Update on robotic cystectomy.

PURPOSE OF REVIEW: This article aims to discuss recently published (2019-2021) studies on robot-assisted radical cystectomy (RARC) with attention to evidence comparing intracorporeal (ICUD) and extracorporeal urinary diversion (ECUD) in terms of intraoperative and perioperative metrics. RECENT FINDINGS: RARC produces equivalent oncological outcomes compared to open radical cystectomy (ORC). The benefits of RARC are most pronounced perioperatively. ICUD has been increasingly used at centers of excellence as it reduces intestinal exposure, which may incrementally minimize morbidity compared to ECUD or ORC. As the learning curve for ICUD diversion has flattened, retrospective analyses have emerged that suggest this technique may hold benefit over both ORC and RARC with ECUD, though current data is conflicting, and a randomized controlled study is forthcoming. SUMMARY: ORC is the current 'gold standard' management for muscle-invasive bladder cancer. Based on the premise of the minimization of perioperative morbidity, the development of RARC, most recently with ICUD, seeks to improve patient outcomes. Despite a protracted learning curve, many expert bladder cancer centers have adopted an intracorporeal approach. As more centers adopt, refine, and climb the learning curve for ICUD, a clearer insight of its effect on morbidity will be revealed-informing further adoption of the technique.

Contemporary Techniques of Prostate Dissection for Robot-assisted Prostatectomy.

BACKGROUND: Over the years, several techniques for performing robot-assisted prostatectomy have been implemented in an effort to achieve optimal oncological and functional outcomes. OBJECTIVE: To provide an evidence-based description and video-based illustration of currently available dissection techniques for robotic prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: A literature search was performed to retrieve articles describing different surgical approaches and techniques for robot-assisted radical prostatectomy (RARP) and to analyze data supporting their use. Video material was provided by experts in the field to illustrate these approaches and techniques. SURGICAL PROCEDURE: Multiple surgical approaches are available: extraperitoneal, transvesical, transperitoneal posterior, transperitoneal anterior, Retzius sparing, and transperineal. Surgical techniques for prostatic dissection sensu strictu are the following: omission of the endopelvic fascia dissection, bladder neck preservation, incremental nerve sparing by means of an antegrade or retrograde approach, and preservation of the puboprostatic ligaments and dorsal venous complex. Recently, techniques for total or partial prostatectomy have been described. MEASUREMENTS: Different surgical approaches and techniques for robotic prostatectomy have been analyzed. RESULTS AND LIMITATIONS: Two randomized controlled trials evaluating the extraperitoneal versus the transperitoneal approach have demonstrated similar results. Level I evidence on the Retzius-sparing approach demonstrated earlier return to continence than the traditional anterior approach. The question whether Retzius-sparing RARP is associated with a higher rate of positive surgical margins is still open due to the intrinsic bias in terms of surgical expertise in the available comparative studies. This technique also offers an advantage in patients who have received kidney transplantation. Retrospective evidence suggests that the more the anatomical dissection (eg., more periprostatic tissue is preserved), the better the functional outcome in terms of continence. Yet, two randomized controlled trials evaluating the different techniques of dissection have so far been produced. Partial prostatectomies should not be offered outside clinical trials. CONCLUSIONS: Several techniques and approaches are available for prostate dissection during RARP. While the Retzius-sparing approach seems to provide earlier return to continence than the traditional anterior transperitoneal approach, no technique has been proved to be superior to other(s) in terms of long-term outcomes in randomized studies. PATIENT SUMMARY: We have summarized available approaches for the surgical treatment of prostate cancer. Specifically, we described the different techniques that can be adopted for the surgical removal of the prostate using robotic technology.

The natural history of untreated muscle-invasive bladder cancer.

