Changes In Hepatocellular Carcinoma Research Articles

Identification of Protein Abundance Changes in Hepatocellular Carcinoma Tissues Using PCT-SWATH.

To rapidly identify protein abundance changes in biopsy-level fresh-frozen hepatocellular carcinoma (HCC). The pressure-cycling technology (PCT) is applied and sequential window acquisition of all theoretical mass spectra (SWATH-MS) workflow is optimized to analyze 38 biopsy-level tissue samples from 19 HCC patients. Each proteome is analyzed with 45 min LC gradient. MCM7 is validated using immunohistochemistry (IHC). A total of 11787 proteotypic peptides from 2579 SwissProt proteins are quantified with high confidence. The coefficient of variation (CV) of peptide yield using PCT is 32.9%, and the R2 of peptide quantification is 0.9729. Five hundred forty-one proteins showed significant abundance change between the tumor area and its adjacent benign area. From 24 upregulated pathways and 13 suppressed ones, enhanced biomolecule synthesis and suppressed small molecular metabolism in liver tumor tissues are observed. Protein changes based on α-fetoprotein expression and hepatitis B virus infection are further analyzed. The data altogether highlight 16 promising tumor marker candidates. The upregulation of minichromosome maintenance complex component 7 (MCM7) is further observed in multiple HCC tumor tissues by IHC. The practicality of rapid proteomic analysis of biopsy-level fresh-frozen HCC tissue samples with PCT-SWATH has been demonstrated and promising tumor marker candidates including MCM7 are identified.

Dynamic Contrast Enhanced MRI Reveals Acute Changes in Vascular Permeability/Perfusion Following Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma

The purpose of this pilot study was to evaluate acute tumor vasculature changes in hepatocellular carcinoma (HCC) using dynamic contrast enhanced MRI (DCE-MRI) following stereotactic body radiation therapy (SBRT). Patients with unresectable HCC based on multiphase imaging and treated with SBRT were eligible. Patients were required to have Child-Turcotte-Pugh A/B liver disease with 1-3 lesions amenable to SBRT with a tumor size ≤ 15 cm (single lesion or sum of lesions). A baseline MRI was performed within 2 weeks prior to the first fraction of SBRT. SBRT was delivered using a 2 or 3 arc volumetric arc therapy plan with 6 or 10 MV photons with a dose of 7.5 Gy. Following SBRT, post-treatment imaging was performed by either 6 or 24 hours after the first fraction. All research MRI scans were performed with a 3T whole-body MRI. DCE-MRI was performed with 60 dynamic cycles at a temporal resolution of 6 seconds. Contrast infusion (Gadobenate, 0.5 mL/sec) was initiated at the 10th dynamic cycle. DCE-MRI data were analyzed with the modified Brix’s pharmacokinetic model. The uni-directional exchange rate constants kep (interstitial space to blood plasma) and kpe (blood plasma to interstitial space) were reported as measures of vascular permeability/perfusion. Statistical analysis was performed using the Wilcoxon rank sum test. Eight patients (7 male/1 female) were enrolled with a median age of 65 years (range 48-79). Ten tumors were evaluated and treated with a median tumor size of 5.9 cm (range 1.6-12 cm). Five patients (7 tumors) completed post-treatment imaging between 20-24 hours post-SBRT while the remaining 3 patients (3 tumors) completed post-SBRT imaging 2-6 hours after treatment. Pharmacokinetic analysis of DCE-MRI revealed significant changes in tumor permeability/perfusion after a single fraction of SBRT. The exchange rate kpe showed a rapid increase within 6 hours post-SBRT (median 1005%, range 115∼1030%) followed by a subsequent decrease by 24 hours (median -24%, range -75∼17%, P=0.02). A similar trend was also observed for kep. However, it was of smaller magnitude and did not reach statistical significance (an initial increase in the 6-hour time window: median 105%, range -50∼218%; and a subsequent return to near baseline by 24 hours post-treatment: median 1%, range -29∼155%; P=0.7). Our preliminary results suggest that SBRT may trigger a rapid increase in tumor permeability/perfusion within 6 hours of radiation therapy delivery. The magnitude of this effect is subsequently diminished or reversed by 24 hours post-treatment. This 6-hour time window may provide an opportunity for better accessibility and efficacy when delivering chemotherapy or molecularly targeted agents in conjunction with moderate SBRT doses.

