Nicolas von Landenberg

Peri-operative allogeneic blood transfusion does not adversely affect oncological outcomes after radical cystectomy for urinary bladder cancer: a propensity score-weighted European multicentre study

To evaluate the effect of peri‐operative blood transfusion (PBT) on recurrence‐free survival, overall survival, cancer‐specific mortality and other‐cause mortality in patients undergoing radical cystectomy (RC), using a contemporary European multicentre cohort.

Liver Disease in Men Undergoing Androgen Deprivation Therapy for Prostate Cancer

Purpose: Androgen deprivation therapy is associated with the development of diabetes and metabolic syndrome. To our knowledge its effect on the development of nonalcoholic fatty liver disease, a condition which frequently co‐occurs with metabolic syndrome and other subsequent liver conditions such as liver cirrhosis, hepatic necrosis or any liver disease, has not been investigated. Materials and Methods: We identified 82,938 men 66 years old or older who were diagnosed with localized prostate cancer in the SEER (Surveillance, Epidemiology and End Results)‐Medicare database from 1992 to 2009. Men with preexisting nonalcoholic fatty liver disease, liver disease, diabetes or metabolic syndrome were excluded from study. Propensity score adjusted, competing risk regression models were created to compare the risk of nonalcoholic fatty liver disease in men who were vs were not treated with androgen deprivation. We also explored the influence of cumulative exposure to androgen deprivation therapy, calculated as monthly equivalent doses of gonadotropin‐releasing hormone agonists/antagonists (fewer than 7, 7 to 11 or more than 11 doses). Results: Overall 37.5% of men underwent androgen deprivation therapy. They were more likely to be diagnosed with nonalcoholic fatty liver disease (HR 1.54, 95% CI 1.40–1.68), liver cirrhosis (HR 1.35, 95% CI 1.12–1.60), liver necrosis (HR 1.41, 95% CI 1.15–1.72) and any liver disease (HR 1.47, 95% CI 1.35–1.60). A dose‐response relationship was observed between the number of androgen deprivation therapy doses, and nonalcoholic fatty liver disease and any liver disease. Conclusions: Androgen deprivation therapy in men with prostate cancer is associated with the diagnosis of nonalcoholic fatty liver disease. The usual limitations of an observational study design apply, including possible inaccuracy in defining outcomes in a population based registry.

Short‐term external ureter stenting shows significant benefit in comparison to routine double‐J stent placement after ureterorenoscopic stone extraction: A prospective randomized trial – the Fast track stent study (FaST)

To determine whether short‐term stenting using an external ureter catheter following ureterorenoscopic stone extraction provides a better outcome in comparison to double‐J stent ureteral stenting.

Testing the external validity of the EORTC randomized trial 30904 comparing overall survival after radical nephrectomy vs nephron-sparing surgery in contemporary North American patients with renal cell cancer

EORTC 30904 reported that for solitary renal mass <=5cm, radical nephrectomy (RN) is associated with higher overall survival compared with nephron sparing surgery (NSS). This trial remains the only available level one evidence on this subject. To test external validity of the trial, patients who met clinical and pathological inclusion criteria of EORTC 30904 within the National Cancer Database (NCDB) were identified. We found that median age (60years in NCDB vs. 62years in trial) and median clinical tumour size (30mm in both) were similar between the cohorts. These two variables are most important determinants of mortality and stage of cancer, respectively, implying that the trial was able to recruit patients virtually representative of those seen in “real-world” practice. Moreover, in NCDB, more patients had clear-cell histology (81.9% vs. 62.9% in trial) and high-grade disease (21.1% vs. 11.2% in trial), implying more aggressive tumors compared to the trial. Arguably, these patients are better served with RN which has a higher probability of completely eradicating the tumor, making the results of the trial even more relevant to practice. Our results indicate that EORTC 30904 cohort was not significantly different from the NCDB cohort in a manner that could influence reported trial outcomes. This article is protected by copyright. All rights reserved.

