular filtration rate from 1 year after surgery was calculated according to the presence or absence of acute kidney injury. An impact of acute kidney injury on postoperative renal impairment, defined as a ≥25% estimated glomerular filtration rate decrease, was evaluated. Results Overall, 21 (8.0%) patients experienced grade 1 acute kidney injury after clampless partial nephrectomy, and grade ≥2 acute kidney injury was not observed. High tumor complexity was the only independent predictor of acute kidney injury. Estimated glomerular filtration rate in patients with acute kidney injury improved within 1 year, and annual estimated glomerular filtration rate changes were similar among patients with or without acute kidney injury. Ultimately, 13 (5.0%) patients showed postoperative renal impairment during the median follow-up period of 37 months. Advanced age and diabetes mellitus were independent risk factors for renal impairment, but acute kidney injury was not. Conclusions The incidence and severity of acute kidney injury after clampless partial nephrectomy are low. Low-grade acute kidney injury after clampless partial nephrectomy does not seem to affect intermediate-term renal function.

OBJECTIVE To develop a computer-aided diagnosis (CAD) algorithm with a deep learning architecture for detecting prostate cancer on magnetic resonance imaging (MRI) to promote global standardisation and diminish variation in the interpretation of prostate MRI. PATIENTS AND METHODS We retrospectively reviewed data from 335 patients with a prostate-specific antigen level of

Purpose To investigate the value of computed (c) diffusion-weighted imaging (DWI) in assessing prostate cancer aggressiveness. Materials and methods Fifty-five patients with peripheral zone prostate cancer who underwent prebiopsy 1.5T magnetic resonance imaging (including native DWI at b-values of 0 and 1000 s/mm2 ) were included. cDWI signal intensities of peripheral zone prostate cancer and nonmalignant prostate tissue were measured. Association between changes in monoexponentially calculated cDWI signals according to different b-values and primary Gleason grades were assessed. Results The cDWI signal intensity of prostate cancer was lower at b = 0 s/mm2 and higher at b = 1000 s/mm2 compared to nonmalignant prostate tissue. The b-value at which the signal intensities of prostate cancer and nonmalignant prostate tissue were equal was defined as the "iso-b-value." On multivariate analysis, only the iso-b-value was a significant predictor of primary Gleason grade 4/5 cancer (P = 0.001). The area under the curve (AUC) of the iso-b-value for diagnosing primary Gleason grade 4/5 cancer was 0.94, and significantly higher than that of the tumor apparent diffusion coefficient (ADC) value with an AUC of 0.68 (P Conclusion cDWI with iso-b-value-based semiquantitative analysis was found to be useful for predicting the aggressiveness of prostate cancer and may potentially outperform tumor ADC measurements in this setting. Level of evidence 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:490-496.

Objectives To identify prostatic quadrants that could be preserved without intervention, using diffusion-weighted magnetic resonance imaging (DWI) and extended core biopsy, as a step toward implementation of quadrant-based focal ablation with potential preservation of erectile and ejaculatory functions, based on comparisons with unilateral hemi-gland ablation. Patients and Methods We conducted a prebiopsy DWI study including 648 quadrants in 162 men who underwent 14-core biopsy including anterior sampling and radical prostatectomy (RP) for localised cancer. Imaging and pathology were analysed on a quadrant basis. Each quadrant was assessed through four-core sampling. Predictive performance of DWI and biopsy for quadrant status was analysed. Results On RP specimens, 170 anterior (52.5%) and 172 posterior quadrants (53.1%) harboured significant cancer. Negative predictive values of DWI, biopsy, and their combination for significant cancer were 79.7%, 70.6%, and 91.1%, respectively, in anterior quadrants, and 78.5%, 81.3%, and 91.7%, respectively, in posterior quadrants. DWI incrementally improved the negative predictive values of biopsy in anterior (P < 0.001) and posterior quadrants (P = 0.025), without untoward impacts on positive predictive values. Negative findings on both DWI and biopsy were identified in posterior quadrants of 109 sides (33.6%), but in entire hemi-glands of 54 sides (16.7%). Conclusions The combination of DWI and 14-core biopsy including anterior sampling efficiently identifies quadrants without significant cancer in men with localised prostate cancer; the remaining quadrants, therefore, could be potential candidate areas for focal ablation. Focal therapy designed based on quadrant-based assessment could be superior to unilateral hemi-gland ablation for preservation of posterior quadrants and retaining of sexual function in more sides.

