Laparoscopic versus Ultrasound-Guided Transversus Abdominis Plane Block for Postoperative Analgesia Management after Radical Prostatectomy: Results from a Single Center Study.

(1) Background: Regional anesthesia, achieved through nerve blocks, has gained widespread acceptance as an effective pain management approach. This research aimed to evaluate the efficacy of laparoscopic (LAP) transversus abdominis plane (TAP) block in patients undergoing laparoscopic radical prostatectomy. (2) Methods: From January 2023 to July 2023, 60 consecutive patients undergoing minimally invasive radical prostatectomy were selected. Patients were split into two groups receiving ultrasound-guided (US) or laparoscopic-guided TAP block. The primary outcome was a pain score expressed by a 0-10 visual analog scale (VAS) during the first 72 h after surgery. (3) Results: Both LAP-TAP and US-TAP block groups were associated with lower pain scores postoperatively. No statistically significant differences were observed between the two groups in surgery time, blood loss, time to ambulation, length of stay, and pain after surgery (all p > 0.2). In the LAP-TAP block group, the overall operating room time was significantly shorter than in the US-TAP block group (140 vs. 152 min, p = 0.04). (4) Conclusions: The laparoscopic approach, compared to the US-TAP block, was equally safe and not inferior in reducing analgesic drug use postoperatively. Moreover, the intraoperative LAP-TAP block seems to be a time-sparing procedure that could be recommended when patient-controlled analgesia cannot be delivered.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Radiomic Machine-Learning Analysis of Multiparametric Magnetic Resonance Imaging in the Diagnosis of Clinically Significant Prostate Cancer: New Combination of Textural and Clinical Features.

BACKGROUND: The aim of our study was to develop a radiomic tool for the prediction of clinically significant prostate cancer. METHODS: From September 2020 to December 2021, 91 patients who underwent magnetic resonance imaging prostate fusion biopsy at our institution were selected. Prostate cancer aggressiveness was assessed by combining the three orthogonal planes-Llocal binary pattern the 3Dgray level co-occurrence matrix, and other first order statistical features with clinical (semantic) features. The 487 features were used to predict whether the Gleason score was clinically significant (≥7) in the final pathology. A feature selection algorithm was used to determine the most predictive features, and at the end of the process, nine features were chosen through a 10-fold cross validation. RESULTS: The feature analysis revealed a detection accuracy of 83.5%, with a clinically significant precision of 84.4% and a clinically significant sensitivity of 91.5%. The resulting area under the curve was 80.4%. CONCLUSIONS: Radiomic analysis allowed us to develop a tool that was able to predict a Gleason score of ≥7. This new tool may improve the detection rate of clinically significant prostate cancer and overcome the limitations of the subjective interpretation of magnetic resonance imaging, reducing the number of useless biopsies.

Accuracy of elastic fusion biopsy: Comparing prostate cancer detection between targeted and systematic biopsy.

INTRODUCTION: When performing targeted biopsy (TBx), the need to add systematic biopsies (SBx) is often debated. Aim of the study is to evaluate the added value of SBx in addition to TBx in terms of prostate cancer (PCa) detection rates (CDR), and to test the concordance between multiparametric magnetic resonance imaging (mpMRI) findings and fusion biopsy results in terms of cancer location. METHODS: We performed a retrospective, multicentric study that gathered data on 1992 consecutive patients who underwent elastic fusion biopsy between 2011 and 2020. A standardized approach was used, with TBx (2-4 cores per target) followed by SBx (12-14 cores). We assessed CDR of TBx, of SBx, and TBx+SBx for all cancers and clinically significant PCa (csPCa), defined as ISUP score ≥2. CDR was evaluated according to radiological and clinical parameters, with a particular focus on PI-RADS 3 lesions. In a subgroup of 1254 patients we tested the discordance between mpMRI findings and fusion biopsy results in terms of cancer location. Uni- and multivariable logistic regression analyses were performed to identify predictors of CDR. RESULTS: CDR of TBx+SBx was 63.0% for all cancers and 38.8% of csPCa. Per-patient analysis showed that SBx in addition to TBx improved CDR by 4.5% for all cancers and 3.4% for csPCa. Patients with lesions scored as PI-RADS 3, 4, and 5 were diagnosed with PCa in 27.9%, 72.8%, and 92.3%, and csPCa in 10.7%, 43.6%, and 69.3%, respectively. When positive, PI-RADS 3 lesions were ISUP grade 1 in 61.1% of cases. Per-lesion analysis showed that discordance between mpMRI and biopsy was found in 56.6% of cases, with 710 patients having positive SBx outside mpMRI targets, of which 414 (58.0%) were clinically significant. PSA density ≥0.15 was a strong predictor of CDR. CONCLUSIONS: The addition of systematic mapping to TBx contributes to a minority of per-patient diagnoses but detects a high number of PCa foci outside mpMRI targets, increasing biopsy accuracy for the assessment of cancer burden within the prostate. High PSA-density significantly increases the risk of PCa, both in the whole cohort and in PI-RADS 3 cases.

