**3.4 The ultrasound value in HCC "screening"**

90 Liver Tumors

Spectral Doppler characteristics of early HCC overlap those of the dysplastic nodule, as they are represented by the presence of portal venous signal type or arterial type with normal RI (well differentiated HCC) or increased RI (moderately or poorly differentiated HCC). The

On CEUS examination, early HCC has an iso- or hypervascular appearance during the arterial phase followed by wash out during portal venous and late phase. There are studies showing that the wash out process is directly correlated with the size and features of neoplastic circulatory bed. Thus, highly differentiated HCC illustrates the phenomenon of late or even very late "wash out" while poorly differentiated HCC has an accelerated wash out at the end of arterial phase (Strobel et al, 2005; von Herbay et al, 2009; Jang et al, 2009). It is therefore mandatory to analyze all these three phases of CEUS examination for a proper characterization of liver nodules. Tumor wash out at the end of the arterial phase allows the HCC diagnosis with a predictability of 89.5%. Some authors consider that early pronounced contrast enhancement of a nodule within 1-2 cm developed on a cirrhotic liver is sufficient for HCC diagnosis (Jang et al, 2009). These results prove that for a correct characterization of the lesions it is necessary to extend the examination time to 5 minutes or even longer (von

Fig. 11. Early hepatocellular carcinoma (2D, CFM). The 2D examination reveals a solid, hypoechoic nodule in IVth liver segment, without encapsulation. CFM shows a central vessel

Fig. 12. Early hepatocellular carcinoma (2D, CFM). "Nodule in nodule" image: small

with ramifications to the periphery. The underlying liver is cirrhotic.

hypoechoic early HCC inside monitored dysplastic nodule.

CFM exploration identifies a chaotic vessels pattern.

Herbay et al, 2009).

Baseline 2D ultrasound has an important role in surveillance programs for patients at risk to develop HCC (Bruix & Sherman, 2011). The examination has an acceptable sensitivity which increases with the tumor size. Sensitivity varies between 42% for lesions <1 cm and 95% for tumors larger than 1 cm, and specificity can reach 90% (Andreana et al, 2009). Optimal time interval for ultrasound screening of "at risk" population is 6 months as it results from clinical trials that investigated the tumor size doubling time (Bruix, 2005; Maruyama et al, 2008). For a recently developed nodule the dimensional criteria will be taken into account. Thus, for a nodule with a size of less than 10 mm the patient will be reevaluated by ultrasound every 3 months, as the growth trend is an indication for completion of investigations with other diagnostic procedures; at a size between 10 - 20 mm two concordant imaging procedures are necessary, supplemented if necessary by an ultrasound guided biopsy; at a size over 20 mm one single dynamic imaging technique with characteristic appearance is enough for positive diagnostic. In uncertain cases complementary dynamic imaging techniques or biopsy should be performed. When Doppler exploration is not enough, CEUS examination will be performed (Gaiani et al, 2001). One should always keep in mind the risk of false positive results for HCC in case of cholangiocarcinomas so complementary diagnostic procedures should be considered (Bruix & Sherman, 2011).

The effectiveness of screening programs is proved by an increase in detection rate of HCC <2 cm (from <5% in the 90s in Europe to > 30% today in Japan) with curative therapy options (Llovet & Bruix 2008). The main problem of ultrasound screening is that, in order to be cost-effective, it should be applied to the general population and not in tertiary hospitals. This raises the importance of the operator and equipment dependent part of the ultrasound examination (Bruix et al, 2001). The efficiency of such a program is linked to the functional liver parenchyma of the cirrhotic patient. Therefore, some authors argue that screening should be excluded in patients with etiologies that prevent curative treatment or in patients with advanced liver disease (Child-Pugh class C) (Zapata et al, 2010).

After curative therapies (surgical resection, local ablative therapies) continuing ultrasound screening is recommended first at 1 month then at 3 months intervals after the therapy to assess the effectiveness of therapy and to detect other nodules.
