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Abstract. Background. Recently, an innovative tool called “proficiency score” was introduced to assess the learning curve for robot-assisted radical prostatectomy (RARP). However, the initial study only focused on patients with low-risk prostate cancer for whom pelvic lymph node dissection (PLND) was not required. To address this issue, we aimed to validate proficiency scores of a contemporary multicenter cohort of patients with high-risk prostate cancer treated with RARP plus extended PLND by trainee surgeons. Material and methods. Between 2010 and 2020, 4 Italian institutional prostate-cancer datasets were merged and queried for “RARP” and “high-risk prostate cancer.” High-risk prostate cancer was defined according to the most recent European Association of Urology guidelines as follows: prostate-specific antigen >20 ng/mL, International Society of Urological Pathology ≥4, and/or clinical stage (cT) ≥ 2c on preoperative imaging. The selected cohort (n = 144) included clinical cases performed by trainee surgeons (n = 4) after completing their RARP learning curve (50 procedures for low-risk prostate cancer). The outcome of interest, the proficiency score, was defined as the coexistence of all the following criteria: a comparable operation time to the interquartile range of the mentor surgeon at each center, absence of any significant perioperative complications Clavien-Dindo Grade 3–5, no perioperative blood transfusions, and negative surgical margins. A logistic binary regression model was built to identify the predictors of 1-year trifecta achievement in the trainee cohort. For all statistical analyses, a 2-sided p < 0.05 was considered significant. Results. A proficiency score was achieved in 42.3% patients. At univariable level, proficiency score was associated with 1-year trifecta achievement (odds ratio, 8.77; 95% confidence interval, 2.42–31.7; p = 0.001). After multivariable adjustments for age, nerve-sparing, and surgical technique, the proficiency score independently predicted 1-year trifecta achievement (odds ratio, 9.58; 95% confidence interval, 1.83–50.1; p = 0.007). Conclusions. Our findings support the use of proficiency scores in patients and require extended PLND in addition to RARP.

Few data are available on survival outcomes of partial nephrectomy performed for cystic renal tumors. We present the first long-term oncological outcomes of cystic (cystRCC) versus pure clear cell renal cell carcinoma (ccRCC) in a propensity score-matched (PSM) analysis. Our “renal cancer” prospectively maintained database was queried for “cystRCC” or “ccRCC” and “off-clamp robotic partial nephrectomy” (off-C RPN). The two groups were compared for age, gender, tumor size, pT stage, and Fuhrman grade. A 1:3 PSM analysis was applied to reduce covariate imbalance to p = 0.146) was found between the two cohorts. Conversely, 10-year disease-free survival probability (DFS) was less favorable for pure ccRCC than cystRCC (66.69% versus 90.1%, p = 0.035). At univariable regression analysis, ccRCC histology was the only independent predictor of DFS probability (HR 2.96 95% CI 1.03–8.47, p = 0.044). At the 10-year evaluation, cystRCC showed favorable oncological outcomes after off-C RPN. Pure clear cell variant histology displayed a higher rate of disease recurrence than cystic lesions.

Background: Prostate cancer (PCa) management is moving towards patient-tailored strategies. Advances in molecular and genetic profiling of tumor tissues, integrated with clinical risk assessments, provide deeper insights into disease aggressiveness. This study aims to offer a comprehensive overview of the pivotal genomic tests supporting PCa treatment decisions, analyzing—through real-world data—trends in their use and the growth of supporting literature evidence. Methods: A retrospective analysis was conducted using the extensive PearlDiver™ Mariner database, which contains de-identified patient records, in compliance with the Health Insurance Portability and Accountability Act (HIPAA). The International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify patients diagnosed with PCa during the study period—2011 to 2021. We determined the utilization of primary tissue-based genetic tests (Oncocyte DX®, Prolaris®, Decipher®, and ProMark®) across all patients diagnosed with PCa. Subsequently, within the overall PCa cohort, patients who underwent radical prostatectomy (RP) and received genetic testing postoperatively were identified. The yearly distribution of these tests and the corresponding trends were illustrated with graphs. Results: During the study period, 1,561,203 patients with a PCa diagnosis were recorded. Of these, 20,748 underwent tissue-based genetic testing following diagnosis, representing 1.3% of the total cohort. An increasing trend was observed in the use of all genetic tests. Linear regression analysis showed a statistically significant increase over time in the use of individual tests (all p-values < 0.05). Among the patients who underwent RP, 3076 received genetic analysis following surgery, representing 1.27% of this group. Conclusions: Our analysis indicates a growing trend in the utilization of tissue-based genomic testing for PCa. Nevertheless, they are utilized in less than 2% of PCa patients, whether at initial diagnosis or after surgical treatment. Although it is anticipated that their use may increase as more scientific evidence becomes available, their role requires further elucidation.

