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We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤.004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling. The predictive value of insulin-like growth factor-I (IGF-1) and its binding proteins were assessed in 735 patients treated with RNU for UTUC. Lower plasma levels of IGFBP-2 and -3 are significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU and help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling. [ABSTRACT FROM AUTHOR]

Background. Cancer stem cells (CSC) and their role in tumorigenesis of various solid tumors have been studied in past decades. Urothelial CSC were first identified 10 years ago and subsequent studies have been performed with the aim to identify reliable markers of CSC. So far, a few studies have investigated a relationship between CSC markers expression in urothelial carcinoma tissue and histopathological characteristics of the tumor. Methods. In our study, we evaluated an immunoexpression of the CSC markers CD24, CD44, CD66 and CD133 in tissue sections of urothelial carcinoma (all tumor grades and stages were included), urothelial carcinoma in situ and non-neoplastic urothelium, totally 218 specimens were enrolled. Results. All studied molecules were expressed either in tumor tissue and non-neoplastic urothelium. Urothelial carcinomas of higher tumor grade and stage expressed molecules CD24 and CD133 significantly more frequently whereas molecules CD44 and CD66 did not show significant association with tumor histopathological features. Conclusions. Our results showed that studied molecules are not suitable for direct detection of CSC in urothelial carcinoma tissue sections, but an expression of molecules CD24 and CD133 is significantly related to urothelial carcinoma grade and stage, which are both important prognostic indicators and therefore an expression of these markers might have a potential prognostic value. [ABSTRACT FROM AUTHOR]

Objective: Immunocytochemistry has attained a marginal role in urology so far. Combining the morphological and immunophenotypical changes of the urothelial cells retrieved from urine is a logical approach. The study aimed to analyse the diagnostic potential of immunocytological staining in the detection of high‐grade and low‐grade urothelial carcinoma. Methods: Freshly voided urine was collected from 152 consecutive individuals, cytology classes were determined and cell blocks produced. A total of 77 patients were diagnosed with urothelial carcinoma and 75 patients had various benign urological conditions. Immunocytochemistry was performed using four antibodies: p53, MCM2, MCM5 and Ki‐67. A diagnostic power to detect low grade and high‐grade urothelial carcinoma was analysed for each antibody and their combinations with cytology. Results: There were no significant differences between patients with low‐grade tumours and control group. Antibodies p53 and Ki‐67 slightly improved the sensitivity of urinary cytology while maintaining its specificity. The best negative predictive value was demonstrated in combinations of cytology and MCM5 (88.9%) and cytology, p53 and MCM5 (90.6%). In the diagnosis of high‐grade tumours, all antibodies apart from MCM2 yielded better sensitivity and specificity than cytology alone (receiver operating characteristic curves: p53 = 0.853, MCM5 = 0.931, and Ki‐67 = 0.895). Combined with cytology, the sensitivities went even higher for the cost of lower specificity. The best diagnostic performance was observed in the combination of MCM5 and Ki‐67 (sensitivity = 96.2%; specificity = 80%). Conclusions: Immunocytochemistry with p53, MCM5 and Ki‐67 antibodies can improve the diagnostic power of urinary cytology in the detection and follow‐up of urinary bladder urothelial carcinoma. The study aimed to analyze the diagnostic potential of immunocytological staining in the detection and follow‐up of high grade and low grade urothelial carcinoma. A diagnostic performance of four selected antibodies and their combinations with urine cytology was evaluated. [ABSTRACT FROM AUTHOR]

Objective: The methodology of cell blocks (CBs) has long been an integrated part of cytology. However, there are very few data on CBs derived from urine. Their main disadvantage is a lack of cellularity, which limits their broader clinical applicability. Factors affecting cellular adequacy in urine remain unclear. We assessed the impact of basic clinical and cytopathological factors on the adequacy of cellularity in urinary CBs. Methods: Freshly voided urine was collected from 401 consecutive individuals. Of these, 167 patients were diagnosed with urothelial carcinoma. The remaining 234 patients had various benign urological conditions. Papanicolaou classes were determined and CBs produced. Cellular adequacy was