Application value of contrast-enhanced ultrasound in the preoperative evaluation of renal cell carcinoma histological classification and RENAL score

Introduction

Renal cell carcinoma (RCC) is the most prevalent malignant renal tumor, accounting for approximately 85% of renal cancers, and is primarily treated with surgical resection, including radical nephrectomy (RN) and partial nephrectomy (PN) (1). The histological classification is typically clear cell renal cell carcinoma (ccRCC), accounting for approximately 70% of cases, and tends to invade blood vessels and undergo early metastasis (2). The 5-year survival rate of ccRCC is 68.9%, which is significantly lower than that of papillary renal cell carcinoma (pRCC; 87.4%) and chromophobe renal cell carcinoma (chRCC; 86.7%) (3). A histologic diagnosis of RCC is typically established following surgical removal of renal tumors or biopsy, but has certain drawbacks, such as reduced sensitivity due to tumor size, heterogeneity, and the potential for complications (such as bleeding). The RENAL (radius, exophytic/endophytic, nearness, anterior/posterior, and location) score is a preoperative grading system for renal tumors, which comprehensively evaluates the preoperative characteristics of renal tumors based on imaging anatomy, objectively evaluates the difficulty of surgery, and guides clinical rational selection of surgical methods and treatment strategies (4,5). The histological classification of RCC and RENAL score can critically inform treatment decision-making (i.e., RN or PN) and the prognosis of patients.

Conventional ultrasound (gray-scale and Doppler ultrasound), serves as the first-line imaging modality employed for the evaluation of RCC, but its diagnostic accuracy is limited. Contrast-enhanced ultrasound (CEUS) can dynamically display blood distribution and microcirculation perfusion in real time without causing nephrotoxicity. Unlike those of contrast-enhanced computed tomography (CECT), the contrast agents of ultrasound are purely intravascular and primarily eliminated through respiration in 15 minutes after injection. At present, the recommended applications of CEUS include the differentiation between solid renal tumors and pseudotumors, the characterization of complex cysts and indeterminate renal lesions, and the follow-up of nonsurgically treated renal masses (6). The purpose of this study was to examine the value of CEUS in preoperative evaluation of the histological classification and RENAL score of RCC. We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-694/rc).

Methods

Subjects

Between March 2021 and November 2023, a consecutive series of patients with renal tumors who underwent CEUS examination within 1 week prior to treatment at Lanzhou University Second Hospital were enrolled. The inclusion criteria were a histopathological diagnosis of renal tumor and available preoperative CEUS imaging. The exclusion criteria were non-RCC (non-renal cell tumors and benign tumors), unavailability of CECT images, and cystic renal tumors (Figure 1). This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the ethics committee of Lanzhou University Second Hospital (No. 2023A-557). Due to the retrospective nature of the study, the requirement for informed consent was waived.

Figure 1 Flow diagram illustrating exclusion criteria and categorization method adopted in this study. CEUS, contrast-enhanced ultrasound; CECT, contrast-enhanced computed tomography; RCC, renal cell carcinoma; ccRCC, clear cell renal cell carcinoma; nccRCC, non-clear cell renal cell carcinoma; RENAL, radius, exophytic/endophytic, nearness, anterior/posterior, and location.

CEUS examination

The patient was examined in a lateral position (or the supine position or prone position depending on the specific situation), and the long-axis and short-axis sections of the kidney were carefully scanned to select the optimal section for displaying the tumor. CEUS examination was conducted using one of three color Doppler ultrasound diagnostic instruments: the APLIO I800 (Canon, Tokyo, Japan) with the i8CX1 convex array probe (1–8 MHz), the EPIQ 7 (Philips Healthcare, Best, The Netherlands) with the C5-1 convex array probe (1–5 MHz), or the ACUSON Sequoia (Siemens Healthineers, Erlangen, Germany) with the 5C1 convex array probe (1–5 MHz) at a low mechanical index. A suspension (1.2–2.4 mL) of the contrast agent (SonoVue, Bracco, Milan, Italy) was rapidly injected into the antecubital vein of the patient, after which a 5-mL flush of saline was administered. Patients were advised to maintain a calm and regular respiration throughout the process. The ultrasound machine’s timer was initiated when the contrast agent was administered. Each CEUS imaging acquisition was recorded for a minimum of 2 continuous minutes, with the data subsequently being stored on the instrument workstation. The interval between repeated CEUS was more than 15 minutes. All ultrasound images were measured and interpreted by the same observer with more than 5 years of CEUS experience and who was blinded to the final diagnosis of patients.

