BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is 3rd leading cause of cancer in Korea and the prognosis for HCC patients is poor. For assessing the present treatment outcome, this study analyzed the three-year survival rate (3-YSR) and the prognostic factors for patients with HCC in Korea. METHODS: Between November 2000 and December 2003, 905 patients with HCC who were diagnosed and treated at the National Cancer Center Korea were enrolled in this study. The clinical variables, tumor characteristics and survival periods were analyzed. RESULTS: The mean age of all patients was 56.2+/-10.3 years and 732 (80.9%) patients were male (M:F=4.2:1). 508 (56.1%) patients died and the median survival period was 15.3 months. The overall 3-YSR of the patients with modified UICC stage I, II, III, IVa and IVb were 67.4%, 65.2%, 30.7%, 9.0% and 5.0%, respectively. The modified UICC stage could not differentiate stage I from II, and stage IVa from IVb, on the 3-YSR. The 3-YSR of the Child-Pugh class A patients with modified UICC stage I or II was 85.4% by surgical resection and it was 69.6% by transcatheter chemoembolization (TACE), respectively (P= .461), and those values for patients with stage III were 49.2% and 36.8%, respectively (P=.081). As compared with systemic chemotherapy or conservative therapy, TACE increased the survival rate more for the Child-Pugh class A patients with stage IV. The independent prognostic factors were serum AFP, portal vein thrombosis, the Child-Pugh classification and the stage of HCC. CONCLUSIONS: This follow-up study will be helpful in assessing the results of treatments for HCC and it will provide data for the establishment of a more effective treatment strategy.
Survival Rate ; Survival Analysis ; Neoplasm Staging ; Middle Aged ; Male ; Liver Neoplasms/*mortality/pathology/physiopathology/therapy ; Humans ; Female ; Carcinoma, Hepatocellular/*mortality/pathology/physiopathology/therapy ; Aged

OBJECTIVETo investigate the anti-proliferative effects of curcumol, an herbal extract from curcuma, in human hepatocarcinoma HepG2 cells, and its possible molecular mechanism.

METHODThe effects of curcumol on human hepatocarcinoma cells were assessed in vitro. Proliferation of HepG2 cells treated with various concentration (2.5-10 mg x L(-1)) of curcumol was determined using the MTT assay and the distribution of cell cycle of HepG2 cells was analyzed using the FCM technique. Expression of 14 cell cycle regulation-related genes were assessed by TaqMan real-time polymerase chain reaction (RT-PCR) method and Western blot.

RESULTCurcumol significantly inhibited the proliferation of HepG2 cells and induced G1 phase arrest in a dose- and time-dependent manner. The mRNA levels of pRB1, cyclin D1, CDK2, CDK8 and p27KIP1 were elevated, while cyclin A1 decreased, in both of the low (25 mg x L(-1)) and the high dose (100 mg x L(-1)) treatment of curcumol. There were no significant changes in the expression of either cyclin E1 or CDK4. The expression of p53 and its target genes p21WAF1 and Wip1 protein were increased.

CONCLUSIONCurcumol can inhibit the proliferation of HepG2 cells in vitro and induce G1 arrest of cell cycle through mechanisms activating p53 and pRB pathways that involve genes of cyclin A1, CDK2, CDK8, p21WAF1 and p27KIP1.

Carcinoma, Hepatocellular ; drug therapy ; physiopathology ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; physiopathology ; Sesquiterpenes ; pharmacology

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan(R)) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.
Antiviral Agents/therapeutic use ; Carcinoma, Hepatocellular/epidemiology/physiopathology ; Chronic Disease ; *Elasticity Imaging Techniques ; Hepatitis B/drug therapy/physiopathology ; Hepatitis C/drug therapy/physiopathology ; Humans ; Liver Cirrhosis/*diagnosis/ultrasonography ; Liver Neoplasms/epidemiology/physiopathology ; Recurrence

