Yoshihiro Furuichi

Hepatocellular carcinoma treated with sorafenib: early detection of treatment response and major adverse events by contrast-enhanced US

Early prediction of tumour response and major adverse events (AEs), especially liver failure, in patients with hepatocellular carcinoma (HCC) is essential for maximizing the clinical benefits of sorafenib. To evaluate the usefulness of dynamic contrast‐enhanced ultrasound (DCE‐US) for the early prediction of tumour response and major AEs in HCC patients.

Memory Th1 Cells Augment Tumor-Specific CTL following Transcutaneous Peptide Immunization

Targeting dendritic cells in vivo by transcutaneous peptide immunization (TCI) represents an efficient immunization strategy to induce tumor-specific CTL because it reflects the physiologic conditions occurring during pathogen infection. Here we show that including a Th1 peptide in TCI can activate preexisting memory Th1 (mTh1) responses and thereby enhance the CTL response. For this purpose, peptide-25, a major Th1 epitope of Ag85B from Mycobacterium tuberculosis, was selected. We adoptively transferred peptide-25-specific mTh1 cells and hgp100-specific naive CTL (pmel-1 TCR transgenic) into C57BL/6 mice. Subsequently, mice were transcutaneously immunized with CTL peptide (hgp100) and Th1 peptide (peptide-25). Five days after TCI, the frequency and function of pmel-1 cells was monitored by intracellular IFN-gamma staining, ELISPOT, and in vivo cytotoxicity assays. TCI efficiently expanded hgp100-specific, IFN-gamma-producing, strongly cytotoxic CD8(+) T cells. Concurrent activation of mTh1 cells by peptide-25 induced a 1.5-fold increase in the number of hgp100-specific CTL with enhanced effector functions. Furthermore, TCI elicited not only prophylactic but also therapeutic antitumor responses that were augmented by peptide-25. These results show that TCI facilitates peptide-specific activation of CD4(+) T cells, responsible for the augmenting effect of peptide-25 on the hgp100-specific CTL response. Because a significant proportion of the Japanese population has been vaccinated with Bacillus Calmette-Guerin, they are likely to possess Ag85B- or peptide-25-specific mTh1 cells. Therefore, concomitant activation of Ag85B- or peptide-25-specific mTh1 cells together with tumor-specific CTL by TCI might augment antitumor immune responses in a sizeable fraction of patients.

Relationship between the Status of Blood Supply in the Non-hypervascularHepatocellular Nodules among Chronic Liver Diseases and the HypervascularChange

Objectives: We observed the time-course changes of blood flow in non-hypervascular hepatocellular nodules that showed hypointensity in the hepatobiliary phase on Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI), and evaluated the relationship between hypervascular change and the status of blood supply in the nodules. Methods: The study included 69 hepatocellular nodules in 33 patients demonstrating hypointensity in the hepatobiliary phase on EOB-MRI and showing non-hypervascular features on CT during hepatic arteriography (CTHA) performed during the same period. Results: In relation to blood flow on CTHA/ CT during arterial portography (CTAP), the cumulative rate of hypervascular change at 52 weeks was 0.0% for iso/iso, 29.7% for hypo/iso, 61.5% for iso/hypo, and 55.0% for hypo/hypo. Multivariate analysis using COX proportional hazards regression showed that CTAP findings (hypodensity) and CTHA findings (hypo-density) were significant variables for hypervascular change. Conclusions: In cases of non-hypervascular hepatocellular tumors, nodules with decreased arterial or portal blood flow that show hypointensity in the hepatobiliary phase on EOB-MRI are likely to develop into typical hepatocellular carcinoma in a shorter time.

Focal nodular hyperplasia-like lesion of the liver with focal adenoma features associated with idiopathic portal hypertension

Great progress has been made in the diagnosis of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) in the last few years due to the use of molecular criteria. This has allowed us to identify a new type of hepatic nodule. In this case report, we present a male patient with a hepatic nodule associated with idiopathic portal hypertension (IPH) pathologically exhibiting not only the morphological features of FNH, such as ductular reactions, dilated sinusoids, major vascular abnormalities and an immunohistochemical “map‐like” pattern of glutamine synthetase (GS), but also the immunohistological features of focal HCA, such as strong expression of serum amyloid A and C‐reactive protein and weak expression of GS. As the final diagnosis, the nodule was identified as an FNH‐like lesion with focal inflammatory hepatocellular adenoma.

