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.

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.

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.

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.

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.

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.

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.

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.

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.

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 direct comparison of the diagnostic accuracy of three prostate cancer nomograms designed to predict the likelihood of a positive initial transrectal biopsy.

BACKGROUND: Several tools have been developed to predict the outcome of prostate biopsies performed to diagnosis prostate cancer (PCa). However, few studies have focused on the comparative accuracy of these predictive tools. We aim to establish the predictive accuracy of three commonly used nomograms by comparing their prostate biopsy outcome predictions with actual pathological results. METHODS: From January 2008 to December 2010, 708 consecutive patients with an elevated serum PSA level and/or abnormal DRE were referred to our institution. All data were collected prospectively. All patients underwent a TRUS 12-core biopsy. Probability of a positive biopsy was predicted using three online risk calculation nomograms. The discriminative ability of the nomograms was assessed via AUC and the most accurate model was calibrated and compared to actual biopsy results. RESULTS: Of 667 patients fulfilling all three nomograms criteria, 384 (57.5%) had PCa and 283 (42.5%) did not. AUC for the PCPT-CRC, SWOP-PRI, and Montreal nomograms was 0.68 (95% CI, 0.63-0.72), 0.72 (95% CI, 0.68-0.76), and 0.79 (95% CI, 0.76-0.82), respectively. A comparison of the three models' performance showed that the Montreal model provided the greatest predictive accuracy (P = 0.03). CONCLUSIONS: External validation of three commonly used nomograms designed to predict the likelihood of a positive prostate biopsy reveals the Montreal model was more accurate than either the PCPT-CRC or SWOP-PRI models. The Montreal nomogram achieves a diagnostic accuracy of 79% and is superior to PSA alone though we await further research to define the probability (of cancer) threshold above which a prostate biopsy would be advised.

Quantitative RT-PCR analysis of PSA and prostate-specific membrane antigen mRNA to detect circulating tumor cells improves recurrence-free survival nomogram prediction after radical prostatectomy.

BACKGROUND: Circulating tumor cell (CTC) analysis is a potential new biomarker in prostate cancer. We hypothesize that quantitative detection of CTCs in patients pre- and post-radical prostatectomy (RP) using quantitative TaqMan® fluorogenic RT-PCR will improve the accuracy of the Kattan nomogram to predict the probability of recurrence-free survival (RFS) post-RP. METHODS: Ninty-two patients who underwent RP between 2004 and 2009 had venous blood samples taken pre- (Day - 1) and post-operatively (Day + 7). We performed quantitative Taqman® RT-PCR to detect circulating prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) mRNA. We calculated both the logarithmic ratio of Day + 7/Day - 1 for PSA (PSAr) and PSMA (PSMAr) expression (log(Day+7/Day-1) ) and the Kattan nomogram predicted probability of disease recurrence for each patient. We then analyzed how the AUC-ROC analysis for the Kattan nomogram prediction alone (K) compared to the addition of the PSAr and PSMAr in predicting 5-year RFS. RESULTS: The mean age (years), PSA (ng/ml), and follow-up (mo) was 65.1, 9.13, and 72, respectively. The AUCs for K, PSAr + K, and PSMAr + K were 0.752 (95%CI 0.620-0.860), 0.830 (95%CI 0.740-0.911), and 0.837 (95%CI 0.613-0.923), respectively (P = 0.03). The Kattan 5-year PSA RFS was 75%. The actual 5-year PSA RFS survival rate was 77%. CONCLUSIONS: Data from modern quantitative RT-PCR to detect circulating prostate-derived PSA and PSM mRNA pre- and post-RP improves the accuracy of the Kattan nomogram to predict biochemical recurrence.

Influence of positive surgical margin status after radical nephroureterectomy on upper urinary tract urothelial carcinoma survival.