OBJECTIVE: We wanted to investigate the prevalence and causative factors of extrahepatic arterial blood supply to hepatocellular carcinoma (HCC) at its initial presentation and during chemoembolization. MATERIALS AND METHODS: Between February 1998 and April 2000, consecutive 479 patients with newly diagnosed HCC were prospectively enrolled into this study. A total of 1629 sessions of transcatheter arterial chemoembolization (TACE) were performed in these patients (range: 1-15 sessions; mean: 3.4 sessions) until April 2004. For each TACE procedure, we determined the potential extrahepatic collateral arteries (ExCAs) depending on the location of the tumor, and we performed selective angiography of all suspected collaterals that could supply the tumor. The prevalence of ExCAs and the causative factors were analyzed. RESULTS: At initial presentation, 82 (17%) of these 479 patients showed 108 ExCAs supplying tumors. Univariate analysis showed that tumor size (p < 0.01), patient age (p = 0.02), a surface location (p < 0.01), and a bare area location (p < 0.01) were significantly associated with the presence of ExCAs. Multiple logistic regression analysis showed that only tumor size was predictive of ExCA formation (p < 0.01, odds ratio = 1.737, confidence interval: 1.533 to 1.969). During repeated TACE sessions, 97 additional ExCAs were detected in 70 (14%) patients. The cumulative probability of ExCAs in patients with a large tumor (> or = 5 cm) was significantly higher than that for those patients with a small tumor (< 5 cm) (p < 0.01). CONCLUSION: The presence of ExCAs supplying HCC is rather common, and the tumor size is a significant causative factor for the development of these collateral arteries.
Neovascularization, Pathologic/*etiology/physiopathology/radiography ; Middle Aged ; Male ; Logistic Models ; Liver Neoplasms/physiopathology/*therapy ; Humans ; Female ; Collateral Circulation/drug effects/physiology ; Chemoembolization, Therapeutic/*methods ; Carcinoma, Hepatocellular/physiopathology/*therapy ; Angiography ; Aged, 80 and over ; Aged ; Adult

Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Hepatocellular/drug therapy/physiopathology/*radiography ; Female ; Humans ; Liver Neoplasms/drug therapy/physiopathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Niacinamide/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/*therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo investigate intratumoral microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and to evaluate their significance.

METHODSMVD and expression of VEGF and BFGF in cancerous tissues were examined in forty specimens resected from patients with HCC using immunohistochemical methods. Among these patients, 20 patients received 1 to 7 treatments of TACE prior to II-phase surgical resection (TACE group), the other 20 patients were treated by operation without receiving any other treatment preoperatively (surgical group). There was no significant difference in clinical features between the two groups. MVD was assessed by counting immunostained endothelial cells within a certain area, and staining intensity of VEGF was assessed quantitatively with computer-assisted image analyzer. The expression of BFGF was determined by cell-positive or cell-negative.

RESULTSThe average MVD was 130.51 75.5 in TACE group and 152.35 58.80 in surgical group. There was no significant difference between the two groups (t=-1.021, P=0.341). Staining intensity of VEGF was 645.60 543.27 in TACE group, higher than in surgical group (158.28 188.48, t=281, P<0.001). BFGF-positive rate was 35% in TACE group and 40% in surgical group. There was no significant difference (x(2)=0.107, P=0.744).

CONCLUSIONSThe results indicate that survived cancerous tissue has rich vascularity and the expression of VEGF of the cancerous cells can be enhanced by TACE which may play an important role in reestablishment of blood supply to tumor after TACE.

Carcinoma, Hepatocellular ; metabolism ; pathology ; physiopathology ; therapy ; Catheterization ; Embolization, Therapeutic ; Endothelial Growth Factors ; biosynthesis ; Fibroblast Growth Factor 2 ; biosynthesis ; Humans ; Liver Neoplasms ; metabolism ; pathology ; physiopathology ; therapy ; Lymphokines ; biosynthesis ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVETo examine apoptosis of SMMC-7721 hepatocarcinoma cells induced by total flavonoids of Oxytropis falcata (TFOF) and its preliminary mechanism.

METHODSMMC-7721 cells were treated for 24 h with TFOF in different concentrations. Inhibition on proliferation of SMMC-7721 cells was assessed by MTT assay. The morphology of treated SMMC-7721 cells was observed by optical microscope. Effect of TFOF on the nuclear morphology of cells was analyzed using Hoechst 33258 staining by fluorescence microscope. Annexin V-FITC/PI staining and flow cytometric measurement were used for investigating the effect of TFOF on induction of apoptosis in SMMC-7721 cells and cell cycle analysis.

RESULTThe results of MTT assay showed that TFOF could induce cytotoxicity in SMMC-7721 cells in a dose-dependent manner. Hoechst 33258 staining analysis indicated that TFOF caused typical characteristics of apoptotic programmed cell death, such as cell shrinkage, apoptotic body formation etc. Flow cytometric analysis demonstrated that TFOF caused a dose-dependent apoptosis of SMMC-7721 cells and arrested cell cycle in G1 phase.

CONCLUSIONIt suggested that TFOF inhibit proliferation of SMMC-7721 cells by inducing apoptosis of the cells and arresting cell cycle in G1 phase.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; physiopathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Liver Neoplasms ; drug therapy ; physiopathology ; Oxytropis ; chemistry

OBJECTIVETo study the inhibitory effects of celecoxib, a cyclooxygenase-2 inhibitor, on the proliferation of hepatocellular carcinoma cells.

