Robot-assisted intracorporeal orthotopic bladder substitution after radical cystectomy: perioperative morbidity and oncological outcomes - a single-institution experience.

OBJECTIVE: To report a single-institution experience with totally intracorporeal neobladder urinary diversion (UD) after robot-assisted laparoscopic radical cystectomy (RARC). PATIENTS AND METHODS: A total of 158 patients underwent totally intracorporeal neobladder UD after RARC between 2003 and 2016. Patient demographics, intraoperative and pathological data, 30- and 90-day perioperative mortality and complications were recorded. Complications were classified according to the modified Clavien-Dindo classification. The 5-year overall (OS) and cancer-specific survival (CSS) rates were estimated by Kaplan-Meier plots. RESULTS: Most of the patients were male (84%) and had clinical T Stage ≤2 (87%). The mean operation time was 359 (SD ±98) min, with a median (range) estimated blood loss of 300 (50-2200) mL. Most of the men (86%) received a nerve-sparing procedure and 38% of the females an organ-sparing approach. A lymph node dissection was performed in 156 (99%) patients, with a median (range) yield of 23 (7-48) nodes. Conversion to open surgery occurred in five patients (3%). We recorded negative margins in 156 patients (99%). The median (range) follow-up was 34 (1-170) months, with 30- and 90-day mortality rates of 0%. Clavien-Dindo Grade III-IV complications occurred in 29 of 158 (18%) patients at 30-days and in eight of 158 (5%) between 30-90 days, resulting into a 90-day overall high-grade complication rate of 23%. The unadjusted estimated 5-years recurrence-free survival, CSS and OS rates were 70%, 72%, and 71%, respectively. CONCLUSION: In our present series the complication and oncological results were similar to open RC series, suggesting that RARC followed by totally intracorporeal neobladder UD is a safe and feasible alternative.

Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium.

BACKGROUND: While studying a urothelium-derived inhibitory factor in guinea pig urinary bladders we observed considerable release of prostanoids, including PGD2-like activity. The present study was carried out to identify the prostanoids and to study their roles in modulating guinea pig urinary bladder motility. METHODS: Release of PGE2 and PGD2 in isolated guinea pig urinary bladder preparations was analyzed by high performance liquid chromatography (HPLC) combined with bioassay on bladder strips. Isolated urothelium-intact (UI) or -denuded (UD) bladder strips were subjected to electrical field stimulation (EFS) and applications of PGE2 and PGD2. RESULTS: A resting release of 95±9 (n=5) nggtissue(-1)h(-1) PGE2-like activity and 210±34 (n=4) nggtissue(-1)h(-1) PGD2-like activity was found, where PGD2-like was subject to marked spontaneous inactivation during isolation. Prostanoids release was decreased by 70-90% by the cyclo-oxygenase inhibitor diclofenac in UI preparations. Urothelium removal decreased prostanoids release by more than 90%. PGE2 increased basal tone and spontaneous contractions, whereas PGD2 had little or no effect on these. Exogenous PGE2 enhanced and PGD2 inhibited contractile responses to EFS, exogenous acetylcholine- and ATP, whereas PGD2 caused marked dose-dependent inhibition. PGE2 and PGD2 effects were more pronounced in diclofenac-treated UD tissues. CONCLUSIONS: PGD2 and PGE2 are released from guinea pig bladder urothelium and PGD2 has inhibitory effects on bladder motility, mainly through a postjunctional action on smooth muscle responsiveness. GENERAL SIGNIFICANCE: The release and inhibitory effects merit further studies in relation to normal biological function as well as overactive bladder syndrome.

The European Association of Urology Robotic Urology Section (ERUS) survey of robot-assisted radical prostatectomy (RARP).