Ultrasound features

The conventional ultrasound qualitative features of the tumor, including echogenicity (hypo-, iso-, slightly hyper-, or hybrid-echoic), internal homogeneity (homogeneous or heterogeneous), intrarenal lesion:kidney ratio (≤50% or >50%), position (horizontal or vertical), internal color Doppler flow imaging (CDFI) after CEUS (grade: 0, 1, 2, or 3; form: 0, rodlike, or dendritic), calcification (presence or absence), and internal anechoic region (presence or absence) were recorded (Figure 2). In accordance with the Adler stratifications of vascularity (7), the internal CDFI was divided into the following four levels: 0, nonvascular; 1, low vascular; 2, moderately vascular; and 3, marked vascular. Furthermore, the wash-in and wash-out of the contrast agent were observed dynamically. The peak enhancement (hyper-, iso-, or hypoenhancement), enhancement homogeneity (homogeneous or heterogeneous), internal nonenhanced region (0, ≤50%, or >50%), and wash-in (fast, synchronous, or slow) were analyzed and recorded (Figure 2). As for CEUS quantitative parameters, the arrive time (AT) was defined as the time when the contrast agent arrived at the tumor or the renal corte, and was normalized as the ∆AT_tumor-cortex by subtracting the value of the tumor from that of the cortex. The time-intensity curve (TIC) and related parameters were automatically produced via external software (VueBox, Bracco) in line with the delineation of the regions of interest (ROIs) of the renal cortex, local tumor, and largest range of tumor (Figures 3,4). The related parameters were time to peak (TTP) and ROI area (Area).

Figure 2 The conventional ultrasound and CEUS features investigated in this study. CEUS, contrast-enhanced ultrasound.

Figure 3 A 57-year-old man who underwent partial nephrectomy with pathological confirmation ccRCC in the left kidney. (A) Conventional ultrasound revealed a slightly hyperechoic tumor (arrows) with heterogeneous echogenicity, vertical position, and multiple small internal anechoic regions, which was about 3.8 cm × 2.7 cm in size and had an intrarenal lesion:kidney ratio ≤50%. (B) Color Doppler flow imaging revealed the internal blood flow of level 3 (marked vascular) and rodlike form after CEUS. (C) CEUS revealed fast wash-in (12 s) and heterogeneous hypoenhancement in the cortical phase (19 s). (D) CEUS revealed hyperenhancement in the parenchymal phase (31 s). (E,F) Delineation of regions of interest and the time-intensity curves (blue indicates a mandatory region, pink indicates the cortex, green indicates the largest tumor range, and red indicates local tumor). ∆AT_tumor-cortex =−1 s, Area_max =9.36 cm²; TTP_tumor =12.902 s; RENAL score = 8 × (R–1, E–1, N–3, A–X, L–3). 1/3: R, E, N, and L are scored on a scale of 1 or 3; X: uncertain location. ccRCC, clear cell renal cell carcinoma; CEUS, contrast-enhanced ultrasound; AT, arrive time; Area, region of interest area; TTP, time to peak; RENAL, radius, exophytic/endophytic, nearness, anterior/posterior, and location.

Figure 4 A 47-year-old woman who underwent partial nephrectomy with pathological confirmation of chRCC in the left kidney. (A) Conventional ultrasound revealed an isoechoic tumor (arrows) with homogeneous echogenicity and horizontal position, which was about 5.3 cm × 4.0 cm in size, and an intrarenal lesion:kidney ratio ≤50%. (B) Color Doppler flow imaging revealed level 0 (nonvascular) internal blood flow after CEUS. (C) CEUS revealed synchronous wash-in (13 s) and homogeneous hypoenhancement in the cortical phase (17 s). (D) CEUS revealed hypoenhancement in the parenchymal phase (33 s). (E,F) Delineation of regions of interest and the time-intensity curves (blue indicates a mandatory region, pink indicates the cortex, green indicates the largest tumor range, and yellow indicates local tumor). ∆AT_tumor-cortex =0 s; Area_max =13.53 cm²; TTP_tumor =8.702 s; RENAL score = 10 × (R—2, E—2, N—3, A—X, L—3). 2/3: R, E, N, and L are scored on a scale of 2 or 3; X: uncertain location. chRCC, chromophobe renal cell carcinoma; CEUS, contrast-enhanced ultrasound; AT, arrive time; Area, region of interest area; TTP, time to peak; RENAL, radius, exophytic/endophytic, nearness, anterior/posterior, and location.

