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Hepatobiliary & Pancreatic Diseases International 2002年第3期1卷 349-353页

作者： Zhao-You Tang the liver cancer institute & Zhongshan Hospital, fudan university, Shanghai 200032, China liver cancer Inst./Zhongshan Hosp. Fudan University Shanghai 200032 China

Background: More than two decades have gone by since the early report of resection for small hepatocel- lular carcinoma (HCC), which resulted in improved prognosis of HCC. Objective: To review the past and recent data, and prospect the future in this field. Data sources: Literature and recent data from the liver cancer institute of fudan university, Shang- hai, China. Data synthesis: 1232 patients with small HCC from the institute were analyzed between 1960-1984 (n= 107) and 1985-1999 (n=1125). The increase of li- mited resection rate from 69.5 % to 82.5 % contribu- ted in part to the increase of resectability from 76.6 % to 95.5 %, decrease of operative mortality from 2.4 % to 1.2 %, and improvement of 5-year sur- vival after resection (from 53.1% to 64.0%). The 5-year survival was higher after limited resection than after lobectomy, being 64.4 % versus 55.9%. The 5-year survival after resection was superior to that after cryosurgery and other regional cancer therapies (32.8 %). However, molecular studies found that biological characteristics were only slightly better in small HCC than in large HCC. Conclusions: Resection remains the treatment choice for small HCC with compensated liver function, while regional cancer therapies and liver transplanta- tion are alternatives for patients with incompensated liver function. Biological characteristics remain the leading factor influencing prognosis of small HCC.

关键词： hepatocellular carcinoma small hepatocellular carcinoma resection regional cancer therapy biological characteristics

Prognostic role of diabetes mellitus in hepatocellular carcinoma patients after curative treatments:a meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2011年第4期10卷 346-355页

作者： Wei-Min Wang,Yang Xu,Xin-Rong Yang,Yao-Hui Wang,Hai-Xiang Sun and Jia Fan institute of Biomedical Sciences,fudan university,Shanghai 200032,China Key Laboratory of Carcinogenesis and cancer Invasion,Ministry of Education,and liver cancer institute,Zhongshan Hospital,fudan university,Shanghai 200032,China fudan university Shanghai cancer Center,Shanghai 200032,China institute of Biomedical Sciences Fudan University Shanghai 200032 China Key Laboratory of Carcinogenesis and cancer Invasion Ministry of Education and Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai 200032 China fudan university Shanghai cancer Center Shanghai 200032 China

BACKGROUND:The prognostic role of diabetes mellitus (DM) coexisting with hepatocellular carcinoma (HCC) remains *** clarify its impact on survival in HCC patients after curative treatments,a meta-analysis was *** SOURCES:Eligible studies were identified through multiple search strategies in the databases PubMed (MEDLINE),EMBASE,the Cochrane Library and ACP Journal Club between January 1950 and March *** studies fulfilled the inclusion criteria,and data were aggregated comparing overall survival and recurrence-free survival in HCC patients according to DM ***:The pooled hazard ratios (HRs) estimate for overall survival was 1.34 (95% CI,1.18-1.51;P<0.0001) and for recurrence-free survival was 1.48 (95% CI,1.00-2.18;P<0.0001),showing a worse survival for HCC with coexisting ***,the patients with DM had a shorter survival time in HCV-related HCC (HR=1.71;95% CI,1.10-2.66;P=0.016),while HBV-related cases were not significantly different (HR=1.29;95% CI,0.69-2.40;P=0.182).Meanwhile,the coexistence of DM impaired overall survival in HCC patients with a small tumor burden (HR=1.63;95% CI,1.25-2.12;P<0.0001).CONCLUSION:HCC patients with coexisting DM have a shorter survival time and a higher risk for tumor recurrence after curative treatments,while the precise value should be defined in more clinical trials with consistent methodology,especially prospective studies.

关键词： hepatocellular carcinoma diabetes mellitus prognostic factors survival meta-analysis

Recurrence and metastasis of hepatocellular carcinoma: progress and prospects

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Hepatobiliary & Pancreatic Diseases International 2002年第1期1卷 35-41页

作者： Xin-Da Zhou From the liver cancer institute, Zhong Shan Hospital, fudan university Medical Center, Shanghai 200032, China liver cancer institute Zhong Shan Hospital Fudan University Medical Center Shanghai 200032 China

