Hepatocellular carcinoma treated with transarterial chemoembolization: Evaluation with parametric contrast-enhanced ultrasonography.

AIM: To evaluate the response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) using a simplified protocol of parametric contrast-enhanced ultrasound (pCEUS). METHODS: Eighteen patients with HCC (18 target tumors, diameter: 2.8-12 cm) were evaluated before, and 20 d after TACE. The distribution and morphology of TACE-induced necrosis in these tumors precluded accurate evaluation by visual assessment or by simple measurements. For pCEUS, a 4.8 mL bolus of SonoVue (Bracco, Milan, Italy) was intravenously administered and analysis of tumor perfusion during the initial phase of enhancement (0-30 s post injection) was performed with dedicated software (Qontrast, Bracco, Milan, Italy). Time-intensity curves were plotted and three parameters were calculated: peak intensity (PI, in percentage %), time to peak (TTP in seconds, s) and area under the curve during wash-in (AUC-WI, in arbitrary units, a.u). Magnetic resonance imaging was the standard imaging modality for post-treatment evaluation. Changes in tumor size were recorded and response was assessed according to response evaluation criteria in solid tumors criteria. RESULTS: A statistically significant decrease in PI and AUC-WI was observed in the treated tumors post TACE; PIpre: 21.5% ± 8.7% (mean ± SD), PIpost: 12.7% ± 6.7%, P < 0.001, AUC-WI pre: 17493 ± 9563 a.u, AUC-WI post: 9585 ± 5494 a.u, P < 0.001. A slight increase in TTP was noted post TACE, but this was not statistically significant; TTP pre: 13.1 ± 4.3 s, TTP post: 13.6 ± 4.2 s , P = 0.058). The changes in the aforementioned parameters were not accompanied by significant tumor shrinkage. CONCLUSION: pCEUS, even when limited to the study of the arterial phase of tumoral enhancement, can detect and quantify early perfusional changes in HCC post TACE.

Intermediate and advanced hepatocellular carcinoma treated with the antiangiogenic agent sorafenib. Evaluation with unenhanced and contrast-enhanced ultrasonography.

AIMS: To evaluate the sonographic changes observed in hepatocellular carcinoma (HCC) post antiangiogenic treatment with sorafenib. PATIENTS AND METHODS: Twenty one intermediate or advanced HCC patients (19 men, 2 women; mean age: 66.8 years; 32 target tumors-TTs) received sorafenib as monotherapy and were studied with unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) with a second generation echo-enhancer (SonoVue) at bimonthly intervals. Changes in lesional size, echotexture and enhancement were evaluated. Response was classified according to RECIST (Response Evaluation Criteria In Solid Tumors) and modified (m) RECIST. RESULTS: Cystic changes were detected on US in 4 patients (7 lesions); CEUS showed a significant (51-100%) decrease of viable, enhancing TTs in the aforementioned patients. Four additional patients (5 lesions) showed a 73-87% decrease of their viable TTs on CEUS, but no changes on US. 13/21 patients showed less than 30% decrease, no change, or increase of their viable TTs. Based on the last sonographic evaluation, response was as follows: RECIST- Complete Response, CR (n=0), Partial Response, PR (n=1), Stable Disease, SD (n=16), Progressive Disease, PD (n=4); mRECIST- CR (n=2), PR (n=6), SD (n=11), PD (n=2). The 8 responders (CR+PR) according to mRECIST had significantly longer mean overall survival (OS) compared to the 13 non-responders (21.5 vs 12.2 months, p=0.018, Kaplan-Meier method). However, statistical significance was reduced (p=0.065) after adjustment for BCLC and Child's class. CONCLUSION: US may occasionally detect changes indicative of the effect of sorafenib on HCC, but CEUS is required to evaluate and grade post-therapeutic reduction of tumoral enhancement. The latter is likely to correlate with OS.

Contrast-enhanced ultrasonography with intraarterial administration of SonoVue for guidance of transarterial chemoembolization: an initial experience.

