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Background: Little is known regarding functional outcomes after robot-assisted radical cystectomy (RARC) and intracorporeal neobladder (ICNB) reconstruction. Objective: To report on urinary continence (UC) and erectile function (EF) at 12 mo after RARC and ICNB reconstruction and investigate predictors of these outcomes. Design, setting, and participants: We used data from a multi-institutional database of patients who underwent RARC and ICNB reconstruction for bladder cancer. Surgical procedure: The cystoprostatectomy sensu stricto followed the conventional steps. ICNB reconstruction was performed at the physician's discretion according to the Studer/Wiklund, S pouch, Gaston, vescica ileale Padovana, or Hautmann technique. The techniques are detailed in the video accompanying the article. Measurements: The outcomes measured were UC and EF at 12 mo. Results and limitations: A total of 732 male patients were identified with a median age at diagnosis of 64 yr (interquartile range 58–70). The ICNB reconstruction technique was Studer/Wiklund in 74%, S pouch in 1.5%, Gaston in 19%, vescica ileale Padovana in 1.5%, and Hautmann in 4% of cases. The 12-mo UC rate was 86% for daytime and 66% for nighttime continence, including patients who reported the use of a safety pad (20% and 32%, respectively). The 12-mo EF rate was 55%, including men who reported potency with the aid of phosphodiesterase type 5 inhibitors (24%). After adjusting for potential confounders, neobladder type was not associated with UC. Unilateral nerve-sparing (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.88–7.85; p < 0.001) and bilateral nerve-sparing (OR 6.25, 95% CI 3.55–11.0; p < 0.001), were positively associated with EF, whereas age (OR 0.93, 95% CI 0.91–0.95; p < 0.001) and an American Society of Anesthesiologists score of 3 (OR 0.46, 95% CI 0.25–0.89; p < 0.02) were inversely associated with EF. Conclusions: RARC and ICNB reconstruction are generally associated with good functional outcomes in terms of UC. EF is highly affected by the degree of nerve preservation, age, and comorbidities. Patient summary: We investigated functional outcomes after robot-assisted removal of the bladder in terms of urinary continence and erectile function. We found that, in general, patients have relatively good functional outcomes at 12 months after surgery.

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.

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.

Objective: Technical skills in robot-assisted radical prostatectomy (RARP) are not mandated by the Intercollegiate Surgical Curriculum Programme. The European Association of Urology Robotic Urology Section (ERUS) developed a structured curriculum; however, surgeons’ outcomes data from subsequent independent practice are limited. We describe the initial post-ERUS curriculum RARP outcomes for a United Kingdom (UK)-based surgeon. Patients and methods: This was a prospective single surgeon cohort study of 272 patients who underwent RARP between February 2016 and October 2019 in a high-volume UK centre and who were followed up at approximately 3 and 12 months. Positive surgical margins (PSMs), and 3- and 12-month continence rates were obtained and used to generate learning curves, with point of plateau estimated from logarithmic trendlines. Results: Overall (⩾3 mm) PSM rate for pT2 was 14.9% (5.4%) and pT3 was 22.6% (3.2%). Where data were available, 70.5% (of n=251) and 95.5% (of n=154) patients achieved social continence (0–1 pads) at 3 and 12 months, respectively. PSM and 3-month social continence rates plateaued at ~175 and ~100 cases, respectively. Conclusion: Following completion of the ERUS RARP curriculum, early oncological and functional outcomes consistent with published standards are rapidly achievable in independent practice. These data exemplify the potential value of a standardised RARP training curriculum to mitigate possible compromises in outcomes. Level of evidence: IV

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

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

Supplemental material, Sehmbi_(2020)_JCU_Supplementary_Table_S1 for Early outcomes of robot-assisted radical prostatectomy following completion of a structured training curriculum: a single surgeon cohort study by Arjan S Sehmbi, Ashwin N Sridhar, Kanagasabai Sahadevan, Bhavan P Rai, Pamela Nwangwu, Anna Mohammed, Alex Freeman, Alexandre Mottrie, Mats J Olsson, N Peter Wiklund, M Senthil Nathan, Timothy P Briggs, John D Kelly and Prabhakar Rajan in Journal of Clinical Urology

Robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) treatment has been widely adopted with limited evidence for long-term (5 yr) oncologic efficacy.To evaluate long-term oncologic outcomes following RARP.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.RARP as monotherapy.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.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. PSM3mm/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.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.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.

