External validation of yonsei nomogram predicting chronic kidney disease development after partial nephrectomy: An international, multicenter study.

OBJECTIVE: To externally validate Yonsei nomogram. METHODS: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis. RESULTS AND LIMITATION: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. CONCLUSIONS: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.

Is off-clamp robot-assisted partial nephrectomy beneficial for renal function? Data from the CLOCK trial.

OBJECTIVES: To compare the functional outcomes of on- vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT). MATERIALS AND METHODS: The CLOCK study (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy; NCT02287987) is a multicentre RCT including patients with normal baseline function, two kidneys and masses with RENAL scores ≤ 10. Pre- and postoperative renal scintigraphy was prescribed. Renal defatting and hilum isolation were required in both study arms; in the on-clamp arm, ischaemia was imposed until the completion of medullary renorraphy, while in the off-clamp condition it was not allowed throughout the procedure. The primary endpoint was 6-month absolute variation in estimated glomerular filtration rate (AV-GFR); secondary endpoints were: 12, 18 and 24-month AV-GFR; 6-month estimated glomerular filtration rate variation >25% rate (RV-GFR >25); and absolute variation in ipsilateral split renal function (AV-SRF). The planned sample size was 102 + 102 cases, after taking account crossover of cases to the alternate study arm; a 1:1 randomization was performed. AV-GFR and AV-SRF were compared using analysis of covariation, and RV-GFR >25 was assessed using multivariable logistic regression. Intention-to-treat (ITT) and per-protocol analyses (PP) were performed. RESULTS: A total of 160 and 164 patients were randomly assigned to on- and off-clamp RAPN, respectively; crossover was observed in 14% and 43% of the on- and off-clamp arms, respectively. We were unable to find any statistically significant difference between on- vs off-clamp with regard to the primary endpoint (ITT: 6-month AV-GFR -6.2 vs -5.1 mL/min, mean difference 0.2 mL/min, 95% confidence interval [CI] -3.1 to 3.4 [P = 0.8]; PP: 6-month AV-GFR -6.8 vs -4.2 mL/min, mean difference 1.6 mL/min, 95% CI -2.3 to 5.5 [P = 0.7]) or with regard to the secondary endpoints. The median warm ischaemia time was 14 vs 15 min in the ITT analysis and 14 vs 0 min in the PP analysis. CONCLUSION: In patients with regular baseline function and two kidneys, we found no evidence of differences in functional outcomes for on- vs off-clamp RAPN.

Assessing the impact of socio-economic determinants on access to care, surgical treatment options and outcomes among patients with renal mass: Insight from the universal healthcare system.

OBJECTIVE: To assess whether socio-economic disparities exist on access to care, treatment options and outcomes among patients with renal mass amenable of surgical treatment within the universal healthcare system. METHODS: Data of consecutive patients submitted to partial nephrectomy (PN) or radical nephrectomy (RN) at our Institution between 2017 and 2020 were retrospectively evaluated. Patients were grouped according to their income level (low, intermediate, and high) based on the Indicator of Equivalent Economic Situation national criterion. Survival analysis was performed. Cox regression models were employed to analyse the impact of socio-economic variables on survival outcomes. RESULTS: One thousand forty-two patients were included (841 PN and 201 RN). Patients at the lowest income level were found more likely symptomatic and with a higher pathological tumour stage in the RN cohort (p > 0.05). The guidelines adherence on surgical indication rate as well as the access to minimally invasive surgery did not differ according to patient's income level in both cohorts (p > 0.05). Survival curves were comparable among the groups. Cox regression analysis showed that none of the included socio-economic variables was associated with survival outcomes in our series. CONCLUSIONS: Universal healthcare system may increase the possibility to ensure egalitarian treatment modalities for patients with renal cancer.

Prediction of significant renal function decline after open, laparoscopic, and robotic partial nephrectomy: External validation of the Martini's nomogram on the RECORD2 project cohort.

