T. Bernatik

Contrast-enhanced Ultrasound for the Characterization of Focal Liver Lesions – Diagnostic Accuracy in Clinical Practice (DEGUM multicenter trial)

PURPOSE To evaluate the diagnostic benefit of contrast-enhanced ultrasound for the differential diagnosis of liver tumors in clinical practice. MATERIALS AND METHODS From May 2004 to December 2006 1349 patients (male 677, female 672) with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by contrast-enhanced ultrasound using a standardized protocol (pulse/phase inversion imaging, mechanical index < 0.4). The Tumor status was assessed based on the vascularity pattern and contrast enhancement seen in focal lesions during the arterial, portal, and late phase. The diagnosis established after contrast-enhanced ultrasound was compared to histology (> 75% cases) or in some cases to CT or MRI. RESULTS The final diagnosis of hepatic tumors included 573 benign hepatic tumors (hemangiomas n = 242, focal nodular hyperplasia n = 170, hepatocellular adenoma n = 19, other benign lesions n = 142) and 755 malignant hepatic tumors (metastases n = 383, hepatocellular carcinoma n = 279, other malignant lesions n= 93). The overall diagnostic accuracy of contrast-enhanced ultrasound in comparison to the correct final diagnosis based on the combined gold standard was 90.3%. Contrast-enhanced ultrasound was able to correctly assess 723/755 malignant lesions (sensitivity 95.8%) and 476/573 benign lesions (specificity 83.1%). The positive predictive value of contrast-enhanced ultrasound for the diagnosis of a malignant tumor was 95.4% and the negative predictive value of contrast-enhanced ultrasound was 95.7%. CONCLUSION Contrast-enhanced ultrasound clearly improves the differential diagnosis of hepatic tumors and is very helpful in clinical practice when B-scan or power Doppler morphological criteria are missing.

Tumor-Specific Vascularization Pattern of Liver Metastasis, Hepatocellular Carcinoma, Hemangioma and Focal Nodular Hyperplasia in the Differential Diagnosis of 1349 Liver Lesions in Contrast-Enhanced Ultrasound (CEUS)

AIM To evaluate the incidence and diagnostic accuracy of tumor-specific vascularization pattern in contrast-enhanced ultrasound (CEUS) in the differential diagnosis of liver tumors in clinical practice. MATERIALS AND METHODS From May 2004 to December 2006 1349 patients (male 677, female 672) with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by CEUS using a standardized protocol (pulse/phase inversion imaging, mechanical index < 0.4). Vascularity pattern and contrast enhancement pattern were analyzed in focal lesions during the arterial, portal, and late phase. The tumor-specific diagnosis established after CEUS was compared to histology (> 75 % cases) or in some cases to CT or MRI. RESULTS The final diagnosis of 573 benign hepatic tumors included hemangiomas (n = 242) and focal nodular hyperplasia (n = 170), other benign lesions (n = 161). Tumor-specific vascularization pattern such as a wheel-spoke pattern and arterial hyperenhancement followed by isoenhancement in the late phase in FNH or a nodular peripheral enhancement and partial or complete fill-in pattern in hemangiomas could be assessed in the majority, but not all lesions. The diagnostic accuracy of CEUS was 83.1 % for all benign lesions and 82.2 % for hemangioma and 87.1 % for FNH. The final diagnosis of 755 malignant hepatic tumors included metastases n = 383, hepatocellular carcinoma n = 279 and other malignant lesions n = 93. Late phase hypoenhancement was seen in almost all liver metastases (94.7 %) The diagnostic accuracy of CEUS was 95.8 % for all malignant lesions and 91.4 % for liver metastases and 84.9 % for hepatocellular carcinomas. CONCLUSION Tumor-specific vascularization pattern in CEUS have a high diagnostic impact on the overall high diagnostic accuracy of CEUS for the differential diagnosis of hepatic tumors in clinical practice.

Contrast-Enhanced Ultrasound (CEUS) for the characterization of focal liver lesions - prospective comparison in clinical practice: CEUS vs. CT (DEGUM multicenter trial). Parts of this manuscript were presented at the Ultrasound Dreiländertreffen 2008, Davos.

AIM The aim of our study was to evaluate the diagnostic value of Contrast-Enhanced Ultrasound (CEUS) for the characterization of focal liver lesions in a prospective multi-center study in clinical practice. For this purpose CEUS was compared with the spiral-CT (SCT), the standard radiological method. MATERIAL AND METHODS 1349 patients with unclear liver lesions after fundamental ultrasound diagnostics including color doppler analysis were examined with standardized CEUS (pulse inversion method, mechanical index < 0.4) from May 2004 to December 2006 in 14 hospitals in a prospective study. The enhancement of contrast medium in the liver tumors was analyzed according to known tumor-specific vascular patterns, using standardized documentation and analysis methods for the differentiation of tumor differentiation (malign or benign) and tumor specification (entity). A subcollective of 267 patients was additionally examined by standardized SCT method. Final diagnosis was based on histology, SCT or MRI in typical findings of liver hemangioma and FNH and on proved clinical data and additional follow up. RESULTS The subcollective of 267 patients was divided in two subgroups. In 109 of these patients (subgroup A) there was no histological verification, diagnoses based on clear SCT-findings in 79 cases of hemangioma or FNH, as well as in 20 cases with a clear clinical diagnosis. 6 cases (5.5 %) remained unclear. In this subgroup the assessment of tumor differentiation was concordant with CEUS in 90 cases, discordant in 19 cases and the assessment of tumor specification was concordant in 82 and and discordant in 27 cases. In 158 patients (subgroup B) a histological finding was also present, only in 4 cases no definitive tumor diagnosis was achieved. In this subgroup assessment of tumor differentiation with CEUS and SCT was concordant in 124 cases and discordant in 30 cases (CEUS/SCT: sensitivity 94.0 / 90.7 %, specificity 83.0 / 81.5 %, PPV 91.6 / 91.5 %, NPV 87.5 / 80.0 %, accuracy 90.3 / 87.8 %). Tumor specification matched in 103cases and were different in 51 cases (CEUS/SCT: sensitivity 95.3 / 90.6 %, specificity 83.7 / 81.6 %, PPV 92.7 / 91.4 %, NPV 89.1 / 80.0 %, accuracy 91.6 / 87.7 %). A statistically significant difference could not be established. The analysis of particular tumor specification showed a statistically non significant slight advantage in tumor differentiation for CEUS in the case of hemangioma, FNH, HCC and metastases. CONCLUSION In a multi-center approach under routine clinical conditions, this prospective study demonstrates CEUS to be of equal rank to the CT-scan in regard to the assessment of tumor differentiation and specification. No statistically significant differences could be established. CEUS should be employed before computed tomography is performed for the differentiation of liver tumors, because radiation exposure and invasive biopsies can be avoided in veritable numbers of cases, when precise clinical evaluation of the findings is implemented.