BACKGROUND: The influence of a positive surgical margin (PSM) on survival outcome of post radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UUT-UC) is unclear. The objectives of this study were to determine the significance of PSM on cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS) post RNU. METHODS: From a multicenter collaborative database, data on SM status, stage, grade, lymph node status, lymphovascular invasion (LVI), tumor location, follow-up, and survival was retrieved for 472 patients. Patients underwent open RNU with bladder cuff excision. Clinicopathological features were compared using χ(2) or Fisher exact test and unpaired t test for categorical and continuous variables, respectively. Survival was estimated using the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards regression models were calculated. RESULTS: Median follow-up was 27.5 months (12.1-49.3 months). PSM was identified in 44 patients (9.3%) and correlated with pT stage (p = 0.002), grade (p < 0.001), LVI (p < 0.001), and location (p < 0.001). Univariate analyses revealed that PSM was a poor prognostic factor for CSS, RFS, and MFS (p = 0.003, 0.04, and <0.001, respectively). The 5-yr CSS and MFS for PSM was 59.1 and 51.6%, respectively, compared with 83.3 and 79.3% for patients with negative SM. Multivariate analyses revealed that SM status was an independent predictor of MFS [hazard ratio 2.7; p = 0.001). CONCLUSIONS: PSM after RNU is an important prognostic factor for developing UUT-UC metastases. The status of the surgical margin should be systematically reported on the pathological report and may be a useful variable to include in nomogram risk prediction tools.

Potential role of photodynamic techniques combined with new generation flexible ureterorenoscopes and molecular markers for the management of urothelial carcinoma of the upper urinary tract.

OBJECTIVES: • To discuss how the development of new generation flexible ureterorenoscopes in combination with photodynamic diagnosis (PDD) improves the assessment of urothelial cell carcinoma of the upper urinary tract (UUT-UCC). • Ultimately, this may allow accurate tumour classification and the ability to select which patients would benefit from conservative treatment as opposed to radical surgery. MATERIALS AND METHODS: • We conducted an exhaustive Pubmed literature search using a combination of keywords including: ureterorenoscopy, UUT-UCC diagnosis, PDD, narrow band imaging, conservative treatment UUT-UCC and molecular urinalysis. • We then selected salient high calibre articles relevant to our objective. RESULTS: • We give specific consideration to anatomical aspects of UUT-UCC investigation, PDD in UCC, aminolevulinic acid and its derivatives, autofluorescence, narrow band imaging, molecular marker analysis and the recent advances in ureterorenoscopic technology. • The traditional pitfalls of UUT-UCC diagnosis, namely poor visualisation and difficulty in obtaining representative histological samples, are being circumvented by the introduction of modern digital flexible ureteroscopes that can be combined with PDD and molecular analysis to improve tumour classification, deferring to conservative treatment accordingly. CONCLUSION: • The accuracy of the diagnostic work-up of UUT-UCC is improving due to advances in technology, pharmaceutical agents and incorporation of molecular markers, all factors allowing us to characterise tumours of the UUT more definitively.

Is there a contemporary role for percutaneous needle biopsy in the era of small renal masses?

OBJECTIVE: To evaluate based on the best available data whether there is a contemporary role for percutaneous needle biopsy in the era of small renal masses. PATIENTS AND METHODS: SRMs are acknowledged to be tumours less than 4cm and account for 48%-66% of new kidney cancers. Renal mass biopsy (RMB), traditionally limited to specific clinical scenarios and with inherent diagnostic accuracy problems has increased in popularity in recent years and is a potential valuable tool in the assessment of SRMs. Our discussion focuses on these issues. We performed a thorough Medline literature review using a combination of the following keywords; small renal mass, renal biopsy, percutaneous renal biopsy, renal mass biopsy and renal cell carcinoma. We identified the seminal articles with data/information pertaining to renal mass biopsy in small renal masses. RESULTS: The facts that 1) a significant number of SRMs are diagnosed in an elderly patient cohort, 2) 20% of SRMs are benign on formal histology, 3) there are various management strategies now available and 4) modern RMB has a diagnostic accuracy >90% with few complications, are all reasons why there has been renewed interest in RMB. CONCLUSION: There is a contemporary role for RMB in the era of SRM as the incorporation of molecular profiling of tissue from RMB would augment our ability to risk stratify SRMs on an individual patient basis and adopt management accordingly. However, clinical judgement is paramount as there remains an unpredictable non-negligible risk of disease progression and metastasis whilst on surveillance.

Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: genomics towards personalized medicine.

