The Prognostic Value of the Circulating Tumor Cell-Based Four mRNA Scoring System: A New Non-Invasive Setting for the Management of Bladder Cancer.

Bladder cancer (BC) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to the search for new biomarkers and strategies. Our pilot study aimed to identify a prognostic gene signature in circulating tumor cells (CTCs) isolated by ScreenCell devices from muscle invasive and non-muscle invasive BC patients. Through the PubMed database and Cancer Genome Atlas dataset, a panel of 15 genes modulated in BC with respect to normal tissues was selected. Their expression was evaluated in CTCs and thanks to the univariate and multivariate Cox regression analysis, EGFR, TRPM4, TWIST1, and ZEB1 were recognized as prognostic biomarkers. Thereafter, by using the risk score model, we demonstrated that this 4-gene signature significantly grouped patients into high- and low-risk in terms of recurrence free survival (HR = 2.704, 95% CI = 1.010−7.313, Log-rank p < 0.050). Overall, we identified a new prognostic signature that directly impacted the prediction of recurrence, improving the choice of the best treatment for BC patients.

Diagnostic performance of the Bladder EpiCheck methylation test and photodynamic diagnosis-guided cystoscopy in the surveillance of high-risk non-muscle invasive bladder cancer: A single centre, prospective, blinded clinical trial.

PURPOSE: Currently, bladder cancer (BC) surveillance consists of periodic white light cystoscopy and urinary cytology (UC). However, both diagnostic tools have limitations. Therefore, to improve the management of recurrent BC, novel, innovative diagnostic tests are needed. The primary aim of this study was to determine the diagnostic performance of Bladder EpiCheck (BE) and photodynamic diagnosis (PDD) guided cystoscopy in the surveillance of high-risk BC. A secondary aim was to compare Bladder EpiCheck (BE) and PDD-guided cystoscopy findings with whose of UC to design a diagnostic algorithm that facilitates clinical decision making. PATIENTS AND METHODS: This was a prospective, blinded, single-arm, single-visit cohort study. All patients were under surveillance for high-risk non-muscle-invasive bladder cancer, and underwent cystoscopy with PDD and a BE test. Those who received a histological diagnosis were used as a reference population. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of BE, PDD-guided cystoscopy, and UC for identifying biopsy-confirmed BC lesions. The diagnostic power of the test was assessed by determining the area under the curve (AUC). RESULTS: Forty patients were enrolled. For BE, the AUC was 0.95, and BC recurrence was detected at a sensitivity of 100% and specificity of 90.9%. For PDD, the AUC was 0.51, with a sensitivity and specificity of 61% and 41%, respectively. BE was combined with UC to create a decision-making algorithm capable of reducing the number of follow-up cystoscopies needed. CONCLUSION: BE is a very accurate diagnostic tool that has the potential to be useful in the surveillance of high-risk BC patients. Especially when combined with UC, it may be used to reduce the number of cystoscopies needed throughout follow-up. Conversely, the use of PDD as a diagnostic tool in such patients should be reconsidered. However, due to the small sample size of this study, a larger prospective clinical trial should be performed to confirm findings.

Correlation between High PD-L1 and EMT/Invasive Genes Expression and Reduced Recurrence-Free Survival in Blood-Circulating Tumor Cells from Patients with Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: PD-L1 represents a crucial immune checkpoint molecule in the tumor microenvironment, identified as a key target for cancer immunotherapy. A correlation between PD-L1 and EMT-related genes expression in various human cancers has been suggested. METHODS: By ScreenCell filtration, digital droplet PCR and confocal microscopy analysis, we aimed to investigate the expression of PD-L1 and EMT/invasive genes (TWIST1, ZEB1, VIMENTIN, TIMP2) in circulating tumor cells (CTCs) collected from the blood of non-muscle-invasive bladder cancer (NMIBC) patients, assessing the prognostic value of these biomarkers in the disease. Welchs' test and Mann-Whitney U test, correlation index, Kaplan-Meier, Univariate and Multivariate Cox hazard proportional analysis were used. RESULTS: Higher PD-L1, TIMP2 and VIM mRNA levels were found in pT1 compared to pTa NMIBC. As evaluated by Kaplan-Meier and Univariate and Multivariate Cox analysis, enhancement of PD-L1, TWIST1 and TIMP2 expression reduces the recurrent free survival in NMIBC patients. CONCLUSIONS: High PD-L1, TWIST1 and TIMP2 mRNAs mark the recurrent-NMIBC patients and by reducing the RFS represent negative prognostic biomarkers in these patients.