Impact of adequate pelvic lymph node dissection on overall survival after radical cystectomy: A stratified analysis by clinical stage and receipt of neoadjuvant chemotherapy

PURPOSE An adequate pelvic lymph node dissection (LND) during radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) has been shown to provide a survival benefit. We designed a study to assess the effect of adequate LND on overall survival (OS) according to cT stage and receipt of neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS We identified 16,505 patients with localized BCa who received RC in the National Cancer Database (2004-2012). Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox regression analyses were used to compare OS between patients who received adequate LND (defined as ≥10 nodes removed) and those who did not, stratified by cT stage and receipt of NAC. RESULTS Overall 8,673 (52.55%) patients underwent adequate LND at RC for localized BCa. Median time to last follow-up was 55.49 months (IQR, 34.73-75.96 months). IPTW-adjusted Kaplan-Meier curves showed that median OS was improved in patients who received adequate LND (60.06 vs. 46.88 months). In patients who did not receive NAC, adequate LND was associated with an OS benefit for cT1/a/cis, cT2, and cT3/4 disease (P ≤ 0.008). Among patients who received NAC, adequate LND was not associated with any OS difference regardless of cT stage. CONCLUSION Our data suggest that patients who did not receive NAC benefit from an adequate LND. However, the receipt of an adequate LND was not associated with an OS benefit in patients pretreated with NAC. Our study indicates that the receipt of NAC may eradicate micrometastatic disease, and thus limit the benefit of an adequate LND.

MP91-04 ADVERSE EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY FOR MEN, A MATCHED COHORT STUDY

INTRODUCTION AND OBJECTIVES: To evaluate role of lowintensity shock wave therapy (LI-SWT) in penile rehabilitation (PR) post nerve sparing radical cysto-prostatectomy (NS-RCP). METHODS: Eighty seven sexually active men with muscle invasive bladder cancer were enrolled in this prospective study. After bilateral NS-RCP with orthotopic diversion (W-Pouch) by a single expert surgeon between January 2015 & October 2016, patients were randomized into 3 groups (29 patients/group). SWL Group received 12 sessions of penile LI-SWT (2/week for 3 weeks, then 3 weeks free of treatment, then 2/week for another 3 weeks). Phosphodiesterase type-5 inhibitors (PDE5i) Group received oral PDE5i of 50 mg /day for 6 months. Control Group was followed up only without any therapy. Patients were assessed before surgery and at 1 (FU1), 3 (FU2), 6 (FU3) and 9-month (FU4) post operatively. Effectiveness was assessed by IIEF-15 questionnaire and erection hardness score (EHS). RESULTS: Mean age was 54.1 5.9 years with mean followup period 15.9 4.2 months. There were no statistically significant differences regarding preoperative patients demographic data & tumor criteria. At FU1; All patients have insufficient erection for vaginal penetration. EHS < 2; with decrease of preoperative IIEF-EF mean score from 28 to 6.6. In SWL group; At FU2; 17/29 patients regained potency which is maintained in 15 only at FU3&4. However; 6 of remaining 12 patients regained & maintained potency at FU3&4. Statistical evaluation showed significant increase in IIEF-EF score from 6.6 at FU1 to 23 at FU2, 24 at FU3 and 24.5 at FU4 ( P <0.001). In PDE5i group; At FU2; 16/29 patients regained & maintained potency at FU3&4. However; 7 of remaining 13 patients regained & maintained potency at FU3&4. Statistical evaluation showed significant increase in IIEF-EF score from 6.6 at FU1 to 22.8 at FU2, 24 at FU3 and 24.7 at FU4 (P <0.001). In Control group; At FU2; 12/29 patients regained & maintained potency at FU3&4. However; 6 of remaining 17 patients regained & maintained potency at FU3&4. Statistical evaluation showed no significant difference in potency recovery rates at FU2 & FU3,4 among the groups ( P 1⁄4 0.14 & P 1⁄4 0.24 respectively). Potency recovery rates at FU2 were 58.6% vs 55.2% vs 41.4% in SWL, PDE5i and Control group, respectively. While potency recovery rates at FU3,4 were 72.4% vs 79.3% vs 62.1% in SWL, PDE5i and Control group, respectively. CONCLUSIONS: LI-SWT is safe and as effective as oral PDE5i in PR post NS-RCP. A large-scale study is required to determine the value of this treatment modality in ED post NS-RCP.

