Preoperative Cell-Free DNA (cfDNA) in Muscle-Invasive Bladder Cancer Treatment Outcome.

BACKGROUND: Tumor heterogeneity and lack of personalized prognosis leads to bladder cancer (BlCa) patients' lifelong surveillance with invasive interventions, highlighting the need for modern minimally invasive tools for disease management. Herein, we have evaluated the clinical utility of preoperative serum cell-free DNA (cfDNA) in ameliorating patients' risk-stratification and prognosis. METHODS: cfDNA was purified from 190 preoperative BlCa patients and 26 healthy individuals' serum samples and quantified by 2 assays: an in-house quantitative real-time PCR (qPCR) assay using LEP as reference control and a direct fluorometric assay using Qubit HS dsDNA. Capillary electrophoresis was performed in 31 samples for cfDNA fragment profiling. Tumor relapse/progression and metastasis/death were used as clinical endpoints for non-muscle-invasive bladder cancer and muscle-invasive bladder cancer (MIBC), respectively. RESULTS: cfDNA profiling by capillary electrophoresis highlighted that total and fragment-related cfDNA levels were significantly increased in BlCa and associated with advance disease stages. Evaluation of cfDNA levels by both Qubit/qPCR displayed highly consistent results (rs = 0.960; P < 0.001). Higher cfDNA was correlated with MIBC and stronger risk for early metastasis (Qubit:hazard ratio [HR] = 3.016, P = 0.009; qPCR:HR = 2.918, P = 0.004) and poor survival (Qubit:HR = 1.898, P = 0.042; qPCR:HR = 1.888, P = 0.026) of MIBC patients. Multivariate cfDNA-fitted models led to superior risk stratification and net benefit for MIBC prognosis compared to disease established markers. CONCLUSIONS: Elevated preoperative cfDNA levels are strongly associated with higher risk for short-term metastasis and poor outcome of MIBC, supporting modern noninvasive disease prognosis and management.

Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm.

Recently approved agents for post-vascular endothelial growth factor/post-vascular endothelial growth factor receptor (VEGF/VEGFR) inhibitors treatment of metastatic renal-cell carcinomas (mRCC), such as axitinib, nivolumab, and cabozantinib were shown to improve prognosis and substituted everolimus in this setting. We studied practice patterns, efficacy, and tolerability of these agents in a real-world series of Greek patients. We included patients with mRCC who received everolimus, axitinib, or nivolumab after progression on first-line anti-VEGF/VEGFRs therapy. Patients were stratified into three groups. Group A received nivolumab with or without cabozantinib at some point in their disease. Group B received axitinib but without nivolumab or cabozantinib. Group C received only everolimus among the four approved agents. Overall, 131 patients were included in the analysis. Everolimus and nivolumab were mainly used in the second line, while axitinib and cabozantinib were mostly used in the third and fourth lines. Median overall survival (OS) from first-line initiation was 8.7 [95% confidence interval (CI), 4-not reached], 3.6 (95% CI, 2-6), and 2.1 years (95% CI, 1.4-2.6) for Group A, B, and C, respectively ( P < 0.001). Median OS from the initiation of second-line therapy was 3.5, 2.7, and 1.3 years, respectively ( P < 0.001). There was no impact of first-line agent or treatment timing on survival. International Metastatic Renal Cell Carcinoma Database Consortium risk stratification was associated with OS. Toxicities observed were within expected frequencies. Grade ≥3 events were rare. Adoption of modern standards in everyday treatment of mRCC results in prolongation of survival. Real-world datasets are the new landmarks of survival for future research.

Deregulated Expression of IL-37 in Patients with Bladder Urothelial Cancer: The Diagnostic Potential of the IL-37e Isoform.

