Application of three-dimensional Superb micro-vascular imaging (3D-SMI) combined with quantitative blood flow analysis in the noninvasive diagnosis of renal tumors

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

To investigate whether iodine content can discriminate between benign or malignant renal tumors, malign tumor subtypes, low-grade and high-grade tumors on rapid kv-switching dual-energy CT (rsDECT). This prospective study enrolled 95 patients with renal tumors who underwent rsDECT for tumor characterization between 2016 and 2018. Attenuation on true and virtual unenhanced images, absolute enhancement and enhancement ratio and iodine content of each lesion on nephrographic phase iodine density images were measured. Histopathological diagnosis was obtained following either surgery or core biopsy. Eighty-five tumors were renal cell carcinoma (RCC) (56 clear cell, 20 papillary, 9 chromophobe) and 10 were benign (6 angiomyolipoma,4 oncocytoma). 46 tumors were low-grade and 23 high-grade. There was significant difference between iodine content of clear cell and non-clear cell (papillary + chromophobe) RCC (p < 0.001). However, no significant iodine content differences were found between papillary and chromophobe RCC, benign and malignant tumors, low-grade and high-grade tumors. The best cut-off iodine content for differentiating clear cell from non-clear cell RCC was 3.2mg/ml and clear cell from papillary RCC was 2.9mg/ml with a high sensitivity and specificity. Also, significant difference was found between attenuation values of true and virtual unenhanced images (p = 0.007). Mean iodine content, absolute enhancement and enhancement ratio were highly correlated. rsDECT contributes to renal tumor characterization by showing higher iodine content in clear cell RCCs compared with non-clear cell RCCs.

Cytogenetic and molecular genetic techniques have been used in demonstrating the chromosomal abnormalities which characterize specific subtypes of renal cell carcinoma (RCC). The aim of this study was to determine the efficiency of fluorescent in situ hybridization (FISH) technique in characterizing various subtypes of RCC based on the presence of specific chromosome abnormalities found in each RCC subtype. FISH was performed on touch imprint smears from eight renal cell carcinomas histologically confirmed by established criteria. In four tumors with histologic features of chromophobe renal cell carcinoma (ChRCC), interphase FISH was performed using centromeric probes for chromosomes 1, 2, 6, 10, 12, 17 and 21. All four ChRCC tumors showed one FISH signal corresponding to one copy number for each of these chromosomes. Two papillary RCCs included in this study showed trisomy 7 and 17, and loss of chromosome Y, using the corresponding chromosome centromeric probes. Similarly, we tested two clear cell RCCs for chromosome 3 short arm deletion with DNA probe 3p21.3. Both tumors showed loss of 3p21.3 signal. We conclude that interphase FISH performed on touch imprint smears is a relatively simple, rapid and reliable method for detecting chromosome abnormalities which are specific for various subtypes of RCC.

The development of consensus classifications for renal epithelial neoplasia in 1996 and 1997 led to the recognition of renal adenoma, renal oncocytoma and metanephric adenoma/adenofibroma as benign tumors and conventional (clear cell) renal cell carcinoma (RCC), papillary RCC, chromophobe RCC and collecting duct carcinoma as malignant morphotypes. While the overwhelming majority of renal adenomas and metanephric adenomas are benign, malignant transformation of both types have been described and genetic predictors of malignant transformation are as yet unknown. The main groups of malignant renal tumors are associated with characteristic genetic changes; conventional RCC (-3p), papillary RCC (+7, +17, -Y), chromophobe RCC (hypodiploid). Recent studies have also shown focal loss of heterozygosity of 3p segments in papillary and chromophobe RCC, indicating that 3p mutations are not confined to the conventional RCC morphotype and suggesting the presence of an important tumor suppressor gene at this site. Sarcomatoid metaplasia may occur in any morphotype and this is associated with a poor prognosis. More recently additional varieties of conventional RCC (multilocular cystic RCC), collecting duct carcinoma (medullary renal carcinoma) and papillary RCC (Types 1 and 2), each showing a characteristic morphology, have been recognized.

