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Background & aims: Hepatic iron accumulation can accelerate liver injury in patients with various chronic liver diseases and lead to hepatocarcinogenesis. We elucidated the impact of serum levels of ferritin on the prognosis of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) in a large cohort. Methods: We retrospectively analyzed 578 treatment-naïve HCC patients who underwent RFA. We divided our cohort into four groups by the quartile points of serum ferritin level: G1 (≤55 ng/mL, n = 148), G2 (56–130 ng/mL, n = 142), G3 (131–243 ng/mL, n = 144) and G4 (≥244 ng/mL, n = 144). We analyzed the recurrence and survival of patients using the Kaplan–Meier method. We also evaluated pathological iron deposition among patients with a solitary tumor smaller than 2 cm. Results: The cumulative rates of overall recurrence and survival at 5 years were 81.6% and 66.3%, respectively. The serum levels of ferritin were correlated with pathological iron deposition. There were no significant differences in recurrence and survival rates according to serum levels of ferritin and pathological hepatic iron deposition. Conclusions: Serum levels of ferritin do not affect the prognosis of HCC patients undergoing RFA. [ABSTRACT FROM AUTHOR]

Immunohistochemical analysis using specific antibodies is a useful and convenient method to detect proteins altered by somatic mutations. We previously generated the rat monoclonal antibody MsMab-2, which recognizes isocitrate dehydrogenase (IDH)1 R132L and IDH2 R172M. In the present study, we used an immunohistochemical method to examine MsMab-2 immunoreactivity in 95 cases of intrahepatic cholangiocarcinoma, including five IDH1 R132L and one IDH2 R172M mutant cases confirmed by direct sequencing. Tissue microarray section slides of all IDH1/2-mutant and wild-type cases, as well as whole section slides of IDH1 R132L and IDH2 R172M cases were immunostained using an autostainer. All IDH1 R132L cases showed positive staining for MsMab-2, while other IDH1/2 mutant and IDH1/2 wild-type cases were negative. Tumor cells of the immunopositive cases invariably showed strong reactivity using whole-section slides. We consider immunohistochemical analysis using MsMab-2 to be a useful means of detecting IDH1 R132L. Further analysis of its effectiveness against IDH2 R172M is necessary because of the small sample size in this study. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the clinicopathologic significance of intratumoral lymphoplasmacytic infiltration in a large cohort of patients with solitary hepatocellular carcinoma (HCC). Based on examination of hematoxylin and eosin-stained sections, significant infiltration was defined as dense lymphoplasmacytic infiltration, either multifocal or diffuse, in 2 or more fields under low-power magnification. Of 544 cases, 216 (39.7%) were positive for significant infiltration (HCC-LI group), while 328 (60.3%) were negative (HCC-NLI group). There were no significant between-group differences in patient age, sex, or background etiology. The lower incidence of Child-Pugh stage B (P = 0.001) and lower level of indocyanine green retention rate at 15 minutes (P < 0.001) in the HCC-LI group indicated better liver function in this group. Histologically, tumors were significantly smaller in size in the HCC-LI group than in the HCC-NLI group (P < 0.001). In addition, prominent neutrophilic infiltration, interstitial fibrosis and tumor steatosis were significantly more frequent (P < 0.001) in the HCC-LI group, while tumor necrosis was significantly less frequent (P = 0.008). Kaplan-Meier analyses revealed that overall and recurrence-free survival were significantly better in the HCC-LI group (P < 0.001). Multivariate Cox regression analysis showed that intratumoral lymphoplasmacytic infiltration was independently prognostic of both overall and recurrence-free survival (P < 0.001), with absence of infiltration showing high Cox-hazard ratios for poor prognosis. In conclusion, intratumoral lymphoplasmacytic infiltration, as determined by assessment of hematoxylin and eosin-stained slides, was significantly associated with the clinical and pathologic features of HCC and has profound prognostic importance. [ABSTRACT FROM AUTHOR]

Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities. [ABSTRACT FROM AUTHOR]

Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed to improve the visibility of photoacoustic signals emitted from deeply-located lesions. [ABSTRACT FROM AUTHOR]

