Liver Resection for Spontaneous Rupture of Primary Hepatocellular Carcinoma

Objective To study the effect of liver resection for spontaneous rupture of primary hepatocellulal carcinoma (PHCC). Methods The clinical data of 12 patients with ruptured PHCC treated by liver resection in Xiangya Hospital since 1970 were analyzed retrospectively. Results There were 10 males and 2 females with mean age of 42 (ranged 22–65) years in this series. Of the 12 patients, 11 underwent emergent hepatectomy and one 2-stage hepatectomy, including left segmental liver resection in 6 patients, left median lobectomy in 1, left hemihepatectomy in 1, partial right hepatectomy in 2, and tumor resection in 2. There was no operative death in 11 patients with liver function in grade A of Child-Paugh classification, but 1 patient with grade B liver function died of liver failure after operation. The operative mortality was 8.3%. In 11 survived patients, the postoperative median survival time was 16.5 months. The 1?, 3?, 5-year survival rate was 72.7%, 18.2%, 9.1% respectively; among them one patient has been alive free of the tumor for 25 years and 9 months. Conclusion Liver resection is the best treatment for ruptured PHCC when possible, which can result in long survival time. Key words liver resection - spontaneous ruptare - primary hepatocellular carcinoma

Combination of serum tumor markers dickkopf-1,DCP and AFP for the diagnosis of primary hepatocellular carcinoma

Objective:To evaluate the detection accuracy of the biomarkers dickkopf-1,DCP and AFP as a serum biomarker panel by comparing the sensitivity of the panel with those of the individual biomarkers.Methods:The study was composed of three groups,one with HCC patients,one with non-HCC liver diseases and one with healthy controls.Serum AFP was measured using a chemiluminescence assay and serum dickkopf-1 and DCP were measured with ELISA.The sensitivity and specificity of the biomarkers were analyzed as single parameters and as a serum panel.Results:The HCC group showed higher levels of dickkopf-1,DCP and AFP than the other two groups(P<0.05).Dickkopf-1 showed better sensitivity(73.26%vx.58.13%.P<0.05) and better specificity(44.00%vs.29.00%,P>0.05) than AFP.DCP also had better sensitivity(74.42%vs.58.13%.P<0.05) than AFP,but their specificity was similar(30.00%vs.29.00%.P>0.05).The combination of the biomarkers as a scrum panel produced much better sensitivity(93.02%) and specificity(78.00%) than each of the markers individually(P<0.05).Conclusion:The combination of AFP.DCP and dickkopf-1 as a biomarker panel can significantly improve the detection power with much higher sensitivity and specificity for HCC than any of the biomarkers alone.The tests are convenient and inexpensive,and may serve as a valuable addition to current options for the diagnosis of HCC.

Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: a prospective study

Objective: To observe the clinical efficacy of tran- scatheter arterial chemoembolization (TACE) and TACE+MLT (melatonin) on inoperable advanced primary hepatocellular carcinoma. Methods: From January 1997 to January 1998, one hundred patients with inoperable advanced primary hepatocellular carcinoma were treated separately by TACE (50) and TACE+MLT (20 mg/d at 8:00 PM orally, 7 days before TACE) (50). Results: The effective rates (WHO standards) of TACE and TACE+MLT were 16% and 28% respec- tively (P<0.05). After TACE or TACE+MLT, the resection rate at two-stage of TACE was 4% or 14% (P<0. 01). The 0.5-, 1- and 2-year survival rates in the TACE group were 82%, 54% and 26% respectively; in the TACE+MLT group 100%, 68% and 40% respectively. The results were significantly better in the TACE+MLT group than in the TACE group. MLT could protect liver function from the damage caused by TACE. The IL-2 levels of all pa- tients significantly increased, whereas sIL-2R expres- sions decreased after TACE+MLT as compared with the TACE group (P<0.01). Conclusions: With definite protection and treatment effect on the liver function damage caused by TACE, MLT can enhance the immunological activities of pa- tients. It also can improve the effect of TACE by in- creasing the survival and resection rate after two- stage operation.

