Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19.

Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g., IL6, CCL20) or clinical hallmarks of COVID-19 (e.g., neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Analysis of an independent cohort of 108 patients from a different center (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover hospital blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19.

Ventilatory inefficiency adversely affects outcomes and longer-term survival after planned colorectal cancer surgery.

BACKGROUND: Impaired cardiorespiratory reserve is an accepted risk factor for patients having major surgery. Ventilatory inefficiency, defined by an elevated ratio of minute ventilation to carbon dioxide excretion (VE/VCO2), and measured by cardiopulmonary exercise testing (CPET), is a pathophysiological characteristic of patients with cardiorespiratory disease. We set out to evaluate the prevalence of ventilatory inefficiency in a colorectal cancer surgical population, and its influence on surgical outcomes and long-term cancer survival. METHODS: In this retrospective study of 1375 patients who had undergone preoperative CPET followed by colorectal cancer surgery, we used receiver operating characteristic curve analysis to identify an optimal value of VE/VCO2 associated with 90-day mortality. Binary logistic regression was used to evaluate whether this degree of ventilatory inefficiency was independently associated with decreased survival, both after surgery and in the longer term. RESULTS: We identified an optimal VE/VCO2 >39 cut-off for predicting 90-day mortality; 245 patients (17.8%) had VE/VCO2 >39, of which 138 (10% of total cohort) had no known cardiorespiratory risk factors. Ventilatory inefficiency was independently associated with death at 90-days (8.2% mortality vs 1.9%; adjusted odds ratio [OR], 4.04; 95% confidence interval [CI], 2.09-7.84), with death after unplanned critical care admission (OR=4.45; 95% CI, 1.37-14.46) and with decreased survival at 2 yr (OR=2.21; 95%, 1.49-3.28) and 5 yr (OR=2.87; 95% CI, 1.54-5.37) after surgery. CONCLUSIONS: A significant proportion of patients having colorectal cancer surgery have ventilatory inefficiency observed on CPET, the majority of whom have no history of cardiorespiratory risk factors. This group of patients has significantly decreased survival both after surgery and in the long-term, irrespective of cancer stage. Survival might be improved by formal medical evaluation and intervention in this group.

Cardiopulmonary Exercise Testing Has no Additive Incremental Value to Standard Scoring Systems when Risk Stratifying for Bariatric Surgery.

BACKGROUND: Cardiopulmonary exercise testing (CPET) can identify patients at risk of adverse post-operative outcomes following major abdominal surgery including bariatric surgery. Scoring systems that also aim to predict post-operative outcome in this group include the validated obesity surgery mortality risk score (OSMRS). This study aims to investigate if CPET has additive value to other scoring systems in predicting post-operative outcomes following bariatric surgery. METHODS: Data was collected retrospectively on 398 patients who underwent CPET between October 2008 and April 2013. CPET data, medical history, complication rates and length of stay (LOS) were obtained from patient records. Data was analysed to investigate the relationship between CPET and other scoring systems with post-operative outcome. RESULTS: Two hundred and fifty patients underwent Roux-en-Y gastric bypass or sleeve gastrectomy. Median LOS was 4 days (IQR 4-6 days) and 41 patients (16.4 %) developed a complication. Adjusted data showed a risk difference for complications of 17 % (95 % CI 9-25 %) between high- and low-risk patients stratified by OSMRS alongside a 27 % (95 % CI 12-45 %) longer LOS. Variation in AT or peak VO2 showed no significant relationship with complications or LOS. Amongst high OSMRS risk patients, there was no significant difference in complications or LOS when CPET data was added to this analysis. CONCLUSIONS: Cardiopulmonary exercise testing adds no incremental value in predicting post-operative outcomes in the bariatric population compared to the OSMRS, which is strongly predictive of length of stay and complication following bariatric surgery.

Comparison of esophageal Doppler and plethysmographic variability index to guide intraoperative fluid therapy for low-risk patients undergoing colorectal surgery.