Comparative analysis of tumor-associated vascular changes following TACE alone or in combination with sorafenib treatment in HCC: A retrospective study.

The objective of the present study was to investigate the tumor-associated vascular changes in hepatocellular carcinoma (HCC) following treatment with transarterial chemoembolization (TACE) combined with sorafenib. The data of 20 patients were retrospectively analyzed. Patients underwent treatment depending on their chosen regimens (orally administered sorafenib was recommended, however the cost prevented some study articipants from selecting this course). Based on this, the patients were divided into TACE combined with sorafenib (TS) (n=10) and TACE-only treatment groups (n=10). Digital subtraction angiography images of all patients were analyzed by 2 radiologists who were blind to the type of treatment administered. The diameters of the hepatic and proper hepatic arteries, and hepatic artery branches (tumor-associated arteries), the splenic, left gastric and gastroduodenal arteries or portal veins (non-tumor-associated arteries) and the number of microvascular vessels were compared prior to and following sorafenib treatment in the TS group, between the first and second sessions of TACE in the TACE-only group and between the TS and TACE-only groups. In the TS group, the diameters of the hepatic and proper hepatic arteries, their branches and the number of microvascular vessels were significantly decreased following sorafenib treatment (P<0.05), while the diameters of the splenic, gastroduodenal and left gastric arteries were not significantly altered (P>0.05). In the TACE-only group, the diameters of the hepatic, proper hepatic, splenic, left gastric and gastroduodenal arteries were not significantly different between the first and second TACE sessions (P>0.05), while the diameters of the hepatic artery branches and the number of microvascular vessels were significantly altered (P<0.05). TACE combined with sorafenib significantly decreased the diameters of the tumor-associated arteries and the number of tumor microvascular vessels when compared with TACE treatment alone (P<0.05). No significant difference in the diameters of the portal vein and its branches between the two groups was observed (P>0.05). Treatment with TACE combined with sorafenib may significantly affect the tumor-associated vasculature compared with treatment with TACE alone in HCC.

The role of dynamic contrast-enhanced MRI analysis of perfusion changes in hepatocellular carcinoma

Background Dynamic contrast-enhanced (DCE)-MRI functional imaging is primarily focused on quantitative evaluation of tumoral perfusion and permeability, thus enabling an insight into the pathophysiology of tissue and serving as early noninvasive biologic markers of tumorigenesis. Aim The aim was to evaluate the functional role of DCE-MRI analysis of perfusion changes in hepatocellular carcinoma (HCC). Patients and methods A total of 43 patients with liver cirrhosis having 65 HCCs all underwent 3 T multiphase DCE-MRI assessment. Maximum relative enhancement, area under curve, wash-in ratio, wash-out ratio, time to arrival, and time to peak semiquantitative measurements were analytically compared between the hepatocellular carcinogenic lesions and the adjacent lesion-free liver cirrhosis. Results Comparison of different perfusion metrics across hepatocellular carcinogenic lesions and adjacent lesion-free liver cirrhosis revealed exceling statistical significance. Diagnostic accuracies were highest when using wash-out ratio (86.2%) to detect HCC from background cirrhosis, whereas they were lowest using area under the curve (67.7%). Implementing wash-in ratio (81.9%), as a first-pass perfusion metric, surpassed its counterpart, maximum relative enhancement (73.4%), in diagnostic reliability. Regarding the timing of flow dynamics, time to arrival (84.1%) was more important than time to peak (78.1%) as a diagnostic indicator of hepatocarcinogenesis. Conclusion Multiphase DCE-MRI perfusion analyses provide quantitative hemodynamic metrics that promise potential usefulness as noninvasive biomarkers in the detection of HCC.

Comparison of hepatic and serum lipid signatures in hepatocellular carcinoma patients leads to the discovery of diagnostic and prognostic biomarkers.