What's known on the subject? and What does the study add? Sporadic clear cell Renal Cell Carcinoma (ccRCC) is dominated by nutations of the VHL gene located on chromosome 3p in up to 90% of cases. This gene plays a critical role in hypoxia response, including stimulation of neoangiogenesis. Since 2006, anti-angiogenci therapies targeting this pathway are used in metastatic patients with objective response rate as high as 45%. However, these treatments don't target directly the tumour cell, allowing the potential for disease progession despite treatment. Large scale analysis recently showed that substantial genetic heterogeneity exists in ccRCC. Associated alterations include genes implicated in methylation regulation in 15% of cases, underlying the importance of epigenetic modifications, and truncating mutations in chromatin remodelling complex PRMB1 in 41% of cases. Systematic screening of these tumours is a way to fully determine the somatic genetic architecture of RCC in order to improve tumour classification, to develop prognostic and predictive markers and to target new molecular pathways involved in carcinogenesis. • A critical review is provided of the recent progress in oncogenetics applied to renal cell carcinoma (RCC) by highlighting our current understanding of the genetic pathways involved in carcinogenesis and its current and future clinical application. • RCC comprises a model of translational research because an improved understanding of molecular pathways has led to several targeted therapy options for patients with metastatic RCC. • Alteration of the product of the Von Hippel-Lindau gene/hypoxia inductible factor/vascular endothelial growth factor pathway is well characterized in carcinogenesis and is the target of the current therapies for metastatic RCC. • However, substantial genetic heterogeneity exists in this cancer and current treatments do not target directly the tumour cell. • Improving overall survival still remains a challenging objective but, currently, there is a lack of prognostic and predictive biomarkers for response to treatment. • Further information is awaited from the genomic approach to tumour classification, prognostic markers and predictive indicators of response to the treatment, as well as the personal susceptibility of developing RCC when exposed to risk factors. • Recent technological developments, such as large-scale analysis and high-speed sequencing, will allow the systematic screening of tumours to fully determine the somatic genetic architecture of RCC.

The role of American Society of Anesthesiologists scores in predicting urothelial carcinoma of the upper urinary tract outcome after radical nephroureterectomy: results from a national multi-institutional collaborative study.

UNLABELLED: Study Type--Prognosis (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinoma (UUT-UC) is a rare disease, usually treated by nephroureterectomy, occurring in a population with a median age of 70 years and with frequent tobacco use and other comorbidities. We know that the American Society of Anesthesiologists (ASA) score has prognostic value in urological oncology but this has not been assessed in UUT-UC. Using a multi-institutional French database, we have shown that the 5-year cancer-specific survival differed significantly between ASA 1, ASA 2 and ASA 3 patients (83.8%, 76.9% and 70.6%, respectively; P = 0.01). ASA status had a significant impact on cancer-specific survival in univariate and multivariate analyses, with a threefold higher risk of mortality at 5 years for ASA 3 compared with ASA 1 patients (P = 0.04). OBJECTIVE: • To evaluate the impact of American Society of Anesthesiologists (ASA) scores on the survival of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS: • A retrospective multi-institutional cohort study of the French collaborative national database of UUT-UC treated by RNU in 20 centres from 1995 to 2010. • The influence of age, gender and ASA score on survival was assessed using a univariable and multivariable Cox regression analysis with pathological features used as covariables. RESULTS: • Overall, 554 patients were included. The median follow-up was 26 months (10-48 months), and the median age was 69.5 years (61-76 years). In total, 114 (20.6%) patients were classified as ASA 1, 326 (58.8%) as ASA 2 and 114 (20.6%) as ASA 3. • The 5-year recurrence-free survival (P = 0.21) and metastasis-free survival (P = 0.22) were not significantly different between ASA 1 (52.8% and 76%), ASA 2 (51.9% and 75.3%) and ASA 3 patients (44.1% and 68.2%, respectively). • The 5-year cancer-specific survival differed significantly between ASA 1, ASA 2 and ASA 3 patients (83.8%, 76.9% and 70.6%, respectively; P = 0.01). • ASA status had a significant impact on cancer-specific survival in univariate and multivariate analyses, with a threefold higher risk of mortality at 5 years for ASA 3 compared with ASA 1 patients (P = 0.04). CONCLUSIONS: • ASA classification correlates significantly with cancer-specific survival after RNU for UUT-UC. • It is a further pre-operative clinical variable that can be incorporated into future risk prediction tools for UUT-UC to improve their accuracy.