OBJECTIVES: Martini et al. developed a nomogram to predict significant (>25%) renal function loss after robot-assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini's nomogram on a large, national, multi-institutional data set including open, laparoscopic, and robot-assisted partial nephrectomy. METHODS: Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini's nomogram were applied to each approach predicting renal function loss at all the specific timeframes. RESULTS: Multivariable models showed high area under the curve for robot-assisted partial nephrectomy at 6- and 12-month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot-assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was <70% at 48 months of follow-up. CONCLUSIONS: Martini's nomogram is a valid tool for predicting the decline in renal function at 6 and 12 months after robot-assisted partial nephrectomy and laparoscopic partial nephrectomy, whereas it showed a lower performance at longer follow-up and in patients treated with open approach at all these time cutoffs.

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer.

BACKGROUND: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence. METHODS: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc). DISCUSSION: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered.

Contrast-enhanced ultrasound (CEUS) imaging for active surveillance of small renal masses.

PURPOSE: To assess the safety and efficacy of contrast-enhanced ultrasound (CEUS) imaging for monitoring small (< 4 cm) renal masses (SRM) in patients undergoing active surveillance (AS). METHODS: We retrospectively selected all consecutive patients with SRMs who underwent AS for at least 6 months at our Institution between January 2014 and December 2018. CEUS imaging was performed by two experienced genitourinary radiologists at established time points. The accuracy of CEUS for monitoring SRM size was compared with that of CT scan. For solid SRMs, four enhancement patterns (EP) were recorded. Radiological progression was defined as SRM growth rate ≥ 5 mm/year. RESULTS: Overall, 158/1049 (15.1%) patients with SRMs underwent AS. At a median follow-up of 25 months (IQR 13-39), no patient died due to renal cell carcinoma (RCC). No patients experienced CEUS-related adverse events. There was a large variability in the pattern of growth of SRMs (overall median growth rate: 0.40 mm/year), with 9.5% of SRMs showing radiological progression. The median SRM size was comparable between CEUS and CT scan examinations at all time points. The vast majority (92.7%) of SRMs did not show a change in their EP over time; and there was no association between the SRM's EP and radiological progression or SRM size. Overall, 43 (27.2%) patients underwent delayed intervention (DI); median SRM size, and median growth rate were significantly higher in these patients as compared to those continuing AS. CONCLUSION: In experienced hands, CEUS is a safe and effective strategy for active monitoring of SRMs in well-selected patients undergoing AS.

Perioperative outcomes of robotic and laparoscopic adrenalectomy: a large international multicenter experience.

BACKGROUND: The aim of the study was to describe the surgical outcomes of a retrospective series of consecutive patients treated with laparoscopic and robotic approach for adrenal masses in two tertiary referral centers. METHODS: We retrospectively gathered data of 477 patients submitted to adrenalectomy performed at two Institutions from March 2008 to February 2018 by six highly experienced surgeons. We excluded from the analysis 43 patients that had an open approach for tumors or for anesthetic contraindications to minimally invasive surgery (MIS). Patients were selected for surgery after a radiologic and an endocrinology work up. Preoperative, perioperative and postoperative data were recorded. RESULTS: Overall, 477 patients were included in the study. The robotic and the laparoscopic group included 110 and 367 patients, respectively. The preoperative characteristics were similar in both groups except for ASA score with a median (IQR) of 3 and 2 in the robotic and in the laparoscopic group, respectively (p = 0.03). Tumor size of adrenal tumors treated robotically (4, IQR 2.6-6 cm) was significantly larger than those treated laparoscopically (3, IQR 2.3-4.1 cm) (p = 0.01). The intraoperative complication rates were similar between robotic and laparoscopic groups (6.3% and 6%, respectively). The postoperative complication rate was 5.4% for robotic group and similarly 3.5% for laparoscopic adrenalectomy strategy. We analyzed the tumor ≥ 6 cm, with 29 patients in the robotic group and 43 in the laparoscopic one, with an overall complication rate of 19.5%. At multivariable analyses tumor size (OR 1.287; CI 1.128-1.468; p < 0.001) was the only independent predictor of overall complication. CONCLUSION: Adrenal tumors can be safely treated either by robotic or laparoscopic strategy. MIS seems to be feasible also in larger adrenal masses (≥ 6 cm). Tumor size represents the only predictive factors for overall complication.

Transperitoneal vs retroperitoneal minimally invasive partial nephrectomy: comparison of perioperative outcomes and functional follow-up in a large multi-institutional cohort (The RECORD 2 Project).

