Objective: To clarify the value of contrast-enhanced harmonic ultrasonography (US) with Sonazoid, a second-generation US contrast agent, in the differential diagnosis of liver tumors compared to dynamic CT. Methods: A total of 249 hepatic nodules in 214 patients were studied; these included 177 hepatocellular carcinomas (HCCs), 42 liver metastases, 20 liver hemangiomas, 6 dysplastic nodules and 4 focal nodular hyperplasias (FNHs). After the injection of Sonazoid, nodules were scanned using real-time contrast-enhanced harmonic US in the vascular phases, i.e. the early and late vascular phases, and the Kupffer phase. Results: Six enhancement patterns were identified to be significant for the differential diagnosis of hepatic tumors. In HCCs, the presence of intratumoral vessels supplied from the periphery and fast washout (sensitivity, 96.6%; specificity, 94.4%) were the most typical characteristics. In metastases, the presence of rim-like enhancement with peripheral tumor vessels (sensitivity, 88.1%; specificity, 100%) was the typical pattern. In hemangiomas, the presence of intratumoral hypoperfusion images with globular or cotton wool-like pooling, which continue to the late vascular phase (sensitivity, 90.0%; specificity, 99.6%), was typical. In dysplastic nodules, the presence of portal enhancement without arterial supply in the early vascular phase and the presence of intratumoral uptake in the Kupffer phase (sensitivity, 83.3%; specificity, 100%) were the most typical patterns. In FNHs, the presence of a spoke-wheel pattern in the early vascular phase with dense staining in the late vascular phase, and positive uptake within the nodule in the Kupffer phase (sensitivity, 100%; specificity, 100%) were the most typical patterns. Conclusion: Contrast-enhanced harmonic US with Sonazoid allowed intimate vascular and Kupffer imaging and, therefore, is useful for the differential diagnosis of hepatic tumors.

Background: Although hepatic arterial infusion chemotherapy (HAIC) using low-dose 5-fluorouracil (5-FU) and cisplatin (low-dose FP) is commonly used for advanced hepatocellular carcinoma (HCC) with vascular invasion in Japan, few reports have investigated the efficacy and safety of this approach. We investigated the efficacy and toxicity of HAIC using low-dose FP for patients with advanced HCC as a phase II trial. Methods: Low-dose FP consisted of a continuous arterial infusion of 5-FU (250–500 mg/day, 5 days/week, for the first 2 weeks) and cisplatin (10 mg/day, 5 days/week, for the first 2 weeks). Then, 5-FU (1,000 mg/body for 5 h) and cisplatin (10 mg/body) were administered once weekly. Results: In these patients treated with low-dose FP, the response rate was 38.5%, the median time to progression was 4.1 months (95% CI 2.1–6.1 months) and the median survival time was 15.9 months (95% CI 9.8–22.0 months). The most frequent adverse events were myelosuppression such as neutropenia or thrombocytopenia. Conclusions: HAIC using low-dose FP is an effective treatment option for locally advanced HCC. However, it is not well tolerated hematologically because of potent pancytopenia and poor hepatic reserve. Therefore, this regimen should be performed carefully with regular monitoring of hematological function.

Objective: The aim of this study was to investigate liver fibrosis using non-invasive Real-time Tissue Elastography® (RTE) and transient elastography (FibroScan®) methods. Methods: RTE, FibroScan and percutaneous liver biopsy were all performed on patients with chronic liver disease, particularly hepatitis C, to investigate liver fibrosis. Results: FibroScan and RTE were compared for fibrous liver staging (F stage), which was pathologically classified using liver biopsy. In FibroScan, significant differences were observed between F1/F3 and F2/F4, but no such differences were observed between F1/F2, F2/F3 and F3/F4. In RTE, significant differences were observed between F1/F2, F2/F3 and F2/F4. But for F3/F4, no significant differences were observed. Conclusion: FibroScan and RTE correlated well with F staging of the liver. In particular RTE was more successful than FibroScan in diagnosing the degree of liver fibrosis.

Background: The purpose of this study was to investigate if Sonazoid-enhanced harmonic ultrasonography (US) could be used to evaluate the responses of hepatocellular carcinomas (HCCs) to treatment with transcatheter arterial chemoembolization (TACE). Patients and Methods: Forty-three HCCs that had been treated by TACE were evaluated by Sonazoid-enhanced harmonic US and dynamic computed tomography (CT) approximately 1 week after their treatment. The detection rates of residual tumor blood supply using the two modalities were compared. Two months after chemoembolization, 16 of the 43 HCCs, which had no additional local treatment, were followed up with dynamic CT. The results of contrast-enhanced harmonic US and dynamic CT 1 week after chemoembolization were analyzed and compared with follow-up dynamic CT results. Results: The detection rates of positive enhancement with Sonazoid-enhanced harmonic US and dynamic CT 1 week after TACE were 25 (58.1%) of 43 lesions and 17 (39.5%) of 43 lesions, respectively. Sonazoid-enhanced harmonic US was significantly more sensitive than dynamic CT in depicting the residual tumor blood supply to HCCs 1 week after TACE (p < 0.01; χ² test). The Sonazoid-enhanced harmonic US results of the 16 lesions 1 week after chemoembolization were consistent with the follow-up results of dynamic CT 2 months after chemoembolization. Conclusions: Sonazoid-enhanced harmonic US appears to be a highly sensitive and accurate modality for evaluating responses of HCCs shortly after TACE.

Objective: This study was undertaken to assess the outcome of potentially curative radiofrequency ablation (RFA) therapy for early-stage hepatocellular carcinoma (HCC) in patients with Child-Pugh stage A cirrhosis. Methods: This study retrospectively evaluated clinical outcomes in a cohort of 171 Child-Pugh stage A cirrhotic patients who received RFA for naïve HCC within the Milan criteria. The median follow-up period was 36.7 months. Results: Cumulative survival rates estimated by the Kaplan-Meier method for all patients were 98.8, 91.1 and 76.8% at 1, 3 and 5 years, respectively. Cumulative probabilities of local tumor recurrence at 1, 2 and 3 years were 9.0, 14.1 and 17.7%, respectively. Cumulative survival rates in patients without local tumor recurrence were 96.6, 94.6 and 84.4% at 1, 3 and 5 years, respectively, compared with patients with local tumor recurrence (96.6, 74.8 and 42.1% at 1, 3 and 5 years, respectively; p = 0.0002). Cox regression analysis showed that low serum albumin (p = 0.009, RR 3.04, CI 1.32–6.98), high range of PIVKA-II (prothrombin induced by vitamin K absence or agonist II) (p = 0.025, RR 2.57, CI 1.13–5.89), with multiple (less than 3) nodules (p = 0.021, RR 2.61, CI 1.15–5.91), and with local tumor recurrence (p = 0.004, RR 3.62, CI 1.51–8.69) were significant risk factors for death. Conclusion: Initial complete response of curative RFA therapy in patients with Child-Pugh stage A cirrhosis and early-stage HCC is associated with improved survival. Therefore, clinicians should aim to achieve complete ablation of all detectable HCC nodules with adequate safety margins.