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Objective: To assess the utility of multiparametric MRI and clinical indicators in distinguishing nuclear grade and survival of clear cell renal cell carcinoma (ccRCC) complicated with venous tumor thrombus (VTT)., Materials and Methods: This study included 105 and 27 patients in the training and test sets, respectively. Preoperative MRI, including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), was performed. Renal lesions were evaluated for IVIM-DWI metrics and conventional MRI features. All the patients had postoperative histologically proven ccRCC and VTT. An expert uropathologist reviewed all specimens to confirm the nuclear grade of the World Health Organization/ International Society of Urological Pathology (WHO/ISUP) of the tumor. Univariate and multivariable logistic regression analyses were used to select the preoperative imaging features and clinical indicators. The predictive ability of the logistic regression model was assessed using receiver operating characteristic (ROC) analysis. Survival curves were plotted using the Kaplan-Meier method., Results: High WHO/ISUP nuclear grade was confirmed in 69 of 105 patients (65.7%) in the training set and 19 of 27 patients (70.4%) in the test set, respectively (P = 0.647). D p_ROI_Low , tumor size, serum albumin, platelet count, and lymphocyte count were independently related to high WHO/ISUP nuclear grade in the training set. The model identified high WHO/ISUP nuclear grade well, with an AUC of 0.817 (95% confidence interval [CI]: 0.735-0.899), a sensitivity of 70.0%, and a specificity of 77.8% in the training set. In the independent test set, the model demonstrated an AUC of 0.766 (95% CI, 0.567-0.966), a sensitivity of 79.0%, and a specificity of 75.0%. Kaplan-Meier analysis showed that the predicted high WHO/ISUP nuclear grade group had poorer progression-free survival than the low WHO/ISUP nuclear grade group in both the training and test sets (P = 0.001 and P = 0.021)., Conclusions: IVIM-DWI-derived parameters and clinical indicators can be used to differentiate nuclear grades and predict progression-free survival of ccRCC and VTT., Competing Interests: Declarations. Ethical approval: The institutional review board approved this study (internal registration number: S2021-070-01) and waived informed consent for the training set, and informed consent was obtained in the prospective test set. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Rationale and Objective: Accurate differentiation between benign and malignant cystic renal masses (CRMs) is challenging in clinical practice. This study aimed to develop MRI-based machine learning models for differentiating between benign and malignant CRMs and compare the best-performing model with the Bosniak classification, version 2019 (BC, version 2019)., Methods: Between 2009 and 2021, consecutive surgery-proven CRM patients with renal MRI were enrolled in this multicenter study. Models were constructed to differentiate between benign and malignant CRMs using logistic regression (LR), random forest (RF), and support vector machine (SVM) algorithms, respectively. Meanwhile, two radiologists classified CRMs into I-IV categories according to the BC, version 2019 in consensus in the test set. A subgroup analysis was conducted to investigate the performance of the best-performing model in complicated CRMs (II-IV lesions in the test set). The performances of models and BC, version 2019 were evaluated using the area under the receiver operating characteristic curve (AUC). Performance was statistically compared between the best-performing model and the BC, version 2019., Results: 278 and 48 patients were assigned to the training and test sets, respectively. In the test set, the AUC and accuracy of the LR model, the RF model, the SVM model, and the BC, version 2019 were 0.884 and 75.0%, 0.907 and 83.3%, 0.814 and 72.9%, and 0.893 and 81.2%, respectively. Neither the AUC nor the accuracy of the RF model that performed best were significantly different from the BC, version 2019 (P = 0.780, P = 0.065). The RF model achieved an AUC and accuracy of 0.880 and 81.0% in complicated CRMs., Conclusions: The MRI-based RF model can accurately differentiate between benign and malignant CRMs with comparable performance to the BC, version 2019, and has good performance in complicated CRMs, which may facilitate treatment decision-making and is less affected by interobserver disagreements., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest related to this work., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features., Patients and Methods: We retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method. The optimal cut-off value of the Ki-67 expression for predicting survival was determined by the minimum P-value method. Clinicopathological data were compared based on Ki-67 status (low versus high expression). Univariate and multivariate Cox regression analysis was used to explore independent predictors., Results: A total of 202 patients (median age, 58 years [IQR, 52-65 years], 147 men) with ccRCC and tumor thrombus were included in the study. The optimal cut-off value of Ki-67 for predicting survival was 30%. 