INTRODUCTION AND OBJECTIVES:The presence of tertiary pattern 5 (TP5) on radical prostatectomy specimens has been associated with worse long-term outcomes. However, the molecular underpinnings of TP...

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.

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.

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

Although open radical cystectomy (ORC) remains the gold standard of care for muscle-invasive bladder cancer, robot-assisted radical cystectomy (RARC) continues to gain wider acceptance. The technique of robot-assisted radical cystectomy (RARC) has evolved significantly since its inception more than 10 years ago. Several high-volume centers have reported standardized techniques with refinements and subsequent oncological and functional outcomes. We summarise published outcomes for totally intracorporeal RARC in the chapter. Totally intracorporeal RARC aims to offer the benefits of a complete minimally invasive approach while replicating the oncologic outcomes of open surgery. In this chapter, we focus on the steps of intracorporeal urinary diversion in RARC, describing our approach, which has been developed over the past 10 years. We have described the Karolinska technique for both intracorporeal ileal conduit formation and neobladder formation. Our structured approach to RARC has enabled us to develop this complex service while maintaining patient outcomes comparable with ORC series. We conclude that the refinement of techniques for RARC and urinary diversion over the past 10 years has made it safe, reproducible, and oncologically sound.

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, Graphical abstract, Highlights • 30% of BCG treated bladder cancer (NMIBC)-patients do not respond to BCG-treatment. • We need to identify BCG failures before the BCG-treatment is given. • Altered NOS2 and NOS3 gene activity may be associated with BCG treatment outcome. • NOS-polymorphisms are possible BCG-failure biomarkers in bladder cancer patients.

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.

Robot-assisted laparoscopic radical prostatectomy has become a widespread technique despite a lack of randomised trials showing its superiority over open radical prostatectomy.To compare in-hospital characteristics and patient-reported outcomes at 3 mo between robot-assisted laparoscopic and open retropubic radical prostatectomy.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.The difference in outcome between the two treatment groups were analysed using logistic regression analysis, with adjustment for identified confounders.Questionnaires were received from 2506 (95%) patients. The robot-assisted surgery group had less perioperative bleeding (185 vs 683 ml, p0.001) and shorter hospital stay (3.3 vs 4.1 d, p0.001) than the open surgery group. Operating time was shorter with the open technique (103 vs 175 min, p0.001) 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.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.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.

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.

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.

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.

The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD 2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD 2 actions in guinea pig out‐flow region and the distribution of DP 1/DP 2 receptors. The effects of PGD 2 on urothelium‐intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP 1/DP 2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP 1/DP 2 receptors. PGD 2 in a dose‐dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD 2 was equally (trigone) or slightly less potent (urethra) compared with PGE 2. Expression of DP 1 and DP 2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP 1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP 2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD 2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP 1 and DP 2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD 2 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.

There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer.To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival.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.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.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 PSA50 was used.This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival.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.

