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Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread. [ABSTRACT FROM AUTHOR]

Introduction: Atezolizumab and bevacizumab (AB) therapy was the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). However, the predictive marker of therapeutic response that can be easily used in clinical practice is still unknown. We prospectively investigated the utility of time-intensity curve (TIC) analysis using contrast-enhanced ultrasound (CEUS) as a predictive indicator of therapeutic response after the start of AB therapy. Methods: Thirty-five patients who received AB therapy for u-HCC were included in this study. TIC analysis was performed in 28 patients who were able to undergo CEUS before and 3–7 days after administration. We analyzed prognostic factors related to the initial therapeutic response and long progression-free survival (PFS). Results: The initial therapeutic response using dynamic computed tomography or Gd-EOB magnetic resonance imaging at 8–12 weeks after administration was partial response/stable disease/progressive disease (PD) in 14/12/9 cases (40/34/26%). Cases with PD (n = 9) had more cases without decreased blood flow in TIC analysis compared with cases with non-PD (100 vs. 18%, p = 0.001). Cases without decreased blood flow in TIC analysis (n = 10) had more cases with PD compared with cases with decreased blood flow (60 vs. 0%, p = 0.001). PFS in patients without decreased blood flow early after the administration was shorter than that in those with decreased blood flow (9.1 vs. 28 weeks, p = 0.0051). Conclusion: Early evaluation by TIC analysis using CEUS may be useful in predicting the therapeutic response in patients treated with AB therapy for u-HCC. [ABSTRACT FROM AUTHOR]

Introduction: Image-guided thermal ablation, preferably with ultrasonography (US), is increasingly used for treatment of small liver tumours. Perfluorobutane-contrast-enhanced US (pCEUS) is a promising tool that may allow for targeting of tumours that are otherwise imperceptible on greyscale US. Although pCEUS has been reported to be effective, the literature has been limited outside of Japan and South Korea. We aimed to provide data that supports the use of pCEUS in the thermal ablation of sonographically occult liver tumours.Methods: We conducted a retrospective single-centre study of 35 consecutive patients who underwent pCEUS-guided ablation of 48 liver tumours with a median size of 1.2 cm. Periprocedural, one-month post-treatment and relevant follow-up imaging studies were reviewed. Electronic records were also obtained, with long-term follow-up data of 12-28 months being available for 32 patients.Results: 36 (75%) tumours that were imperceptible on greyscale US became visible with pCEUS. Overall, complete tumour ablation at one month was 89%. 1 (3%) patient developed a major complication following treatment, while 6 (17%) had minor post-treatment complaints. The local tumour progression rate was 17%, with a median time of 14 months.Conclusion: pCEUS has a role in US-guided thermal ablation of liver tumours, offering a high technical success rate that is comparable to reported data. Additional benefits may include improved procedural time and freedom from ionising radiation. [ABSTRACT FROM AUTHOR]

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology- European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management. [ABSTRACT FROM AUTHOR]

Purpose: This clinical study was conducted to evaluate the safety and short-term outcomes of irreversible electroporation (IRE) for the treatment of patients with hepatocellular carcinoma (HCC) in Japan.Materials and Methods: The study was designed in a prospective setting. Five patients (3 men and 2 women; mean age, 66.6 ± 5.8 years) with 6 HCCs were enrolled and treated using percutaneous ultrasound (US)-guided IRE. Safety was assessed based on adverse events and laboratory values. Local control was assessed using contrast-enhanced US with a perflubutane microbubble contrast agent, contrast-enhanced multiphase CT, and gadoxetic acid-enhanced MRI (EOB-MRI) at designated points.Results: The tumors ranged in diameter from 11 to 28 mm (mean diameter, 17.5 ± 6.3 mm). Five of the 6 tumors (83 %) were successfully treated, with no local recurrence to date (mean follow-up 244 ± 55 days). In 1 lesion located in liver segment 1, residual tumor was diagnosed at 7 days after intervention by follow-up EOB-MRI. No serious complications related to the IRE procedure were observed.Conclusion: The results of this study suggest that image-guided percutaneous IRE can achieve satisfactory local disease control, particularly for small HCCs, and is well tolerated by patients. [ABSTRACT FROM AUTHOR]

Surveillance and diagnostic algorithms for hepatocellular carcinoma (HCC) have already been described in guidelines published by the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver and the European Organisation for Research and Treatment of Cancer (EASL-EORTC), and the Japan Society of Hepatology (JSH), but the content of these algorithms differs slightly. The JSH algorithm mainly differs from the other two algorithms in that it is highly sophisticated and considers the functional imaging techniques of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI) and Sonazoid contrast-enhanced ultrasound (CEUS) to be very important diagnostic modalities. In contrast, the AASLD and EASL-EORTC algorithms are less advanced and suggest that a diagnosis be made based solely on hemodynamic findings using dynamic CT/MRI and biopsy findings. A consensus meeting regarding the JSH surveillance and diagnostic algorithm was held at the 50th Liver Cancer Study Group of Japan Congress, and a 2014 update of the algorithm was completed. The new algorithm reaffirms the very important role of EOB-MRI and Sonazoid CEUS in the surveillance and diagnosis of liver cancer and is more sophisticated than those currently used in the United States and Europe. This is now an optimized algorithm that can be used to diagnose early-stage to classical HCC easily and highly accurately. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: We present the initial steps for 320-detector-row computed tomography arteriography using CO2 gas (320-MDCT CO2 arteriography) to detect the vascular area of malignant liver tumors. Material and methods: This study was approved by the Ethics Committee of our institution. Written prior informed consent was obtained from all patients. We studied six patients with primary and metastatic liver tumors (n = 26) and allergic reactions to iodinated contrast media or a tendency for renal failure. CO2 was injected at 1 ml/sec (volume 8 ml) into the common hepatic artery and a CT scan was acquired 12 seconds after the start of injection. The detection of the vascular area of the tumor or of intratumor air was evaluated with respect to the relationship between the size and location of the tumors. Cramer's V statistic was performed to explore the relationship (p < 0.05). Results: The vascular area was detected in 17 of the 26 tumors (65.4%). There was a correlation between the detection of the adjacent vascular area on CTA images acquired with the use of CO2 and the tumor site observed on previously-acquired MRI or CT images. Conclusion: 320-MDCT CO2 arteriography with microcatheters may be useful for the detection of the vascular area. [ABSTRACT FROM AUTHOR]