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Prostate cancer therapy for locally advanced and metastatic diseases includes androgen deprivation therapy (ADT). Second-generation antiandrogens have a role in castration-resistant prostate cancer. Nevertheless, some patients do not respond to this therapy, and eventually all the patients became resistant. This is due to modifications to intracellular signaling pathways, genomic alteration, cytokines production, metabolic switches, constitutional receptor activation, overexpression of some proteins, and regulation of gene expression. The aim of this review is to define the most important mechanisms that drive this resistance and the newest discoveries in this field, specifically for enzalutamide and abiraterone, with potential implications for future therapeutic targets. Furthermore, apalutamide and darolutamide share some resistance mechanisms with abiraterone and enzalutamide and could be useful in some resistance settings.

Robot-assisted radical prostatectomy (RARP) is the most adopted treatment for localized prostate cancer. The aim of this study was to explore the learning curves (LC) for overall and site-specific positive surgical margins (PSM) occurrence after RARP of multiple surgeons within a step-structured mentor-initiated training program. The study included consecutive patients undergoing RARP between January 2013 and March 2020, by three surgeons: a mentor and his two trainees. Prospectively collected patients’ data were retrospectively analyzed. The cumulative summation (CUSUM) method was used to generate the LCs, with turning points indicating the number of cases to reach proficiency levels. Furthermore, the association between PSM and surgical experience was evaluated, adjusting for case mix. A total of 761 consecutive patients were included, 370 treated by the Mentor surgeon, 247 and 144 treated, respectively, by the two Trainees. Mentor and Trainees had similar PSM rates (31.6% vs 28.0% vs 31.3%, p  = 0.6). CUSUM charts showed different LC shapes for different PSM locations (postero-lateral, bladder neck, apex, and multifocal/> 3 mm). Surgical experience was significantly associated with overall, postero-lateral, and multifocal/> 3 mm PSMs, in the Mentor series only. Trainees reached their turning points after far fewer cases then the Mentor, both for overall (12 and 31 vs 153), postero-lateral (24 and 30 vs 120), and multifocal/> 3 mm PSMs (9 and 31 vs 153). The achievement of stable SM proficiency takes involved different LCs depending on the prostatic location being considered. Monitoring site-specific LC can indicate the surgical steps for which there may be still room for further technical refinements, even when an apparent proficiency status seems achieved.

Purpose The knowledge of periprostatic nerve fiber (pNF) is still incomplete by means of conventional MRI. The purpose of our study was to demonstrate if DTI imaging is able to depict anatomical features of pNF. Methods For this retrospective study, fifty-six patients (mean age 63.5 years), who underwent 1.5-T prostate MRI, including 32 directions DTI, were enrolled between October 2014 and December 2018. ANOVA test and Student’s t -test were performed between the mean values of the number, FA values, and fiber length of pNF between base and mid-gland, mid-gland and apex, base and apex, right and left side, and anterior and posterior face of the prostate. A qualitative analysis was performed to detect the main orientation of pNF through a colorimetric 3D tractographic reconstruction. Results The number of pNF showed a decrease from the base (322) to mid-gland (248) and apex (75) ( p  < 0.05). The FA values were higher at base and mid-gland (0.435 and 0.456) compared to the apex (0.313) (p < 0.05). The length of pNF was higher at apex (13.4 mm) compared to base (11.5 mm) and mid-gland (11.7 mm) ( p  < 0.05). The number of pNF was higher on the posterior face compared to the anterior face at base (186 vs 137), ( p  < 0.001). The FA values were higher on the posterior face compared to the anterior face at base (0.452 vs 0.417), mid-gland (0.483 vs 0.429), and apex (0.42 vs 0.382), ( p  < 0.05). The length of the pNF was higher in the posterior (14.7 mm) than in the anterior face (12 mm) at apex ( p < 0.001). The main orientation of pNF was longitudinal in all patients (56/56, 100%). Conclusions DTI imaging has been demonstrated able to depict anatomical features of pNF.