STUDY OBJECTIVE: This study aims to investigate if there is equivalence in volumes of fluid administered when intravenous fluid therapy is guided by Pleth Variability Index (PVI) compared to the established technology of esophageal Doppler in low-risk patients undergoing major colorectal surgery. DESIGN: Randomized controlled trial. SETTING: Operating room. PATIENTS: Forty low-risk patients undergoing elective colorectal surgery. INTERVENTION: Patients were monitored by esophageal Doppler and PVI probes and were randomized to have fluid therapy directed by using one of these technologies, with 250 mL boluses of colloid to maintain a maximal stroke volume, or a PVI of less than 14%. MEASUREMENTS: Absolute volumes of fluid volumes given intraoperatively were measured as were 24 hours fluid volumes. Perioperative measurements of lactate and base excess were recorded as were postoperative complications. MAIN RESULT: There was no significant difference between PVI and esophageal Doppler groups in mean total fluid administered (1286 vs 1520 mL, P=.300) or mean intraoperative fluid balance (+839 v+1145 mL, P=.150). CONCLUSIONS: PVI offers an entirely non-invasive alternative for goal-directed fluid therapy in this group of patients.

Postoperative nomogram to predict cancer-specific survival after radical nephroureterectomy in patients with localised and/or locally advanced upper tract urothelial carcinoma without metastasis.

OBJECTIVE: To propose and validate a nomogram to predict cancer-specific survival (CSS) after radical nephroureterectomy (RNU) in patients with pT1-3/N0-x upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: The international and the French national collaborative groups on UTUC pooled data from 3387 patients treated with RNU. Only 2233 chemotherapy naïve pT1-3/N0-x patients were included in the present study. The population was randomly split into the development cohort (1563) and the external validation cohort (670). To build the nomogram, logistic regressions were used for univariable and multivariable analyses. Different models were generated. The most accurate model was assessed using Harrell's concordance index and decision curve analysis (DCA). Internal validation was then performed by bootstrapping. Finally, the nomogram was calibrated and externally validated in the external dataset. RESULTS: Of the 1563 patients in the nomogram development cohort, 309 (19.7%) died during follow-up from UTUC. The actuarial CSS probability at 5 years was 75.7% (95% confidence interval [CI] 73.2-78.6%). DCA revealed that the use of the best model was associated with benefit gains relative to prediction of CSS. The optimised nomogram included only six variables associated with CSS in multivariable analysis: age (P < 0.001), pT stage (P < 0.001), grade (P < 0.02), location (P < 0.001), architecture (P < 0.001) and lymphovascular invasion (P < 0.001). The accuracy of the nomogram was 0.81 (95% CI, 0.78-0.85). Limitations included the retrospective study design and the lack of a central pathological review. CONCLUSION: An accurate postoperative nomogram was developed to predict CSS after RNU only in locally and/or locally advanced UTUC without metastasis, where the decision for adjuvant treatment is controversial but crucial for the oncological outcome.

Impact of the length of time between diagnosis and surgical removal of urologic neoplasms on survival.

OBJECTIVE: Our aim was to assess the effect of surgical wait time on the survival of patients with urological neoplasms, including prostate, bladder, penile, and testicular cancers and upper tract tumours (UTUC). MATERIALS AND METHODS: Current, relevant studies were identified from the literature. Keywords used for article retrieval were as follows: delay; surgery; prostate cancer; urothelial carcinoma; renal cell carcinoma; testicular cancer; bladder; renal pelvis; ureter; and survival. RESULTS: Regarding the length of surgical wait time, it does not matter in cases of incidental T1a renal cell carcinomas. In other cases of renal cell carcinomas, surgery should be considered within <1 month; it is of crucial importance in bladder cancer and should be <1 month for a TURBT in cases of non-muscle-invasive bladder cancer and <1 month for a radical cystectomy in cases of muscle-invasive bladder cancer; it is important in invasive UTUC and should be <1 month for a radical nephroureterectomy; it is not crucial in cases of low-risk prostate cancer. In any other case, radical prostatectomy should be considered within <2 months; it is important in testicular cancer and should be fewer than 10 days for an orchiectomy. CONCLUSION: Prolonged surgical wait times have an impact on the overall quality of life and anxiety of the patient. Extending the wait time beyond a given threshold can also have a negative impact on the patient's clinical outcomes, but this threshold differs between urological neoplasms.

Hereditary-like urothelial carcinomas of the upper urinary tract benefit more from adjuvant cisplatin-based chemotherapy after radical nephroureterectomy than do sporadic tumours.