Serum levels of chromogranin are not predictive of poorly differentiated prostate cancer: Results from a multicenter radical prostatectomy cohort.

BACKGROUND: Recently a possible link between elevated Chromogranin A (CgA) levels and poorly differentiated prostate cancer has been proposed. The aim of our study was to explore the association of CgA levels and the risk of poorly differentiated prostate cancer (PCa) in men undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: From 2012 onwards, 335 consecutive men undergoing RRP for PCa at three centers in Italy were enrolled into a prospective database. Body mass index (BMI) was calculated before RRP. Blood samples were collected and tested for total prostate-specific antigen (PSA) levels and chromogranin A (CgA). We evaluated the association between serum levels of CgA and upstaging and upgrading using logistic regression analyses. RESULTS: Median age and preoperative PSA levels were 65 years (interquartile range [IQR]: 60-69) and 7.2 ng/ml (IQR: 5.3-10.4), respectively. Median BMI was 26.1 kg/m2 (IQR: 24-29) with 56 (16%) obese (BMI ≥ 30 kg/m2 ). Median CgA levels were 51 (39/71). Overall, 129/335 (38,5%) presented an upstaging, and 99/335 (30%) presented an upgrading. CgA was not a predictor of upstaging or upgrading on RP. CONCLUSIONS: In our multicenter cohort of patients, CgA is not a predictor of poorly differentiated PCa on radical prostatectomy. According to our experience, CgA should not be considered a reliable marker to predict poorly differentiated or advanced prostate cancer.

Health-related quality of life 24 months after prostate cancer diagnosis: an update from the Pros-IT CNR prospective observational study.

BACKGROUND: This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study. METHODS: Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), RT plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain. RESULTS: Overall, 1537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, P<0.001 and -19.7, P<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, P=0.02) and RT plus ADT groups at 12 months (-10.3, P=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, P<0.001, -37.8, P<0.001, -20.4, P<0.001, respectively). CONCLUSIONS: Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.

The waiting time for prostate cancer treatment in Italy: analysis from the PROS-IT CNR Study.

BACKGROUND: Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact on oncological and functional outcomes has not been well established. METHODS: Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated. RESULTS: The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT>90 days. At 6 months from diagnosis the mean SF-12 score for the emotional-psychological component was significantly lower in WT≥90 days group (P=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups. CONCLUSIONS: In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT>90 days. WT might have no impact on functional and oncological outcome.

Minimally Invasive Buccal Mucosa Dorsal Graft for Female Distal Urethroplasty.

