Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. This paper summarized a decade's studies on HCC metastasis at the Liver Cancer Institute of Fudan University. We have established a stepwise metastatic human HCC model system, which included a metastatic HCC model in nude mice (LCI-D20), a HCC cell line with high metastatic potential (MHCC97), a relatively low metastatic potential cell clone (MHCC97L) and several stepwise high metastatic potential cell clones (MHCC97H, HCCLM3, and HCCLM6) from their parent MHCC97 cell. Endeavors have been made for searching human HCC metastasis-related chromosomes/proteins/genes. Monogene-based studies revealed that HCC invasion/metastasis was similar to that of other solid tumors, and the biological characteristics of small HCC were only slightly better than that of large HCC. Using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), genotyping, cDNA microarray, and 2-dimensional gel electrophoresis, we obtained some interesting results. In particular, in collaboration with the National Institute of Health (NIH) in the United States, we generated a molecular signature that can classify metastatic HCC patients, identified osteopontin as a lead gene in the signature, and found that genes favoring metastasis progression were initiated in the primary tumors. We also found that chromosome 8p deletion, particularly in the region of 8p23, was associated with HCC metastasis. Cytokeratin 19 was identified as one of the proteins, which was found in MHCC97H, but not in MHCC97L cells. Experimental interventions using the high metastatic nude mice model have provided clues for the prevention of HCC metastasis. Translation from workbench to bedside demonstrated that serum VEGF, microvessel density, and p53 scoring may be of value for the prediction of postoperative metastatic recurrence. Interferon alpha proved effective for the prevention of recurrence both experimentally and clinically. In conclusion, HCC metastasis that probably initiated in the primary tumor is a multigene-involved, multistep, and changing process. The further elucidation of the mechanism underlying HCC metastasis will provide a more solid basis for the prediction and prevention of the metastatic recurrence of HCC.

IFN alpha treatment improved the overall survival of patients with HBV-related HCC after curative resection, probably by postponing recurrence.

BACKGROUND Recently, the implementation of screening programs using α‐fetoprotein (AFP) and ultrasonography in high risk populations has identified increasing numbers of patients with small hepatocellular carcinoma (small HCC). The aim of this study was to summarize the authors' experience in patients who underwent hepatectomy for small HCC and the factors that influence or improve long term survival. METHODS The study included 1000 patients who underwent hepatectomy for small HCC (≤ 5 cm) and compared them with 1366 patients who underwent hepatectomy for large HCC (> 5 cm) during the same period. A Cox proportional‐hazards model was used for multivariate analysis of prognostic factors. RESULTS Comparison between patients with small HCC (n = 1000 patients) and patients with large HCC (n = 1366 patients) revealed that those with small HCC had a higher resection rate (93.6% [1000 of 1068 patients] vs. 55.7% [1366 of 2451 patients]; P < 0.01), a higher curative resection rate (80.5% [805 of 1000 patients] vs. 60.7% [829 of 1366 patients]; P < 0.01), a lower operative mortality rate (1.5% [15 of 1000 patients] vs. 3.7% [50 of 1366 patients]; P < 0.01), better differentiation of tumor cells (Edmondson Grade 3–4; 14.9% vs. 20.1%; P < 0.01), a higher incidence of single nodule tumors (82.6% vs. 64.4%; P < 0.01), a higher proportion of well encapsulated tumors (73.3% vs. 46.3%; P < 0.01), a lower incidence of tumor emboli in the portal vein (4.9% vs. 20.8%; P < 0.01), and higher survival rates after undergoing resection (5 years: 62.7% vs. 37.1%; P < 0.01; 10 years: 46.3% vs. 29.2%; P < 0.01). No significant difference was found between survival after undergoing minor resection (n = 949 patients) or lobectomy (n = 51 patients) in patients with small HCC (P > 0.05). Reresection for subclinical recurrence or solitary pulmonary metastasis after small HCC resection was undertaken in 84 patients. CONCLUSIONS Resection is still the modality of first choice for the treatment of patients with small HCC. Minor resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality, and reresection for subclinical recurrence or solitary pulmonary metastasis was important approach to prolonging survival further. Cancer 2001;91:1479–86. © 2001 American Cancer Society.

No abstract

The purpose of our study was to examine the roles of green tea drinking, other risk and protective factors, and polymorphism of susceptibility genes such as GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the risk of stomach cancer. A population-based case-control study was conducted in Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415 healthy control subjects. Epidemiological data were collected by in-person interviews using a standard questionnaire. Polymorphisms of susceptibility genes were assayed by PCR-RFLP techniques. A multigenetic index was created by summing up the number of risk genotypes. The data were analyzed using the logistic regression model. A reverse association between green tea drinking and risk of stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95% confidence interval [CI] 5 0.34-1.01). Dose-response relationship was shown (p-trend < 0.05). A higher score on the multigenetic index was associated with increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI 5 1.02-4.79) for those with at least 3 risk genotypes compared to those with <2 risk genotypes. Green tea drinking was suggested to have more than multiplicative interactions with alcohol consumption with an adjusted OR for interaction of 4.57 (95% CI 5 1.62-12.89), and with higher multigenetic index with adjusted OR for interaction of 2.31 (95% CI 5 0.88-6.03). The protective effect of green tea drinking was observed on the risk of stomach cancer and the possible effect modification by susceptibility genes was suggested. ' 2005 Wiley-Liss, Inc.

Our present findings strongly suggest that mutations of beta-catenin, as well as overexpression of beta-catenin and the Tcf-4 gene, independently activate the Wnt pathway in HCC, with the target gene most likely to be C-myc.

Surgical removal of primary tumors and BDT is safe and beneficial to the HCC patients with BDT. Early detection, diagnosis, and surgical treatment are the key points to prolong the survival time of patients.

Aim: This retrospective study was undertaken to analyze the outcome of hepatic resection in hepatocellular carcinomas (HCCs) that shrunk after transcatheter hepatic arterial chemoembolization (TACE) in 65 patients with unresectable HCCs between June 1987 and September 1996. Materials and Methods: Among these 65 patients, the median diameter of the tumor was 9.9 cm (5.6–20.0) prior to the first TACE, after 1–6 times of TACE (median 3) the median tumor diameter reduced to 3.7 cm (1.9–12.5) prior to resection. The duration between the last TACE treatment and sequential resection varied from 1 to 9 months (median 2.5). Serum α-fetoprotein (AFP) levels were abnormal in 39 out of the 65 patients. In AFP producing HCCs, the AFP level returned to normal (≤20 µg/l) in 14 out of 39 patients (35.9%). Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in 61 patients, right hemihepatectomy in 1, left trisegmentectomy in 2, and left hemihepatectomy in 1. Results: Tumor necrosis ranged from 40 to 100% and pathologically and complete tumor necrosis occurred in 11 patients (16.9%). Of 14 patients with AFP levels decreased to normal, 10 still had microscopic living tumor foci. The 1-, 3- and 5-year survival rates of the 65 patients were 80.0, 65.0 and 56.0% respectively. Conclusion: TACE treatment can provide a chance of tumor resection for those patients with initially judged unresectable HCCs, and liver resection should be performed when the tumor has shrunk to be resectable, even when the AFP level has returned to normal.