OBJECTIVE: To evaluate surgeons adherence to current clinical practice, with the available evidence, for robot-assisted radical prostatectomy (RARP) and offer a baseline assessment to measure the impact of the Pasadena recommendations. Recently, the European Association of Urology Robotic Urology Section (ERUS) supported the Pasadena Consensus Conference on best practices in RARP. SUBJECTS AND METHODS: This survey was performed in January 2012. A specific questionnaire was sent, by e-mail, to 145 robotic surgeons who were included in the mailing-list of ERUS members and working in different urological institutions. Participating surgeons were invited to answer a multiple-choice questionnaire including 24-items evaluating the main RARP surgical steps. RESULTS: In all, 116 (79.4%) invited surgeons answered the questionnaire and accepted to participate to the ERUS survey. In all, 47 (40.5%) surgeons performed >100 RARPs; 41 (35.3%) between 50 and 100, and 28 (24.1%) <50 yearly. The transperitoneal, antegrade technique was the preferred approach. Minimising bladder neck dissection and the use of athermal dissection of the neurovascular bundles (NVBs) were also popular. There was more heterogeneity in the use of energy for seminal vesicle dissection, the preservation of the tips of the seminal vesicle and the choice between intra- and interfascial planes during the antero-lateral dissection of the NVBs. There was also large variability in the posterior and/or anterior reconstruction steps. CONCLUSIONS: The present study is the first international survey evaluating surgeon preferences during RARP. Considering that the results were collected before the publication of the Pasadena recommendations, the data might be considered an important baseline evaluation to test the dissemination and effects of the Pasadena recommendations in subsequent years.

Total intracorporeal robotic cystectomy: are we there yet?

PURPOSE OF REVIEW: To provide discussion on several recently published case series describing complete intracorporeal robotic cystectomy. Are we making a complex and expensive procedure more challenging or are there patient benefits to be realized from a complete minimally invasive approach? We discuss how effective and cost-efficient a complete intracorporeal approach is, review the updates and comment on the future direction of robot-assisted radical cystectomy (RARC). RECENT FINDINGS: Several centers have recently reported a series of RARC with intracorporeal urinary diversion. Baseline demographics, complication rates and oncological outcome data were comparable to previously published open radical cystectomy series, as well as robotic cystectomy with extracorporeal urinary diversion series. In centers experienced in robotics, comparable outcomes were achieved early in the series with no significant difference in lymph node yields, positive surgical margin rates or complication rates. However, operation times and patient's length of stay (LOS) continued to improve, suggesting that aspect of the learning curve is longer than previously thought. Benefits such as decreased blood loss and reduced LOS, commonly associated with minimally invasive surgery, were seen and while costs of RARC remain prohibitive, reducing operative times and LOS will improve cost analysis. SUMMARY: RARC with totally intracorporeal urinary diversion is technically feasible with good early and intermediate-term oncological and complication rate results. High-volume centers with expertise can deliver a complete intracorporeal robotic cystectomy with no increase in the complication rates or additional costs compared to RARC with extracorporeal urinary diversion. Further long-term oncological and functional data and the results of prospective randomized controlled trials are both pending to confirm these findings.

Characteristics Contributing to Survival Differences Between Black and White Patients Following Cystectomy.

PURPOSE: Examine patient, tumor, and treatment characteristics effect on the disparity between black and white patients with muscle-invasive bladder cancer (MIBC) who undergo radical cystectomy (RC). METHODS: 1,286 black patients in the 2004 to 2016 National Cancer Database fit inclusion criteria. A tapered match was performed from 17,374 white patients sequentially matched to the black cohort on demographics (age, gender, insurance, income, education, county, diagnosis year), presentation (demographic variables, stage, grade, tumor size, Charlson score), and treatment (demographic and presentation variables, lymph node count, hospital volume, neoadjuvant chemotherapy [NAC], treatment delay), creating 3 matched cohorts. Chi-square and Kruskal-Wallis tests were used to compare cohorts. Kaplan-Meier analysis was used to compare 5-year overall survival (OS). RESULTS: 5-year OS rate was 40.4% and 35.6% for unmatched white and black cohorts (P < 0.001), respectively. Following demographics and presentation match, 5-year OS rate for white patients decreased to 39.2% (P = 0.003) and 39.10% (P = 0.019), respectively. After treatment match, 5-year OS rate decreased to 36.7% for white patient (P = 0.32). Following presentation match, 7.2% of black patients vs. 5.8% of white patients had treatment delay, and 10.1% of black patients vs. 11.2% of white patients received NAC. The treatment match resulted in a 0.3% difference between groups for treatment delay and NAC. CONCLUSIONS: Our analysis demonstrates that disparity between black and white patients with muscle-invasive bladder cancer exists in demographic-, presentation-, and treatment-related variables. Treatment variables may be a large contributing factor to survival disparities. Further research is needed to identify social, biological, and organizational inputs that contribute to these disparities.

