Robotic-assisted microsurgery in andrology: a systematic review.

Robot-assisted surgery is the gold standard of treatment in many fields of urology. In this systematic review, we aim to report its usage in andrology and to evaluate any advantages. A systematic search of the PubMed and Cochrane Library databases was conducted to identify articles referring to robotic-assisted microsurgery in andrology. The search strategy was in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook. The articles were then reviewed by two authors. A qualitative analysis of the articles that met the inclusion criteria was performed. Thirty-one articles that met the inclusion criteria were reviewed. The first results for robot-assisted vasovasostomy (RAVV) are encouraging as excellent patency rates, short operative times, and learning curves were achieved. Interestingly, patency rates were greater in some case series for RAVV than for microsurgical vasovasostomy, with a statistically significant difference. In addition, robot has been shown to be of great use in bypassing fibrotic changes in cases of iatrogenic vasal injuries, difficulties encountered with traditional microsurgery. In addition, the feasibility of robot-assisted microsurgery has been proven for varicocelectomy and microsurgical denervation of the spermatic cord, with acceptable improvement in sperm parameters and pain, respectively. The current evidence suggests that there are potential advantages of the use of robots in andrology. However, for robotic surgery to become incorporated into the daily use of the andrologists, large, multicenter randomized trials are needed. As robotics systems are becoming standard in urology practice, it is reasonable for one to believe that they will also find their place in andrology.

ΔNp63 transcript loss in bladder cancer constitutes an independent molecular predictor of TaT1 patients post-treatment relapse and progression.

PURPOSE: Bladder cancer represents a major cause of malignancy-related morbidity and the most expensive per-patient-to-treat cancer, due to the lifelong surveillance of the patients. Accurate disease prognosis is essential in establishing personalized treatment decisions; yet optimum tools for precise risk stratification remain a competing task. In the present study, we have performed the complete evaluation of TP63 clinical significance in improving disease prognosis. METHODS: The levels of ΔNp63 and TAp63 transcripts of TP63 were quantified in 342 bladder tissue specimens of our screening cohort (n = 182). Hedegaard et al. (Cancer Cell 30:27-42. doi:10.1016/j.ccell.2016.05.004, 2016) (n = 476) and TCGA provisional (n = 413) were used as validation cohorts for NMIBC and MIBC, respectively. Survival analysis was performed using recurrence and progression for NMIBC or mortality for MIBC as endpoint events. Bootstrap analysis was performed for internal validation, while decision curve analysis was used for the evaluation of the clinical net benefit on disease prognosis. RESULTS: ΔNp63 was significantly expressed in bladder tissues, and was found to be over-expressed in bladder tumors. Interestingly, reduced ΔNp63 levels were correlated with muscle-invasive disease, high-grade tumors and high-EORTC-risk NMIBC patients. Moreover, ΔNp63 loss was independently associated with higher risk for NMIBC relapse (HR = 2.730; p = 0.007) and progression (HR = 7.757; p = 0.016). Hedegaard et al. and TCGA validation cohorts confirmed our findings. Finally, multivariate models combining ΔΝp63 loss with established prognostic markers led to a superior clinical benefit for NMIBC prognosis and risk stratification. CONCLUSIONS: ΔΝp63 loss is associated with adverse outcome of NMIBC resulting in superior prediction of NMIBC early relapse and progression.

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.

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.

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.

High grade myofibroblastic sarcoma of paratesticular soft tissues.

Tumors of the paratesticular region most often arise from the soft tissue surrounding the spermatic cord and the epididymis or from the soft tissue (dartos muscle) of the scrotal wall. Paratesticular tumors, despite their rarity, present a high incidence of malignancy (30%), and the therapeutic approach of choice is surgical resection with negative margin. The grade, the histology type, the presence of metastases during the diagnosis, the size of the tumor, the age of the patients, and the surgical margins are all important prognostic factors. We present a case report of a 86-year-old patient with a high grade paratesticular and scrotum sarcoma of soft tissues which was presented as a hard painful mass of the scrotum. The patient was subjected to high ligation of the spermatic cord and received no further treatment and 6 months after the operation no local or systematic recurrence was observed.

Metastasis to sartorius muscle from a muscle invasive bladder cancer.

Bladder cancer constitutes the ninth most common cancer worldwide and approximately only 30% of cases are muscle invasive at initial diagnosis. Regional lymph nodes, bones, lung, and liver are the most common metastases from bladder cancer and generally from genitourinary malignancies. Muscles constitute a rare site of metastases from distant primary lesions even though they represent 50% of total body mass and receive a large blood flow. Skeletal muscles from urothelial carcinoma are very rare and up to date only few cases have been reported in the literature. We present a rare case of 51-year-old patient with metastases to sartorius muscle 8 months after the radical cystectomy performed for a muscle invasive bladder cancer.