Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

Impact of neoadjuvant chemotherapy on survival and recurrence patterns after robot-assisted radical cystectomy for muscle-invasive bladder cancer: Results from the International Robotic Cystectomy Consortium.

OBJECTIVES: To analyze the impact of neoadjuvant chemotherapy on survival and recurrence patterns in muscle-invasive bladder cancer after robot-assisted radical cystectomy. MATERIALS AND METHODS: The International Robotic Cystectomy Consortium database was reviewed to identify patients who underwent robot-assisted radical cystectomy for muscle-invasive bladder cancer between 2002 and 2019. Survival outcomes, response rates, and recurrence patterns were compared between patients who received neoadjuvant chemotherapy and those who did not. Survival distributions were estimated using Kaplan-Meier analyses and compared using the log-rank test. RESULTS: A total of 1370 patients with muscle-invasive bladder cancer were identified, of whom 353 (26%) received neoadjuvant chemotherapy. After a median follow-up of 27 months, neoadjuvant chemotherapy recipients had higher 3-year overall survival (74% vs 57%; log-rank P < 0.01), 3-year cancer-specific survival (83% vs 73%; log-rank P = 0.03), and 3-year relapse-free survival (64% vs 48%; log-rank P < 0.01). Neoadjuvant chemotherapy was a predictor of higher overall survival, cancer-specific survival, and relapse-free survival in univariate but not multivariate analysis. Pathological downstaging (46% vs 23%; P < 0.01), complete responses (24% vs 8%; P < 0.01), and margin negativity (95% vs 91%; P < 0.01) at robot-assisted radical cystectomy were more common in the neoadjuvant chemotherapy group. Neoadjuvant chemotherapy recipients had lower distant (15% vs 22%; P < 0.01) but similar locoregional (12% vs 13%; P = 0.93) recurrence rates. CONCLUSIONS: In this analysis from a large international database, patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy before robot-assisted radical cystectomy had higher rates of survival, pathological downstaging, and margin-negative resections. They also experienced fewer distant recurrences.

Morbidity and mortality after robot-assisted radical cystectomy with intracorporeal urinary diversion in octogenarians: results from the European Association of Urology Robotic Urology Section Scientific Working Group.

OBJECTIVES: To evaluate the postoperative complication and mortality rate following laparoscopic radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) in octogenarians. PATIENTS AND METHODS: We conducted a retrospective analysis comparing postoperative complication and mortality rates depending on age in a consecutive series of 1890 patients who underwent RARC with ICUD for bladder cancer between 2004 and 2018 in 10 European centres. Outcomes of patients aged <80 years and those aged ≥80 years were compared with regard to postoperative complications (Clavien-Dindo grading) and mortality rate. Cancer-specific mortality (CSM) and other-cause mortality (OCM) after surgery were calculated using the non-parametric Aalen-Johansen estimator. RESULTS: A total of 1726 patients aged <80 years and 164 aged ≥80 years were included in the analysis. The 30- and 90-day rate for high-grade (Clavien-Dindo grades III-V) complications were 15% and 21% for patients aged <80 years compared to 11% and 13% for patients aged ≥80 years (P = 0.2 and P = 0.03), respectively. In a multivariable logistic regression analysis adjusting for pre- and postoperative variables, age ≥80 years was not an independent predictor of high-grade complications (odds ratio 0.6, 95% confidence interval 0.3-1.1; P = 0.12). The non-cancer-related 90-day mortality was 2.3% for patients aged ≥80 years and 1.8% for those aged <80 years, respectively (P = 0.7). The estimated 12-month CSM and OCM rates for those aged <80 years were 8% and 3%, and for those aged ≥80 years, 15% and 8%, respectively (P = 0.009 and P < 0.001). CONCLUSIONS: The minimally invasive approach to RARC with ICUD for bladder cancer in well-selected elderly patients (aged ≥80 years) achieved a tolerable high-grade complication rate; the 90-day postoperative mortality rate was driven by cancer progression and the non-cancer-related rate was equivalent to that of patients aged <80 years. However, an increased OCM rate in this elderly group after the first year should be taken into account. These results will support clinicians and patients when balancing cancer-related vs treatment-related risks and benefits.

Neoadjuvant Chemotherapy is Not Associated with Adverse Perioperative Outcomes after Robot-Assisted Radical Cystectomy: A Case for Increased Use from the IRCC.