Background Robot-assisted radical cystectomy (RARC) may reduce morbidity after cystectomy. Descriptions of the surgical techniques of RARC with intracorporeal orthotopic neobladder or ileal conduit are sparse and oncologic and functional outcome data have not been reported. Objective We present our technique with RARC and intracorporeal urinary diversion (neobladder or ileal conduit) and present oncologic and functional outcomes, as well as complication rates. Design, setting, and participants Single-hospital institution case-series from 2004 to 2009 including 45 selected patients (38 male, 7 female) with high-grade and/or muscle-invasive urothelial cancer of the bladder. Surgical procedure We performed RARC; pelvic lymph node dissection using three different templates; and a totally intracorporeal urinary diversion, either orthotopic neobladder ( n =36) or ileal conduit ( n =9). Measurements Perioperative variables, pathology data, early and late complication rates, urinary continence, potency, and cancer-specific survival were evaluated as outcome measures. Results and limitations Median patient age, operative time, estimated blood loss, and lymph node yield were 62 yr (range: 37–79), 477min (range: 325–760), 550ml (range: 200–2200), and 19 (range: 10–52), respectively. Nine patients were diagnosed with positive lymph nodes. Surgical margins were clear in all but one patient. Early complications occurred in 18 patients (40%). Median postoperative stay was 9 d (range: 4–78), and median postoperative follow-up time was 25 mo. Four patients died due to metastatic disease. The study is limited by a relative small sample size and no comparative group. Conclusions RARC with totally intracorporeal urinary diversion is technically feasible with good intermediate-term oncologic results. This is a nonrandomised study including a limited number of patients with a restricted follow-up time, however, and so precautions must be considered when interpreting the outcomes.

What's known on the subject? and What does the study add? Robotic-assisted radical cystectomy and pelvic lymphadenectomy have previously been described with an extracorporeal urinary diversion. In this study we describe the technique with totally intracorporeal RARC and orthotopic neobladder. OBJECTIVE • The aim of this report is to describe our surgical technique of robotic assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion in patients with urinary bladder cancer. PATIENTS AND METHODS • A total of 45 patients (7 women and 38 men) with high-grade and/or muscle-invasive urothelial cancer of the bladder underwent RARC and intracorporeal urinary diversion at our department. • Orthotopic ileal neobladder was performed in 36 patients and ileal conduit was performed in 9 patients. RESULT • Except in two patients that operation was converted to open surgery during the reconstruction of the orthotopic neobladder, the procedure was performed totally intracorporeal. • The operations time, estimated blood loss and length for hospital stay were decreased over the time. CONCLUSION • RARC with totally intracorporeal urinary diversion is feasible.

OBJECTIVE To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day. RESULTS Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.

The purpose of this study was to investigate if the ProMIS™ simulator could serve as a training platform for the da Vinci® surgical system and if this constellation could prove construct validity.The da Vinci system was connected to the ProMIS simulator, which registered objective data concerning how the surgeon performed in the box environment related to time, path, and smoothness. Five experienced robotic surgeons passed four different surgical tasks with progressive difficulty. A novice group-constituted of 13 consultants and 6 residents, none of them with any previous experience in the da Vinci system-passed the same tasks and the data were compared with the results from the expert group.A statistically significant difference between experts and novices was demonstrated in all tasks concerning time and smoothness. For the parameter path, significant difference was only noted in the more complex tasks.Our study showed that ProMis could differentiate between experienced robotic surgeons and novices, thereby proving construct validity. Smoothness appeared to be the most sensitive objective parameter in our study. Tasks with high complexity are recommended when designing the program for robotic training.

Purpose of review The prevalence of robot-assisted radical cystectomy is steadily increasing. We review the recent literature evaluating this technique as a minimally invasive alternative to open radical cystectomy for the treatment of bladder cancer. Recent findings Within the last year, numerous robot-assisted radical cystectomy case series with larger cohorts have been published, providing new insights regarding perioperative morbidity and early oncologic outcomes. With appropriate experience, this procedure offers the potential benefits of decreased blood loss and transfusion rates, reduced analgesic requirements, and shorter hospital stay relative to the open approach. Recent data from a nonrandomized study demonstrate fewer postoperative complications with robot-assisted radical cystectomy. Short-term oncologic outcomes in the absence of patient selection appear to be equivalent to contemporary open radical cystectomy series. A small prospective, randomized trial comparing open and robotic radical cystectomy demonstrated equivalent lymph node yields. Summary Robot-assisted radical cystectomy is an emerging minimally invasive approach to radical cystectomy. Early data suggest potential benefits in perioperative morbidity with equivalent short-term oncologic outcomes as compared with open radical cystectomy. Long-term follow-up and larger prospective, randomized comparisons with open radical cystectomy are needed as this technique continues to be evaluated.

