OBJECTIVEThe purpose of this study was to compare MRI findings of solitary hypovascular hepatic nodules, benign and malignant, to identify their MRI characteristics.

METHODSWe retrospectively assessed solitary hypovascular hepatic nodules ≤ 3 cm in 135 patients, among them there were 55 malignant nodules [29 peripheral nodules of cholangiocarcinoma, PCC, and 26 hepatic metastases, HM] and 80 benign nodules [48 inflammatory myofibroblastic tumors, IMT, and 32 hepatic hemangioma, HG], proved by surgery, biopsy or follow-up imaging. Unenhanced and dynamic enhanced MRI findings of the 135 patients were analyzed retrospectively. Statistical analysis included Chi-square test or Fisher's exact test, and receiver operating characteristic (ROC) curve.

RESULTSThere was significant difference (P < 0.05) between the malignant group and benign group in terms of location, margin, T2WI signal intensity, heterogeneity or homogeneity of the nodule, and type and degree of peritumoral and intratumoral enhancement. Area under the curve at the first film reading by three radiologists was 0.678 ± 0.047, 0.920 ± 0.022 at the second time, and there was a significant difference (Z = 5.22, P < 0.05) between them.

CONCLUSIONSOur data indicated that solitary hypovascular hepatic nodules show unenhanced and dynamic enhanced MRI features. Therefore, MR imaging combined with clinical and biochemical data does provide reliable information for a proper diagnosis of such hepatic lesions and differentiation of malignant from benign nodules.

Cholangiocarcinoma ; pathology ; Diagnosis, Differential ; Hemangioma ; pathology ; Humans ; Liver ; blood supply ; pathology ; Liver Neoplasms ; blood supply ; pathology ; Magnetic Resonance Imaging ; ROC Curve ; Retrospective Studies

Carcinoma, Hepatocellular ; diagnosis ; pathology ; DNA ; blood ; DNA Methylation ; Humans ; Liver Neoplasms ; diagnosis ; pathology ; Polymerase Chain Reaction ; methods

We report an extremely rare case of a diffuse hepatic hemangiomatosis without extrahepatic involvement in an adult. The imaging findings of this tumor were similar to those of a hepatic hemangioma and included contrast enhancement with a centripetal filling pattern of the entire hepatic tumor on the delayed phase of a dynamic CT and inhomogeneous diffuse uptake of the entire tumor on blood-pool images obtained five hours later on a 99mTc-labeled red blood cell scan. Despite its rarity, diffuse hepatic hemangiomatosis can be suggested in adult patients with diffusely involved hepatic tumors showing the radiological findings of a hepatic hemangioma.
Adult ; Female ; Gated Blood-Pool Imaging ; Hemangioma/*diagnosis/pathology/ultrasonography ; Humans ; Liver Neoplasms/*diagnosis/pathology/ultrasonography ; Tomography, X-Ray Computed

OBJECTIVEProtein induced by vitamin K absence or antagonist II (PIVKA II), also called des-gamma carboxy prothrombin (DCP), is a sensitive marker for the diagnosis of hepatocellular carcinoma (HCC), in Japan and the United States since the sensitive kits were available (1998). PIVKA II is not used in clinical diagnosis in China so far. The aim of this study was to assess the diagnostic value of PIVKA II in Chinese patients with HCC.

METHODSSerum PIVKA II and alpha-fetoprotein (AFP) levels were determined in 60 patients with HCC and 30 patients with cirrhosis not carrying HCC.

RESULTSThe mean serum concentration of PIVKA II in HCC patients (784.3 +/- 1364.1 mean +/- s) was higher than that in cirrhosis patients (16.1 +/- 31.7); this difference was highly significant (P < 0.0001). When the cutoff level of 40 mAU/ml was used as the level of discriminating HCC from cirrhosis, 51.7% of patients (31/60) with HCC had PIVKA II values above this level (sensitivity). Only 4 patients with cirrhosis had such high PIVKA II levels. Thus, the specificity of this test was 86.7% (26/30). Total accuracy was 62.2% [(31 + 26)/(60 + 30)]. Seven of 19 small HCCs (36.84%) had PIVKA II values above the cutoff level. Concentrations of AFP above 20 ng/ml were observed in 34 of 60 patients with HCC (56.7%) and in 11 patients with cirrhosis (36.7%). Eleven of 26 patients with HCC (46.2%) without increased AFP had concentrations of PIVKA II greater than 40 mAU/ml. No significant correlation was found between serum levels of AFP and PIVKA II that were measured in 60 HCC patients (rs = 0.101, P = 0.247). Combining the information from PIVKA II and AFP showed an increase of approximately 21.6% over AFP and 26.7% over PIVKA II alone. For small HCC patients, combining the information from PIVKA II and AFP showed an increase of approximately 15.8% over AFP alone and 21.1% over PIVKA II alone.

