Robotic Medtronic Hugo™ RAS System Is Now Reality: Introduction to a New Simulation Platform for Training Residents.

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 Impact of Metastasectomy on Survival Outcomes of Renal Cell Carcinoma: A 10-Year Single Center Experience.

OBJECTIVES: The role of surgical metastasectomy (MST) in solitary or oligometastasis from renal cell carcinoma (RCC) and its impact on survival outcomes remains poorly addressed. We evaluated the impact of MST on overall survival (OS) in patients with oligometastatic (m)RCC. MATERIALS AND METHODS: The institutional renal cancer prospective database was examined for cases treated with partial or radical nephrectomy who developed metastatic disease during follow-up. Patients with evidence of clinical metastasis at first diagnosis were excluded. Patients considered unfit for MST received systemic treatment (ST); all others received MST. The impact of MST vs. the ST only cohort was assessed with the Kaplan-Meier method. Age, gender, bilaterality, histology, AJCC stage of primary tumor, surgical margins, local vs. distant metastasis and MST were included in univariable and multivariable regression analyses to assess the predictors of OS. RESULTS: Overall, at a median follow-up of 16 months after primary treatment, 168 patients with RCC developed asynchronous metastasis at the adrenal gland, lung, liver, spleen, peritoneal, renal fossa, bone, nodes, brain and thyroid gland. Nine patients unfit for any treatment were excluded. The site of metastasis was treated with surgical MST (77/159, 48.4%), with or without previous or subsequent ST, while 82/159 cases (51.2%) received ST only. The 2-year, 5-year and 10-year OS probabilities were 93.8%, 82.8% and 79.5%, respectively. After multivariable analysis, MST and the primary tumor AJCC stage were independent predictors of OS probabilities (p = 0.019 and p = 0.035, respectively). After Kaplan-Meier analysis, MST significantly improved OS probabilities versus patients receiving ST (p < 0.001). LIMITATIONS: The main drawbacks of our research were the small sample size from a single-tertiary referral institution, as well as the absent or different ST lines in the cohort of patients receiving MST. CONCLUSIONS: When an NED status is achievable, surgical MST of mRCC significantly impacts OS, delaying and not precluding further subsequent ST.

Assessing the Trade-off Between the Safety and Effectiveness of Off-clamp Robotic Partial Nephrectomy for Renal Masses with a High RENAL Score: A Propensity Score-matched Comparison of Perioperative and Functional Outcomes in a Multicenter Analysis.

BACKGROUND: Tumors with a high nephrometry score represent a challenging surgical scenario for which robotic partial nephrectomy (RPN) is a primary option in expert hands. OBJECTIVE: To compare perioperative and functional outcomes of off-clamp and on-clamp RPN in patients with renal masses with a high RENAL score (≥9). DESIGN, SETTING, AND PARTICIPANTS: For this retrospective analysis, an RPN data set including 1604 patients treated at three institutions between 2003 and 2021 was queried for cases with a RENAL score ≥9. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used 1:1 propensity score matching (PSM) to select a cohort in which imbalances between the off-clamp and on-clamp groups were minimized. We used χ2 and Student t tests to compare categorical and continuous variables, respectively. The Kaplan-Meier method was used to compare the probability of having an estimated glomerular filtration rate (eGFR) ≥45 ml/min during follow-up. Univariable and multivariable analyses were performed to identify predictors of a trifecta outcome (negative surgical margin status, no Clavien-Dindo grade ≥3 complications, eGFR decline ≤30%) and of retaining eGFR ≥45 ml/min over time. RESULTS AND LIMITATIONS: From an overall cohort of 354 patients (142 on-clamp, 212 off-clamp), a homogeneous PSM cohort of 78 patients in each group was selected (p ≥ 0.17). In the PSM cohort, operative time was significantly shorter in the off-clamp group (p < 0.001). There were no differences between the groups in the rates of severe complications (p = 0.32) and positive surgical margins (p = 0.24). The rate of trifecta achievement was significantly higher in the off-clamp group (83.3% vs 67.9%; p = 0.03). Warm ischemia time >20 min was independently negatively associated with trifecta achievement (odds ratio 0.32, 95% confidence interval 0.14-0.74). Moreover, the off-clamp group had a significantly higher probability of retaining eGFR ≥45 ml/min over time (3 yr: 95.9% vs 81.6%; p = 0.03); every 1-min increase in warm ischemia time reduced this probability by 1.3%. CONCLUSIONS: We found a favorable trade-off between the benefits and risks of off-clamp RPN, with similar perioperative outcomes and a net benefit in terms of trifecta achievement and long-term renal function outcomes in comparison to on-clamp RPN. PATIENT SUMMARY: The complexity of surgery for kidney tumors can be assessed using the RENAL score, which is a measure of the location and size of a kidney tumor. In a multicenter series of patients with tumors with a high RENAL score, we compared outcomes between strategies with (on-clamp) and without (off-clamp) clamping of kidney blood vessels during robot-assisted removal of part of the affected kidney. We found that off-clamp surgery results in better postoperative kidney function.