Statistical analysis

The data were analyzed using SPSS 26 (IBM Corp., Armonk, NY, USA). Measurement data that exhibited a normal distribution are expressed as the mean standard deviation. In order to conduct a comparison of the mean values of independent samples, an independent samples t-test or an approximate t-test was employed based on the results of the homogeneity test of variance. Furthermore, the count data were compared with the χ² test or the Fisher exact test. Subsequently, receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic performance. The cutoff value was determined via the Youden index (defined as the sensitivity plus specificity minus 1). Binary logistic regression was used to analyze the independent risk factors of ccRCC. Ultrasound features (P≤0.001) were included in logistic regression analysis, and clinical information such as sex and body mass index (BMI) was also included to eliminate the influence of confounding factors. The diagnostic performance of CEUS and CECT in distinguishing ccRCC from non-clear cell renal cell carcinoma (nccRCC) was compared with the McNemar test. Consequently, a two-tailed P value <0.05 was considered to indicate statistical significance.

Results

This study included 246 patients (including 154 males and 92 females), comprising 248 RCCs, which were classified into two groups: ccRCC and nccRCC. Other general information is presented in Tables 1,2. The mean age of the patients was 57.1±10.5 years (range, 24–83 years). Two patients were diagnosed as bilateral ccRCC. All RCCs were confirmed via surgical pathology with 196 ccRCCs and 52 nccRCCs (Table 1). As is shown in Table 2, the proportion of males in the ccRCC group (129/196, 65.8%) was significantly higher than that in the nccRCC group (26/52, 50.0%) (P=0.036), but sex was not an independent risk factor of ccRCC. The BMI in the ccRCC group (24.7±3.5 kg/m²) was significantly higher than that of the nccRCC group (23.2±3.0 kg/m²) (P=0.009), and a higher BMI was an independent risk factor of ccRCC. The ROC curve was plotted for BMI in differentiating the ccRCC and nccRCC, with a maximum Youden index of 0.222 (cutoff value 22.3 kg/m²; P=0.015). In addition, the sensitivity, specificity, area under the curve (AUC), and 95% confidence interval (CI) were 76.0%, 53.8%, 0.610, and 0.525–0.694, respectively. This suggests that a BMI >22.3 kg/m² is associated with ccRCC. Moreover, the possibility of abnormal serum calcium in the ccRCC group (18/192, 9.4%) was significantly higher than that in the nccRCC group (0/52, 0.0%) (P=0.016). However, no significant differences were observed with regard to age, laterality, tumor size, or symptom.

Differences in ultrasound features between the two groups

As presented in Table 3, statistically significant differences were observed in terms of internal homogeneity, intrarenal lesion:kidney ratio, position, internal blood flow after CEUS, calcification, and the internal anechoic region in two groups. Compared to the nccRCC group, the ccRCC group had significantly higher measures for the following features: possibility of heterogeneity (P=0.033), intrarenal lesion:kidney ratio >50% (P=0.019), vertical position (P=0.027), high CDFI grade (P=0.039), dendritic form after CEUS (P=0.023), no calcification (P=0.039), and internal anechoic region (P=0.001). The presence of internal anechoic region was more likely to indicate ccRCC (169/196, 86.2%) than nccRCC (34/52, 65.4%) (P=0.001) but was not an independent risk factor of ccRCC (Table 4). There was no significant difference in echogenicity.

With regard to the CEUS features, statistically significant differences between the two groups were observed in peak enhancement, enhancement homogeneity, internal nonenhanced region, wash-in, ∆AT_tumor-cortex, TTP_tumor, and Area_max. The possibility of hyperenhancement (P<0.001), heterogeneous enhancement (P<0.001), internal nonenhanced region ≤50% (P=0.001), and fast wash-in (P<0.001) in the ccRCC group was significantly higher than that in the nccRCC group. Furthermore, peak enhancement, enhancement homogeneity, internal nonenhanced region, and wash-in were independent risk factors of ccRCC (Table 4). Moreover, in the ccRCC group, the ∆AT_tumor-cortex (P=0.012) and Area_max (P=0.045) were lower while the TTP_tumor was shorter (P=0.022).

