Growth of Carbon Nanofibers and Carbon Nanotubes by Chemical Vapour Deposition on Half-Heusler Alloys: A Computationally Driven Experimental Investigation.

The possibility of directly growing carbon nanofibers (CNFs) and carbon nanotubes (CNTs) on half-Heusler alloys by Chemical Vapour Deposition (CVD) is investigated for the first time, without using additional catalysts, since the half-Heusler alloys per se may function as catalytic substrates, according to the findings of the current study. As a carbon source, acetylene is used in the temperature range of 700-750 °C. The n-type half-Heusler compound Zr0.4Ti0.60.33Ni0.33Sn0.98Sb0.020.33 is utilized as the catalytic substrate. At first, a computational model is developed for the CVD reactor, aiming to optimize the experimental process design and setup. The experimental process conditions are simulated to investigate the reactive species concentrations within the reactor chamber and the activation of certain reactions. SEM analysis confirms the growth of CNFs with diameters ranging from 450 nm to 1 µm. Raman spectroscopy implies that the formed carbon structures resemble CNFs rather than CNTs, and that amorphous carbon also co-exists in the deposited samples. From the characterization results, it may be concluded that a short reaction time and a low acetylene flow rate lead to the formation of a uniform CNF coating on the surface of half-Heusler alloys. The purpose of depositing carbon nanostructures onto half-Heusler alloys is to improve the current transfer, generated from these thermoelectric compounds, by forming a conductive coating on their surface.

[Urinary retention and postrenal kidney injury]. / Harnverhalt und postrenales Nierenversagen.

In men aged 40-83 years, the overall incidence of urinary retention is 4.5-6.8 cases per 1000 men per year. The incidence increases significantly with age, so that a man in his 70 s has a 10% chance and a man in his 80 s has a more than 30% chance of experiencing an episode of acute urinary retention [1]. The goal of diagnosis is to quickly reach a finding through clinical examination and ultrasound to be able to relieve the bladder. The first maneuver is catheterization, followed by, if necessary, initiation of pharmacological therapy that targets the underlying cause. Despite the high association of urinary retention with benign prostatic hyperplasia (BPH), a comprehensive history and diagnosis are crucial to identify possible rare and complex causes and to enable targeted treatment. The challenge lies in finding the balance between rapid symptomatic treatment and thorough investigation of atypical and rare pathologies to develop individually adapted and effective therapy strategies.

Urodynamic Parameters and Continence Outcomes in Asymptomatic Patients with Ileal Orthotopic Neobladder: A Systematic Review and Metanalysis.

INTRODUCTION: The orthotopic neobladder is the type of urinary diversion (UD) that most closely resembles the original bladder. However, in the literature the urodynamic aspects are scarcely analysed. OBJECTIVE: To provide the first systematic review (SR) on the urodynamic (UDS) outcomes of the ileal orthotopic neobladders (ONB). Continence outcomes are also presented. METHODS: A PubMed, Embase and Cochrane CENTRAL search for peer-reviewed studies on ONB published between January 2001-December 2022 was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. RESULTS AND CONCLUSION: Fifty-nine manuscripts were eligible for inclusion in this SR. A great heterogeneity of data was encountered. Concerning UDS parameters, the pooled mean was 406.2 mL (95% CI: 378.9-433.4 mL) for maximal (entero)cystometric capacity (MCC) and 21.4 cmH2O (95% CI: 17.5-25.4 cmH2O) for Pressure ONB at MCC. Postvoid-residual ranged between 4.9 and 101.6 mL. The 12-mo rates of day and night-time continence were 84.2% (95% CI: 78.7-89.1%) and 61.7% (95% CI: 51.9-71.1%), respectively.Despite data heterogeneity, the ileal ONB seems to guarantee UDS parameters that resemble those of the native bladder. Although acceptable rates of daytime continence are reported the issue of high rates of night-time incontinence remains unsolved. Adequately designed prospective trials adopting standardised postoperative care, terminology and methods of outcome evaluation as well as of conduction of the UDS in the setting of ONB are necessary to obtain homogeneous follow-up data and to establish UDS guidelines for this setting.

Photodynamic Therapy: Current Trends and Potential Future Role in the Treatment of Bladder Cancer.

Bladder cancer (BC) is the 10th most common cancer in the world. The therapeutic spectrum of BC is broad and is constantly expanding. Despite the wide clinical use of photodynamic diagnosis (PTD) for BC, PDT has not been sufficiently investigated in the treatment landscape of BC. We performed an online search of the PubMed database using these keywords: photodynamic therapy, bladder cancer, urothelial carcinoma, in vivo, in vitro, cell line, animal model. Reviews, case reports, and articles devoted to photodynamic diagnostics and the photodynamic therapy of tumors other than urothelial carcinoma were excluded. Of a total of 695 publications, we selected 20 articles with clinical data, 34 articles on in vivo PDT, and 106 articles on in vitro data. The results presented in animal models highlight the potential use of PDT in the neoadjuvant or adjuvant setting to reduce local recurrence in the bladder and upper urinary tracts. Possible regimens include the combination of PDT with intravesical chemotherapy for improved local tumor control or the integration of vascular-targeted PDT in combination with modern systemic drugs in order to boost local response. We summarize available evidence on the preclinical and clinical application of PDT for urothelial carcinoma in order to explain the current trends and future perspectives.

European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2023 Guidelines.

CONTEXT: We present an overview of the updated 2023 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). OBJECTIVE: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the MMIBC guidelines has been performed annually since 2017. Searches cover the Medline, EMBASE, and Cochrane Libraries databases for yearly guideline updates. A level of evidence and strength of recommendation are assigned. The evidence cutoff date for the 2023 MIBC guidelines was May 4, 2022. EVIDENCE SYNTHESIS: Patients should be counselled regarding risk factors for bladder cancer. Pathologists should describe tumour and lymph nodes in detail, including the presence of histological subtypes. The importance of the presence or absence of urothelial carcinoma (UC) in the prostatic urethra is emphasised. Magnetic resonance imaging (MRI) of the bladder is superior to computed tomography (CT) for disease staging, specifically in differentiating T1 from T2 disease, and may lead to a change in treatment approach in patients at high risk of an invasive tumour. Imaging of the upper urinary tract, lymph nodes, and distant metastasis is performed with CT or MRI; the additional value of flurodeoxyglucose positron emission tomography/CT still needs to be determined. Frail and comorbid patients should be evaluated by a multidisciplinary team. Postoperative histology remains the most important prognostic variable, while circulating tumour DNA appears to be an interesting predictive marker. Neoadjuvant systemic therapy remains cisplatin-based. In motivated and selected women and men, sexual organ-preserving cystectomy results in better functional outcomes without compromising oncological outcomes. Robotic and open cystectomy have comparable outcomes and should be combined with (extended) lymph node dissection. The diversion type is an individual choice after taking patient and tumour characteristics into account. Radical cystectomy remains a highly complex procedure with considerable morbidity and risk of mortality, although lower rates are observed for higher hospital volumes (>20 cases/yr). With proper patient selection, trimodal therapy (chemoradiation) has comparable outcomes to radical cystectomy. Adjuvant chemotherapy after surgery improves disease-specific survival and overall survival (OS) in patients with high-risk disease who did not receive neoadjuvant treatment, and is strongly recommended. There is a weak recommendation for adjuvant nivolumab, as OS data are not yet available. Health-related quality of life should be assessed using validated questionnaires at baseline and after treatment. Surveillance is needed to monitor for recurrent cancer and functional outcomes. Recurrences detected on follow-up seem to have better prognosis than symptomatic recurrences. CONCLUSIONS: This summary of the 2023 EAU guidelines provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology guidelines panel on muscle-invasive and metastatic bladder cancer has released an updated version of the guideline containing information on diagnosis and treatment of this disease. Recommendations are based on studies published up to May 4, 2022. Surgical removal of the bladder and bladder preservation are discussed, as well as updates on the use of chemotherapy and immunotherapy in localised and metastatic disease.

Current knowledge on multiple sclerosis pathophysiology, disability progression assessment and treatment options, and the role of autologous hematopoietic stem cell transplantation.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects nearly 2.8 million people each year. MS distinguishes three main types: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). RRMS is the most common type, with the majority of patients eventually progressing to SPMS, in which neurological development is constant, whereas PPMS is characterized by a progressive course from disease onset. New or additional insights into the role of effector and regulatory cells of the immune and CNS systems, Epstein-Barr virus (EBV) infection, and the microbiome in the pathophysiology of MS have emerged, which may lead to the development of more targeted therapies that can halt or reverse neurodegeneration. Depending on the type and severity of the disease, various disease-modifying therapies (DMTs) are currently used for RRMS/SPMS and PPMS. As a last resort, and especially in highly active RRMS that does not respond to DMTs, autologous hematopoietic stem cell transplantation (AHSCT) is performed and has shown good results in reducing neuroinflammation. Nevertheless, the question of its potential role in preventing disability progression remains open. The aim of this review is to provide a comprehensive update on MS pathophysiology, assessment of MS disability progression and current treatments, and to examine the potential role of AHSCT in preventing disability progression.

[Using the DFree device for balanced bladder management]. / Der Einsatz des DFree-Ultraschallsensors für ein ausgewogenes Blasenmanagement.

BACKGROUND: Bladder dysfunctions, regardless of their origin, have significant psychosocial effects. Depending on the existing disorder and bladder functionality, behavioural therapy and supporting tools are the first choice of therapy but the need for medication, intervention and surgery is significant. OBJECTIVE: The DFree ultrasonic sensor enables sonographic measurement of bladder filling and feeds this back to the sensor wearer via an app. The primary outcome of the study was the influence of the DFree on the quality of life of the patients. Secondary endpoints were usefulness and user-friendliness of the DFree device as well as the self-reported degree of autonomy. METHODS: In the present pilot study, 18 urological patients with various bladder dysfunctions were equipped with the DFree ultrasonic sensor for at least 12 hours daily over a period of three months. The parameters were collected at baseline (T1) and at end of the study (T2) using the Kings Health Questionnaire (KHQ) and the German version of the Client Satisfaction Questionnaire (ZUF-8) (quantitative data) as well as guided interviews (qualitative data). RESULTS: Improvement in bladder dysfunction based on the KHQ could not be statistically confirmed. However, the average value based on the ZUF-8 showed satisfaction with the DFree. In the interviews at T2, the participants gave a positive feedback with specific suggestions for improving user-friendliness. The device was described as helpful and easy to use. CONCLUSIONS: The DFree ultrasonic sensor is a new technical tool in the treatment of bladder dysfunctions. Improving specific technical details could increase the user-friendliness as well as the usefulness of the device.

Practice change: No benefit of extended lymphadenectomy at radical cystectomy in patients with muscle invasive bladder cancer.

For many decades, extended pelvic lymph node dissection has been an integral part during radical cystectomy for patients with muscle invasive bladder cancer. This practice was based on large retrospective meta-analyses suggesting an oncologic benefit to an extended dissection. This mini review and meta-analysis includes the two available randomized trials in the current literature. Therefore, it can be considered as the strongest level of evidence regarding the prognostic benefit of an extended pelvic lymphadenectomy. Based on current randomized data, standard pelvic lymph node dissection up to the level of iliac bifurcation is sufficient, and extension of the dissection above this level does not provide any additional oncologic benefit.

Role of inguinal and pelvic lymph node dissection for primary urethral carcinoma: a systematic review.

PURPOSE OF REVIEW: Primary urethral carcinoma (PUC) is a rare urologic tumor. There is limited evidence on this entity. This review summarizes the existing evidence on lymph node dissection (LND) in patients with PUC. RECENT FINDINGS: We performed a systematic search of the PubMed, EMBASE, and Web of Science databases to evaluate the impact of inguinal and pelvic LND on the oncological outcomes of PUC and to identify indications for this procedure. RESULTS: Three studies met the inclusion criteria. The cancer detection rate in clinically nonpalpable inguinal lymph node (cN0) was 9% in men and 25% in women. In clinically palpable lymph node (cN+), the malignancy rate was 84% and 50% in men and women, respectively. Overall cancer detection rate in pelvic lymph nodes in patients with cN0 was 29%. Based on tumor stage, the detection rate was 11% in cT1-2 N0 and 37% in cT3-4 N0. Nodal disease was associated with higher recurrence and worse survival. Pelvic LND seems to improve overall survival for patients with LND regardless of the location or stage of lymph nodes. Inguinal LND improved overall survival only in patients with palpable lymph nodes. Inguinal LND had no survival benefit in patients with nonpalpable lymph nodes. SUMMARY: The available, albeit scarce, data suggest that inguinal LND derives the highest benefit in women and in patients with palpable inguinal nodes, whereas the benefit of pelvic LND seems to be more pronounced across all stages of invasive PUC. Prospective studies are urgently needed to further address the prognostic benefit of locoregional LND in PUC.