BACKGROUND: Aim of this study was to evaluate and compare perioperative outcomes of transperitoneal (TP) and retroperitoneal (TR) approaches in a multi-institutional cohort of minimally invasive partial nephrectomy (MI-PN). MATERIAL AND METHODS: All consecutive patients undergone MI-PN for clinical T1 renal tumors at 26 Italian centers (RECORd2 project) between 01/2013 and 12/2016 were evaluated, collecting the pre-, intra-, and postoperative data. The patients were then stratified according to the surgical approach, TP or RP. A 1:1 propensity score (PS) matching was performed to obtain homogeneous cohorts, considering the age, gender, baseline eGFR, surgical indication, clinical diameter, and PADUA score. RESULTS: 1669 patients treated with MI-PN were included in the study, 1256 and 413 undergoing TP and RP, respectively. After 1:1 PS matching according to the surgical access, 413 patients were selected from TP group to be compared with the 413 RP patients. Concerning intraoperative variables, no differences were found between the two groups in terms of surgical approach (lap/robot), extirpative technique (enucleation vs standard PN), hilar clamping, and ischemia time. Conversely, the TP group recorded a shorter median operative time in comparison with the RP group (115 vs 150 min), with a higher occurrence of intraoperative overall, 21 (5.0%) vs 9 (2.1%); p = 0.03, and surgical complications, 18 (4.3%) vs 7 (1.7%); p = 0.04. Concerning postoperative variables, the two groups resulted comparable in terms of complications, positive surgical margins and renal function, even if the RP group recorded a shorter median drainage duration and hospital length of stay (3 vs 2 for both variables), p < 0.0001. CONCLUSIONS: The results of this study suggest that both TP and RP are feasible approaches when performing MI-PN, irrespectively from tumor location or surgical complexity. Notwithstanding longer operative times, RP seems to have a slighter intraoperative complication rate with earlier postoperative recovery when compared with TP.

Mechanically Interlocked Nitrogenated Nanographenes.

Herein, we report the synthesis of mechanically interlocked nitrogenated nanographenes. These systems have been obtained by clipping different tetralactam macrocycles around a 1.9 nm dumbbell-shaped nitrogenated nanographene. Thermal, optoelectronic, and electrochemical characterization of the different mechanically interlocked nanographenes evidence enhanced thermal and photochemical stability, and also absorption and emission properties that vary with the structure of the macrocycle.

Impact of Resection Technique on Perioperative Outcomes and Surgical Margins after Partial Nephrectomy for Localized Renal Masses: A Prospective Multicenter Study.

PURPOSE: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury). MATERIALS AND METHODS: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement. RESULTS: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement. CONCLUSIONS: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

Safety of on- vs off-clamp robotic partial nephrectomy: per-protocol analysis from the data of the CLOCK randomized trial.

PURPOSE: To compare the safety of on- vs off-clamp robotic partial nephrectomy (RAPN). METHODS: 302 patients with RENAL masses ≤ 10 were randomized to undergo on-clamp (150) vs off-clamp (152) RAPN (CLOCK trial-ClinicalTrials.gov NCT02287987) at seven institutions by one experienced surgeon per institution. Intra-operative data, complications, and positive surgical margins were compared. RESULTS: Due to a relevant rate of shift from the assigned treatment, the per-protocol analysis only was considered and the data from 129 on-clamp vs 91 off-clamp RAPNs analyzed. Tumor size (off-clamp vs on-clamp, 2.2 vs 3.0 cm, p < 0.001) and RENAL score (5 vs 6, p < 0.001) significantly differed. At univariate analysis, no differences were found regarding intra-operative estimated blood loss (off- vs on-clamp, 100 vs 100 ml, p = 0.7), post-operative complications rate (19% vs 26%, p = 0.2), post-operative anemia (Hb decrease > 2.5 g/dl 26% vs 27%, p = 0.9; transfusion rate 3.4% vs 6.3%, p = 0.5; re-intervention due to bleeding 1.1% vs 4%, p = 0.4), acute kidney injury (4% vs 6%, p = 0.8), and positive surgical margins (3.5% vs 8.2%, p = 0.1). At multivariate analysis accounting for tumor diameter and complexity, considering the on-clamp group as the reference category, a significant difference was noted in the off-clamp group exclusively for blood loss (OR 0.3, 95% CI 0.09-0.52, p = 0.008). CONCLUSIONS: The on-clamp and off-clamp approaches for RAPN showed a comparable safety profile.

