Manabu Morimoto

Midterm Outcomes in Patients With Intermediate-Sized Hepatocellular Carcinoma: A Randomized Controlled Trial for Determining the Efficacy of Radiofrequency Ablation Combined With Transcatheter Arterial Chemoembolization

To improve the efficacy of radiofrequency ablation (RFA) for the treatment of intermediate‐sized hepatocellular carcinomas (HCCs), the authors compared RFA combined with transcatheter arterial chemoembolization (TACE) to RFA alone.

Contrast-enhanced, wide-band harmonic gray scale imaging of hepatocellular carcinoma correlation with helical computed tomographic findings

We evaluated the usefulness of contrast‐enhanced, wide‐band harmonic gray scale imaging for the diagnosis of hepatocellular carcinoma and compared it with helical computed tomography. Forty‐eight patients with 61 hepatocellular carcinoma lesions were scanned by contrast‐enhanced, wide‐band harmonic gray scale imaging after an intravenous bolus injection of the contrast agent Levovist. Fifty‐seven of the 61 hepatocellular carcinoma lesions showed hypervascular enhancement, and intratumoral vessels could be observed in 40 of the 57 lesions. Helical computed tomography revealed a high‐attenuation area in 54 of the 61 lesions, whereas the other lesions showed an equivocal‐attenuation area. Contrast‐enhanced, wide‐band harmonic gray scale imaging is a useful method for diagnosing the vascularity of hepatocellular carcinoma.

Ablation therapy guided by contrast-enhanced sonography with Sonazoid for hepatocellular carcinoma lesions not detected by conventional sonography.

We evaluated the usefulness of contrast‐enhanced harmonic gray scale sonography with a newly developed sonographic contrast medium as a means of guidance for percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography.

The role of hepatitis B virus-specific memory CD8 T cells in the control of viral replication

BACKGROUND/AIMS The aim of this study is to clarify the differences of host immune responses between acute self-limited and chronic persistent hepatitis B virus (HBV) infections by quantitative and qualitative analysis of HLA-A*2402-restricted HBV-specific CD8+ T cells. METHODS HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HBV were analyzed by flow cytometry using two HLA-A*2402-HBV peptide tetrameric complexes. RESULTS High numbers of HBV-specific CD8+ T cells were detected in acute phase PBMCs from most individuals with acute HBV infection while the number of these cells was greatly reduced in recovery phase PBMCs. HBV-specific CD8+ T cells were not detected in PBMCs from individuals with chronic HBV infection except for one patient during acute exacerbation. HBV-specific CD8+ T cells were induced by in vitro peptide stimulation in PBMCs from chronic HBV carriers with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. CD28CD45RA phenotype analysis showed that HBV-specific CD8+ T cells in acute phase PBMCs predominantly express a memory T cell phenotype. CONCLUSIONS HBV-specific memory CD8+ T cells may play a crucial role in complete clearance of HBV from patients with acute HBV hepatitis.

Efficacy of Fusion Imaging Combining Sonography and Hepatobiliary Phase MRI With Gd-EOB-DTPA to Detect Small Hepatocellular Carcinoma

OBJECTIVE We evaluated the efficacy of fusion imaging that fuses conventional sonography images with hepatobiliary phase contrast-enhanced MR images obtained with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) as the reference image for the detection of hepatocellular carcinomas (HCCs). SUBJECTS AND METHODS Eighty-seven HCCs with a maximum diameter of between 1 and 3 cm at the time of diagnosis were enrolled in this prospective study. We compared the detection rates of HCCs using three sonography modalities: conventional sonography, late phase of contrast-enhanced sonography with Sonazoid, and fusion imaging combining conventional sonography and the hepatobiliary phase of contrast-enhanced MRI with Gd-EOB-DTPA as the reference image. The comparisons were made using the McNemar test. RESULTS The detection rate of HCCs using fusion imaging (98%, 85/87) was significantly higher than the detection rates using conventional sonography (76%, 66/87) and contrast-enhanced sonography (83%, 72/87) (p<0.01, for both). For small HCCs (maximum diameter, 1-2 cm), the detection rate using fusion imaging (97%, 59/61) was also significantly higher than those using conventional sonography (66%, 40/61) and contrast-enhanced sonography (80%, 49/61) (p<0.01, for both). The detection rate for atypical HCCs was also significantly higher using fusion imaging (95%, 18/19) than using conventional sonography (53%, 10/19) and contrast-enhanced sonography (26%, 5/19) (p<0.01, for both). CONCLUSION Fusion imaging combining conventional sonography and the hepatobiliary phase of contrast-enhanced MRI with Gd-EOB-DTPA is more sensitive than conventional sonography or contrast-enhanced sonography for detecting HCCs, especially small or atypical HCCs.