Background: Recurrence after resection of hepatocellu-lar carcinoma(HCC) is a major obstacle to improveprognosis. Therefore, further improvement of long-term survival may depend on prevention and treat-ment of the recurrent ***: To evaluate the progress of surgery forHCC, the risk factors for recurrence, and clinical andbasic studies on the prevention and management of re-currence and metastasis after resection of *** sources: A review of currently available data inthe mentioned *** synthesis: Encouraging changes in the prognosticpattern were observed when the primary liver cancer(PLC) data of 1958-1967 (n=118), 1968-1977 (n=356), 1978-1987(n=715) and 1988-1997 (n=2038)were compared. The 5-year survival was 2.8%, 7.3%,27.1% and 52.5%, respectively, and the 10-yearsurvival 2.8%, 4.3%, 19.8% and 39.9%, respective-ly. Risk factors for recurrence included symptomaticpatient, high γ-glutamyl-peptidase (γ-PGT), largetumor size, portal vein embolus, advanced tumorstage, etc. Active hepatitis activity in the nontumorousliver and perioperative transfusion enhanced the re-currence. Molecular research into the invasiveness ofHCC identified some factors positively related to inva-siveness: p16 and p53 mutation, H-ras, c-cerbB2,mdm2, transforming growth factor (TGF), epidermalgrowth factor receptor (EGF-R), matrix metallopro-teinase-2 (MMP-2), urokinasetype plasminogen acti-vator (uPA), its receptor (uPA-R) and inhibitor(PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF),platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF).In contrast, some factors were negatively related toHCC invasiveness: nm23-H1, Kai-1, tissue inhibitor ofmetalloproteinase-2 (TIMP-2), integrin 5, and E-cadherin. Re-resection of subclinical recurrence yield-ed a 5-year survival of 56.0% calculated from the firstresection (n=202) .Postoperative transarterialchemoembolization (TACE, n=103), hepatic

关键词： hepatocellular carcinoma resection recurrence tumor invasiveness prognosis

Chromosomal aberrations related to metastasis of human solid tumors

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World Journal of Gastroenterology 2002年第5期8卷 769-776页

作者： Lun-Xiu Qin liver cancer institute and Zhongshan Hospital,fudan university,Shanghai,China liver cancer institute Zhongshan Hospital Fudan University Shanghai China. lxqin@***

The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic *** does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor *** the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have *** is still controversial with the association between

关键词：染色体变异实质肿瘤肿瘤转移综述

Hepatocellular Carcinoma-Cause,Treatment and Metastasis

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World Journal of Gastroenterology 2001年第4期7卷 445-454页

作者： Zhao-You Tang liver cancer institute & Zhongshan Hospital of fudan university Professor of Surgery Chairman.liver cancer institute of fudan university(previous liver cancer institute of Shanghai Medical university)136 Yixueyuan Road,Zhongshan Hospital,Shanghai 200032,China. liver cancer institute of fudan university 136 Yixueyuan Road Zhongshan Hospital Shanghai 200032 China. zytang@***

In the recent decades, the incidence of hepatocellular carcinoma (HCC) has been found to be increasing in males in some countries. In China, HCC ranked second of cancer mortality since 1990s. Hepatitis B and C viruses (HBV and HCV) and dietary aflatoxin intake remain the major causative factors of HCC. Surgery plays a major role in the treatment of HCC, particularly for small HCC. Downstaging unresectable huge HCC to smaller HCC and followed by resection will probably be a new approach for further study. liver transplantation is indicated for small HCC, however, some issues remain to be *** modes of 'regional cancer therapy for HCC' have been tried. Systemic chemotherapy has been disappointing in the past but the future can be ***, such as cytokines, differentiation inducers,anti-angiogenic agents, gene therapy and tumor vaccine will probably play a role, particularly in the prevention of tumor recurrence. HCC invasiveness is currently the major target of study. Tremendous works have been done at the molecular level, which will provide clues for biomarker of HCC progressionas well as targets for intervention.

关键词： Carcinoma, Hepatocellular liver Neoplasms Animals Humans

The prognostic molecular markers in hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第3期8卷 385-392页

作者： Lun-Xiu Qin Zhao-You Tang,liver cancer institute and Zhongshan Hospital,fudan university,Shanghai,China liver cancer institute and Zhongshan Hospital Fudan university 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) leve

关键词： Apoptosis Carcinogens Carcinoma, Hepatocellular Cell Adhesion Cell Division Cell Nucleus Extracellular Matrix Genes, p53 Humans liver Neoplasms Neovascularization, Pathologic Ploidies Prognosis Proteome Telomerase Tumor Markers, Biological

Hepatocellular carcinoma with obstructive jaundice: diagnosis, treatment and prognosis

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World Journal of Gastroenterology 2003年第3期9卷 385-391页

作者： Lun-Xin Qin Zhao-You Tang liver cancer institute and Zhongshan Hospital, fudan university, Shanghai, China liver cancer institute Fudan University 136 Yi Xue Yuan Road Shanghai 200032 China. zytang@***

