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The intermediate stage of hepatocellular carcinoma (HCC) comprises a highly heterogeneous patient population and therefore poses unique challenges for therapeutic management, different from the early and advanced stages. Patients classified as having intermediate HCC by the Barcelona Clinic Liver Cancer (BCLC) staging system present with varying tumor burden and liver function. Transarterial chemoembolization (TACE) is currently recommended as the standard of care in this setting, but there is considerable variation in the clinical benefit patients derive from this treatment.In April 2012, a panel of experts convened to discuss unresolved issues surrounding the application of current guidelines when managing patients with intermediate HCC. The meeting explored the applicability of a subclassification system for intermediate HCC patients to tailor therapeutic interventions based on the evidence available to date and expert opinion. The present report summarizes the proposal of the expert panel: four substages of intermediate HCC patients, B1 to B4.

Purpose: Sorafenib is the reference therapy for advanced hepatocellular carcinoma (HCC). There is no method for predicting in the early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography allows assessment of tissue elasticity, we investigated the role of this ultrasound-based technique in the early prediction of tumor response to sorafenib in a HCC mice model.Materials and Methods: HCC subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle (17 mice) or treatment with sorafenib (19 mice). Strain elastosonography (Esaote, Italy) of the tumor mass was performed at different time points (day 0, + 2 and + 14 from treatment start) until the mice were sacrificed (day + 14). At the same time points, the volume was calculated with ultrasonography.Results: Sorafenib-treated mice showed a smaller increase in tumor size on day + 14 in comparison to vehicle-treated mice (tumor volume increase + 175 % vs. + 382 %, p = 0.009). The median tumor elasticity increased in both groups on day + 2 (+ 5.65 % and + 3.86 %, respectively) and decreased on day + 14 (-3.86 % and -3.63 %, respectively). However, among Sorafenib-treated tumors, 13 mice with a growth percentage delta < 200 % (considered as good treatment response) showed an increase in elasticity on day + 2 (+ 8.9 %, range -12.6 - + 64) while the other 6 with a growth percentage delta > 300 % (considered as poor treatment response) showed a decrease in elasticity (-17 %, range -30.2 - + 15.3) (p = 0.044).Conclusion: Elastosonography appears to be a promising noninvasive new technique for the early treatment prediction of HCC tumor response to sorafenib. Specifically, an early increase in tumor elasticity (corresponding to tumors becoming softer) is associated with a good response.

Purpose: Several manufacturers have implemented their ultrasound (US) equipements with shear wave elastography (SWE) very recently, so that there is still a lack of data about clinical performances of many of them in evaluating liver stiffness (LS). Since the introduction of first SWE device, the number of biopsies has dramatically dropped, hence new techniques can be hardly validated versus histology. Possibly already validated systems should be considered as reference standards. The aim of this study is to investigate the correlation between point SWE (pSWE) on MyLab Twice (Esaote, Genova, Italy) and two-dimensional SWE (2DSWE) on Aixplorer (SuperSonic Imagine, Aix-en-Provence, France) as reference. Materials and methods: Consecutive healthy and liver disease patients (regardless of etiology) accessing the US lab were considered. Exclusion criteria were focal liver lesions, age 35, severe extrahepatic comorbidities. LS was sampled intercostally from at least one intercostal space with both equipments. 110 LS measurements were obtained with both techniques from the same intercostal space and tested with Pearson correlation, Lin's correlation concordance coefficient (CCC) and Bland-Altman analysis (BA p 20 KPa) which does not affect staging of disease as such patients are anyhow classified as in cirrhotic stage.