[Position paper of the working group Urological Acute Medicine]. / Positionspapier des Arbeitskreises "Urologische Akutmedizin".

Emergency patients with acute genitourinary system diseases are frequently encountered in both outpatient and clinical emergency structures. It is estimated that one-third of all inpatients in a urology clinic initially present as an emergency. In addition to general emergency medicine knowledge, specialized urologic expertise is a prerequisite for the care of these patients, which is needed early and specifically for optimal treatment outcomes. It must be taken into account that, on the one hand, the current structures of emergency care still lead to delays in patient care despite positive developments in recent years. On the other hand, most hospital emergency facilities need urologic expertise on site. In addition, politically intended changes in our health care system, which drive an increasing ambulantization of medicine and condition a further centralization of emergency clinics, become effective. The aim of the newly established working group "Urological Acute Medicine" is to ensure and further improve the quality of care for emergency patients with acute genitourinary system diseases and, in consensus with the German Society of Interdisciplinary Emergency and Acute Medicine, to define precise task distributions and interfaces of both specialities.

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.

The Role of Local Agents for the Treatment of Localized Upper Tract Urothelial Carcinoma: A Review of the Current Evidence.

Kidney-sparing surgery (KSS) for upper urinary tract urothelial carcinoma (UTUC) is a promising alternative to radical nephroureterectomy, especially for low-risk cases. However, due to the established risk of ipsilateral UTUC recurrence caused by the implantation of floating neoplastic cells after endoscopic resection, adjuvant endocavitary (endoureteral) instillations have been proposed. Instillation therapy may be also used as primary treatment for UTUC. The two most studied drugs that have been evaluated in both the adjuvant and primary setting of endocavitary instillation are mitomycin C and Bacillus Calmette-Guerin. The current paper provides an overview of the endocavitary treatments for UTUC, focusing on methods of administration, novel formulations, oncologic outcomes (in terms of endocavitary recurrence and progression), as well as on complications. In particular, the role of UGN-101 as a primary chemoablative treatment of primary noninvasive, endoscopically unresectable, low-grade, UTUC has been analysed. The drug achieved a complete response rate of 58% after the induction cycle, with a durable response independently of the maintenance cycle. The cumulative experience on the role of UUT instillation therapy appears encouraging; however, no definitive conclusions can be drawn about its therapeutic benefit. Given the current state of the art, any decision to administer adjuvant endoureteral therapy for UTUC should be carefully weighed against the potential adverse events. Nevertheless, newer investigations that improve visualization during ureteroscopy, genomic characterization, novel drugs and innovative strategies of improved drug delivery are under evaluation. The landscape of KSS for the treatment of the UTUC is evolving and seems promising.

Metabolic regulation of the neural stem cell fate: Unraveling new connections, establishing new concepts.

The neural stem cell niche is a key regulator participating in the maintenance, regeneration, and repair of the brain. Within the niche neural stem cells (NSC) generate new neurons throughout life, which is important for tissue homeostasis and brain function. NSCs are regulated by intrinsic and extrinsic factors with cellular metabolism being lately recognized as one of the most important ones, with evidence suggesting that it may serve as a common signal integrator to ensure mammalian brain homeostasis. The aim of this review is to summarize recent insights into how metabolism affects NSC fate decisions in adult neural stem cell niches, with occasional referencing of embryonic neural stem cells when it is deemed necessary. Specifically, we will highlight the implication of mitochondria as crucial regulators of NSC fate decisions and the relationship between metabolism and ependymal cells. The link between primary cilia dysfunction in the region of hypothalamus and metabolic diseases will be examined as well. Lastly, the involvement of metabolic pathways in ependymal cell ciliogenesis and physiology regulation will be discussed.

[Gender-associated differences in bladder cancer]. / Geschlechtsassoziierte Unterschiede beim Harnblasenkarzinom.