OBJECTIVE: To describe the natural history of untreated muscle-invasive bladder cancer (MIBC) and compare the oncological outcomes of treated and untreated patients. PATIENTS AND METHODS: We utilised a database encompassing all patients with newly diagnosed bladder cancer in Stockholm, Sweden between 1995 and 1996. The median follow-up for survivors was 14.4 years. Overall, 538 patients were diagnosed with bladder cancer of whom 126 had clinically localised MIBC. Patients were divided into two groups: those who received radical cystectomy or radiation therapy, and those who did not receive any form of treatment. Multivariable Cox or competing-risks regressions were adopted to predict metastasis, overall survival (OS), and cancer-specific mortality (CSM), when appropriate. Analyses were adjusted for age at diagnosis, sex, tumour stage, clinical N stage, and treatment. RESULTS: In all, 64 (51%) patients did not receive any definitive local treatment. In the untreated group, the median (interquartile range) age at diagnosis was 79 (63-83) vs 69 (63-74) years in the treated group (P < 0.001). Overall, 109 patients died during follow-up. At 6 months after diagnosis, 38% of the untreated patients had developed metastatic disease and 41% had CSM. The 5-year OS rate for untreated and treated patients was 5% (95% confidence interval [CI] 1, 12%) vs 48% (95% CI 36, 60%), respectively. Patients not receiving any treatment had a 5-year cumulative incidence of CSM of 86% (95% CI 75, 94%) vs 48% (95% CI 36, 60%) for treated patients. Untreated patients had a higher risk of progression to metastatic disease (hazard ratio [HR] 2.40, 95% CI 1.28, 4.51; P = 0.006), death from any cause (HR 2.63, 95% CI 1.65, 4.19; P < 0.001) and CSM (subdistribution HR 2.02, 95% CI 1.24, 3.30; P = 0.004). CONCLUSIONS: Untreated patients with MIBC are at very high risk of near-term CSM. These findings may help balance the risks vs benefits of integrating curative intent therapy particularly in older patients with MIBC.

Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer.

BACKGROUND: Achieving a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) has been associated with improved overall survival (OS). This study was aimed at evaluating the impact of pathologic downstaging (pDS; ie, a pT stage at least 1 stage lower than the pre-NAC cT stage) on the OS of patients with MIBC treated with NAC. METHODS: The Retrospective International Study of Cancers of the Urothelial Tract (RISC) and the National Cancer Database (NCDB) were queried for cT2-4N0M0 patients treated with NAC. A multivariable Cox model including either pDS or pCR was generated. A nested model was built to evaluate the added value of pDS (excluding patients achieving a pCR) to a model including pCR alone. C indices were computed to assess discrimination. NCDB was used for validation. The treatment effect of NAC versus cystectomy alone in achieving pDS was estimated through an inverse probability-weighted regression adjustment. RESULTS: Overall, 189 and 2010 patients from the RISC and NCDB cohorts, respectively, were included; pDS and pCR were achieved by 33% and 35% and by 20% and 15% in RISC and NCDB, respectively. In both data sets, pDS and pCR were associated with better OS and C indices. Adding pDS excluding pCR to the model with pCR fit the data better (likelihood ratio, P = .019 for RISC and P < .001 for NCDB), and it yielded better discrimination (incremental C index, 4.2 for RISC and 1.6 for NCDB). The treatment effect of NAC in achieving pDS was 2.07-fold (P < .001) in comparison with cystectomy alone. CONCLUSIONS: A decrease of at least 1 stage from the cT stage to the pT stage is associated with improved OS in patients with MIBC treated with NAC.

Robot-assisted extended lymphadenectomy in prostate cancer.

INTRODUCTION: The extent of lymph node dissection (LND) and its potential survival benefit are still a matter of debate. Aim of our review was to summarize the latest literature data regarding the surgical templates, the potential oncological benefits, the functional outcomes and the complications of extended lymph node dissection (eLND) during robot-assisted radical prostatectomy (RARP). EVIDENCE ACQUISITION: We systematically reviewed all relevant studies using PubMed, MEDLINE, Embase, American Urological Association (AUA), European Society of Medical Oncology (ESMO) and European Association of Urology (EAU) guidelines. EVIDENCE SYNTHESIS: A narrative synthesis of all relevant publications on surgical templates, complications, oncological and functional outcomes of robot assisted eLND was undertaken. CONCLUSIONS: A great deal of evidence supports that an extended template of LND is not only technically feasible but also safe in the context of RARP. It is really promising that in the era of minimally invasive surgery, parameters like the lymph node yield and the detection rates of positive lymph nodes during LND have become highly comparable with open series. The extended approach has already proved its benefits in terms of proper patient staging but more studies are needed with regard to functional outcomes and oncological benefits of this procedure.