PURPOSE: We sought to determine the trend of neoadjuvant chemotherapy use for nonmetastatic muscle invasive urothelial bladder cancer and whether it is associated with adverse perioperative morbidity after robot-assisted radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the IRCC (International Robotic Cystectomy Consortium) database between 2006 and 2017. After excluding patients with nonmuscle invasive bladder cancer the patients were divided into 2 groups, including those who did vs did not receive neoadjuvant chemotherapy. Data were reviewed for demographics, preoperative, operative and 90-day perioperative outcomes. We used the Cochran-Armitage trend test to assess trends of neoadjuvant chemotherapy associations with high grade and overall complications with time. Multivariate stepwise regression analyses were done to determine whether neoadjuvant chemotherapy was associated with prolonged operative time, 90-day postoperative complications, readmissions, reoperations and mortality after robot-assisted radical cystectomy. RESULTS: A total of 298 patients (26%) received neoadjuvant chemotherapy. These patients were younger (age 67 vs 69 years, p=0.01) and more frequently had an ASA™ (American Society of Anesthesiologists™) score of 3 or greater (62% vs 55%, p=0.02) and pathological T3 stage or greater disease (28% vs 22%, p=0.04). The use of neoadjuvant chemotherapy increased significantly from 10% in 2006 to 2007 to 42% in 2016 to 2017 (p <0.01). On multivariate analysis neoadjuvant chemotherapy was not significantly associated with prolonged operative time, hospital stay, 90-day postoperative complications, reoperation or mortality. Neoadjuvant chemotherapy was associated with 90-day readmissions after robot-assisted radical cystectomy (OR 5.90, 95% CI 3.30-10.90, p <0.01). CONCLUSIONS: Neoadjuvant chemotherapy utilization has significantly increased in the last decade. It was not associated with perioperative surgical morbidity after robot-assisted radical cystectomy.

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.

Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe).

OBJECTIVE: To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis. PATIENTS AND METHODS: Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC. RESULTS: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis. CONCLUSIONS: OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study.

PURPOSE: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking. METHODS: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not. RESULTS: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81). CONCLUSION: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

Ten-Year Oncologic Outcomes Following Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: Radical cystectomy is the gold standard for nonmetastatic muscle invasive bladder cancer and for refractory nonmuscle invasive disease. Compared to open radical cystectomy, robot-assisted radical cystectomy has been shown to provide comparable early oncologic outcomes and improved perioperative outcomes. However, there is a paucity of data on long-term oncologic outcomes and concerns about a higher incidence of local recurrence after robot-assisted radical cystectomy. We report 10-year oncologic outcomes following robot-assisted radical cystectomy using a multinational database. MATERIALS AND METHODS: We retrospectively reviewed the prospective International Robotic Cystectomy Consortium database. Consecutive patients who underwent robot-assisted radical cystectomy 10 years ago or earlier were included in analysis. Data were reviewed for demographics, and perioperative, pathological and oncologic outcomes. Kaplan-Meier curves were used to depict recurrence-free, disease specific and overall survival. Multivariate stepwise Cox regression models were applied to identify variables associated with recurrence-free, disease specific and overall survival. RESULTS: We identified 446 patients with a median age of 67 years (IQR 59-76). Of the patients 10% received neoadjuvant chemotherapy, 51% experienced any complication, 23% had high grade complications and 4% died within 3 months of robot-assisted radical cystectomy. Disease was pT3 or greater in 43% of patients and pN+ in 24% while a positive soft tissue surgical margin was observed in 7%. At a median followup of 5 years (IQR 2-10, maximum 14) local and distant recurrence had developed in 15% and 29% of patients, respectively. Ten-year recurrence-free, disease specific and overall survival rates were 59%, 65% and 35%, respectively. Patients with pT3 or greater and pN+ disease showed worse recurrence-free, disease specific and overall survival. CONCLUSIONS: Long-term oncologic outcomes, and recurrence rates and patterns after robot-assisted radical cystectomy seem comparable to those in open series. Advanced disease stage and positive surgical margins remain the main determinants of survival after radical cystectomy.

Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study.

OBJECTIVE: To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of <3 months. PATIENTS AND METHODS: We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at ≥25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually. RESULTS: PSMAV in the highest tertile (≥25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis. CONCLUSIONS: The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

Syn-Dihydroxylation of Alkenes Using a Sterically Demanding Cyclic Diacyl Peroxide.