Identification of hepatitis B virus-specific CTL epitopes presented by HLA-A*2402, the most common HLA class I allele in East Asia

BACKGROUND/AIMS The aim of this study was to identify and characterize hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTL) epitopes presented by human leukocyte antigen (HLA)-A*2402, most common HLA class I allele in East Asia. METHODS HLA-A*2402-restricted CTL epitopes were identified by reverse immunogenetics. Immunogenecity of these epitopes was investigated using peripheral blood mononuclear cell (PBMC) from HLA-A24+ patients with acute hepatitis B. RESULTS An HLA-A*2402 stabilization assay demonstrated that 36 of 63 HBV peptides carrying HLA-A*2402 anchor residues have high- and medium-HLA-A*2402 binding affinity. Two (C117-125 and P756-764) of the 36 peptides induced peptide-specific CTLs. CTL clones and lines specific for these peptides killed HBV recombinant vaccinia virus-infected target cells expressing HLA-A*2402, indicating that these two peptides are CTL epitopes presented by HLA-A*2402. These two peptides were able to induce specific CTLs in 7 and 11 of 12 HLA-A24+ patients with acute hepatitis B, respectively. CONCLUSIONS We identified two immunodominant CTL epitopes restricted by HLA-A*2402. Because HLA-A*2402 is the most common allele in East Asia, a region in which there are approximately 200 million HBV carriers, these epitopes will be useful for analysis of CTL responses in patients from East Asia.

C-arm cone beam CT for hepatic tumor ablation under real-time 3D imaging.

OBJECTIVE We describe our experience with the application of a novel technology in which fluoroscopy and 3D imaging from C-arm cone beam CT systems are combined with integrated navigation software. CONCLUSION We applied this technology to five cases in which radiofrequency ablation was performed for hepatocellular carcinoma. Technical success was achieved without treatment-related complications in all cases. We conclude that this novel technology is potentially useful for targeting hepatic lesions.

Higher discontinuation and lower survival rates are likely in elderly Japanese patients with advanced hepatocellular carcinoma receiving sorafenib

Aim:  Sorafenib is approved for the treatment of advanced hepatocellular carcinoma (HCC) in Japan; however, its tolerability and efficacy in elderly patients with HCC have not been clarified. We aimed to evaluate the tolerability and efficacy of sorafenib with increasing age.

Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens.

Background : Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours.

Focal Liver Tumors: Characterization with 3D Perflubutane Microbubble Contrast Agent–enhanced US versus 3D Contrast-enhanced Multidetector CT

PURPOSE To investigate the potential application of contrast material-enhanced three-dimensional (3D) ultrasonography (US), as compared with contrast-enhanced 3D computed tomography (CT), for characterization of focal liver tumors. MATERIALS AND METHODS Institutional review board approval and informed patient consent were obtained. One hundred thirty-nine patients with focal liver tumors-77 hepatocellular carcinomas (HCCs), 33 metastases, 23 hemangiomas, and six focal nodular hyperplasias (FNHs)-who were examined at 3D US enhanced with a perflubutane microbubble contrast agent and at 3D contrast-enhanced multidetector CT were retrospectively identified. Two readers blindly reviewed the multiplanar images and angiograms reconstructed with both modalities and classified the depicted lesions according to diagnostic criteria based on their experience and published findings. Sensitivity, specificity, positive predictive value (PPV), area under the receiver operating characteristic curve (A(z)), intermodality agreement, and interreader agreement were assessed. RESULTS Readers 1 and 2 had concordant US and CT findings for 115 (83%) and 116 (83%) of the 139 lesions, respectively, with moderate to excellent (kappa = 0.55-0.81) intermodality agreement. There were no significant differences between the two modalities: Sensitivity was 83% or greater with both modalities, specificity was 87% or greater with contrast-enhanced US and 92% or greater with contrast-enhanced CT, the PPV was 71% or greater with both modalities, and the A(z) was at least 0.89 with US and at least 0.92 with CT. Interreader agreement was good to excellent (kappa > or = 0.76) with both modalities. CONCLUSION Contrast-enhanced 3D US potentially can be used to characterize focal liver tumors.