Study Type - Preference (prospective cohort) Level of Evidence 4 OBJECTIVES: To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary blad ...

We analyzed whether the NOS2 promoter microsatellite (CCTTT)n polymorphism influences bladder cancer pathogenesis.We genotyped 359 patients with bladder cancer in a population based cohort and 164 population controls by DNA fragment analysis and sequencing. Genotypes were combined with information on tumor stage, grade and stage, grade progression and cancer specific death. Clinical followup was 5 years.We divided (CCTTT)n alleles into short-10 or fewer, intermediate-11 or 12 and long-13 or greater repeats. Patients homozygous for 13 or longer (CCTTT)n repeats were at decreased odds ratio for bladder cancer (p = 0.010). However, after illness developed they were at 3-fold increased hazard ratio for stage progression (p = 0.062) and 4-fold increased hazard ratio for death from bladder cancer (p = 0.056). We discovered what is to our knowledge a previously undescribed polymorphism at position 23105343 (C/T). There was no difference in frequency between bladder cancer cases and population controls for this polymorphism. No associations were found between tumor stage, grade or stage and grade progression. However, patients with bladder cancer with the heterozygous CT genotype were at 3-fold increased hazard ratio of death from cancer (p = 0.011).Nitric oxide can induce proliferation or apoptosis depending on the cellular context. Results suggest that the (CCTTT)n NOS2 microsatellite may influence bladder cancer risk and aggressiveness. This polymorphism may have an impact on disease pathogenesis, possibly by affecting intracellular nitric oxide levels.

Beta-tubulin isotype III is a microtubule component associated with resistance to chemotherapy and poor outcome in various cancers. This study aimed to investigate its expression in prostate cancer and its role as a prognostic factor in this setting.A tissue microarray was constructed of 289 prostate cancers from radical prostatectomy specimens with a median follow-up of 48.9 months. Slides were immunostained for β-tubulin III. The intensity and extent of immunoreactivity and their product [immunoreactivity product (IRP)] were evaluated.Tubulin III was expressed in the cytoplasm of prostate cancer cells but not in benign glands. Only 11.6% of cancers were positive for tubulin III. Among low-grade (Gleason score 5-6) and high-grade (Gleason score 7-10) cancers, 6.0% and 16.6% were positive, respectively (p = 0.006). β-Tubulin III expression was more often seen in high-stage disease and more often in metastases (62.5%) than in primary lesions (11.6%) (p0.001). The intensity, extent and IRP of tubulin III all predicted biochemical recurrence in univariate Cox analysis (p = 0.02, p = 0.048 and p = 0.012, respectively). IRP was an independent predictor of prognosis when adjusted for serum prostate-specific antigen in a multivariate Cox analysis (p = 0.005), but not when the Gleason score was added to the model (p = 0.17).β-Tubulin III predicts biochemical recurrence after radical prostatectomy in a subset of patients. Its practical utility is limited by the low number of cases positive for this biomarker.

Nitrite has been implicated in carcinogenesis, especially under acidic conditions such as in the stomach or in urine, where it forms nitrosating species that can react with secondary amines to form nitrosamines. Recent studies have shown that nitrite and acid form a variety of other nitrogen oxides in vivo including nitric oxide-a compound with documented antitumor activity. Here we tested the effects of nitrite on bladder tumor cells incubated in mildly acidified urine. Nitrite (50 microM) inhibited thymidine incorporation in human T24 bladder cancer cells. This inhibition required slight acidification (pH 5.5-6), and no effect of nitrite could be observed at pH 7. Nitrite effects were further augmented in the presence of ascorbic acid, whereas ascorbic acid alone had no effect. The effects were paralleled by formation of nitric oxide gas. We here demonstrate an inhibitory effect of nitrite on cancer cell replication at concentrations and acidity commonly found in urine and gastric juice. The inhibitory effect is likely caused by nitric oxide and possibly other reactive nitrogen oxides formed from acidified nitrite.

OBJECTIVES To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer. PATIENTS AND METHODS We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval. RESULTS We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for 'never washing hands' before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI. CONCLUSIONS We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI.