Human Urinary Volatilome Analysis in Renal Cancer by Electronic Nose.

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.

Cefiderocol Efficacy in a Real-Life Setting: Single-Centre Retrospective Study.

The current carbapenem-resistant gram-negative bacteria (CR-GN) treatment guidelines lack strong evidence about cefiderocol (CFD) efficacy against CR-GN, especially CRAB. The study's purpose is to evaluate the effectiveness of CFD in a real-life setting. We made a single-center retrospective study of 41 patients who received CFD in our hospital for several CR-GN infections. Bloodstream infections (BSI) affected 43.9% (18/41) of patients, while CRAB affected 75.6% (31/41) of isolated CR-GN patients. Thirty-days (30-D) all-causes mortality affected 36.6% (15/41) of patients, while end-of-treatment (EOT) clinical cure affected 56.1% (23/41). Finally, microbiological eradication at EOT affected 56.1% (23/41) of patients. Univariate and multivariate analysis showed that septic shock is an independent factor associated with mortality. Subgroup analyses showed no difference in CFD effectiveness between monotherapy and combination therapy.

Sutureless Purely Off-Clamp Robot-Assisted Partial Nephrectomy: Avoiding Renorrhaphy Does Not Jeopardize Surgical and Functional Outcomes.

To compare outcomes of sutureless (SL) vs. renorrhaphy (RR) off-clamp robotic partial nephrectomy (ocRPN), we retrospectively analyzed procedures performed at our center, from January 2017 to April 2021, for cT1-2N0M0 renal masses. All the patients with a minimum follow-up < 1 month were excluded from the analysis. The trifecta rate defined surgical quality. Any worsening from chronic kidney disease (CKD) I-II to ≧ IIIa (from IIIa to ≧ IIIb, and from IIIb to ≧ IV) was considered as significant stage migration (sCKDsm). A 1:1 propensity score-matched (PSM) analysis minimized baseline imbalances between SL and RR cohorts in terms of age, gender, ASA score, baseline estimated glomerular filtration rate (eGFR), tumor size, and RENAL score. Logistic regression analyses identified predictors of trifecta achievement. Kaplan-Meier (KM) analysis assessed the impact of RR on significant chronic kidney disease sCKDsm-free survival (SMFS), while Cox regression analyses identified its predictors. Overall, 531 patients were included, with a median tumor size of 3.5 cm (IQR: 2.7-5); 70 (13%) presented with a cT2 mass. An SL approach was pursued in 180 cases, but 10 needed conversion to RR. After PSM analysis, patients receiving SL showed a higher trifecta rate (94% vs. 84%; p = 0.007). SMFS probabilities were comparable at KM analysis (log-rank = 0.69). Age (OR: 0.97; 95%CI: 0.95-0.99; p = 0.01), a RENAL score ≧ 10 (OR: 0.29; 95%CI: 0.15-0.57; p < 0.001), and RR (OR: 0.34; 95%CI: 0.17-0.67; p = 0.002) were independent predictors of trifecta achievement. Age (OR: 1.04; 95%CI: 1.003-1.07; p = 0.03) and baseline eGFR (OR: 0.99; 95%CI: 0.97-0.99; p = 0.05) independently predicted sCKDsm. Compared to RR, our experience seems to show that the SL approach significantly increased the probabilities of achieving the trifecta in the observed group of cases.

Purely Off-Clamp Laparoscopic Partial Nephrectomy Stands the Test of Time: 15 Years Functional and Oncologic Outcomes from a Single Center Experience.

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.

On-Clamp vs. Off-Clamp Robot-Assisted Partial Nephrectomy for cT2 Renal Tumors: Retrospective Propensity-Score-Matched Multicenter Outcome Analysis.