Cellular and molecular immune components play a crucial role in the development and perpetuation of human malignancies, shaping anti-tumor responses. A novel immune regulator is interleukin-37 (IL-37), already shown to be involved in the inflammation associated with the pathophysiology of many human disorders, including cancer. The interplay between tumor and immune cells is of great importance, especially for highly immunogenic tumors such as bladder urothelial carcinoma (BLCA). This study aimed to investigate the potential of IL-37 and its receptor SIGIRR (single immunoglobulin IL-1-related receptor) to serve as prognostic and/or diagnostic markers in patients with BLCA. To this end, a series of bioinformatics tools processing -omics datasets and specifically designed qPCR assays on human BLCA tumors and cancer cell lines were utilized. Bioinformatics analysis revealed that IL-37 levels correlate with BLCA tumor development and are higher in patients with longer overall survival. Furthermore, mutations on SIGIRR are associated with enhanced infiltration of the tumor by regulatory T cells and dendritic cells. Based on the qPCR validation experiments, BLCA epithelial cells express the IL-37c and IL-37e isoforms, while the latter is the predominant variant detected in tumor biopsies, also associated with higher grade and the non-muscle-invasive type. This is the first time, to the best of our knowledge, that IL-37 and SIGIRR levels have been assessed in BLCA tumor lesions, and associations with pathological and survival parameters are described, while a transcript variant-specific signature is indicated to have a diagnostic potential. These data strongly indicate the need for further investigation of the involvement of this cytokine and interconnected molecules in the pathophysiology of the disease and its prospective as a therapeutic target and biomarker for BLCA.

Evaluation of the Small Heat Shock Protein Family Members HSPB2 and HSPB3 in Bladder Cancer Prognosis and Progression.

Bladder cancer (BlCa) represents the sixth most commonly diagnosed type of male malignancy. Due to the clinical heterogeneity of BlCa, novel markers would optimize treatment efficacy and improve prognosis. The small heat shock proteins (sHSP) family is one of the major groups of molecular chaperones responsible for the maintenance of proteome functionality and stability. However, the role of sHSPs in BlCa remains largely unknown. The present study aimed to examine the association between HSPB2 and HSPB3 expression and BlCa progression in patients, and to investigate their role in BlCa cells. For this purpose, a series of experiments including reverse transcription-quantitative PCR, Western blotting, MTT assay and flow cytometry were performed. Initial analyses revealed increased vs. human transitional carcinoma cells, expression levels of the HSPB2 and HSPB3 genes and proteins in high grade BlCa cell lines. Therefore, we then evaluated the clinical significance of the HSPB2 and HSPB3 genes expression levels in bladder tumor samples and matched adjusted normal bladder specimens. Total RNA from 100 bladder tumor samples and 49 paired non-cancerous bladder specimens were isolated, and an accurate SYBR-Green based real-time quantitative polymerase chain reaction (qPCR) protocol was developed to quantify HSPB2 and HSPB3 mRNA levels in the two cohorts of specimens. A significant downregulation of the HSPB2 and HSPB3 genes expression was observed in bladder tumors as compared to matched normal urothelium; yet, increased HSPB2 and HSPB3 levels were noted in muscle-invasive (T2-T4) vs. superficial tumors (TaT1), as well as in high-grade vs. low-grade tumors. Survival analyses highlighted the significantly higher risk for post-treatment disease relapse in TaT1 patients poorly expressing HSPB2 and HSPB3 genes; this effect tended to be inverted in advanced disease stages (muscle-invasive tumors) indicating the biphasic impact of HSPB2, HSPB3 genes in BlCa progression. The pro-survival role of HSPB2 and HSPB3 in advanced tumor cells was also evident by our finding that HSPB2, HSPB3 genes expression silencing in high grade BlCa cells enhanced doxorubicin toxicity. These findings indicate that the HSPB2, HSPB3 chaperone genes have a likely pro-survival role in advanced BlCa; thus, they can be targeted as novel molecular markers to optimize treatment efficacy in BlCa and to limit unnecessary interventions.

28S rRNA-Derived Fragments Represent an Independent Molecular Predictor of Short-Term Relapse in Prostate Cancer.

