New Intravesical Agents for BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer.

BACKGROUND: With the exception of the FDA-approved valrubicin and pembrolizumab, there are no standard second-line treaments for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC). OBJECTIVES: To provide a systematic review of the novel intravesically administered therapeutic agents for the salvage treatment of BCG-unresponsive NMIBC. METHODS: Online search of the PubMed, EMBASE and Web of Science databases was performed. The endpoints of this review were to evaluate the efficacy of the agents in terms of complete response rates (CR) and durability of CR, overall survival, recurrence-free survival and cancer-specific survival and to report on their toxicity profile. A search on Clinicaltrials.gov was performed to identify ongoing clinical trials. RESULTS: 14 studies were included in this review. The critical clinical need for the development of an effective, safe and durable intravesical drug for the salvage treatment of high-risk NMIBC seems to be met mainly by intravesical gene therapy; in fact, data support the FDA-approved nadofaragene firadenovec as a potentially important therapeutic advancement in this context. Promising results are also being obtained by the combination of N-803/BCG and by innovative drug delivery systems. CONCLUSIONS: Considering the plethora of novel intravesical treatments that have completed phase II evaluation, one can reasonably expect that clinicians will soon have at their disposal new agents and treatment options for BCG-unresponsive NMIBC. In the near future, it will be up to the urologist to identify, for each specific patient, the right agent to use, based on safety, results and cost-effectiveness.

Melatonin Preserves the Postharvest Quality of Cut Roses through Enhancing the Antioxidant System.

The vase life of cut rose is relatively short, therefore; preserving its postharvest quality via eco-friendly approaches is of particular economic importance. From the previous literature, despite melatonin (MT) plays diverse important roles in the postharvest quality maintenance, its impact on preserving the postharvest quality of cut flowers is really scarce. This research therefore was undertaken to find out the possibility of exogenous MT as an eco-friendly preservative to extend the vase life of cut roses. The flowering stems of Rosa hybrida cv. 'First Red' were pulsed in MT solutions at 0, 0.1, 0.2 and 0.3 mM for 30 min and then transferred to distilled water for evaluation. The vase life was significantly prolonged and relative water content was considerably maintained due to MT application compared to the control, more so with 0.2 mM concentration which nearly doubled the vase life (1.9-fold) higher than the control. SEM investigation showed that MT treatment reduced the stomatal aperture in lower epidermis which was widely opened in control flowers. MT treatment significantly increased the phenol content, glutathione (GSH) content and CAT, APX and GR enzyme activities compared to untreated flowers. Additionally, the radical scavenging capacity in MT-treated flowers was considerably higher than that of control and therefore MT treatment reduced H2O2 production and lipid peroxidation, which altogether reflected in membrane stability maintenance.

Exploring the Potential Enhancing Effects of Trans-Zeatin and Silymarin on the Productivity and Antioxidant Defense Capacity of Cadmium-Stressed Wheat.

Pot trials were performed to explore the impacts of seed priming (SPr) plus leaf treatment (LTr) with trans-zeatin-type cytokinin (tZck; 0.05 mM) and silymarin (Sim; 0.5 mM) on growth, yield, physio-biochemical responses, and antioxidant defense systems in Cd-stressed wheat. tZck + Sim applied as SPr + LTr was more effective than individual treatments, and the impacts were more pronounced under stress conditions. Cd stress (0.6 mM) severely declined growth and yield traits, and photosynthesis efficiency (pigment contents, instantaneous carboxylation efficiency, and photochemical activity) compared to the control. These negative impacts coincided with increased levels of Cd2+, O2•- (superoxide), H2O2 (hydrogen peroxide), MDA (malondialdehyde), and EL (electrolyte leakage). Non-enzymatic and enzymatic antioxidant activities, and tZck and Sim contents were also increased. However, tZck + Sim increased photosynthesis efficiency, and further boosted antioxidant activities, and contents of tZck and Sim, while minimizing Cd2+ levels in roots, leaves, and grains. The levels of O2•-, H2O2, MDA, and EL were also minimized, reflecting positively on growth and productivity. tZck + Sim applied as SPr + LTr was highly effective in promoting antioxidants and photosynthesis machineries, minimizing oxidative stress biomarkers and Cd2+ levels, boosting tolerance to Cd stress, and improving wheat productivity under Cd stress.