METHODSThe in vitro inhibitory effects of celecoxib at different concentrations and for different treatment time lengths on human liver cancer cell line SMMC-7,721 were observed with MTT assay, and flow cytometry was performed to detect the cell cycle changes. The in vivo tumor inhibition effect of celecoxib was evaluated in Kunming mice bearing transplanted tumor derived from liver cancer cell line H22 transplantation.

RESULTCelecoxib significantly inhibited the in vitro growth of human liver cancer cell line SMMC-7721 in a time- and dose-dependent manner. A 36-hour celecoxib treatment (40 micromol/L) resulted in decreased SMMC-7721 cell proliferation and an increase of the cell percentage in G1 phase from 44.7% to 49.9% with decreased cell percentage in S and G(2)/M phases from 55.4% to 50.1%. In the mice bearing H22 transplanted tumor, celecoxib showed significant inhibitory effect on the growth and local metastasis of the transplanted tumor.

CONCLUSIONCelecoxib can inhibit the proliferation of different liver cancer cell lines both in vitro and in vivo, and therefore may serve as an important candidate drug for prevention and treatment of hepatocellular carcinoma.

Animals ; Carcinoma, Hepatocellular ; drug therapy ; physiopathology ; Celecoxib ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; physiopathology ; Mice ; Neoplasm Transplantation ; Pyrazoles ; pharmacology ; therapeutic use ; Sulfonamides ; pharmacology ; therapeutic use

OBJECTIVETo compare the efficacies of portal vein stenting and transcatheter arterial chemoembolization (TACE) combined therapy performed with or without endovascular implantation of iodine-125 (125I) seeds strand in patients with hepatocellular carcinoma (HCC) and main portal vein tumor thrombus (MPVTT).

METHODSOne-hundred-and-six patients with HCC complicated by MPVTT who were treated with portal vein stents and TACE, either with (Group A, n=56) or without (Group B, n=50) endovascular implantation of 125I seeds strand, between July 2005 and April 2011, were retrospectively analyzed. Overall survival, stent patency, and procedure-related adverse events were compared between the two groups.

RESULTSThe technical success rate was 100% for placement of 125I seeds strands and stents in the obstructed main portal vein. No serious procedure-related adverse events were recorded. Group A had significantly higher median survival (335 days vs. group B: 146 days; P=0.001, hazard ratio (HR)=2.244). Additionally, group A had significantly higher median stent patency (400 days vs. group B: 190 days; P=0.005, HR=2.479).

CONCLUSIONThe combination therapeutic strategy of portal vein stenting and TACE with endovascular implantation of 125I seeds strands improves the survival of HCC patients with MPVTT complication.

Carcinoma, Hepatocellular ; complications ; therapy ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Female ; Humans ; Iodine Radioisotopes ; administration & dosage ; therapeutic use ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Portal Vein ; physiopathology ; surgery ; Retrospective Studies ; Stents ; Treatment Outcome ; Venous Thrombosis ; complications ; therapy

OBJECTIVETo explore the surgical risk, perioperative outcome and the response of patients with hepatocellular carcinoma (HCC) after preoperative transcatheter arterial chemoembolization (TACE).

METHODSA retrospective case-matched study was conducted to compare the characteristics and corresponding measures of patients in the preoperative TACE group and the control group without TACE. A total of 105 patients (82 patients with selective and dynamic region-specific vascular occlusion to perform hepatectomy for patients with complex hepatocellular carcinoma) was included in this study, in which 35 patients underwent TACE therapy, and a 1:2 matched control group of 70 subjects.

RESULTSThe patients of preoperative TACE therapy group had a higher level of γ-glutamyl transpeptidase before operation (119.52±98.83) U/L vs. (67.39±61.25) U/L (P=0.040). The operation time was longer in the TACE group than that in the control group but with a non-significant difference (232.60±95.43) min vs. (218.70±75.13) min (P=0.052). The postoperative recovery of liver function and severe complications in the preoperative TACE group were similar to that in the control group (P>0.05). There were no massive hemorrhage, biliary fistula and 30-d death neither in the treatment group and matched control group.

CONCLUSIONSPreoperative TACE therapy has certain negative effect on liver function. It is preferable to use selective and dynamic region-specific vascular occlusion technique during hepatectomy and combine with reasonable perioperative treatment for this group of patients, that can ensure safety of patients and promote their rapid recovery.

Carcinoma, Hepatocellular ; blood supply ; therapy ; Case-Control Studies ; Chemoembolization, Therapeutic ; adverse effects ; methods ; Hepatectomy ; methods ; Humans ; Liver ; physiopathology ; Liver Neoplasms ; blood supply ; therapy ; Operative Time ; Preoperative Period ; Recovery of Function ; Retrospective Studies ; gamma-Glutamyltransferase ; analysis