Background Bladder leiomyosarcoma is the most frequent mesenchymal neoplasm of the bladder. However, the rarity of the disease and some morphological aspects could give serious problems to differential diagnosis. Case presentation A 86-year-old male patient was referred to our institution to undergo endoscopic low-urinary-tract re-evaluation 2 months after the detection of a “low-grade urothelial neoplasia” in urinary cytology. A TURBT (transurethral resection of bladder tumor) was performed and revealed a tumor extending for 3.5 cm with thin stalk peduncle on the left lateral wall of the bladder, cephalad and lateral to the left ureteral orifice. The exophytic part of the tumor was resected with the underlying bladder wall. Histologically, the tumor showed a quite complex pattern, composed of spindle cells, with often invasion to the surrounding bladder muscular wall, and the presence of numerous multinucleated, osteoclast-like giant cells, scattered throughout the neoplasia. Conclusions Here we report a unique case of urinary bladder leiomyosarcoma with osteoclast-like multinucleated giant cells (OGCs). These cells, confounding the morphological aspect, indeed showed an immunohistochemical phenotype of non-neoplastic origin (most likely a histiocyte/macrophage differentiation). We feel that the presence of the OGCs within this tumor is reactive. Nevertheless, more research is necessary to understand the role of OGCs in urinary bladder tumors and leiomyosarcoma, in paticular.

Introduction Complete ureteral avulsion represents a rare and fearsome complication of ureteroscopy, reported in less than 1% of cases. In literature there are few reports and different options are presented for its treatment. We present a case of a ureteral avulsion managed with ileal ureter replacement. Case presentation A 67‐year‐old man with a left proximal ureter stone was treated at our department with ureteroscopy. During retrieval of the instrument a complete ureteral avulsion was discovered, with a so‐called “scabbard lesion”. We decided to proceed with immediate laparotomy and we performed a ileal ureter replacement. Conclusion Ureteral avulsion is a rare complication but must be known as a possible complication in high volume center. There is no standard definition regarding its treatment, and in our experience immediate treatment with ileal ureter replacement proved to be safe and effective without any changes in renal function.

To identify the possible complications after extracorporeal shock wave lithotripsy (SWL) and to suggest how to manage them, the significant literature concerning SWL treatment and complications was analyzed and reviewed. Complications after SWL are mainly connected to the formation and passage of fragments, infections, the effects on renal and nonrenal tissues, and the effects on kidney function. Each of these complications can be prevented adopting appropriate measures, such as the respect of the contraindications and the recognition and the correction of concomitant diseases or infection, and using the SWL in the most efficient and safe way, tailoring the treatment to the single case. In conclusion, SWL is an efficient and relatively noninvasive treatment for urinary stones. However, as with any other type of therapy, some contraindications and potential complications do exist. The strictness in following the first could really limit the onset and danger of the appearance of others, which however must be fully known so that every possible preventive measure be implemented.

Introduction: Radical surgery is the \"gold standard\" for treatment of invasive penile carcinoma but very poor aesthetic, functional and psychological outcomes have been reported. Our purpose was to assess the impact of organ potency-sparing surgery in locally confined carcinoma of the penis. Materials and Methods: We evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2), treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of cavernosal apexes, or glandulectomy and limited apical resection in cases of Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15 questionnaire before the appearance of neoplasia (about three months before the surgery) and six months after surgery. Quality of life was evaluated by the Bigelow-Young questionnaire. The scores relating to two weeks prior to the surgery have been compared to those obtained six months after surgery. The statistical analysis was conducted using t-Student for repeated measures and analysis of variance. Results: Six months after surgery 73% of patients reported spontaneous rigid erections, 60% coital activity while 76% of the group treated with urethral glanduloplasty reported normal ejaculation and orgasm, regained an average of 35 days after surgery. The average IIEF-15 scores reported in the entire series in the domains of erection, libido and coital activity of the pre-cancer period were not statistically different than those recorded six months after surgery. In the group treated with glandular reconstruction, pre-and postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were not significantly different. Mean scores of Bigelow-Young questionnaires related to sexual pleasure, familial, social and professional relationships showed significant improvement after surgery. Conclusions: Potency sparing-sparing surgical treatments have a positive impact on a wide spectrum of the patient′s life including family relationships, and social and working conditions.