The Accuracy of Sequential Urethral Frozen Section and its Impact on Urethral Recurrence After Radical Cystectomy.

OBJECTIVE: To assess the accuracy of frozen section analysis (FSA) for detecting and eliminating malignant urethral margins during radical cystectomy (RC) for bladder cancer (BC) and its impact on urethral recurrence. METHODS: Urethral margins were initially examined by FSA in 217 patients at RC. When positive, additional resections were performed. Subsequently, all specimens were re-examined on formalin-fixed, paraffin-embedded sections (FFPE). Malignancy was defined as either the presence of carcinoma in situ, high-grade or invasive tumor cells at the urethral margin. Kaplan-Meier analysis was used to assess the impact of the final urethral margin status on urethral recurrence. Multinomial logistic regression addressed independent risk factors for a positive final urethral margin. RESULTS: At initial examination, urethral margins were positive on FSA and FFPE in 21 (9.7%) and 17 (7.8) patients, respectively. The corresponding sensitivity, specificity, positive and negative predictive values were 88.2%, 97.0%, 71.4% and 99.0% (overall accuracy: 96.3%). After initial FSA, 23 patients (including 2 with equivocal histological findings) received re-resections (median: 1, total range: 1-3). Persistent positive margins were detected on FSA in 10 (43.5%) while none of these margins were positive on FFPE (overall accuracy: 52.2%). A positive urethral FSA at initial assessment was the only independent risk for a positive final urethral margin. The 3-year urethral recurrence-free survival was 99.1% for patients with negative margins on initial assessment (I), 100% for those with negative final margins after re-resection (II) and 83.3% for patients with positive final margins (III; P= .013 for I/II vs. III). CONCLUSIONS: The accuracy of FSA for detecting malignant urethral margins is high on initial examination but drops considerably in case of re-resection while most positive margins at initial FSA are converted to negative final ones on FFPE. Conversion of a positive to a negative margin was associated with a lower risk of urethral recurrence.

The Predictive and Prognostic Value of Precystectomy Serum Gamma-Glutamyltransferase Levels in Patients With Invasive Bladder Cancer.

INTRODUCTION: The aim of the study was to elucidate the predictive and prognostic value of serum gamma-glutamyltransferase (GGT) in patients with invasive bladder cancer (BC). PATIENTS AND METHODS: Preoperative serum GGT concentrations were assessed in 324 patients treated with RC for cM0 BC between 2002 and 2013. Laboratory values were obtained 1 to 3 days prior to RC. Uni- and multivariable analyses were carried out to evaluate clinicopathologic risk factors for survival. The median follow-up was 36 months (IQR: 10-55). RESULTS: Elevated preoperative GGT levels were diagnosed in 77 patients (23.8%). Elevated GGT was significantly associated with higher ECOG PS and tumor stage (both P = .001), lymph-node tumor involvement (P < .001), positive surgical margins (P = .018), lymphovascular invasion (P = .024), muscle-invasive disease at primary diagnosis (P = .033), increased tumor size (P = .035), hydronephrosis at RC (P = .049) and increased preoperative CRP, GPT and GOT levels (both P < .001). Patients with elevated GGT had decreased 3-year overall (49.2% vs. 69.6%; P = .005) and cancer-specific survival (71.1% vs. 80.9%; P = .042) compared with patients with normal levels. On multivariable analysis, advanced tumor stage (P = .032), lymph node positive disease (P = .030), positive soft tissue surgical margins (P = .014), hydronephrosis at RC (both P = .010), higher ECOG performance status and elevated GGT (P = .043) levels were independent predictors of all-cause mortality. CONCLUSION: Elevated preoperative serum GGT levels are associated with increased risk of locally advanced BC and mortality after RC. These data suggest that GGT levels may be useful for improved prognostication in invasive BC.

