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Hepatocellular carcinoma with obstructive jaundice: diagnosis, treatment and prognosis

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

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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

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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

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Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2004年第4期3卷 495-498页

作者： zhao-you tang,xin-Da Zhou, Zeng-Chen Ma, Zhi-Quan Wu, Jia Fan, lun-Xiu qin and Yao Yu shanghai, china liver cancer institute & zhongshan hospital, fudan university, shanghai 200032 , china liver cancer institute of fudan university 136 Yi Xue Yuan Road Zhongshan Hospital Shanghai 200032 China. zytang@***

BACKGROUND: Curable outcome of unresectable hepato- cellular carcinoma ( HCC) was seldom encountered in the past. This study was designed to assess the role of down- staging followed by resection ( downstaging-resection) in the improvement of prognosis of unresectable HCC. METHODS: 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 diame- ter 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) + he- patic artery chemo-infusion ( HAI ) was performed in 65.5% of the patients, HAL + HAI + radiotherapy/radioim- munotherapy 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. RESULTS: 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 un- resectable 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-re- section rate of 34.6%, 16.2% and 1.8% respectively. CONCLUSIONS: 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.

关键词： hepatocellular carcinoma downstaging cytoreduction resection multimodality treatment

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Risk factors for postoperative complications after liver resection

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Hepatobiliary & Pancreatic Diseases International 2005年第3期4卷 370-374页

作者： Hui-Chuan Sun, lun-Xiu qin, Lu Wang, qin-Hai Ye, Zhi-Quan Wu, Jia Fan and zhao-you tang liver cancer institute and zhongshan hospital, fudan university, shanghai 200032, china liver cancer institute and zhongshan hospital Fudan University Shanghai 200032 China. sunhc@***

liver resection is still a complicated operation with a high risk of postoperative morbidity. This study was undertaken to analyze the risk factors for postoperative complications after liver resection. METHODS:From 2001 to 2004, a total of 146 patients underwent liver resection for malignant or benign lesions. Postoperative complications after the resection were classified as surgical and medical, their incidences were analyzed *** risk factors for both surgical and medical complications were analyzed. To increase the safety of liver resection, surgical techniques were modified after April 2003, including control of inflow or outflow and intra- operative test with methylene blue. RESULTS:Before April 2003, a series of 58 patients received liver resection. Modified surgical techniques were used in liver resections for 88 patients after April 2003.A total of 36 patients (24.7%) had postoperative complications. Surgical and medical complications occurred in 24 and 13 patients respectively (One patient had both surgical and medical complications). Perioperative blood transfusion was related to a higher risk of surgical complications (Phospitalization were decreased after the use of modified surgical techniques (Pliver resection may help to decrease postoperative medical complications also.

关键词： hepatocellular carcinoma resection complications

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P53 immunohistochemical scoring:an independent prognostic marker for patients after hepatocellular carcinoma resection

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World Journal of Gastroenterology 2002年第3期8卷 459-463页

作者： lun-Xiu qin zhao-you tang Zeng-Chen Ma Zhi-Quan Wu xin-Da Zhou qing-Hai Ye Yuan Ji Li-Wen Huang Hu-Liang Jia Hui-Chuan Sun Lu Wang,liver cancer institute and zhongshan hospital,fudan university,shanghai,china liver cancer institute & zhongshan hospital Fudan University 136 Yi Xue Yuan Road Shanghai 200032 China.

AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated. RESULTS: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P<0.05) and capsule (P<0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P<0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P<0.01), vascular invasion (RI 0.5271, P<0.01) and capsule (RI-0.8691, P<0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P<0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level. CONCLUSION: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for

关键词： Adolescent Adult Aged Carcinoma, Hepatocellular Female Genes, p53 Humans Immunohistochemistry liver Neoplasms Male Middle Aged Mutation Prognosis Research Support, Non-U.S. Gov't Tumor Markers, Biological Tumor Suppressor Protein p53

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Recent progresses in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma:a review of literatures

Recent progresses in predictive biomarkers for metastatic re...

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第三届中国肿瘤学术大会

作者： lun - Xiu qin, zhao - you tang liver cancer institute and zhongshan hospital, fudan university, shanghai, china

＜正＞ Molecular markers （biomarkers ） for hepatocellular carcinoma （HCC） metastasis and recurrence could provide additional information to that by traditional histopathological features. A large number of biomarkers have been shown to have potential predictive significance. One important aspect of that is to detect the transcripts of tumor associated antigens （such as AFP, MAGEs and CK19） , which is proposed as predictive markers of HCC cells disseminated into the circulation and for metastatic recurrence. Another important aspect is to analyze the molecular markers for cellular malignancy phenotype, including DNA ploidy, cellular proliferation index, cell cycle regulators, oncogenes and tumor suppressors （ especially p53 gene） , as well as telomerase activity. Molecular factors involved in the process of HCC invasion and metastasis, including adhesion molecules （E -cadherin, catenins, ICAM -1, laminin -5, CD44 variants, osteopontin） , proteinases responsible for the degradation of extracellular matrix （MMPs, uPA sytem） , as well as angiogenesis regulators （such as VEGF, inratumor MVD） , have also been shown to be potential predictors for HCC metastatic recurrence and clinical outcomes. One important new trend is to genome - widely delineate biomarkers with expression genomics and proteomics with reference to predicting metastatic recurrence, molecular diagnosis and classification, which has been drawing more attention recently. Body fluid （ particularly blood and urinary） testing for biomarkers is easily accessible and more useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations is another important direction. More attention should be paid to these areas in future. As further understanding of tumor biology, more and more new biomarkers with high sensitivity and specificity for HCC metastatic recurrence could be found and routinely used in clinical assays. However, the combination of the pathological

关键词： hepatocellular carcinoma recurrence metastasis molecular marker biomarker.