The syn-dihydroxylation of alkenes is a highly valuable reaction in organic synthesis. Cyclic acyl peroxides (CAPs) have emerged recently as promising candidates to replace the commonly employed toxic metals for this purpose. Here, we demonstrate that the structurally demanding cyclic peroxide spiro[bicyclo[2.2.1]heptane-2,4'-[1,2]dioxolane]-3',5'-dione (P4) can be effectively used for the syn-dihydroxylation of alkenes. Reagent P4 also shows an improved selectivity for dihydroxylation of alkenes bearing ß-hydrogens as compared to other CAPs, where both diol and allyl alcohol products compete with each other. Furthermore, the use of enantiopure P4 (labeled P4') demonstrates the potential of P4' for a metal-free asymmetric syn-dihydroxylation of alkenes.

Outcomes of Intracorporeal Urinary Diversion after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: This study aimed to provide an update and compare perioperative outcomes and complications of intracorporeal and extracorporeal urinary diversion following robot-assisted radical cystectomy using data from the multi-institutional, prospectively maintained International Robotic Cystectomy Consortium database. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,125 patients from a total of 26 institutions. Intracorporeal urinary diversion was compared with extracorporeal urinary diversion. Multivariate logistic regression models using stepwise variable selection were fit to evaluate preoperative, operative and postoperative predictors of intracorporeal urinary diversion, operative time, high grade complications and 90-day hospital readmissions after robot-assisted radical cystectomy. RESULTS: In our cohort 1,094 patients (51%) underwent intracorporeal urinary diversion. These patients demonstrated shorter operative time (357 vs 400 minutes), less blood loss (300 vs 350 ml) and fewer blood transfusions (4% vs 19%, all p <0.001). They experienced more high grade complications (13% vs 10%, p = 0.02). Intracorporeal urinary diversion use increased from 9% of all urinary diversions in 2005 to 97% in 2015. Complications after this procedure decreased significantly with time (p <0.001). On multivariable analysis higher annual cystectomy volume (OR 1.02, 95% CI 1.01-1.03, p <0.002), year of robot-assisted radical cystectomy (2013-2016 OR 68, 95% CI 44-105, p <0.001) and American Society of Anesthesiologists® score less than 3 (OR 1.75, 95% CI 1.38-2.22, p <0.001) were associated with undergoing intracorporeal urinary diversion. The procedure was associated with a shorter operative time of 27 minutes (p = 0.001). CONCLUSIONS: The use of intracorporeal urinary diversion has increased in the last decade. A higher annual institutional volume of robot-assisted radical cystectomy was associated with intracorporeal urinary diversion as well as with shorter operative time. Although intracorporeal urinary diversion was associated with higher grade complications than extracorporeal urinary diversion, they decreased with time.

Evolution of cystectomy care over an 11-year period in a high-volume tertiary referral centre.

OBJECTIVES: To describe the evolution in radical cystectomy (RC) care over 11 years at a referral centre. PATIENTS AND METHODS: The clinical data of patients undergoing either open RC (ORC) or robot-assisted RC (RARC) for cT1-4aN0M0 bladder cancer (BCa) at our centre between January 2006 and December 2016 were retrospectively evaluated. Crude and propensity score-weighted log-binomial regression analyses were conducted to assess the association between pre- and peri-operative variables and the risk of reoperation, intensive care unit (ICU) admission and death <90 days after RC. RESULTS: A total of 814 patients were considered. The percentage of RARCs performed increased (from 10% to 100%) between 2006 and 2013. Overall, 29% of the patients received neoadjuvant chemotherapy (12-37% from 2006 to 2016). Despite no differences in terms of operating time, pelvic lymph node dissection (PLND) was more commonly attempted during RARC and extended PLND was more frequently performed in the RARC group (72% vs 19%; P < 0.001). Ileal conduit was the preferred urinary diversion in both groups, and more patients in the RARC group underwent neobladder construction (34% vs 14%; P < 0.001). The overall rates of re-intervention, ICU admission and death within 90 days of RC were 8.9%, 5.4% and 2.9%, respectively. On crude analysis, RARC was associated with a reduced risk of ICU admission (relative risk [RR] 0.42, 95% confidence interval [CI] 0.23-0.77; P = 0.005), reintervention (RR 0.58, 95% CI 0.37-0.90; P = 0.015) and death (RR 0.37, 95% CI 0.16-0.85; P = 0.020); however, these risk reductions were not statistically significant on weighted analyses. CONCLUSIONS: The introduction of RARC has coincided with a reduction in the rate of ICU admission, reoperation and death within 90 days of surgery, without compromising operating time, PLND extent or neobladder utilization.