assigned to each CB (acellular, hypocellular, moderate cellularity, high cellularity), and moderately and highly cellular CBs were considered as adequate. Several factors were analysed to find any correlation with the adequacy of the cellularity. Results: In univariate analysis, seven factors significantly correlated with the adequacy of the CBs. In the multivariate model, positive sediment (OR = 3.7), female sex (OR = 2.7), positive urinary cytology (OR = 2.6) and positive leucocyturia (OR = 2.1) were independent predictors of adequate cellularity. Positive predictive value and negative predictive value of the model were 65.0% and 77.7%, respectively. Conclusions: We determined four clinical and cytopathological factors which independently predict adequate cellularity in urinary CBs. Based on these results, several clinical situations have been proposed, in which the highest probability of adequate cellularity in urinary CBs can be achieved. The methodology of cell blocks has been known and used for a long time. However, there is no specific literature on the impacts of adequate cellularity in urine cell blocks. In the current study we assessed clinical and cytopathological factors predictive of adequate cellularity and correlated the results to the most appropriate clinical settings for the use of immunocytochemistry on cell blocks. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Little is known on the association between obesity and urothelial carcinoma of the bladder ( UCB). Most studies have shown that higher body mass index ( BMI) is associated with higher rates of perioperative complications. Only one study specifically investigated obesity and bladder cancer-specific outcomes and reported no significant association between higher BMI and disease-specific survival in patients with UCB treated with radical cystectomy. However, that study was limited by its small sample size and a high rate of preoperative therapies., In contrast to the only previous study evaluating the association of BMI with oncological outcomes in UCB, we found that obesity ( BMI ≥30 kg/m2) was associated with features of biologically aggressive UCB and clinical outcomes after radical cystectomy and, even when adjusting for the effects of standard clinicopathological features, obesity remained an independent predictor of cancer recurrence, cancer-specific mortality and overall mortality., Objective To investigate the association between body mass index ( BMI) and oncological outcomes in patients after radical cystectomy ( RC) for urothelial carcinoma of the bladder ( UCB) in a large multi-institutional series., Patients and Methods Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded., Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality., BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m2)., Results Median BMI was 28.8 kg/m2 (interquartile range 7.9); 25.3% had a BMI <25 kg/m2, 32.5% had a BMI between 25 and 29.9 kg/m2, and 42.2% had a BMI ≥30 kg/m2., Patients with a higher BMI were older ( P < 0.001), had higher tumour grade ( P < 0.001), and were more likely to have positive soft tissue surgical margins ( P = 0.006) compared with patients with lower BMI., In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio ( HR) 1.67, 95% confidence interval ( CI) 1.46-1.91, P < 0.001), cancer-specific mortality ( HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality ( HR 1.81, CI 1.60-2.05, P < 0.001). Themain limitation is the retrospective design of the study., Conclusions Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB., Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cigarette smoking is a common risk factor for developing upper tract urothelial carcinoma (UTUC). Objective: To assess the impact of cigarette smoking status, cumulative smoking exposure, and time from cessation on oncologic UTUC outcomes in patients treated with radical nephroureterectomy (RNU). Design, setting, and participants: A total of 864 patients underwent RNU at five institutions. The median follow-up in this retrospective study was 50 mo. Smoking history included smoking status, quantity of cigarettes per day (CPD), duration in years, and years from smoking cessation. The cumulative smoking exposure was categorized as light-short-term (≤19 CPD and ≤19.9 yr), moderate (all combinations except light-short-term and heavy-long-term), and heavy-long-term (≥20 CPD and ≥20 yr). Interventions: RNU with or without lymph node dissection. No patient received neoadjuvant chemotherapy. Outcome measurements and statistical analysis: Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on oncologic outcomes. Results and limitations: A total of 244 patients (28.2%) never smoked; 297 (34.4%) and 323 (37.4%) were former and current smokers, respectively. Among smokers, 87 (10.1%), 