Carcinoma, Hepatocellular ; blood supply ; therapy ; Chemoembolization, Therapeutic ; Humans ; Liver Neoplasms ; blood supply ; therapy ; Tomography, X-Ray Computed

Carcinoma, Hepatocellular ; blood ; blood supply ; Endothelin-1 ; blood ; Female ; Humans ; Liver Neoplasms ; blood ; blood supply ; Male ; Neovascularization, Pathologic ; metabolism ; Nitric Oxide ; blood ; Vascular Endothelial Growth Factors ; blood

OBJECTIVETo study the clinical value of total hemihepatic vascular exclusion (THHVE) in liver resection for patients with hepatocellular carcinoma (HCC) and impaired liver function.

METHODSThe data of 70 patients who underwent liver resection for HCC with impaired liver function between January 2009 and October 2011 were analyzed retrospectively. THHVE was applied in 38 patients (THHVE group), Pringle maneuver in 25 patients (Pringle group) and no vascular occlusion in 7 patients. In the THHVE group, 36 patients were male, 2 were female, average age was (54 ± 9) years. And in Pringle group, 23 patients were male, 2 were female, average age was (53 ± 10) years. Total intraoperative blood loss, blood transfusion rate, clamping time, postoperative complication rate, postoperative hospital stay and postoperative liver function were compared between the THHVE and Pringle group.

RESULTSTotal blood loss ((317 ± 186) ml vs. (506 ± 274) ml, t = -3.025, P = 0.004) and transfusion rate (10.5% vs. 32.0%, χ(2) = 4.509, P = 0.034) were significantly lower in the THHVE group than in the Pringle group. Although the clamping time was longer ((21 ± 5) minutes vs. (17 ± 5) minutes, t = 3.209, P = 0.002), the total bilirubin levels on postoperative day 3 and 7 and ALT levels on postoperative day 1, 3, 7 were significantly lower in the THHVE group than in the Pringle group, and the pre-albumin level on postoperative day 7 was higher in the THHVE group than in the Pringle group. Total complication rate (26.3% vs. 52.0%, χ(2) = 4.291, P = 0.038) and major complication rate (7.9% vs. 28.0%, χ(2) = 4.565, P = 0.033) were lower in the THHVE group than in the Pringle group. And postoperative hospital stay duration was shorter in the THHVE group than in the Pringle group ((14.0 ± 2.6) d vs. (16.4 ± 4.0) d, t = -2.625, P = 0.012).

CONCLUSIONSTHHVE is a safe and effective technique in liver resection for patients with HCC and impaired liver function. It is associated with less blood loss, lower transfusion requirements, better postoperative liver function recovery, lower postoperative complication rate and shorter postoperative hospital stay.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; surgery ; Female ; Hepatectomy ; methods ; Humans ; Liver ; blood supply ; physiopathology ; Liver Neoplasms ; blood supply ; surgery ; Male ; Middle Aged ; Retrospective Studies

Hepatocellular carcinoma (HCC) remains one of the major public health problems throughout the world. Although originally associated with tumorigenic processes, liver angiogenesis has also been observed in the context of different liver inflammatory, fibrotic, and ischemic conditions. Here we investigate the fractal dimension as a quantitator of non-Euclidean two-dimensional vascular geometry in a series of paired specimens of primary HCC and surrounding non-tumoral tissue, and discuss why this parameter might provide additional information regarding cancer behavior. The application of fractal geometry to the measurement of liver vascularity and the availability of a computer-aided quantitative method can eliminate errors in visual interpretation, and make it possible to obtain closer-to-reality numerals that are compulsory for any measurement process.
Animals ; Biomarkers ; Biomarkers, Tumor ; Biomechanical Phenomena ; Carcinoma, Hepatocellular ; blood supply ; pathology ; Humans ; Liver ; blood supply ; Liver Neoplasms ; blood supply ; pathology ; Neovascularization, Pathologic ; pathology

OBJECTIVETo investigate the relationship between UNC5b gene expression and angiogenesis of hepatocellular carcinoma (HCC).

METHODSIn situ hybridization was performed to detect the expression of UNC5b mRNA in HCC samples, paracarcinomatous liver tissues samples and normal liver samples. The relationship between UNC5b mRNA expression and the HCC clinicopathological features were also analyzed. Human umbilical artery endothelial cells were isolated and stimulated with HCC tissues homogenate, vascular endothelial growth factor and basic fibroblast growth factor. Then RT-PCR was employed to detect the expression of UNC5b mRNA in normal HUAEC as well as activated HUAEC.

RESULTSIn situ hybridization results showed that UNC5b mRNA expression was detected majorly in endothelial cells of all normal liver tissues, and partial PCLTs but was weak or even undetectable in endothelial cells of the corresponding HCC tissues. The expression levels of UNC5b gene in PCLTs were significantly correlated with capsular formation of HCC. Furthermore, RT-PCR results showed that the expression levels of UNC5b mRNA in activated HUAEC were significantly higher than those in normal HUAEC.

CONCLUSIONSDown-regulation of UNC5b gene expression is related to angiogenesis of HCC, which may be associated with the progression of HCC.

Carcinoma, Hepatocellular ; blood supply ; genetics ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; blood supply ; genetics ; Neovascularization, Pathologic ; genetics ; RNA, Messenger ; genetics ; Receptors, Cell Surface ; genetics

OBJECTIVETo explore the angiogenesis and its maturation of hepatocellular carcinoma (HCC) and its correlation with deoxyhemoglobin parameters R2 * and T2 * values and the lesion/muscle R2*, T2 * ratio by using noninvasive magnetic resonance imaging (MRI).