The pathophysiology of cluster headache (CH) is only partly understood. Nitric oxide (NO), a potent vasodilator, has been suggested to be involved, and increased plasma levels of nitrite, a stable product on NO degradation, have been identified in the active period and in remission. The aim of our study was to investigate the role of NO in CH by measuring its oxidation products, nitrite and nitrate, in the cerebrospinal fluid (CSF), a biological compartment closer to the supposed focus of the disorder. We collected CSF from 14 episodic CH patients. Lumbar puncture (LP) was performed at two occasions: in active period between headache attacks, and in remission, not earlier than three weeks after the last CH attack. Eleven healthy volunteers served as controls. To estimate NO production, we determined the levels of NO-oxidation end products (NOx), that is, the sum of nitrite and nitrate, by using capillary electrophoresis. CH patients in the active period had significantly increased NOx levels (mean 9.3, 95% confidence interval [CI] 8.5–10.1) compared with those in remission (mean 7.6, 95% CI 6.9–8.2; p

Background Fluorescent light (FL)–guided cystoscopy induced by 5-aminolevulinic acid (5-ALA) has been reported to detect more tumours compared with standard white-light (WL) cystoscopy. Most reports are from single centres with relatively few patients. Objective To evaluate whether 5-ALA–induced FL and WL cystoscopy at transurethral resection (TUR) is superior compared with standard procedures under WL only with respect to tumour recurrence and progression in patients with non–muscle-invasive bladder cancer. Design, setting, and participants This randomised, multicentre, observer- and pathologist-blinded, prospective phase 3 clinical trial enrolled 300 patients, and of those patients, 153 were randomised to FL cystoscopy and 147 were randomised to standard WL cystoscopy. Intervention All patients were first inspected under WL and all lesions were recorded. Patients randomised to FL underwent a second inspection. TUR was carried out in both groups. Measurements Control cystoscopy under WL was performed in all patients every 3 mo during the first year after randomisation and biannually thereafter. Results and limitations At the first TUR, the mean number of resection specimens per patient was 2.5 (FL: 2.5; WL: 2.4; p =0.37) and the resulting mean number of resected tumours was 1.7 with FL and 1.8 with WL ( p =0.85). More patients were diagnosed with carcinoma in situ (CIS) in the WL group (13%) than in the FL group (4.2%). Within-patient comparison of FL patients only showed that FL detected more lesions than WL. Tumour lesions solely detected by FL cystoscopy that would not otherwise be detected by WL cystoscopy included 52% dysplasia, 33% CIS, 18% papillary neoplasms, 13% pT1, and 7% pTa. Outcome at 12 mo did not show any difference between groups with regard to recurrence-free and progression-free survival rates. Conclusions In this prospective, randomised, multi-institutional study, we found no clinical advantage of FL cystoscopy compared with WL cystoscopy and TUR.

To assess whether diagnostic random bladder biopsies and the detection of concomitant carcinoma in situ (CIS) have an impact on the frequency of intravesical bacille Calmette-Guérin (BCG) instillations or radical cystectomy; and whether this affects the cancer-specific survival in patients with pTaG3 or pT1G1-G3 transitional cell carcinoma of the urinary bladder.A population-based cohort of 538 patients with newly diagnosed bladder cancer was prospectively registered in the Stockholm County during 1995 and 1996 and followed for more than 5 years.Random biopsies were recommended in all patients but the decision to take biopsies was made by the treating urologist and hence performed in 326 out of 538 patients (61%), which revealed concomitant CIS in 47 patients(14%). Sixty out of 103 (58%) patients with pTaG3 or pT1G1-G3 tumours, in whom random biopsies were performed, received intravesical BCG compared with five out of 22 patients (23%) where random biopsies were not taken (p = 0.004). Moreover, 23 out of 103 patients (22%) with pTaG3 or pT1G1-G3 tumours in whom random biopsies were performed underwent radical cystectomy compared with none out of 22 patients (0%) without random biopsies (p = 0.013). The Cox proportional hazard ratio for death due to bladder cancer in patients with pTaG3 or pT1G1-G3 tumours among patients not having versus having undergone random biopsies was 2.5 (95% confidence interval 1.1-5.6).Patients diagnosed in Stockholm in 1995 or 1996 with pTaG3 or pT1G1-G3 bladder tumours having undergone random bladder biopsies more frequently underwent BCG treatment and radical cystectomy and had higher cancer-specific survival than patients who did not undergo random biopsies.

Open radical cystectomy with an appropriate bilateral lymph node dissection (LND) is currently the standard treatment for patients with muscle-invasive bladder cancer. Approximately 25% of patients with stages T1-T4 N0 M0 harbour metastatic lymph nodes at the time of radical cystectomy. Results from open high volume radical cystectomy series suggest that a more extended LND provides the best survival outcomes and the lowest local recurrence rates. Currently, there is controversy whether laparoscopic or robot-assisted extended LND at radical cystectomy is technically feasible and whether it can provide oncological control equivalent to open LND series at the time of radical cystectomy.Laparoscopic LND is technically demanding and requires prolonged operation time. Most studies to date indicate that fewer nodes are removed than with an open approach, putting a question mark to this surgical approach from an oncological point of view. Limited data on lymph node yield using a robot-assisted approach are available; however, several series found similar results as in open series.At present, there is no conclusive evidence showing that laparoscopic LND gives similar results than open LND. Robot-assisted LND is still in its learning curve and more patient series are needed.

Objective To measure nitric oxide gas directly in the uterus of healthy women and patients with suspected pelvic inflammatory disease. Design Pilot case-control study. Setting The emergency department of a university hospital. Patient(s) Twenty premenopausal, nonpregnant women from 18 to 48 years of age with lower abdominal pain and nine healthy women with regular menstrual cycles were included. Intervention(s) We measured nitric oxide levels in air incubated for 5 minutes in a catheter balloon in the uterine cavity. Main Outcome Measure(s) Intrauterine nitric oxide concentration in controls and patients. Result(s) In patients with lower abdominal pain, nitric oxide was almost 100-fold increased in those in whom pelvic inflammatory disease had been diagnosed compared with those in whom appendicitis had been diagnosed with no individual overlap. Uterine nitric oxide levels were uniformly low in healthy women throughout the menstrual cycle, compared with those with pelvic inflammatory disease. Conclusion(s) Nitric oxide gas can be measured directly in the uterine cavity with a fast, simple, and safe method. The levels of nitric oxide are increased in patients with pelvic inflammatory disease.

Surgical flaps are commonly used in the reconstruction of tissue defects after tumour surgery and trauma. Flap failure continues to be a clinical problem and the underlying causes are not fully understood. In the present study a system that generates nitric oxide (NO) in a non-enzymatic fashion was created through the acidification with vitamin C of a cream containing increasing concentrations (0.125%, 0.25%, 0.5%, 1.25% and 2.5%) of nitrite (NO(2)(-)). The cream was applied for 30 min to a modified epigastric island skin flap in the rat. Blood flow in the supplying artery was measured by transit-time ultrasound flowmetry throughout the experiment and superficial skin blood flow was measured by laser Doppler perfusion imaging before and after treatment. Mean arterial blood pressure was also monitored. NO and the gas nitrogen dioxide (NO(2)), which is formed when NO reacts with atmospheric oxygen, were measured above the cream using chemiluminescence. In flaps treated with the NO generating cream, a concentration-dependent increase in blood flow in the supplying artery and flap skin of up to 130% was observed. Cream base alone or cream base acidified with vitamin C had no effect on blood flow. Also, concentration-dependent formation of both NO and NO(2) was seen. NO increases both supplying artery blood flow and superficial cutaneous blood flow in an epigastric island skin flap model in the rat indicating that NO is of importance in flap physiology and possibly also for flap survival.