Contemporary outcomes of patients undergoing robotic-assisted radical cystectomy: A comparative analysis between intracorporeal ileal conduit and neobladder urinary diversions.

Objective: We aimed to compare perioperative and oncologic outcomes for patients undergoing robotic-assisted radical cystectomy (RARC) with intracorporeal ileal conduit (IC) and neobladder (NB) urinary diversion. Methods: Patients undergoing RARC with intracorporeal urinary diversion between January 2017 and January 2022 at the Icahn School of Medicine at Mount Sinai, New York, NY, USA were indexed. Baseline demographics, clinical characteristics, perioperative, and oncologic outcomes were analyzed. Survival was estimated with Kaplan-Meier plots. Results: Of 261 patients (206 [78.9%] male), 190 (72.8%) received IC while 71 (27.2%) received NB diversion. Median age was greater in the IC group (71 [interquartile range, IQR 65-78] years vs. 64 [IQR 59-67] years, p<0.001) and BMI was 26.6 (IQR 23.2-30.4) kg/m2. IC group was more likely to have prior abdominal or pelvic radiation (15.8% vs. 2.8%, p=0.014). American Association of Anesthesiologists scores were comparable between groups. The IC group had a higher proportion of patients with pathological tumor stage 2 (pT2) tumors (34 [17.9%] vs. 10 [14.1%], p=0.008) and pathological node stages pN2-N3 (28 [14.7%] vs. 3 [4.2%], p<0.001). The IC group had less median operative time (272 [IQR 246-306] min vs. 341 [IQR 303-378] min, p<0.001) and estimated blood loss (250 [150-500] mL vs. 325 [200-575] mL, p=0.002). Thirty- and 90-day complication rates were 44.4% and 50.2%, respectively, and comparable between groups. Clavien-Dindo grades 3-5 complications occurred in 27 (10.3%) and 34 (13.0%) patients within 30 and 90 days, respectively, with comparable rates between groups. Median follow-up was 324 (IQR 167-552) days, and comparable between groups. Kaplan-Meier estimate for overall survival at 24 months was 89% for the IC cohort and 93% for the NB cohort (hazard ratio 1.23, 95% confidence interval 1.05-2.42, p=0.02). Kaplan-Meier estimate for recurrence-free survival at 24 months was 74% for IC and 87% for NB (hazard ratio 1.81, 95% confidence interval 0.82-4.04, p=0.10). Conclusion: Patients undergoing intracorporeal IC urinary diversion had higher postoperative cancer stage, increased nodal involvement, similar complications outcomes, decreased overall survival, and similar recurrence-free survival compared to patients undergoing RARC with intracorporeal NB urinary diversion.

The impact of discharge location on outcomes following radical cystectomy.

PURPOSE: Hospital readmission is associated with adverse outcomes and increased cost, and as such, has been identified as a metric for surgical quality and a target for shifts in health policy. However, the disposition of patients who undergo radical cystectomy for bladder cancer and the association between discharge locations and readmission rates is poorly understood. Understanding the patterns and characteristics of readmission after radical cystectomy will help inform discharge planning and expectations and may have long-term impacts on quality and cost of care delivery. We hypothesize that patients will have varying readmission rates based on their discharge location. MATERIALS AND METHODS: An observational analysis of the Nationwide Readmissions Database was performed for all patients who underwent elective radical cystectomy in 2016 to 2017. The patients were grouped by the following criteria: whether they were discharged home, home with care, or to a facility. Univariate analysis was performed using the Chi-square test for categorical variables and the Kruskal-Wallis test for continuous variables. A multivariable logistic regression was conducted to evaluate if discharge locations impact patient readmissions at 30- and 90-days. RESULTS: The final dataset included 4,947 patients discharged home with care, 2,127 patients discharged to home or self-care, and 1,232 patients discharged to a facility. Discharge to a facility was strongly associated with higher 30-day (OR 1.49, CI 1.26-1.76) and 90-day readmission rates (OR 1.46, CI 1.23-1.74). Additionally, home health care was strongly associated with increased 30-day readmission rates (OR 1.22, CI 1.08-1.37) relative to routine discharge home. CONCLUSIONS: Our analysis suggests that discharge location independently predicts readmission following RC. Further study with more granular patient- and system-level data may aid in identifying structural characteristics and processes that can reduce readmissions and their associated economic impact, while maintaining quality of care delivered.