OBJECTIVE: To evaluate the impact of 'hereditary-like' status in upper tract urothelial carcinoma (UTUC) on the survival of patients who have undergone radical nephroureterectomy (RNU) and adjuvant chemotherapy. PATIENTS AND METHODS: A multicentre retrospective study was performed on all patients with high-risk UTUC who underwent RNU and adjuvant cisplatin-based chemotherapy. Using a patient risk identification tool, we distinguished tumours suspected to be hereditary from sporadic tumours and compared survival rates. RESULTS: A total of 112 patients with a median age of 67 years were included. Hereditary-like tumour status was detected in 35 patients (31.3%), while 77 patients (68.7%) had sporadic tumours. The median age was significantly younger in the hereditary-like tumour group (56.0 vs 69.8 years, P < 0.001). Overall survival (OS) after chemotherapy was significantly better in the group with hereditary-like tumours than in the group with sporadic tumours (5-year OS: 48.2 vs 32%; P = 0.008). The cancer-specific survival (CSS) rate was significantly better in the group with 'hereditary-like' tumours than in the group with sporadic tumours (5-year CSS: 58 vs 35%; P = 0.006). Although there was a trend in favour of the hereditary-like tumours, we observed no significant difference regarding progression-free survival (PFS) between the two groups (5-year PFS: 71 vs 52%; P = 0.07). CONCLUSION: Adjuvant chemotherapy after RNU improves survival outcomes in patients with hereditary-like UTUC compared with those with sporadic tumours.

A new proposal to risk stratify urothelial carcinomas of the upper urinary tract (UTUCs) in a predefinitive treatment setting: low-risk versus high-risk UTUCs.

Risk stratification of upper tract urothelial carcinoma (UTUC) patients and tumours is crucial for highlighting that an alternative to radical extirpative surgery now exists and should be considered for all patients who qualify as having low-risk UTUC.

Robot-assisted laparoscopic artificial urinary sphincter insertion in men with neurogenic stress urinary incontinence.

OBJECTIVE: To describe for the first time the technique of robot-assisted artificial urinary sphincter (R-AUS) insertion in male patients with neurogenic incontinence. MATERIALS AND METHODS: From January 2011 to the present date, six patients with spinal cord injury have undergone R-AUS insertion at our academic institution and we have prospectively collected data on pre-, peri- and early postoperative outcomes. A transperitoneal five-port approach was used using a three-arm standard da Vinci® robot (Intuitive Surgical, Sunnyvale, CA, USA) in a 30° reverse Trendelenburg position. The artificial urinary sphincter (AUS) cuff was placed circumferentially around the bladder neck, the reservoir was left intra-abdominally in a lateral vesicular space and the pump was placed in a classic scrotal position. RESULTS: All six patients had successful robotic implantation of the AUS. The median patient age was 51.5 years, the median (range) operating time was 195 (175-250) min with no significant blood loss or intra-operative complications. The median (range) length of hospital stay was 4 (4-6) days. At a median (interquartile range) follow-up of 13 (6-21) months, all six patients had a functioning device with complete continence. To date, we have observed no incidence of early erosion, device infection or device malfunction. CONCLUSIONS: Allowing for the preliminary nature of our data, R-AUS insertion appears safe and technically feasible. Larger studies with long-term follow-up and comparison with open AUS insertion are necessary before definitive statements can be made for R-AUS in respect of complications and functional outcomes.

Distinct patterns and behaviour of urothelial carcinoma with respect to anatomical location: how molecular biomarkers can augment clinico-pathological predictors in upper urinary tract tumours.