We compared perioperative outcomes after on-clamp versus off-clamp robot-assisted partial nephrectomy (RAPN) for >7 cm renal masses. A multicenter dataset was queried for patients who had undergone RAPN for a cT2cN0cM0 kidney tumor from July 2007 to February 2022. The Trifecta achievement (negative surgical margins, no severe complications, and ≤ 30% postoperative estimated glomerular filtration rate (eGFR) reduction) was considered a surrogate of surgical quality. Overall, 316 cases were included in the analysis, and 58% achieved the Trifecta. A propensity-score-matched analysis generated two cohorts of 89 patients homogeneous for age, ASA score, preoperative eGFR, and RENAL score (all p > 0.21). Compared to the on-clamp approach, OT was significantly shorter in the off-clamp group (80 vs. 190 min; p < 0.001), the incidence of sRFD was lower (22% vs. 40%; p = 0.01), and the Trifecta rate higher (66% vs. 46%; p = 0.01). In a crude analysis, >20 min of hilar clamping was associated with a significantly higher risk of sRFD (OR: 2.30; 95%CI: 1.13−4.64; p = 0.02) and with reduced probabilities of achieving the Trifecta (OR: 0.46; 95%CI: 0.27−0.79; p = 0.004). Purely off-clamp RAPN seems to be a safe and viable option to treat cT2 renal masses and may outperform the on-clamp approach regarding perioperative surgical outcomes.

Volatilome Analysis in Prostate Cancer by Electronic Nose: A Pilot Monocentric Study.

Urine analysis via an electronic nose provides volatile organic compounds easily usable in the diagnosis of urological diseases. Although challenging and highly expensive for health systems worldwide, no useful markers are available in clinical practice that aim to anticipate prostate cancer (PCa) diagnosis in the early stages in the context of wide population screening. Some previous works suggested that dogs trained to smell urine could recognize several types of cancers with various success rates. We hypothesized that urinary volatilome profiling may distinguish PCa patients from healthy controls. In this study, 272 individuals, 133 patients, and 139 healthy controls participated. Urine samples were collected, stabilized at 37 °C, and analyzed using a commercially available electronic nose (Cyranose C320). Statistical analysis of the sensor responses was performed off-line using principal component (PCA) analyses, discriminant analysis (CDA), and ROC curves. Principal components best discriminating groups were identified with univariable ANOVA analysis. groups were identified with univariable ANOVA analysis. Here, 110/133 and 123/139 cases were correctly identified in the PCa and healthy control cohorts, respectively (sensitivity 82.7%, specificity 88.5%; positive predictive value 87.3%, negative predictive value 84.2%). The Cross Validated Accuracy (CVA 85.3%, p < 0.001) was calculated. Using ROC analysis, the area under the curve was 0.9. Urine volatilome profiling via an electronic nose seems a promising non-invasive diagnostic tool.

Off-clamp robot-assisted partial nephrectomy for purely hilar tumors: Technique, perioperative, oncologic and functional outcomes from a single center series.

OBJECTIVES: Purely hilar lesions and those abutting the main renal artery or vein may be significantly different in terms of surgical complexity, requiring different resection strategies. To describe surgical technique and to assess its safety, oncologic and functional outcomes of a single centre experience of Off-Clamp Robotic Partial Nephrectomy (Off-C RPN) for purely hilar renal masses. METHODS: The Institutional Review Board renal cancer database was queried for: "robotic", "partial nephrectomy" and "hilar". Baseline imaging was reviewed for all cases to strictly select patients with purely hilar tumors, defined as tumors arising into the renal hilum without any exophytic growth. Off-C RPN with straight access to the hilum was performed in all cases. We reported baseline, perioperative, oncologic and functional outcomes of the institutional series of purely hilar masses treated with Off-C RPN. RESULTS: Between 2011 and 2019, 680 Off-C RPN were performed. Overall, 20 cases were classified as "hilar" renal tumors. Ten lesions abutting the main renal artery or vein were excluded leaving 10 purely hilar cases for analysis. Median operative time was 85 (range 68-115) minutes. No high-grade complications occurred. One patient (10%) required blood transfusion. At a median follow-up of 27 months, one renal recurrence and one newly onset Chronic Kidney Disease stage 3A was observed. CONCLUSIONS: RPN for purely hilar tumors has been poorly addressed and distinguishing purely hilar from tumors abutting the hilar vessels may have significant technical implications. In tertiary referral centers, Off-C RPN for purely hilar tumors provides excellent perioperative, oncologic and functional outcomes.

Characterizing the tumor microenvironment in rare renal cancer histological types.

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 < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.

Genomic and evolutionary classification of lung cancer in never smokers.

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.