Neobladder creation in patients with chronic kidney disease: A viable diversion strategy.

INTRODUCTION: Renal function impairment is often cited as a contraindication to continent diversion strategies. There is little evidence exploring renal function changes between continent and incontinent surgery in patients with preoperative chronic kidney disease (CKD), in particular CKD3B. METHODS: This was a retrospective review of two high-volume centers performing robotic assisted radical cystectomy (RARC) with orthotopic neobladder (ONB) or ileal conduit (IC) between 2014 to 2020. Patients were stratified based on CKD estimated glomerular filtration (eGFR) stage, which was estimated via the CKD-EPI equation. Postoperative renal function was compared for up to 60 months postoperative. Surgical, post-surgical, complications, and readmission data were gathered and compared between all patients RESULTS: 522 cystectomy patients, 430 with IC and 125 with ONB, were included. eGFR decline was statistically significant in a matched cohort of IC and ONB patients only at 3 months. There were no statistically significant differences between readmission rates, time to readmission, or complications. 34.6% of stage 3B patients had hydronephrosis on imaging prior to surgery, compared to 11.4%, 22.1% and 21.8% of CKD stage 1, 2, and 3A patients. CKD stage 3B had statistically and clinically improved eGFR through 24 months. CONCLUSION: ONB surgery may be a viable diversion strategy in patients previously thought to be contraindicated due to low renal function.

Higher preoperative eGFR is a predictor of worse renal function decline after robotic assisted radical cystectomy: Implications for postoperative management.

INTRODUCTION: In patients with muscle invasive bladder cancer or high risk noninvasive bladder cancer, renal function decline is a concern after radical cystectomy with urinary diversion. The pathophysiology of this decline is multifactorial, with subclinical acidosis and metabolic derangements from the diversion thought to contribute. It is unknown whether patients with baseline chronic kidney disease (CKD) are at increased risk of further decline in renal function. METHODS: We performed a retrospective review of two high volume robotic assisted radical cystectomy (RARC) centers between 2016 and 2020. Preoperative demographics and comorbidities were collected. Postoperative estimated glomerular filtration rate (eGFR) was calculated at 12 and 24 months to determine short-term rate in decline of eGFR. Absolute and percent changes in eGFR were calculated. RESULTS: There were a total of 555 patients who underwent RARC. Men comprised 76.2% of the cohort. Neoadjuvant chemotherapy was given in 31% of patients and adjuvant chemotherapy was given in 4.81% of patients. Higher preoperative eGFR (B -0.549, 95% CI -0.708 to -0.391, P < 0.001) and presence of diabetes mellitus (B -15.414, 95% CI -24.820 to -6.008, P = 0.001) were significant predictors of eGFR decline at 12 months. At 24 months, presence of diabetes mellitus (B -11.799, 95% CI -21.816 to -1.782, P = 0.021) and higher preoperative eGFR (B -0.621, 95% CI -0.796 to -0.446, P < 0.001) were correlated with a steeper decline in eGFR. Higher preoperative eGFR was also predictive of upstaging to CKD3 or higher post operatively (OR 1.019, 95% CI 1.004-1.034, P = 0.015). Intracorporeal diversion was protective, whereas presence of hypertension, diabetes mellitus, and higher preoperative eGFR predicted greater decline in eGFR. CONCLUSION: Patients with higher preoperative eGFR and diabetes are at increased risk of renal function decline post RARC at 12 and 24 months. This suggests that patients with risk factors for renal function decline, but otherwise normal renal function at baseline, are a particularly vulnerable population for progression to CKD after RARC and should be counseled and closely followed postoperatively for renal function deterioration.

Robotic-assisted reconstructive urology.

PURPOSE OF REVIEW: The use of robotic surgery in reconstructive urology has steadily increased since the year 2000. Articles in the MEDLINE database (from January 2000 to May 2011) identified using the Boolean search: robotic or robot-assisted and reconstructive surgery and urology. In addition, the reference lists of previously published articles on robotic-assisted reconstructive surgery were checked for additional studies. This review will summarize the current advances in robotic-assisted reconstructive urology. RECENT FINDINGS: Even though many advocate the introduction of robot-assisted technique in reconstructive urology, relatively few studies have been published. Researchers do report shorter hospital stays and less blood loss than are reported for patients operated on with open reconstructive techniques and also report acceptable short-term outcomes. SUMMARY: The current literature shows that complex robot-assisted urological reconstructive surgical procedures may be used for both children and adults. With appropriate experience, this technique offers the expected advantages of decreased blood loss and transfusion rate, reduced analgesic requirements, and early hospital discharge in comparison with the open approach. However, robotic-assisted reconstructive urologic surgery needs to be evaluated in larger randomized studies with long-term follow-up.

