Usefulness of Contrast-Enhanced Intraoperative Ultrasound Using Sonazoid in Patients With Hepatocellular Carcinoma

Objective: To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) using Sonazoid (gaseous perflubutane) in patients with hepatocellular carcinoma (HCC). Background: Contrast-enhanced intraoperative ultrasound using Sonazoid, a novel ultrasonic contrast agent enabling Kupffer imaging, may enable differentiation of HCC among new focal liver lesions found during fundamental intraoperative ultrasound (fundamental-NFLLs). Methods: Between February 2007 and February 2009, a total of 192 consecutive patients were enrolled. Fundamental intraoperative ultrasound and CE-IOUS were performed successively after laparotomy. The vascularity of 1 representative lesion was examined in harmonic mode for approximately 1 minute after the intravenous injection of Sonazoid (vascular phase). Approximately 15 minutes after the vascular phase, total liver scanning in the harmonic mode was commenced (Kupffer phase). One additional injection of Sonazoid was allowed to examine the vascularity of another lesion, if necessary. A tentative diagnosis of HCC was made when a lesion was either hypervascular during the vascular phase or hypoechoic during the Kupffer phase. A final diagnosis of HCC was made on the basis of the results of a histological examination or dynamic computed tomography findings obtained during the 12-month postoperative period. Results: Seventy-nine fundamental-NFLLs were found in 50 patients (26%), 17 (22%) of which were finally diagnosed as HCC. The sensitivity, specificity, and accuracy of CE-IOUS for differentiating HCC among fundamental-NFLLs were 65%, 94%, and 87%, respectively. Contrast-enhanced intraoperative ultrasound identified 21 additional new hypoechoic lesions in 16 patients, of which 14 lesions (67%) in 11 patients were finally diagnosed as HCC. This prospective study protocol was approved by the institutional review board of the Tokyo University Hospital. An English-language summary of the protocol was submitted (registration ID: UMIN000003046) to the Clinical Trials Registry managed by the University Hospital Medical Information Network in Japan (http://www.umin.ac.jp/ctr/index.htm). Conclusions: With help of CE-IOUS using Sonazoid, more accurate intraoperative staging for HCC can be performed.