Tuning the Reactivity of Peroxo Anhydrides for Aromatic C-H Bond Oxidation.

Phenol moieties are key structural motifs in many areas of chemical research from polymers to pharmaceuticals. Herein, we report on the design and use of a structurally demanding cyclic peroxide (spiro[bicyclo[2.2.1]heptane-2,4'-[1,2]dioxolane]-3',5'-dione, P4) for the direct hydroxylation of aromatic substrates. The new peroxide benefits from high thermal stability and can be synthesized from readily available starting materials. The aromatic C-H oxidation using P4 exhibits generally good yields (up to 96%) and appreciable regioselectivities.

Development and validation of surgical training tool: cystectomy assessment and surgical evaluation (CASE) for robot-assisted radical cystectomy for men.

BACKGROUND: We aimed to develop a structured scoring tool: cystectomy assessment and surgical evaluation (CASE) that objectively measures and quantifies performance during robot-assisted radical cystectomy (RARC) for men. METHODS: A multinational 10-surgeon expert panel collaborated towards development and validation of CASE. The critical steps of RARC in men were deconstructed into nine key domains, each assessed by five anchors. Content validation was done utilizing the Delphi methodology. Each anchor was assessed in terms of context, score concordance, and clarity. The content validity index (CVI) was calculated for each aspect. A CVI ≥ 0.75 represented consensus, and this statement was removed from the next round. This process was repeated until consensus was achieved for all statements. CASE was used to assess de-identified videos of RARC to determine reliability and construct validity. Linearly weighted percent agreement was used to assess inter-rater reliability (IRR). A logit model for odds ratio (OR) was used to assess construct validation. RESULTS: The expert panel reached consensus on CASE after four rounds. The final eight domains of the CASE included: pelvic lymph node dissection, development of the peri-ureteral space, lateral pelvic space, anterior rectal space, control of the vascular pedicle, anterior vesical space, control of the dorsal venous complex, and apical dissection. IRR > 0.6 was achieved for all eight domains. Experts outperformed trainees across all domains. CONCLUSION: We developed and validated a reliable structured, procedure-specific tool for objective evaluation of surgical performance during RARC. CASE may help differentiate novice from expert performances.

Early Oncologic Failure after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: We sought to investigate the prevalence and variables associated with early oncologic failure. MATERIALS AND METHODS: We retrospectively reviewed the IRCC (International Radical Cystectomy Consortium) database of patients who underwent robot-assisted radical cystectomy since 2003. The final cohort comprised a total of 1,894 patients from 23 institutions in 11 countries. Early oncologic failure was defined as any disease relapse within 3 months of robot-assisted radical cystectomy. All institutions were surveyed for the pneumoperitoneum pressure used, breach of oncologic surgical principles, and techniques of specimen and lymph node removal. A multivariate model was fit to evaluate predictors of early oncologic failure. The Kaplan-Meier method was applied to depict disease specific and overall survival, and Cox proportional regression analysis was used to evaluate predictors of disease specific and overall survival. RESULTS: A total of 305 patients (22%) experienced disease relapse, which was distant in 220 (16%), local recurrence in 154 (11%), peritoneal carcinomatosis in 17 (1%) and port site recurrence in 5 (0.4%). Early oncologic failure developed in 71 patients (5%) at a total of 10 institutions. The incidence of early oncologic failure decreased from 10% in 2006 to 6% in 2015. On multivariate analysis the presence of any complication (OR 2.87, 95% CI 1.38-5.96, p = 0.004), pT3 or greater disease (OR 3.73, 95% CI 2.00-6.97, p <0.001) and nodal involvement (OR 2.14, 95% CI 1.21-3.80, p = 0.008) was a significant predictor of early oncologic failure. Patients with early oncologic failure demonstrated worse disease specific and overall survival (23% and 13%, respectively) at 1 and 3 years compared to patients who experienced later or no recurrences (log rank p <0.001). CONCLUSIONS: The incidence of early oncologic failure following robot-assisted radical cystectomy has decreased with time. Disease related rather than technical related factors have a major role in early oncologic failure after robot-assisted radical cystectomy.

Impact of suboptimal neoadjuvant chemotherapy on peri-operative outcomes and survival after robot-assisted radical cystectomy: a multicentre multinational study.