Development and validation of non-guided bladder-neck and neurovascular-bundle dissection modules of the RobotiX-Mentor® full-procedure robotic-assisted radical prostatectomy virtual reality simulation.

BACKGROUND: Full-procedure virtual reality (VR) simulator training in robotic-assisted radical prostatectomy (RARP) is a new tool in surgical education. METHODS: Description of the development of a VR RARP simulation model, (RobotiX-Mentor®) including non-guided bladder neck (ngBND) and neurovascular bundle dissection (ngNVBD) modules, and assessment of face, content, and construct validation of the ngBND and ngNVBD modules by robotic surgeons with different experience levels. RESULTS: Simulator and ngBND/ngNVBD modules were rated highly by all surgeons for realism and usability as training tool. In the ngBND-task construct, validation was not achieved in task-specific performance metrics. In the ngNVBD, task-specific performance of the expert/intermediately experienced surgeons was significantly better than that of novices. CONCLUSIONS: We proved face and content validity of simulator and both modules, and construct validity for generic metrics of the ngBND module and for generic and task-specific metrics of the ngNVBD module.

Can anesthetics affect bladder cancer recurrence? Total intravenous versus volatile anesthesia in patients undergoing robot-assisted radical cystectomy: A single institution retrospective analysis.

BACKGROUND: Radical cystectomy is standard of care and part of a multidisciplinary approach for long-term survival in patients with muscle-invasive bladder cancer (MIBC) or high-grade non-MIBC. Recent data have suggested that anesthetic technique can affect long-term survival and recurrence in patients undergoing cancer related surgery. METHODS: The records of all patients who underwent robot-assisted radical cystectomy for high-risk non-MIBC or MIBC at a single academic institution from 2014 to 2020 were retrospectively reviewed. Patients were grouped according to whether they received total intravenous (TIVA) or volatile inhalation anesthesia (VIA). Univariable and multivariable cox proportional hazards models were used to compare hazard ratios for distant recurrence. Kaplan-Meier recurrence-free survival curves were constructed from the date of surgery to recurrence. RESULTS: A total of 231 patients were included, of which 126 (55%) received TIVA and 105 (45%) received VIA. Distant recurrence occurred in 8.7% and 26.7% of patients who received TIVA and VIA, respectively (P < 0.001). Kaplan-Meier analysis demonstrated significant improvement in distant recurrence-free survival with TIVA (log-rank P < 0.001). Multivariable analysis revealed a significant increase in recurrence risk with VIA (HR: 3.4, 95%CI: 1.5-7.7, P < 0.01) and increasing tumor pathological stage (pT2, pT3, pT4, all P < 0.05). CONCLUSIONS: The use of volatile inhalation anesthetics during robot-assisted radical cystectomy may be associated with an increased risk of distant recurrence. Further studies will be necessary to validate these findings.

Implementation of a nonopioid protocol following robot-assisted radical cystectomy with intracorporeal urinary diversion.