Objectives To identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU). Patients and Methods We retrospectively reviewed 754 patients with UTUC without prior or concurrent bladder cancer or distant metastasis at 13 institutions in Japan. Univariate and multivariate Fine and Gray competing risks proportional hazards models were used to examine the cumulative incidence of bladder recurrence of UTUC. A risk stratification model and a nomogram were constructed. Two prediction models were compared using the concordance index (c-index) focusing on predictive accuracy and decision-curve analysis, which indicate whether a model is appropriate for decision-making and determining subsequent patient prognosis. Results The cumulative incidence rates of bladder UTUC recurrence at 1 and 5 years were 15 and 29%, respectively; the median time to bladder UTUC recurrence was 10 months. Multivariate analysis showed that papillary tumour architecture, absence of lymphovascular invasion and higher pathological T stage were both predictive factors for bladder cancer recurrence. The predictive accuracy of the risk stratification model and the nomogram for bladder cancer recurrence were not different (c-index: 0.60 and 0.62). According to the decision-curve analysis, the risk stratification was an acceptable model because the net benefit of the risk stratification was equivalent to that of the nomogram. The overall cumulative incidence rates of bladder cancer 5 years after RNU were 10, 26 and 44% in the low-, intermediate- and high-risk groups, respectively. Conclusions We identified risk factors and developed a risk stratification model for UTUC recurrence in the bladder after RNU. This model could be used to provide both an individualised strategy to prevent recurrence and a risk-stratified surveillance protocol.

Objectives To describe the technical aspects of gasless laparoendoscopic single-port clampless sutureless partial nephrectomy for peripheral renal tumors, and to evaluate its outcomes, including surgical, pathological, and short-term oncological and functional outcomes. Methods Between January 2010 and June 2013, 103 patients with peripheral renal tumors suggestive of renal cell carcinoma underwent gasless laparoendoscopic single-port partial nephrectomy. In all cases, an attempt was made to accomplish partial nephrectomy without vascular clamping using ultrasonic coagulating and bipolar sealing devices. Hemostasis was achieved by coagulation and hemostatic agents without reconstructing the renal parenchyma. Results Of the 103 patients, gasless laparoendoscopic single-port partial nephrectomy was accomplished without vascular clamping and parenchymal suture in all but two patients (98%). Median operative time and blood loss were 191 min and 244 mL, respectively. One patient (1%) received allogeneic blood transfusion. The median postoperative time to full recovery was 3 days. Three major complications (3%, all grade 3 urinary leakage) were observed. Of 92 renal cell carcinoma patients, four (4%) had positive surgical margins, most of which underwent thermal degeneration histologically. In 91 non-metastatic renal cell carcinoma patients, 3-year local recurrence-free, progression-free, cancer-specific and overall survival rates were 100%, 99%, 100%, and 100%, respectively (mean follow-up period, 21 months). In the 103 patients, the median percent decrease in estimated glomerular filtration rate 3 months after partial nephrectomy was 2.4%. Conclusions Gasless laparoendoscopic single-port clampless sutureless partial nephrectomy can be accomplished in almost all cases of peripheral renal tumors. This surgery is technically feasible and safe, yielding acceptable short-term oncological outcomes and maximal preservation of renal function.

OBJECTIVES Patients' use of a head-mounted display during their sonographic examinations could provide them with information about their diseases in real time and might help improve "patient-centered care." We conducted this prospective study to evaluate the feasibility of a modern head-mounted display for patient self-monitoring of sonographic examinations. METHODS In November and December 2013, 58 patients were enrolled. Patients wore a head-mounted display (HMZ-T2; Sony Corporation, Tokyo, Japan) during their sonographic examinations and watched their own images in real time. After the sonographic examinations, the patients completed a questionnaire, in which they evaluated the utility of the head-mounted display, their understanding of their diseases, their satisfaction with using the head-mounted display, and any adverse events. Until November 26, 2013, patients' names were requested on the questionnaire; after that date, the questionnaire was changed to be anonymous. RESULTS Of the 58 patients, 56 (97%) elected to participate in this study. The head-mounted display was reported to have good image quality by 42 patients (75%) and good wearability by 39 (70%). Thirty-six patients (64%) reported they had deepened their understanding of their diseases. There were no major complications, and only 2 patients (4%) had mild eye fatigue. There was no significant association between questionnaire results and patient characteristics. None of the questionnaire results changed significantly after the questionnaire was made anonymous. CONCLUSIONS The use of a modern head-mounted display by patients during sonographic examinations provided good image quality with acceptable wearability. It could deepen their understanding of their diseases and help develop patient-centered care.