PURPOSE: Upper urinary tract urothelial carcinoma (UTUC) shares many similarities with bladder-UC, but there is strong evidence on a clinical, aetiological, epidemiological and genetic level that key differences exist. In this review, we aim to highlight how UTUC differs from bladder-UC and report on the utility of molecular markers in the diagnosis and management of UTUC. MATERIALS AND METHODS: A systematic literature search was conducted using the Medline and Embase databases and specific keyword combinations: 'urothelial carcinoma', 'bladder cancer', 'transitional cell carcinoma', 'upper tract', 'upper urinary tract', 'genetics', 'prognosis' and 'biomarkers'. RESULTS: UTUC has specific acquired (e.g. Balkans nephropathy, phenacetin abuse) and genetic hereditary non-polyposis colorectal cancer risk factors compared with bladder-UC. In general, the molecular biology of UC is broadly similar, irrespective of location in the urinary tract. However, there are distinct genetic (microsatellite instability) and epigenetic (hypermethylation) differences between some UTUC and bladder-UC. Clinical-pathological variables (e.g. hydronephrosis, tumour architecture, tumour location, stage and grade) have independent predictive power in UTUC, but tissue and urinary biomarkers can improve the clinical prediction of recurrence, invasion and survival in UTUC, though the evidence level is weak. CONCLUSIONS: UTUC shares many similarities with bladder-UC, but there is strong evidence that they should be considered as distinct urothelial entities. Prospective multi-institutional studies investigating molecular markers are urgently needed to augment clinic-pathological predictors in UTUC.

Comparing how significantly the pharmacological treatment of genitourinary cancer in a non-curative setting affects endpoints of survival or response.

Prevalence of advanced genitourinary cancer is high considering approximately 70,000 patients die annually of prostate, bladder and kidney cancer in the United States. Treatment is non-curative but along with the aim of relieving symptoms and improving quality of life, patients and doctors are driven by the goal of prolonging life. In modern urological practice, with the ever increasing number of novel therapies, clinical benefit to patients has to be measured by evaluating the trial endpoints of response and survival against adverse events. This is especially true as the population with advanced cancer is increasingly older and co-morbid. Currently, we are in a time of exponential drug development, innumerable registered trials and a vast amount of expenditure on pharmacological cancer treatment. In this era of financial uncertainty, it is even more important for clinicians to objectively assess the benefit of these expensive, moderately effective treatments that still have associated adverse sequelae. We aim to highlight the pivotal data available and put into context the survival benefit we can currently achieve with the pharmacological treatment of advanced genitourinary cancer, allowing us to critically judge whether a potentially toxic systemic treatment is worthwhile or whether it is better to defer to best supportive care. The figures presented are from the key publications that form the basis of international guideline recommendations and are the standard that newly developed treatments must emulate.

Role of pelvic phased array magnetic resonance imaging in staging of prostate cancer specifically in patients diagnosed with clinically locally advanced tumours by digital rectal examination.

OBJECTIVES: To assess the value of dynamic contrast-enhanced magnetic resonance imaging (MRI) for the prediction of extracapsular extension (ECE) in patients with clinical T3 (cT3) prostate cancer (PCa) compared to digital rectal examination (DRE). MATERIALS AND METHODS: A retrospective review of data for patients treated by radical prostatectomy for cT3 PCa was performed. Patients who underwent MRI in the pre-operative work-up were included. The likelihoods of extracapsular extension (T3a) and seminal vesicle invasion (T3b) were scored on the basis of MR images. For data analysis, receiver operating characteristic (ROC) curves were generated. RESULTS: Overall, 70 consecutive patients were included. Mean age was 63.8 (range 45-75) years, and the mean PSA level was 11.3 (range 2.9-26) ng/ml. Pathological analysis of the prostatic specimens confirmed 81.4% (n = 57) had pT3 disease. According to MRI, 57 (81.4%) patients were predicted correctly to have T3 disease. The overstaging (actual pT2) by either DRE or MRI or both was 18.6, 7 or 7%, respectively. The sensitivity, specificity and positive (PPV) and negative predictive values (NPV) of MRI were 94.7, 69, 93 and 75%. The kappa index of concordance between pre-operative MRI stage and pathological stage was 0.68 (P < 0.00001). The performance of MRI for T3 staging was AUC 0.87 (95% CI, 0.77-0.97). CONCLUSIONS: Pre-prostatectomy MRI adds significant incremental value to the assessment of patients with cT3 disease. Its ability to accurately predict and characterize pathological T3 status and its superiority to standard clinical variables (e.g. DRE) confirm its usefulness in pre-operative work-up.

Genetic polymorphisms on 8q24.1 and 4p16.3 are not linked with urothelial carcinoma of the bladder in contrast to their association with aggressive upper urinary tract tumours.