Obstructive jaundice as the main clinical feature is uncommon in patients with hepatocellular carcinoma (HCC). Only 1-12 %of HCC patients manifest obstructive jaundice as the initial complaint. Such cases are clinically classified as 'icteric type hepatoma', or 'cholestatic type of HCC'. Identification of this group of patients is important, because surgical treatment may be beneficial. HCC may involve the biliary tract in several different ways: tumor thrombosis, hemobilia,tumor compression, and diffuse tumor infiltration. Bile duct thrombosis (BDT) is one of the main causes for obstructive jaundice, and the previously reported incidence is 1.2-9 %.BDT might be benign, malignant, or a combination of *** thrombi could be blood clots, pus, or *** thrombi could be primary intrabiliary malignant tumors, HCC with invasion to bile ducts, or metastatic cancer with bile duct invasion. The common clinical features of this type of HCC include: high level of serum AFP; history of cholangitis with dilation of intrahepatic bile duct; aggravating jaundice and rapidly developing into liver dysfunction. It is usually difficult to make diagnosis before operation, because of the low incidence rate, ignorant of this disease, and the difficulty for the imaging diagnosis to find the BDT preoperatively. Despite recent remarkable improvements in the imaging tools for diagnosis of HCC, such cases are still incorrectly diagnosed as cholangiocarcinoma or choledocholithiases. Ultrasonography (US) and CT are helpful in showing hepatic tumors and dilated intrahepatic and/or extrahepatic ducts containing dense material corresponding to tumor debris. Direct cholangiography including percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP)remains the standard procedure to delineate the presence and level of biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) is superior to ERCP in interpreting the cause and

关键词：肝细胞癌梗阻性黄疸合并症肝动脉灌注栓塞化疗诊断临床特点

The prognostic significance of clinical and pathological features in hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第2期8卷 193-199页

作者： Lun-Xiu Qin Zhao-You Tang,liver cancer institute and Zhongshan Hospital,fudan university,Shanghai,China liver cancer institute Zhongshan Hospital 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of patients with HCC still remains dismal. The life expectancy of HCC patients is hard to predict because of the high possibility of postoperative recurrence. Many factors, such as patient's general conditions, macroscopic tumor morphology, as well as tumor histopathology features, have been proven of prognostic significance. Female HCC patient often has a better prognosis than male patient, which might be due to the receptor of sex hormones. Younger patients often have tumors with higher invasiveness and metastatic potentials, and their survival and prognosis are worse than the older ones. Co-existing hepatitis status and hepatic functional reserve have been confirmed as risk factors for recurrence. Serum alpha-fetoprotein (AFP) is useful not only for diagnosis, but also as a prognostic indicator for HCC patients. AFP mRNA has been proposed as a predictive marker of HCC cells disseminated into the circulation and for metastatic recurrence. Many pathologic features, such as tumor size, number, capsule state, cell differentiation, venous invasion, intrahepatic spreading, and advanced pTNM stage, are the best-established risk factors for recurrence and important aspects affecting the prognosis of patients with HCC. Marked inflammatory cell infiltration in the tumor could predict a better prognosis. Clinical stage is still the most important factor influencing on the prognosis. Extratumor spreading and lymph nodal metastasis are independent predictors for poor outcome. Some new predictive systems have recently been proposed. Different strategies of treatment might have significant different effects on the patients' prognosis. To date, surgical resection is still the only potentially curative treatment for HCC, including localized postoperative recurrences. Extent of resection, blood transfusion, occlusion of porta hepatis, and blood loss affect the survival and prognosis of HCC patients. Regional therapies provide alternative ways to improve the prognosis

关键词： Age Factors Carcinoma, Hepatocellular Hepatitis Humans liver Cirrhosis liver Neoplasms Neoplasm Staging Prognosis Recurrence Sex Factors alpha-Fetoproteins

Prognostic significance and clinical relevance of Sprouty 2 protein expression in human hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2012年第2期11卷 177-184页

作者： Kang Song,Qiang Gao,Jian Zhou,Shuang-Jian Qiu,Xiao-Wu Huang,Xiao-Ying Wang and Jia Fan liver cancer institute, Zhongshan Hospitaland institute of Biomedical Sciences , fudan university, Shanghai 200032, China liver cancer institute Zhongshan Hospital Fudan University Shanghai 200032 China institute of Biomedical Sciences Fudan University Shanghai 200032 China

BACKGROUND:In vitro experiments and mice models have confirmed the importance of Sprouty 2(Spry2) in inhibiting tumorigenesis and the progression of human ***,the prognostic value of Spry2 in cancer patients remains *** study is aimed to investigate the clinical relevance and prognostic significance of Spry2 expression in patients with hepatocellular carcinoma(HCC).METHODS:With samples from 240 randomly-selected HCC patients who underwent surgery,immunohistochemistry was used to investigate Spry2 expression on tissue *** correlation of Spry2 expression with survival was estimated by the Kaplan-Meier method and univariate/multivariate Cox proportional hazard regression ***2,ERK and phospho-ERK expression in HCC cell lines was detected by Western ***:Among the patients,86.3%(207 of 240) exhibited down-regulation of Spry2 *** negative for Spry2 showed poorer survival(P=0.002) and increased recurrence(P=0.003).Multivariate analysis further established Spry2 as an independent predictor of postoperative recurrence in HCC patients(HR=1.47;95% CI,1.02-2.08;P=0.037).Downregulation of Spry2 was associated with highly malignant phenotypes like vascular invasion and advanced tumor stages,and was positively correlated with the metastatic potential of HCC cell ***:In the era of molecular targeted therapy,the expression of Spry2 in HCC may have relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.

关键词： hepatocellular carcinoma Sprouty 2 tumor suppressor prognosis