AIMS: To describe the technique and to evaluate the feasibility of contrast-enhanced ultrasound with intraarterial administration of echo-enhancer (i.a CEUS) as a method for guidance of transarterial chemoembolization (TACE). PATIENTS AND METHODS: Twelve patients with 17 target liver tumors underwent superselective TACE, guided with i.a CEUS. After microcatheter placement in a (sub)segmental artery suspected as a tumor feeder, a diluted suspension of SonoVue was injected through the microcatheter, and imaging of the target tumor was performed with a low mechanical index technique and with contrast-specific software. If intraarterial injection of SonoVue was associated with immediate, strong tumoral enhancement, the injected artery was considered as tumor-feeding and TACE was performed, otherwise another artery was evaluated. RESULTS: From 25 segmental or subsegmental arteries evaluated i.a CEUS confirmed that 16 arteries were actually tumor feeders and unequivocal excluding 4 arteries as a tumor arterial supply. The remainder 5 arterial branches could not be safely characterized due to artifacts or technical limitations. In 8 patients in which tumoral vascular supply could not be elucidated by angiography alone, i.a CEUS increased the accuracy of supereselective embolization, and provided other clinically relevant information in 2 of these patients. No adverse effects were observed. CONCLUSIONS: For guidance of superselective TACE i.a CEUS is a safe and feasible method..

Short-term evaluation of liver tumors after transarterial chemoembolization: limitations and feasibility of contrast-enhanced ultrasonography.

PURPOSE: To evaluate the limitations and the feasibility of contrast-enhanced ultrasonography (CEUS) for the assessment of tumor response shortly after transarterial chemoembolization (TACE). MATERIALS AND METHODS: Fifty seven patients (41 patients with hepatomas, 16 patients with metastases) were studied with CEUS before, 1 day after, and 30 days after TACE. A CEUS-efficiency score (CEUS-ES) was calculated, which evaluated: (a) the completeness of visualization of the target tumor(s) (2: good, 1: adequate, 0: poor) and (b) the quality of delineation of post-TACE necroses (2: good, 1: adequate, 0: poor). A CEUS study was considered as "diagnostic," if each of the aforementioned parameters was associated with grade 1 or 2. RESULTS: CEUS studies were "diagnostic" in 36/57 patients (63.1%). Patients with hepatomas were more likely to undergo "diagnostic" CEUS than patients with metastases (70.7% vs. 43.7%, P = 0.0728). Lesions' multiplicity, deep location, hypoenhancement on pretreatment CEUS, and diffuse growth had a statistically significant (P < 0.05) negative impact on CEUS-ES. Hyperechogenicity on pre-treatment, unenhanced US had a non-statistically significant (P = 0.176) negative impact. Differences between "diagnostic" CEUS studies and CT/MR regarding detection of residual tumor were insignificant (P = 0.8178). CONCLUSION: The percentage of lesions which are unsuitable for post-TACE evaluation with CEUS is not negligible. For the rest, the respective role of CEUS is promising.

Unenhanced and contrast-enhanced ultrasonography during hepatic transarterial embolization and chemoembolization with drug-eluting beads.

The purpose of this study was to describe and evaluate the findings of unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) when these modalities are applied during transarterial embolization (TAE) or transarterial chemoembolization (TACE) of liver tumors. Sixteen tumors (9 hepatocellular carcinomas, 5 metastases from colorectal cancer, and 2 hemangiomas) were treated with TAE with microspheres and/or TACE with drug-eluting beads. All of these lesions were studied with intraprocedural unenhanced US and 12 were studied with intraprocedural CEUS. For the latter, a second-generation echo-enhancer (SonoVue; Bracco, Milan, Italy) and a low mechanical index technique were used. Intraprocedural findings were classified according to an arbitrary scale and were compared with pretreatment imaging (CEUS and computed tomography or CEUS and magnetic resonance imaging), with postembolization angiography, and with follow-up results. On unenhanced intraprocedural US, 13 of 16 tumors demonstrated intralesional high-level echoes of varying extent. These feature correlated poorly (r = 0.33, p = 0.097) with and generally underestimated the actual extent of necrosis. Exceptionally, high-level echoes that occupied the largest part of the treated lesions were associated with >50% tumor necrosis. Intraprocedural CEUS clearly depicted immediate partial or complete disappearance of tumor enhancement as a result of TAE/TACE. Three of 6 tumors with complete devascularization on postembolization angiogram showed residual enhancement on intraprocedural CEUS. Intraprocedural CEUS findings correlated closely (r = 0.91, p = 0.002) with follow-up findings. Intraprocedural sonography, particularly with echo-enhancers, could be used for intraprocedural monitoring in selected cases of liver tumors that undergo TAE or TACE.

Contrast-enhanced ultrasonography of hepatocellular carcinoma after chemoembolisation using drug-eluting beads: a pilot study focused on sustained tumor necrosis.

The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% +/- 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% +/- 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.