PURPOSE: Bladder urothelial carcinoma (bladder-UC) displays distinct genotypic differences compared to upper tract UC (UTUC). We recently reported specific 8q24 SNP variants confer susceptibility to UTUC and aggressive disease features. Herein, we evaluate a bladder-UC cohort to see whether similar polymorphisms are linked similarly same way with disease risk and aggressiveness. METHODS: 231 bladder-UC patients and 261 benign controls were matched for gender, age, ethnicity and smoking habits. We retrospectively retrieved information on tumour stage, grade, size, multiplicity, carcinoma in situ and tumour number. DNA was extracted from paraffin-embedded primary bladder-UC samples and blood of benign controls. Genotyping of rs9642880[T] (8q24.1) and rs798766[T] (4p16.3) was performed using commercially available Taqman(®) assays and the ABI™ 7000 Sequence Detector. RESULTS: Using a case-control analysis, bladder-UC risk was increased in individuals carrying the T/T genotype of rs9642880 [OR = 1.72 (95 % CI 1.1-2.8); p = 0.028] and rs798766 [OR = 1.84 (95 % CI 0.9-2.3); p = 0.01]. When analysing parameters of bladder-UC aggressiveness, the T/T genotypes for rs9642880 and rs798766 were not found to be associated with either grade [OR = 0.89 (95 % CI 0.52-1.32; p = 0.68) and OR = 0.95 (95 % CI 0.58-1.48; p = 0.61), respectively] or pathological stage [OR = 0.79 (95 % CI 0.42-1.48; p = 0.46) and OR = 0.90 (95 % CI 0.49-1.61; p = 0.72), respectively]. SNP variability of rs9642880[T] and rs798766[T] is associated with an increased risk of bladder-UC but we did not find an association with disease aggressiveness as we did previously for UTUC. CONCLUSIONS: This is further evidence of the distinct genetic differences that exist between bladder-UC and UTUC, and it is not possible to extrapolate results of genetic studies between these two urothelial disease entities.

A systematic review of the tools available for predicting survival and managing patients with urothelial carcinomas of the bladder and of the upper tract in a curative setting.

OBJECTIVES: To identify the predictive tools which have emerged recently in the field of urothelial carcinomas. MATERIALS AND METHODS: We performed a thorough MEDLINE literature review using a combination of the following keywords: urothelial carcinoma, transitional cell carcinoma, bladder, renal pelvis, ureter, predictive tools, predictive models and nomograms. We found 117 articles, but only the relevant reports were selected. RESULTS: The majority of available tools are prediction models, particularly nomograms. These models combine good performance accuracy with ease of use. They appear to be more accurate than risk grouping or tree modeling and are more suitable for clinicians than artificial intelligence. The most recent nomograms have been designed to be used in daily clinical practice and are even available as computer or smartphone applications. They focus on pathological outcomes or more frequently on survival statistics or recurrence risk after surgery. They provide an accurate prediction of disease evolution and may help clinicians to choose the most appropriate treatment option. However, these prediction tools still need to be validated and regularly utilized. CONCLUSION: Predictive tools represent very helpful clinical decision-making aids but need to be validated in larger populations.

The role of chemotherapy in the treatment of urothelial cell carcinoma of the upper urinary tract (UUT-UCC).

OBJECTIVE: Urothelial cell carcinoma of the upper urinary tract (UUT-UCC) is a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. This review highlights the main chemotherapy regimens available for UUT-UCCs based on the recent literature. MATERIALS AND METHODS: Data on urothelial malignancies and UUT-UCCs management in the literature were searched using MEDLINE and by matching the following key words: urinary tract cancer; urothelial carcinomas; upper urinary tract; carcinoma; transitional cell; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; neoadjuvant treatment; recurrence; risk factors; and survival. RESULTS: No evidence level 1 information from prospective randomized trials was available. Because of its many similarities with bladder urothelial carcinomas, chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. Most teams have proposed a neoadjuvant or an adjuvant treatment based either on the combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) or on gemcitabine/cisplatin (GC). These regimens have been shown to prolong survival moderately. All recent studies have included limited numbers of patients and have reported poor patient outcomes after both neoadjuvant and adjuvant chemotherapy. Regarding metastatic UUT-UCCs, vinflunine has demonstrated moderate activity in these patients with a manageable toxicity. Interestingly, specific molecular markers [microsatellite instability (MSI), E-cadherin, HIF-1α, and RNA levels of the telomerase gene] can provide useful information that can help diagnose and determine patient prognosis in patients with UUT-UCC. CONCLUSION: Chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. However, there is no strong evidence that chemotherapy is effective due to the rarity of the disease and the lack of data in the current literature. Thus, physicians must take into account the specific clinical characteristics of each individual patient with regard to renal function, medical comorbidities, tumor location, grade, and stage, and molecular marker status when determining the optimal treatment regimen for their patients. The ongoing identification of the oncologic mechanisms of this type of cancer might pave the way for the development of specific treatments that are targeted to the characteristics of each patient's tumor in the future.