Differences in Organ System of Distant Metastasis by Renal Cell Carcinoma Subtype

To retrospectively evaluate whether the enhancement patterns of pathologically proved clear cell, papillary, and chromophobe renal cell carcinomas (RCCs) measured on clinical dynamic contrast agent-enhanced magnetic resonance (MR) images permit accurate diagnosis of RCC subtype. This study was Institutional Review Board approved and HIPAA compliant; informed consent was waived. One hundred twelve patients (76 men, 36 women; age range, 25-88 years; mean age, 58.1 years) underwent MR imaging of 113 renal masses (mean diameter, 5.4 cm) with pathologic diagnoses of clear cell (n = 75), papillary (n = 28), or chromophobe (n = 10) RCC. A 1.5-T clinical MR protocol was used before and after (corticomedullary and nephrographic phases) intravenous administration of contrast agent. Region-of-interest measurements within tumor and uninvolved renal cortex were used to calculate percentage signal intensity change and tumor-to-cortex enhancement index. Subtype groups were compared by using linear mixed-effects models. Receiver operating characteristic (ROC) curve analysis was performed for the comparison of clear cell and papillary RCCs. On both the corticomedullary and nephrographic phase images, clear cell RCCs showed greater signal intensity change (205.6% and 247.1%, respectively) than did papillary RCCs (32.1% and 96.6%, respectively) (P < .001). Chromophobe RCCs showed intermediate change (109.9% and 192.5%, respectively). The tumor-to-cortex enhancement indexes at corticomedullary and nephrographic phases were largest for clear cell RCCs (1.4 and 1.2, respectively), smallest for papillary RCCs (0.2 and 0.4, respectively), and intermediate for chromophobe RCCs (0.6 and 0.8, respectively). Signal intensity changes on corticomedullary phase images were the most effective parameter for distinguishing clear cell and papillary RCC (area under ROC curve, 0.99); a threshold value of 84% permitted distinction with 93% sensitivity and 96% specificity. Clear cell, papillary, and chromophobe RCCs demonstrate different patterns of enhancement on two-time point clinical dynamic contrast-enhanced MR images, allowing their differentiation with high sensitivity and specificity.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Objective To evaluate the feasibility of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in showing vascular patterns of renal tumors.Methods The images of 3D-CEUS examination were retrospectively analyzed in one hundred and twenty one renal tumors which were confirmed sequentially by pathology.3D-CEUS was performed after conventional ultrasound and contrast-enhanced ultrasound (CEUS).The 3D-CEUS images were reconstructed by QLAB workstation and classified into 4 grades based on the blood supply characteristics.Results All the tumors were confirmed by pathology and operations,including clear cell renal cell carcinoma (CCRCC) (n=91),papillary renal cell carcinoma (PRCC) (n=5),chromophobe renal cell carcinoma (CRCC) (n=5),renal angiomyolipoma (RAML) (n=19),and cystic nephroma (n=1).Three-dimensional reconstruction could provide clear stereoscopic views of the interested structures and morphological characteristics of lesions.The three-dimensional ultrasonography of a particular renal tumor could be a mixture of different basic grades.There were significant differences between benign and malignant renal tumors in 3D-CEUS.The image quality was the best in early parenchymal phase comparing to other phases.In early parenchymal phase,84 RCCs (83.17%) were tortuous expansive reticular or irregular messy dendritic,61 cases (60.40%) with filling defect areas and 15 cases (14.85%) with pseudocapsules.Grade Ⅲ and Grade Ⅳ were the main vascular patterns in maglinant tumors.In early parenchymal phase,6 RAMLs (31.58%) were nebulous with dendritic in part,12 cases(63.16%) were reticular on the basis of nebulous with homogeneous internal structures.The vascular pattern was shown better in 3D-CEUS than CEUS.Conclusions 3D-CEUS can provide clear stereoscopic structures and morphological characteristics of the lesions,it is a useful adjuvant of CEUS for the diagnosis of renal tumors. Key words: Ultrasonography,three-dimensional; Microbubbles; Kidney neoplasms

Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

Background Renal cell carcinoma is one of the most common malignant tumors in urinary system, seriously affecting people's health and life. This study aimed to evaluate the clinical value of multi-mode color Doppler flow imaging for diagnosis of solid renal tumor. Methods Sixty-six renal solid tumors from 63 patients were examined by color Doppler flow imaging (CDFI), power Doppler flow imaging (PDFI), superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) before surgery. The diagnostic efficacy of the four methods was compared by determining blood flow grade and ring-like blood flow with Adler's method. Chi-square test and Fisher's test were performed to compare the results of sensitivity and specificity among four methods. Results Statistically significant differences in blood flow grade and ring-like blood flow were observed between benign and malignant renal tumors as detected by SMI and CEUS (P < 0.05), whereas no difference was found as detected by CDFI and PDFI (P > 0.05). The results indicated that the sensitivity and specificity of SMI (82.46%, 88.89%) and CEUS (84.21%, 88.89%) were higher than those of CDFI (42.11%, 66.67%) and PDFI (47.37%, 77.78%). Compared with the abilities of CDFI and PDFI, SMI and CEUS can better display the micro-blood flow in the tumors and evaluate the blood flow grading, which indicated that SMI and CEUS may have high values in the differential diagnosis of benign and malignant solid renal tumors. Conclusion SMI and CEUS can improve the sensitivity and specificity of the diagnosis of benign and malignant renal tumors and have a high application value.

Introduction. Renal cell carcinoma (RCC) is the most common malignant renal tumor in adults accounting for 80-90% of primary malignant adult renal neoplasms. RCC represents a very heterogenous groups of tumors with a number of distinct histological varieties, of which the major 3 subtypes are clear cell RCC (70-80%), papillary RCC (13-20%), and chromophobe RCC (5%). Imaging features are varied from solid and relatively homogenous appearance to markedly heterogenous appearance with cystic changes, hemorrhage and necrosis. The use of diffusion weighted imaging (DWI) for RCC subtyping and also for differentiation of high grade and low grade tumors has been showed to be useful in many studies in the literature. Aim. In this study, we aimed to determine the comparative contribution of DWI in differentiation of the clear cell RCC from the major non-clear cell RCC subtypes at standard high b-value (1000 s/mm2) versus low b-value (500 s/mm2). In addition, we also aimed to assess the diagnostic performance of DWI for differentiating high grade clear cell RCC from low grade clear cell RCC based on Fuhrman grades in our patients. Material and methods. 62 cases with a prediagnosis of RCC according to MRI findings including DWI sequence with histological verification and subtyping of renal cortical tumor following a total or partial nephrectomy were included in the study. Results. Among 62 cases, 46 were male and 16 were female, with mean age of 59.5 ± 15.7. Pathological diagnoses of 62 cases were as follows, clear cell RCC, (44) papillary cell RCC (14) and chromophobe cell RCC (4). They were divided into two groups as clear cell RCC group (44 cases) and non-clear cell RCC group (18 cases). There was no statistically significant difference between the mean ADC values of clear cell and non-clear cell groups at b-value of 1000 s/mm2 (p&gt;0.05). However, the mean ADC level for clear cell RCC group at b-value of 500 s/mm2 were significantly higher than for non-clear cell RCC group (p&lt;0.05). When a value of 0.99x10-3 mm2/s was set as cut-off for ADC at b-factor of 500 s/mm2, differentiation was achieved with a high sensitivity (91%) and specificity (56%). Regarding the diagnostic performance of DWI for differentiating high from low Fuhrman grades clear cell RCCs, there was no statistically significant difference between the ADC values of Grade I-II clear cell RCC cases and Grade III-IV clear cell RCC cases at b-factor of 1000 s/mm2 (p&gt;0.05). However, ADC values for grade III-IV group was statistically significantly lower than ADC values for Grade I-II group at b-factor of 500 s/mm2 level. Conclusion. ADC measurements at moderate b-value of 500 s/mm2 were more sensitive in subtyping and grading of RCC cases. This technique can be used in clinical practice as a fast and additional sequence in abdominal MRI.