BackgroundThe goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient’s germline mutation status. PCa has a very high rate of genetic predisposition compared with other cancers in men, with an estimated rate of cancers ascribable to hereditary factors of 5–15%.MethodsA systematic search (PubMed, Web of Science, and ClinicalTrials.gov) of English literature from 2000 to 2022, using the keywords “prostate cancer”, “germline mutations”, “family history”, and “inheritance” was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.ResultsThe search identified 980 publications. Of these, 200 papers were removed before screening (duplicates, non-English literature, and publication year before 2000) and 245 records were excluded after title/abstract screening. Finally, 50 articles were included in the final analysis. We analyze the latest evidence on the genetic basis of PCa predisposition and clinical implications for more personalized screening protocols and therapeutic management of this high-prevalent cancer.DiscussionEmerging data show that germline mutations in homologous recombination genes (BRCA1/2, ATM, CHECK2), in mismatch repair genes (MLH1, MLH2, MSH6), and other additional genes are associated with the development and aggressiveness of PCa. Germline testing and genetic counseling have increasingly important implications in cancer screening and therapeutic decisions making for patients affected by PCa. Patients with localized PCa and some gene mutations are more likely to develop aggressive cancer, so active treatment may be preferable to active surveillance for these patients. Moreover, in patients with metastatic PCa, these gene alterations may be useful biomarkers for predicting response to specific therapy such as PARP inhibitors, recently approved for the treatment of metastatic castration-resistant PCa. The evidence supports recent guidelines and recommendations considering germline genetic testing for patients with a positive family history of PCa or men with high risk or metastatic disease.

Background: Prostate cancer (PCa) screening currently relies on prostate-specific antigen (PSA) testing and digital rectal examination. However, recent large-scale studies have questioned the long-term efficacy of these tests, and biomarkers that accurately identify PCa are needed. Methods: We analysed the levels of circulating microRNAs (miRNAs) in patients with elevated PSA who were diagnosed with either localised PCa ( n =36) or benign prostatic hyperplasia (BPH, n =31) upon biopsy. Real-time RT–PCR with Taqman probes was used to measure plasma levels of miRNAs. To circumvent problems associated with circulating miRNA quantitation, we computed the expression ratios of upregulated and downregulated miRNAs. Results: The miR-106a/miR-130b and miR-106a/miR-223 ratios were significantly different between the biopsy-positive and BPH groups ( P <0.0001), and yielded statistical power values that were >0.99. Both miRNA ratios were highly sensitive and more specific than PSA in discriminating localised PCa from BPH. Receiver operating characteristic curve analysis revealed area under curve values of 0.81 (miR-106a/miR-130b) and 0.77 (miR-106a/miR-223). Conclusions: Testing for circulating miR-106a/miR-130b and miR-106a/miR-223 ratios may reduce the costs and morbidity of unnecessary biopsies and is feasible for large-scale screening, as it requires measuring only three miRNAs.

Overactive bladder (OAB) is a highly prevalent urinary syndrome with a profound impact on quality of life (QoL) of affected patients and their family because of its adverse effects on social, sexual, interpersonal, and professional function. Cost-of-illness analyses showed the huge economic burden related to OAB for patients, public healthcare systems, and society, secondary to both direct and indirect costs; however, intangible costs related to QoL impact are usually omitted from these analyses. Recently many novel treatment modalities have been introduced and the need to apply the modern methodology of health technology assessment to these treatment strategies was immediately clear in order to evaluate objectively their value in terms of both improvement in length/quality of life and costs. Health utilities are instruments that allow a measurement of QoL and its integration in the economic evaluation using the quality-adjusted life-years model and cost-utility analysis. The development of suitable instruments for quantifying utility in the specific group of OAB patients is vitally important to extend the application of cost-utility analysis in OAB and to guide healthcare resources allocation for this disorder. Studies are required to define the cost-effectiveness of available pharmacological and nonpharmacological therapy options for this disorder.