CONCLUSIONPIVKA II is a useful early diagnostic marker for HCC and may be more sensitive when combined with AFP in Chinese patients.

Adult ; Aged ; Aged, 80 and over ; Biomarkers ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; diagnosis ; pathology ; Female ; Humans ; Liver Cirrhosis ; blood ; Liver Neoplasms ; blood ; diagnosis ; pathology ; Male ; Middle Aged ; Protein Precursors ; blood ; Prothrombin ; alpha-Fetoproteins ; analysis

BACKGROUND/AIMS: The extent of hepatic fibrosis is important in chronic liver disease. Liver biopsy is essential for diagnosis of fibrosis. However, biopsy is invasive and may not represent the whole liver state. Serum hyaluronic acid (HA), a major component of connective tissues, was introduced as a useful non-invasive index of hepatic fibrosis. The aim of this study was to evaluate the relationship among HA, the degree of fibrosis, several hematologic and biochemical parameters in patients with chronic liver diseases or post state liver transplantation (PSLT). METHODS: Total 102 cases were divided into 4 groups: 57 chronic hepatitis (CH), 12 cirrhosis, 21 hepatocellular carcinoma (HCC), 12 PSLT. HA was measured by enzyme-linked binding protein assay and evaluated in relation the degree of fibrosis, several hematologic and biochemical parameters. RESULTS: Among four groups, HCC showed the highest HA and HA of HCC significantly higher than that of CH. The degree of fibrosis were correlated with HA. HA was correlated with age, platelet count and albumin but, not with ALT and PT. There is no significant relation between HA and the presence of acute rejection in liver transplantation. CONCLUSIONS: In chronic liver diseases, HA is a useful non-invasive index of hepatic fibrosis and disease severity.
Adolescent ; Adult ; Aged ; Biological Markers/blood ; Carcinoma, Hepatocellular/complications ; Chronic Disease ; Female ; Graft Rejection/diagnosis ; Hepatitis/complications ; Humans ; Hyaluronic Acid/*blood ; Liver/pathology ; Liver Cirrhosis/complications/*diagnosis/pathology ; Liver Neoplasms/complications ; Liver Transplantation ; Male ; Middle Aged

OBJECTIVETo investigate the dynamic expressions of TGF-beta 1 and TGF-beta 1 mRNA at different stages of hepatocellular carcinoma (HCC) development and their use in clinical diagnosis.

METHODSHepatoma models were developed with 2-FAA using male Sprague-Dawley (SD) rats. Morphological changes of the rat liver histological preparations (H and E stained) were studied. The fragment of TGF-beta 1 gene obtained was amplified by nested RT-PCR. Dynamic change of TGF-beta 1 level was quantitatively analyzed by ELISA. The distribution of TGF-beta 1 in the cells and its gene expression were detected in human HCC tissues.

RESULTSThe progressive increases of hepatic TGF-beta 1 and TGF-beta 1 mRNA were observed in rat hepatocytes which progressed from granular degeneration, atypical hyperplasia and finally to HCC development induced by 2-FAA. The expression levels in HCC tissues were significantly higher than those in the normal and degenerative ones. TGF-beta 1 was shown in rat hepatocytes by immunohistochemistry. Plasma TGF-beta 1 was detected in 89.5% of all the patients with HCC, but it was detected in 93.3% of them who had an AFP less than 400 microg/L. TGF-beta 1 mRNA showed a stronger expression in HCC tissues. TGF-beta 1 mRNA was found in peripheral blood mononuclear cells from all HCC patients with extrahepatic metastasis.

CONCLUSIONTGF-beta 1 may participate in hepatocyte canceration. The overexpression of TGF-beta 1 and TGF-beta 1 mRNA could be useful markers for early diagnosis and predicting prognosis of HCC.

Adult ; Aged ; Animals ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; diagnosis ; pathology ; Female ; Humans ; Liver Neoplasms, Experimental ; blood ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; prevention & control ; Prognosis ; RNA, Messenger ; blood ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; blood

OBJECTIVETo assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC).