Robotic treatment for urinary tract endometriosis: preliminary results and surgical details in a high-volume single-Institutional cohort study.

BACKGROUND: Aim of the study was to present the surgical techniques and the postoperative outcomes in women treated with robotic excision for deep endometriosis involving the urinary tract. MATERIALS AND METHODS: We retrospectively reviewed the prospectively recorded clinical data of women consecutively undergoing minimally invasive treatment for complex endometriosis involving urinary tract in our center between January 2012 and June 2018. All the patients received a preoperative multidisciplinary evaluation with the general surgeon, the gynecologist and the urologist due to the frequent concomitant involvement of bowel and genital system. Patients undergoing robotic surgery were treated with the Si or Xi da Vinci surgical system. RESULTS: A total of 74 consecutive patients were enrolled. Twenty-eight (37.8%) patients underwent conventional laparoscopy and 46 (62.2%) robotic surgery. Only patients treated with robotic approach were considered for the final analyses. Overall, 17 (36.9%) patients were treated with partial cystectomy, 13 (28.3%) with ureteral reimplantation, 10 (21.7%) patients were treated with ureteral lysis, 4 (8.7%) with removal of bladder endometrial node without opening the mucosa layer and 2 (4.3%) with ureteral end-to-end anastomosis. Concomitant involvement of bowel and genital system was registered in 14 (30.4%) and 32 (69.5%) patients, respectively. No conversions to laparotomy were recorded. Overall, 5 (10.9%) patients experienced postoperative complications, of which only one was a major complication (Clavien 3b). At a median follow-up of 31.3 (IQR 17.6-43.3) months, 4 (8.7%) patients experienced disease recurrence at the level of urinary tract. CONCLUSIONS: Robotic excision of urological endometriosis represents a safe and effective treatment option, since a limited rate of surgical complications was recorded even in cases of multi-organ disease.

A Prospective, Open-Label Comparison of Tamsulosin plus Serenoa repens and Bovine Colostrum versus Tamsulosin Alone in the Treatment of Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the efficacy and safety of oral supplementation with Serenoa repens (SR) and bovine colostrum (BC) plus tamsulosin (TAM) versus TAM alone over 12 months in men suffering from lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: Between February 2018 and February 2019, men with symptomatic BPH (IPSS ≥10) were prospectively recruited. This prospective, open-label, 12-month study included two different protocols: (1) group A, SR 320 mg/day + BC 30 mg/day + TAM 0.4 mg/day, and (2) group B, TAM 0.4 mg/day only. RESULTS: Overall, 148 patients entered the study, 76 in group A and 72 in group B. At 12 months, the total IPSS had decreased by 5.5 with TAM + SR + BC and by 5.1 with TAM only (p = 0.21). However, when the total IPSS was divided into storage and voiding subscores, at 6 months the storage symptoms had improved significantly more with TAM + SR + BC (-1.6 vs. -0.9 with TAM only, p = 0.02), with the benefit persisting also at the 1-year evaluation (-1.8 vs. -0.8, p = 0.02). Moreover, the improvement in LUTS-related quality of life (QoL) was significantly different between the groups, with a mean decrease in IPSS QoL subscore of -2.5 ± 0.2 for TAM + SR + BC versus -1.8 ± 0.3 for TAM at 6 months (p = 0.04), and of -2.9 ± 0.4 for TAM + SR + BC versus -2.1 ± 0.4 for TAM at 12 months (p = 0.04). Conversely, no significant differences were found in maximal urinary flow rate (p = 0.38), postvoid residual volume (p = 0.12), prostate-specific antigen (p = 0.41), and prostate volume (p = 0.16). CONCLUSION: Combination treatment with SR and BC plus TAM was shown to be more effective than treatment with TAM only in improving IPSS storage and QoL subscores in BPH patients after 6 months and up to 12 months of treatment.

Can cytomegalovirus infection affect male reproductive function? Results of a retrospective single-centre analysis.

