Abstract Context Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC). However, the effect of smoking on outcomes of UC patients remains debated. Objective To integrate ...the available evidence regarding the impact of smoking status and smoking exposure on recurrence, progression, cancer-specific mortality, and any-cause mortality in patients with UC of the bladder (UCB) and upper tract UC (UTUC) treated with transurethral resection of the bladder (TURB), radical cystectomy (RC), or radical nephroureterectomy (RNU). Evidence acquisition A systematic search of the literature was conducted using the Medline, Embase, and Scopus databases, which was limited to articles published in English between January 1974 and March 2013. Articles were also extracted from the reference lists of identified studies and reviews. We selected 29 articles (15 TURB, 7 RC, and 7 RNU) according to predefined inclusion criteria and the Preferred Reporting Items for Systematic Reviews and Meta-analyses. Evidence synthesis The majority of studies demonstrated an association with disease recurrence in patients treated with TURB, while evidence for associations with disease progression, cancer-specific mortality, and any-cause mortality was less abundant. While two studies showed no association of smoking with outcomes of T1 UCB, there was mixed evidence for an association of smoking with response to intravesical therapy. For patients treated with RC, there was minimal support for an association of smoking with all outcomes. In a majority of studies of patients receiving RNU for UTUC, smoking was associated with intravesical recurrence, disease recurrence, cancer-specific mortality, and any-cause mortality. There was also evidence for a beneficial effect of smoking cessation on UC prognosis. Finally, findings regarding gender-specific effects of smoking on prognosis were contradictory. We note that there was marked heterogeneity in patient populations and smoking categorizations across studies, precluding a meta-analysis. Conclusions Smoking may lead to less favorable outcomes for UCB and UTUC patients, and smoking cessation may mitigate this effect. The current evidence base lacks studies on the effects of smoking on prognosis in numerous clinical demographic subgroups of UC patients, as well as prospective investigation of smoking cessation.
Abstract Context This review focuses on risk assessment and prediction tools for bladder cancer (BCa). Objective To review the current knowledge on risk assessment and prediction tools to enhance ...clinical decision making and counseling of patients with BCa. Evidence acquisition A literature search in English was performed using PubMed in July 2013. Relevant risk assessment and prediction tools for BCa were selected. More than 1600 publications were retrieved. Special attention was given to studies that investigated the clinical benefit of a prediction tool. Evidence synthesis Most prediction tools for BCa focus on the prediction of disease recurrence and progression in non–muscle-invasive bladder cancer or disease recurrence and survival after radical cystectomy. Although these tools are helpful, recent prediction tools aim to address a specific clinical problem, such as the prediction of organ-confined disease and lymph node metastasis to help identify patients who might benefit from neoadjuvant chemotherapy. Although a large number of prediction tools have been reported in recent years, many of them lack external validation. Few studies have investigated the clinical utility of any given model as measured by its ability to improve clinical decision making. There is a need for novel biomarkers to improve the accuracy and utility of prediction tools for BCa. Conclusions Decision tools hold the promise of facilitating the shared decision process, potentially improving clinical outcomes for BCa patients. Prediction models need external validation and assessment of clinical utility before they can be incorporated into routine clinical care. Patient summary We looked at models that aim to predict outcomes for patients with bladder cancer (BCa). We found a large number of prediction models that hold the promise of facilitating treatment decisions for patients with BCa. However, many models are missing confirmation in a different patient cohort, and only a few studies have tested the clinical utility of any given model as measured by its ability to improve clinical decision making.
Innate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5- and IL-13-producing type 2 ...ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor-positive ILC2s are a major ILC subtype in the kidney of humans and mice. Short-term IL-33 treatment in mice led to sustained expansion of IL-33 receptor-positive kidney ILC2s and ameliorated adriamycin-induced glomerulosclerosis. Furthermore, the expansion of ILC2s modulated the inflammatory response in the diseased kidney in favor of an anti-inflammatory milieu with a reduction of pathogenic myeloid cell infiltration and a marked accumulation of eosinophils that was required for tissue protection. In summary, kidney-residing ILC2s can be effectively expanded in the mouse kidney by IL-33 treatment and are central regulators of renal repair mechanisms. The presence of ILC2s in the human kidney tissue identifies these cells as attractive therapeutic targets for CKD in humans.
PURPOSE OF REVIEWThe prevalence of obesity has risen dramatically in the general population and among cancer survivors in the last three decades. In this review, we highlight the impact of obesity on ...carcinogenesis and survival with a focus on bladder cancer and renal cell carcinoma (RCC).
RECENT FINDINGSObesity presents an established risk factor for an up to 1.8-fold relative risk of RCC. Data with regard to bladder cancer are less abundant but support this association as well. Possible biological mechanisms involved are the insulin/insulin-like growth factor pathway, sex steroids, adipokines and chronic inflammation as well as treatment disparities within normal weight versus obese patients. With regard to survival, no conclusion can be drawn in either tumor entity at this time because of contradictory findings. These can in part be attributed to methodological limitations, while at the same time data exist to support the notion that obese patients exhibit less aggressive tumors.
SUMMARYObesity drives cancer risk in RCC and potentially bladder cancer. Evidence regarding survival has been contradictory and therefore no clear-cut recommendation can be made regarding weight management in cancer survivors despite to maintain a healthy lifestyle. However, given the future cancer burden that obesity will constitute, physicians should encourage weight loss and help prevent weight gain in the general population.