Objective: This video aims to demonstrate the safety and feasibility of performing deferred cytoreductive nephrectomy (dCN) using robotic assistance in patient treated with immunotherapy for metastatic renal cell carcinoma (mRCC). Patients and surgical procedure: A 62-year-old woman, affected by right metastatic renal cell carcinoma, showed partial response after 4 cycles of Pembrolizumab and Axitinib. Multidisciplinary team consultation decided for cytoreductive right radical nephrectomy with adrenalectomy. After anatomical landmarks identification, inferior vena cava (IVC) was progressively exposed, until identifying the renal hilum. During surgery, small bleeding occurred, and Weck-clips were placed to control the arterial flow. Nephrectomy proceeded without complications. Right adrenal gland, suspected of metastasis, was removed. Results: No intra- and post-operative high-grade Clavien-Dindo complications occurred, and the patient was discharged in post-operative day 3. Final pathology revealed clear cell renal cell carcinoma with sarcomatoid features, Furhman grade 4, with metastatic lesion in the omolateral adrenal gland (pT3a pM1) Conclusion: Robot-assisted dCN is feasible and safe after immune checkpoint inhibitor-based combination therapy in patients affected by mRCC.

Abstract Background Magnetic resonance imaging (MRI) is recommended in patients with upper tract urothelial carcinoma (UTUC) only when computed tomography (CT) is contraindicated. However, CT does not allow distinguishing ureter wall layers, making impossible to assess muscle invasion, a factor contributing to differentiate high- from low-risk UTUCs, which require different therapeutic approaches. We investigated the feasibility of MRI assessment of UTUC muscle invasion. Methods From June 2022 to March 2023, we prospectively enrolled patients suspected of UTUC, i.e., with positive urinary tract ultrasound and/or ureteroscopy, or positive urinary cytology and/or hematuria but negative cystoscopy and bladder ultrasound at two Italian centers. They underwent CT followed by MRI (≤ 24 h apart), independently reported by two experienced radiologists, blinded from histopathology results. After imaging confirmation, they all underwent nephroureterectomy and histopathology analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic curve (AUC) were calculated. Results Thirty-nine lesions were detected in 30 patients on both CT and MRI. Muscle-invasive UTUC prevalence was 81% (21/26) among patients with MRI suspicion and 8% (1/13) among those without MRI suspicion (p

The aim of our study is to evaluate the effectiveness and safety of a sutureless off-clamp robot-assisted partial nephrectomy (sl-oc RAPN), particularly its impact on renal function. A multicenter study was conducted from April 2021 to June 2022. Patients diagnosed with a renal mass of >2 cm and a PADUA score of ≤6 consecutively underwent an sl-oc RAPN procedure. Tumor features, patients characteristics, and intraoperative outcomes were assessed. An evaluation of renal function was performed preoperatively, and again at 1 and 3 months after surgery by measuring the creatinine and blood urea nitrogen levels. The renal function of the two separate kidneys was assessed by a sequential renal scintigraphy performed before and at least 30 days after surgery. A total of 21 patients underwent an sl-oc RAPN. The median age was 64 years (IQR 52/70), the median tumor diameter was 40 mm (IQR 29/45), and the median PADUA score was 4 (3.5/5). The intraoperative outcomes included operative time (OT), 90 (IQR 74/100) min; estimated blood loss (EBL), 150 (IQR 50/300) mL; and perioperative complications, CD > 3 1(5%); only two patients presented positive surgical margins in their final histology (2/21, 10%). Compared to the preoperative value, a decrease in renal function was highlighted with a statistically significant median decrease of 10 mL/min (p < 0.01). The renal scintigraphy showed an overall decrease in renal function compared to the preoperative value, with a range in the operated kidney that varied from 0 to 15 mL/s and from 0% to 40%, with a median value of 4 mL/s and 12%. sl-oc RAPN is a safe procedure, with a minimal impact on kidney function alteration. This technique has proven effective in preserving renal function and maintaining optimal oncological outcomes with limited complications.