Prostate cancer (PCa) is a global health concern, being a leading cause of cancer-related mortality among males. Early detection and accurate prognosis are crucial for effective management. This study delves into the diagnostic and prognostic potential of 28S rRNA-derived fragments (rRFs) in PCa. Total RNA extracted from 89 PCa and 53 benign prostate hyperplasia (BPH) tissue specimens. After 3'-end polyadenylation, we performed reverse transcription to create first-strand cDNA. Using an in-house quantitative real-time PCR (qPCR) assay, we quantified 28S rRF levels. Post-treatment biochemical relapse served as the clinical endpoint event for survival analysis, which we validated internally through bootstrap analysis. Our results revealed downregulated 28S rRF levels in PCa compared to BPH patients. Additionally, we observed a significant positive correlation between 28S rRF levels and higher Gleason scores and tumor stages. Furthermore, PCa patients with elevated 28S rRF expression had a significantly higher risk of post-treatment disease relapse independently of clinicopathological data. In conclusion, our study demonstrates, for the first time, the prognostic value of 28S rRF in prostate adenocarcinoma. Elevated 28S rRF levels independently predict short-term PCa relapse and enhance risk stratification. This establishes 28S rRF as a potential novel molecular marker for PCa prognosis.

The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer.

Genome-wide studies in tumor cells have indicated that chromatin-modifying proteins are commonly mutated in human cancers. The lysine-specific methyltransferase 2C (KMT2C/MLL3) is a putative tumor suppressor in several epithelia and in myeloid cells. Here, we show that downregulation of KMT2C in bladder cancer cells leads to extensive changes in the epigenetic status and the expression of DNA damage response and DNA repair genes. More specifically, cells with low KMT2C activity are deficient in homologous recombination-mediated double-strand break DNA repair. Consequently, these cells suffer from substantially higher endogenous DNA damage and genomic instability. Finally, these cells seem to rely heavily on PARP1/2 for DNA repair, and treatment with the PARP1/2 inhibitor olaparib leads to synthetic lethality, suggesting that cancer cells with low KMT2C expression are attractive targets for therapies with PARP1/2 inhibitors.

Unraveling UCA1 lncRNA prognostic utility in urothelial bladder cancer.

In the era of precision oncology, bladder cancer (BlCa) is characterized by generic patient management and lack of personalized prognosis and surveillance. Herein, we have studied the clinical significance of urothelial cancer associated 1 (UCA1) lncRNA in improving patients' risk stratification and prognosis. A screening cohort of 176 BlCa patients was used for UCA1 quantification. The Hedegaard et al. (n = 476) and The Cancer Genome Atlas (TCGA) provisional (n = 413) were analyzed as validation cohorts for non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. Patients' survival outcome was assessed using recurrence and progression for NMIBC or death for MIBC as clinical endpoint events. Bootstrap analysis was performed for internal validation of Cox regression analysis, whereas the clinical benefit of disease prognosis was assessed by decision curve analysis. UCA1 was significantly overexpressed in bladder tumors compared with normal urothelium, which was confirmed only in the case of NMIBC. Interestingly, reduced expression of UCA1 was correlated with muscle-invasive disease as well as with tumors of higher stage and grade. UCA1 loss was strongly associated with higher risk of short-term relapse [hazard ratio (HR) = 1.974; P = 0.032] and progression to invasive stages (HR = 3.476; P = 0.023) in NMIBC. In this regard, Hedegaard et al. and TCGA validation cohorts confirmed the unfavorable prognostic nature of UCA1 loss in BlCa. Finally, prognosis prediction models integrating UCA1 underexpression and established clinical disease markers contributed to improved stratification specificity and superior clinical benefit for NMIBC prognosis. Underexpression of UCA1 correlates with worse disease outcome in NMIBC and contributes to superior prediction of disease early relapse and progression as well as improved patient stratification specificity.

miR-221/222 cluster expression improves clinical stratification of non-muscle invasive bladder cancer (TaT1) patients' risk for short-term relapse and progression.