Abstract Background Standard survival statistics do not take into consideration the changes in the weight of individual variables at subsequent times after the diagnosis and initial treatment of ...bladder cancer. Objective To assess the changes in 5-yr conditional survival (CS) rates after radical cystectomy for bladder cancer and to determine how well-established prognostic factors evolve over time. Design, setting, and participants We analyzed data from 8141 patients treated with radical cystectomy at 15 international academic centers between 1979 and 2012. Interventions Radical cystectomy and pelvic lymph node dissection. Outcome measurements and statistical analysis Conditional cancer-specific survival (CSS) and overall survival (OS) estimates were calculated using the Kaplan-Meier method. The multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality after stratification by clinical characteristics (age, perioperative chemotherapy status) and pathologic characteristics (pT stage, grade, lymphovascular invasion, pN stage, number of nodes removed, margin status). The median follow-up was 32 mo. Results and limitations The 5-yr CSS and OS rates were 67.7% and 57.5%, respectively. Given a 1-, 2-, 3-, 5- and 10-yr survivorship, the 5-yr conditional OS rates improved by +5.6 (60.7%), +8.4 (65.8%), +7.6 (70.8%), +3.0 (72.9%), and +1.9% (74.3%), respectively. The 5-yr conditional CSS rates improved by +5.6 (71.5%), +9.8 (78.5%), +7.9 (84.7%), +7.2 (90.8%), and 5.6% (95.9%), respectively. The 5- and 10-yr CS improvement was primarily noted among surviving patients with advanced stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS. Findings were confirmed on multivariable analyses. The main limitation was the retrospective design. Conclusions CS analysis demonstrates that the patient risk profile changes over time. The risk of mortality decreases with increasing survivorship. The CS rates improve mainly in the case of advanced stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS.
Background
Number of positive prostate biopsy cores represents a key determinant between high versus very high‐risk prostate cancer (PCa). We performed a critical appraisal of the association between ...the number of positive prostate biopsy cores and CSM in high versus very high‐risk PCa.
Methods
Within Surveillance, Epidemiology, and End Results database (2010–2016), 13,836 high versus 20,359 very high‐risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut‐offs (≥2–≥12) were tested in Kaplan–Meier, cumulative incidence, and multivariable Cox and competing risks regression models.
Results
Among 11 tested positive prostate biopsy core cut‐offs, more than or equal to 8 (high‐risk vs. very high‐risk: n = 18,986 vs. n = 15,209, median prostate‐specific antigen PSA: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut‐off (high‐risk vs. very high‐risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high‐risk PCa.
Conclusions
The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice.
Abstract Background Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTC) in patients with advanced nonmetastatic urothelial carcinoma of the bladder ...(UCB). Objective Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTC in patients with clinically nonmetastatic UCB. Design, setting, and participants Blood samples from 100 consecutive UCB patients treated with radical cystectomy (RC) were investigated for the presence (CellSearch system) of CTC and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization. Intervention Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy. Measurements Outcomes were assessed according to CTC status. HER2 expression of CTC was compared with that of the corresponding primary tumor and lymph node metastasis. Results and limitations CTC were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1–100). Presence, number, and HER2 status of CTC were not associated with clinicopathologic features. CTC-positive patients had significantly higher risks of disease recurrence and cancer-specific and overall mortality ( p values: ≤0.001). After adjusting for effects of standard clinicopathologic features, CTC positivity remained an independent predictor for all end points (hazard ratios: 4.6, 5.2, and 3.5, respectively; p values ≤0.003). HER2 was strongly positive in CTC from 3 of 22 patients (14%). There was discordance between HER2 expression on CTC and HER2 gene amplification status of the primary tumors in 23% of cases but concordance between CTC, primary tumors, and lymph node metastases in all CTC-positive cases (100%). The study was limited by its sample size. Conclusions Preoperative CTC are already detectable in almost a quarter of patients with clinically nonmetastatic UCB treated with RC and were a powerful predictor of early disease recurrence and cancer-specific and overall mortality. Thus CTC may serve as an indication for multimodal therapy. Molecular characterization of CTC may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials.
Abstract Background The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood. Objective To assess gender-specific differences in ...pathologic factors and survival of UCB patients treated with radical cystectomy (RC). Design, setting, and participants Data from 8102 patients treated with RC (6497 men 80% and 1605 women 20%) for UCB between 1971 and 2012 were analyzed. Outcome measurements and statistical analysis Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI). Results and limitations Female patients were older at the time of RC ( p = 0.033) and had higher rates of pathologic stage T3/T4 disease ( p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR ( p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM ( p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05). Conclusions We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.
Severe Peyronie’s disease (PD) and concomitant erectile dysfunction (ED) may require plaque incision/excision and grafting (PIG) as an adjunct to penile prosthesis implantation (IPP). Currently, ...there is no available consensus on the best graft material to use. Our aim was to systematically review graft materials used as patches following PIG + IPP. Literature search was performed in March 2021. Only original articles in English with a series of 10 or more patients were included. Overall, a total of 17 studies were included, corresponding to a cohort of 662 patients. The mean age ranged from 45 to 65 years and most patients had curvatures >45°. Average penile lengthening ranged from 1 to 3.5 cm, average residual curvatures from 0 to 20% and decreased glans sensitivity from 0 to 20%. Eighty to 100% of patients were satisfied with cosmetic and functional results. PIG + IPP with the use of various grafts offers promising results for the treatment of patients suffering from severe PD with concomitant ED. Unfortunately, the absence of high quality and comparative studies makes it difficult to establish the optimum graft. Therefore, the level of experience of the surgical team with one or more methods should guide their choice.
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