巢式RT-PCR定量检测肝癌、癌旁组织及正常肝组织内AFPmRNA

目的 :探讨肝癌、癌旁组织及正常肝组织内AFPmRNA的表达含量。方法 :应用巢式RT PCR定量检测肝癌、癌旁组织及正常肝组织内AFPmRNA。结果 :17例AFP(+ )癌旁组织内AFPmRNA表达强阳性( ) ,其癌旁组织内AFPmRNA表达呈中度阳性 ( )。 15例AFP(- )肝癌、癌旁组织及正常肝组织内AFPmR NA表达弱阳性 (+ )。结论 :AFP(+ )肝癌组织过量表达AFPmRNA基因 ,正常肝组织仅微弱表达AFPmRNA。

Apoptosis of Human Hepatoma Cells Induced by Gynostemma Pentaphyllum Makino

Objective： To identify the proapoptotic effects of Gynostemma pentaphyllum Makino （GpM） on human hepatoma cells. Methods： The effects of GpM on the cell apoptosis of human hepatoma cell line Huh-7 was assessed by flow cytomety. The expression of Bcl-2, Bcl-XL, Bax and Bad molecules in hepatoma cells treated with GpM was detected by Western blot. Results： After treatment with 20 mg/mL GpM for 24 h, 56% of Huh-7 cells were undergoing apoptosis, while cell death was only observed in 12% of humaa fibroblast cells treated with GpM. Western blot demonstrated that, Bcl-2 was markedly decreased in Huh-7 cells treated with GpM. Whereas, Bax was significantly up-regulated in Huh-7 cells treated with GpM. Conclusion： Treatment of human hepatoma cells with GpM induced apoptosis through the down-regulation of Bcl-2, and up-regulation of Bax.

Expression of Lung Resistance Protein （LRP） Gene in Hepatocellular Carcinoma and Its Significance

Objective: To study the multidrug resistance (MDR) mechanism of lung resistance protein (LRP) gene in hepatocellular carcinoma (HCC), and the relations among the expression of the LRP gene and clinicopathologic features, the influence of α-fetoprotein (AFP), and prognosis of patients who received adjuvant chemotherapy after resection of HCC. Methods: The expression of the LRP gene encoding LRP and mRNA LRP was detected in tissues from 54 untreated patients with HCC, adjacent tissues from 24 patients with HCC and archival paraffin-embedded tissues from 12 patients with posthepatitic cirrhosis. The relationship between the LRP gene expression and the change of AFP level was analyzed in the 24 postoperative HCC patients whose AFP was measured after 2 weeks. All of the HCC patients were followed up. Results: The percentage of positive expression of LRP and mRNA LRP in the 3 tissues was 61.1%, 33.3%, 16.7%, and 75.9%, 37.5%, 33.3% respectively. There was significant difference between the untreated HCC tissue and other tissues (P<0.05). No difference existed between the LRP gene expression and clinicopathologic findings, age, sex, and tumor size (P>0.05), but the expression was related to the degree of differentiation of HCC (P<0.05). The effective rate of AFP in the LRP gene positive expression group or in postoperative chemotherapeutic patients was very lower than that in the negative group (P<0.05). Although the mean survival time of postoperative HCC patients in negative LRP gene expression group was longer than that of positive group, there was no difference between them (P<0.05). Conclusion: LRP gene expression is related to MDR of HCC and initiates the intrinsic MDR. Detection of LRP gene expression is of great guiding significance in accessing chemotherapeutic resistance of HCC. As an index to chemotherapy of HCC, detection of LRP expression provides evidence for making individual chemotherapeutic treatment,and reversing MDR in HCC. Although LRP gene expression correlates with the tumor differential degree (P<0.05), it perhaps does not relate with the prognosis of HCC patients.

A Novel Replication-competent Adenovirus CNHK500 in the Treatment of Heptocellular Carcinoma In Vitro

Objective: To evaluate the therapeutic efficacy of replicative adenovirus CNHK500 in the treatment of hepatocellular carcinoma. Methods: Virus proliferation assay, cell viability assay and Western blot were performed to assess the selective replication and cytolysis of CNHK500 in telomerase positive liver cancer cells Hep3B, HepGII, SMMC7721 and in normal cells. Results: The replicative multiples of CNHK500 in HepGII, Hep3B and SMMC7221 after 96 h of virus proliferation were 52 000, 396 984.9 and 632 911.3 fold respectively, similar to those of wtAd5. However, CNHK500 demonstrated more significant attenuated replicative ability in normal cell lines than wtAd5. CNHK500 replicated only 3.1-100 fold at 96 h, while the wtAd5 still reached 3160-17 357 fold. CNHK500 could cause half of HepGII cells death within 7 days at MOI 2, in Hep3B cell lines the IC50 was as low as MOI 0.01, whereas the IC50 in BJ cell was as high as MOI 1000. CNHK500 E1A protein could only be detected in hepatocellular cancer cells but not in normal cells under normoxia. E1B protein could only be detected under hypoxia condition at a MOI of 1. Conclusion: CNHK500 can efficiently replicate in and kill liver cancer cells as well as wtAd5 do while it is severely attenuated in proliferation and cytolysis among normal cells. It would be a prominsing strategy for liver cancer tratment.