Our objective was to investigate whether the chronic cytomegalovirus (CMV) infection can affect semen parameters in men with couple infertility and to assess the impact of male CMV infection on the reproductive outcomes of CMV-seronegative women suffering from tubal factor. Group 1 included CMV IgG-seropositive men, Group 2 CMV IgG-seronegative patients. Seminal parameters, two-pronuclear (2PN) fertilization rate (FR), 1-2-3PN FR, cleavage rate (CR), miscarriage rate (MR), pregnancy rate (PR) and live birth rate (LBR) were collected. Two hundred and twenty-two men were included: 115 (51.8%) in Group 1 and 107 (48.2%) in Group 2. There was reported a low trend towards higher sperm concentration/ml, total sperm count and viability in CMV IgG-seronegative males, compared to CMV IgG-seropositive (p > .05). Semen volume, pH, motility and normal sperm morphology were similar among groups. Considering the subgroup of men, partners of CMV IgG-seronegative females, 65 couples (29.2%) were selected. Median 2PN FR was 67%, total FR 83%, CR 100%, PR/cycle 26.2%, MR 10.8%, LBR/cycle 15.4%. No significant differences were found regarding the reproductive outcomes between CMV IgG-seropositive men and those seronegative. CMV did not seem to play a key role in male reproductive function, as well as in influencing sperm fertility potential in the assisted reproductive outcomes.

Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective.

Systemic treatment of renal cancer (RCC) has undergone remarkable changes over the past 20 years with the introduction of immunotherapeutic agents targeting programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) axis, as a single-agent or combined with anti-CTLA-4 monoclonal antibodies (MoAbs) or a multi-target vascular endothelial growth factor-(VEGF) tyrosine kinase inhibitor (TKI). In this paper, we review the main evidence on the use of Immune Checkpoint Inhibitors (ICIs) for RCC treatment from the first demonstration of activity of a nivolumab single agent in a phase I trial to the novel combination strategies (anti-PD-1 plus anti-CTLA4 or anti-PD-1 plus TKI). In addition, we discuss the use of anti-PD-1/PD-L1 agents in patients with non-clear cells and rare histological subtype RCC. Then, we critically examine the current findings in biomarkers that have been proposed to be prognostic or predictive to the response of immunotherapy including immune gene expression signature, B7-H1 expression, PBRM1 loss of function, PD-L1 expression, frame shift indel count, mutations in bromodomain-containing genes in patients with MiT family translocation RCC (tRCC), high expression of the T-effector gene signature, and a high myeloid inflammation gene expression pattern. To date, a single biomarker as a predictor of response has not been established. Since the dynamic behavior of the immune response and the different impact of ICI treatment on patients with specific RCC subtypes, the integration of multiple biomarkers and further validation in clinical trials are needed.

Predictors of the Transition from Off to On Clamp Approach during Ongoing Robotic Partial Nephrectomy: Data from the CLOCK Randomized Clinical Trial.

PURPOSE: We sought to identify predictive factors of the transition from off clamp to on clamp robotic partial nephrectomy following an intraoperative decision. MATERIALS AND METHODS: In the multicenter, randomized, prospective CLOCK (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy) trial 152 and 149 of the 301 patients with a localized renal mass were assigned to undergo off clamp and on clamp robotic partial nephrectomy, respectively. Surgery was done at a total of 7 referral institutions by 1 surgeon per institution. A localized renal mass was defined as having a R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, location relative to polar lines, hilar) score less than 10. Surgeons had similar experience with at least 100 previous robotic partial nephrectomies. All patients underwent a preoperative and a 6-month renal scan. The current study deals with one of the secondary end points of the trial, comparing cases finalized as clampless (off robotic partial nephrectomy group) with those which were converted (shift robotic partial nephrectomy group). RESULTS: Of the 152 patients randomized to off clamp 61 (40%) were shifted to clamp with a median ischemia time of 15 minutes. In the shift robotic partial nephrectomy group the masses were larger (3.5 vs 2.2 cm) and more complex (R.E.N.A.L. score 7 vs 6). A significant association with transition was found for tumor diameter (OR 1.4) and the R.E.N.A.L. score continuously (OR 1.4) and when recoded in groups, including 4-no risk (referent OR 1), 5-6-low risk (OR 1.8), 7-8-intermediate risk (OR 3.6) and 9 or greater-high risk (OR 6.6). The shift robotic partial nephrectomy group had longer operative time, higher blood loss and increased performance of 2-layer renorrhaphy. No significant differences were noted in postoperative complications or renal function after 6 months. CONCLUSIONS: The transition from off to on clamp robotic partial nephrectomy is associated with renal mass diameter and complexity. Under the specific conditions of the current trial no harm was related to this decision.