Intravesical BCG treatment causes a long-lasting reduction of recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer.

PURPOSE: To analyse if BCG treatment leads to long-term reduction of recurrence, progression, and cancer-specific mortality (CSM) in patients with high-risk NMIBC. MATERIALS AND METHODS: 140 patients with high-risk NMIBC were drawn from a population-based cohort of 538 patients with newly diagnosed bladder cancer in the Stockholm County between 1995 and 1996. Data were collected prospectively, and a final follow-up for recurrence, progression, and CSM was performed after 15 years. Patients that received BCG were compared with patients who did not receive BCG. Survival analysis was done with Kaplan-Meier estimates and Mantel-Cox log-rank test. Multivariable Cox proportional regression with stepwise selection was performed to verify the statistical significance of clinicopathological factors of prognostic importance. Results were displayed in Hazard ratios and a p < 0.05 was considered to be statistically significant. RESULTS: With a median follow-up of 100 months (2-182), 76 patients recurred; 50 progressed to muscle invasion; and 92 died of whom 38 died from bladder cancer. After 15-year follow-up, there was a statistically significant reduction in rate for recurrence (HR 0.40, p < 0.0001) and progression (HR 0.52, p = 0.038), but not for CSM, in patients that received BCG compared to those who did not. CONCLUSIONS: In this group, BCG in high-risk NMIBC patients reduced the long-term risk of recurrence and progression. The effect on CSM is yet to be clarified.

Is the open cystectomy era over? An update on the available evidence.

In 2018, robot-assisted radical cystectomy will enter its 15th year. In an era where an effort is being made to standardize complication reporting and videos of the procedure are readily available, it is inevitable and justified that like everything novel, robot-assisted radical cystectomy should be scrutinized against the gold standard, open radical cystectomy. The present comparison is focused on several parameters: oncological, functional and complication outcomes, and direct and indirect costs. Meta-analysis and prospective randomized trials comparing robot-assisted radical cystectomy versus open radical cystectomy have been published, showing an oncological equivalence and in some cases an advantage of robot-assisted radical cystectomy in terms of postoperative morbidity. In the present review, we attempt to update the available knowledge on this debate and discuss the limitations of the current evidence that prevent us from drawing safe conclusions.

Oncologic Outcomes After Robot-assisted Radical Prostatectomy: A Large European Single-centre Cohort with Median 10-Year Follow-up.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) treatment has been widely adopted with limited evidence for long-term (>5 yr) oncologic efficacy. OBJECTIVE: To evaluate long-term oncologic outcomes following RARP. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 885 patients who underwent RARP as monotherapy for PCa between 2002 and 2006 in a single European centre and followed up until 2016. INTERVENTION: RARP as monotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence (BCR)-free survival (BCRFS), salvage therapy (ST)-free survival (STFS), prostate cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method, and event-time distributions were compared using the log-rank test. Variables predictive of BCR and ST were identified using Cox proportional hazards models. RESULTS AND LIMITATIONS: We identified 167 BCRs, 110 STs, 16 PCa-related deaths, and 51 deaths from other/unknown causes. BCRFS, STFS, CSS, and OS rates were 81.8%, 87.5%, 98.5%, and 93.0%, respectively, at median follow-up of 10.5 yr. On multivariable analysis, the strongest independent predictors of both BCR and ST were preoperative Gleason score, pathological T stage, positive surgical margins (PSMs), and preoperative prostate-specific antigen. PSM >3mm/multifocal but not ≤3mm independently affected the risk of both BCR and ST. Study limitations include a lack of centralised histopathologic reporting, lymph node and post-operative tumour volume data in a historical cohort, and patient-reported outcomes. CONCLUSIONS: RARP appears to confer effective long-term oncologic efficacy. The risk of BCR or ST is unaffected by ≤3mm PSM, but further follow-up is required to determine any impact on CSS. PATIENT SUMMARY: Robot-assisted surgery for prostate cancer is effective 10 yr after treatment. Very small (<3mm) amounts of cancer at the cut edge of the prostate do not appear to impact on recurrence risk and the need for additional treatment, but it is not yet known whether this affects the risk of death from prostate cancer.

