Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome.

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5-8% of all kidney cancer cases and is associated with syndromes such as von Hippel-Lindau syndrome, Birt-Hogg-Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available.

Robotic bladder diverticulectomy with concurrent management of bladder outlet obstruction: A choice to consider.

INTRODUCTION: Acquired bladder diverticula (BD) are associated with bladder outlet obstruction. The aim of our study is to analyse the improvement in lower urinary tract symptoms (LUTS) in patients who underwent robot-assisted bladder diverticulectomy (RABD) combined with transurethral prostatectomy (TURP). MATERIAL AND METHODS: A prospectively single-centre, single surgeon cohort of four patients with posterolateral BD due to bladder outlet obstruction (BOO) undergoing RABD combined with TURP between 2018 and 2023 was analysed. RESULTS: Median age and maximum BD diameter were 73.5 years and 16 cm, respectively. All patients had severe LUTS and elevated postvoid residual (PVR). Preliminary uroflowmetry revealed bladder outlet obstruction with a median of maximum urine flow rate of 8.5 ml/s. The median operative time and blood loss were 212 min and 100 ml, respectively. No intraoperative complications were recorded. The median length of stay was 4 days. The International Prostate Symptom Score (IPSS) and PVR were compared between baseline, 1 month and 6 months after surgery. IPSS significantly decreased from 24 (IQR 24-25) preoperatively compared to the postoperative, at 1 month follow up 7 (IQR 6-8) (p < 0.0001). PVR significantly decreased too from 165 (IQR 150-187) to 35 ml (IQR 25-42) (p < 0.0001). In transitioning from the 1-month follow-up to the 6-month follow-up, no substantial statistical improvement was observed. CONCLUSION: Concomitant performance of TURP with RABD is feasible and safe. Diverticulectomy in addiction at the endoscopic procedure should be discussed with patients who have obstructive lower urinary tract symptoms as viable alternative to single procedure individually performed.

Metastatic Castration-Resistant Prostate Cancer: Insights on Current Therapy and Promising Experimental Drugs.

The therapeutic landscape of metastatic hormone sensitive and metastatic castration-resistant prostate cancer (mCRPC) is rapidly changing. We reviewed the current treatment options for mCRPC, with insights on new available therapeutic strategies. Chemotherapy with docetaxel or cabazitaxel (for patients progressing on docetaxel), as well as treatment with androgen receptor axis targeted therapies, and Radium-223 are well-established treatment options for patients with mCRPC. The advent of theragnostic in prostate cancer established Lutetium-177 (177Lu)-PSMA-617 as a new standard of care for PSMA-positive mCRPC previously treated with ARAT and taxane-based chemotherapy. Olaparib, a poly-ADP-ribose polymerase (PARP) inhibitor, is approved for selected patients with mCRPC progressed on ARATs and in combination with abiraterone acetate as first-line treatment for mCRPC. Immunotherapy showed limited efficacy in unselected patients with mCRPC and novel immunotherapy strategies need to be explored. The search for biomarkers is a growing field of interest in mCRPC, and predictive biomarkers are needed to support the choice of treatment and the development of tailored strategies.

Management of Urinary Incontinence Following Radical Prostatectomy: Challenges and Solutions.

Urinary incontinence is a common and debilitating problem in patients undergoing radical prostatectomy. Current methods developed to treat urinary incontinence include conservative treatments, such as lifestyle education, pelvic muscle floor training, pharmacotherapy, and surgical treatments, such as bulking agents use, artificial urinary sphincter implants, retrourethral transobturator slings, and adjustable male sling system. Pelvic floor muscle exercise is the most common management to improve the strength of striated muscles of the pelvic floor to try to recover the sphincter weakness. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and a-adrenergic drugs have been proposed as medical treatments for urinary incontinence after radical prostatectomy. Development of new surgical techniques, new surgical tools and materials, such as male slings, has provided an improvement of outcomes after UI surgery. Such improvement is still ongoing, and the uptake of new devices might lead to even better outcomes after UI surgery.