The Efficacies of 1-Methylcyclopropene and Chitosan Nanoparticles in Preserving the Postharvest Quality of Damask Rose and Their Underlying Biochemical and Physiological Mechanisms.

Preserving the flower shelf life of damask rose is a crucial matter in promoting its economic viability. Chitosan nanoparticles (CSNPs) and 1-methylcyclopropene (1-MCP) may potentially decrease the postharvest loss of several horticultural commodities, but no findings on damask rose have been published. Therefore, the aim of this research was to study the effect of 1-MCP (400 mg m-3) and either the pre- or postharvest application of CSNPs (1%) on maintaining the quality of damask rose flowers during storage at 4 or 20 °C. The shelf life of damask rose has been significantly extended, along with a reduction in weight loss due to 1-MCP, CSNPs and pre-CSNP treatments. 1-MCP or CSNP applications have resulted in a higher relative water content, volatile oil, total anthocyanins, total carotenoids, total phenolics and antioxidant activity. Ethylene evolution, H2O2 generation and malondialdehyde content were significantly decreased due to 1-MCP or CSNPs treatment, and hence, the cell membrane functions have been maintained. The 1-MCP or CSNP-treated flowers have shown higher activities of catalase and ascorbate peroxidase and lower activities of polyphenol oxidase and lipoxygenase in comparison to untreated flowers. Our results showed that the postharvest application of 1-MCP or CSNPs is a very promising method to maintain the postharvest quality of damask rose during storage.

Ginger Extract and Fulvic Acid Foliar Applications as Novel Practical Approaches to Improve the Growth and Productivity of Damask Rose.

Plant biostimulants (BIOs) have been identified as among the best agricultural practices over the past few decades. Ginger extract (GE) and fulvic acid (FA) are a new family of multifunctional BIOs that positively affect development processes in plants. However, the underlying mechanisms that influence these development processes are still unknown. The objective of this study was to determine how GE and FA affect the plant growth and productivity in damask rose. Furthermore, the mechanisms of these BIOs that regulate the performance of this plant were investigated. Damask rose plants were foliar-sprayed with GE (5, 10 and 15 mg L-1) or FA (1, 3 and 5 g L-1), while control plants were sprayed with tap water. The results showed that GE or FA foliar applications enhanced plant height and branch number much more than the control; however, FA treatment was more effective than GE. Intriguingly, flower number, flower yield, relative water content, and total chlorophyll content were all improved by either GE or FA, paying attention to reducing the blind shoot number per plant. Relative to the control, foliar application with 15 mg L-1 GE or 3 mg L-1FA increased the flower number by 16.11% and 19.83% and the flower yield per hectare by 40.53% and 52.75%, respectively. Substantial enhancements in volatile oil content and oil yield were observed due to GE and FA treatments, especially with the highest concentrations of both BIOs. The treatments of GE and FA considerably improved the total soluble sugars, total phenolic content, total anthocyanin content, and total carotenoid content, more so with FA. Additionally, the contents of N, P, K, Mg, Fe, and Zn elements were also enhanced by applying either GE or FA, especially at higher levels of both BIOs. In sum, our findings illuminate the potential functions of exogenous application of GE and FA in improving the growth, flower yield, and volatile oil yield in damask rose through enhancing the phytochemical and nutrient profiles. Applications of GE and FA can, thus, be a promising approach for enhancing the productivity of damask rose.

How salt stress-responsive proteins regulate plant adaptation to saline conditions.