BACKGROUND: Female urethral stricture (FUS) represents a sporadic condition. There is a lack of data and standardized guidelines on diagnostics and therapeutics. Several surgical techniques have been described for FUS urethroplasty, among which the flap-based or graft-based ones are most reported. Buccal mucosa graft (BMG) represents the gold standard for male urethroplasty, and this can theoretically be applied also to FUS treatment. OBJECTIVE: To describe and present preliminary results of a novel minimally invasive technique for buccal mucosa dorsal graft (mini-dorsal BMG) urethroplasty for the treatment of FUS. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study on buccal mucosa dorsal graft urethroplasty for the treatment of FUS. SURGICAL PROCEDURE: Every patient was placed in lithotomic position. Two stiches were placed at 10 and 2 o'clock positions to facilitate the dorsal median urethrotomy. The margins of the incised dorsal urethra at the 12 o'clock position are then dissected from the periurethral tissue. This dissection results in an elliptical raw area between the edges of the urethra over the periurethral tissue. The harvested BMG was fixed with several quilting sutures, using 5-0 and 4-0 absorbable sutures, to cover the raw area. The margins of the graft were sutured to the edges of the incised urethra. MEASUREMENTS: A chart review was performed. RESULTS AND LIMITATIONS: Thirteen patients underwent the mini-dorsal-BMG technique. The median preoperative uroflow was 5.6 (3-13) ml/s, and the median postoperative value was 23.4 (14-58) ml/s. CONCLUSIONS: The mini-dorsal-BMG technique for the treatment of FUS gives good results with low complication rates. Other series and long-term follow-up are necessary to confirm the reproducibility of this technique. PATIENT SUMMARY: We present the technical aspects and the promising preliminary results of a novel surgical technique for the treatment of female urethral stricture by using the buccal mucosa to correct this invalidating disease.

Bioethical implications of robotic surgery in urology: a systematic review.

INTRODUCTION: Robotic technologies are being increasingly implemented in healthcare, including urology, and holding promises for improving medicine worldwide. However, these new approaches raise ethical concerns for professionals, patients, researchers and institutions that need to be addressed. The aim of this review was to investigate the existing literature related to bioethical issues associated with robotic surgery in urology, in order to identify current challenges and make preliminary suggestions to ensure an ethical implementation of these technologies. EVIDENCE ACQUISITION: We performed a review of the pertaining literature through a systematic search of two databases (PubMed and Web of Science) in August 2020. EVIDENCE SYNTHESIS: Our search yielded 76 articles for full-text evaluation and 48 articles were included in the narrative review. Several bioethical issues were identified and can be categorized into five main subjects: 1) robotic surgery accessibility (robotic surgery is expensive, and in some health systems may lead to inequality in healthcare access. In more affluent countries the national distribution of several robotic platforms may influence the centralization of robotic surgery, therefore potentially affecting oncological and functional outcomes in low-volume centers); 2) safety (there is a considerable gap between surgical skills and patients' perception of competence, leading to ethical consequences on modern healthcare. Published incidence of adverse events during robotic surgery in large series is between 2% and 15%, which does not significantly differ amongst open or laparoscopic approaches); 3) gender gap (no data about gap differences in accessibility to robotic platforms were retrieved from our search); 4) costs (robotic platforms are expensive but a key reason why hospitals are willing to absorb the high upfront costs is patient demand. It is possible to achieve cost-equivalence between open and robotic prostatectomy if the volume of centers is higher than 10 cases per week); and 5) learning curve (a validated, structured curriculum and accreditation has been created for robotic surgery. This allows acquisition and development of basic and complex robotic skills focusing on patient safety and short learning curve). CONCLUSIONS: Tech-medicine is rapidly moving forward. Robotic approach to urology seems to be accessible in more affluent countries, safe, economically sustainable, and easy to learn with an appropriate learning curve for both sexes. It is mandatory to keep maintaining a critical rational approach with constant control of the available evidence regarding efficacy, efficiency and safety.

Computer-Aided Diagnosis Improves the Detection of Clinically Significant Prostate Cancer on Multiparametric-MRI: A Multi-Observer Performance Study Involving Inexperienced Readers.

Recently, Computer Aided Diagnosis (CAD) systems have been proposed to help radiologists in detecting and characterizing Prostate Cancer (PCa). However, few studies evaluated the performances of these systems in a clinical setting, especially when used by non-experienced readers. The main aim of this study is to assess the diagnostic performance of non-experienced readers when reporting assisted by the likelihood map generated by a CAD system, and to compare the results with the unassisted interpretation. Three resident radiologists were asked to review multiparametric-MRI of patients with and without PCa, both unassisted and assisted by a CAD system. In both reading sessions, residents recorded all positive cases, and sensitivity, specificity, negative and positive predictive values were computed and compared. The dataset comprised 90 patients (45 with at least one clinically significant biopsy-confirmed PCa). Sensitivity significantly increased in the CAD assisted mode for patients with at least one clinically significant lesion (GS > 6) (68.7% vs. 78.1%, p = 0.018). Overall specificity was not statistically different between unassisted and assisted sessions (94.8% vs. 89.6, p = 0.072). The use of the CAD system significantly increases the per-patient sensitivity of inexperienced readers in the detection of clinically significant PCa, without negatively affecting specificity, while significantly reducing overall reporting time.