We compared hepatic and serum lipid changes in hepatocellular carcinoma (HCC) patients to have a better understanding of the molecular pathogenesis of this disease and discovery novel lipid biomarkers. Hepatic and serum lipid profiling was conducted in paired liver and serum samples from 50 HCC patients and 24 healthy controls. A total of 20 hepatic and 40 serum lipid signatures were identified, yet there was hardly any significant correlation between them. The results indicated that triglycerides and phosphatidylcholines contributed significantly to altered hepatic lipids, whereas triglycerides and phosphatidylethanolamine-based plasmalogens (PEp) contributed most to altered serum lipids. In serum, PEp (36:4) and (40:6) showed a fair capability to discriminate HCC patients from healthy controls, and were significantly associated with HCC tumor grades (p < 0.05), and thus were identified as potential diagnostic and prognostic biomarkers of HCC. These findings were confirmed by a validation study conducted in an independent cohort consisting of 18 HCC, 20 cirrhosis patients, and 20 healthy controls. This study suggests that hepatic and serum lipid signatures of HCC have to be considered as mostly independent, and the results imply potential roles of PEp species, particularly PEp (36:4) and (40:6), as serum biomarkers for HCC diagnosis and progression.

The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B.

The HCC risk decreases beyond year 5 of ETV/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially ≥50 years), lower platelets, and liver stiffness ≥12 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444-1453).

Detection and differentiation of early hepatocellular carcinoma from cirrhosis using CT perfusion in a rat liver model

Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in hepatocellular carcinoma (HCC). Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investigate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic (ROC) curves. Male Wistar rats were randomly divided into control (n=20) and experimental (n=70) groups. Diethylnitrosamine (DEN) was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion (HPP), hepatic arterial fraction (HAF), hepatic arterial perfusion (HAP), hepatic blood volume (HBV), hepatic blood flow (HBF), mean transit time (MTT) and permeability of capillary vessel surface (PS) data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats (control, pre-carcinoma and early HCC groups) using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan. For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups (P<0.05). HAF had the highest areas under the ROC curves: 0.80 (control vs pre-carcinoma groups) and 0.95 (control vs early HCC groups) with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 (control vs pre-carcinoma groups) and 0.92 (control vs early HCC groups) with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.

Evaluation of Tumor Microenvironment Changes in Hepatocellular Carcinoma After Stereotactic Body Radiation Therapy Using Functional Magnetic Resonance Imaging

Evaluation of Tumor Microenvironment Changes in Hepatocellular Carcinoma After Stereotactic Body Radiation Therapy Using Functional Magnetic Resonance Imaging

Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery.

To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. • Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. • Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. • Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma.

C-arm computed tomography and volume perfusion computed tomography (VPCT)-based assessment of blood volume changes in hepatocellular carcinoma in prediction of midterm tumor response to transarterial chemoembolization: a single center retrospective trial.

BackgroundThis study aims to evaluate immediate changes in perfusion parameters in hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) in C-arm computed tomography (CT) and volume perfusion CT (VPCT) and prediction of midterm tumor response.MethodsTwenty-five patients (median age 66, range 61 to 75 years) with 62 HCC lesions undergoing TACE received immediate pre- and post-interventional assessment by C-arm CT and VPCT. Cross-sectional imaging was analyzed at baseline and approximately 12 weeks after TACE according to modified RECIST criteria. Outcome was defined as objective response (OR, > 30 % reduction of viable tumor) or non-OR. Perfusion parameters were evaluated in C-arm CT [parenchymal blood volume (PBV)] and VPCT [blood volume (BV) and blood flow (BF)]. Ratios of perfusion parameters before and after TACE within the tumor and the non-affected liver parenchyma were calculated.ResultsCorrelation between tumor PBV and BV revealed a moderate correlation (rho = 0.45, p = 0.005). In non-affected liver parenchyma, a significant decrease in PBV was seen, compared to a significant increase in BF and BV. Perfusion ratios in HCC lesions were significantly (p < 0.05) increased in OR group compared to non-OR patients in C-arm CT and VPCT: PBV ratio (0.95 (0.06) to 0.67 (0.38), BV ratio 0.63 (0.34) to 0.15 (0.6), and BF ratio 0.6 (0.32) to 0.22 (0.51). Logistic regression including PBV and BF allowed prediction of OR (sensitivity 88 %/specificity of 83 %).ConclusionsPerfusion parameters acquired by C-arm CT and VPCT cannot simply be substituted by each other, but show similar capability in prediction of midterm tumor response.

Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge.