In the USA, the incidence of bladder cancer is three-times higher in men than in women and it is the fourth most common cancer in men after prostate, lung and colorectal cancer. Muscle-invasive urothelial urinary bladder cancer has a very high mortality rate. This is regardless of intensive therapeutic efforts such as radical surgery in combination with oncological treatment options. The development of treatments with better outcomes regarding disease-specific survival and treatment-inflicted morbidity is likely to occur over the next few years. The significance of meta-analyses on the effect of neoadjuvant chemotherapy, the development of sentinel node dissection and the impact of the introduction of robot-assisted surgery on the possibility of performing minimally invasive surgery in advanced bladder cancer patients is discussed.

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.

Improved oxygenation has previously been shown in patients with acute lung injury when ventilated in prone position. We hypothesized that this was due to higher regional production of nitric oxide in dorsocaudal lung regions. We measured nitric oxide synthase mRNA expression and nitric oxide production by citrulline assay in ventral and dorsal lung tissue from patients. In volunteers, regional lung perfusion in prone and supine postures was assessed by single photon emission computed tomography using (99m)Tc macroaggregated albumin before and after inhibition of nitric oxide synthase by N(G)-monomethyl-L-arginine infusion. Nitric oxide synthase mRNA expression and nitric oxide production were significantly higher in dorsal compared with ventral lung regions. In supine posture, lung perfusion was shifted to ventral parts during nitric oxide synthase inhibition, whereas in the prone posture lung perfusion remained unchanged. Our results suggest a role for endogenous nitric oxide in regulation of regional pulmonary perfusion.

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.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.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.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.

We performed a systematic literature review to assess the current status of a totally intracorporeal robot-assisted radical cystectomy (RARC) approach. The current 'gold standard' for radical cystectomy remains open radical cystectomy. RARC has lagged behind robot-assisted prostatectomy in terms of adoption and perceived patient benefit, but there are indications that this is now changing. There have been several recently published large series of RARC, both with extracorporeal and with intracorporeal urinary diversions. The present review focuses on the totally intracorporeal approach. Radical cystectomy is complex surgery with several important outcome measures, including oncological and functional outcomes, complication rates, patient recovery and cost implications. We aim to answer the question of whether there are advantages to a totally intracorporeal robotic approach or whether we are simply making an already complex procedure more challenging with an associated increase in complication rates. We review the current status of both oncological and functional outcomes of totally intracorporeal RARC compared with standard RARC with extraperitoneal urinary diversion and with open radical cystectomy, and assess the associated short- and long-term complication rates. We also review aspects in training and research that have affected the uptake of RARC. Additionally we evaluate how current technology is contributing to the future development of this surgical technique.

We analyzed the associations of the NOS2 (CCTTT)n promoter polymorphism to lung cancer risk and tumor histology in smokers and non-smokers. We also investigated lung cancer long-term survival in relation to the polymorphism, smoking data, histology, age at diagnosis, and gender. One hundred eighty-five lung-cancer patients and 164 matched controls, where non-smokers were enriched among the lung cancer cases, were genotyped by fragment analysis and sequencing. Genotypes were combined with information on histology, patient smoking status, and cancer-specific death, using a 20-year follow-up. We divided the (CCTTT)n alleles into short (n ≤ 10), intermediate (n = 11-12), and long (n ≥ 13). Patients homozygous for short repeats had significantly increased risk of lung cancer (p = 0.030) compared to carriers of two long alleles (LL). Lack of long allele was associated with a significantly increased lung cancer risk overall (p = 0.011), especially among non-smokers (p = 0.001). A significantly higher lung cancer survival was seen in non-smokers compared to smokers (p = 0.046) and in low-dose smokers compared to high-dose smokers at the time of diagnosis (p = 0.028). Moreover, non-smoking patients with squamous cell carcinoma (p = 0.015) or adenocarcinoma (p = 0.024) showed a significantly lower survival compared to other lung carcinomas. Nitric oxide can induce proliferation as well as apoptosis depending on cellular context. Our results suggest that the (CCTTT)n NOS2 microsatellite may influence the risk of developing lung cancer, especially in non-smokers, possibly by affecting intracellular nitric oxide levels. Our results also give additional information about the yet poorly understood etiological and prognostic differences between lung cancer in non-smokers and smokers.