KEY MESSAGE: An overview is presented of recent advances in our knowledge of candidate proteins that regulate various physiological and biochemical processes underpinning plant adaptation to saline conditions. Salt stress is one of the environmental constraints that restrict plant distribution, growth and yield in many parts of the world. Increased world population surely elevates food demands all over the globe, which anticipates to add a great challenge to humanity. These concerns have necessitated the scientists to understand and unmask the puzzle of plant salt tolerance mechanisms in order to utilize various strategies to develop salt tolerant crop plants. Salt tolerance is a complex trait involving alterations in physiological, biochemical, and molecular processes. These alterations are a result of genomic and proteomic complement readjustments that lead to tolerance mechanisms. Proteomics is a crucial molecular tool that indicates proteins expressed by the genome, and also identifies the functions of proteins accumulated in response to salt stress. Recently, proteomic studies have shed more light on a range of promising candidate proteins that regulate various processes rendering salt tolerance to plants. These proteins have been shown to be involved in photosynthesis and energy metabolism, ion homeostasis, gene transcription and protein biosynthesis, compatible solute production, hormone modulation, cell wall structure modification, cellular detoxification, membrane stabilization, and signal transduction. These candidate salt responsive proteins can be therefore used in biotechnological approaches to improve tolerance of crop plants to salt conditions. In this review, we provided comprehensive updated information on the proteomic data of plants/genotypes contrasting in salt tolerance in response to salt stress. The roles of salt responsive proteins that are potential determinants for plant salt adaptation are discussed. The relationship between changes in proteome composition and abundance, and alterations observed in physiological and biochemical features associated with salt tolerance are also addressed.

Exogenous Gibberellic Acid or Dilute Bee Honey Boosts Drought Stress Tolerance in Vicia faba by Rebalancing Osmoprotectants, Antioxidants, Nutrients, and Phytohormones.

The use of growth regulators such as gibberellic acid (GA3) and biostimulants, including diluted bee honey (Db-H) can improve drought tolerance in many crops, including the faba bean (Vicia faba L.). Db-H contains high values of osmoprotectants, mineral nutrients, vitamins, and many antioxidants making it an effective growth regulator against environmental stress effects. Therefore, the present study was planned to investigate the potential improvement in the faba bean plant performance (growth and productivity) under full watering (100% of crop evapotranspiration (ETc)) and drought stress (60% of ETc) by foliar application of GA3 (20 mg L-1) or Db-H (20 g L-1). The ameliorative impacts of these growth regulators on growth, productivity, physio-biochemical attributes, nutrient status, antioxidant defense system, and phytohormones were evaluated. GA3 or Db-H attenuated the negative influences of drought stress on cell membrane stability, ion leakage, relative water content, nutrient status, leaf pigments related to photosynthesis (chlorophylls and carotenoids), and efficiency of the photosystem II (PSII in terms of Fv/Fm and performance index), thus improving faba bean growth, green pod yield, and water use efficiency. Drought stress caused an abnormal state of nutrients and photosynthetic machinery due to increased indicators of oxidative stress (malondialdehyde (MDA), hydrogen peroxide (H2O2) and superoxide (O2•-)), associated with increased osmoprotectants (proline, glycine betaine, soluble sugars, and soluble protein), non-enzymatic antioxidants (ascorbic acid, glutathione, and α-tocopherol), and enzymatic antioxidant activities (superoxide dismutase, catalase, glutathione reductase, and ascorbate peroxidase). However, foliar-applied GA3 or Db-H mediated further increases in osmoprotectants, antioxidant capacity, GA3, indole-3-acetic acid, and cytokinins, along with decreased levels of MDA and abscisic acid. These results suggest the use of GA3 or Db-H at the tested concentrations to mitigate drought-induced damage in bean plants to obtain satisfactory growth and productivity under a water deficit of up to 40%.

Exogenous Sodium Nitroprusside Mitigates Salt Stress in Lentil (Lens culinaris Medik.) by Affecting the Growth, Yield, and Biochemical Properties.

