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.
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.
Objectives
To report surgical technique, perioperative, oncological, and mid‐term functional outcomes in a single‐center purely off‐clamp robotic partial nephrectomy series for totally endophytic ...masses.
Methods
A retrospective analysis of a prospectively collected, institutional review board‐approved renal cancer database was carried out to include patients with a totally endophytic renal tumor treated with off‐clamp robotic partial nephrectomy between January 2013 and December 2020 at our center. Our database was queried to identify cases that had been assigned 3 points for the “E” domain of the R.E.N.A.L. nephrometry score and 3 points for the “exophytic rate” domain of the PADUA (Preoperative Aspects and Dimensions Used for an Anatomical) nephrometry score. Preoperative indocyanine green renal mass marking was performed in 33 patients, in whom the tumor was vascularized by a specific feeding artery. Surgical steps, perioperative, oncological and functional data were reported.
Results
Fifty‐six consecutive patients with totally endophytic renal masses were treated. The median tumor diameter was 3 cm, and median PADUA and R.E.N.A.L. scores were both 10. The median operative time was 82 min. Low‐grade Clavien complications occurred in two patients (3.6%) and high‐grade Clavien complications were observed in four patients (7.1%). Positive surgical margins were detected in one patient; 2‐year recurrence‐free, cancer‐specific, and overall survival rates were 100%, 100%, and 98.2%, respectively. At a median follow‐up of 24 months, new onset of chronic kidney disease stage 3b occurred in one patient. At last follow‐up, the median estimated glomerular filtration rate was 77 mL/min, with a median estimated glomerular filtration rate percent decrease of 5.5%. Trifecta was achieved in 91% of patients.
Conclusions
Purely off‐clamp robotic partial nephrectomy is a feasible and safe surgical approach, even in totally endophytic renal tumors, providing a favorable perioperative complications rate, excellent oncological outcomes, and negligible impact on renal function at mid‐term follow‐up. Indocyanine green preoperative marking of endophytic renal tumors represents a useful tool for rapid intraoperative identification of the mass, real‐time control of resection margins, and a more precise dissection.
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.
There is paucity of data about functional outcomes of Robot-assisted Radical Cystectomy (RARC) with intracorporeal orthotopic neobladder (ICON), and the impact of learning curve (LC) on those ...outcomes remains to be addressed. The aim of this study was to report long-term functional outcomes of our single center series of RARC with ICON, assessing the role of LC in their achievement.
Patients treated with Robot assisted radical cystectomy with intracorporeal orthotopic neobladder in our center between January 2012 and August 2019 were retrospectively analyzed. Preoperative, clinical, perioperative, pathologic and functional data were reported. The first cases were divided in tertiles, for assessing the impact of learning curve on the outcomes evaluated. Long-term functional outcomes of the whole cohort were evaluated.
Overall, 167 patients were included. Concerning tertiles analysis, operative time (P<0.001), incidence of low (P=0.002) and high grade (P=0.001) complications and hospital stay (P=0.04) decreased significantly over time. Day-time continence recovery probability was significantly lower in the initial case series (1-yr rate 68.4%, 87% and 89.8 for I, II and III tertile, respectively; P=0.04;). Accordingly, Trifecta achievement was significantly higher in II and III tertiles (P=0.01). At a median follow- up of 34 months, the incidence of significant renal function deterioration of the whole cohort was 16.7%. Overall, 12, 24 and 60-mo day-time continence rates were 74.8%, 82.7% and 82.7%.
Patients treated at the beginning of the learning curve show worse perioperative and functional results. Once standardized the procedure, complications rates, hospital stay, and day-time continence recovery experienced a significant improvement. At a long-term analysis of functional outcomes of our patients, renal function preservation and continence recovery results are encouraging.