Diagnostic and prognostic potential of the proteomic profiling of serum-derived extracellular vesicles in prostate cancer.

Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-ß5, Survivin, TGF-ß, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follow-up cohort generated a protein signature with prognostic significance. Our results confirm that serum-derived EV cargo may be exploited to improve the current diagnostic procedures while providing potential prognostic and predictive information. The approach proposed here has been already applied to tumor entities other than PCa, thus proving its value in translational medicine and paving the way to innovative, clinically meaningful tools.

How uro-oncology has been affected by COVID-19 emergency? Data from Piedmont/Valle d'Aosta Oncological Network, Italy.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic has dramatically hit all Europe and Northern Italy in particular. The reallocation of medical resources has caused a sharp reduction in the activity of many medical disciplines, including urology. The restricted availability of resources is expected to cause a delay in the treatment of urological cancers and to negatively influence the clinical history of many cancer patients. In this study, we describe COVID-19 impact on uro-oncological management in Piedmont/Valle d'Aosta, estimating its future impact. METHODS: We performed an online survey in 12 urological centers, belonging to the Oncological Network of Piedmont/Valle d'Aosta, to estimate the impact of COVID-19 emergency on their practice. On this basis, we then estimated the medical working capacity needed to absorb all postponed uro-oncological procedures. RESULTS: Most centers (77%) declared to be "much"/"very much" affected by COVID-19 emergency. If uro-oncological consultations for newly diagnosed cancers were often maintained, follow-up consultations were more than halved or even suspended in around two out of three centers. In-office and day-hospital procedures were generally only mildly reduced, whereas major uro-oncological procedures were more than halved or even suspended in 60% of centers. To clear waiting list backlog, the urological working capacity should dramatically increase in the next months; delays greater than 1 month are expected for more than 50% of uro-oncological procedures. CONCLUSIONS: COVID-19 emergency has dramatically slowed down uro-oncological activity in Piedmont and Valle d'Aosta. Ideally, uro-oncological patients should be referred to COVID-19-free tertiary urological centers to ensure a timely management.

How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study.

PURPOSE: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. METHODS: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). RESULTS: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. CONCLUSIONS: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

En-bloc endoscopic enucleation of the prostate: a systematic review of the literature.

INTRODUCTION: Transurethral resection of the prostate (TURP) remains the gold standard for treatment of benign prostatic hyperplasia (BPH). Yet, the introduction of lasers for the treatment of LUTS due to BPO has dramatically changed the surgical landscape of benign prostatic obstruction (BPO) treatment. Recently, "en-bloc" techniques have shown to prove advantageous in terms of better visualization, more prompt identification of the surgical capsule and the correct plane to dissect. Herein we provide a comprehensive overview of available series of en-bloc enucleation of the prostate, focusing on surgical techniques, perioperative and functional outcomes. EVIDENCE ACQUISITION: A systematic review of the literature was performed according to PRISMA recommendations and was conducted on surgical techniques and perioperative outcomes of minimally invasive en-bloc surgery for prostate adenoma detachment. EVIDENCE SYNTHESIS: Overall, 16 studies with 2750 patients between 2003 and 2019 were included. Specific technical nuances have been described to maximize perioperative outcomes of en-bloc prostatic enucleation, including early apical release, horse-shape incisions, inverted U-shape tractions and low power. Overall, regardless of the energy employed, en-bloc prostatic enucleation achieved favorable outcomes including low risk of major complications and quality of life improvement. However, a great heterogeneity of study design, patients' inclusion criteria, prostate volume and en-bloc surgical strategy was found. CONCLUSIONS: En-bloc endoscopic enucleation of the prostate has been shown to be technically feasible and safe, with potential technical advantages over the classic three-lobe technique. Larger comparative studies are needed to evaluate the ultimate impact of the en-bloc approach on postoperative outcomes, in light of the surgeon's learning curve.