Clinical heterogeneity of bladder cancer prognosis requires the identification of bladder tumors' molecular profile to improve the prediction value of the established and clinically used markers. In this study, we have analyzed miR-221/222 cluster expression in bladder tumors and its clinical significance for patients' prognosis and disease outcome. The study included 387 tissue specimens. Following extraction, total RNA was polyadenylated at 3'-end and reversed transcribed. SYBR-Green based qPCR assays were performed for the quantification of miR-221/222 expression. Extensive statistical analysis was completed for the evaluation of miR-221/222 cluster's clinical significance. The expression of miR-221/222 is significantly downregulated in tumors compared to normal urothelium, while ROC curve and logistic regression analysis highlighted cluster's discriminatory ability. However, miR-222 levels were increased in muscle-invasive (T2-T4) compared to superficial tumors (TaT1), and in high compared to low-grade tumors. Kaplan-Meier survival curves and Cox regression analysis revealed the stronger risk of TaT1 patients overexpressing miR-222 for disease short-term relapse and progression following treatment. Moreover, multivariate Cox models highlighted the independent prognostic value of miR-222 overexpression for TaT1 patients' poor prognosis. Finally, the analysis of miR-222 expression improved significantly the positive prediction strength of the clinically used prognostic markers of tumor stage, grade, EORTC risk-stratification and recurrence at the first follow-up cystoscopy for TaT1 patients' outcome, and resulted to higher clinical net benefit following decision curve analysis. In conclusion, the expression of miR-221/222 cluster is deregulated in bladder tumors and miR-222 overexpression results to a superior positive prediction of TaT1 patients' short-term relapse and progression.

Loss of GAS5 tumour suppressor lncRNA: an independent molecular cancer biomarker for short-term relapse and progression in bladder cancer patients.

BACKGROUND: Bladder cancer (BlCa) heterogeneity and the lack of personalised prognosis lead to patients' highly variable treatment outcomes. Here, we have analysed the utility of the GAS5 tumour-suppressor lncRNA in improving BlCa prognosis. METHODS: GAS5 was quantified in a screening cohort of 176 patients. Hedegaard et al. (2016) (n = 476) and TCGA provisional (n = 413) were used as validation cohorts. Survival analysis was performed using recurrence and progression for NMIBC, or death for MIBC. Internal validation was performed by bootstrap analysis, and decision curve analysis was used to evaluate the clinical benefit on disease prognosis. RESULTS: GAS5 levels were significantly downregulated in BlCa and associated with invasive high-grade tumours, and high EORTC-risk NMIBC patients. GAS5 loss was strongly and independently correlated with higher risk for NMIBC early relapse (HR = 2.680, p = 0.011) and progression (HR = 6.362, p = 0.035). Hedegaard et al. and TCGA validation cohorts' analysis clearly confirmed the association of GAS5 loss with NMIBC worse prognosis. Finally, multivariate models incorporating GAS5 with disease established markers resulted in higher clinical benefit for NMIBC prognosis. CONCLUSIONS: GAS5 loss is associated with adverse outcome of NMIBC and results in improved positive prediction of NMIBC patients at higher risk for short-term relapse and progression, supporting personalised prognosis and treatment decisions.

Current Clinical Practice Guidelines for the Treatment of Renal Cell Carcinoma: A Systematic Review and Critical Evaluation.

