Prospective study of differential diagnosis of hepatic tumors by pattern-based classification of contrast-enhanced sonography

AIM: To prospectively evaluate the usefulness of a pattern-based classification of contrast-enhanced sonographic findings for differential diagnosis of hepatic tumors. METHODS: We evaluated the enhancement pattern of the contrast-enhanced sonography images in 586 patients with 586 hepatic lesions, consisting of 383 hepatocellular carcinomas, 89 metastases, and 114 hemangiomas. After injecting a galactose-palmitic acid contrast agent, lesions were scanned by contrast- enhanced harmonic gray-scale sonography in three phases: arterial, portal, and late. The enhancement patterns of the initial 303 lesions were classified retrospectively, and multiple logistic regression analysis was used to identify enhancement patterns that allowed differentiation between hepatic tumors. We then used the pattern-based classification of enhancement we had retrospectively devised to prospectively diagnose 283 liver tumors. RESULTS: Seven enhancement patterns were found to be significant predictors of different hepatic tumors. The presence of homogeneous or heterogeneous enhancement both in the arterial and portal phase was the typical enhancement pattern for hepatocellular carcinoma, while the presence of peritumoral vessels in the arterial phase and ring enhancement or a perfusion defect in the portal phase was the typical enhancement pattern for metastases, and the presence of peripheral nodular enhancement both in the arterial and portal phase was the typical enhancement pattern forhemangioma. The sensitivity, specificity, and accuracy of prospective diagnosis based on the combinations of enhancement patterns, respectively, were 93.2%, 96.2%, and 94.0% for hepatocellular carcinoma, 87.9%, 99.6%, and 98.2% for metastasis, and 95.6%, 94.1%, and 94.3% for hemangioma. CONCLUSION: The pattern-based classification of the contrast-enhanced sonographic findings is useful for differentiating among hepatic tumors.

Contrast enhanced ultrasound of hepatocellular carcinoma

Sonazoid(Daiichi Sankyo,Tokyo,Japan),a secondgeneration of a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent,has been used clinically in patients with liver tumors and for harmonic gray-scale ultrasonography(US)in Japan since January 2007.Sonazoid-enhanced US has two phases of contrast enhancement:vascular and late.In the late phase of Sonazoid-enhanced US,we scanned the whole liver using this modality at a low mechanical index(MI)without destroying the microbubbles, and this method allows detection of small viable hepatocellular carcinoma(HCC)lesions which cannot be detected by conventional US as perfusion defects in the late phase.Re-injection of Sonazoid into an HCC lesion which previously showed a perfusion defect in the late phase is useful for confirming blood flow intothe defects.High MI intermittent imaging at 2 frames per second in the late phase is also helpful in differentiation between necrosis and viable hypervascular HCC lesions.Sonazoid-enhanced US by the coded harmonic angio mode at a high MI not only allows clear observation of tumor vessels and tumor enhancement, but also permits automatic scanning with Sonazoidenhanced three dimensional(3D)US.Fusion images combining US with contrast-enhanced CT or contrastenhanced MRI have made it easy to detect typical or atypical HCC lesions.By these methods,Sonazoidenhanced US can characterize liver tumors,grade HCC lesions histologically,recognize HCC dedifferentiation, evaluate the efficacy of ablation therapy or transcatheter arterial embolization,and guide ablation therapy for unresectable HCC.This article reviews the current developments and applications of Sonazoid-enhanced US and Sonazoid-enhanced 3D US for diagnosing and treating hepatic lesions,especially HCC.

Differentiation of focal liver lesions using three-dimensional ultrasonography: Retrospective and prospective studies

AIM: To differentiate focal liver lesions based on enhancement patterns using three-dimensional ultrasonography (3D US) with perflubutane-based contrast agent.METHODS: Two hundred and eighty two patients with focal liver lesions,including 168 hepatocellular carcinomas (HCCs),63 metastases,40 hemangiomas and 11 focal nodular hyperplasias (FNHs),were examined by 3D US with perflubutane-based contrast agent.Tomographic ultrasound images and sonographic angiograms were reconstructed.Among 282 lesions,enhancement patterns of 163 lesions between January 2007 and October 2007 were analyzed retrospectively.Then from November 2007 to May 2008,compared with contrast-enhanced (CE) 2D US,CE 3D US was performed on 119 lesions for prospective differential diagnosis.Sensitivity,specificity,area under receiver operating characteristic curve (Az) and inter-reader agreement were assessed.RESULTS: With the tridimensional view,dominant enhancement patterns were revealed as diffuse enhancement or peripheral ring-like enhancement,followed with washout change for HCCs or metastases,respectively,and peripheral nodular enhancement or diffuse enhancement with spoke-wheel arteries,followed by persistent enhancement for hemangiomas or FNHs,respectively.At CE 3D US,the prospective differentiation of lesions showed sensitivity 92% (mean for two readers),specificity 91% and Az value 0.95 for HCCs,84%,97%,and 0.95 for metastases,91%,98%,and 0.98 for hemangiomas and 80%,99%,and 0.99 for FNHs,respectively,while good to excellent inter-reader agreement was achieved.No significant difference exists between prospective diagnosis accuracy at CE 3D US and that at CE 2D US.CONCLUSION: CE 3D US provides a spatial perspective for liver tumor enhancement,and could help in differentiating focal liver lesions.

Successful initial ablation therapy contributes to survival in patients with hepatocellular carcinoma

AIM: To evaluate the outcome predictors of percu- taneous ablation therapy in patients with unresectable hepatocellular carcinoma (HCC), especially to identify whether the initial treatment response contributes to the survival of the patients. METHODS: The study cohort included 153 patients with single (102) and two or three (51) HCC nodules 5 cm or less in maximum diameter. As an initial treatment, 110 patients received radiofrequency ablation and 43 patients received percutaneous ethanol injection. RESULTS: The Kaplan-Meier estimates of overall 3- and 5-year survival rates were 75% and 59%, respectively. The log-rank test revealed statistically significant differences in the overall survivals according to Child- Pugh class (P = 0.0275), tumor size (P = 0.0130), serum albumin level (P = 0.0060), serum protein induced by vitamin K absence or antagonist Ⅱ level (P = 0.0486), and initial treatment response (P = 0.0130). The independent predictors of survival were serum albumin level (risk ratio, 3.216; 95% CI, 1.407-7.353; P = 0.0056) and initial treatment response (risk ratio, 2.474; 95% CI, 1.076-5.692; P = 0.0330) based on the Cox proportional hazards regression models. The patients had a serum albumin level 3.5 g/dL and the 3- and 5-year survival rates of 86% and 82%. CONCLUSION: In HCC patients treated with percutaneous ablation therapy, serum albumin level and initial treatment response are the independent outcome predictors.