331 (38.3%), and 202 (23.4%) were light-short-term, moderate, and heavy-long-term smokers, respectively. Current smoking status, smoking ≥20 CPD, ≥20 yr, and heavy-long-term smoking were associated with advanced disease (p values ≤0.004), greater likelihood of disease recurrence (p values ≤0.01), and cancer-specific mortality (p values ≤0.05) on multivariable analyses that adjusted for standard features. Patients who quit smoking ≥10 yr prior to RNU did not differ from never smokers regarding advanced tumor stages, disease recurrence, and cancer-specific mortality, but they had better oncologic outcomes then current smokers and those patients who quit smoking <10 yr prior to RNU. The study is limited by its retrospective nature. Conclusions: Cigarette smoking is significantly associated with advanced disease stages, disease recurrence, and cancer-specific mortality in patients treated with RNU for UTUC. Current smokers and those with a heavy and long-term smoking exposure have the highest risk for poor oncologic outcomes. Smoking cessation >10 yr prior to RNU seems to mitigate some detrimental effects. These results underscore the need for smoking cessation and prevention programs. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the impact of variant histologies of urothelial carcinoma of the bladder (UCB) on oncologic outcomes after radical cystectomy (RC). Materials and Methods: Data from 1984 UCB patients treated by RC without preoperative chemo- or radiotherapy were reviewed for histological differentiation and variants. We analysed the differences between pure UCB and UCB with variant histology, and those between the different histological variants using various stratifications. Results: Overall, 488 (24.6%) patients had UCB variants with squamous cell (11.4%) and glandular differentiation (3.8%) being the most common. Histological UCB variants were associated with advanced tumour stage, lymphovascular invasion and lymph node metastasis (all p-values<0.01) when compared to pure UCB. In univariable analyses, patients with non-squamous UCB variants were at significantly higher risk for disease recurrence and cancer-specific mortality than those with pure UCB patients (p-values=0.001) and those with squamous cell differentiated UCB (p-values=0.04); the latter two had the same risk. In multivariable analyses that adjusted for the effects of standard clinicopathologic characteristics, variant UCB histology was not associated with both survival end-points. In patients treated with adjuvant chemotherapy (n =492) there was no difference in cancer-specific survival between pure UCB, squamous cell differentiated UCB and other histological UCB variants. Conclusions: A quarter of UCB patients treated with RC harboured histological UCB variants. Variant UCB histologies were associated with features of biologically aggressive disease. While variant UCB histology was associated with worse outcomes in univariable analyses, this effect did not remain significant in multivariable analyses. [Copyright &y& Elsevier]

Abstract: Background: Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard of care for high-risk non–muscle-invasive and muscle-invasive bladder cancer (BCa). Objective: To develop a model that allows quantification of the likelihood that a pathologically node-negative patient has, indeed, no positive nodes. Design, setting, and participants: We analyzed data from 4335 patients treated with RC and PLND without neoadjuvant chemotherapy at 12 international academic centers. Interventions: Patients underwent RC and PLND. Outcome measurements and statistical analysis: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative as a function of the number of examined nodes. Results and limitations: Overall, the probability of missing a positive node decreases with the increasing number of nodes examined (52% if 3 nodes are examined, 40% if 5 are examined, and 26% if 10 are examined). The proportion of having a positive node increased proportionally with advancing pathologic T stage and lymphovascular invasion (LVI). Patients with LVI who had 25 examined nodes would have a pNSS of 80% (pT1), 88% (pT2), and 66% (pT3–T4), whereas 10 examined nodes were sufficient for pNSS exceeding 90% in patients without LVI and pT0–T2 tumors. This study is limited because of its retrospective design and multicenter nature. Conclusions: We developed a tool that estimates the likelihood of lymph node (LN) metastasis in BCa patients treated with RC by evaluating the number of examined nodes, the pathologic T stage, and LVI. The pNSS indicates the adequacy of nodal staging in LN-negative patients. This tool could help to refine clinical decision making regarding adjuvant chemotherapy, follow-up scheduling, and inclusion in clinical trials. [Copyright &y& Elsevier]