Transurethral resection biopsy as part of a saturation biopsy protocol: a cohort study and review of the literature.

OBJECTIVE: To evaluate the prostate cancer (CaP) detection rate and morbidity of performing a transurethral resection biopsy of the prostate (TURBP) at the same time as a saturation biopsy (SBx). PATIENTS: A total of 102 men with previous negative transrectal ultrasound (TRUS) biopsies underwent a SBx under formal anaesthesia. Fifty-four [54 (52.9%)] had a combined SBx and TURBP (Group 1) and 48 (47.1%) had a SBx only (Group 2). RESULTS: The CaP detection rate in Group 1 was 38.9% (21/54), which was significantly higher than the detection rate of 27.1% (13/48) in Group 2 (P = 0.005). CaP was detected via TURBP in 12 patients (22.2%) from Group 1, including 8 (14.8%) patients who had CaP solely in their TURBP chips. According to the D'Amico classification, 66.6% (14/21) of the cancers in Group 1 were intermediate (n = 4) or high risk (n = 10). Of the 8 'TURBP only' cancers, 75% (6/8) were intermediate (n = 2) or high risk (n = 4). Seven of these eight patients went on to have a radical prostatectomy (RP) but only 2 (28.6%) were found to have a pure anterior/transition zone (TZ) tumor. The postoperative urinary retention and emergency admission rates for Groups 1 and 2 were 29.6% (16/54) vs. 16.6% (8/48) (P = 0.095) and 11.1% (6/54) vs. 5.5% (2/48) (n = 0.17). There was no difference in terms of hematuria (P = 0.54), urinary tract infection (UTI) (P = 0.22), or sepsis (P = 0.21), and patients in Group 1 spent an average of 0.5 days longer in hospital (1.9 vs. 1.4; P = 0.008). CONCLUSIONS: TURBP in association with SBx increases the detection of clinically important CaP. However, this does have to be balanced against the small increased incidence of urinary retention, emergency re-admission, and longer hospital stay.

Prediction of cancer specific survival after radical nephroureterectomy for upper tract urothelial carcinoma: development of an optimized postoperative nomogram using decision curve analysis.

PURPOSE: We conceived and proposed a unique and optimized nomogram to predict cancer specific survival after radical nephroureterectomy in patients with upper tract urothelial carcinoma by merging the 2 largest multicenter data sets reported in this population. MATERIALS AND METHODS: The international and the French national collaborative groups on upper tract urothelial carcinoma pooled data on 3,387 patients treated with radical nephroureterectomy for whom full data for nomogram development were available. The merged study population was randomly split into the development cohort (2,371) and the external validation cohort (1,016). Cox regressions were used for univariable and multivariable analyses, and to build different models. The ultimate reduced nomogram was assessed using Harrell's concordance index (c-index) and decision curve analysis. RESULTS: Of the 2,371 patients in the nomogram development cohort 510 (21.5%) died of upper tract urothelial carcinoma during followup. The actuarial cancer specific survival probability at 5 years was 73.7% (95% CI 71.9-75.6). Decision curve analysis revealed that the use of the best model was associated with benefit gains relative to the prediction of cancer specific survival. The optimized nomogram included only 5 variables associated with cancer specific survival on multivariable analysis, those of age (p = 0.001), T stage (p <0.001), N stage (p = 0.001), architecture (p = 0.02) and lymphovascular invasion (p = 0.001). The discriminative accuracy of the nomogram was 0.8 (95% CI 0.77-0.86). CONCLUSIONS: Using standard pathological features obtained from the largest data set of upper tract urothelial carcinomas worldwide, we devised and validated an accurate and ultimate nomogram, superior to any single clinical variable, for predicting cancer specific survival after radical nephroureterectomy.