Background: Head-to-head comparisons between ileal conduit (IC) and orthotopic neobladder (ONB) in terms of peri- and postoperative outcomes and complications, in the specific setting of robot-assisted radical cystectomy (RARC), are not available. Objective: To address the impact of the type of urinary diversion (UD, IC vs ONB) on RARC morbidity, as well as operative time (OT), length of stay (LOS), and readmissions. Design, setting, and participants: Urothelial bladder cancer patients treated with RARC at nine high-volume European institutions between 2008 and 2020 were identified. Intervention: RARC with either IC or ONB. Outcome measurements and statistical analysis: Intra- and postoperative complications were collected and reported according to the Intraoperative Complications Assessment and Reporting with Universal Standards recommendations and European Association of Urology guidelines, respectively. Multivariable logistic regression models tested the impact of UD on outcomes, after adjustment for clustering at single hospital level. Results and limitations: Overall, 555 nonmetastatic RARC patients were identified. In 280 (51%) and 275 (49%) patients, an IC and an ONB were performed, respectively. Eighteen intraoperative complications were recorded. The rates of intraoperative complications were 4% in IC patients and 3% in ONB patients (p = 0.4). The median LOS and readmission rates were 10 versus 12 d (p

Background: Our study aims to assess the feasibility and the reproducibility of fluorescent confocal microscopy (FCM) real-time assessment of urethral and ureteral margins during open radical cystectomy (ORC) for bladder cancer (BCa). Methods: From May 2020 to January 2022, 46 patients underwent ORC with intraoperative FCM evaluation. Each specimen was intraoperatively stained for histopathological analysis using FCM, analyzed as a frozen section (FSA), and sent for traditional H&E examination. Sensitivity, specificity, positive predictive value (PPV), and the negative predictive value (NPV) of FCM and FSA were assessed and compared with H&E for urethral and ureteral margins separately. Results: The agreement was evaluated through Cohen’s κ statistic. Urethral diagnostic agreement between FCM and FSA showed a κ = 0.776 (p < 0.001), while between FCM and H&E, the agreement was κ = 0.691 (p < 0.001). With regard to ureteral margins, an overall agreement of κ = 0.712 (p < 0.001) between FCM and FSA and of κ = 0.481 (p < 0.001) between FCM and H&E was found. Conclusions: FCM proved to be a safe, feasible, and reproducible method for the intraoperative assessment of urethral and ureteral margins during ORC. Compared to standard FSA, FCM showed adequate diagnostic performance in detecting urethral and ureteral malignant involvement.

Off-clamp partial nephrectomy represents one of the latest developments in nephron-sparing surgery, with the goal of preserving renal function and reducing ischemia time. The aim of this study was to evaluate and compare the functional, oncologic, and perioperative outcomes between off-clamp robot-assisted partial nephrectomy (off-C RAPN) and off-clamp open partial nephrectomy (off-C OPN) through a propensity score-matched (PSM) analysis. A 1:1 PSM analysis was used to balance variables potentially affecting postoperative outcomes. To report surgical quality, 1 year trifecta was used. Univariable Cox regression analysis was performed to identify predictors of trifecta achievement. The Kaplan–Meier method was used to compare cancer-specific survival (CSS), overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) probabilities between groups. Overall, 542 patients were included. After PSM analysis, two homogeneous cohorts of 147 patients were obtained. The off-C RAPN cohort experienced shorter length of stay (LoS) (3.4 days vs. 5.4 days; p < 0.001), increased likelihoods of achieving 1 year trifecta (89.8% vs. 80.3%; p = 0.03), lower postoperative Clavien–Dindo ≤ 2 complications (1.3% vs. 18.3%, p < 0.001), and lower postoperative transfusion rates (3.4% vs. 12.2%, p = 0.008). At univariable analysis, the surgical approach (off-C RAPN vs. off-C OPN, OR 2.22, 95% CI 1.09–4.46, p = 0.02) was the only predictor of 1 year trifecta achievement. At Kaplan–Meier analysis, no differences were observed between the two groups in terms of OS (log-rank p = 0.451), CSS (log-rank p = 0.476), DFS (log-rank p = 0.678), and MFS (log-rank p = 0.226). Comparing RAPN and OPN in a purely off-clamp scenario, the minimally invasive approach proved to be a feasible and safe surgical approach, with a significantly lower LoS and minor rate of postoperative complications and transfusions as a result of improved surgical quality expressed by higher 1 year trifecta achievement.