Soil salinity disrupts the physiological and biochemical processes of crop plants and ultimately leads to compromising future food security. Sodium nitroprusside (SNP), a contributor to nitric oxide (NO), holds the potential to alleviate abiotic stress effects and boost tolerance in plants, whereas less information is available on its role in salt-stressed lentils. We examined the effect of exogenously applied SNP on salt-stressed lentil plants by monitoring plant growth and yield-related attributes, biochemistry of enzymes (superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)) amassing of leaf malondialdehyde (MDA) and hydrogen peroxide (H2O2). Salinity stress was induced by NaCl application at concentrations of 50 mM (moderate salinity) and 100 mM (severe salinity), while it was alleviated by SNP application at concentrations of 50 µM and 100 µM. Salinity stress severely inhibited the length of roots and shoots, the relative water content, and the chlorophyll content of the leaves, the number of branches, pods, seeds, seed yield, and biomass per plant. In addition, MDA, H2O2 as well as SOD, CAT, and POD activities were increased with increasing salinity levels. Plants supplemented with SNP (100 µM) showed a significant improvement in the growth- and yield-contributing parameters, especially in plants grown under moderate salinity (50 mM NaCl). Essentially, the application of 100 µM SNP remained effective to rescue lentil plants under moderate salinity by regulating plant growth and biochemical pathways. Thus, the exogenous application of SNP could be developed as a useful strategy for improving the performance of lentil plants in salinity-prone environments.

Protective Effects of Taif Rosewater Against Testicular Impairment Induced By Lead Intoxication In Rats.

This study explored treatment with Taif rosewater (RW) to protect against lead acetate-(PbAc) induced male testicular impairment. Male Wistar rats were divided into four groups and provided drinking water containing 4% Taif RW, PbAc, 4% Taif RW followed by PbAc or normal water (controls). Serum for hormonal assays and testicular tissue for histopathological and immunohistochemical examinations and molecular study were obtained. Epididymal spermatozoa were collected for analysis. PbAc significantly reduced serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH) and testosterone, as well as sperm count and motility percentage. It also caused a significant reduction in SOD and catalase activities, testicular CYTP450SCC , CYP17α, StAR mRNA expressions and the percentage of Bcl-2 immunoreactivity. The percentage of caspase-3 and NF-ĸB immunoreactivities, as well as sperm abnormalities, was increased, as did the testicular degeneration associated with vacuolation and necrosis of spermatogenic cells. Pretreatment with Taif RW significantly reduced the negative effects of PbAc as shown by the increases in serum gonadotropins level, SOD and catalase activities, and percentage of Bcl-2 immunoreactivity, decreases in the percentage of caspase-3 and NF-ĸB immunoreactivities, and improved testicular histology and sperm parameters. These data provide evidence that Taif RW protects against testicular toxicity caused by PbAc.

Seasonal Variability of Elemental Composition and Phytochemical Analysis of Moringa oleifera Leaves Using Energy-Dispersive X-ray Fluorescence and Other Related Methods.

The elemental contents and the phytochemical components of Moringa oleifera are crucial for nutrition and medical purposes. Therefore, the monthly and seasonal variations of the elemental composition and phytochemical analysis of Moringa oleifera leaves collected from the same ecological area have been investigated. For this purpose, Moringa oleifera leaves were collected monthly from the same tree's branches during the whole year from January 2019 to December 2019. A non-destructive elemental analysis technique was used, namely energy-dispersive X-ray fluorescence spectrometry. The seasonal variations are different from one season to another. The highest concentrations of Mo, Cr, Fe, Ti, and Si were found during winter, whereas the highest concentrations of Br, Cl, and Cu were found during the summer seasons. Based on Pearson's correlation analysis, a strong correlation between Ca and Sr was found, whereas Sr has a negative correlation with other detected elements. Similarly, Cu and Zn as well as Br and Cl have a strong correlation. Remarkable different concentrations were found during May which has the lowest positive correlation. The phytochemical analysis revealed that Moringa oleifera leaves collected during the spring season resulted in the highest chlorophyll content, phenol content, and the greatest scavenging activity. Therefore, the mineral contents and phytochemical compounds are affected by the changing of the seasons of the year. Collectively, the current results are useful for optimizing the harvest time of Moringa oleifera leaves with respect to the quality.