Effects of kanglaite capsules combined with transcatheter arterial chemoembolization （TACE） on patients with mid or late-stage primary hepatocellular carcinoma （HCC）

Objective： To observe the clinical effects of kanglaite （KLT） capsules combined with transcatheter arterial chemoembolization （TACE） in treating patients with mid or late-stage primary hepatocellular carcinoma （HCC）. Methods： Sixty-five cases were randomly divided into 2 groups, 32 patients in combination group received the treatment of KLT capsules ＋ TACE and 33 patients in control group were treated with TACE alone. The objective response rate （RR）, serum alpha fetoprotein （AFP）, peripheral blood T lymphocyte subgroups （T-LS）, quality of life （QOL）, time to progression （TTP） and adverse reaction were observed and compared between 2 groups. Results： The objective response rate and serum alpha fetoprotein levels had no significant difference between the two groups （P 〉 0.05）. Combination group was superior to control group in quality of life （QOL）, time to progression （TTP）, peripheral blood T lymphocyte subgroups （CD3＋, CD4＋, CD4＋／CD8 ratio） and liver adverse reactions, with significant differences （P 〈 0.05）. Conclusion： KLT capsules combined with TACE is an effective method to treat primary hepatocellular carcinoma （HCC） patients who have lost the opportunity of surgical therapy.

Thirty-one patients with primary hepatocellular carcinoma survived for more than 5 years after hepatectomy

Objective: To investigate the factors affecting progno- sis of patients with primary hepatocellular carcinoma (PHC) after resection. Methods: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were followed up for more than 5 years. Thirty-one of the patients who had sur- vived for more than 5 years were compared with 56 patients who had survived for less than 5 years. Results: Early detection of tumor, radical resection, number of tumors, capsule formation, operation safe distance, presence of portal tumor embolus, pre- sence of cirrhosis and tumor size were important fac- tors affecting the prognosis of patients with PHC. The proportion of small liver cancer in the patients who had survived for more than 5 years was greatly larger than that in the control group. Conclusions: Early detection of tumor and radical re- section are of value in raising the 5-year survival rate. Much remains to be investigated about the rela- tionship between safe margin distance and prognosis of patients with PHC.

Analysis of tumor recurrence factors in patients of primary hepatocellular carcinoma with postoperative transcatheter arterial chemoembolization (TACE)

Objective： The aim of the study was to analyze the tumor recurrence factors in patients of primary hepatocellular carcinoma （PHC） with postoperative transcatheter arterial chemoembolization （TACE）. Methods： A total of 121 cases of PHC by TACE after 1-2 months of surgery was retrospectively analyzed, followed up and analyzed the free survival time and the factors related to tumor-free survival. Results： In all 121 cases, 1-, 2-, and 3-year tumor-free survival rates were 72.73%, 46.21% and 26.93%, respectively. Gender, age, HBV infection, tumor size, capsule is complete, degree of differentiation and the presence of vascular thrombosis were put into the COX proportional hazards model of survival time to select the influential variables. In the clinical data of all variables entering COX proportional hazards model, tumor size, tumor differentiation and the presence of vascular thrombosis were statistically significant contributions to the model. In the tumor diameter less than or equal 10 cm [P = 0.040, Exp （B） = 2.210], vascular thrombosis [P = 0.039, Exp （B） = 2.922] and the lower degree of tumor differentiation [P = 0.035, Exp （B） = 3.038], the risk of tumor recent recurrence increased. Conclusion： Tumor size, differentiation, and the presence of vascular thrombosis are the independent risk factors affecting the prognosis of PHC after TACE.