Diagnostic performance of CEUS and CECT in differentiating between ccRCC and nccRCC

As is shown in Table 5, the diagnostic performance in the differentiation of ccRCC and nccRCC were good for both CEUS and CECT: sensitivity were 99.5% and 91.8%; specificity were 80.8% and 84.6%; positive predictive value were 95.1% and 95.7%; negative predictive value were 97.7% and 73.3%; accuracy were 95.6% and 90.3%, respectively. There was no statistically significant difference in differentiating ccRCC and nccRCC between the two diagnostic tools (P=0.130).

Ultrasound features to evaluate the RENAL score

As is shown in Tables 6,7, there was a significant difference in RENAL score based on ultrasound features between RN and PN group (P<0.001). In addition, between the RN and PN groups, there were significant differences in the radius (P<0.001), exophytic/endophytic (P<0.001), nearness (P<0.001), and location (P<0.001) features of the RENAL score based on ultrasound features; however, there was no significant difference in the anterior/posterior feature (P=0.661).

Discussion

CEUS has recently been endorsed by guidelines as the recommended strategy for the diagnosis of renal tumors (6). Subsequent to the administration of ultrasound contrast agents, two distinct phases are defined: the cortical phase (<25 s) and the parenchymal phase (25 s to 4 min). CEUS is an imaging modality without nephrotoxic effects, which allows for its repeated use even in patients with limited renal function. CEUS qualitative analysis of the RCC can be conducted with the adjacent renal cortex at the same depth serving as a reference and includes peak enhancement, enhancement homogeneity, enhancement pattern (centripetal, centrifuge, integral, or hybrid), enhancement margin (well-defined or ill-defined), enhancement shape (regular or irregular), internal nonenhanced region, perilesional rim-like enhancement (presence or absence, the time of appearance, and complete or incomplete), and the time of wash in, peak, and wash out. The administration of an intravenous bolus of the ultrasound contrast agent can facilitate the visualization of perfusion and regression of renal microcirculation, which can then be subjected to quantitative evaluation by quantitative analysis software. In this study, external software (VueBox) was used to quantitatively analyze CEUS through the depiction of TICs derived from ROIs. Additionally, most of the CEUS quantitative parameters were normalized by subtracting the value of the tumor from that of the cortex. For brevity, we only describe the statistically significant CEUS qualitative and quantitative features in this paper.

As shown in Table 2, the proportion of males in the ccRCC group (129/196, 65.8%) was significantly higher than that in the nccRCC group (26/52, 50.0%) (P=0.036), but sex was not an independent risk factor of ccRCC (Table 4). Furthermore, we found that the BMI in the ccRCC group (24.7±3.5 kg/m²) was significantly higher than that of the nccRCC group (23.2±3.0 kg/m²) (P=0.009), and the higher BMI was an independent risk factor of ccRCC (Table 4). The ROC curve was plotted for BMI in differentiating of the ccRCC and nccRCC and the maximum Youden index was 0.222 (cutoff value 22.3 kg/m²; P=0.015). Additionally, the sensitivity, specificity, AUC, and 95% CI were 76.0%, 53.8%, 0.610, and 0.525–0.694, respectively. This implies that a BMI >22.3 kg/m² may indicate ccRCC. The relevant guidelines (2,8) hold that obesity is both a risk and a protective factor. Cancer risk and cancer-specific survival rate are positively correlated with BMI, but the overall survival rate of obese patients with RCC is improved with targeted therapy. Moreover, weight loss can reduce cancer-specific mortality. Graff et al. (9) examined three prospective studies and confirmed that obesity is a risk factor for total and fatal RCC but further found that BMI at diagnosis is a suboptimal prognostic, as patients who have lost weight are likely to have more aggressive cancer. In our study, we found that the likelihood of abnormal serum calcium in the ccRCC group (18/192, 9.4%) was significantly higher than that in the nccRCC group (0/52, 0.0%) (P=0.016). The serum calcium concentration of 5 patients was higher than the normal value (2.11–2.52 mmol/L), and that in the remaining 13 patients was lower. Further investigations consisting of larger-sample, multicenter, and prospective studies are needed to corroborate these findings.