159 (78.7%) and 43 (21.3%) patients were included in the low-expression and high-expression groups. Patients with Ki-67 high expression had significantly worse recurrence-free survival (P < 0.001) and cancer-specific survival (P < 0.001). Ki-67 high expression was associated with adverse pathological features, including tumor necrosis, ISUP nuclear grade, sarcomatoid differentiation, perirenal fat invasion, renal pelvis invasion, and inferior vena cava wall invasion (all P < 0.050). Ki-67 expression ≥ 30% (P = 0.016), tumor side (P = 0.003), diabetes (P = 0.040), blood loss (P = 0.016), inferior vena cava wall invasion (P = 0.016), and sarcomatoid differentiation (P = 0.014) were independent predictors of cancer-specific survival., Conclusion: The optimal cut-off level of Ki-67 in predicting the prognosis of ccRCC and tumor thrombus was 30%. The high expression of Ki-67 was associated with the aggressive pathological phenotype and poor prognosis., Competing Interests: Declaration of Competing Interest No potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking., Purpose: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (D t , D p , f, and ADC) and the apparent diffusion coefficient (ADC) value., Study Type: Retrospective., Population: One hundred and nineteen patients (aged 55.8 ± 11.5 years, 85 male) with histologically-proven RCC and VTT who underwent radical resection., Field Strength/sequences: 3.0-T; two-dimensional single-shot diffusion-weighted echo planar imaging sequence at 9 b-values (0-800 s/mm 2 )., Assessment: IVIM parameters and ADC values of the primary tumor and the VTT were calculated. The VTT consistency (friable vs. solid) was determined through intraoperative findings of two urologists. The accuracy of VTT consistency classification based on the individual IVIM parameters of primary tumors and of VTT, and based on models combining parameters, was assessed. Type of operation, intra-operative blood loss, and operation length were recorded., Statistical Tests: Shapiro-Wilk test; Mann-Whitney U test; Student's t-test; Chi-square test; Receiver operating characteristic (ROC) analysis. Statistical significance level was P < 0.05., Results: Of the enrolled 119 patients, 33 patients (27.7%) had friable VTT. Patients with friable VTT were significantly more likely to experience open surgery, have significantly more intraoperative blood loss, and significantly longer operative duration. The area under the ROC curve (AUC) values of D t of the primary tumor and VTT in classifying VTT consistency were 0.758 (95% CI 0.671-0.832) and 0.712 (95% CI 0.622-0.792), respectively. The AUC value of the model combining D p and D t of VTT was 0.800 (95% CI 0.717-0.868). Furthermore, the AUC of the model combining D p and D t of VTT and D t of the primary tumor was 0.886 (95% CI 0.814-0.937)., Conclusion: IVIM-derived parameters had the potential to predict VTT consistency of RCC., Evidence Level: 3 Technical Efficacy: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: To strengthen the recognition of mucinous tubular and spindle cell carcinomas of the kidney (MTSCC-Ks) by analyzing CT and MR imaging findings of MTSCC-Ks., Materials and Methods: This study retrospectively enrolled ten patients with pathologically confirmed MTSCC-Ks from 2007 to 2020. The main observed imaging characteristics included growth pattern, signal characteristics on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), hemorrhage, necrosis, cystic degeneration, lipid component, pseudocapsule and the enhancement pattern. Apparent diffusion coefficient (ADC) value of MTSCC-Ks and normal renal cortex were measured, respectively. All imaging features were evaluated in consensus by two genitourinary radiologists., Results: All patients (53.1 ± 6.5 years, male to female, 3:7) presented with a solitary renal tumor with the mean diameter of 3.5 ± 0.4 cm. All lesions showed iso- or slight hypoattenuation on non-contrast CT with no hemorrhage but cystic degeneration (10%) and necrosis (10%). On T2WI, all lesions showed predominantly slight hypointensity with focal hyperintensity. The ADC value of MTSCC-Ks was 0.845 ± 0.017 × 10 -3 mm 2 /s, and ADC tumor -to-ADC renal cortex value was 0.376 ± 0.084. Pseudocapsules existed in all MTSCC-Ks on MRI. There were seven lesions showed heterogeneous enhancement, while three lesions showed homogeneous enhancement. Among them, six MTSCC-Ks showed slight multiple patchy enhancement (60%) in the corticomedullary phase, while the remaining MTSCC-Ks showed homogeneously slight enhancement (30%) or slightly stratified enhancement (10%). All MTSCC-Ks exhibited slow and progressive enhancement in the late phases., Conclusion: Iso- or slight hypoattenuation on CT, slight hypointensity with focal hyperintensity on T2WI, marked diffusion restriction on DWI and ADC map, slight multiple patchy enhancement in the corticomedullary phase, and slow and progressive enhancement in the late phases are the imaging features of MTSCC-Ks, which may facilitate the diagnosis of MTSCC-Ks., (© 2022. The Author(s) under exclusive licence to Japan Radiological Society.)

Renal cell carcinoma (RCC) is a major health issue. Whereas localized disease can be cured surgically, there is no effective therapy for metastatic disease. The development of an effective therapy will require an understanding of the pathways that are important in RCC carcinogenesis and progression. Using genomic profiling of patient-matched tissue, we have identified aberrations in the transforming growth factor beta (TGFbeta) signaling pathway in RCC. We observed loss of type III TGFbeta receptor (TBR3) expression in all RCC samples. This suggests that TBR3 loss is an early event in RCC carcinogenesis and plays a sentinel role in the acquisition of a tumorigenic phenotype. We also observed subsequent loss of type II TGFbeta receptor (TBR2) expression in metastatic RCCs. We propose that loss of TBR3 is necessary for RCC carcinogenesis, and that loss of TBR2 leads to acquisition of a metastatic phenotype. To this end, we have identified a human renal cell carcinoma line (UMRC6) that is representative of localized, nonmetastatic RCC, reflecting a loss of TBR3, but not TBR2 expression. Another cell line, UMRC3, is highly metastatic, having lost TBR3 and TBR2 expression. We demonstrate functional loss of TGFbeta responsiveness in these cell lines as observed through phenotypic and transcriptional responsiveness to exogenous TGFbeta. Restoring TBR2 and TBR3 expression in UMRC3 cells attenuates cell proliferation, completely restores TGFbeta-mediated transcriptional responses, and completely blocks anchorage independent-growth: while restoration of TBR2 partially restores TGFbeta-mediated signaling. Based on these data, we propose that dysregulation in TGFbeta signaling, through stepwise loss in receptor expression, plays a prominent role in RCC carcinogenesis and progression. In addition, these studies unequivocably demonstrate a link between loss of TBR3 and a human disease.