Challenging Residual Contamination of Instruments for Robotic Surgery in Japan

To the Editor—Infectious complications after surgery are drivers of both costs and morbidity. We therefore read with considerable interest the recent paper “Challenging Residual Contamination of Instruments for Robotic Surgery in Japan” by Saito et al. In their study, the authors assess residual protein concentration on reusable surgical instruments both immediately following surgery and after standard hospital cleaning. They found that, compared to traditional open instruments, robotic surgical instruments retained significantly more residual protein both immediately after surgery and after routine cleaning. Robot-assisted surgery is an approach that has grown in popularity over the past decade. It has now become the most widely used approach for many common operations in the developed world. In robotic surgery, instruments and cameras are inserted through small laparoscopic port sides and the surgeon sits at a console and manipulates the surgical instruments under direct video control. These robotic instruments contain miniaturized mechanical and electronic components that may be more difficult to clean than traditional surgical instruments. Saito et al placed both robotic and open instruments in an ultrasonic sink and used sterile water flushes in combination with ultrasonication and protein assays to infer the amount of protein on instruments after surgery and after routine cleaning. They found that robotic surgical instruments had both higher residual protein concentration compared with open surgical instruments and a slower rate of decline in protein concentration. These results make sense; instruments with complex miniaturized mechanical components have an exponentially larger surface area and probably should retain more protein compared to open surgical instruments, many of which are simple metal grasping tools like scissors or forceps. There are, however, some key questions that this paper does not address. First, the authors did not control for size or surface area of instruments: robotic surgical instruments have a vastly greater length and surface area. In addition, the largest part of the robotic surgical instrument never enters the patient and is purely used to attach the instrument to the surgical robot. Another study of cleaning methods for robotic surgical devices showed false-positive results after cleaning robotic instruments because it was not clear whether the protein or substances were obtained from the distal working part or from the shaft. Second, the total number of instruments used during the operation was not assessed. For example, robot-assisted prostatectomy may be performed with a total of only 5 robotic instruments (2 needle drivers, a grasper, bipolar forceps, scissors, and large grasping forceps), whereas open surgery may require a larger number of individual instruments. A typical open prostatectomy may require multiple pairs of long and short forceps, both toothed and smooth, as well as many instruments that are obsolete in robotic surgery such as retractors, sponge sticks, or scalpels. Comparing the aggregate protein remaining on all instruments used in an operation may be more relevant than the per-instrument concentration. Another methodological point relates to the measurement of protein remaining on the instruments. With the exception of rare entities like prion diseases, protein itself does not have the ability to cause wound infections. Why not perform assays that specifically measure pathogenic organisms (eg, cultures or PCR assays)? This approach would probably provide a more clinically relevant measure of whether viruses or bacteria are being retained on robotic instruments after cleaning. Finally, and most importantly, there is a practical question: How do the findings of higher residual protein on robotic surgical instruments impact actual clinical outcomes? An extensive body of observational data suggests that minimally invasive surgeries may have lower rates of infectious complications than open surgeries. Recently, 2 prospective randomized trials found no higher rates of infectious complications with robotic cystectomy and prostatectomy than with open operations. While the precise impact of robotic surgery on postoperative complications remains a topic of debate and active research, there is certainly no evidence for exponentially greater infectious rates with robotic surgical instruments. In addition, the proven incidence of infection due to surgical devices is very low. Surgical wound infections are vastly more likely to be due to contamination from the patient’s skin flora. Thus, benefits due to smaller incision could easily outweigh any theoretical increase in risk due to retained biomaterial on instruments. The results of Saito et al underscore one of the ways that robotic surgical instruments differs from traditional open surgical instruments: The former tend to have a larger amount of residual protein left after cleaning, which makes sense given their design and size. While novel approaches for cleaning surgical instruments should adapt to new types of instruments, this should not dissuade innovators. Ultimately, new technologies and techniques are judged by their clinical outcomes. Specifically, the evaluation of novel techniques should include careful assessment of infectious risks in concert with careful basic scientific research. At the end of the day, this is what matters for patients, surgeons, and other stakeholders. infection control & hospital epidemiology

Racial disparity in quality of care and overall survival among black vs. white patients with muscle-invasive bladder cancer treated with radical cystectomy: A national cancer database analysis