PurposeTo evaluate the utility of oxygen challenge and report on temporal changes in blood oxygenation level‐dependent (BOLD) contrast in normal liver, hepatocellular carcinoma (HCC) and background fibrosis.Materials and MethodsEleven volunteers (nine male and two female, mean age 33.5, range 27–41 years) and 10 patients (nine male and one female, mean age 68.9, range 56–87 years) with hepatocellular carcinoma on a background of diffuse liver disease were recruited. Imaging was performed on a 3T system using a multiphase, multiecho, fast gradient echo sequence. Oxygen was administered via a Hudson mask after 2 minutes of free‐breathing. Paired t‐tests were performed to determine if the mean pre‐ and post‐O2 differences were statistically significant.ResultsIn patients with liver fibrosis (n = 8) the change in T2* following O2 administration was elevated (0.88 ± 0.582 msec, range 0.03–1.69 msec) and the difference was significant (P = 0.004). The magnitude of the BOLD response in patients with HCC (n = 10) was larger, however the response was more variable (1.07 ± 1.458 msec, range –0.93–3.26 msec), and the difference was borderline significant (P = 0.046). The BOLD response in the volunteer cohort was not significant (P = 0.121, 0.59 ± 1.162 msec, range –0.81–2.44 msec).ConclusionThis work demonstrates that the BOLD response following oxygen challenge within cirrhotic liver is consistent with a breakdown in vascular autoregulatory mechanisms. Similarly, the elevated BOLD response within HCC is consistent with the abnormal capillary vasculature within tumors and the arterialization of the blood supply. Our results suggest that oxygen challenge may prove a viable BOLD contrast mechanism in the liver. J. Magn. Reson. Imaging 2016;44:739–744.

Unusual computed tomography features of ruptured sarcomatous hepatocellular carcinoma

Sarcomatous change in hepatocellular carcinoma (HCC) is an uncommon histologic variant of HCC, characterized by the proliferation of spindle cells or bizarre giant cells. Poor outcome has been reported in most cases after diagnosis. Here, we report the first case of a sarcomatous HCC with complete central necrosis and rupture of the liver capsule. The patient received target therapy with sorafenib, but died of progressive intra-abdominal carcinomatosis 3 months after treatment. We reviewed the published reports of 13 patients with sarcomatous HCC that included computed tomography features and found that our patient was the only one to have received sorafenib. It appears that this patient's life span was not significantly prolonged with the use of sorafenib.

STEAP4 Inactivation Correlates Poor Prognosis and might be a Possible Cause of steatotic Change in Hepatocellular Carcinoma, Detected by Triple-Combination Array Analysis

In the present study, we originally designed triple-combination array analysis to identify tumor related genes in Hepatocellular Carcinoma (HCC). Using this method, the six transmembrane epithelial antigen of prostate family 4 (STEAP4), it was reported association with obesity and insulin-resistance, was detected as a candidate tumor suppressor gene. We found 32 of 48 (66.7%) tumor tissues showed STEAP4 promoter hypermethylation, and its expression level was significantly reduced in tumor tissues (p<0.0001). Methylated cases demonstrated significantly poorer recurrence-free survival (p=0.0462) and overall survival (p=0.0411). Triple-combination array analysis represents a useful technique for identifying novel tumor-related genes in HCC.

Paracrine Hedgehog signaling drives metabolic changes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role of Hh-dependent myofibroblasts in hepatocarcinogenesis is unknown. Here, we used human HCC samples, a mouse HCC model, and hepatoma cell/myofibroblast cocultures to examine the hypothesis that Hh signaling modulates myofibroblasts' metabolism to generate fuels for neighboring malignant hepatocytes. The results identify a novel paracrine mechanism whereby malignant hepatocytes produce Hh ligands to stimulate glycolysis in neighboring myofibroblasts, resulting in release of myofibroblast-derived lactate that the malignant hepatocytes use as an energy source. This discovery reveals new diagnostic and therapeutic targets that might be exploited to improve the outcomes of cirrhotic patients with HCCs.

Contrast Enhanced Transrectal Ultrasound for the Detection of Prostate Cancer: A Randomized, Double-Blind Trial of Dutasteride Pretreatment