Accuracy of magnetic resonance imaging to identify pseudocapsule invasion in renal tumors.

PURPOSE: To evaluate accuracy of MRI in detecting renal tumor pseudocapsule (PC) invasion and to propose a classification based on imaging of PC status in patients with renal cell carcinoma. METHODS: From January 2017 to June 2018, 58 consecutive patients with localized renal cell carcinoma were prospectively enrolled. MRI was performed preoperatively and PC was classified, according to its features, as follows: MRI-Cap 0 (absence of PC), MRI-Cap 1 (presence of a clearly identifiable PC), MRI-Cap 2 (focally interrupted PC), and MRI-Cap 3 (clearly interrupted and infiltrated PC). A 3D image reconstruction showing MRI-Cap score was provided to both surgeon and pathologist to obtain complete preoperative evaluation and to compare imaging and pathology reports. All patients underwent laparoscopic partial nephrectomy. In surgical specimens, PC was classified according to the renal tumor capsule invasion scoring system (i-Cap). RESULTS: A concordance between MRI-Cap and i-Cap was found in 50/58 (86%) cases. ρ coefficient for each MRI-cap and iCap categories was: MRI-Cap 0: 0.89 (p < 0.0001), MRI-Cap1: 0.75 (p < 0.0001), MRI-Cap 2: 0.76 (p < 0.0001), and MRI-Cap3: 0.87 (p < 0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and AUC were: MRI-Cap 0: Se 97.87% Spec 83.3%, PPV 95.8%, NPV 90.9%, and AUC 90.9; MRI-Cap 1: Se 77% Spec 95.5%, PPV 83.3%, NPV 93.5%, and AUC 0.86; MRI-Cap 2- iCap 2: Se 88% Spec 90%, PPV 79%, NPV 95%, and AUC 0.89; MRI-Cap 3: Se 94% Spec 95%, PPV 88%, NPV 97%, and AUC 0.94. CONCLUSIONS: MRI-Cap classification is accurate in evaluating renal tumor PC features. PC features can provide an imaging-guided landmark to figure out where a minimal margin could be preferable during nephron-sparing surgery.

Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases.

The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients' life and aggressive forms still remain difficult to treat. Ethical issues related to the use of embryonic stem cells, has fueled research on adult, patient-specific pluripotent stem cells as a model for discovery and therapeutic development, but to date, normal and cancerous renal experimental models are lacking. Several research groups are focusing on the development of organoid cultures. Since organoids mimic the original tissue architecture in vitro, they represent an excellent model for tissue engineering studies and cancer therapy testing. We established normal and tumor renal cell carcinoma organoids previously maintained in a heterogeneous multi-clone stem cell-like enriching medium. Starting from adult normal kidney specimens, we were able to isolate and propagate organoid 3D-structures composed of both differentiated and undifferentiated cells while expressing nephron specific markers. Furthermore, we were capable to establish organoids derived from cancer tissues although with a success rate inferior to that of their normal counterpart. Cancer cultures displayed epithelial and mesenchymal phenotype while retaining tumor specific markers. Of note, tumor organoids recapitulated neoplastic masses when orthotopically injected into immunocompromised mice. Our data suggest an innovative approach of long-term establishment of normal- and cancer-derived renal organoids obtained from cultures of fleshly dissociated adult tissues. Our results pave the way to organ replacement pioneering strategies as well as to new models for studying drug-induced nephrotoxicity and renal diseases. Along similar lines, deriving organoids from renal cancer patients opens unprecedented opportunities for generation of preclinical models aimed at improving therapeutic treatments.

Correction: Metabolic syndrome increases the risk of upgrading and upstaging in patients with prostate cancer on biopsy: a radical prostatectomy multicenter cohort study.