OBJECTIVES: To evaluate the effect of suboptimal dosing on the outcomes of patients who received neoadjuvant chemotherapy (NAC) and robot-assisted radical cystectomy (RARC). PATIENTS AND METHODS: We retrospectively reviewed 336 consecutive patients with urothelial carcinoma of the bladder who were treated with NAC and RARC at three academic institutions. Outcomes were compared among three groups: patients who received optimal NAC; patients who received suboptimal NAC; and those who did not receive NAC. To adjust for potential baseline differences between the three groups, propensity-score-based matching was performed. The suboptimal dose group was defined as those who received <3 cycles of cisplatin-based chemotherapy, received a decreased dosage, or those not treated with cisplatin. Primary outcomes analysed were recurrence-free survival (RFS) and overall survival (OS). Secondary outcomes were peri-operative complications and readmissions after RARC. RESULTS: After propensity-score matching, 69 patients in the cohort received optimal-dose NAC, 41 received suboptimal NAC and 69 did not receive NAC. Complication rates and readmission rates did not differ significantly among the three groups. On multivariable analysis, suboptimal NAC and no NAC were independent predictors of worse RFS (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2-5.7, P = 0.01 and HR 2.4, 95% CI 1.28-5.16, P = 0.01) and worse OS (HR 4.5, 95% CI 1.6-15.0, P < 0.01 and HR 4.9, 95% CI 1.9-15.6, P < 0.01) in patients who received NAC and RARC. Failure to achieve pathological complete response (ypT0N0) was also an independent predictor of worse RFS (HR 6.6, 95% CI 1.3-20.9; P = 0.02) and OS (HR 4.9, 95% CI 1.8-15.3; P = 0.02). CONCLUSION: Optimal NAC resulted in a better RFS and OS when compared with suboptimal or no NAC. Suboptimal and no NAC were associated with worse OS and RFS. These findings will facilitate improved patient counseling and treatment selection.

Development of a patient and institutional-based model for estimation of operative times for robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVES: To design a methodology to predict operative times for robot-assisted radical cystectomy (RARC) based on variation in institutional, patient, and disease characteristics to help in operating room scheduling and quality control. PATIENTS AND METHODS: The model included preoperative variables and therefore can be used for prediction of surgical times: institutional volume, age, gender, body mass index, American Society of Anesthesiologists score, history of prior surgery and radiation, clinical stage, neoadjuvant chemotherapy, type, technique of diversion, and the extent of lymph node dissection. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with surgical time. The data were split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated recursively on the resultant data sets until the permutation tests showed no significant association with operative time. RESULTS: In all, 2 134 procedures were included. The variable most strongly associated with surgical time was type of diversion, with ileal conduits being 70 min shorter (P < 0.001). Amongst patients who received neobladders, the type of lymph node dissection was also strongly associated with surgical time. Amongst ileal conduit patients, institutional surgeon volume (>66 RARCs) was important, with those with a higher volume being 55 min shorter (P < 0.001). The regression tree output was in the form of box plots that show the median and ranges of surgical times according to the patient, disease, and institutional characteristics. CONCLUSION: We developed a method to estimate operative times for RARC based on patient, disease, and institutional metrics that can help operating room scheduling for RARC.

Mild Aliphatic and Benzylic Hydrocarbon C-H Bond Chlorination Using Trichloroisocyanuric Acid.

We present the controlled monochlorination of aliphatic and benzylic hydrocarbons with only 1 equiv of substrate at 25-30 °C using N-hydroxyphthalimide (NHPI) as radical initiator and commercially available trichloroisocyanuric acid (TCCA) as the chlorine source. Catalytic amounts of CBr4 reduced the reaction times considerably due to the formation of chain-carrying ·CBr3 radicals. Benzylic C-H chlorination affords moderate to good yields for arenes carrying electron-withdrawing (50-85%) or weakly electron-donating groups (31-73%); cyclic aliphatic substrates provide low yields (24-38%). The products could be synthesized on a gram scale followed by simple purification via distillation. We report the first direct side-chain chlorination of 3-methylbenzoate affording methyl 3-(chloromethyl)benzoate, which is an important building block for the synthesis of vasodilator taprostene.

Calcium carbide catalytically activated with tetra-n-butyl ammonium fluoride for Sonogashira cross coupling reactions.

We report a novel method for the direct synthesis of mono- and bis-arylated alkynes utilizing catalytically activated CaC2 as the alkyne component. This fluoride-activated cross coupling reaction provides advantages over existing methods regarding operational simplicity, use of readily available starting materials, and low cost.