Synergistic Action of Clonorchiasis,HBV Infection and Alcohol Consumption on Primary Hepatocellular Carcinoma

OBJECTIVE It has been recognized that HBV infection and alcohol consumption are two important risk factors for primary hepatocellular carcinoma （HCC）. Recently, the role of clonorchiasis as a risk factor for HCC is controversial. We aimed to investigate whether these factors increase the risk of HCC in Guangxi, China. METHODS A hospital-based, case-control study of HCC was conducted from July 2005 to July 2007. We enrolled 500 consecutive patients with HCC as an experimental group and 500 patients without tumor in liver as a control group. The risk factors that the patients were exposed to were assessed. RESULTS Comparing the risks of developing the HCC, we found out the following results. The risk of developing HCC for the patients with clonorchiasis was 5 folds of that for the patients without clonorchiasis （OR = 5.0; 95% CI： 3.1-8.1）, and the risk for the patients with alcohol consumption was 3 folds of that for the patients without drinking alcohol （OR = 3.4; 95% CI： 2.3-4.9）, and similarly, the risk for the patients with HBV infection was 21 times of that for the patients without HBV infection （OR = 20.6; 95% CI： 14.3-29.7）. According to crossover analysis, there was significant interaction among clonorchiasis, HBV infection and alcohol consumption, with synergistic indices greater than 1. The etiologic fractions attributed to these interactions [EF （A × B）] are 0.7465, 0.5789 and 0.5506, respectively. CONCLUSION Clonorchiasis, HBV infection and heavy alcohol consumption are independent risk factors for developing HCC in our population in Guangxi, and as they can interact synergistically, the risk of developing HCC is increased. Data from this study may indicate new prevention strategies of developing HCC in high-risk individuals.

Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)is an effective treatment for primary hepatocellular carcinoma(PHC).Radioactive iodine therapy has been used in the treatment of advanced PHC,especially in patients with portal vein tumor thrombosis.However,data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce.AIM To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography(CT).METHODS For this study,98 advanced PHC patients were recruited and divided randomly into the study and control groups.Patients in the study group were treated with TACE combined radioactive iodine implantation therapy.Patients in the control group were treated with only TACE.The tumor lesion length,clinical effect,serum alpha-fetoprotein(AFP)and CT perfusion parameters were compared before and after therapy,and statistical analysis was performed.RESULTS There was no significant difference in tumor length and serum AFP between the study and control groups(P>0.05)before treatment.However,the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy.After 3 mo of treatment,the complete and partial remission rate of the study group was 93.88%,which was significantly higher than the control group(77.55%)(P<0.05).Before treatment,there were no significant differences between the two groups on the perfusion CT variables,including the lesion blood volume,permeability surface,blood flow,hepatic artery flow and mean transit time(P>0.05).After 3 mo of treatment,all perfusion CT variables were lower in the study group compared to the control group(P<0.05).The survival time of patients in the study group was 22 mo compared to 18 mo in the control group,which was significantly different[log rank(Mantel-Cox)=4.318,P=0.038].CONCLUSION TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions,thereby improving the clinical efficacy and prolonging the survival time of patients.

EXPRESSION OF CELLULAR ONCOGENES IN HUMAN PRIMARY HEPATOCELLULAR CARCINOMA

With DNA-mRNA hybridization in situ technique, the expression of five oncogenes, c-N-ras, c-Ki-ras. c-Ha-ras, c-myc and c-fos, was observed in two cases of human hepatocellular carcinoma. The expression of c-N-ras & c-fos was greatly enhanced in tumor tissues of the two cases, and about 25% -50% of the tumor cells showed positive expression. The other three oncogenes namely c-Ki-ras, c-Ha-ras & c-myc, were not detected in these two carcinomas or in the non-cancerous liver tissues adjacent to the carcinomas. It is surmised that c-N-ras and c-fos may play coordinative role in maintaining the malignant phenotype of human primary hepatocellular carcinoma.