The identification of clinically significant disease is crucial for optimal treatment of prostate cancer. Selective detection of prostate cancer with increased microvessel density is possible with contrast enhanced ultrasound. Preliminary studies suggest that pretreatment with a 5α-reductase inhibitor may improve the efficiency of contrast enhanced ultrasound targeted biopsy. This study was designed to quantify prostate cancer detection with contrast enhanced ultrasound with or without short-term pretreatment with dutasteride. In this randomized, double-blind, placebo controlled trial of oral dutasteride pretreatment, contrast enhanced ultrasound findings were graded and used to direct targeted biopsy (up to 6 cores per prostate). A blinded 12-core systematic biopsy was subsequently performed on every subject based on standard medial and lateral sampling of each sextant. Of 311 subjects who underwent randomization, 272 completed participation. Positive biopsies were obtained in 276 of 3,264 (8.5%) systematic cores and 203 of 1,237 (16.4%) targeted cores (OR 2.1, 95% CI 1.7-2.6, p <0.001). ROC analysis for the detection of all prostate cancers demonstrated an increase in diagnostic accuracy from pre-contrast imaging to contrast enhanced ultrasound (A(z) 0.60 vs 0.64, p = 0.005). For the detection of high grade cancer (Gleason score 7 or greater) ROC analysis demonstrated improved accuracy for pre-contrast imaging (A(z) 0.74) and contrast enhanced ultrasound (A(z) 0.80, p = 0.0005). For the detection of high grade cancer with greater than 50% biopsy core involvement, excellent accuracy was demonstrated with pre-contrast and contrast enhanced ultrasound, A(z) 0.83 and 0.90, respectively (p = 0.001). Pretreatment with dutasteride had no significant impact on the detection of prostate cancer (p = 0.97). Contrast enhanced ultrasound targeted biopsy provides a significant benefit for the detection of high grade/high volume prostate cancer.

Overexpression of the structural maintenance of chromosome 4 protein is associated with tumor de-differentiation, advanced stage and vascular invasion of primary liver cancer

Structural maintenance of chromosome 4 (SMC4) is associated with tumorigenesis. The present study aimed at detecting SMC4 expression in primary liver cancer and its association with clinicopathological patient data. A total of 72primary liver cancer tissues and 6 liver cell lines were assessed for expression of SMC4 mRNA and protein with qRT-PCR, western blotting and immunohistochemistry, respectively. SMC4 siRNAs were constructed to knockdown SMC4 expression, and phenotypic changes of hepatocellular carcinoma (HCC) cells were analyzed using flow cytometry and cell viability assays. The data showed that SMC4 mRNA and protein were highly expressed in HCC tissues compared to the normal tissues. Immunohistochemical analysis revealed that 52of 72 (72.2%) paraffin-embedded primary liver cancer tissues displayed strong cytoplasmic staining of SMC4 protein, whereas only 6 (8.3%) normal liver tissues showed immunostaining of SMC4. Statistical analysis showed that SMC4 expression was significantly associated with tumor size, de-differentiation, advanced stages and vascular invasion of the primary liver cancers. Moreover, knockdown of SMC4 expression reduced HCC cell proliferation. These data demonstrated that expression of SMC4 protein may be useful for the early detection and prediction of primary liver cancer progression.

Chromosome genetic changes in hepatocellular carcinoma with double exposure to hepatitis B virus/aflatoxin B1 : A preliminary study from Guangxi

Objective To study the chromosome genetic changes in hepatocellular carcinoma (HCC) with double exposure to hepatitis B virus/aflatoxin B1 (HBV/AFB1) in Guangxi.Method Differences in genomic alterations in 32 patients with HCC were analyzed using comparative genomic hybridization(CGH).Results (1) The majority of chromosome copy number in the 32 HCC samples had varying degrees of change.The amplification of chromosome regions were 1q,7q,8q,with the high frequency regions being 1q,8q.The deletion of chromosome regions were 1p,4q,8p,9p,13q,14q,16p,16q,17p,18q,19p,Y,with the high frequency regions being 1p,4q,8p,16q,17p,19p;(2) There were also some high copy number amplification or deletion of small regions,such as 2p25.1-p25.2,3q22.3-q23,7p14.1-p14.3,and 9p13.2-9p21; (3) Hierarchical clustering analysis showed that the rate of deletion of chromosome 13q decreased progressively in the following 4 groups:-HBsAg(+)/AFB1 (+),HBsAg(+)/AFB1 (-),HBsAg( - )/AFB1 ( + ),and HBsAg( - )/AFB1 (-) (x2=6.452,P＜0.05).4p was found mainly to be amplified in the HBsAg(+)/AFB1(-)group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg( - )/AFB1(-) groups.19q was found mainly to be amplified in the HBsAg(+)/AFB1(+) group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg(-)/AFB1(-) groups.Conclusion The chromosome genetic changes of HCC in Guangxi showed multiplicity.The deletion of chromosome 19p,2p25.1-25.2,3q22.3-q23,7p14.1-p14.3 and amplification of chromosome 9p13.2-9p21 are probably unique genetic characteristics of HCC in this region.The combined effects of Hepatitis B virus and aflatoxin B1 may contribute to deletion of chromosome 13q of HCC in Guangxi. Key words: Guangxi area; Hepatocellular carcinoma; Hepatitis B virus; Aflatoxin B1; Chromosome; Array CGH

