Simplified PADUA Renal (SPARE) Nephrometry Scoring System: External Validation, Interobserver Variability, and Comparison with RENAL and PADUA in a Single-center Robotic Partial Nephrectomy Series.

BACKGROUND: The RENAL (radius [R], exophytic/endophytic [E], nearness to collecting system/sinus [N], anterior/posterior [A], and location relative to polar lines [L]) and the PADUA (preoperative aspects and dimensions used for an anatomical classification) scores help in quantifying tumor complexity. However, nephrometry scoring systems have low interobserver variability. To simplify and improve score reproducibility, a new Simplified PADUA Renal (SPARE) scoring system was introduced. OBJECTIVE: To externally validate the SPARE nephrometry scoring system and to determine its interobserver variability. DESIGN, SETTING, AND PARTICIPANTS: A total of 202 patients were included in the analysis. We performed a retrospective analysis of robot-assisted partial nephrectomy (RAPN) cases for a single renal mass performed at a single academic institution during the period 2008-2018. For each renal mass, PADUA, RENAL, and SPARE nephrometry scores were calculated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three urology residents (URs), two urology attendings (UAs), two radiology residents (RRs), and one radiology attending (RA) retrospectively reviewed computed tomography scans blinded to clinical outcomes. The accuracy of the SPARE nephrometry score in the prediction of any complication (Clavien grade ≥1) was compared with other scoring systems in a univariable and a multivariate fashion. The area under the curve (AUC) and kappa statistics were used to assess interobserver variability of the SPARE score. RESULTS AND LIMITATIONS: The SPARE score was not inferior to the PADUA and RENAL scores (AUC 0.61, 0.59, and 0.57, respectively, p = 0.43). Patients with intermediate to high SPARE scores had longer operative time (158 vs 135 min, p = 0.10) and a higher rate of complications (28% vs 14%, p = 0.012). Univariable analysis predicting overall complications showed that RRs performed slightly better than URs and UAs using the SPARE score. Interobserver agreement was 84% between an RA and an RR (kappa 0.42), 85% between an RA and a UA (kappa 0.39), and 85% between an RA and a UR (kappa 0.45). CONCLUSIONS: These findings confirm that the SPARE nephrometry scoring system is a reproducible and easy tool offering overall fair interobserver agreement regardless of years of training or type of practice, while maintaining the predictive capabilities of more established nephrometry scores. PATIENT SUMMARY: In this study, a novel and simple classification system was assessed using a sample of cases from our institution to define surgical complexity renal masses detected on radiological imaging. Our findings suggest that this tool can be useful in clinical practice to facilitate the characterization of renal masses and predict the complications of surgical treatment.

Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics.

BACKGROUND: Tumor initiating stem-like cells (TISCs) are a subset of neoplastic cells that possess distinct survival mechanisms and self-renewal characteristics crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by TGFß has been recently linked to the acquisition of TISC characteristics in breast cancer. In HCC, a TISC and EMT phenotype correlates with a worse prognosis. In this work, our aim is to elucidate the underlying mechanism by which cells acquire tumor initiating characteristics after EMT. METHODS: Gene and protein expression assays and Nanog-promoter luciferase reporter were utilized in epithelial and mesenchymal phenotype liver cancer cell lines. EMT was analyzed with migration/invasion assays. TISC characteristics were analyzed with tumor-sphere self-renewal and chemotherapy resistance assays. In vivo tumor assay was performed to investigate the role of Snail1 in tumor initiation. CONCLUSION: TGFß induced EMT in epithelial cells through the up-regulation of Snail1 in Smad-dependent signaling. Mesenchymal liver cancer post-EMT demonstrates TISC characteristics such as tumor-sphere formation but are not resistant to cytotoxic therapy. The inhibition of Snail1 in mesenchymal cells results in decreased Nanog promoter luciferase activity and loss of self-renewal characteristics in vitro. These changes confirm the direct role of Snail1 in some TISC traits. In vivo, the down-regulation of Snail1 reduced tumor growth but was not sufficient to eliminate tumor initiation. In summary, TGFß induces EMT and TISC characteristics through Snail1 and Nanog up-regulation. In mesenchymal cells post-EMT, Snail1 directly regulates Nanog expression, and loss of Snail1 regulates tumor growth without affecting tumor initiation.