Case study to assess the safety of irreversible electroporation near the heart

IntroductionIrreversible electroporation (IRE) is a promising technique for the focal treatment of soft tissue tumors. Even though the local application of an excessive electric field is a potential cause of cardiac arrhythmias, initial clinical studies have shown that IRE is generally safe when cardiac gating is employed.Case descriptionIn this case report, we observed an episode of ventricular extrasystoles without hemodynamic changes during which time the synchronization device failed to operate properly, with pulses delivered not in the absolute refractory period but in the relative refractory period.Discussion and evaluationAt present, persons performing IRE must keep in mind that there is a small but real risk of synchronization failure even when a cardiac synchronization device is used.ConclusionIt is advisable to err on the side of caution when treating lesions near the heart.

Flexible imaging color enhancement improves visibility of transnasal endoscopic images in diagnosing esophageal varices: a multicenter prospective blinded study.

To clarify the usefulness of transnasal esophagogastroduodenoscope (N‐EGD) with all flexible imaging color enhancement (FICE) patterns (0–9) for the diagnosis of esophageal varices (EV).

Branched-chain amino acid-enriched nutrient increases blood platelet count in patients after endoscopic injection sclerotherapy.

Protein and energy malnutrition is a severe problem for patients with liver cirrhosis (LC) and fasting often induces starvation which is a vitally important outcome. Dietary restriction is essential for endoscopic injection sclerotherapy (EIS) in patients with risky esophageal varices, thereby creating the possible exacerbation of nutritional state and inducing liver dysfunction. Whether EIS induces nutritional deficiency in LC patients and the effects of branched‐chain amino acid (BCAA)‐enriched nutrient are prospectively investigated.

Obliteration of gastric varices improves the arrival time of ultrasound contrast agents in hepatic artery and vein

Liver cirrhosis (LC) is accompanied by hepatic arterializations, intrahepatic shunts, and hyperdynamic circulations. These changes shorten the arrival time (AT) of ultrasound contrast agents to the hepatic vein (HV). Whether treatment of gastric fundal varices (GVs) by balloon‐occluded transvenous obliteration (B‐RTO) improves the AT in LC patients was prospectively investigated.

Viscoelasticity Measurement in Rat Livers Using Shear-Wave US Elastography

To investigate the usefulness of shear-wave speed and dispersion slope measurements obtained, using an ultrasound elastography system in rat livers with various degrees of necroinflammation and fibrosis. A total of 25 male Sprague Dawley rats were randomly divided into 5 groups of 5 rats each: G0 (control), G1 (CCl4 injected twice a week for 1 wk), G2 (CCl4 injected four times a wk for 1 wk), G3 (CCl4 injected twice a wk for 6 wk) and G4 (CCl4 injected twice a wk for 10 wk). The shear-wave speed (m/s) and the dispersion slope ([m/s]/kHz) were measured. Histologic features (inflammation, necrosis and fibrosis) were used as reference standards. In multivariable analysis with histologic features as independent variables, the fibrosis grade was significantly related to shear-wave speed (p < 0.05) and the necrosis grade was significantly related to dispersion slope (p < 0.05). Dispersion slope is more useful than shear-wave speed for predicting the degree of necroinflammation.

Restoration of natural killer cell activity by interferon-free direct-acting antiviral combination therapy in chronic hepatitis C patients: Restoration of NK activity by DAAs

Interferon‐free direct‐acting antiviral (DAA) therapy is an effective treatment for chronic hepatitis C (CH(C)) patients. Activity of natural killer (NK) cells was reported to be impaired in patients with hepatitis C virus infection. The aim of this study was to examine whether DAA therapy could restore NK activity in patients with CH(C).