METHODSA total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed.

RESULTSs CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05).

CONCLUSIONPositive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.

Carcinoma, Hepatocellular ; blood ; diagnosis ; Case-Control Studies ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Portal Vein ; pathology ; Prognosis

Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 mul of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC.
Adult ; Aged ; Biomarkers, Tumor/blood/genetics ; Carcinoma, Hepatocellular/blood/diagnosis/*genetics ; Exosomes/genetics ; Female ; Gene Expression Profiling ; Humans ; Liver/pathology ; Liver Neoplasms/blood/diagnosis/*genetics ; Male ; MicroRNAs/blood/*genetics ; Middle Aged

OBJECTIVETo establish a serum protein fingerprint model for prediction of liver metastasis from colorectal cancer by SELDI-TOF-MS analysis, and to determine the differentiatial proteins associated with the metastatic liver cancers.

METHODSData were collected from the Department of General Surgery in Zhongshan Hospital. A group of patients with colorectal cancer (CRC) without liver metastasis (n = 36) and another group with liver metastasis (n = 36) were included in this study. Serum samples were collected from peripheral venous blood before operation. Special serum protein or peptide fingerprint was determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The obtained data were analyzed by Biomarker Wizard software to screen the serum protein markers discriminating colorectal cancer patients with and without liver metastasis. A serum protein fingerprint model was established. This model was blindly verified in of CRC patients with and 44 cases without liver metastasis.

RESULTSComparing the characteristic proteins in those two groups of patients, 10 specific protein peaks were identified with statistical significance (P < 0.05). According to m/z growing from small to large, they were: 2398, 2814, 4084, 4289, 4465, 6422, 6619, 11 482, 11 649 and 13 714. The predictive model had a sensitivity of 91.7% and a specificity of 97.2%. The validation showed a sensitivity of 75.0% and a specificity of 81.8%.

CONCLUSIONA predictive model based on differentiatial serum protein fingerprint with high sensitivity and specificity has been successfully established. It should be a very useful tool in detection and diagnosis of liver metastasis in colorectal cancer patients.

Aged ; Biomarkers, Tumor ; blood ; Blood Proteins ; analysis ; Colorectal Neoplasms ; blood ; pathology ; Female ; Humans ; Liver Neoplasms ; blood ; diagnosis ; secondary ; Male ; Middle Aged ; Neoplasm Proteins ; blood ; Peptide Mapping ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

BACKGROUND/AIMS: Serum alpha-fetoprotein (AFP) is frequently used for the diagnosis of hepatocellular carcinoma (HCC). Most available data concerning AFP came from studies of patients with chronic hepatitis B or mixed etiologies. Studies concerning the diagnostic value of AFP for HCV-related liver cirrhosis (LC) are limited. We evaluated the factors influencing AFP elevation in the absence of HCC and analyzed the diagnostic value of serum AFP in HCC surveillance of HCV-related LC patients. METHODS: We enrolled 55 patients of HCV-related LC with HCC and 62 patients without HCC as a case-control study were analyzed. The sensitivity and specificity were calculated and the clinical and biochemical factors influencing serum AFP levels. RESULTS: The sensitivities and specificities of serum AFP for the detection of HCC in HCV-related LC were 72.7% and 59.7% for AFP> or =20 ng/mL, and 47.3% and 92.5% for AFP> or =100 ng/mL, respectively. Elevated serum AST was independently associated with elevated serum AFP level in HCV-related LC. In cases of AST< or =2 x upper limit of normal (ULN), the specificity of AFP> or =100 ng/mL for the diagnosis of HCC was 100%. However, in case of AST>2 x ULN, the specificity was 85.0% for AFP> or =100 ng/mL and 95.0% for AFP> or =200 ng/mL. CONCLUSIONS: Serum AST levels influence serum AFP level in HCV-related LC. In cases of AST< or =2 x ULN, AFP greater than 100 ng/mL highly indicates HCC in HCV-related LC, but not in case of AST>2 x ULN.
Aged ; Carcinoma, Hepatocellular/complications/*diagnosis/pathology ; Diagnosis, Differential ; Female ; Hepatitis C/*complications/immunology/virology ; Humans ; Liver Cirrhosis/*virology ; Liver Neoplasms/complications/*diagnosis/pathology ; Male ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Tumor Markers, Biological/*blood ; alpha-Fetoproteins/*analysis