A prospective comparison of the pathologic and surgical outcomes obtained after elective treatment of renal cell carcinoma by open or robot-assisted partial nephrectomy.

OBJECTIVE: To prospectively compare surgical and pathologic outcomes obtained by elective robot-assisted (RAPN) or open partial nephrectomy (OPN) for small renal cell carcinoma (RCC). MATERIALS AND METHODS: Between 2008 and 2010, after protocol design and patient consent, we prospectively collected clinical data for 100 patients who concurrently underwent either OPN (58) or RAPN (42) by an individual experienced surgeon. Clinical data included age, BMI, and past medical history. Operative data included operative time, warm ischemia time (WIT), and estimated blood loss (EBL). Postoperative outcomes included hospital stay (LOS), creatinine variation, Clavien complications, pathologic results, and survival. We stratified the complexity of the renal tumor using the R.E.N.A.L Nephrometry score. RESULTS: Of note, RAPN was superior to OPN in terms of EBL (median 143 mL vs. 415; P < 0.001) and LOS (median 3.8 days vs. 6.8; P < 0.0001). The median WIT for the RAPN group was 17.5 minutes (vs. 17.1 OPN; P = 0.3)) and the mean strict operative time was 134.8 minutes (vs. 128.4 OPN; P = 0.097). Regarding immediate, early, and short-term complications, variation of creatinine levels, and pathologic margins, the rates were equivalent for both groups (P > 0.05). According to the R.E.N.A.L nephrometry scores, both groups (RAPN/OPN) had similar rates (%) of low (81/72.4) and intermediate (19/20.7) complexity tumors, though there were 4 high complexity tumors in OPN group (vs. 0; P = 0.03). CONCLUSION: We found that RAPN is superior to the reference standard (OPN) surgical treatment of small RCCs in terms of blood loss and length of hospital stay with equivalent complications, warm ischemia time, and effect on renal function. Larger randomized trials with longer follow-up will give us further information and insight into the oncologic equivalence.

The presence of detrusor muscle in the pathological specimen after transurethral resection of primary pT1 bladder tumors and its relationship to operator experience.

INTRODUCTION: To assess the quality of transurethral resection of bladder tumors (TURBTs) performed by "senior" and "junior" urologists for pT1 tumors in terms of detrusor muscle (DM) presence and recurrence rate at 3 month first cystoscopy (RR-FC). Non-muscle invasive bladder cancer (NMIBC) is a heterogeneous group with differing biological potentials. Tumors invading lamina propria (pT1) have an increased propensity for recurrence and progression. Accurate staging at the time of primary TURBT, including the presence of DM, is crucial to avoid understaging and unnecessary delay in definitive treatment. MATERIALS AND METHODS: We analyzed our maintained bladder tumor database (TURBTs from 2002 to 2009) and selected patients diagnosed with pT1 bladder tumors. Data on surgeon status, tumor characteristics (size, TNM stage 2009, grade, DM presence) and RR-FC were retrieved. Surgeons were stratified into "senior" and "junior" according to the years of prior training. RESULTS: Of the 340 TURBTs for pT1 tumors, "senior" and "junior" surgeons performed 237 (69.7%) and 103 (30.3%), respectively. Overall, 238 (70%) TURBTs had DM in the specimen, including 175 (73.8%) and 63 (61.3%) for the "senior" and "junior" operators, respectively (p = 0.02). The overall RR-FC was 37.4% (n = 127) and was significantly different for DM presence and DM absence (30.7% versus 52.9%; p = 0.01). On multivariate analysis, tumor recurrence was associated with "junior" operator experience independent of the presence or absence of DM (OR = 2.33 [1.45-3.74]) p = 0.01). CONCLUSIONS: The presence of DM in a primary TURBT for pT1 NMIBC is directly associated with operator experience, with an associated increased 3 month recurrence rate for "junior" resectionists.