(1) Background: Prostate Cancer (PCa) may be incidentally diagnosed during the microscopic evaluation of resected tissue from BPH surgeries, characterizing the clinical condition known as incidental PCa (iPCa). This study aims to assess the prevalence of iPCa following BPH surgery to evaluate the associated surgical procedures and to scrutinize preoperative and postoperative management. (2) Methods: A retrospective analysis was conducted using the PearlDiver™ Mariner database, containing patient records compiled between 2011 and 2021. International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify the population and outcomes. Our primary objective was to assess the prevalence of iPCa, categorized by the type of procedures, and to evaluate the subsequent treatment strategies. The secondary aim was to assess the impact of prostate biopsy (PB) and prostate MRI on iPCa detection. (3) Results: The overall cohort, accounting for 231,626 patients who underwent BPH surgery, exhibited a 2.2% prevalence rate of iPCa. The highest rate was observed for TURP (2.32%), while the lowest was recorded for RASP (1.18%). Preoperative MRI and PB demonstrated opposing trends over the years. Of the 5090 patients identified with iPCa, nearly 68% did not receive active treatment. The most common treatments were RT and ADT; 34.6% underwent RT, 31.75% received ADT, and 21.75% were treated with RT+ADT. RP was administered to approximately 9% of patients undergoing endoscopic procedures. Multivariate logistic regression analysis revealed age and openSP as additional risk factors for iPCa. Conversely, PB and MRI before surgery were linked to a decreased risk. (4) Conclusions: The contemporary prevalence of iPCa after BPH surgery is

Background: To optimize results reporting after penile cancer (PC) surgery, we proposed a Tetrafecta and assessed its ability to predict overall survival (OS) probabilities. Methods: A purpose-built multicenter, multi-national database was queried for stage I–IIIB PC, requiring inguinal lymphadenectomy (ILND), from 2015 onwards. Kaplan–Meier (KM) method assessed differences in OS between patients achieving Tetrafecta or not. Univariable and multivariable regression analyses identified its predictors. Results: A total of 154 patients were included in the analysis. The 45 patients (29%) that achieved the Tetrafecta were younger (59 vs. 62 years; p = 0.01) and presented with fewer comorbidities (ASA score ≥ 3: 0% vs. 24%; p < 0.001). Although indicated, ILND was omitted in 8 cases (5%), while in 16, a modified template was properly used. Although median LNs yield was 17 (IQR: 11–27), 35% of the patients had Tetrafecta cohort displayed significantly higher OS probabilities (Log Rank = 0.01). Uni- and multivariable logistic regression analyses identified age as the only independent predictor of Tetrafecta achievement (OR: 0.97; 95%CI: 0.94–0.99; p = 0.04). Conclusions: Our Tetrafecta is the first combined outcome to comprehensively report results after PC surgery. It is widely applicable, based on standardized and reproducible variables and it predicts all-cause mortality.

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.

Background: Nephron-sparing surgery represents the gold standard treatment for organ-confined renal tumors. We present 15-years of outcomes after off-clamp laparoscopic partial nephrectomy (ocLPN). Methods: a retrospective analysis was performed on patients who underwent ocLPN between May 2001 and December 2005. Baseline demographic, clinical, pathologic, surgical, functional and survival data were collected. The Kaplan–Meier method evaluated group-specific oncologic outcomes at 5, 10 and 15 years and the log rank test assessed differences between groups. The same analysis investigated the probabilities of developing a significant renal function impairment (sRFI) and achieving ROMeS. Cox analyses identified predictors of this latter tricomposite outcome. Results: We included 63 patients whose median tumor size was 3 cm (IQR:2–4). At 15 years, the chances of developing local recurrence, metachronous renal cancers or distant metastases were 2 ± 2%, 23 ± 6% and 17 ± 5%, respectively. Consequently, disease-free, cancer-specific and overall-survival probabilities were 68 ± 6%, 90 ± 4% and 72 ± 6%. MCRSS and UCISS well predicted oncologic outcomes. Overall, nine (14%) patients experienced an sRFI and 33 (52%) achieved ROMeS. Age (HR: 1.046; p = 0.033) and malignant histology (low-risk cancers HR: 3.233, p = 0.048) (intermediate/high risk cancers HR: 5.721, p = 0.023) were independent predictors of ROMeS non-achievement. Conclusions: At 15 years from ocLPN, most of patients will experience both excellent functional and oncologic outcomes.