Effect of Comorbidity on Prostate Cancer-Specific Mortality: A Prospective Observational Study.

Purpose To determine the effect of comorbidity on prostate cancer (PCa)-specific mortality across treatment types. Patients and Methods These are the results of a population-based observational study in Sweden from 1998 to 2012 of 118,543 men who were diagnosed with PCa with a median follow-up of 8.3 years (interquartile range, 5.2 to 11.5 years) until death from PCa or other causes. Patients were categorized by patient characteristics (marital status, educational level) and tumor characteristics (serum prostate-specific antigen, tumor grade and clinical stage) and by treatment type (radical prostatectomy, radical radiotherapy, androgen deprivation therapy, and watchful waiting). Data were stratified by Charlson comorbidity index (0, 1, 2, or ≥ 3). Mortality from PCa and other causes and after stabilized inverse probability weighting adjustments for clinical patient and tumor characteristics and treatment type was determined. Kaplan-Meier estimates and Cox proportional hazards regression models were used to calculate hazard ratios. Results In the complete unadjusted data set, we observed an effect of increased comorbidity on PCa-specific and other-cause mortality. After adjustments for patient and tumor characteristics, the effect of comorbidity on PCa-specific mortality was lost but maintained for other-cause mortality. After additional adjustment for treatment type, we again failed to observe an effect for comorbidity on PCa-specific mortality, although it was maintained for other-cause mortality. Conclusion This large observational study suggests that comorbidity affects other cause-mortality but not PCa-specific- mortality after accounting for patient and tumor characteristics and treatment type. Regardless of radical treatment type (radical prostatectomy or radical radiotherapy), increasing comorbidity does not seem to significantly affect the risk of dying from PCa. Consequently, differences in oncologic outcomes that were observed in population-based comparative effectiveness studies of PCa treatments may not be a result of the varying distribution of comorbidity among treatment groups.

Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy.

BACKGROUND: There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer. OBJECTIVE: To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival. DESIGN, SETTING, AND PARTICIPANTS: An observational population-based Swedish study from 1996 to 2010 of men at high risk of disseminated prostate cancer (prostate-specific antigen [PSA] >50) initially treated by radical therapy (radiation therapy [n=630] or radical prostatectomy [n=120]) or androgen deprivation therapy (n=17 602), and followed for up to 15 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-cancer and other-cause mortality was estimated for the treatment groups. We also matched the two cohorts for grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and found androgen deprivation therapy patient matches for 575 of the radical therapy patients, and then repeated comparative effectiveness analyses. RESULTS AND LIMITATION: Prostate-cancer mortality was substantially greater in the androgen deprivation therapy group compared with the radically treated one, in unmatched (9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched cohorts, initial androgen deprivation therapy was associated with nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses suggested that the findings were robust, although the general limitations of nonrandomized studies remain. Further, the study cohort may have included men with both systemic and nonsystemic disease, as a sole eligibility criterion of PSA >50 was used. CONCLUSIONS: This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival. PATIENT SUMMARY: This large Swedish study suggests that men with prostate cancer that has spread beyond the prostate benefit from treating the prostate itself with radiation therapy or surgery rather than treating the disease with hormones alone.

Prostaglandin D2 effects and DP1 /DP2 receptor distribution in guinea pig urinary bladder out-flow region.

The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD2 actions in guinea pig out-flow region and the distribution of DP1 /DP2 receptors. The effects of PGD2 on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP1 /DP2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP1 /DP2 receptors. PGD2 in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD2 was equally (trigone) or slightly less potent (urethra) compared with PGE2 . Expression of DP1 and DP2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP1 and DP2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD2 may therefore be a modulator of the bladder out-flow region, possibly having a function in regulation of micturition and a role in overactive bladder syndrome.

Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

PURPOSE: Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. MATERIALS AND METHODS: All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. RESULTS: BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. CONCLUSIONS: Our results suggest that the investigated polymorphisms influence patient response to BCG-treatment and thus may serve as possible markers for identification of BCG-failures.

Localization of P2X receptor subtypes 2, 3 and 7 in human urinary bladder.

BACKGROUND: Voiding dysfunctions are a common problem that has a severe negative impact on the quality of life. Today there is a need for new drug targets for these conditions. The role of ATP receptors in bladder physiology has been studied for some time, primarily in animal models. The aim of this work is to investigate the localization of the ATP receptors P2X2, P2X3 and P2X7 and their colocalization with vimentin and actin in the human urinary bladder. METHODS: Immunohistochemical analysis was conducted on full-thickness bladder tissues from fundus and trigonum collected from 15 patients undergoing open radical cystectomy due to chronic cystitis, bladder cancer or locally advanced prostate cancer. Colocalization analyses were performed between the three different P2X subtypes and the structural proteins vimentin and actin. Specimens were examined using epifluorescence microscopy and correlation coefficients were calculated for each costaining as well as the mean distance from the laminin positive basal side of the urothelium to the vimentin positive cells located in the suburothelium. RESULTS: P2X2 was expressed in vimentin positive cells located in the suburothelium. Less distinct labelling of P2X2 was also observed in actin positive smooth muscle cells and in the urothelium. P2X3 was expressed in vimentin positive cells surrounding the smooth muscle, and in vimentin positive cells located in the suburothelium. Weaker P2X3 labelling was seen in the urothelium. P2X7 was expressed in the smooth muscle cells and the urothelium. In the suburothelium, cells double positive for P2X2 and vimentin where located closer to the urothelium while cells double positive for P2X3 and vimentin where located further from the urothelium. CONCLUSION: The results from this study demonstrate that there is a significant difference in the expression of the purinergic P2X2, P2X3 and P2X7 receptors in the different histological layers of the human urinary bladder.

Enhanced recovery protocols (ERP) in robotic cystectomy surgery. Review of current status and trends.

Open radical cystectomy with pelvic lymphadenectomy and urinary diversion is associated with a high complication rate. Robotic-assisted laparoscopic radical cystectomy is increasingly performed in many urologic surgical departments in an effort to reduce surgical stress and decrease perioperative morbidity. Robotic cystectomy survival studies demonstrate similar oncologic outcomes compared to the open procedure. Enhanced recovery protocols (ERP) after major surgery are multimodal perioperative interventions to reduce surgical stress, complications, and patient convalescence. Evidence for different ERP interventions are currently mainly from colorectal surgery and recently adapted to major urologic operations including cystectomy. Guidelines for perioperative care after open radical cystectomy for bladder cancer were recently published, but these recommendations may differ when considering a robotic approach. Therefore, we look at the current evidence for ERP in both open and robotic radical cystectomy and the potential for improving ERPs in robotic cystectomy by utilizing a totally intracorporeal robotic cystectomy approach. We also present the Karolinska ERP currently utilized in totally intracorporeal robotic cystectomy.

Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2.

BACKGROUND AND PURPOSE: We have described a urothelium-dependent release of PGD2 -like activity which had inhibitory effects on the motility of guinea pig urinary bladder. Here, we have pharmacologically characterized the receptors involved and localized the sites of PGD2 formation and of its receptors. EXPERIMENTAL APPROACH: In the presence of selective DP and TP receptor antagonists alone or combined, PGD2 was applied to urothelium-denuded diclofenac-treated urinary bladder strips mounted in organ baths. Antibodies against PGD2 synthase and DP1 receptors were used with Western blots and for histochemistry. KEY RESULTS: PGD2 inhibited nerve stimulation -induced contractions in strips of guinea pig urinary bladder with estimated pIC50 of 7.55 ± 0.15 (n = 13), an effect blocked by the DP1 receptor antagonist BW-A868C. After blockade of DP1 receptors, PGD2 enhanced the contractions, an effect abolished by the TP receptor antagonist SQ-29548. Histochemistry revealed strong immunoreactivity for PGD synthase in the urothelium/suburothelium with strongest reaction in the suburothelium. Immunoreactive DP1 receptors were found in the smooth muscle of the bladder wall with a dominant localization to smooth muscle membranes. CONCLUSIONS AND IMPLICATIONS: In guinea pig urinary bladder, the main effect of PGD2 is an inhibitory action via DP1 receptors localized to the smooth muscle, but an excitatory effect via TP receptors can also be evoked. The urothelium with its suburothelium might signal to the smooth muscle which is rich in PGD2 receptors of the DP1 type. The results are important for our understanding of regulation of bladder motility.