EXPRESSION OF FcγR AND REGULATION OF rIFNγ ON FcγR EXPRESSION ON PATIENTS WITH PRIMARY HEPATOCELLULAR CARCINOMA

The level of FcγR on peripheral blood mononuclear cells (PBMC) was determined by ABC-ELIsA in 43 patients with primary hepatocellular carcinoma (PHC) and in 8 patients with space-occupying benign lesion (BL) in liver, twelve patients who received carcinomaectomy were followed up to detect their FcγR.Nine PBMC samples from PHC were treated with rIFNγ-The results showed that: 1. the level of FcγR in PHC patients was significantly lower than that in BL and In normal control; 2. the expression of FcγR was enhanced in postoperated PHC patients; and 3. the production of IFNγ in PHC patients was defective. The level of FcγR on PBMC was increased obviously in PHC after PBMC being treated with rIFNγ but was still lower than that in control. These results suggested; (1) FcyR detection is helpful tor distinguishing malignant liver lesion from benign; (2) the inhibited expression of FcγR in PHC could be related to some factors secreted by cancer tissues and also to low level of IFNγ; and (3) IFNγstimulates the expression of FcyR in vitro as one of the anti-tumor mechanism forIFNγ.

Clinical effect of Cidan capsule on primary hepatocellular carcinoma in 325 cases

OBJECTIVE： To observe the clinical effect of Cidan capsules, a traditional Chinese medicine applied as an antitumor drug for decades, on the treatment of primary hepatocellular carcinoma（HCC）. A two-month experiment was carried out. METHODS： A total of 325 patients with primary HCC were randomly divided into 3 groups. The 125 patients in Group A were treated with Cidan capsules exclusively. The 100 patients in Group B were treated with Cidan capsules combined with chemotherapy. And as control group, the 100 patients in Group C were treated by chemotherapy only. The efficacy of Cidan was analyzed by monitoring associated symptoms and liver function tests and measuring the levels of the NK cell, CD3, CD4, CRJ and CD8, alpha fetoprotein（AFP）. The evaluation of Cidan＇s effects on enhancing the patients＇ life quality was through clinical and pathological observations. RESULTS： The result showed that the steady rate following the standard for evaluation of Kamofsky was over 87.0% in group B, 72.0% in Group A and 57.0% in Group C, respectively. The life quality of the patients treated with Cidan capsules and chemotherapy was improved more obviously than that in Group A and C. The NK cell,CD3, CD4,CRJ and CD8 in Group C were obviously decreased, while those in Group A and Group B were without apparent vacillation. AFP descended markedly in Group A and B, but did not in Group C. CONCLUSION： Cidan capsules combined with chemotherapy had superior curative effects on primary HCC.

Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21^(WAF1) expression and hepatic apoptosis

AIM To detect the expression of caspase 3gene in primary human hepatocellular carcinoma（HCC）and investigate its relationship to p21WAF1gene expression and HCC apoptosis.METHODS In situ hybridization was employedto determine caspase 3 and p21WAF1expression inHCC.In situ end-labeling was used to detecthepatocytic apoptosis in HCC.RESULTS Twenty-one of 39（53.8%）cases ofHCC were found to express caspase 3transcripts,while 45.2% of HCC failed toexpress caspase 3.Non-cancerous adjacent livertissues showed more positive caspase 3（87.5%,7/8）as compared with HCC（P【0.05）.The expression of caspase 3 is correlated withHCC differentiation,72.2%（13/18）ofmoderately to highly differentiated HCC showedcaspase 3 transcripts positive,while only 38.1%of poorly differentiated HCC harbored caspase 3transcripts（P【0.05）.No relationship wasfound between caspase 3 expression and tumorsize or grade or metastasis,although 52.5%（5/8）of HCC with metastasis were caspase 3positive and a little higher than that with nometastasis（51.6%,P】0.05）.Expression of caspase 3 alone did not affect the apoptosisindex（AI）of HCC.The AI was 7.12%o in caspase3-positive tumors（n=21）,while in caspase 3-negative cases（n=18）6.59%0（P】0.05）.Expression of caspase 3 clearly segregated withp21WAF1positive tumors as compared withp21WAF1-negative cases（16 of 23,69.6% versus5 of 16,31.3%）with statistical significance（P=0.017）.In the cases with positive caspase 3and negative p21WAF1,the Al was found slightlyhigher,but with no statistical significance,thanthat with expression of p21WAF1and caspase 3（7.21‰ vs 6.98‰,P】0.05）.CONCLUSION Loss of caspase 3 expressionmay contribute to HCC carcinogenesis,althoughthe expression of caspase 3 does not correlatewell with cell apoptosis in HCC.p21WAF1may bemerely one of the inhibitors which can reducecaspase 3 mediated cell apoptosis in HCCs.

Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma

AIM:To evaluate the diagnostic value of glypican-3(GPC3) in serum and liver for primary hepatocellular carcinoma(HCC).METHODS:Serum levels of GPC3 and α-fetoprotein(AFP) were measured in 75 patients with primary HCC and 32 patients with liver cirrhosis.Expression of GPC3 and AFP in 58 HCC and 12 cirrhotic specimens was detected with immunohistochemical staining.RESULTS:When the cut-off value of serum GPC3 was set at 300 ng/L,its sensitivity and specificity for HCC were 47.0% and 93.5%,respectively.Among the 14 patients with HCC at stage according to the Barcelona Clinic Liver Cancer staging system,the serum GPC3 level was higher than 300 ng/L in 50%(7/14) patients,the serum AFP level was not ≥ 400 μg/L in any patient.Combined serum AFP and GPC3 significantly increased the sensitivity to the diagnosis of HCC.The GPC3 expression was detected in cytoplasm of HCC cells but not in hepatocytes and bile ducts of benign tumors.Among the 58 HCC patients,the GPC3 was expressed in 100%(28/28) patients with their serum AFP level ≥ 400 μg/L,and in 90%(27/30) patients with their AFP level < 400 μg/L,respectively.The GPC3 was weakly or negatively expressed in all paracarcinomatous and cirrhotic tissue samples.AFP positive HCC cells were only found in 1 out of the 58 HCC patients.CONCLUSION:GPC3 protein is a sensitive and specific serum marker for diagnosis of early HCC.Its expression in liver tissues can be used to discriminate tumor cells from benign hepatic cells.

FADD and TRADD expression and apoptosis in primary hepatocellular carcinoma

AIM To investigate the clinical features ofFADD and TRADD expressions in primaryhepatocellular carcinoma(HCC)and todetermine their relationship with hepaticapoptosis.METHODS FADD and TRADD expressions weredetected by immunohistochemistry and hepaticapoptosis were determined by in situ end-labeling(ISEL).RESULTS Ten(25.6%)cases of HCC weredetected to express FADD protein.The positiverate in HCC is lower than that in non-cancerousadjacent liver tissues(62.5%)(P【0.05).Inthose of grade Ⅰ-Ⅱ,8(38.1%)cases wereFADD positive,while only 2/18(11.1%)casesof grade Ⅲ-Ⅳ had detectable FADD protein(P【0.05).No relationship was found betweenFADD expression and other clinical features,such as gender,age,tumor size,differentiationor metastasis.ISEL positive cells can be seen inall cases of HCC.The hepatic apoptosis wasassociated with FADD expression as moreapoptotic cells were detected in those caseswhich had moderately to strongly positiveFADD,as compared with negative or weakpositive FADD cases(P【0.05).No relationshipwas found between FADD expression and hepaticapoptosis in non-cancerous adjacent livertissues.Fifteen of 39(38.5%)cases of HCCwere found positive for TRADD protein,andsimilar positive rate(37.5%)in non-cancerousadjacent liver tissues(P】0.05).The expressionof TRADD is correlated with HCC differentiation, as only 22.2% of moderately to highlydifferentiated HCC showed positive TRADDprotein,while as high as 52.4% of poorlydifferentiated HCC had TRADD(P【0.05),Norelationship was found between TRADDexpression and gender,age,tumor size or gradeor metastasis,although 42.9% of HCC of gradeⅠ/Ⅱ showed positive TRADD which wasslightly higher than that of grade Ⅲ/Ⅳ(33.3%,P】0.05).Hepatic apoptosis was not related toTRADD expression in HCC or non-cancerousadjacent liver tissues.CONCLUSION Loss of FADD expression playsan important role in HCC carcinogenesis,andexpression of TRADD also contributes to HCCdevelopment.The cell apoptosis in HCC isassociated with FADD expression.However,theexpression of TRADD does not correlate wellwith hepatic apoptosis in HCC.