As seen in Table 3, statistically significant differences were observed in terms of internal homogeneity, intrarenal lesion:kidney ratio, position, internal blood flow after CEUS, calcification, and internal anechoic region between the two groups. Compared with the nccRCC group, the ccRCC group had significantly higher measurements in terms of the possibility of heterogeneity (P=0.033), intrarenal lesion:kidney ratio >50% (P=0.019), high CDFI grade (P=0.039), and dendritic form (P=0.023) after CEUS, which may be related to the higher degree of malignancy, richer blood vessels, and more active cell proliferation of ccRCC. Furthermore, the ccRCC group exhibited a higher prevalence of vertical position (86/196, 43.9%) compared to the nccRCC group (14/52, 26.9%) (P=0.027). This may be attributed to the fact that ccRCC exhibits rapid growth and is highly malignant, capable of transcending gravitational forces and infiltrating and destroying surrounding tissues. In addition, calcification was more common in the nccRCC group (29/52, 55.8%) than in the ccRCC group (78/196, 39.8%) (P=0.039). This could be because calcification often occurs in rare subtypes of RCC, such as MiT family translocation RCC (10,11). As for internal anechoic region, it is mostly caused by necrosis (common in ccRCC and pRCC) or cystic change (most common in pRCC). In our study, the presence of an internal anechoic region was more associated with ccRCC (169/196, 86.2%) than with nccRCC (34/52, 65.4%) (P=0.001) but was not an independent risk factor for ccRCC (Table 4). In addition, in our previous study, we found that necrosis is an independent risk factor for invasive RCC (12). The above results suggest that if we exclude pRCC (caused by cystic change or necrosis), the presence of an internal anechoic region may suggest that the tumor is more malignant (ccRCC, mainly caused by necrosis). Moreover, there was no significant difference in echogenicity between the ccRCC and pRCC groups.

With regard to the CEUS-based qualitative features, statistically significant differences were observed in peak enhancement, enhancement homogeneity, internal nonenhanced region, wash-in, ∆AT_tumor-cortex, TTP_tumor, and Area_max between the two groups. The likelihood of hyperenhancement (P<0.001), heterogeneous enhancement (P<0.001), internal nonenhanced region ≤50% (P=0.001), and fast wash-in (P<0.001) in the ccRCC group was significantly higher than that in the nccRCC group. Furthermore, peak enhancement, enhancement homogeneity, an internal nonenhanced region, and wash-in were independent risk factors of ccRCC (Table 4). These findings are consistent with those of previous studies. For instance, on CEUS, ccRCC is more likely to show hyperenhancement, heterogeneous enhancement, and fast wash-in, while pRCC is more likely to show hypoenhancement, heterogeneous enhancement, and slow wash-in; moreover, typical chRCC is more likely to show hypoenhancement, homogeneous enhancement, and slow wash-in, while MiT family translocation RCC is more likely to show hypoenhancement, heterogeneous enhancement, and synchronous wash-in. Apart from those mentioned above, the common characteristics of RCC are fast wash-out and perilesional rim-like enhancement (13-15). The formation of perilesional rim-like enhancement is associated with the swelling growth of tumor and compression of peritumoral tissue (12). It has been suggested that the presence of perilesional rim-like enhancement may be inversely related to tumor size (16). In our study, an internal nonenhanced region >50% was more common in the nccRCC group (10/52, 19.2%) than in the ccRCC group (7/196, 3.6%) (P=0.001). This may be related to the low degree of malignancy of nccRCC, which contributes to the late appearance of symptoms (such as flank pain, visible hematuria, or palpable abdominal mass) and treatment, or to the composition of nccRCC (such as cystic change). As for CEUS quantitative features, the ccRCC group had a lower ∆AT_tumor-cortex (P=0.012) and shorter TTP_tumor (P=0.022) than did the nccRCC group. Similar results were found by Sun et al. (14), Li et al. (17), and Lu et al. (18). In our study, the data regarding tumor size were obtained from pathological gross specimens, CECT, and CEUS, but the differences between the two groups were not statistically significant (all P values >0.05) (Table 2). However, the Area_max was lower in the ccRCC group than in the nccRCC group (P=0.045) and might prove useful in more precisely measuring the tumor range prior to operation.

Of the 196 ccRCCs in our study, 1 ccRCC was misdiagnosed by CEUS as nccRCC, and 16 ccRCCs were misdiagnosed by CECT as nccRCCs. Among the 52 nccRCCs, 10 nccRCCs were misdiagnosed by CEUS as ccRCCs, and 8 nccRCCs were misdiagnosed by CECT as ccRCCs. In our study, the differential diagnostic performance of ccRCC and nccRCC by CEUS was comparable to that of CECT and had high sensitivity. The preoperative differentiation between ccRCC and nccRCC is a well-known radiographic diagnostic challenge and is especially important due to their vastly different treatments and prognoses. CEUS is a useful method which can be used to clinically differentiate between ccRCC and nccRCC and in our study, yielded a sensitivity of 99.5% (195/196), a specificity 80.8% (42/52), a positive predictive value of 95.1% (195/205), a negative predictive value of 97.7% (42/43), and an accuracy of 95.6% (237/248), indicating performance comparable to that of CECT. Similar results were reported by Liang et al. (19), Fang et al. (20), Marschner et al. (21), and Zhao et al. (22). Additionally, Fang et al. (20) found that CEUS could better display the circular perfusion of RCC than could CECT (P<0.05).

We additionally found there to be a significant difference between the RN and PN group in terms of the RENAL score based on ultrasound features. The RENAL score is based on five critical and reproducible anatomical features of solid renal masses. Of the five components, four are scored on a 1-, 2-, or 3-point scale with the 5th indicating the anterior or posterior location of the mass relative to the coronal plane of the kidney (23). As is shown in Tables 6,7, there were significant differences in the radius (P<0.001), exophytic/endophytic (P<0.001), nearness (P<0.001), and location (P<0.001) ultrasound features of the RENAL score between the RN and PN group. Ultrasound features can be used for determining RENAL score of RCC before operation. Watts et al. (24) reported that the radius, exophytic/endophytic, and nearness features in the RENAL score were associated with significant changes in warm ischemic time and operative time. Moreover, the radius and exophytic/endophytic features were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery. Recent reports (25,26) have described the use of nomograms that accurately predict estimated glomerular filtration rate reduction after PN that incorporate the RENAL score in addition to sex, age, and preoperative renal function. Therefore, we plan to include clinical information such as hospitalization time, blood loss, operation time, and complications in a follow-up study and conduct survival analysis to further determine the value of ultrasound features in the preoperative evaluation of operation complexity.

Ultrasound-guided biopsy and pathological examination also play important roles in the accurate preoperative diagnosis of RCC. Fluorescence confocal microscopy can provide real-time digital imaging of fresh tissues without further routine pathology. This allows for the real-time microscopic examination of cells and structures with high-resolution visualization (27). Mir et al. (28) reported that the consistency between ex vivo fluorescence confocal microscope analysis and definitive hematoxylin and eosin staining was 100%. CEUS can significantly improve the positive rate of puncture biopsy and when combined with fluorescence confocal microscope technology, can provide an accurate diagnosis before operation, demonstrating good application prospects.

Through the intravenous injection of microbubble contrast agent, CEUS can directly display the macroscopic and microvascular systems of tissues and organs, realizing the dynamic real-time assessment of blood perfusion and local microcirculation. Based on this, TICs can be drawn, and RCC can be qualitatively and quantitatively analyzed. Due to its speed, convenience, safety, efficacy, cost-effectiveness, repeatability, and high resolution, CEUS has broad application prospects in the diagnosis and treatment of RCC. As discussed above, CEUS has considerable value as a diagnostic imaging modality for the precise diagnostic work-up and follow-up of renal tumors, providing higher spatial and temporal resolutions than those of computed tomography and magnetic resonance imaging.

Certain limitations to this study should be acknowledged. Given the retrospective design, there was a possible bias in the sample size of the two groups and the calculated cutoff value, which should be verified through future prospective studies. In addition, this study was conducted at a single center with a relatively limited sample size. Moreover, CEUS examination was conducted with three different color Doppler ultrasound diagnostic instruments, each equipped with a separate convex array probe, which might have influenced the results. Further large-sample, multicenter studies should be conducted to confirm our findings.

Conclusions

Features based on conventional ultrasound and CEUS may help differentiate ccRCC from nccRCC, possess considerable potential in the characterization preoperative complexity, and could provide more precise and useful information for diagnosis and treatment. CEUS has the capacity to optimize the treatment plan in a noninvasive manner and improve the prognosis of patients, and its performance should be examined in multicenter, large-cohort, prospective research.

Acknowledgments

The authors would like to thank all the team members at the Ultrasound Medical Center, Lanzhou University Second Hospital, for their helpful cooperation.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-694/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-694/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions relating to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the ethics committee of Lanzhou University Second Hospital (No. 2023A-557). Due to the retrospective nature of the study, the requirement for informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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