Contrast-enhanced Ultrasound: Improving the Preoperative Staging of Hepatocellular Carcinoma and Guiding Individual Treatment

Aim: To investigate the clinical role of contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging to improve the preoperative staging of hepatocellular carcinoma (HCC) and guide surgical decision-making.

Methods: Sixty-nine patients who underwent liver resection for HCC in our center were enrolled prospectively in the study. CEUS and CE-CT/MRI were performed before surgery. Intraoperative ultrasound (IOUS) was carried out after liver mobilization. Lesions depicted by each imaging modality were counted and mapped. To investigate the impact of tumor size on the study, we divided the patients into two groups, the "Smaller group"(S-group, ≤ 5 cm in diameter) and the "Larger-group" (L-group, > 5 cm in diameter). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CE-CT/MRI, CEUS, IOUS, CEUS+CE-CT/MRI and the tumor node metastasis staging of tumors were calculated and compared. Changes in the surgical strategy as a result of CEUS and IOUS were analyzed.

Results: One hundred and twenty-seven nodules, comprising 94 HCCs confirmed by histopathology and 33 benign lesions confirmed by histopathology and follow-up, were identified in 69 patients. The overall diagnostic sensitivity rates of CE-CT/MRI, CEUS, IOUS and CEUS+ CE-CT/MRI were 78.7%, 89.4%, 89.4% and 89.4%, respectively. There was a significant difference between CEUS + CE-CT/MRI and CE-CT/MRI (P = 0.046). Combining CEUS with CT or MRI increased, the diagnostic specificity compared with CT/MRI, CEUS and IOUS, and this difference was statistically significant (100%, 72.7%, 97.0%, and 69.7%, P = 0.004, P = 0.002, P = 0.002, respectively). The diagnostic accuracy was significantly higher for CEUS + CT/MRI compared with CT/MRI (92.1% vs 77.2%, P = 0.001). The TNM staging of tumors based on CEUS + CE-CT/MRI approximated to the final pathological TNM staging (P = 0.977). There was a significant difference in the accuracy of TNM staging when comparing CEUS + CE-CT/MRI with CE-CT/MRI (P = 0.002). Before surgery, strategies were changed in 15.9% (11/69) of patients as a result of CEUS. Finally, only 5.7% (4/69) of surgical strategies were changed because of IOUS findings. In the S-group, CEUS revealed 12 false positive lesions, including seven false positive lesions that were diagnosed by preoperative imaging examinations and five by IOUS. In contrast, in the L-group, IUOS revealed eight new malignant lesions; six of these lesions were true HCCs that were also identified by preoperative CEUS.

Conclusion: CEUS combined with CT or MRI improves the accuracy of preoperative staging for hepatocellular carcinoma and may help to guide individualized treatment for patients with HCC. CEUS may better identify non-malignant lesions in patients with small tumors and discover new malignant lesions in patients with large tumors.