METHODST2 *, R2 * values and the lesion/muscle R2 *, T2 * ratio in tumor periphery and center were calculated via series T2 * images in a total of 31 patients with surgically and pathologically confirmed HCC. After surgery, all sections were obtained from the specimen periphery in accordance with the MR analyzed areas. Continuous slices of each lesion were stained with hematoxylin-eosin (HE), and immunohistochemical staining was performed in vascular endothelial growth factor (VEGF), Flk-1, proliferating cell nuclear antigen (PCNA), CD34, and alpha smooth muscle actin (SMA). The expressions of VEGF, Flk-1, and PCNA index (PI) were evaluated. According to CD34 and SMA, some vascular parameters, including number, mean vessel area, total vessel area, circumference, diameter, distance between adjacent vessels, and variety index of microvessel and mature vessel, were calculated with a computed analysis system. The amounts of arterioles and veinlets, mature vessel index, and mean perfused fraction (mPF) were also recorded. All vessel parameters were compared with the calculated values of MRI.

RESULTSR2 * value or lesion/muscle R2 * ratio decreased and T2 * value or the lesion/muscle T2 * ratio increased in HCC when compared with hepatic parenchyma (P < 0.05); however, those values between lesion periphery and center and among different pathological grades were not significantly different (P > 0.05). T2 * value and the lesion/muscle T2 * ratio significantly decreased when the expression of VEGF was positive (P < 0.05). T2 * value was negatively correlated with microvessel amount (P = 0.047, r = - 0.639), while T2 * value and the lesion/muscle T2 * ratio were positively correlated with mPF (P = 0.040, r = 0.655; P = 0.048, r = 0.40, respectively). R2 * value was also positively correlated with mean area (P = 0.028, r = 0.688), total area (P = 0.021, r = 0.712) or circumference (P = 0.037, r = 0.663) of microvessel, and negatively correlated with mPF (P = 0.024, r = - 0.702). Meanwhile, the lesion/muscle R2 * ratio was positively correlated with mean area (P = 0.043, r = 0.647) and circumference (P = 0.026, r = 0.694) of microvessels.

CONCLUSIONR2 * or T2 * value may be influenced by the variation of deoxyhemoglobin caused by the heterogeneity of angiogenesis.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; Female ; Hemoglobins ; Humans ; Liver ; pathology ; Liver Neoplasms ; blood supply ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Neovascularization, Pathologic

OBJECTIVETo explore the relationship between the expression of cyclooxygenase-2 (COX-2) and angiogenesis in hepatocellular carcinoma.

METHODSForty Wistar rats were divided into two groups: a model group (30 rats) and a normal group (10 rats). Hepatocellular carcinoma was induced with 0.01% diethylnitrosamine (DEN) in the model group rats. The rats were sacrificed in batches at the 6th, 12th and 18th week of the experiment. Histological sections of liver tissues were made using routine methods. The expressions of COX-2, VEGF, VEGFR-2/KDR, and MMP-2 protein in the liver tissues were evaluated using immunohistochemical methods.

RESULTSIn liver sections from the model group there were marked pathological changes (steatosis, cell infiltration, cirrhosis and liver cancer). The expressions of VEGF, VEGFR-2/KDR, and MMP-2 in those liver tissues were remarkably increased during the hepatocellular carcinogenesis. Microvessel density (MVD) was also obviously raised during the process of the cancer development. There was a direct correlation between the MVD and VEGF/KDR/MMP-2 (r=0.858, 0.788, 0.684, respectively; all P less than 0.01). There was also a direct correlation between the COX-2 and VEGF/KDR/MMP-2/MVD (r=0.771, 0.599, 0.690, 0.788, respectively; all P < 0.01).

CONCLUSIONCOX-2 can promote tumor angiogenesis during rat hepatocellular carcinogenesis. This may be one of the mechanisms in which COX-2 promotes carcinomas.

Animals ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Cyclooxygenase 2 ; biosynthesis ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Neovascularization, Pathologic ; Rats ; Rats, Wistar

OBJECTIVETo explore the roles of vascular endothelial growth factor (VEGF) in microvessel angiogenesis, development and metastasis of hepatocellular carcinoma (HCC).

METHODSThe cellular distributions of VEGF expression and microvascular density (MVD) in 36 HCCs were investigated, and the levels of total RNA and VEGF were detected in HCCs, Para cancerous, and distal cancerous tissues, respectively.

RESULTSThe incidence of VEGF was 63.9% in 36 cases of HCCs, 78.3% in non-encapsulated HCCs, and 90.9% in HCCs with extrahepatic metastasis, respectively. The VEGF expression was tightly correlated with MVD (t=4.49, P<0.01). No significant difference was found between VEGF or MVD and tumor diameter or differentiation degree. The level of total RNA in HCCs was lower but the VEGF level significantly higher than those of Para cancerous or distal cancerous ones (q=6.10, P<0.01).

CONCLUSIONThe present data suggest that VEGF over expression and MVD abnormality are useful markers for vascular invasion and metastasis of liver tumors.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; pathology ; Female ; Humans ; Liver Neoplasms ; blood supply ; pathology ; Male ; Middle Aged ; Vascular Endothelial Growth Factor A ; analysis ; physiology

Carcinoma, Hepatocellular ; blood supply ; diagnostic imaging ; Humans ; Liver Neoplasms ; blood supply ; diagnostic imaging ; Microvessels ; diagnostic imaging ; Neovascularization, Pathologic ; diagnostic imaging ; Tomography, X-Ray Computed ; methods

OBJECTIVETo explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM.

METHODSNinety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC.

RESULTS12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01).

CONCLUSIONVM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology