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Castán et al.                                                                                                                                           Radiology of hepatocarcinoma in non-cirrhotic patients

                  A                                           vascular pattern in HCC, more frequent in those that
                                                              are moderately differentiated [11]  [Figure 4]. Contrast
                                                              agent flows exclusively through the intravascular
                                                              space, without passing to the interstitial liquid, thus
                                                              explaining some differences with the typical features
                                                              found in CT or MRI. However, other reports have not
                                                              found significant differences. Wilson et al. [12]  reported
                                                              no  differences  in  the  dynamic  behavior  among
                                                              CEUS, MRI and CT. Giorgio et al. [13]  did not find any
                                                              difference between CEUS and CT. Nevertheless,
                                                              Liu  et al. [14]   reported  different  results  for  small
                                                              lesions detected by CEUS and CT. In their report, a
                  B                                           good correlation was found between both imaging
                                                              techniques among lesions greater than 2 cm, but
                                                              there was a low correlation among lesions measuring
                                                              1-2 cm. Possible explanations for this discrepancy are
                                                              the different distribution of contrast agents, the various
                                                              thickness of the slices of CT, and the effect of the
                                                              direct time changes measured with CEUS. A cirrhotic
                                                              background may also cause atypical patterns due to
                                                              the progressive arterialization of the small lesions.
                                                              These results suggest that more research is needed
                                                              to determine the usefulness of CEUS in the diagnosis
                                                              of HCC.
           Figure  3:  (A)  Abdominal  ultrasound  B-mode  showing  large
           heterogeneous mass with hyper- and hypoechoic areas is observed   On the other hand, some papers found that the
           in right hepatic lobe. Peritumoral vascular flow is demonstrated by
           Doppler (B)                                        presence  of  wash-in/wash-out  in  CEUS  of  liver
                                                              lesions is highly suggestive of cholangiocarcinoma
           vascular flow can be demonstrated [Figure 3].      (CC), thus inducing false positive results of HCC.
                                                              This was observed by Liu et al. [15]  in 92.3% of HCC
           According  to  clinical  practice  guidelines  of  the   and in 85.7% of CC found in 819 patients. However,
           European Association for the Study of the Liver    CC lesions had an earlier washout than HCC lesions
           (EASL), [10]  a monitoring program must be carried out   (media of 27.5 vs. 70.1 s). Up to 68.5% of CC had
           in patients at high risk for HCC, which mainly includes   a ring enhancement, while it was present in just
           patients with liver cirrhosis. Abdominal ultrasound   2.0% of HCC. They concluded that an enhancement
           is the diagnostic method used and surveillance is   and washout time longer than 43 s plus a non-ring
           conducted every six months. The main limitation    enhancement had a 64.1% sensitivity and a 97.4%
           of ultrasound is the detection of small tumors (<   specificity for HCC lesions equal or smaller than 5 cm.
           2  cm). They  can  go  undetected  in  livers  with  a
           heterogeneous diffuse nodular pattern base. However,   Ohno et al. [16]  observed a linear correlation between
           in expert hands, sensitivity is up to 89% and specificity   blood  flow  of  the  lesion  and  blood  flow  of  the
           is up to 90%.                                      rest of the parenchyma with CEUS in 7 patients,
                                                              using perflubutane as contrast agent. This activity
           Contrast-enhanced ultrasound                       proves the presence of intratumoral angiogenesis,
           Contrast enhanced ultrasound (CEUS) monitors time   thus enabling CEUS for measuring response to
           changes more directly and allows the dynamic study of   antiangiogenic therapies, even though the sample
           the lesion. Contrast consists of sulphur hexachloride   size was small in this report.
           microbubles of 2.5 μm of diameter. Since it is not
           nephrotoxic and presents few secondary effects, it is   Nevertheless, the role of CEUS in diagnosis and
           useful in patients with nephropathies and in those with   staging of HCC is limited and it is not considered
           known adverse reactions to other contrast agents.   a  first  line  diagnostic  tool  in  EASL  or American
           CEUS is valuable as a diagnostic tool, as a guide for   Association for the Study of Liver Diseases (AASLD)
           biopsy and as a measure of treatment response.     guidelines.

           Similarly to CT and MRI, CEUS shows a typical      CEUS is useful for guiding biopsies. Spârchez et al. [17]
             4                                                                                                      Hepatoma Research ¦ Volume 3 ¦ January 12, 2017
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