The landscape of local and systemic therapy of renal cell carcinoma (RCC) is rapidly changing. The increase in the incidental finding of small renal tumors has increased the application of nephron-sparing procedures, while ten novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin pathways, or inhibiting the interaction of the programmed death 1 receptor with its ligand, have been approved since 2006 and have dramatically improved the prognosis of metastatic RCC (mRCC). These rapid developments have resulted in continuous changes in the respective Clinical Practice Guidelines/Expert Recommendations. We conducted a systematic review of the existing guidelines in MEDLINE according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement, aiming to identify areas of agreement and discrepancy among them and to evaluate the underlying reasons for such discrepancies. Data synthesis identified selection criteria for nonsurgical approaches in renal masses; the role of modern laparoscopic techniques in the context of partial nephrectomy; selection criteria for cytoreductive nephrectomy and metastasectomy in mRCC; systemic therapy of metastatic non-clear-cell renal cancers; and optimal sequence of available agents in mRCC relapsed after anti-VEGF therapy as the major areas of uncertainty. Agreement or uncertainty was not always correlated with the availability of data from phase III randomized controlled trials. Our review suggests that the combination of systematic review and critical evaluation can define practices of wide applicability and areas for future research by identifying areas of agreement and uncertainty among existing guidelines. IMPLICATIONS FOR PRACTICE: Currently, there is uncertainity on the role of surgery in MRCC and on the choice of available guidelines in relapsed RCC. The best practice is individualization of targeted therapies. Systematic review of guidelines can help to identify unmet medical needs and areas of future research.

Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.

PURPOSE: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. METHODS: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. RESULTS: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). CONCLUSION: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed.

Role of coagulation factors in urological malignancy: A prospective, controlled study on prostate, renal and bladder cancer.

OBJECTIVES: To study the behavior of specific coagulation factors in different types of non-metastatic urological cancers, and to identify their possible role as diagnostic and prognostic markers. METHODS: This was a prospective controlled study, which included three cancer patient groups and a control group of healthy individuals. The cancer subgroups consisted of renal (n = 44), prostate (n = 56) and bladder cancer (n = 47). We excluded patients receiving anticoagulant therapy, or with significant comorbidity. In all patients, certain coagulation parameters were measured (prothrombin time, international normalized ratio, partial thromboplastin time, D-dimers, fibrinogen, F1 + 2, thrombin-antithrombin complex). Statistical analysis was carried out to explore the association of hemostasis markers with tumor-nodes-metastasis stage, Gleason score, transitional cell carcinoma grade, Fuhrman grade and prostate-specific antigen. RESULTS: Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV). CONCLUSIONS: The coagulation pathway seems to be activated in urological malignancies. Specific panels of coagulation factors might play a role as screening or prognostic tools in earlier stages of renal, prostate and bladder cancer. Further research should also focus on their role in the association of cancer with thromboembolic events.

Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

Primary adenocarcinoma of the seminal vesicles. A review of the literature.

Primary adenocarcinoma of the seminal vesicles (SV) are extremely rare and approximately only 60 cases have been reported in the literature. Due to the lack of specific symptoms the patients often present in an advanced stage of their disease. The only clinical examination that can indicate the presence of a neoplasm in the SVs is the digital rectal examination (DRE). Serum prostatic specific antigen (PSA) and prostate specific acid phosphatase (PAP) are usually normal in patients with primary adenocarcinoma of the SV and only CA-125 can be proved a useful blood biomarker contributing to the diagnosis and the follow up of the SV adenocarcinoma. Computed tomography (CT) and magnetic resonance imaging (MRI) and FDG-PET/CT have been used for the diagnosis and the staging of the SV adenocarcinoma. Various combinations of radical surgery, radiotherapy androgen deprivation therapy and chemotherapy have been proposed for the management of the disease but the prognosis is poor and the mean survival is two years after the diagnosis.

In the search of novel urine biomarkers for the early diagnosis of prostate cancer. Intracellular or secreted proteins as the target group? Where and how to search for possible biomarkers useful in the everyday clinical practice.