Holmium:YAG Laser for the Treatment of Genital and urethral Warts: Multicentre Prospective Evaluation of Safety and Efficacy.

Introduction: Genital condylomatosis is a highly contagious disease caused by the human papilloma virus (HPV). The aim of this prospective multicentre study was to evaluate the safety and efficacy of the Holmium:YAG (yttrium-aluminium-garnet) laser in the treatment of genital and intra-urethral warts; the secondary aim was to assess the patients' postoperative satisfaction and cosmetic results. Methods: From December 2016 to March 2019, patients with genital warts were prospectively enrolled in three hospitals. The inclusion criteria were male gender, age over 18 years-old and treatment-naïve. External and urethral genitalia warts were treated by the Holmium YAG laser. The follow-up analysis consisted of physical examination, flexible urethro-cystoscopy in case of meatal lesions, and administration of Dermatology Quality of Life Index (DLQI) and Patient Global Impression of Improvement (PGI-I) questionnaires at 1, 3, 6 and 12 months after surgery and subsequently yearly. Results: Sixty patients were enrolled. The single treatment was effective in 57/60 patients (95%). At a mean follow-up of 26 months, recurrences occurred in 8 patients (13.3%). No peri- or post-operative complication occurred. An improvement in pre-operative condition was highlighted with PGI-I and DLQI questionnaires. Conclusion: Our prospective multicentre study showed that holmium laser surgery seems to be a safe and effective treatment for external genital and urethral warts. Good dermatological outcomes aid to further improve patient satisfaction.

Influence of COVID-19 pandemic on stress levels of urologic patients.

INTRODUCTION: Several studies have shown the consequences of COVID-19 pandemic on perceived stress of different populations, but none of them analyzed urological patients who underwent elective surgery. METHODS: We enrolled prospectively patients who underwent elective surgery between March and October 2020. A survey on COVID-19 and the 4-item Perceived Stress Scale (PPS-4) questionnaire were administered at hospital admission. Demographic and medical history data were also collected. Uni- and multivariate analyses were performed to identify independent predictors of higher PSS-4 values (≥7). RESULTS: A total of 200 patients were enrolled. Mean PSS-4 value resulted 6.04. Patients with PSS-4 value ≥7 resulted 43.5% (87/200). In multivariate analysis, PSS-4 value ≥7 was independently associated (p < 0.05) with female gender (OR 6.42), oncological disease (OR 2.87), high (>5 in a range between 0 and 10) fear of intrahospital transmission of SARS-CoV-2 infection (OR 4.75), history of bladder instillation (OR 0.26), and current smokers (OR 0.27). CONCLUSION: High PSS-4 values at hospital admission in urologic surgical patients are positively correlated with female gender, fear of intrahospital transmission of SARS-CoV-2 infection, and oncological disease. PSS-4 questionnaire could be useful to select patients for whom a preadmission counselling is necessary to improve the management of their high stress level.

Detection of urinary miRNAs for diagnosis of clear cell renal cell carcinoma.

The lack of symptoms at the early stages of clear cell renal cell carcinoma (ccRCC) allows the tumour to metastasize, leading to a dramatic reduction in patient survival. Therefore, we studied and set up a method based on urinary microRNAs (miRNAs) for the diagnosis of ccRCC. First, miRNA expression in ccRCC specimens and kidney tissues from healthy subjects (HSs) was investigated through analysis of data banks and validated by comparing expression of miRNAs in ccRCC and adjacent non-cancerous kidney tissue specimens by RT-qPCR. Subsequently, we developed an algorithm to establish which miRNAs are more likely to be found in the urine of ccRCC patients that indicated miR-122, miR-1271, and miR-15b as potential interesting markers. The evaluation of their levels and three internal controls in the urine of 13 patients and 14 HSs resulted in the development of a score (7p-urinary score) to evaluate the presence of ccRCC in patients. The resulting area under the Receiver Operating Characteristic (ROC) curve, sensitivity, and specificity were equal to 0.96, 100% (95% CI 75-100%), and 86% (95% CI 57-98%), respectively. In conclusion, our study provides a proof of concept that combining the expression values of some urinary miRNAs might be useful in the diagnosis of ccRCC.

Surgical wound closure by staples or sutures?: Systematic review.

