**4.2 Ultrasound monitoring ablative therapies (alcoholization - PEI, radiofrequency ablation - RFA)**

Ablative therapies are considered curative treatments for HCC together with surgical resection and liver transplantation and they are indicated for early tumor stages in patients with good liver function (Bruix & Sherman, 2005; Bruix & Sherman, 2011). Also they are successfully applied in the treatment of liver metastases, where surgical resection is contraindicated. They are chemical (intratumoral ethanol injection) or thermal (radiofrequency, laser or microwave ablation). They are applied in order to obtain a full therapeutic response, without affecting liver function. Complete response is locally proved by complete tumor necrosis with a safety margin around the tumor.

2D ultrasound, Doppler ultrasound and especially CEUS can play an important role in pretherapeutic staging, particularly when sectional imaging investigations (CT, MRI) provide uncertain results or are contraindicated. During the interventional procedure, ultrasound

b. partial response, defined as more than 50% reduction in total tumor enhancement in all measurable lesions, determined by two observations not less than 4 weeks apart

d. progressive disease, defined as 25% increase in size of one or more measurable lesions

The efficiency of 2D ultrasound is low in assessing the effects of HCC or metastasis therapy, as it is unable to differentiate viable tumor tissue from post-therapy tumor necrosis. However, it is able to detect the appearance of new lesions and to assess the occurrence of any complications of disease progression (ascites or portal vein thrombosis). Color Doppler ultrasound can be useful sometimes being able to show the presence of intratumoral vasculature as a sign of incomplete therapy or intratumoral recurrence. The absence of Doppler signal does not exclude the presence of viable tumor tissue. CEUS exploration, by its ability to enhance intra-lesion microcirculation, has proved its utility in monitoring therapeutic efficacy. Its indications are defined for HCC ablative treatments (pre, intra and post-therapy), while monitoring of systemic therapies of HCC and metastases are not validated indications at this time, but with proved efficacy in extensive clinical trials (Claudon et al, 2008). CEUS examination cannot completely replace the other imaging diagnostic methods currently in use because of the known limitations of the ultrasound method (operator/ equipment dependent, ultrasound examination limitations). In addition to bloating, in cancer patients post-therapy steatosis occurs, which prevent deep visibility. Spiral CT scan remains the method of choice in monitoring cancer therapies because it provides an overview of tumor extension and it is not limited by bloating or steatosis

Gadolinium MRI examination is a procedure used more and more often, and its advantages are the absence of irradiation and its high sensitivity in tumor vasculature detection, especially in smaller tumors (Dromain et al, 2002). However it remains an expensive and not a very accessible procedure, although it has a high specificity. Currently, CEUS and MRI are

**4.2 Ultrasound monitoring ablative therapies (alcoholization - PEI, radiofrequency** 

by complete tumor necrosis with a safety margin around the tumor.

Ablative therapies are considered curative treatments for HCC together with surgical resection and liver transplantation and they are indicated for early tumor stages in patients with good liver function (Bruix & Sherman, 2005; Bruix & Sherman, 2011). Also they are successfully applied in the treatment of liver metastases, where surgical resection is contraindicated. They are chemical (intratumoral ethanol injection) or thermal (radiofrequency, laser or microwave ablation). They are applied in order to obtain a full therapeutic response, without affecting liver function. Complete response is locally proved

2D ultrasound, Doppler ultrasound and especially CEUS can play an important role in pretherapeutic staging, particularly when sectional imaging investigations (CT, MRI) provide uncertain results or are contraindicated. During the interventional procedure, ultrasound

c. stable disease (is not described by a, b, or d)

(Bartolozzi et al, 1999).

**ablation - RFA)** 

considered complementary methods to CT scan.

or the appearance of new lesions (Bruix et al, 2001).

**4.1 Techniques for evaluating the efficiency of therapy** 

allows guidance of the needle into the tumor. CEUS allows guidance in areas of viable tissue and avoids intratumoral necrotic areas. CEUS also allows assessment of therapeutic effect immediately post-procedure (with the possibility of reintervention in case of partial response) (Claudon et al, 2008). To accurately assess the effectiveness of treatment it is mandatory to compare the tumor diameter before therapy with the ablation area. The volume of damaged tissue must be higher than the initial tumor volume. CEUS appearance is that of central nonenhanced area showing a peripheral homogeneous hyperenhanced rim due to post-procedure inflammation. 24 hours after the procedure the inflammatory peripheral rim is thinning and the necrotic area appears larger than at the previous examination. Thus, a possible residual tumor may appear more evident. Residual tumor has poorly defined edges, irregular shape, and the tumor diameter is unchanged. Residual tumor tissue is evidenced at the periphery of the tumor as an eccentric area behaving as the original tumor at CEUS examination, with arterial hyperenhancement and portal and late wash-out. Ultrasound examination 24 hours after the procedure, including CEUS, can show apart from the character of the lesion any potential post-intervention complications (e.g. active bleeding).

In the first days after RFA both CEUS and spiral CT have low sensitivity in assessing therapeutic efficacy. CT sensitivity 24 hours post-therapy is reported to be even lower than CEUS (Vilana et al, 2006). Difficulties in CEUS examination result from post-lesion hyperemia, presence of intratumoral air, ultrasound limitations (too deep lesion or the presence of fatty liver) or lack of patient's cooperation (immediately after therapy). For this reasons contrast imaging (CT or CEUS) control should be performed one month after ablation to confirm the result of the therapy (Spârchez et al, 2009).

Local recurrence is defined as recurrence of a hyperenhanced area at tumor periphery in the arterial phase, with portal and late wash-out. Sometimes, especially for HCC treated by alcoholization (PEI) hyperenhanced septa or vessels can be shown inside the lesion (Spârchez et al, 2009).

In case of successful treatment, US monitoring using CEUS is performed every three months. Although CE-CT and/or MRI are considered the method of choice in post-therapy monitoring, CEUS can be used in follow-up protocols (Claudon et al, 2008), its diagnostic accuracy being equivalent to that of CE-CT or MRI (Frieser et al, 2011).

Fig. 13. Assessment of therapeutic efficacy on ultrasound (2D, CFM, CEUS). US exam shows vascular Doppler signal at CFM (left) and CEUS examination reveals incomplete therapy (right).