PURPOSE: The implementation of robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) for management of patients with muscle-invasive or high-risk noninvasive bladder cancer has increased in utilization over the last decade. Here, we seek to describe institutional opioid prescription and utilization patterns following implementation of a nonopioid (NOP) perioperative pain management protocol in patients who received RARC with ICUD. MATERIALS AND METHODS: The records of all patients who underwent RARC that utilized a NOP perioperative pain management protocol at a single academic institution from 2016 to 2020 were retrospectively reviewed. Descriptive statistical analyses were performed. For comparison, we included 74 consecutive patients who received the same NOP protocol with extracorporeal urinary diversion (ECUD). RESULTS: A total of 116 patients who received ICUD were included in our analysis. The median operation time for the ICUD group was 305 minutes (interquartile range [IQR]: 262-352). 12.1% (n = 14) of patients who underwent ICUD required narcotics during inpatient hospitalization. For these patients, the median morphine milligram equivalent requirement was 52.0 (IQR: 7.62-157). Additionally, only 12.1% (n = 14) of patients were prescribed opioids postoperatively at discharge. We identified that within 6 months of surgery only 5 (4.3%) patients required a second narcotic prescription. Furthermore, of patients who did not use mu-opioid blockers, a minority experienced postoperative ileus (15.7%, n = 16). 30- and 90-day all Clavien complication rates for patients were 44.8% (n = 52) and 49.1% (n = 57), respectively. Nineteen (16.4%) patients were readmitted within 30 days of discharge, of which none were pain related. When compared to ECUD, patients who received ICUD experienced similar complication and readmission rates. CONCLUSIONS: The implementation of a NOP protocol for patients undergoing RARC with ICUD allows for both decreased postoperative narcotic use and reduced need for narcotic prescriptions at discharge with acceptable complication and readmission rates.

Role of the Innate Immune System in the Development, Progression, and Therapeutic Response of Bladder Cancer.

Effector cells from the innate immune system are capable of cellular killing, recruitment and priming of adaptive cells. As the role of the tumor microenvironment in the control and elimination of cancer continues to be elucidated, interest has grown in understanding how the innate immune system can be harnessed to increase tumor immune infiltration and improve cancer therapeutics. Measurements of cytokines levels in urinary-based assays have shown the relevance of the bidirectional activation pathway between the innate and adaptive immune systems in patients with bladder cancer, underscoring the key role of innate immunity in priming and directing the antitumor response. PATIENT SUMMARY: Systemic and intravesical immunotherapies are currently available for bladder cancer. However, these agents are effective only in a subset of patients. We consider how integration of scientific breakthroughs on innate immunity may open a new window of potential therapeutic targets that could increase the efficacy of available agents.

Comparison of 3D printed prostate models with standard radiological information to aid understanding of the precise location of prostate cancer: A construct validation study.

BACKGROUND: To investigate the reliability with which healthcare professionals with different levels of expertise are able to impart the exact location of prostate cancer (PCA) after (A) reading written magnetic resonance imaging (MRI) reports, (B) attending MRI presentations in multidisciplinary team meetings (MDT), and (C) examining 3D printed prostate models, which represents a new technology to describe the location of PCA lesions. METHODS: We used three different PCA cases to assess the three information tools. Construct validation was performed using two healthcare groups with different levels of expertise: (1) Nine expert urologists in PCA, and (2) nine medical students. After each information tool, the study participants plotted the tumor location in a 2-dimensional prostate diagram. A scoring system was established to evaluate the drawings in terms of accuracy of plotting tumor position. Data are shown as median scores with interquartile range. RESULTS: Within the expert group, no significant difference was seen in the overall scoring results between the information tools (p = 0.34). Medical students performed significantly worse with MDT information (p = 0.03). Experts performed better in all three information tools compared to students, resulting in a significantly 25% higher overall total score (25.0[22.3-26.7] vs. 20.0[15.0-24.0], p<0.001). The difference was largest after MDT information, with experts showing a 49% better scoring (p<0.001), and second largest with the 3D printed models, showing a 17% better scoring of the experts (p = 0.07). No difference was found in the written MRI report scoring results between experts and students. CONCLUSIONS: 3D printed models provided better orientation guide to medical students compared to MDT MRI presentations. This indicates that the 3D printed models might be easier to understand than the current gold standard MDT conferences. Therefore, 3D models may play an increasingly important role in providing guidance for orientation for less experienced individuals, such as surgical trainees.

Erectile Function and Oncologic Outcomes Following Open Retropubic and Robot-assisted Radical Prostatectomy: Results from the LAParoscopic Prostatectomy Robot Open Trial.

