Zhao-You Tang

Focal nodular hyperplasia (FNH) is a rare benign hepatic lesion, which is usually asymptomatic and solitary. Complications such as rupture and bleeding are extremely rare and only five cases have existed since 1975. We report a case of a 26‐year‐old woman with spontaneous rupture and hemorrhage of huge FNH presenting as acute abdomen. Different to previously recorded cases, this case was concomitant with multiple hepatic adenomas, which was misdiagnosed as rupture of hepatocellular carcinoma (HCC) with multiple intrahepatic spreading in another hospital. Our case highlights thepossible association between the size of FNH and the risk of rupture, and emphasizes the need to consider this in making treatment decisions. Although a conservative approach for asymptomatic FNH is well established, the potential for surgical intervention should always be considered, especially for large FNH. We recommend surgical resection of large FNH (>5 cm), symptomatic or not, rather than observation.

To explore in-vivo targeted imaging techniques for liver cancer detection using quantum dots (QDs) labeled probes in a nude mouse model of human hepatocellular carcinoma. Mercaptoacetic acid (MAA) modified QDs were linked to mouse-anti-human alpha-fetoprotein (AFP) monoclonal antibody to form water soluble QD-AFP-Ab probes, which were validated by spectra analyses and transmission electron microscope. The probes were firstly used to detect AFP antigen in human hepatocellular carcinoma cell line HCCLM6 in-vitro by one-step immunofluorescence method. In-vivo tumor xenografts and lung metastases models were then established by inoculation of HCCLM6 cells subcutaneously and into the tail vein of nude mice, respectively. QD-AFP-Ab probes were injected into the tail vein of the tumor bearing mice for live animal fluorescence imaging. Spectra of tumor and normal tissue were analyzed under illumination of Ti: sapphire laser. Serum levels of alanine amino transferase, aspartate amino transferase, blood urea nitrogen and creatinine were determined by conventional biochemical analysis. The liver, spleen, lungs, kidneys, heart and brain of the experimental nude mice were investigated for nonspecific uptake of the probes by confocal microscope. The QD-AFP-Ab probes had broad excitation spectra and high fluorescence intensity. They could specifically and efficiently recognize AFP antigen in hepatocellular carcinoma cells. Tumor targeting imaging using these probes were successful without any acute toxicity to the experimental animals. Spectra analysis showed that the probes per field were lower in the centre than the periphery of the tumor. Non-specific uptake of QD-AFP-Ab probes occurred mainly in the liver, spleen and lungs. QD-AFP-Ab probes have good optical properties and biocompatibility for in-vivo targeted imaging of hepatocellular carcinoma. Such approach promises to be highly desirable for molecular targeted research of liver cancer.

Background/Aims: Recurrence after resection of hepatocellular carcinoma (HCC) is a frequent event. This study evaluated the effect of postoperative interferon α (IFN α) treatment on recurrence and survival in patients with hepatitis B virus (HBV)-related HCC. Method: Two hundred and thirty six patients were randomized after resection into IFN α treatment (5 mu i.m. tiw for 18 months) and control groups. Treatment was terminated if recurrence was diagnosed, and recurrence was managed the same way in both groups. Statistical analysis was based on the method of intent-to-treat. Results: The two groups were comparable in all clinicopathological parameters. The median overall survival was 63.8 months in the treatment group and 38.8 months in the control group (P=0.0003); the median disease-free survival period was 31.2 versus 17.7 months (P=0.142). Fever, leucocytopenia, and thrombocytopenia were adverse effects in the treatment group, but were mostly manageable. Conclusions: IFN α treatment improved the overall survival of patients with HBV-related HCC after curative resection, probably by postponing recurrence.

Purpose: We demonstrated that chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma (HCC). This study assesses the value of circulating plasma DNA level and its allelic imbalance (AI) on chromosome 8p in the prediction of HCC prognosis. Methods: Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. The HCC and adjacent non-tumor liver tissues were obtained from surgical specimens. Plasma DNA was extracted and quantified. Two microsatellite markers on chromosome 8p, D8S258 and D8S264, were selected and used in the AI analysis. Results: The circulating plasma DNA level was found to closely associate with tumor size (P=0.008) and TNM stage (P=0.040), negatively associate with the 3-year disease-free survival (DFS) (P=0.017) and overall survival (OS) (P=0.001). AI at D8S258 in plasma DNA was significantly correlated with tumor differentiation (P=0.050), TNM stage (P=0.010), and vascular invasion (P=0.023), negatively correlated with the 3-year DFS (P=0.005) and OS (P=0.036). However, AI at D8S264 was only closely associated with 3-year DFS (P=0.014). Combined detection of AI at D8S258 and circulating plasma DNA level was independently associated with DFS (P=0.018) and OS (P=0.002) of patients with HCC. For patients with both AI at D8S258 and a higher level of plasma DNA, the 3-year DFS and 3-year OS rates were decreased remarkably (P=0.014 and 0.044). Conclusion: Combination of circulating plasma DNA level and AI at D8S258 might be an independent predictor for prognosis of HCC patients.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and ranks second in China. The prognosis of HCC remains dismal mainly because of its late diagnosis, especially in patients with coexisting chronic liver diseases. To identify serum biomarkers for HCC, sera from 20 healthy volunteers, 20 hepatitis B virus (HBV) infected patients and 20 HCC patients were selected for screening study and same number of sera into the same three groups were used for validation study. A strategy including sonication, albumin and immunoglobulin G (IgG) depletion and desalting was optimized for screening differentially expressed proteins of low abundance in serum. By 2‐DE image analysis and MALDI‐TOF‐MS/MS identification, eight proteins including heat‐shock protein 27 (HSP27), alpha‐fetoprotein (AFP), α‐1 antitrypsin, clusterin, caeruloplasmin, haptoglobin α2 chain, tranferrin and transthyretin were found significantly changed among the healthy, HBV and HCC groups. Further validation study by Western blot showed the detection of HSP27 in 90% HCC sera and two HBV sera, but in none of normal sera. Thus, 2‐DE based serum proteome analysis can be useful in the screening of serum biomarkers for HCC and HSP27 could aid in the diagnosis of HCC though further validation is needed.