Abnormal β-catenin gene expression with invasiveness of primary hepatocellular carcinoma in China

AIM To study the abnormal expression of β-catenin gene and its relationship with invasiveness of primary hepatocellular carcinoma among Chinese people.METHODS Thirty-four hepatocellular carcinoma (HCC) specimens and adjacent para-cancerous tissues, 4 normal liver tissues were immunohistochemically stained to study subcellular distribution of β-catenin. Semiquantitive analysis of expression of β-catenin gene exon 3 mRNA was examined by RT-PCR and in situ hybridization. The relationship between expressions of both β-catenin protein, mRNA and clinicopathological characteristics of HCC was also analyzed.RESULTS Immunohistochemistry showed that all normal liver tissues and para-cancerous tissues examined displayed membranous type staining for β-catenin protein,occasionally with weak expression in the cytoplasm.While 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei. The accumuled type Labling Index (LI) of cancer tissue and paracancarous tissue was (59.9 ± 26.3) and (18.3 ± 9.7)respectively (P＜0.01). Higher accumulated type LI was closely related with invasiveness of HCC. Results of RTPCR showed the β-catenin gene exon 3 mRNA Expression Index (El) of 34 HCCs was higher than that of paracancerous tissue and normal liver tissue. Using in situ hybridization, the signal corresponding to β-catenin gene exon 3 mRNA was particularly strong in cytoplasm of HCC when compared with those of para-cancerous and normal liver tissues. Over expression of β-catenin exon 3 was also found to be correlated with high metastatic potential of HCC.CONCLUSION Abnormal expression of β-catenin gene may contribute importantly to the invasiveness of HCC among Chinese people.

Relationship between expression of Smac and Survivin and apoptosis of primary hepatocellular carcinoma

BACKGROUND: T he second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of Smac/DIABLO in various cancers including hepatocellular carcinoma (HCC). This study was undertaken to investigate the expression of Smac and Survivin and their relationship with the apoptosis in primary HCC. METHODS: The expression of Smac and Survivin proteins was evaluated by immunohistochemistry. The mRNA expression of Smac and Survivin was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in HCC tissues of 50 patients, para-carcinoma tissues of 20 patients, and normal liver tissues of 15 patients. RESULTS: Smac mRNA was detected by RT-PCR in HCC tissues of 21 (42.0%) of the 50 patients, para-carcinoma tissues of 19 (95.0%) of the 20 patients, and normal liver tissues of 15 (100%) of the 15 patients. Survivin mRNA was found in HCC tissues of 46 of the 50 patients, para- carcinoma tissues of 2 of the 20 patients, and normal liver tissues of 0 of 15 patients. Immunohistochemistry revealed Smac protein in HCC tissues of 20 patients (40.0%), in para-carcinoma tissues of 18 patients (90.0%), and normal liver tissues of 15 patients (100.0%). The expression of Smac was significantly different in HCC tissues and non- HCC tissues. Survivin protein was found in HCC tissuesin 45 patients, para-carcinoma tissues in 2 patients, and normal liver tissues in none of the patients. The expression of Survivin was significantly different in HCC tissues and non-HCC tissues. CONCLUSION: Smac inhibits apoptosis of HCC cells by suppression of Survivin, and the two genes probably form an important link in the signal pathway of HCC cells.

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.

Diagnostic value of imaging examinations in patients with primary hepatocellular carcinoma

Primary hepatocellular carcinoma(PHC) includes hepatocellular carcinoma, intrahepatic cholangiocarcinoma and other pathological types and is characterized by rapid progression. Most of the clinical diagnoses are made at late stage or when distant metastasis occurs, increasing the difficulty of treatment and resulting in a poor prognosis. Therefore, the early diagnosis of PHC plays an important role in timely treatment and the improvement of prognosis. The gold standard for the diagnosis of primary liver cancer is liver biopsy, but it has limitations as an invasive examination. Presently, imaging has become the first choice for the diagnosis of liver cancer. We here summarize the new methods and techniques of imaging in diagnosis and evaluation of primary liver cancer in recent years, including ultrasonography, computed tomography perfusion imaging, diffusion-weighted imaging technology-voxel incoherent motion, diffusion tensor imaging, iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantification, dynamic enhanced magnetic resonance imaging and hepatocyte-specific contrast medium imaging. Imaging diagnosis can not only evaluate the degree of differentiation, blood supply and perfusion, and invasiveness of the lesion, but also predict the prognosis, evaluate liver function, andprovide references for clinical diagnosis and treatment.