Usefulness of CT texture analysis in differentiating benign and malignant renal tumours

The clinical staging of renal cortical tumors traditionally has not evaluated the potential effect of histological subtypes on survival. Evidence suggests that conventional clear cell renal cell carcinoma (RCC) and nonconventional clear cell RCC (chromophobe and papillary) have different metastatic potential. Using a large renal tumor database, we examined the effect of tumor histology on the pattern of metastasis and patient survival. All patients with nonmetastatic renal cortical tumors undergoing partial or radical nephrectomy were identified from a renal tumor database between July 1989 and July 2002. Kaplan-Meier and Cox regression tests were used for statistical analysis. Analysis revealed 1057 patients: 794 with conventional clear cell RCC, 157 with papillary RCC, and 106 with chromophobe RCC. Metastasis occurred in 95 conventional clear cell RCC, 9 papillary RCC, and 6 chromophobe RCC with a median follow-up of 34.6, 43.0, and 33.2 months, respectively. Using log-rank analysis, chromophobe and papillary RCC were associated with an improved disease-free survival at 5 years (P =.009 and.015, respectively). Multivariate analysis revealed tumor size, stage, and chromophobe histology as significant variables for disease progression. Renal cortical tumors have distinct histological subtypes with varying degrees of metastatic potential. Conventional clear cell RCC, which comprises two thirds of renal cortical tumors presenting with localized disease, has a less favorable outcome when compared with papillary and chromophobe RCC. Controlling for size and stage, chromophobe, and not papillary, RCC was a significant variable for disease progression compared with conventional clear cell RCC. Knowledge of renal cortical tumor histological subtype is critical for projecting prognosis, tailoring follow-up strategies, and designing clinical trials.

Prognostic Factors of Papillary Renal Cell Carcinoma: Results From a Multi-Institutional Series After Pathological Review

The purpose of this study is to evaluate quantitative analysis of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of renal tumor histotypes. Between January 2010 and December 2013, 106 clear cell renal cell carcinomas (RCCs) (mean [± SD] diameter, 3.7 ± 1.8 cm), 34 angiomyolipomas (mean diameter, 4.1 ± 1.4 cm), 25 papillary RCCs (mean diameter, 3.5 ± 1.1 cm), and 28 chromophobe RCCs (mean diameter, 2.9 ± 0.9 cm) underwent CEUS quantitative analysis. The dynamic vascular pattern was analyzed with the Fisher exact chi-square test, and rise time, time to peak (TTP), and tumor-to-cortex enhancement ratio were analyzed with the independent-sample t test. Dynamic vascular pattern types I and III (hyperenhancement) were more common among clear cell RCCs, whereas type II (hypoenhancement) was more common among angiomyolipomas, papillary RCCs, and chromophobe RCCs. Irrespective of dynamic vascular pattern class, the rise time and TTP were the shortest in clear cell RCCs and were equal in angiomyolipomas, papillary, and chromophobe RCCs. The tumor-to-cortex enhancement ratio was the highest in clear cell RCCs, was second highest in angiomyolipomas, and was lowest but equal in papillary and chromophobe RCCs. Clear cell RCCs and angiomyolipomas accounted for the majority of the hyperenhancing group. The tumor-to-cortex enhancement ratio of clear cell RCCs was higher than that of angiomyolipomas. With tumor-to-cortex enhancement ratio greater than 146.0% as the cutoff to differentiate clear cell RCC from angiomyolipoma in the hyperenhanced group, the sensitivity and specificity were each 71.4%. In the hypoenhanced group, the tumor-to-cortex enhancement ratio was the same in clear cell RCCs and angiomyolipomas but was higher in papillary and chromophobe RCCs. With tumor-to-cortex enhancement ratio greater than 54.2% as the cutoff point to differentiate clear cell RCCs from papillary and chromophobe RCCs, the sensitivity and specificity were 95.5% and 94.8%, respectively, whereas with a tumor-to-cortex enhancement ratio greater than 57.4% as the cutoff point to differentiate angiomyolipomas from papillary and chromophobe RCCs, the sensitivity and specificity were 90.0% and 96.4%, respectively. Quantitative analysis of CEUS can show quantification of enhancement features of different renal tumor histotypes and may be helpful in their differential diagnosis.