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Associations between tumor grade, contrast-enhanced ultrasound features, and microvascular density in patients with clear cell renal cell carcinoma: a retrospective study.

Background
Clear cell renal cell carcinoma (ccRCC) comprises 70% of all renal cell carcinomas (RCCs). Currently, the most important prognostic factor for this type of carcinoma is the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. However, nonsurgical methods are rarely used to determine a tumor's WHO/ISUP grade, thus limiting the development of nonsurgical therapies. Due to variations in microvascular density (MVD) at different stages of tumor growth, contrast-enhanced ultrasound (CEUS) features may provide a noninvasive method for evaluating the WHO/ISUP grade of ccRCC.


Methods
In this study, we analyzed confirmed cases of ccRCC using CEUS features. We also used CD34 and CD31 antibodies to determine MVD. The heterogeneity of CD34 and CD31 expressions were used to determine different degrees of angiogenesis.


Results
When compared to WHO/ISUP grade I/II (G1/G2) tumors, grade III/IV (G3/G4) tumors had reduced peak intensity (PI) (P=0.006), time to peak (TTP) (P<0.001), and relative enhancement percentage index (∆PI%) (P<0.001). However, the frequency of incomplete pseudocapsule (P=0.049) and slow wash-in (P=0.001) was significantly higher in G3/G4 tumors. A cut-off value of ∆PI% <33.15% (P<0.001) allowed identification of G3/G4 tumors with an area under the curve (AUC) of 0.80 [95% confidence interval (CI): 0.70 to 0.91) and a sensitivity of 80%. The mean CD34+ MVD (P<0.001) and CD31+ MVD (P<0.001) were significantly lower in G3/G4 tumors. A positive correlation was revealed between ∆PI% and MVD. There was a statistically significant difference in the density of undifferentiated vessels between the slow wash-in and fast wash-in cases (P<0.001).


Conclusions
The features of CEUS are effective for differentiating G3/G4 tumors from G1/G2. There was a positive correlation detected between ∆PI% and MVD, and the density of undifferentiated vessels showed a significant difference between slow wash-in and fast wash-in cases. These findings indicate that CEUS can enable the sonographic visualization of tumor angiogenesis and thus be considered an acceptable method for the nonsurgical assessment of tumor microvascular distribution and grade.