Prognostic significance of previous tonsillectomy after radical cystectomy for bladder cancer.

Introduction: To examine whether previous tonsillectomy (TE) impacts on survival after radical cystectomy (RC) for bladder cancer (BC).Patients and Methods: A total of 320 patients were staged cM0 and underwent RC for BC between 2002 and 2013. We retrospectively investigated whether patients had undergone TE prior to RC. Chi-square/Fisher-Exact test was carried out to compare clinicopathological features between the TE- and non-TE-group. Kaplan-Meier analysis with log-rank test was used to estimate recurrence-free survival (RFS) and multivariable Cox-regression analysis of risk factors of recurrence. The median follow-up was 31 months (interquartile range: 9-54).Results: A history of TE was present in 18 of the 320 patients (5.6%). All TEs were performed for benign conditions. TE prior to RC was associated with a history of appendectomy (p = 0.045), lower age at RC (p = 0.029), tumor unifocality (p < 0.001), advanced histopathological tumor stage (p = 0.015), non-pure urothelial carcinoma (p = 0.025), lymphovascular invasion (p = 0.035) and receipt of palliative chemotherapy (p = 0.004). The 3-year RFS was 39.2% for patients with previous TE and 62.4% for those without (p = 0.008). In multivariable analysis, adjusted for all significant parameters of univariable analysis, lymph-node tumor involvement (p = 0.017), positive surgical margins (p = 0.047), tumor grade (p = 0.032), advanced tumor stage (≥pT3a; p = 0.049) and a history of TE (p = 0.021) remained independent prognosticators of recurrence.Conclusion: In this series, previous TE was an independent predictor of recurrence after RC for BC. Further studies are needed to assess whether TE induces immunological alterations that might exert adverse effects on cancer progression of patients with invasive BC.

Impact of drought on growth, photosynthesis, osmotic adjustment, and cell wall elasticity in Damask rose.

The response of Damask rose to drought and the underlying mechanisms involved are not known. In this study, vegetative, propagated rose plants were grown under control and water-deficit conditions in a greenhouse at Taïf University, south-west of Saudi Arabia. Control plants were irrigated to field capacity (FC), while water-stressed plants were irrigated to either 50% FC (mild stress) or 25% FC (severe stress). After 60 days, leaf, stem and root fresh and dry weights (g plant-1), photosynthetic activity, leaf water potential (Ψw), leaf water content (WC), apoplastic water fraction (AWF), osmotic potential at full turgor (Ψs100) and turgor loss point (Ψs0), cell wall elasticity, osmotic adjustment (OA), and some solutes (K+, Ca2+, Cl-, proline and soluble carbohydrates) were evaluated. Water stress significantly decreased fresh and dry weights of R. damascena and all photosynthetic parameters, apart from leaf temperature, which increased. Severe water stress (25% FC) resulted in more negative Ψs100 and Ψs0 values than the mild water stress and control. The AWF did not significantly change in response to water stress. The leaf bulk modulus of elasticity (ε) increased from 2.5 MPa under well-watered conditions to 2.82 and 3.5 MPa under mild and severe water stress, respectively. R. damascena experienced OA in response to water stress, which was due to the active accumulation of soluble carbohydrates and, to a lesser degree, proline under mild stress, along with tissue dehydration (passive OA) under severe stress. Overall, we identified two important mechanisms of drought tolerance in R. damascena-osmotic and elastic adjustment-but they could not offer resistance to water stress beyond 25% FC.

Prognostic impact of tumor-associated immune cell infiltrates at radical cystectomy for bladder cancer.