Tumour contact surface area as a predictor of postoperative complications and renal function in patients undergoing partial nephrectomy for renal tumours.

OBJECTIVES: To evaluate the ability of original tumour contact surface area (CSA) to predict postoperative complications and renal function impairment in a series of patients who underwent elective partial nephrectomy (PN) for renal masses. MATERIALS AND METHODS: We analysed the clinical records of 531 consecutive patients who underwent elective PN because of a suspicion of kidney cancer at five academic, high-volume centres between January 2014 and December 2016. Each participating centre evaluated prospectively the radiological images to evaluate the CSA and to assign a PADUA score. Several expert surgeons performed the surgical procedures in each participating centre. Binary logistic regression was used to perform both univariable and multivariable analyses to identify predictors of postoperative complications. Linear regression analysis was used to identify independent predictors of absolute change in estimated glomerular filtration rate (eGFR; ACE). RESULTS: The median (interquartile range) CSA value was 14.2 (7.4-25.1) cm2 . A total of 349 tumours (65.7%) had a CSA ≤ 20 cm2 and the remaining 182 (34.3%) had a CSA > 20 cm2 . PNs were performed using an open approach in 237 (44.6%) cases, a pure laparoscopic approach in 152 cases (28.6%), and a robot-assisted approach in the remaining 142 cases (26.7%). Multivariable analyses found that only age (odds ratio [OR] 1.037, 95% confidence interval [CI] 1.018-1.057) and PADUA score (OR 1.289, 95%CI 1.132-1.469) were independent predictors of postoperative complications. Tumour CSA (OR 1.020, 95%CI 1.010-1.030) was found to be an independent predictor of postoperative complications only when PADUA score was removed from the model. Age (from -0.639 to -0.306; P < 0.001); body mass index (from 0.267 to 1.076; P = 0.001), age-adjusted Charlson score (from -3.193 to -0.259; P = 0.02), preoperative eGFR value (from -0.939 to -0.862; P < 0.001) and tumour CSA (from -0.260 to -0.048; P = 0.005) were found to be independent predictors of ACE. CONCLUSIONS: Tumour CSA is an independent predictor of postoperative renal function. Conversely, at multivariable analysis, PADUA score outperformed tumour CSA to predict postoperative complications after PN. The complexity of The Leslie et al. formula for calculating tumour CSA is a potential limitation with regard to its diffusion and application in clinical practice.

The Simplified PADUA REnal (SPARE) nephrometry system: a novel classification of parenchymal renal tumours suitable for partial nephrectomy.

OBJECTIVE: To simplify the original Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification of renal tumours, generating a new system able to predict equally or better the risk of overall complications in patients undergoing partial nephrectomy (PN); and to test if the addition of the contact surface area (CSA) parameter improves the accuracy of the original PADUA and new Simplified PADUA REnal (SPARE) nephrometry classification systems. PATIENTS AND METHODS: We analysed the clinical records of 531 patients who underwent PN (open, laparoscopic and robot-assisted) for renal tumours at five tertiary academic referral centres from January 2014 to December 2016. The ability of each variable included in the PADUA classification to predict overall complications was tested using binary logistic regression analysis. The variables that were not statistically significant were excluded from the SPARE classification. In addition to the original PADUA and SPARE systems, another two models were generated adding tumour CSA. Receiver operating characteristic curve analysis was used to compare the ability of the four different models to predict overall complications. Binary logistic regression was used to perform both univariable and multivariable analyses looking for predictors of postoperative complications. Linear regression analysis was used to identify independent predictors of absolute change in estimated glomerular filtration rate (eGFR; ACE). RESULTS: The SPARE nephrometry score system including: (i) rim location, (ii) renal sinus involvement, (iii) exophytic rate, and (iv) tumour dimension; showed equal performance in comparison with the original PADUA score (area under the curve [AUC] 0.657 vs 0.664). Adding tumour CSA to the original PADUA (AUC 0.661) or to the SPARE (AUC 0.658) scores did not increase the accuracy of either system to predict overall complications. The SPARE system (odds ratio 1.2, 95% confidence interval 1.1-1.3) was an independent predictor of postoperative overall complications. Age (P < 0.001), body mass index (P < 0.001), Charlson Comorbidity Index (P = 0.02), preoperative eGFR (P < 0.001), and tumour CSA (P = 0.005) were independent predictors of ACE. Limitations include the retrospective design and the lack of central imaging review. CONCLUSIONS: The new SPARE score is comprised of only four variables instead of the original six and its accuracy to predict overall complications is similar to that of the original PADUA score. Addition of tumour CSA was not associated with an increase in prognostic accuracy. The SPARE system could replace the original PADUA score to evaluate the complexity of tumours suitable for PN.