Purpose: To investigate the effects on sensitivity to fluoropyrimidine and endothelial cell (EC) migration by transfection with thymidine phosphorylase (TP) cDNA to a hepatocellular carcinoma (HCC) cell line SMMC-7721. Methods: SMMC-7721 was transfected with pcDNA3.1/zeo (+) with human TP cDNA. TP mRNA expression was determined by RT–PCR. Sensitivity to fluoropyrimidine was determined by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Induction of EC migration was detected by Boyden chamber assay. Results: The construction of pcDNA3.1/zeo(+)-TP was verified by digestion with restriction endonuclease Apa1. When comparison was made between SMMC-7721 cell clone transfected with pcDNA3.1/zeo(+)-TP (S-TP) and control clone transfected with pcDNA3.1/zeo(+) (S-vector), we found that TP mRNA expression level was much higher in S-TP, being 2.09±0.16 vs 0.48±0.06 in S-vector (P50; 56.81±9.85 μmol/l vs 162.25±11.03 μmol/l, PP<0.01). Conclusion: Sensitivity to 5′-dFUrd could be enhanced by transfection with TP cDNA for SMMC-7721 cells. However, EC migration was also promoted at the same time. Therefore, transfection with TP alone might have no potential to enhance anti-tumoral effects of fluoropyrimidine in HCC.

AIM: To elucidate the molecular mechanisms of the inhibitory effects of IFN-α on tumor growth and metastasis in MHCC97 xenografts. METHODS: Three thousand international units per milliliter of IFN-α-treated and -untreated MHCC97 cells were enrolled for gene expression analysis using cDNA microarray. The mRNA levels of several differentially expressed genes in cDNA microarray were further identified by Northern blot and RT-PCR. RESULTS: A total of 190 differentially expressed genes including 151 IFN-α-repressed and 39 -stimulated genes or expressed sequence tags from 8 464 known human genes were found to be regulated by IFN-α in MHCC97. With a few exceptions, mRNA levels of the selected genes in RT-PCR and Northern blot were in good agreement with those in cDNA microarray. CONCLUSION: IFN-α might exert its complicated anti-tumor effects on MHCC97 xenografts by regulating the expression of functional genes involved in cell metabolism, proliferation, morphogenesis, angiogenesis, and signaling.

Curable outcome of unresectable hepatocellular carcinoma (HCC) was seldom encountered in the past. This study was designed to assess the role of downstaging followed by resection (downstaging-resection) in the improvement of prognosis of unresectable HCC. During the period of 1958-2003, a total of 1085 patients were verified surgically to be unresectable. Of these patients, 139 received downstaging-resection, with a rate of 84.2% for coexisting cirrhosis and a median tumor diameter of 11.1 cm. Resection of the right lobe, hepatic hilum and bilateral cancer accounted for 97.8% of the patients. Downstaging including hepatic artery ligation (HAL)+hepatic artery chemo-infusion (HAI) was performed in 65.5% of the patients, HAL+HAI+radiotherapy/radioimmunotherapy in 29.5%, and HAL or HAI alone in 5.0%. Retrospective analysis was made of the survival of patients with unresectable HCC, downstaging-resection rate and treatment pattern. In the 139 patients with downstaging-resection, the median interval between the first and second operation was 7.2 months and the 5-year survival rate calculated from the first operation was 48.7%. In the 1085 patients with unresectable HCC, their 5-year survival was 0% in the period of 1958-1973, 11.5% in the period of 1974-1988 and 19.3% in the period of 1989-2003. These figures were correlated with the increasing downstaging-resection rate from 0%, 9.0% to 15.6%, and the increasing percentage of triple or double combination treatment from 32.2%, 60.4% to 69.7%. The 5-year survival in triple treatment group was 24.9%, double treatment 15.2%, and single treatment only 10.9%, which was also correlated with the downstaging-resection rate of 34.6%, 16.2% and 1.8% respectively. Downstaging-resection plays a role in improving prognosis of unresectable HCC. Triple and double treatments provide a higher downstaging-resection rate and may result in better prognosis.

To investigate the function of the KIAA0008 gene, one of the leading genes in the signature associated with hepatocellular carcinoma (HCC) metastasis selected by cDNA microarray, and especially its possible roles in invasion and metastasis of hepatocellular carcinoma.