Impact of Histology and Tumor Grade on Clinical Outcomes Beyond 5 Years of Follow-Up in a Large Cohort of Renal Cell Carcinomas.

INTRODUCTION: The optimal length for clinical follow-up of renal cell carcinoma (RCC) patients is unclear. We evaluated the impact of ISUP/WHO tumor grade and histological subtype on short- and long-term survival and risk of recurrence/metastasis in a large cohort of RCC patients. PATIENTS AND METHODS: We studied 1679 RCC patients from a single referral center in Italy. Adjusted hazard ratios for overall survival were estimated using Cox regression models. Adjusted absolute risk of developing recurrence or metastasis was computed considering competing risks of mortality. RESULTS: During up to 13 years of follow-up, 175 (10.4%) RCC patients died, of whom 92% beyond 5 years. Hazard ratio of grade IV clear cell carcinomas (ccRCC) was 3.82 compared to grade II. Notably, 33% of recurrences and 56% of distant metastases occurred beyond 5 years of follow-up. The estimated probabilities of recurrence/metastasis were 15% and 45% within and beyond 5 years of follow-up, respectively. After 5 years, the absolute risk of recurrences increased also for papillary renal cell carcinoma type I (35.2%) and grade I ccRCC (17%). CONCLUSION: After 5 years of follow-up, both risk of mortality and recurrences or metastases were high and were modified by histological types and tumor grade. These data strongly support histology- and grade-tailored surveillance strategies and long-term follow-up for RCC patients.

Urine LOX-1 and Volatilome as Promising Tools towards the Early Detection of Renal Cancer.

Renal cell carcinoma (RCC) represents around 3% of all cancers, within which clear cell RCC (ccRCC) are the most common type (70-75%). The RCC disease regularly progresses asymptomatically and upon presentation is recurrently metastatic, therefore, an early method of detection is necessary. The identification of one or more specific biomarkers measurable in biofluids (i.e., urine) by combined approaches could surely be appropriate for this kind of cancer, especially due to easy obtainability by noninvasive method. OLR1 is a metabolic gene that encodes for the Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), implicated in inflammation, atherosclerosis, ROS, and metabolic disorder-associated carcinogenesis. Specifically, LOX-1 is clearly involved in tumor insurgence and progression of different human cancers. This work reports for the first time the presence of LOX-1 protein in ccRCC urine and its peculiar distribution in tumoral tissues. The urine samples headspace has also been analyzed for the presence of the volatile compounds (VOCs) by SPME-GC/MS and gas sensor array. In particular, it was found by GC/MS analysis that 2-Cyclohexen-1-one,3-methyl-6-(1-methylethyl)- correlates with LOX-1 concentration in urine. The combined approach of VOCs analysis and protein quantification could lead to promising results in terms of diagnostic and prognostic potential for ccRCC tumors.

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.

Impact of learning curve on perioperative outcomes of off-clamp minimally invasive partial nephrectomy: propensity score matched comparison of outcomes between training versus expert series.

BACKGROUND: Off-clamp robotic partial nephrectomy (Off C-RPN) is a challenging technique, hard to teach since bleeding control is not easily reproducible in training settings. We compared perioperative outcomes of two propensity score matched (PSM) cohorts of patients undergone Off C-RPN by either a training or an expert surgeon in the same Institution. METHODS: The prospectively maintained "renal cancer" database was queried for "off-clamp," "robotic," "partial nephrectomy" performed between January 2017 and June 2018. Achievement of main outcomes along the learning curve of training surgeon was assessed with logistic regression and Lowess analysis. A 1:1 PSM analysis generated two populations homogeneous for demographics, ASA score, tumor size, nephrometry score, baseline hemoglobin and estimated glomerular filtration rate (eGFR). Multiple tumors, and imperative indications were excluded. Categorical and continuous variables were compared by χ2 and t-test. RESULTS: Overall, 111 were treated by the expert, 51 by the training surgeon, respectively. Training surgeon experienced a significant decrease of console time (P=0.01). Patients treated by the expert surgeon had significantly larger tumors, higher PADUA and ASA scores (all P≤0.04). After applying the PSM, two cohorts of 29 patients, homogeneous for all baseline demographic and clinical variables (all P≥0.34) were selected. Hilar clamping was never necessary. Hospital stay, hemoglobin and eGFR at discharge, complication and positive surgical margins rates were comparable between the two cohorts (all P≥0.15). CONCLUSIONS: Our results proved that the impact of learning curve on outcomes of Off C-RPN is negligible after completion of a proper training in minimally invasive surgery.