Analysis of acetylation and tri-methylation of the same residue of histone molecules might identify a subset of hepatocellular carcinoma (HCC) with aggressive behavior. In the present study, we examined acetylation and tri-methylation of lysine 27 on histone H3 (H3K27ac and H3K27me3, respectively) because these two modifications are known to exhibit opposite effects (enhancing and silencing) on gene expression. Neoplastic and non-neoplastic tissues from 198 HCC cases were immunostained with specific monoclonal antibodies against H3K27ac and H3K27me3. The stained tissues were evaluated by an image analyzing program to generate histological scores (H-scores, range 0–300), which were determined by multiplying the percentage of positive-stained cells with the classified immunohistochemical marker intensity (0–3). HCC tissues showed significantly higher H3K27ac (156.7±86.8) and H3K27me3 H-scores (151.8±78.1) compared with the background liver (40.3±33.0 and 64.7±45.6, respectively) (both P<0.001). The cases with H-scores of high-H3K27ac/high-H3K27me3 (n = 54) showed significant correlation with poor differentiation of morphology (P<0.01) and p53-positive staining (P<0.05), and poor prognosis (P<0.01). Confocal microscopy revealed segregated intranuclear localization of both modifications in the individual cancer cells: H3K27ac localization in central euchromatin regions and H3K27me3 in peripheral heterochromatin regions. Concurrent acetylation and methylation at H3K27 occurs in HCC cells in association with p53 abnormalities. These findings demonstrate that image analyzer-assisted H-scores of H3K27ac and H3K27me3 identified an aggressive subgroup of HCC, and could serve as a prognostic marker for HCC. [ABSTRACT FROM AUTHOR]

The article presents a research which examined the potential of using Fluorescent imaging using indocyanine green (ICG) in detecting liver cancer. The result found that ICG-fluorescent imaging enables sensitive identification of small and identifiable liver cancers in real time which enhances the accuracy of liver resection and operative staging. It further states that ICG-fluorescent imaging has identified all of the microscopically confirmed metastases in surgical specimens.

Abstract: We studied the possibility of using high-intensity focused ultrasound (HIFU) together with a microbubble agent to treat hepatocellular carcinoma. Development of liver tumors in rats was induced by administration of Dimethylnitrosamin (100ppm). Rats with liver tumors were anesthetized, underwent laparotomy, and were given the microbubble agent Levovist or saline intravenously. After the injection, the liver was exposed to HIFU for 30s (2.18MHz, 600W/cm2, 40mm in diameter). Immediately after HIFU exposure, ultrasound images of the HIFU area were evaluated. Then the liver was excised and the volume of coagulated tissue was measured. The mean volumes of hyperechoic areas after HIFU were as follows (mm3, Levovist versus saline: 355.3±180.7 versus 47.4±35.6, P <0.001, n =13). The volumes of liver tissue coagulated by HIFU were as follows (mm3, Levovist versus saline: 275.3±120.0 versus 60.1±23.6, P <0.001, n =13). On microscopic examination of areas exposed to HIFU, implosion cysts were seen, and many cancer cells were found to have been destroyed completely (loss of cell membranes or nuclei). In conclusion, the microbubble agent Levovist can increase the volume of tissue coagulated by HIFU. [Copyright &y& Elsevier]

Abstract: A 42-year-old man suffering from haemophilia A and coinfection of human immunodeficiency virus (HIV) and hepatitis C virus was referred to our institution because of multiple liver tumours. He had been receiving highly active antiretroviral therapy for HIV infection. Ultrasonography showed multiple hypoechoic space-occupying lesions in the liver. Contrast-enhanced dynamic computed tomography (CT) and magnetic resonance imaging revealed multiple ring-enhanced hypervascular lesions in the liver. An ultrasonography-guided biopsy was performed and histological evaluation indicated one of the lesions to be combined hepatocellular and cholangiocarcinoma and others to be non-neoplastic. The patient underwent partial hepatic resection and is currently alive without recurrence for 15 months. Multiple ring-enhanced lesions have been undetectable in postoperative follow-up CT examinations. [Copyright &y& Elsevier]