A proportion of hereditary upper urinary tract urothelial carcinomas are misclassified as sporadic according to a multi-institutional database analysis: proposal of patient-specific risk identification tool.

UNLABELLED: What's known on the subject? and What does the study add? Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant multi-organ cancer syndrome. Upper urinary tract urothelial carcinomas belong to HNPCC-related tumours and rank third within this group after colorectal and endometrial cancer. However, many urologists are not aware of this association and it is presumed that some hereditary cancers are misclassified as sporadic and that their incidence is underestimated. Consequently, family members of patients with upper urinary tract urothelial carcinomas secondary to HNPCC may be denied appropriate surveillance and early detection. A significant proportion of patients (21.3%) with newly diagnosed upper urinary tract urothelial carcinomas may have underlying HNPCC. Demographic and epidemiological characteristics suggest different mechanisms of carcinogenesis among this population. Recognition of such potential is essential for appropriate clinical and genetic management of patients and family. In order to help to identify these patients, we propose a patient-specific checklist. OBJECTIVE: • To identify, based on previously described clinical criteria, hereditary upper urinary tract urothelial carcinomas (UUT-UCs) that are likely to be misclassified as sporadic although they may belong to the spectrum of hereditary non-polyposis colorectal cancer (HNPCC) associated cancers. PATIENTS AND METHODS: • We identified, using established clinical criteria, suspected hereditary UUT-UC among 1122 patients included in the French national database for UUT-UC. • Patients were considered at risk for hereditary status in the following situations: age at diagnosis <60 years with no previous history of bladder cancer; previous history of HNPCC-related cancer regardless of age; one first-degree relative with HNPCC-related cancer diagnosed before 50 years of age or two first-degree relatives diagnosed regardless of age. RESULTS: • Overall, 239 patients (21.3%) were considered to be at risk of hereditary UUT-UC. • Compared with sporadic cases, hereditary cases are more likely to be female (P= 0.047) with less exposure to tobacco (P= 0.012) and occupational carcinogens (P= 0.037). A greater proportion of tumours were located in the renal pelvis (54.5% vs 48.4%; P= 0.026) and were lower grade (40% vs 30.1%; P= 0.015) in the hereditary cohort. • The overall, cancer-specific and recurrence-free survival rates were similar in both cohorts. • We propose a patient-specific risk identification tool. CONCLUSIONS: • A significant proportion (21.3%) of patients with newly diagnosed UUT-UC may have underlying HNPCC as a cause. • Recognition of such potential and application of a patient-specific checklist upon diagnosis will allow identification and appropriate clinical and genetic management for patient and family.

Prospective comparison of short-term functional outcomes obtained after pure laparoscopic and robot-assisted laparoscopic sacrocolpopexy.

OBJECTIVE: To prospectively compare short-term functional outcomes achieved by laparoscopic or robot-assisted sacrocolpopexy for pelvic organ prolapse. MATERIALS AND METHODS: We prospectively collected clinical and operative data over 24 months for female patients who underwent either pure laparoscopic sacrocolpopexy (LSCP) or robot-assisted laparoscopic sacrocolpopexy (RALSCP). Clinical data included age, BMI and assessment of PFDI-20 score. Perioperative data included operative time and complications. Post-operative outcomes included hospital stay, length of catheterisation, pain and functional outcomes as assessed by clinical examination and PFDI-20 score assessment. RESULTS: Overall, 67 women with a median age of 65 were included: 47 in the LSCP arm and 20 in the RALSCP arm. RALSCP was superior in terms of blood loss (median 55mls vs. 280; P = 0.03) and strict operative time (median 125 min vs. 220; P < 0.0001), but this time advantage was nullified when comparing overall operating room time (215 min vs. 220). With a median follow-up of 16 months, the overall anatomic repair rate was 98.5%, and there was an improvement in overall PFDI-20 score before and after surgery (P = 0.001) but with no difference between the two surgical approaches. CONCLUSIONS: RALSCP allows for a safe and effective repair of pelvic organ prolapse in female patients. Whilst being equivalent to LSCP in terms of functional outcome, it is superior in terms of blood loss and strict operative time. These results are based on short-term assessment, and further studies of larger populations with longer follow-up and objective assessments of outcome are needed to make any definitive statement.