El presente estudio tiene por objetivo rastrear, analizar y describir la historia de las palabras sedán, jeep y sidecar usadas actualmente en español para designar unos determinados vehículos de motor, y demostrar con precisión cómo estas unidades léxicas se han ido introduciendo en la lengua castellana, sobre todo teniendo en cuenta su carácter de préstamos o extranjerismos tomados de la lengua inglesa y la importancia que estos tienen para llenar vacíos terminológicos en cualquier ámbito y en cualquier idioma. Asimismo, las informaciones históricas que aquí se recogen acerca de estos tres vocablos podrán emplearse como material para la compilación de un diccionario histórico del que carece actualmente la lengua española.

We have carefully read the comment by May et al. [...]

IntroductionMitotane, the only drug approved by the Food and Drug Administration (FDA) for the treatment of adrenocortical carcinoma, is associated with several side effects including neurotoxicity. The aim of our study is to investigate the relationship between mitotane plasma levels and neurological toxicity.MethodsWe have considered five patients affected by adrenocortical carcinoma treated with mitotane. The neurological assessment included a neurological examination, an electroencephalogram, event-related potentials (P300), and a neuropsychological assessment. All of the patients were first considered at the onset of symptoms of neurotoxicity or when mitotanemia levels were above 18 mg/L, for the second time at mitotanemia normalization and subsequently at its further increase, or in case of persistent neurological abnormalities, some months after normalization.ResultsAt the first neurotoxicity, four patients showed impaired neurological examination, electroencephalogram, and P300; three patients had impaired neuropsychological assessment; one patient, only P300. At mitotanemia normalization, the neurological examination became normal in all patients and electroencephalogram normalized in one patient, improved in another one, continuing to be altered in the other three. P300 latency and neuropsychological assessment normalized in two patients and persisted altered in the patient experiencing long-term mitotane toxicity. At the third evaluation, in the patient with prolonged mitotane toxicity, the normal mitotanemia in the previous 9 months restored P300 and improved the electroencephalogram but not the neuropsychological assessment. In the two patients experiencing a further rise of mitotanemia, neurological examination was normal but P300 and electroencephalogram were altered.ConclusionThe results of our study highlighted the presence of neurophysiological and neuropsychological abnormalities associated with mitotane values above 18 mg/L.

Abstract The tumor microenvironment (TME), including immune cells, cancer‐associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high‐grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial‐to‐mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann–Whitney and Kruskal–Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53–4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22–5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42–3.9]). Spatial analysis revealed CD3+ T‐cell and CD20+ B‐cell expressions in CDC to be higher at the proximal (p

Background: Robotic-assisted simple prostatectomy (RASP) proved to be a sound and effective procedure for bladder outlet obstructive symptoms relief. Routinely, the transvesical (Freyer) or transcapsular (Millin) techniques are performed. A novel approach of near-infrared fluorescence imaging (NIFI)-guided urethra-sparing robot-assisted prostatectomy (Madigan) was recently introduced. Objectives: The aim of our study was to evaluate the long-term functional outcomes between the Millin, Freyer, and Madigan RASP. Design: This is a single-center, retrospective evaluation of a prospectively maintained Institutional Review Board–approved database. Methods: Data from patients who have undergone RASP in our center were prospectively collected. Demographics, prostate size, and preoperative flowmetry parameters were assessed. Questionnaires such as International Index of Erectile Function (IIEF), and International Consultation on Incontinence Questionnaire (ICIQ), International prostatic symptoms score (IPSS) with its quality of life (QoL) score, Male Sexual Health Questionnaire (MSHQ), Overactive bladder questionnaire (OABQ) were administered to every patient preoperatively and during follow-up. We tested composite outcomes (trifecta) defined as a combination of postoperative Q-max >15 ml/s, IPSS score 0) and the erectile function maintenance (∆IEEF