OBJECTIVES To examine the impact of race on quality of care and overall survival (OS) among patients with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) in the U.S. MATERIALS & METHODS Our cohort consisted of 12,652 patients receiving RC for MIBC within the National Cancer Database from 2004 to 2012. Patients were stratified by race (Black non-Hispanic vs. White non-Hispanic) and imbalances in patient characteristics mitigated using propensity score weighting. Logistic and Cox regressions examined the impact of race on quality of care metrics (receipt of pelvic lymph node dissection (PLND), lymph node count, hospital volume, length of stay, delay of treatment) and on OS. The difference in OS was expressed as Delta, and stratified by facility-type, hospital volume, and region. RESULTS Blacks were less likely to receive PLND (odds ratio [OR] 0.70, 95% confidence interval [CI]: 0.55-0.91), or to have a greater number of lymph nodes removed (OR 0.76, 95%CI: 0.64-0.90). They exhibited greater length of stay (OR 1.34, 95%CI: 1.13-1.59), and delay of RC among recipients of neoadjuvant chemotherapy (OR 2.59, 95%CI: 1.77-3.85) (all P ≤ 0.001). Notably, utilization of neoadjuvant chemotherapy in advanced disease stages was more common in blacks (OR 2.82, 95%CI: 1.93-4.13, P < 0.001). Additionally, Black race was associated with inferior OS (Hazard ratio 0.87, 95%CI: 0.79-0.97, P < 0.014). Disparities in OS varied based on facility type and geographical region, but not hospital volume. Specifically, Blacks had worse OS when treated in a community cancer program (Delta 0.42, 95%CI: 0.28-0.57,P < 0.001), or within New England/Middle Atlantic region (Delta 0.16, 95% CI: 0.07-0.24,P < 0.001). CONCLUSION Black race is an independent predictor of inferior quality of care and OS in patients undergoing RC for MIBC. Survival disparities vary based on geographical region and facility type. Notably, the OS disparity appears to have narrowed in comparison to previous studies.

Conditional analyses of recurrence and progression in patients with TaG1 non–muscle-invasive bladder cancer

OBJECTIVE To determine conditional recurrence-free survival (RFS) and progression-free survival (PFS) and improve decision-making toward surveillance protocols and scheduling. Furthermore, evaluating the evolution of predictors for disease recurrence over time, because TaG1 non-muscle-invasive bladder cancer harbors a risk of disease recurrence and progression. MATERIAL AND METHODS The retrospective multicenter design study includes 1,245 TaG1 bladder cancer patients with median follow-up of 62.7 (interquartile range: 34.3-91.1) months. Conditional RFS and PFS estimates were calculated using the Kaplan-Meier method. Multivariable Cox regression model was calculated proportional for the prediction of recurrence and progression (covariables: age, tumor size, multiple tumors, prior recurrence, and immediate postoperative instillation of chemotherapy). RESULTS After 3 months without event, the conditional RFS and PFS (to ≥pT2) rates for 5 additional years without event were 57.5% and 93.4%, respectively. Given a 1-, 2-, 3-, and 5-year survival, the conditional RFS rates for 5 additional years without event improved by +9.8 (67.3%), +5.2 (72.5%), +6.5 (79.0%), +2.0 (81.0%), and +1.0% (82.0%), respectively. In contrast, the 5-year conditional PFS rates were more or less stable with 94.3% after 1 year to 94.1% after 5 years. Multivariable analyses showed decreasing impact of risk parameters on RFS estimates over time. Based on these findings, we suggest a risk stratification to individualize follow-up for intermediate risk TaG1. Main limitation was the retrospective design. CONCLUSIONS Conditional-survival analyses demonstrates that the patient risk profile changes over time. RFS rates rise with increasing survival whereas PFS rates were stable. The impact of prognostic features decreases over time. Our findings can be used for patient counseling and planning of personalized follow-up.

De novo neurogenic bladder dysfunction after salvage lymph node dissection in patients with nodal recurrence of prostate cancer

To examine the impact of Salvage lymph node dissection (SLND) on bladder function and oncological outcome in hormone naïve patients with nodal recurrence of prostate cancer (PCa) after radical prostatectomy (RP).