Expressions of chromogranin A and cathepsin D in human primary hepatocellular carcinoma

AIM To determine the expression and clinicalsignificance of chromogranin A and cathepsin Din hepatocellular carcinoma(HCC).METHODS Double immunofluorescence stain-ing techniques combined with laser confocalscanning microscopy(LSCM)was used toinvestigate chromogranin A and cathepsin Dexpressions in 85 HCC patients.RESULTS Cathepsin D was expressed in :3normal liver tissues,while in HCC the stainingshowed regional variation and the fraction ofstrongly stained cells increased as the tumorsbecame less differentiated and usually clinicallymore malignant.Cells which showed strongpositivity for cathepsin D were present in 71/85(83.5%)cases.Strong expression of cathepsinD in cancer cells was related tohistopathological features.They were morecommon in grade 3-4(26/28,92.9%)and grade2(46/53,86.8%)tumors than in grade 1 tumors(1/4,25.0%)(P【0.01).No significantcorrelation was found between age andcathepsin D expression.In patients with positivecathepsin D reaction,the mean age was 52.1±2.8 years(range 32-68 years)and in the groupwith negative reaction,the mean age was 51.3±4.5 years(range 28-71 years).No obvious relationship was observed between CgAexpression in cancer cells and thehistopathological features.The CgA positiverate was 75.0%(3/4)in grade 1,71.7%(38/53)in grade 2,and 71.4%(20/28)in grade 3-4(P】0.05)tumors.The coexpression of CgA andcathepsin D was found by double labeledimmunofluorescence staining techniques.Theprocessing of cathepsin D was disturbed in HCCcells and accumulated in the cells.Cathepsin Dhad proteolytic activity and autocrine mitogeniceffect,suggesting their functions in invasion.These findings demonstrated that the expressionof cathepsin D in HCC had prognostic value.CONCLUSION Chromogranin A and cathepsin Dare expressed in a high proportion of HCC andthe existence of cathepsin D in HCC might berelated to processing of CgA.This is clearly asubject for further studies because of itspotential clinical applications.

Primary hepatocellular carcinoma and metabolic syndrome:An update

Hepatocellular carcinoma(HCC) is the most common primary liver malignancy. The incidence of hepatocellular carcinoma has increased dramatically by 80% over the past two decades in the United States. Numerous basic science and clinical studies have documented a strong association between hepatocellular carcinoma and the metabolic syndrome. These studies have documented that, in most patients, non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, which may progress to hepatocellular carcinoma through the cirrhotic process. However, minority of patients with non-alcoholic fatty liver disease may progress to hepatocellular carcinoma without cirrhosis.This review summarizes the current literature of the link between hepatocellular carcinoma and metabolic syndrome with special emphasis on various components of the metabolic syndrome including risk of association with obesity, diabetes mellitus, hyperlipidemia,and hypertension. Current understanding of pathophysiology, clinical features, treatments, outcomes,and surveillance of hepatocellular carcinoma in the background of metabolic syndrome and non-alcoholic fatty liver disease is reviewed. With the current epidemic of metabolic syndrome, the number of patients with non-alcoholic fatty liver disease is increasing.Subsequently, it is expected that the incidence and prevalence of HCC will also increase. It is very important for the scientific community to shed more light on the pathogenesis of HCC with metabolic syndrome,both with and without cirrhosis. At the same time it is also important to quantify the risk of hepatocellular carcinoma associated with the metabolic syndrome in a prospective setting and develop surveillance recommendations for detection of hepatocellular carcinoma in patients with metabolic syndrome.