The use of robotic surgery (RS) in urology has grown exponentially in the last decade, but RS training has lagged behind. The launch of new robotic platforms has paved the way for the creation of innovative robotics training systems. The aim of our study is to test the new training system from Hugo™ RAS System–Medtronic. Between July 2020 and September 2022, a total of 44 residents from urology, gynaecology and general surgery at our institution participated in advanced robotic simulation training using the Hugo™ RAS simulator. Information about sex, age, year of residency, hours spent playing video games, laparoscopic or robotic exposure and interest in robotics (90.9% declared an interest in robotics) was collected. The training program involved three robotic exercises, and the residents performed these exercises under the guidance of a robotics tutor. The residents’ performance was assessed based on five parameters: timing, range of motion, panoramic view, conflict of instruments and exercise completion. Their performance was evaluated according to an objective Hugo system form and a subjective assessment by the tutor. After completing the training, the residents completed a Likert scale questionnaire to gauge their overall satisfaction. The rate of the residents’ improvement in almost all parameters of the three exercises between the first and the last attempts was statistically significant (p < 0.02), indicating significant progress in the residents’ robotic surgical skills during the training. The mean overall satisfaction score ± standard deviation (SD) was 9.4 ± 1.2, signifying a high level of satisfaction among the residents with the training program. In conclusion, these findings suggest that the training program utilizing the Hugo™ RAS System is effective in enhancing robotic surgical skills among residents and holds promise for the development of standardized robotics training programs in various surgical specialties.

The advent of robotic surgical systems had a significant impact on every surgical area, especially urology, gynecology, and general and cardiac surgery. The aim of this article is to delineate robotic surgery, particularly focusing on its historical background, its evolution, its present status, and its future perspectives. A comprehensive literature review was conducted upon PubMed/MEDLINE, using the keywords “robotic surgical system”, “robotic surgical device”, “robotics AND urology”. Additionally, the retrieved articles’ reference lists were investigated. Analysis concentrated on urological surgical systems for laparoscopic surgery that have been given regulatory approval for use on humans. From the late 1980s, before daVinci® Era in 2000s, ancestor platform as Probot® and PUMA 560 were described to outline historical perspective. Thus, new robotic competitors of Intuitive Surgical such as Senhance®, Revo-I®, Versius®, Avatera®, Hinotori®, and HugoTM RAS were illustrated. Although daVinci® had high level competitiveness, and for many years represented the most plausible option for robotic procedures, several modern platforms are emerging in the surgical market. Growing competition through unique features of the new robotic technologies might extend applications fields, improve diffusion, and increase cost-effectiveness procedures. More experiences are needed to identify the role of these new advancements in surgical branches and in healthcare systems.

Several efforts in recent years have been made to predict urinary continence (UC) recovery after radical prostatectomy. The aim of our study was to investigate the impact of surgical urethral length preservation (SULP) on urinary continence after LARP (laparoscopic-assisted radical prostatectomy). We retrospectively queried our datasets from May 2021 to May 2022. After the application of exclusion criteria, a total of 100 patients who underwent LARP for prostate cancer at our institution were enrolled. Through a sterile ruler inserted by a 12 mm trocar, the length of the membranous urethra spared during LARP was assessed intra-operatively. The baseline and peri- and postoperative data of patients were collected, and UC was defined as 0 or 1 on a safety pad. The median SULP was 20.5 mm (IQR, 14.5–25), and the median intraoperative EBL were 150 mL (IQR, 100–200). The Kaplan–Meier curve showed a significant difference at 20 mm, which was used as the cut-off value for SULP (log-rank test, p < 0.001). Multivariate Cox proportional hazards models showed that SULP and EBL < 250 mL were associated with UC recovery (all p < 0.02). Surgical urethral length preservation seemed to improve early UC recovery after LARP. Further multicentric studies are needed to confirm our findings.

Abstract 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-β5, Survivin, TGF-β, 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.