OBJECTIVES: To assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC). MATERIAL AND METHODS: A total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan-Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10-55). RESULTS: Of the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence. CONCLUSIONS: In this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer.

The prognostic impact of hexaminolevulinate-based bladder tumor resection in patients with primary non-muscle invasive bladder cancer treated with radical cystectomy.

PURPOSE: To investigate whether hexaminolevulinate-based (HAL) bladder tumor resection (TURBT) impacts on outcomes of patients with primary non-muscle-invasive bladder cancer (NMIBC) who were eventually treated with radical cystectomy (RC). METHODS: A total of 131 consecutive patients exhibiting NMIBC at primary diagnosis were retrospectively investigated whether they had undergone any HAL-guided TURBT prior to RC. Uni- and multivariable analyses were used to evaluate the impact of HAL-TURBT on cancer-specific (CSS) and overall survival (OS). The median follow-up was 38 months (IQR 13-56). RESULTS: Of the 131 patients, 69 (52.7%) were managed with HAL- and 62 (47.3%) with white light (WL)-TURBT only prior to RC. HAL-TURBT was associated with a higher number of TURBTs prior to RC (p = 0.002) and administration of intravesical chemotherapy (p = 0.043). A trend towards a higher rate of tumor-associated immune cell infiltrates in RC specimens (p = 0.07) and a lower utilization rate of post-operative systemic chemotherapy (p = 0.10) was noted for patients who were treated with HAL-TURBT. The 5-year CSS/OS was 90.9%/74.5% for the HAL-group and 73.8%/55.8% for the WL-group (p = 0.042/0.038). In multivariable analysis, lymph node tumor involvement (p = 0.007), positive surgical margins (p = 0.001) and performance of WL-TURBT only (p = 0.040) were independent predictors for cancer-specific death. CONCLUSIONS: The present data suggest that the resection of NMIBC under HAL exerts a beneficial impact on outcomes of patients who will need to undergo RC during their course of disease. This finding may be due to improved risk stratification as the resection under HAL may allow more patients to be treated timely and adequately.

Radical Cystectomy in Female Patients - Improving Outcomes.

PURPOSE OF REVIEW: To review the methods of improving surgical, oncological, and functional outcomes in women with bladder cancer treated with radical cystectomy. RECENT FINDINGS: Οrthotopic urinary diversion (ONB) is a safe option for well-selected women as it combines high rates of daytime and nighttime continence with exceptional oncologic outcomes. It is considered safe even for patients with limited lymph node disease and trigone involvement, as long as a preoperative biopsy of the bladder neck or an intraoperative frozen section analysis of distal urethral margin rules out malignant disease. Nerve-sparing techniques have shown promising results. For well-selected patients with early invasive disease, sparing of internal genitalia has proven to be oncologically safe. Yet, generally accepted and evidence-based oncological and functional follow-up schemes for women after radical cystectomy are still lacking. Properly designed prospective studies are needed with adequate number of participants in order to safely conclude about a broader use of pelvic organ-sparing cystectomy.

Prognostic Significance of Incidental Prostate Cancer at Radical Cystoprostatectomy for Bladder Cancer.

OBJECTIVE: The aim of the study was to evaluate the impact of the clinical significance of incidental prostate cancer (PC) on overall survival (OS) after radical cystoprostatectomy (RC) for bladder cancer (BC). METHODS: A total of 822 consecutive men underwent RC in 3 academic centers between 1996 and 2011. The clinical significance of incidental PC was determined according to the Epstein criteria. The Kaplan-Meier analysis with log-rank was used to investigate the impact of PC on OS and univariate and multivariate Cox regression analyses for risk factors of OS. The median follow-up was 36 months (interquartile range 10-49). RESULTS: Of the 822 men, 117 (14.2%) had clinically significant, 243 (29.6%) insignificant and 462 (56.2) no PC at RC. Men with PC were at higher risk for lymphovascular invasion (LVI) of BC compared to men without PC (p < 0.001). The 5-year OS for men with clinically significant, insignificant and no PC was 33.3, 51.3 and 51.5%, respectively (p = 0.050). In the subgroup of pN0 patients (n = 601), clinically significant PC was significantly associated with inferior OS (p = 0.044) but not in multivariable analysis (p = 0.46). CONCLUSIONS: We did not find the clinical significance of incidental PC to be an independent predictor. However, the positive correlation between incidental PC and LVI of BC deserves further investigation.