This comprehensive review aims to explore the applications of indocyanine green (ICG) in robot-assisted urological surgery through a detailed examination of fluorescence-guided techniques. An ...extensive literature search was conducted in PubMed/MEDLINE, EMBASE and Scopus, using keywords such as "indocyanine green," "ICG", "NIRF", "Near Infrared Fluorescence", "robot-assisted", and "urology". Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. The integration of the Firefly
technology in the Da Vinci
robotic system has opened new avenues for the advancement and exploration of different urological procedures. ICG is a fluorophore widely used in near-infrared fluorescence-guided techniques. The synergistic combination of intraoperative support, safety profiles and widespread availability comprises an additional asset that empowers ICG-guided robotic surgery. This overview of the current state of the art illustrates the potential advantages and broad applications of combining ICG-fluorescence guidance with robotic-assisted urological surgery.
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).
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.
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%.
Urinary let-7c cluster evaluation may improve prognosis, identifying patients at risk of progression and addressing early radical treatment.
New insights in the urinary microbiome have led to a better understanding being built of the shifts in bacterial representations from health to disease; these hold promise as markers for diagnosis ...and therapeutic responses. Although several efforts have been made to identify a “core urinary microbiome”, different fingerprints have been identified in men and women that shift with age. The main bacterial groups overall include Firmicutes, Actinobacteria, Fusobacteria, and Bacteroidetes. Although patients with bladder cancer have a microbiome that is similar to that of healthy individuals, differences have been observed at the species level with Fusobacterium nucleatum and Ralstonia, and at the genus level with Cutibacterium. Different bacterial representations may influence extracellular matrix composition, affecting tumor metastatic spreading and tumorigenic metalloproteinase expression. Furthermore, gene expression affecting targets of immune therapy, such as PD-L1, has been associated with changes in bacterial representations and therapeutic response to BCG. This comprehensive review aims to examine the influence of the urinary microbiome in bladder cancer.
The aim of this study was to investigate the impact of computer aided diagnostic (CAD) system on the detection rate of prostate cancer (PCa) in a series of fusion prostate biopsy (FPB).
Two ...prospective transperineal FPB series (with or without CAD assistance) were analyzed and PCa detection rates compared with per-patient and per-target analyses. The χ
and Mann-Whitney test were used to compare categorical and continuous variables, respectively. Univariable and multivariable regression analyses were applied to identify predictors of any and clinically significant (cs) PCa detection. Subgroup analyses were performed after stratifying for PI-RADS Score and lesion location.
Out of 183 FPB, 89 were performed with CAD assistance. At per-patient analysis the detection rate of any PCa and of cs PCa were 56.3% and 30.6%, respectively; the aid of CAD was negligible for either any PCa or csPCa detection rates (P=0.45 and P=0.99, respectively). Conversely in a per-target analysis, CAD-assisted biopsy had significantly higher positive predictive value (PPV) for any PCa versus MRI-only group (58% vs. 37.8%, P=0.001). PI-RADS Score was the only independent predictor of any and csPCa, either in per-patient or per-target multivariable regression analysis (all P<0.029). In a subgroup per-patient analysis of anterior/transitional zone lesions, csPCa detection rate was significantly higher in the CAD cohort (54.5%vs.11.1%, respectively; P=0.028), and CAD assistance was the only predictor of csPCa detection (P=0.013).
CAD assistance for FPB seems to improve detection of csPCa located in anterior/transitional zone. Enhanced identification and improved contouring of lesions may justify higher diagnostic performance.
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;
< 0.001), increased likelihoods of achieving 1 year trifecta (89.8% vs. 80.3%;
= 0.03), lower postoperative Clavien-Dindo ≤ 2 complications (1.3% vs. 18.3%,
< 0.001), and lower postoperative transfusion rates (3.4% vs. 12.2%,
= 0.008). At univariable analysis, the surgical approach (off-C RAPN vs. off-C OPN, OR 2.22, 95% CI 1.09-4.46,
= 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
= 0.451), CSS (log-rank
= 0.476), DFS (log-rank
= 0.678), and MFS (log-rank
= 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.
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