Objectives To investigate the oncological and functional outcome of distal ureterectomy compared with nephroureterectomy in the management of distal ureteral urothelial carcinoma. Methods Using a database including upper urinary tract urothelial carcinoma patients (n = 1329), 282 patients were identified with urothelial carcinoma localized in the distal ureter on clinical evaluation. To adjust for potential baseline differences between groups, 43 patients undergoing distal ureterectomy were matched with 86 patients undergoing nephroureterectomy using propensity scoring. Cox regression models tested the effect of surgery type on recurrence-free survival and cancer-specific survival. Estimated glomerular filtration rate was measured before and after surgery. Results The median follow-up period was 50 months. There were no significant differences in 5-year recurrence-free survival and cancer-specific survival rates between the distal ureterectomy and nephroureterectomy groups (P = 0.22 and P = 0.70, respectively). Multivariate analysis showed that surgery type was not associated with recurrence-free survival and cancer-specific survival (P = 0.90 and P = 0.28, respectively). In the subanalysis, recurrence-free survival and cancer-specific survival in the distal ureterectomy group were equivalent to those of the nephroureterectomy group in both pTa-1 and pT2-4 patients. Renal function was better preserved in the distal ureterectomy group than in the nephroureterectomy group (rate of change in estimated glomerular filtration rate 2% vs −20%; P

Objectives To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. Methods We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease (Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m2) as follows

We present an application of a new three-dimensional head-mounted display system that combines a high-definition three-dimensional organic electroluminescent head-mounted display with a high-definition three-dimensional endoscope to minimally invasive surgery, using gasless single-port radical nephrectomy procedures as a model. This system presents the surgeon with a higher quality of magnified three-dimensional imagery in front of the eyes regardless of head position, and simultaneously allows direct vision by moving the angle of sight downward. It is also significantly less expensive than the current robotic surgery system. While carrying out gasless single-port radical nephrectomy, the system provided the surgeon with excellent three-dimensional imagery of the operative field, direct vision of the outside and inside of the patient, and depth perception and tactile feedback through the devices. All four nephrectomies were safely completed within the operative time, blood loss was within usual limits and there were no complications. The display was light enough to comfortably be worn for a long operative time. Our experiences show that the three-dimensional head-mounted display system might facilitate maneuverability and safety in minimally invasive procedures, without prohibitive cost, and thus might mitigate the drawbacks of other three-dimensional vision systems. Because of the potential benefits that this system offers, it deserves further refinements of its role in various minimally invasive surgeries.