Currently, in clinical practice there are still no useful markers available that are able to diagnose renal cancer in the early stages in the context of population screening. This translates into very high costs for healthcare systems around the world. Analysing urine using an electronic nose (EN) provides volatile organic compounds that can be easily used in the diagnosis of urological diseases. Although no convincing results have been published, some previous studies suggest that dogs trained to sniff urine can recognize different types of tumours (bladder, lung, breast cancer) with different success rates. We therefore hypothesized that urinary volatilome profiling may be able to distinguish patients with renal cancer from healthy controls. A total of 252 individuals, 110 renal patients and 142 healthy controls, were enrolled in this pilot monocentric study. For each participant, we collected, stabilized (at 37 °C) and analysed urine samples using a commercially available electronic nose (Cyranose 320®). Principal component (PCA) analyses, discriminant analysis (CDA) and ROC curves were performed to provide a complete statistical analysis of the sensor responses. The best discriminating principal component groups were identified with univariable ANOVA analysis. The study correctly identified 79/110 patients and 127/142 healthy controls, respectively (specificity 89.4%, sensitivity 71.8%, positive predictive value 84.04%, negative predictive value 80.37%). In order to test the study efficacy, the Cross Validated Accuracy was calculated (CVA 81.7%, p < 0.001). At ROC analysis, the area under the curve was 0.85. The results suggest that urine volatilome profiling by e-Nose seems a promising, accurate and non-invasive diagnostic tool in discriminating patients from controls. The low costs and ease of execution make this test useful in clinical practice.

Abstract Background High grade non-muscle-invasive bladder cancer (HG-NMIBC) is a heterogeneous disease with variable risk of progression. Urinary microRNAs are promising biomarkers for BC detection and surveillance. Let-7c-5p miRNA, clustered with miR-99a-5p and -125b-5p, is deregulated in cancer, including BC. The aim of this study is to evaluate urinary let-7c cluster expression in Ta/T1 HG-NMIBC patients and its impact on progression-free survival (PFS). Methods Quantitative Real-Time-Polymerase-Chain-Reaction (qRT-PCR) was used to analyze the let-7c cluster expression in 57 urine and 49 neoplastic paired tissue samples prospectively collected from transurethral resection (TUR) HG-NMIBC patients. Twenty urine and 10 bladder tissue samples were collected and analyzed as normal controls. QRT-PCR was also used to detect intra−/extra-cellular let-7c cluster in BC cells. Receiver Operating Characteristic (ROC) curves were used to identify urinary miRNAs cut-off values predicting T-stage and PFS. Uni/multivariable Cox regression was performed to identify predictors of PFS. A nomogram predicting progression risk and a decision curve analysis (DCA) were performed. Results Urinary let-7c was significantly up-regulated in patients compared with controls, while the whole cluster was down-regulated in tumor tissues. Supporting these findings, in vitro comparison of extra−/intra-cellular ratios of cluster levels between BC cells, showed a higher ratio for let-7c in HG-NMIBC versus low-grade cells. Urinary let-7c cluster expression was increased in higher T-stage and was an independent predictor of progression. Lower EORTC-score and downregulation of urinary cluster were predictors of higher PFS on univariable Cox regression, while on multivariable analysis only cluster expression was an independent progression predictor. On DCA, a benefit was evident for patients with a PFS probability > 20%. Conclusions Urinary let-7c cluster evaluation may improve prognosis, identifying patients at risk of progression and addressing early radical treatment.

Insufficient physical activity (PA) may be a shared risk factor for the development of both metabolic syndrome (MetS) and prostate cancer (PCa). To investigate this correlation and to develop a nomogram able to predict tumor diagnosis. Between 2016 and 2018, a consecutive series of men who underwent prostate biopsy at three institutions were prospectively enrolled. PA was self-assessed by patients through the Physical Activity Scale for the Elderly (PASE) questionnaire; MetS was assessed according to Adult Treatment Panel III criteria. A logistic regression analyses was used to identify predictors of PCa diagnosis and high-grade disease (defined as International Society of Uro-Pathology grade >2 tumors). A nomogram was then computed to estimate the risk of tumor diagnosis. A total of 291 patients were enrolled; 17.5% of them (n = 51) presented with MetS. PCa was diagnosed in 110 (38%) patients overall while 51 presented high-grade disease. At multivariable analysis, age (OR 1.04; 95%CI: 1.00–1.08; p = 0.048), prostate volume (PV) (OR 0.98; 95%CI: 0.79–0.99; p = 0.004), suspicious digital rectal examination (OR 2.35; 95%CI: 1.11–4.98; p = 0.02), total PSA value (OR 1.12; 95%CI: 1.05–1.2; p < 0.001), and PASE score (OR 0.99; 95%CI: 0.98–0.99; p = 0.01) were independent predictors of tumor diagnosis. The latter two also predicted high-grade PCa. MetS was not associated with PCa diagnosis and aggressiveness. The novel nomogram displayed fair discrimination for PCa diagnosis (AUC = 0.76), adequate calibration (p > 0.05) and provided a net benefit in the range of probabilities between 20% and 90%. reduced PA was associated with an increased risk of PCa diagnosis and high-grade disease. Our nomogram could improve the selection of patients scheduled for prostate biopsy at increased risk of PCa.