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Diagnosis and treatment of hepatic angiomyolipoma in 26 cases

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World Journal of Gastroenterology 2003年第8期9卷 1856-1858页

作者： Ning Ren lun-Xiu qin zhao-you tang Zhi-Quan Wu Jia Fan, liver cancer institute and zhongshan hospital, fudan university, shanghai 200032, china liver cancer institute Fudan University Shanghai 200032 China. ningren@***

AIM: To summarize the experience of the diagnosis and treatment of hepatic angiomyolipoma (HAML).METHODS: The clinical, imaging and pathological features,and treatment strategies of 26 patients with HAML treated at the authors′institute between October 1998 and January 2003 were retrospectively analyzed. All the patients received liver resection and were followed up till the *** assays were performed with a panel of ***: There was an obvious female predominance (21:5), and most of the patients (18/26) had no *** high echo was found in ultrasonography and punctiform or filiform vascular distribution pattern was found in color Doppler-sonography in most of the lesions (21/26).All of the 5 lesions further enhanced with Levovist showed early and prolonged enhancement. At contrast-enhanced spiral CT, the soft-tissue components of 24 lesions were markedly enhanced in the arterial phase and 18 lesions remained enhanced in the portal venous phase. MRI was performed in 9 patients, and showed hypointensity or hyperintensity on T1-weighted images and heterogeneous hyperintensity on T2-weighted images. Histopathologically,all lesions were composed of adipose tissues, smooth muscle and blood vessels with different proportions. Most lesions showed positive immunohistochemical staining for HMB45(26/26), A103 (24/26) and SMA (24/26). All of the 26 patients showed a benign course with no sign of ***: Preoperative radiological diagnosis of HAML is possible. The demonstration of intratumoral fat and central vessels is helpful in the diagnosis. HMB45, A103 and SMA are promising markers for pathologic diagnosis of HAML,and surgical resection is effective for the treatment of HAML.

关键词：肝血管肌脂瘤肝肿瘤 CT诊断手术治疗

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Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

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World Journal of Gastroenterology 2001年第5期7卷 597-601页

作者： zhao-you tang Fan-Xian Sun Jian Tian Sheng-Long Ye Yin-Kun Liu Kang-Da Liu Qiong Xue Jie Chen Jing-Lin Xia lun-Xiu qin Hui-Chuan Sun Lu Wang Jian Zhou Yan Li Zeng-Chen Ma xin-Da Zhou Zhi-Quan Wu Zhi-Ying Lin Bing-Hui Yang liver cancer institute of fudan university and zhongshan hospital,shanghai 200032,china liver cancer institute of fudan university (previous liver cancer institute of shanghai Medical university)136 Yixueyuan Road Zhongshan Hospital Shanghai 200032China. zytang@***

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

关键词： Animals Carcinoma, Hepatocellular Disease Models, Animal Humans liver Neoplasms, Experimental Mice Mice, Nude Research Support, Non-U.S. Gov't Tumor Cells, Cultured

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Focal nodular hyperplasia of the liver in 86 patients

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Hepatobiliary & Pancreatic Diseases International 2007年第1期6卷 52-57页

作者： Shen, Ying-Hao Fan, Jia Wu, Zhi-Quan Ma, Zeng-Chen Zhou, xin-Da Zhou, Jian Qiu, Shuang-Jian qin, lun-Xiu Ye, qin-Hai Sun, Hui-Chuan Huang, Xiao-Wu tang, zhao-you fudan Univ Zhongshan Hosp Dept Liver Surg Shanghai 200032 Peoples R China

BACKGROUND: Focal nodular hyperplasia (FNH), the second most common benign hepatic tumor after hemangioma, is characterized by a stellate central scar and hyperplastic nodules. Although some large FNH may be associated with significant symptoms, more frequently they are discovered incidentally on physical examination or the work-up of unrelated symptoms. Since its nature and pathogenesis are still controversial, accurate diagnosis of FNH based on clinical presentation and radiographic studies is difficult. The purpose of this study was to explore the diagnosis and treatment of FNH. METHODS: Eighty-six FNH patients confirmed pathologically were treated at the liver cancer institute in our hospital from 1996 to 2006. Their clinical manifestions, imaging presentation, pathological findings, and surgical results were analyzed retrospectively. RESULTS: Of the 86 patients with 99 foci, 54 were male and 32 female, with a mean age of 37 years. Eighty patients had a single solitary focus and 6 had multiple foci. Tumor diameter was less than 5 cm in 69 patients, 5-10 cm in 15, and more than 10 cm in 2. The overall rate of correct preoperative diagnosis was 59.3% (51/86) including 32.9% (26/79) by color Doppler flow imaging (CDFI), 60.3% (35/58) by CT, and 77.4% (24/31) by MRI. All the 86 patients underwent resection with good curative effect. CONCLUSIONS: CT and MRI are important diagnostic methods for FNH but it is difficult to make a definite preoperative diagnosis for partial classical and all non-classical FNH patients. We suggest that patients with clinical symptoms or with indefinite diagnosis should accept surgical removal.

关键词： liver focal nodular hyperplasia diagnosis treatment

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