Study Type – Prognosis (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? The additional use of anti-androgen (deferred combined androgen blockade [CAB] therapy) for patients with castration-resistant prostate cancer (CRPC) initially treated with androgen deprivation monotherapy (ADMT) can provide a clinical response, although the reported response rates vary widely. Our previous study, which reported a response rate of 66% to deferred CAB therapy, suggested that deferred CAB responders would also respond better to subsequent therapies than non-responders because the difference in cancer-specific survival between the deferred CAB responders and the non-responders was much larger than the progression-free survival rates for the responders. The present study showed that PSA response to deferred CAB therapy predicts clinical outcomes after subsequent oestrogen and docetaxel therapy. We propose that PSA response to deferred CAB be used for planning individualized treatment that includes secondary hormonal therapy and chemotherapy. OBJECTIVE • To evaluate whether there is any association between prostate-specific antigen (PSA) response to deferred combined androgen blockade (CAB) therapy using bicalutamide in patients with castration-resistant prostate cancer (CRPC), initially treated with castration monotherapy, and the clinical outcomes after subsequent oestrogen and docetaxel therapies. PATIENTS AND METHODS • Fifty-six patients with advanced prostate cancer, who were refractory to both initial castration monotherapy and subsequent deferred CAB, received oestrogen therapy (estramustine phosphate 140 or 280 mg/day in 50 patients, diethylstilbestrol diphosphate 100 mg/day orally in six patients). Of the 56 patients, 33 underwent docetaxel therapy (median dose 55 mg/m2, every 4–8 weeks, median 6 courses) when they became refractory to oestrogen therapy. • A deferred CAB response was defined as a decrease of >50% in PSA levels after the addition of bicalutamide. The difference in cancer-specific survival (CSS) after confirmation of resistance to initial castration monotherapy between the deferred CAB responders and the non-responders was evaluated, and outcomes after oestrogen and docetaxel therapies were also compared between the two groups. RESULTS • A response to deferred CAB was observed in 27 (48%) of the 56 patients. There was no significant difference between the responders and the non-responders in pretreatment clinical variables, including Gleason score, metastatic sites, PSA level at diagnosis, and PSA nadir during castration monotherapy. • A deferred CAB response was a significant predictor of CSS after confirmation of resistance to initial castration monotherapy. • The deferred CAB responders had significantly longer progression-free survival (PFS) (median 3.2 months in the responders, 2.1 month in the non-responders, P= 0.04) and CSS (median 3.0 years in the responders, 1.5 years in the non-responders, P= 0.04) after oestrogen therapy. Likewise, PFS (median 8.2 months in the responders, 2.2 months in the non-responders, P < 0.01) and CSS (median not reached in the responders, 1.4 years in the non-responders, P < 0.01) after docetaxel therapy was significantly longer in the deferred CAB responders. CONCLUSION • PSA response to deferred CAB predicts clinical outcomes after subsequent oestrogen and docetaxel therapies in patients with CRPC, and provides useful information for planning individualized optimum treatment courses that include secondary hormonal therapy and chemotherapy.

We have recently reported favorable responses to a combination treatment comprising cimetidine, a cyclooxygenase-2 inhibitor and a renin-angiotensin-system inhibitor in metastatic renal cell carcinoma (RCC). In view of the potential synergistic effects of these three agents and interferon-α (I-CCA therapy), we conducted a phase-II trial to examine the efficacy and toxicity of I-CCA as first-line treatment. Fifty-one patients with advanced RCC received natural interferon-α (3-6 million U thrice/week) and cimetidine (800 mg), cyclooxygenase-2 inhibitor meloxicam (10 mg), and renin-angiotensin-system inhibitor candesartan (4 mg) or perindopril (4 mg) orally daily. Memorial Sloan-Kettering Cancer Center prognostic categories were favorable, intermediate and poor in 10 (20%), 31 (61%) and 10 (20%) patients, respectively. The primary end-point was the objective response rate (ORR) and the secondary end-points included clinical benefit, progression-free survival (PFS), overall survival (OS) and safety. Median follow-up was 19 months. Complete response (CR) was observed in four patients (8%) and partial response in seven (14%), yielding an ORR of 22%. None of the four patients who achieved CR relapsed during the 16- to 81-month follow up. The ORR were 17% in the favorable- or intermediate-risk group and 40% in the poor-risk group. The other 24 patients (45%) had stable disease for at least 6 months, resulting in a clinical benefit rate of 67%. The median PFS and OS were 12 and 30 months, respectively. Grade 3/4 toxicities were never observed. The I-CCA therapy, providing favorable responses and low toxicity profiles, is worthy of further consideration as a first-line therapy for metastatic RCC.