Purpose The typical appearance of focal nodular hyperplasia (FNH) in radiological contrast techniques (helical CT or MRI) includes homogeneous enhancement in the arterial phase, but the exact timing for the best visualization of this pattern is unknown. The aim of the present study was to assess the ultrasound pattern of FNH with special attention to real-time contrast-enhanced ultrasonography (CEUS) appearance and specifically to the timing of perfusion patterns. Materials and methods 72 patients (60 females, 12 males) with a total of 90 FNH nodules with a diameter ranging from 8 to 100 mm (mean +/- SD, 40.6 +/- 21.5 mm) were examined continuously for at least 4 minutes using CnTI and CPS methods (ESAOTE, Genoa, Italy and Acuson-Siemens) after bolus injection of SonoVue (BRACCO, Milan, Italy). Results 87 of 90 nodules showed the typical coin-like hyperechogenicity in the arterial phase. The remaining three nodules were all in the same patient and were diagnosed as FNH after resection. Contrast started to appear within the lesions after a mean of 15.7 +/- 4.6 seconds (range 7 - 27 s) and reached peak signal intensity, with the greatest differentiation between the lesion and the surrounding parenchyma, at around 22.6 +/- 7.0 seconds (range 14 - 72 s). In the late phase, 65 lesions (72.2 %) became isoechoic (after a mean of 80.8 +/- 85.7 s, range 20 - 300 s), 22 (24.4 %) slightly hyperechoic and 3 (3.3 %) faintly hypoechoic. Conclusion FNH shows a typical homogeneous hyperechoic pattern during the arterial phase in real-time CEUS which disappears slowly on average but occasionally even as soon as 20 seconds after contrast injection. If the first scans are taken later than 20 seconds after injection (which is still considered to be a full arterial phase), the ultrasound hyperechogenicity may be missed in some cases. Real-time study of these lesions is therefore strongly recommended to avoid possible false-negative results.

PURPOSE: Hepatic hydrothorax is defined as the accumulation of pleural effusion in a cirrhotic patient in the absence of pulmonary or cardiac disease. Peritoneal fluid can pass into the pleural space through diaphragmatic fenestrations. The demonstration of such passage is important to establish the diagnosis of hepatic hydrothorax and can be achieved by intraperitoneal injection of nuclear contrast agents. Our aim was to evaluate the ability of contrast enhanced ultrasound in the detection of peritoneal-pleural communications. MATERIALS AND METHODS: Seven patients with cirrhotic ascites and pleural effusion were studied in order to make a diagnosis of hepatic hydrothorax. SonoVue was injected into the peritoneal cavity (9.8 mL), and the peritoneal and pleural cavities were monitored by ultrasound. All patients were then studied using a nuclear scan. RESULTS: Passage of SonoVue from the peritoneal to the pleural cavities was seen in 5 patients. In 2 patients, no passage of contrast agent was detectable. Nuclear scan was consistent with contrast enhanced ultrasound in all patients. CONCLUSION: This study shows that the presence of peritoneal-pleural communications can be demonstrated by real time contrast enhanced ultrasound, whose results are comparable to those of nuclear scan. Contrast enhanced ultrasound is cheaper and could theoretically be performed wherever ultrasound facilities are available.

Aims: Portal venous thrombosis (PVT) is considered an absolute contraindication to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) when neoplastic PVT cannot be excluded. Aim of the study is to assess whether imaging techniques allow evaluation of nature of PVT in HCC-patients allowing safe selection of candidates to LT. Methods: We analyzed 34 HCC-patients with PVT detected at the time of assessment for LT or developed while on the waiting list. The benign nature of the thrombus was established using the following criteria: lack of vascularization of the thrombus at contrast enhanced ultrasound with SonoVue and ceCT or ceMRI, steadiness/regression of thrombosis during follow-up, absence of mass-forming aspects of PVT on ultrasound examination, absence of features of disruption of the vessel walls, and negative biopsy of the thrombus in case of uncertainty. Patients who did not fulfill the criteria for benignity of PVT were excluded from the waiting list. Results: The outcome of 34 patients analyzed is as follows: 13 were listed and transplanted, with no sign of malignant PVT at explant pathological examination; 9 were admitted in the list and are actively waiting. Two patients died for HCC unrelated causes while actively listed. Of the remaining 10 patients, 7 were not included or excluded from the list for the suspicion or confirmation of malignant PVT, whereas 3 were included and subsequently excluded for progression of HCC without evidence of malignant PVT. Conclusions: Imaging techniques allow safe not-invasive assessment of the nature of PVT in HCC-candidates to LT.