OBJECTIVE: To search which category of proteins can be detected in urine in order to examine subsequently its ability to improve our accuracy for the diagnosis of Prostate Cancer (PCa) as biomarkers in clinical useful fluids like urine and serum. Material and method(s): Urine samples of 127 patients were obtained after a vigorous transrectal prostatic massage to both lobes. The patients were considered to have a high risk for PCa according to their PSA (> 4 ng/ml), their digital rectal examination (DRE) (positive for suspicious prostatic lesions) or to their abnormal PSA kinetics (PSA velocity (PSAV > 0.75 ng/mL). All patients subsequently were subjected to an extended 10-core per prostatic lobe TRUS-b (total 20 prostatic samples). The proteins that were chosen to be detected in the urine samples with Western-blot, as possible biomarkers, were Glutathione peroxidase 3 precursor (GPx3), Cofilin-1 (CFL1), Heat shock protein-90ß (HSP 90ß), Zinc alpha 2-glycoprotein (ZAG) and secreted protein acidic and rich in cysteine (SPARC).These proteins have been detected previously in the prostatic tissue by proteomics proving their discriminative ability between patients with prostate cancer and benign prostatic hyperplasia. RESULT(S): From the five proteins, only the secreted Zinc alpha 2-glycoprotein was detected in urine showing a promising ability in the improvement of our diagnostic accuracy for the early diagnosis of prostate cancer. CONCLUSIONS: From various categories of proteins that have already been detected in the tissue of prostate by proteomics, only secreted protein Zinc alpha 2-glycoprotein showed a clear signal in the urine, proving its discriminative potential for the early diagnosis of PCa.

Uncovering the clinical utility of miR-143, miR-145 and miR-224 for predicting the survival of bladder cancer patients following treatment.

Accurate prognosis is a key factor in establishing optimal therapeutic decisions; yet in the case of bladder cancer (BlCa) current prognostic indicators cannot ensure optimal disease management. Here, we aimed to evaluate the previously unexplored clinical potential of the urological cancer-related miR-145, miR-143 and miR-224 in BlCa. A total of 279 bladder tissue specimens were included in this study (133 BlCa, 107 adjacent normal and 39 healthy samples). Total RNA was extracted from tissues, it was polyadenylated and reverse transcribed to cDNA. The expression of target molecules was measured via quantitative real-time PCR. The expression levels of both miR-143 and miR-145 were significantly decreased, whereas those of miR-224 were increased in BlCa. Receiver operating characteristic curve analysis indicated a significant discriminatory capacity for miR-143/miR-145 levels. Important associations with disease aggressiveness were observed for all three microRNAs; elevated levels were observed in tumors of higher stage and grade, as well as in 'high-risk' TaT1 patients. More importantly, high miR-143/145 levels could effectively prognose inferior overall survival for muscle-invasive patients and could independently predict the progression of superficial tumors. Finally, the combination of miR-143/145 overexpression with the widely used prognostic markers of European Organization for Research and Treatment of Cancer-risk groups or recurrence at the first follow-up cystoscopy resulted to a superior positive prediction of non-muscle-invasive bladder cancer short-term progression compared with the use of the abovementioned markers alone. The cancer-related miR-143, miR-145 and miR-224 were investigated for the first time in the clinical setting of BlCa, and miR-143/145 cluster constitutes a novel marker helpful for providing an enhanced prediction of oncologic outcome for BlCa patients.

Change of practice patterns in urology with the introduction of the Da Vinci surgical system: the Greek NHS experience in debt crisis era.

OBJECTIVE: To determine the attitudinal change for urologic surgery in Greece since the introduction of the da Vinci Surgical System (DVS). We describe contemporary trends at public hospital level, the initial Greek experience, while at the same time Greece is in economic crisis and funding is under austerity measures. MATERIALS AND METHODS: We retrospectively analyzed annualized case log data on urologic procedures, between 2008 (installation of the DVS) and 2013, from "Laiko'' Hospital in Athens. We evaluated, using summary statistics, trends and institutional status regarding robot-assisted surgery (RAS). We also analyzed the relationship between the introduction of RAS and change in total volume of procedures performed. RESULTS: 1578 of the urological procedures performed at "Laiko'' Hospital were pooled, 1342 (85%) being open and 236 RAS (15%). We observed a 6-fold increase in the number of RAS performed, from 7% of the total procedural volume (14/212) in 2008 to 30% (96/331) in 2013. For radical prostatectomy, in 2008 2% were robot-assisted and 98% open while in 2013, 46% and 54% respectively. Pyeloplasty was performed more often using the robot-assisted method since 2010. RAS-dedicated surgeons increased both RAS and the total number of procedures they performed. From 86 in 2008 to 145 in 2013, with 57% of them being RAS in 2013 as compared to 13 % in 2008. CONCLUSIONS: Robot-assisted surgery has integrated into the armamentarium for urologic surgery in Greece at public hospital level. Surgical robot acquisition is also associated with increased volume of procedures, especially prostatectomy, despite the ongoing debate over cost-effectiveness, during economic crisis and International Monetary Fund (IFN) era.