BACKGROUND: Whether surgeons perform better utilising a robot-assisted laparoscopic technique compared with an open approach during prostate cancer surgery is debatable. OBJECTIVE: To report erectile function and early oncologic outcomes for both surgical modalities, stratified by prostate cancer risk grouping. DESIGN, SETTING, AND PARTICIPANTS: In a prospective nonrandomised trial, we recruited 2545 men with prostate cancer from seven open (n=753) and seven robot-assisted (n=1792) Swedish centres (2008-2011). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinometrically-validated questionnaire-based patient-reported erectile function was collected before, 3 mo, 12 mo, and 24 mo after surgery. Surgeon-reported degree of neurovascular-bundle preservation, pathologist-reported positive surgical margin (PSM) rates, and 2-yr prostate-specific antigen-relapse rates were measured. RESULTS AND LIMITATIONS: Among 1702 preoperatively potent men, we found enhanced erectile function recovery for low/intermediate-risk patients in the robot-assisted group at 3 mo. For patients with high-risk tumours, point estimates for erectile function recovery at 24 mo favoured the open surgery group. The degree of neurovascular bundle preservation and erectile function recovery were greater correlated for robot-assisted surgery. In pT2 tumours, 10% versus 17% PSM rates were observed for open and robot-assisted surgery, respectively; corresponding rates for pT3 tumours were 48% and 33%. These differences were associated with biochemical recurrence in pT3 but not pT2 disease. The study is limited by its nonrandomised design and relatively short follow-up. CONCLUSIONS: Earlier recovery of erectile function in the robot-assisted surgery group in lower-risk patients is counterbalanced by lower PSM rates for open surgeons in organ-confined disease; thus, both open and robotic surgeons need to consider this trade-off when determining the plane of surgical dissection. Robot-assisted surgery also facilitates easier identification of nerve preservation planes during radical prostatectomy as well as wider dissection for pT3 cases. PATIENT SUMMARY: For prostate cancer surgery, an open operation reduces erection problems in high-risk cancers but has higher relapse rates than robotic surgery. Relapse rates appear similar in low/intermediate-risk cancers and the robot appears better at preserving erections in these cases.

Systematic Review of Comorbidity and Competing-risks Assessments for Bladder Cancer Patients.

CONTEXT: Radical cystectomy continues to be associated with a significant risk of morbidity and all-cause mortality (ACM). Practice pattern data demonstrating underuse of surgery for patients with muscle-invasive and high-risk non-muscle invasive bladder cancer (BC) have been linked to the advanced age and higher comorbidity status of such patients, which suggests that rates of ACM as well as cancer-specific mortality should be incorporated into patient counseling and guideline recommendations. OBJECTIVE: To review the literature on risk assessment tools for preoperative comorbidity in BC that may aid in treatment decision-making. EVIDENCE ACQUISITION: A systematic search was conducted using Ovid and Medline according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2017 reporting on comorbidity risk assessment (CRA) tools for BC. Prospective and retrospective studies were included. EVIDENCE SYNTHESIS: There are no published randomized control trials comparing CRA tools for BC. Patients undergoing radical cystectomy with combined high-risk comorbidity and performance scores may face up to a sevenfold greater risk of other-cause mortality compared to those with low scores. The Charlson Comorbidity Index is one of the most widely studied indices for 90-d perioperative mortality and overall and cancer-specific survival, with an area under the receiver operating characteristic curve of up to 0.810. Prospective studies of CRA tools for BC have consistently shown that patients with higher comorbidity have worse outcomes. While not specific for BC, comorbidity indices provide useful assessment of competing risks. Competing-risks assessment tools are lacking, with limited studies assessing the impact of these tools on treatment decision-making by patients and providers. We provide the impetus for incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients. CONCLUSIONS: CRA tools should be incorporated into preoperative treatment counseling and the assessment of postoperative outcomes. While retrospective evidence supports the use of CRA tools for BC, further comparative studies evaluating the effectiveness of these tools and identifying the patients most likely to benefit from a treatment according to competing-risks assessment are needed. PATIENT SUMMARY: In this review we explored the clinical evidence for comorbidity risk assessment tools in bladder cancer. We found evidence to support incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients.

Early Recurrence Patterns Following Totally Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS) Scientific Working Group.

Recurrence following radical cystectomy often occurs early, with >80% of recurrences occurring within the first 2 yr. Debate remains as to whether robot-assisted radical cystectomy (RARC) negatively impacts early recurrence patterns because of inadequate resection or pneumoperitoneum. We report early recurrence patterns among 717 patients who underwent RARC with intracorporeal urinary diversion at nine different institutions with a minimum follow-up of 12 mo. Clinical, pathologic, radiologic, and survival data at the latest follow-up were collected. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method, and Cox regression models were built to assess variables associated with recurrence. RFS at 3, 12, and 24 mo was 95.9%, 80.2%, and 74.6% respectively. Distant recurrences most frequently occurred in the bones, lungs, and liver, and pelvic lymph nodes were the commonest site of local recurrence. We identified five patients (0.7%) with peritoneal carcinomatosis and two patients (0.3%) with metastasis at the port site (wound site). We conclude that unusual recurrence patterns were not identified in this multi-institutional series and that recurrence patterns appear similar to those in open radical cystectomy series. PATIENT SUMMARY: In this multi-institutional study, bladder cancer recurrences following robotic surgery are described. Early recurrence rates and locations appear to be similar to those for open radical cystectomy series.