The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) play crucial roles in vasculogenesis and angiogenesis. Angiogenesis is an important mechanism in many physiological and pathological processes, and is involved in endothelial cell proliferation, migration, and survival, then leads to further tubulogenesis, and finally promotes formation of vessels. This series of signaling cascade pathways are precisely mediated by VEGF/VEGFR-2 system. The VEGF binding to the IgD2 and IgD3 of VEGFR-2 induces the dimerization of the receptor, subsequently the activation and trans-autophosphorylation of the tyrosine kinase, and then the initiation of the intracellular signaling cascades. Finally the VEGF-activated VEGFR-2 stimulates and mediates variety of signaling transduction, biological responses, and pathological processes in angiogenesis. Several crucial phosphorylated sites Tyr801, Try951, Try1175, and Try1214 in the VEGFR-2 intracellular domains mediate several key signaling processes including PLCγ-PKC, TSAd-Src-PI3K-Akt, SHB-FAK-paxillin, SHB-PI3K-Akt, and NCK-p38-MAPKAPK2/3 pathways. Based on the molecular structure and signaling pathways of VEGFR-2, the strategy of the VEGFR-2-targeted therapy should be considered to employ in the treatment of the VEGF/VEGFR-2-associated diseases by blocking the VEGF/VEGFR-2 signaling pathway, inhibiting VEGF and VEGFR-2 gene expression, blocking the binding of VEGF and VEGFR-2, and preventing the proliferation, migration, and survival of vascular endothelial cells expressing VEGFR-2.

Abstract 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.

Objective: Cross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism (viz. failure of serum TSH to reach target levels, if hypothyroidism is primary).Further to evaluating the magnitude of sub-optimally treated primary hypothyroidism as a result of co-ingestion of those medications, we wished to ascertain whether the above complications would occur during a low number of years under polypharmacy. Method: In this retrospective study in collaboration with 8 family physicians, we enrolled adults with primary hypothyroidism under L-T4 therapy that, for 2 years minimum, was not associated with those medications (non-exposure, baseline) and that, for another 2 years minimum, it was (exposure). Outcomes were serum levels and proportions of serum TSH levels >4.12 mU/L, and proportions of complications. Complications were aggravation of pre-existing or de novo onset of any of metabolic syndrome, impaired fasting glycemia (IFG), diabetes mellitus, dyslipidemia, hypertension, coronary heart disease (CHD), cerebrovascular disease (CVD). Result: A total of 114 patients were enrolled. Duration of exposure to the interfering medication was 32.1 ± 6.9 months (median 31; range 24–55). Compared with non-exposure, the exposure period resulted in greater TSH levels (2.81 ± 3.62 [median 1.79] vs 1.27 ± 1.34 [median 0.93], P = 2.2 × 10−20) and proportions of values >4.12 mU/L (18.5% vs 4.7%, P = 1.2 × 10−7). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 mU/L were greater than in the 36 complication-free patients (22% vs 11%, P = 0.018). Conclusion: During a median period of 31 months, there are relevant consequences for L-T4 treated adult hypothyroid patients resulting from hyperthyrotropinemia caused by medications impairing L-T4 absorption. This should be taken into account by future guidelines on hypothyroidism management. Keywords: Subclinical hypothyroidism, Levothyroxine malabsorption, Diabetes mellitus, Dyslipidemia, Hypertension, Cardiovascular diseases