Fluorescence-guided bladder tumour resection: impact on survival after radical cystectomy.

PURPOSE: To investigate whether photodynamic diagnosis (PDD)-guided bladder tumour resection (TUR-BT) is of prognostic value in patients undergoing subsequent radical cystectomy (RC) for bladder cancer (BC). METHODS: In 224 consecutive patients who underwent RC and bilateral pelvic lymphadenectomy for BC between 2002 and 2010 (median follow-up 29 months [IQR 8-59]), we retrospectively investigated whether patients had previously undergone PDD-guided (hexaminolevulinate [HAL] vs. 5-aminolevulinate [ALA]) versus white light (WL)-TUR-BT. Kaplan-Meier analysis was used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) using log-rank and Cox regression model for uni- and multivariable analysis. RESULTS: Of the 224 patients, 66 (29.5 %) underwent HAL-, 23 (10.3 %) ALA- and 135 (60.2 %) WL-TUR-BT before RC. The 3-year RFS/CSS/OS was 77.8/83.9/74.0 % for HAL-, 53.6/74.5/60.9 % for ALA- and 52.4/59.7/56.5 % for WL-TUR-BT (p = 0.002/0.023/0.037 for HAL vs. WL/ALA). PDD-TUR-BT was associated with a higher number of TUR-BTs before RC (p < 0.001) and re-resections (p = 0.015), a longer time between the first TUR-BT and RC (p = 0.044) and a lower rate of post-operative systemic chemotherapy (p = 0.001). In multivariable analysis, performance of HAL-TUR-BT, pathologic tumour and nodal stage as well as soft tissue surgical margin status were independent predictors for RFS, CSS and OS. CONCLUSIONS: This series indicates for the first time that HAL-guided TUR-BT is an independent predictor for improved survival after RC.

Prognostic relevance of postoperative platelet count in upper tract urothelial carcinoma after radical nephroureterectomy.

AIM OF THE STUDY: To assess the impact of perioperative platelet count (PLT) kinetics on recurrence-free survival (RFS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: From three prospectively maintained databases of three tertiary care centres a total of 269 patients undergoing RNU without perioperative treatment between 1996 and 2011 were considered for this analysis. Pre- and postoperatively elevated PLT count was defined as >400×10(9)/L. PLT levels were measured 1-3 days preoperatively and 7-10 days postoperatively. The median follow-up was 24 months (Interquartile range (IQR): 10-52). A new weighted scoring model was developed to predict recurrence after RNU based on significant parameters of multivariable analysis. RESULTS: The 5-year RFS in patients with preoperatively normal and elevated PLT count was 58.3% and 29.3%, respectively (p<0.001). The 5-year-RFS was 57.6% in patients with normal postoperative PLT count and 29.7% in those with elevated PLT levels (p<0.001). In multivariable analysis, pT-stage, lymphovascular invasion, ureteral margin status and postoperative thrombocytosis remained independent predictors for RFS. The 5-year RFS in patients with a score of 0 (low-risk), 1 (intermediate-risk) and 2-4 (high-risk) was 77.7%, 47.5% and 12.3%, respectively (p<0.001). Consideration of the variable postoperative thrombocytosis in the final model increased its predictive accuracy by 1.9% with a concordance index of 0.758 (p=0.015). CONCLUSION: PLT kinetics is significantly associated with RFS after RNU for UTUC. We constructed a simple, PLT-based prognostic model for recurrence after RNU.