Short-term results after robot-assisted laparoscopic radical prostatectomy compared to open radical prostatectomy.

BACKGROUND: Robot-assisted laparoscopic radical prostatectomy has become a widespread technique despite a lack of randomised trials showing its superiority over open radical prostatectomy. OBJECTIVE: To compare in-hospital characteristics and patient-reported outcomes at 3 mo between robot-assisted laparoscopic and open retropubic radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: A prospective, controlled trial was performed of all men who underwent radical prostatectomy at 14 participating centres. Validated patient questionnaires were collected at baseline and after 3 mo by independent health-care researchers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The difference in outcome between the two treatment groups were analysed using logistic regression analysis, with adjustment for identified confounders. RESULTS AND LIMITATIONS: Questionnaires were received from 2506 (95%) patients. The robot-assisted surgery group had less perioperative bleeding (185 vs 683 ml, p<0.001) and shorter hospital stay (3.3 vs 4.1 d, p<0.001) than the open surgery group. Operating time was shorter with the open technique (103 vs 175 min, p<0.001) compared with the robot-assisted technique. Reoperation during initial hospital stay was more frequent after open surgery after adjusting for tumour characteristics and lymph node dissection (1.6% vs 0.7%, odds ratio [OR] 0.31, 95% confidence interval [CI 95%] 0.11-0.90). Men who underwent open surgery were more likely to seek healthcare (for one or more of 22 specified disorders identified prestudy) compared to men in the robot-assisted surgery group (p=0.03). It was more common to seek healthcare for cardiovascular reasons in the open surgery group than in the robot-assisted surgery group, after adjusting for nontumour and tumour-specific confounders, (7.9% vs 5.8%, OR 0.63, CI 95% 0.42-0.94). The readmittance rate was not statistically different between the groups. A limitation of the study is the lack of a standardised tool for the assessment of the adverse events. CONCLUSIONS: This large prospective study confirms previous findings that robot-assisted laparoscopic radical prostatectomy is a safe procedure with some short-term advantages compared to open surgery. Whether these advantages also include long-term morbidity and are related to acceptable costs remain to be studied. PATIENT SUMMARY: We compare patient-reported outcomes between two commonly used surgical techniques. Our results show that the choice of surgical technique may influence short-term outcomes.

Cascade bioassay evidence for the existence of urothelium-derived inhibitory factor in Guinea pig urinary bladder.

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1-5 µM in the presence of scopolamine 5-30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor.

Secondary stimulation from Bacillus Calmette-Guérin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells.

The anti-tumour mechanisms following Bacillus Calmette-Guérin (BCG) treatment of bladder-cancer remain largely unknown. Previous studies have shown involvement of nitric-oxide (NO) formation in the BCG-mediated effect. We analyzed the effects of macrophage secreted factors (MSFs) from BCG-stimulated RAW264.7 cells on the bladder-cancer cell line MBT2. Direct treatment with BCG did not induce NO in MBT2-cells whereas supernatant from BCG-stimulated macrophages increased NOS2 mRNA and protein expression, NO concentrations and cell-death. Blocking NO-synthesis with the NOS-inhibitor L-NAME did not affect levels of cell-death suggesting cytotoxic pathways involving other signalling molecules than NO. Several such candidate genes were identified in a microarray.