A two staged treatment procedure for the difficult to treat bladder neck contractures with concomitant incontinence. In the search of a solution to a complex problem.

OBJECTIVE: To examine the efficacy of a two staged treating strategy with the use of a non-permanent urethral ALLIUM(®) stent for the management of recurrent bladder neck stenosis and subsequently the use of an artificial sphincter AUS800(®) by AMS for the management of the incontinence. MATERIALS AND METHODS: We progressively identified patients eligible for the study creating a population of cases with recurrent bladder neck stenosis and concomitant incontinence occurring after the last intervention for the stenosis. Efficacy for the treatment of the stenosis was defined as no recurrence both prior and post to the sphincter placement and efficacy for the treatment of the incontinence was defined as continence (0-1pads) after the sphincter placement. RESULTS AND LIMITATIONS: 14 white males with a mean age of 66.21, ranging from 59 to 73 years consisted the population of the study. All patients had severe stress incontinence following the last transurethral resection. The efficacy of the treatment of the bladder neck stenosis was 93% (13/14) while the efficacy for the treatment of the incontinence was 100%. A single patient had a recurrent bladder neck stenosis after the artificial sphincter placement and was treated with transurethral resection using a long pediatric 13 F resectoscope at 12 months. Our limitations is the absence of a control group and the small number of patients enrolled, with a relatively short time of follow up. CONCLUSIONS: In our series we propose the use of a non-permanent urethral ALLIUM(®) stent for 6 months in order to control the growth of fibrotic scar tissue, a further 6 months follow up for recurrence, and then placement of an artificial sphincter. The results are very promising both on stabilizing the vesicourethral stenosis, and on patient safety and tolerability.

Correcting and sharing our complications. Misplacement of pigtail catheter, during a Robot Assisted Pyeloplasty. Clinical findings, diagnosis, possible causes and endoscopic treatment.

OBJECTIVE: Robotic assisted pyeloplasty (RAP) is rapidly adopted by surgeons around the world. We present a unique complication of the technique, consisting of pigtail misplacement, which was endoscopically resolved. We discuss the clinical findings, differential diagnosis and principles of endoscopic treatment. MATERIALS AND METHODS: A 41 years old female patients underwent transperitoneal right side RAP with the Hynes-Anderson technique for ureteropelvic junction obstruction. Pigtail was placed intraoperatively in an antegrade fashion. Post operative course appeared normal but Kidney-Ureterer-Bladder(KUB) X-ray, revealed a misplaced pigtail. Patient underwent a semirigid ureterorenoscopy demonstrating that the pigtail was exiting the collecting system in the rear line of suturing between continuous sutures. Pigtail was retrieved with a stone retrieval forceps with short upward motions in the renal pelvis under fluoroscopy and then removed from patient, in order to avoid stressing the anastomosis. No leakage was noted in fluoroscopy, a pigtail was correctly placed and patient recovery was uneventful. RESULTS: Retrograde pyelography was the key to accurate diagnosis and endoscopic treatment, because the exact point of exit and anastomosis integrity were established. Retrieval of the pigtail was the most challenging part. Lack of proper visualization and mobilization of the rear part of the anastomosis during surgery, combined with lack of tactile feedback, because of robotic instrumentation, were of critical importance in the manifestation of such a mishap. Endoscopy facilitated case resolve, but proper handling is required to protect the anastomosis. CONCLUSIONS: The introduction of novel techniques can carry the burden of novel complications. A surgeon must always keep in mind the complications inherent to the technique and at the same time the limitations of the equipment used, especially the lack of tactile feedback in robotic instrumentation.