AIM: To compare the effects of sutures and staples for skin closure of surgical wounds. MATERIAL AND METHODS: We included published and unpublished randomized controlled trials (RCTs) and cluster-randomized trials comparing staples with sutures. Patients were adults (aged 18 years or over) who had undergone any type of surgery. The primary outcomes were risk of overall and severe wound infection. Secondary outcomes included length of hospital stay, readmission rate, adverse events, patient satisfaction with cosmetic results, postoperative pain. RESULTS: Forty-two very low to low quality RCTs with a total of 11,067 patients were included. Sutures resulted in slightly fewer overall wound infections (4.90%) compared to staples (6.75%) but it is uncertain whether there is a difference between the groups (risk ratio [RR] 1.20, 95% confidence intervals [CI] 0.80-1.79; patients = 9864; studies = 34; I = 70%). The evidence was also insufficient to state a difference in terms of severe wound infection (staples 1.4% vs sutures 1.3%; RR 1.08, 95% CI 0.61-1.89; patients = 3036; studies = 17; I = 0%), grade of satisfaction (RR 0.99, 95% CI 0.91-1.07; patients = 3243; studies = 14; I = 67%) and hospital stay. Staples may increase the risk of adverse events (7.3% for staples vs 3.5% for sutures; RR 2.00, 95% CI 1.44-2.79; patients = 6246; studies = 21; I = 33%), readmission rate (RR 1.28, 95% CI 0.18-9.05; patients = 2466; studies = 5; I = 66%) and postoperative pain (standardized mean difference [SMD] 0.41,95%CI -0.35 to 1.16; I = 88%, patients = 390 patients, studies = 5). CONCLUSIONS: Due to the lack of high quality evidence, we could not state if sutures are better than staples in terms of wound infection, readmission rate, adverse events, and postoperative pain. With a low quality of evidence, sutures reduce postoperative pain and improve grade of satisfaction with the cosmetic outcome.

Role of miRNAs in prostate cancer: Do we really know everything?

Many different genetic alterations, as well as complex epigenetic interactions, are the basis of the genesis and progression of prostate cancer (CaP). This is the reason why until now the molecular pathways related to development of this cancer were only partly known, and even less those that determine aggressive or indolent tumour behaviour. MicroRNAs (miRNAs) represent a class of about 22 nucleotides long, small non-coding RNAs, which are involved in gene expression regulation at the post-transcriptional level. MiRNAs play a crucial role in regulating several biological functions and preserving homeostasis, as they carry out a wide modulatory activity on various molecular signalling pathways. MiRNA genes are placed in cancer-related genomic regions or in fragile sites, and they have been proven to be involved in the main steps of carcinogenesis as oncogenes or oncosuppressors in many types of cancer, including CaP. We performed a narrative review to describe the relationship between miRNAs and the crucial steps of development and progression of CaP. The aims of this study were to improve the knowledge regarding the mechanisms underlying miRNA expression and their target genes, and to contribute to understanding the relationship between miRNA expression profiles and CaP.

Uroflow stop test with electromyography: a novel index of urinary continence recovery after RARP.

PURPOSE: Urinary incontinence (UI) is one of the most bothersome surgical side effects after robot-assisted radical prostatectomy (RARP). Alteration of both smooth and striate urethral sphincter occurs after RARP. Since the contraction of perineal muscles is involved in the complex mechanism of urinary continence, the uroflow stop test (UST) seems to predict early continence recovery after RARP. The UST was added of perineal surface electromyography (EMG) evaluation to evaluate the latency time (LT) between muscular contraction and the complete stop of urine flow. Our aim was to present UST-EMG as a new tool in the investigation of UI, implying pelvic floor integrity, and to evaluate whether an early return (≤ 3 months) to preoperative LT could be associated with early recovery of UC (≤ 3 months). METHODS: After prospectively enrolling 137 patients who underwent RARP with a minimum follow-up of 6 months, we identified two groups: Group 1 (93 patients) with early (≤ 3 months) pre-surgical LT recovery and Group 2 (44 patients) with late > 3 months or not able to reach pre-surgical LT recovery. RESULTS: Between the two groups, there were significant differences in terms of different surgical technique (nerve-sparing versus non-nerve-sparing) and pads use at 3 and 6 months after RARP (p < 0.05). No differences were recorded neither in postoperative maximum flow-rate, nor in postoperative symptoms score. CONCLUSIONS: UST with EMG can be considered as a noninvasive, reproducible and easily performable tool. LT is applicable in the clinical evaluation to predict urinary continence recovery after RARP.