On-clamp versus purely off-clamp robot-assisted partial nephrectomy in solitary kidneys: comparison of perioperative outcomes and chronic kidney disease progression at two high-volume centers.

BACKGROUND: Minimal literature describes the impact of hilar control on the progression to chronic kidney disease (pCKD) after robotic partial nephrectomy (RPN) in solitary kidneys (SK). The aim of this study was to compare purely off-clamp (ocRPN) vs. on-clamp robotic partial nephrectomy (onRPN) in SK and to identify predictors of pCKD at two high-volume centers. METHODS: Between December 2013 and October 2019, 54 patients with SK underwent ocRPN and onRPN for renal tumors at two institutions. Baseline and perioperative data were analyzed. Newly onset of CKD stage 3b,4,5 (CKD3b,4,5) was assessed by Kaplan-Meier curves and compared for warm ischemia time (WIT) with the log-rank test. Cox regression analysis was used to identify predictors of pCKD. RESULTS: At a median follow-up of 13 months (IQR 6.3-34), newly onset of CKD3b and CKD 4.5 were observed in 11.1% and 7.4% of patients, respectively. onRPN was associated with a higher risk of progression to CKD 3b,4,5 stages (P=0.034) and higher rate of perioperative complications (P=0.03). On univariable analysis eGFR at discharge (eGFRd), positive surgical margins status (PSM) and WIT were predictors of newly onset of CKD3b,4,5 (each P<0.05). Multivariable analysis identified eGFRd (HR 0.88; CI 95% 0.81-0.96) and WIT (HR 1.09; CI 95% 1.02-1.16) as independent predictors of pCKD (each P<0.01). Main limitations include the retrospective nature of the study, the short-term follow-up and the lack of data adjustment for parenchymal volume loss. CONCLUSIONS: eGFRd and WIT during RPN are independent predictors of pCKD in SK. In this setting a critical reduction of WIT should be achieved according to the oncologic outcome. In patients with SK, WIT represents the only surgical modifiable factor of RPN for avoiding a quicker onset of pCKD.

Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication.

Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options. We collected 26 CDC cases, and we assessed HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in-situ hybridization (FISH) according to 2018 ASCO/CAP HER2-testing recommendations. Six out of twenty-six (23%) tumors showed HER2 positive staining. In particular, 3+ score was present in 2/6 cases (33%), 2+ in 3/6 cases (50%) and 1+ in 1/6 cases (17%). The 6 HER2+ tumors were also analyzed by FISH to assess gene copy number. One out of six CDC with IHC 3+ was also HER2 amplified, showing an average HER2 copy number ≥4.0 (10.85) and a HER2/CEP17 ratio ≥ (5.63), while the 5/6 cases were HER2 negative. Based on the 2018 ASCO/CAP guidelines overall, 2/26 CDC cases (8%) were HER2+. The present study provides evidence for testing, in future studies, HER2 to assess its clinical value as a novel target for the treatment of this highly malignant cancer.

Impact of Clinical Response to Neoadjuvant Chemotherapy in the Era of Robot Assisted Radical Cystectomy: Results of a Single-Center Experience.

BACKGROUND: Response to neoadjuvant chemotherapy (NACT) has been proven to be an established prognostic factor after open radical cystectomy (ORC). We evaluated the impact of NACT on survival outcomes of a single-institution robotic radical cystectomy (RARC) series. METHODS: From January 2012 to June 2020, 79 patients were identified. Baseline, demographic, perioperative, and pathologic data were described. Kaplan-Meier with the log-rank test was used to compare overall survival (OS) differences between complete, partial, and no-NACT responders, respectively. Univariable and multivariable regression analyses were performed to identify predictors of OS. RESULTS: Complete, partial, and absent response to NACT were recorded in 43 (54.4%), 21 (19%), and 15 (26.6%) patients, respectively. A complete response to NACT displayed a trend toward significant higher OS (p = 0.03). In univariable analysis, significant predictors of lower OS were hypertension (HR 3.37; CI 95% 1.31-8.62; p = 0.01); advanced nodal involvement (HR 2.41; CI 95% 0.53-10.9; p < 0.001); and incomplete response to NACT (HR 0.41; CI 95% 0.18-0.95; p = 0.039). In multivariable analysis, the only independent predictor of worse OS was advanced pathologic N stages (HR 10.1; CI: 95% CI 2.3-44.3; p = 0.002). CONCLUSIONS: Complete response to NACT is associated with increased OS probability, but significant nodal residual disease remains the only independent predictor of OS after RARC.