BACKGROUND AND OBJECTIVES: Although the incidence of bladder cancer among women is lower, they tend to more often have advanced disease at presentation with a more aggressive course. It is still unclear which factors are responsible for the poorer prognosis of bladder cancer in women. MATERIALS AND METHODS: Original papers and reviews from 2004 until 2022 were identified in a PubMed search and evaluated. RESULTS: Multiple factors are likely responsible for the different courses of bladder cancer in women versus men. In the literature, epidemiologic and clinical aspects are discussed. Furthermore, genetic and hormonal causes and the role of the urobiome have been the focus of discussion more recently. CONCLUSIONS: Earlier diagnosis and better surgical treatment could lead to a more favorable course of bladder cancer in women. Further analyses of genetic, hormonal, und microbiological factors could open new perspectives in the prevention, diagnosis, and treatment of bladder cancer.

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 CAG-triplet in the androgen receptor gene and single-nucleotide polymorphisms in androgen pathway genes in patients with concomitant bladder and prostate cancer.

PURPOSE: To test the hypothesis whether the number of the C(ytosine)-A(denine)-G(uanine) triplets in the androgen receptor (AR-) gene and further single-nucleotide polymorphisms in the androgen-responsive element of the promoter region of genes regulating the androgen pathway influence oncologic outcomes in patients with concomitant bladder (BC) and prostate cancer (PC) at a predisposing level. MATERIAL AND METHODS: A cohort of 36 patients was treated with radical cystectomy and histologically exhibited invasive BC and incidental PC. The number of cytosine-adenine-guanine (CAG)-triplets (rs4045402) in the AR gene was assessed in tumor-free lymph nodes as well as rs743572 in the CYP17A1 gene and rs676033, rs523349, rs9282858 in the SRD5A2. In addition, the clinical significance of incidental PC based on the Epstein-criteria was assessed with regard to BC-specific recurrence-free survival (RFS). The median follow-up was 26 months (range: 4-68). RESULTS: Patients with clinically significant PC had worse BC-specific RFS compared with patients with insignificant PC (P = 0.016). Patients with a PC volume of >0.2 cm3 had shorter 3-year BC-specific RFS compared with patients with a PC volume ≤0.2 cm3 (P = 0.025). The median number of CAG-triplets was 24 (mean ± SEM: 23 ± 2, interquartile range: 22-25, total range 18-29). Patients with a CAG-triplet number <23 exhibited significantly decreased 3-year BC specific RFS compared with patients with ≥23 repeats (27% vs. 65%; P = 0.026). No further significance were noted for the other tested SNPs and survival. CONCLUSIONS: A detailed description of incidental PC at radical cystoprostatectomy (RC) may be of greater prognostic importance than previously assumed in the literature. The CAG-repeat in the AR gene may predispose to worse oncologic outcomes after RC and should be further evaluated in larger studies.

Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial.

The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggests patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab.

The role of single-nucleotide polymorphisms of the 8q24 chromosome region in patients with concomitant bladder and prostate cancer.

OBJECTIVE: To assess whether single-nucleotide polymorphisms (SNPs) of the 8q24 chromosome region are associated with recurrence-free survival (RFS) after radical cystoprostatectomy (RC) in patients with concomitant bladder (BC) and prostate cancer (PC). MATERIALS AND METHODS: A cohort of thirty-six patients treated with RC and pelvic lymph node dissection and histologically exhibited invasive BC and incidental PC. Using Sanger sequencing, a total of seven SNPs in the androgen-responsive element of the promoter region of the following genes were assessed in tumor-free lymph nodes and correlated with oncological outcomes: PSCA (rs2294008, rs2978974, rs1045531, rs3736001), MYC (rs6983267), FXBO32 (rs7830622), and MIR151A (rs14974929). The median follow-up was 26 months (range: 4-68). RESULTS: In a dominant model, patients exhibiting rs2978974 as a minor allelic variant of the PSCA gene had worse RFS (32 vs. 75%, p = 0.015). No associations were found for the other SNPs. CONCLUSIONS: These data suggest that the rs2978974 of the PSCA gene correlates with inferior BC-specific RFS after RC and should be further evaluated in larger studies.

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.