OBJECTIVE To investigate the interactions between inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in response to ischaemia-reperfusion (I/R) of rabbit bladder. MATERIALS AND METHODS Rabbit bladders were exposed to 2 h of ischaemia by bilaterally clamping the major arteries entering the bladder and then a subsequent 36 h of reperfusion (I/R) with or without intraperitoneal administration of a selective iNOS inhibitor n-(3-(amynomethyl)benzyl)acetamidine (1400W) or a selective COX-2 inhibitor NS-398 given 1 h before killing. The bladder tissues were processed for isometric tension experiments, enzymatic NOS activitiy, tissue contents of nitrite/nitrate (NOX), cyclic guanosine monophosphate (cGMP) and COX activity determined by prostaglandin E2 (PGE2) production. RESULTS iNOS and constitutive NOS (cNOS) activities, NOX and PGE2 contents in the bladder tissues at 36 h after reperfusion were significantly higher than those in the sham group with no significant increase in cGMP. Treatment with 1400W abrogated the increases in iNOS activity and NOX as well as PGE2 without changing cNOS activity. In the tension experiments, a NOS substrate, l-arginine, induced detrusor contraction only in the I/R group, which was inhibited by 1400W or NS-398 but not by a selective soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazole[4,3-a]quinoxalin-1-one (ODQ). 8-Br-cGMP induced detrusor relaxation in the sham and I/R groups. Also, l-arginine increased NOX and PGE2 in the bladder tissues only in the I/R group, which were inhibited by pretreatment with 1400W. While, l-arginine increased cGMP contents in the I/R group and this increase was suppressed by ODQ but not by 1400W. CONCLUSION These results show that NO derived from an up-regulation of iNOS after I/R increases COX-2-derived PG via a cGMP-independent mechanism. NO-mediated activation of COX-2 may be an important mechanism for the modulation of bladder function after I/R injury.

OBJECTIVES To investigate the effects of reactive oxygen species (ROS) on the micturition reflex in vivo, especially in bladder afferent signalling in rats, as several pathophysiological conditions in the urinary bladder (e.g. ischaemia/reperfusion and inflammation) are characterized by the formation of ROS. MATERIALS AND METHODS Adult female Sprague-Dawley rats under urethane anaesthesia (normal or pretreated with 125 mg/kg capsaicin, subcutaneously, 4 days before) were assessed by continuous cystometrography (CMG) with or without the intravesical administration of H(2)O(2) (0.003-3%) to stimulate ROS damage. To investigate the mechanism of H(2)O(2), catalase (a H(2)O(2) scavenger) was applied intravesically (2000 IU/mL), or rats were given intravenous injections with superoxide dismutase (SOD, 20,000 IU/kg, a superoxide anion scavenger), dimethylthiourea (DMTU, 100 mg/kg, a hydroxyl radical scavenger), deferoxamine (20 mg/kg, an iron-chelator that prevents the formation of hydroxyl radical), indomethacin (3 mg/kg, a cyclooxygenase inhibitor) or ketoprofen (1 mg/kg, a cyclooxygenase inhibitor) just before or during the intravesical administration of H(2)O(2). Prostaglandin (PG) levels (PGE(2) and 6-keto-PGF(1 alpha)) were measured in the bladder of rats treated with intravesical 0.3% H(2)O(2) for 30 min with or without indomethacin. RESULTS Intravesical administration of H(2)O(2) induced detrusor overactivity, as shown by a reduction in the mean (sem) intercontraction interval (ICI), in a dose-dependent manner in normal rats (0.3% H(2)O(2,) P < 0.01, 36.2 (4.7)% of the control ICI). H(2)O(2)-induced detrusor overactivity was almost abolished by catalase and significantly suppressed by DMTU, deferoxamine, capsaicin pretreatment, indomethacin or ketoprofen but not by SOD. The level of PGs was significantly increased by H(2)O(2) instillation, and indomethacin significantly inhibited the increase in PGs. CONCLUSION These results indicate that oxidative stress induced by H(2)O(2) activates capsaicin-sensitive C-fibre afferent pathways, at least in part, mediated via stimulation of the cyclooxygenase pathway, thereby inducing detrusor overactivity. Thus, rats treated with intravesical H(2)O(2) appear to be a suitable model for the study of detrusor overactivity.

Fistula formation between the upper urinary tract and bowel is an uncommon complication in urogenital diseases. We present a rare case of focal xanthogranulomatous pyelonephritis with a renocolic fistula. This is the first case where a parapelvic cyst obstructs the caliceal outflow and leads to the formation of a renocolic fistula in renal inflammatory disease. It is difficult to make a preoperative diagnosis of focal xanthogranulomatous pyelonephritis with widespread involvement that is caused by non-calculous urinary tract obstruction.