The original version of this Article contained an error in the spelling of the authors Cosimo De Nunzio, Aldo Brassetti, Giuseppe Simone, Riccardo Lombardo, Riccardo Mastroianni, Devis Collura, Giovanni Muto, Michele Gallucci and Andrew Tubaro, which were incorrectly given as De Nunzio Cosimo, Brassetti Aldo, Simone Giuseppe, Lombardo Riccardo, Mastroianni Riccardo, Collura Devis, Muto Giovanni, Gallucci Michele and Tubaro Andrea. This has now been corrected in both the PDF and HTML versions of the Article.

Renal cancer: new models and approach for personalizing therapy.

BACKGROUND: Clear cell RCC (ccRCC) accounts for approximately 75% of the renal cancer cases. Surgery treatment seems to be the best efficacious approach for the majority of patients. However, a consistent fraction (30%) of cases progress after surgery with curative intent. It is currently largely debated the use of adjuvant therapy for high-risk patients and the clinical and molecular parameters for stratifying beneficiary categories. In addition, the treatment of advanced forms lacks reliable driver biomarkers for the appropriated therapeutic choice. Thus, renal cancer patient management urges predictive molecular indicators and models for therapy-decision making. METHODS: Here, we developed and optimized new models and tools for ameliorating renal cancer patient management. We isolated from fresh tumor specimens heterogeneous multi-clonal populations showing epithelial and mesenchymal characteristics coupled to stem cell phenotype. These cells retained long lasting-tumor-propagating capacity provided a therapy monitoring approach in vitro and in vivo while being able to form parental tumors when orthotopically injected and serially transplanted in immunocompromised murine hosts. RESULTS: In line with recent evidence of multiclonal cancer composition, we optimized in vitro cultures enriched of multiple tumor-propagating populations. Orthotopic xenograft masses recapitulated morphology, grading and malignancy of parental cancers. High-grade but not the low-grade neoplasias, resulted in efficient serial transplantation in mice. Engraftment capacity paralleled grading and recurrence frequency advocating for a prognostic value of our developed model system. Therefore, in search of novel molecular indicators for therapy decision-making, we used Reverse-Phase Protein Arrays (RPPA) to analyze a panel of total and phosphorylated proteins in the isolated populations. Tumor-propagating cells showed several deregulated kinase cascades associated with grading, including angiogenesis and m-TOR pathways. CONCLUSIONS: In the era of personalized therapy, the analysis of tumor propagating cells may help improve prediction of disease progression and therapy assignment. The possibility to test pharmacological response of ccRCC stem-like cells in vitro and in orthotopic models may help define a pharmacological profiling for future development of more effective therapies. Likewise, RPPA screening on patient-derived populations offers innovative approach for possible prediction of therapy response.

Accuracy of elastic fusion biopsy in daily practice: Results of a multicenter study of 2115 patients.

OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables. RESULTS: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate.

Metabolic syndrome increases the risk of upgrading and upstaging in patients with prostate cancer on biopsy: a radical prostatectomy multicenter cohort study.

BACKROUND: Recently metabolic syndrome has been associated to an increased risk of advanced disease. Aim of our study is to investigate the association of metabolic syndrome (MetS) with the risk of prostate cancer (PCa) upgrading and upstaging after radical prostatectomy (RP). METHODS: From 2012 and 2016, 400 consecutive men underwent RP at three referral centers in Italy and were enrolled into a prospective database. Blood pressure, body mass index and waist circumference were measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Logistic regression analyses were used to assess the association between MetS, defined according to Adult Treatment Panel III, and the risk of upgrading and upstaging), using the new Prognostic Grade Group (PGG) classification system. RESULTS: Overall 148/400 (37%) men were diagnosed with MetS and most of these reported up-grading (54.5%) and up-staging (56.8%). These events were significantly more common in this population and MetS was a risk factor for up-staging and up-grading on multivariable analysis. Patients with MetS presented worst accuracy (72 vs. 84%; p = 0.001) and worst kappa coefficient of agreement (k = 0.439 ± 0.071 vs. k = 0.553 ± 0.071) between needle biopsy and radical prostatectomy specimens when compared to patients without MetS. CONCLUSIONS: MetS represents a significant risk factor for upgrading and upstaging. Accuracy of PGG system on biopsy is poor in patients with MetS, therefore results should be evaluated carefully in this population.