Malignant Fibrous Histiocytoma of the Kidney Treated with Nephrectomy and Adjuvant Radiotherapy: A Case Report

Malignant fibrous histiocytoma (MFH) usually presents in the extremities or retroperitoneum. Cases involving the kidney are rare and portend a poor prognosis. Although radical nephrectomy is the most beneficial curative choice for this neoplasm, patients are often treated with adjuvant chemotherapy due to high risk of local recurrence and distant metastases. We describe a case of a 68-year-old woman affected by MFH, treated with both nephrectomy and radiotherapy without systemic therapy showing an unexpected twenty-four-month postsurgery survival outcome

Leptin as a metabolic link to multiple sclerosis.

Clinical and experimental data, together with epidemiological studies, have suggested that the pathogenesis of multiple sclerosis (MS) might involve factors that link the immune system with metabolic status. Moreover, recent research has shown that leptin, the adipocyte-derived hormone that controls food intake and metabolism, can promote experimental autoimmune encephalomyelitis, an animal model of MS. In patients with MS, the association of leptin with disease activity has been dissected at the molecular level, providing new mechanistic explanations for the role of this hormone in MS. Here, we review the intricate relationship between leptin and other metabolic modulators within a framework that incorporates the latest advances linking the CNS, immune tolerance and metabolic status. We also consider the translational implications of these new findings for improved management of MS

Modulation of complement activation by pentraxin-3 in prostate cancer.

Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12-36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration

Presence and severity of lower urinary tract symptoms are inversely correlated with the risk of prostate cancer on prostate biopsy

BACKGROUND: The assessment of lower urinary tract symptoms (LUTS) is common part of urological investigation. Furthermore, patients bother of prostate cancer (PCa) when they are affected of LUTS. This study was aimed to determine whether the presence and severity of LUTS, as assessed by the International Prostate Symptoms Score (IPSS), could help to identify patients at higher risk of prostate cancer (PCa) on prostate biopsy (PBx). In this effort, an initial PCa predictive model was calculated and IPSS was subsequently added. The diagnostic accuracy of both models was compared. METHODS: The analysis of prospectively collected data of patients scheduled for PBx at four academic hospitals between January 2012 and June 2015 was performed. Univariate and multivariate analysis assessed the correlation between the IPSS and the risk of being diagnosed with PCa; Receiver operator characteristic curve (ROC) analysis evaluated the predictive models including or not the IPSS. RESULTS: Of the 1366 enrolled patients, 706 (52%) were diagnosed with PCa. Patients with PCa had a significantly lower IPSS (10.6 +/- 7.4 vs. 12.7 +/- 8.1) than those with benign diagnosis. Multivariate logistic regression analysis showed that age, prostate-specific antigen (PSA), prostate volume and IPSS were the most significant predictors of PBx outcome, (OR 1.61, P=0.001; OR 1.20, P=0.001; OR 0.97, P=0.001; OR 0.74, P=0.004; respectively). ROC curve analysis showed that the addition of IPSS to the predictive model based on age, PSA, DRE and prostate volume significantly improved the model diagnostic accuracy (AUC: 0.776 vs. 0.652; P=0.001). CONCLUSIONS: Presence and severity of LUTS are inversely correlated with the risk of being diagnosed with PCa at PBx. Incorporating the IPSS into predictive models may reduce the risk of unnecessary PBxs.info:eu-repo/semantics/publishedVersio

Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The study population consisted of patients scheduled for transurethral resection of bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladder tumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 and ClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2 and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-risk NMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expression levels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins. Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpP levels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTC scores showed that Mfn2 downregulation was significantly associated with disease progression. In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared to non-lesional bladder tissue and Mfn2 expression predicted disease progression

Liquid biopsy biomarkers in urine: a route towards molecular diagnosis and personalized medicine of bladder cancer

Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we summarized the state of the art on different available tests concerning their potential clinical applications for BC detection, prognosis, surveillance and response to therap

Artificial Intelligence and Machine Learning in Prostate Cancer Patient Management-Current Trends and Future Perspectives

Artificial intelligence (AI) is the field of computer science that aims to build smart devices performing tasks that currently require human intelligence. Through machine learning (ML), the deep learning (DL) model is teaching computers to learn by example, something that human beings are doing naturally. AI is revolutionizing healthcare. Digital pathology is becoming highly assisted by AI to help researchers in analyzing larger data sets and providing faster and more accurate diagnoses of prostate cancer lesions. When applied to diagnostic imaging, AI has shown excellent accuracy in the detection of prostate lesions as well as in the prediction of patient outcomes in terms of survival and treatment response. The enormous quantity of data coming from the prostate tumor genome requires fast, reliable and accurate computing power provided by machine learning algorithms. Radiotherapy is an essential part of the treatment of prostate cancer and it is often difficult to predict its toxicity for the patients. Artificial intelligence could have a future potential role in predicting how a patient will react to the therapy side effects. These technologies could provide doctors with better insights on how to plan radiotherapy treatment. The extension of the capabilities of surgical robots for more autonomous tasks will allow them to use information from the surgical field, recognize issues and implement the proper actions without the need for human intervention

The Discipline of Pediatric Urology: Prerogatives and Necessities

To the Editor, The aim of this “position paper” is to describe the discipline of Pediatric Urology with its clinical and cultural competencies, represent the reasons for legitimizing its existence, and reinforce its importance in the “scenario” of the National Italian Healthcare System. The requisites and the educational requirements were defined by both the Italian Ministry of Health with the State-Regions Conference, and the European Union [...

SelectMDx and Multiparametric Magnetic Resonance Imaging of the Prostate for Men Undergoing Primary Prostate Biopsy: A Prospective Assessment in a Multi-Institutional Study

Prostate-specific antigen (PSA) testing as the sole indication for prostate biopsy lacks specificity, resulting in overdiagnosis of indolent prostate cancer (PCa) and missing clinically significant PCa (csPCa). SelectMDx is a biomarker-based risk score to assess urinary HOXC6 and DLX1 mRNA expression combined with traditional clinical risk factors. The aim of this prospective multi-institutional study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) when predicting PCa in prostate biopsies. Overall, 310 consecutive subjects were included. All patients underwent mpMRI and SelectMDx prior to prostate biopsy. SelectMDx and mpMRI showed sensitivity and specificity of 86.5% vs. 51.9%, and 73.8% vs. 88.3%, respectively, in predicting PCa at biopsy, and 87.1% vs. 61.3%, and 63.7% vs. 83.9%, respectively, in predicting csPCa at biopsy. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. With analysis of strategies assessed to define the best diagnostic strategy to avoid unnecessary biopsy, SelectMDx appeared to be a reliable pathway after an initial negative mpMRI. Thus, biopsy could be proposed for all cases of mpMRI PI-RADS 4-5 score, and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1-3 score followed by a positive SelectMDx

Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy

Importance: Stratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments. Objective: To evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM. Design, Setting, and Participants: This population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023. Main Outcomes and Measures: Primary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria. Exposures: Radical prostatectomy or radiotherapy. Results: A total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category. Conclusions and Relevance: These findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.</p