Recent advances of miRNA involvement in hepatocellular carcinoma and cholangiocarcinoma

MicroRNAs (miRNAs), which are a class of highly evolutionarily conserved non-coding RNAs, modulate gene expression and are regulated by specific genes. Several studies have shown that the expression of miRNAs is deregulated in Hepatitis C virus (HCV) & Hepatitis B virus (HBV) infection, liver cancer progression, tumor invasion and metastasis. There are a number of high-quality review articles relative to the general role of miRNA alterations in carcinogenesis and specific reviews dealing with the miRNA changes in hepatocellular carcinoma (HCC) and cholangio-carcinoma (CCA). Since primary liver cancer is predominantly comprised of HCC and intrahepatic cholangiocarcinoma (ICC), in the present review we specifically focus on recent advances of miRNAs related to tumorigenesis, invasion and metastasis of primary liver cancer, with special emphasis on their relationships to their target genes. HCV & HBV are major causes of liver disease, including acute and chronic hepatitis, liver cirrhosis, and HCC, while HCV infection is a risk factor for ICC. We also discuss the mi-RNA alterations involved in HCV & HBV infection. We briefly describe advances in molecular signaling of miRNAs in liver cancers and present insights into new therapeutic clues that target liver cancer.

US-CT 3D dual imaging by mutual display of the same sections for depicting minor changes in hepatocellular carcinoma

The purpose of this study was to evaluate the usefulness of ultrasound-computed tomography (US-CT) 3D dual imaging for the detection of small extranodular growths of hepatocellular carcinoma (HCC). The clinical and pathological profiles of 10 patients with single nodular type HCC with extranodular growth (extranodular growth) who underwent a hepatectomy were evaluated using two-dimensional (2D) ultrasonography (US), three-dimensional (3D) US, 3D computed tomography (CT) and 3D US-CT dual images. Raw 3D data was converted to DICOM (Digital Imaging and Communication in Medicine) data using Echo to CT (Toshiba Medical Systems Corp., Tokyo, Japan), and the 3D DICOM data was directly transferred to the image analysis system (ZioM900, ZIOSOFT Inc., Tokyo, Japan). By inputting the angle number (x, y, z) of the 3D CT volume data into the ZioM900, multiplanar reconstruction (MPR) images of the 3D CT data were displayed in a manner such that they resembled the conventional US images. Eleven extranodular growths were detected pathologically in 10 cases. 2D US was capable of depicting only 2 of the 11 extranodular growths. 3D CT was capable of depicting 4 of the 11 extranodular growths. On the other hand, 3D US was capable of depicting 10 of the 11 extranodular growths, and 3D US-CT dual images, which enable the dual analysis of the CT and US planes, revealed all 11 extranodular growths. In conclusion, US-CT 3D dual imaging may be useful for the detection of small extranodular growths.

Magnetic resonance spectroscopy on hepatocellular carcinoma after transcatheter arterial chemoembolization

Proton magnetic resonance spectroscopy (MRS) of the liver in vivo is in experimental phase. MRS observation on liver cancer after transcatheter arterial chemoembolization (TACE) has seldom been reported. This study was to investigate the value of MRS in assessing the metabolic changes of hepatocellular carcinoma (HCC) after TACE. Twenty-five consecutive patients with pathologically-confirmed HCC received 1H MRS of all hepatic lesions using 1.5T whole body MR scanner before TACE and at 3-10 days after TACE. Choline-to-lipid (Cho/Lip), glucogen/glucose-to-lipid (Glu/Lip), and glytamine/glutamate-to-lipid (Glx/Lip) ratios were measured and analyzed statistically. The Cho/Lip, Glu/Lip, and Glx/Lip ratios were 0.21 +/- 0.08, 0.11 +/- 0.05, 0.28 +/- 0.10 before TACE, respectively, and were 0.10 +/- 0.08, 0.07 +/- 0.07, 0.18 +/- 0.12 after TACE, respectively, with significant differences (P < 0.05). Using MRS can evaluate the early metabolic responses of HCC to TACE.