Nomogram for predicting the likelihood of postoperative surgical complications in patients treated with partial nephrectomy: a prospective multicentre observational study (the RECORd 2 project).

OBJECTIVE: To identify meaningful predictors and to develop a nomogram of postoperative surgical complications in patients treated with partial nephrectomy (PN). PATIENTS AND METHODS: We prospectively evaluated 4308 consecutive patients who had surgical treatment for renal tumours, between 2013 and 2016, at 26 Italian urological centres (RECORd 2 project). A multivariable logistic regression for surgical complications was performed. A nomogram was created from the multivariable model. Internal validation processes were performed using bootstrapping with 1000 repetitions. RESULTS: Overall, 2584 patients who underwent PN were evaluated for the final analyses. The median (interquartile [IQR]) American Society of Anesthesiologists (ASA) score was 2 (2-3). In all, 72.4% of patients had clinical T1a (cT1a) stage tumours. The median (IQR) Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 7 (6-8). Overall, 34.3%, 27.7%, 38% of patients underwent open PN (OPN), laparoscopic PN (LPN), and robot-assisted PN (RAPN). Overall and major postoperative surgical complications were recorded in 10.2% and 2.5% of patients, respectively. At multivariable analysis, age, ASA score, cT2 vs cT1a stage, PADUA score, preoperative anaemia, OPN and LPN vs RAPN, were significant predictive factors of postoperative surgical complications. We used these variables to construct a nomogram for predicting the risk of postoperative surgical complications. At decision curve analysis, the nomogram led to superior outcomes for any decision associated with a threshold probability of >5%. CONCLUSION: Several clinical predictors have been associated with postoperative surgical complications after PN. We used this information to develop and internally validate a nomogram to predict such risk.

The diagnosis and treatment of urogenital schistosomiasis in Italy in a retrospective cohort of immigrants from Sub-Saharan Africa.

OBJECTIVES: To evaluate ultrasound and praziquantel to, respectively, assess and reduce urogenital schistosomiasis (UGS)-associated morbidity in migrants from Sub-Saharan Africa (SSA). METHODS: Migrants from SSA with UGS attending three Italian centres for tropical diseases during 2011-2016 were retrospectively enrolled. Data on clinical symptoms, routine laboratory, parasitological tests, and ultrasound reported as per the WHO-Niamey protocol were collected at baseline and at available follow-up visits after treatment with praziquantel 40 mg/kg/day for 3 days. RESULTS: One hundred and seventy patients with UGS were enrolled and treated with praziquantel. Baseline ultrasonography showed urinary tract abnormalities in 115/169 patients (68%); the mean global Schistosoma haematobium score was 2.29 (SD 2.84, IQR 0-2), the mean urinary bladder intermediate score 1.75 (SD 1.73, IQR 0-2), and the mean upper urinary tract intermediate score 0.54 (SD 2.37, IQR 1-10). Abnormalities were more common among the 111 (65%) who were symptomatic (p < 0.02; OR 2.53; 95% CI 1.19-5.35). Symptoms started in 94/111 (85%) before arriving (median 63 months, IQR 12-119). At follow-up, we observed a significant reduction in the prevalence of UGS-related symptoms, blood, urine, and ultrasound abnormalities. CONCLUSIONS: Our study results support the use of ultrasound and praziquantel for assessing and reducing UGS-associated morbidity in migrants. Health-seeking behaviour, diagnostic, and treatment delays contribute to the advanced pathology and qualified treatment success. To ensure earlier treatment, based on our findings, clinical experience, and available literature, we propose an algorithm for the diagnosis and clinical management of UGS. Multicentre studies are needed to improve the management of subjects with UGS in non-endemic countries.