Contribution of Contrast‐Enhanced Sonography With Perfluorobutane Microbubbles for Diagnosis of Recurrent Hepatocellular Carcinoma

Abstract

he frequent recurrence of hepatocellular carcinoma despite radical treatment such as surgical resection or radiofrequency ablation is an extremely difficult problem. To control the progression to advanced hepatocellular carcinoma and Buyanjargal Shagdarsuren, MD, Hideyuki Tamai, MD, PhD, Naoki Shingaki, MD, Yoshiyuki Mori, MD, Shuya Maeshima, MD, Junya Nuta, MD, Yoshimasa Maeda, MD, Kosaku Moribata, MD, PhD, Toru Niwa, MD, PhD, Hisanobu Deguchi, MD, Izumi Inoue, MD, PhD, Takao Maekita, MD, PhD, Mikitaka Iguchi, MD, PhD, Jun Kato, MD, PhD, Masao Ichinose, MD, PhD Received August 20, 2015, ORIGINAL RESEARCHObjectives-The role of contrast-enhanced sonography in the diagnosis of recurrent hepatocellular carcinoma is still unclear. This study aimed to clarify the usefulness and limitations of contrast-enhanced sonography with a perfluorobutane microbubble contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) after contrast-enhanced computed tomography (CT) for diagnosis of recurrent hepatocellular carcinoma and to establish its optimal use.Methods-A total of 514 patients, who were suspected to have recurrent hepatocellular carcinoma on contrast-enhanced CT, underwent contrast-enhanced sonography. Of 514 suspicious lesions, 484 were diagnosed as recurrent hepatocellular carcinomas, including 142 recurrent hepatocellular carcinomas measuring 1 cm or smaller in diameter. The largest lesion was evaluated in each patient. A final diagnosis of recurrent hepatocellular carcinoma after contrast-enhanced CT was reached on the basis of the typical hallmarks of hepatocellular carcinoma on any of the other contrast imaging modalities or by resected tissue or tumor enlargement during follow-up.Results-The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of contrast-enhanced CT were 68%, 93%, 99%, 15%, and 70%, respectively, and the values of contrast-enhanced sonography were 91%, 100%, 100%, 31%, and 91%, excluding 60 unassessable lesions on contrast-enhanced sonography. The diagnostic rate for recurrent hepatocellular carcinoma on contrast-enhanced sonography for lesions with an atypical enhancement pattern on contrast-enhanced CT was 71%. On multivariate analysis of factors contributing to the unassessability of contrastenhanced sonography, lesion size, location, and abdominal wall thickness were independent factors.Conclusions-Although the assessability of contrast-enhanced sonography depends on lesion size, location, and abdominal wall thickness, contrast-enhanced sonography after contrast-enhanced CT is useful for confirmative diagnosis of small recurrent hepatocellular carcinoma with an atypical enhancement pattern on contrast-enhanced CT, even for lesions measuring 1 cm or smaller in diameter.

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid

“…With this technique, scanning is conducted at a low MI, using a pulse inversion mode or amplitude modulation mode that changes the amplitude or the phase of the emission phase and receives nonlinear signals during continuous real-time scanning. The level of low MI in this technique usually ranges from 0.2 to 0.3 [10,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. However, the range of MI can be reduced to 0.1 [3,[38][39][40][41] and can be expanded to 0.4 [3].…”

“…Imaging acquisition during the vascular phase is principally similar to that of other second-generation UCAs, in that the vascular phase includes the arterial, portal venous, and late phases, when microbubbles are confined to the vascular space following IV UCA injection, with slow degradation over 5 minutes [10,26,[43][44][45]. For the arterial phase, the time window for imaging acquisition begins as early as 10-20 seconds [10,37,40,45], continues to 30-50 seconds for optimal timing [10,31,37,38,40,45], and is considered to last up to 1 minute after UCA injection [24,26,28,32,34,38,45]. Nonlinear signals during this phase reflect the arterial enhancement of an organ or a lesion, providing information on its arterial supply or vascularity.…”

“…Nonlinear signals during this phase reflect the arterial enhancement of an organ or a lesion, providing information on its arterial supply or vascularity. The portal venous phase starts from 30 to 50 seconds [10,40,42,45], continues to 80-90 seconds for optimal timing [26,31,37,38], and is considered to last until 2 minutes after UCA injection [10,[24][25][26]37,38,40,42,45]. The late vascular phase continues after the portal venous phase, and is defined to last until microbubbles disappear from the vascular space [10,31,38,40,45].…”

“…The late vascular phase continues after the portal venous phase, and is defined to last until microbubbles disappear from the vascular space [10,31,38,40,45]. Depending upon the study design, the portal and/or late vascular phases are not necessarily obtained within the three parts of the vascular phase [22][23][24][25][27][28][29][32][33][34][35][36][37]41,42,[46][47][48].…”

“…Following the late vascular phase, an additional and specific phase is available with Sonazoid CEUS, and this is referred to as the postvascular phase [2,4,49]. The postvascular phase follows the late vascular phase, and the corresponding imaging acquisition window is generally considered to begin 10 minutes after the contrast injection when microbubbles are sufficiently accumulated in the Kupffer cells by phagocytosis and are nearly removed from circulation; this phase persists for several hours [22,[24][25][26]28,29,[31][32][33][34][40][41][42]45,46,50]. Most malignant lesions become hypoechoic from the portal phase to the postvascular phase, whereas most benign hepatocyte-origin lesions are iso-or hyperechoic during these phases.…”