Neuroprotection by selective inhibition of inducible nitric oxide synthase after experimental brain contusion.

The inflammatory response is thought to be important for secondary damage following traumatic brain injury (TBI). The inducible nitric oxide synthase (iNOS) isoform is a mediator in inflammatory reactions and may catalyze substantial synthesis of NO in the injured brain. This study was undertaken to analyze neuronal degeneration and survival, cellular apoptosis and formation of nitrotyrosine following treatment with the iNOS-inhibitor L-N-iminoethyl-lysine (L-NIL) in a model of brain contusion. A brain contusion was produced using a weight-drop device in 30 rats. The animals received treatment with L-NIL or NaCl at 15 min and 12 h after the injury and were sacrificed at 24 h or 6 days after trauma. iNOS activity was measured at 24 h post-trauma by the conversion of L-[U- ( 14 )C]arginine to L-[U-( 14 )C]citrulline and immunohistochemistry for iNOS. Peroxynitrite formation was indirectly assessed by nitrotyrosine (NT) immunohistochemistry. Neuronal degeneration and survival were assessed by Fluoro-Jade (FJ) and NeuN stainings, and cellular death by TUNEL staining. iNOS activity but not iNOS immunoreactivity was significantly reduced in animals that received L-NIL. Neuronal degeneration (FJ) and NT immunoreactivity were significantly reduced at 24 h. Neuronal survival was unchanged at 24 h but increased at 6 days in L-NIL-treated animals. Cellular apoptosis of ED-1 and NeuN positive cells was significantly reduced following L-NIL treatment at 6 days after trauma. We demonstrated neuroprotection by selective inhibition of iNOS after trauma. L-NIL appeared to protect the injured brain by limiting peroxynitrite formation. Our findings support a putative harmful role of iNOS induction early after TBI.

Introducing an enhanced recovery programme to an established totally intracorporeal robot-assisted radical cystectomy service.

OBJECTIVE: The aim of this study was to assess the effect of introducing an enhanced recovery programme (ERP) to an established robot-assisted radical cystectomy (RARC) service. MATERIALS AND METHODS: Data were prospectively collected on 221 consecutive patients undergoing totally intracorporeal RARC between December 2003 and May 2014. The ERP was specifically designed to support an evolving RARC service, where increasing proportions of patients requiring radical cystectomy underwent RARC. Patient demographics and outcomes before and after implementation of the ERP were compared. The primary endpoint was length of stay (LOS). Secondary outcomes included age, American Society of Anesthesiologists (ASA) score, preoperative staging, operative time, complications and readmissions. Differences in outcomes between patients before and after implementation of ERP were tested with the Jonckheere-Terpstra trend test and quantile regression with backward selection. RESULTS: Following implementation of the ERP, the demographics of the patients (n = 135) changed, with median age increasing from 66 to 70 years (p < 0.01), higher ASA grade (p < 0.001), higher preoperative stage cancer (pT ≥ 2, p < 0.05) and increased likelihood of undergoing an ileal conduit diversion (p < 0.001). Median LOS before ERP was 9 days [interquartile range (IQR) 8-13 days] and after ERP was 8 days (IQR 6-10 days) (p < 0.001). ASA grade and neoadjuvant chemotherapy also affected LOS (p < 0.05 and p < 0.01, respectively). There was no significant difference in 30 day complication rates, readmission rates or 90 day mortality, with 59% experiencing complications before ERP implementation and 57% after implementation. The majority of complications were low grade. CONCLUSIONS: Patient demographics changed as the RARC service evolved from selected patients to a general service. Despite worsening demographics, LOS decreased following ERP implementation. This evidence-based ERP safely standardized perioperative care, resulting in decreased LOS and decreased variability in LOS.