Expression Profiles of TRAIL Receptors and Their Clinical Significance in Human Hepatocellular Carcinoma

Objective To investigate the expression profiles and their clinical significance of TRAIL receptors (TRAILR) in human hepatocellular carcinoma (HCC). Methods The expression profiles of TRAILR were determined in 60 samples from hepatocellular carcinoma, 20 from normal liver tissue and two HCC cell lines HepG2, SMMC-7721 by in situ hybridization. Results Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples (higher DR expression level and lower DcR expression level) were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. The expression level of DR was correlated with HCC differentiation and stage. The weaker expression was more commonly found in HCC with poor differentiation and late stage, while the stronger expression was more common in HCC with middle to high-differentiation and early stage. No relationship was found between DR and gender, age, negative or positive HBsAg, tumor size, grade or metastasis. Multidrug resistance cell lines expressed lower level DR. Conclusion TRAILR expression was prevalent and discrepancy of receptor types was exited in HCC. Loss of DcR1 may contribute for TRAIL therapy for HCC. Key words TRAILR - apoptosis - hepatocellular carcinoma Supported by the Major Fundation of Ministry of Health, NO. 2001–2003

Protocol of Interventional Treatment for Hepatocellular Carcinoma

To establish a reasonable protocol for interventional treatment ofhcpatocellular carcinoma (HCC). Methods: The data of 1000 HCC patients treated by different kinds ofinterventional treatments were reviewed with their results of biochemistry, imaging, pathology andsurvival rate evaluated. The values as well as the pros and cons of these various kinds ofinterventional treatments were compared in order to find an optimal protocol. Results:Segmental-transcatheter oil chemoembolization (S-TOCE) could more effectively eradicate the tumoryet inflicting less damage on the noncancerous hepatic tissue and giving much higher survival ratethan the conventional transcatheter oil chemoembolization (C-TOCE). Precutaneous ethanol injection(PEI) in combination with chemoembolization could eliminate the residual tumor and significantlyincrease the survival rate without damaging the noncancerous hepatic tissue. The living quality orsurvival rate could be improved by choosing different ways of interventional treatments to cut downthe complications. Conclusion: The selection of different interventional treatments should bo doneaccording to the size and type of HCC. Active management is indicated for different complicationspresenting along with HCC.

Bacterial infections in cirrhotic patients with hepatocellular carcinoma

AIMS To establish the prevalence of bacterial infection in cir- rhotic patients with hepatocellular carcinoma(HCC). METHODS All 719 cirrhotic patients with HCC were investigat- ed retrospectively for the prevalence of bacterial infections. RESULTS The incidence of bacterial infection was 15.4% (111/719).According to Child-Pugh classification,the inci- dences of bacterial infection in class A,B and C were 2.3%,8. 0%,and 26.4 %,respectively.The bacterial infection increased with the severity of cirrhosis and severe bacterial infections usual- ly occurred in Child-Pugh class B and C patients. CONCLUSIONS The susceptibility of HCC patients to bacterial infection is mainly due to the underlying cirrhosis and not to the HCC itself.

Determination of IL-2/IL-2R system in patients with liver cirrhosis.and carcinoma

AIMS To.determine the interleuking-2 and interleukin- 2 receptor (IL-2/IL-2R) system in patients with liver cirrhosis and carcinoma and compare their immune functions. The clinical significance is also discussed. METHODS Fifty patients with Liver cirrhosis (LC), 50 patients with hepatocellular carcinoma (HCC) and 30 normal controls were studied. The expression of mlL-2R was examined by immunofluorescence. IL-2's activity and serum level of soluble interleukin-2 recep- tor (sIL-2R) were measured by enzyme linked im- munosorbent assay. RESULTS IL-2's activity and the percentage of mIL- 2R expression in carcinoma were significantly lower than those in cirrhosis (P<0.01) and controls (P< 0.01),while the IL-2's activity and the expression of mlL-2R in cirrhosis were also lower than normal controls (P<0.05). The serum level of sIL-2R in carcinoma was significantly higher than that in cirrhosis (P<0.05) and controls (P<0.01),and the level in cirrhosis was higher than in controls (P<0.05). CONCLUSIONS Patients with liver cirhosis and car- cinoma share the decreased immune function of similar nature,but the latter has a more profound degree. Such resemblance in immune disturbances may be the important factor affecting the carcinogenesis of cirrhotic liver.

Histopathological study of hepatocellular carcinoma after transcatheter hepatic arterial embolization

AIMS To study the histopathological changes in hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS Histopathological analysis was made in 39 cases of liver neoplasms after TAE and 11 cases of liver neoplasms after digital selective angiography (DSA), including pathological type, histological grade, necrotic degree, capsule, times of treatment, injured vessel and lymphocyte infiltration. RESULTS Six cases with 100% necrosis, 14 cases with 30% 95% necrosis, 19 cases with 0% 5% necrosis after TAE and 11 cases without necrosis after DSA were found histologically. The necrosis was related to the pathological type, capsule, injured vessels, but not to the histological grade, time of treatment and lymphocyte infiltration of the liver neoplasms. CONCLUSIONS TAE is an effective therapy for the late stage HCC. The encapsulated HCC is a preferable indicator for TAE.

Fixed-Tumor Vaccine: A Practical Formulation with Cytokine-Microspheres for Protective and Therapeutic Antitumor Immunity

Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragments combined with sustained-releasers of cytokines and a non-toxic adjuvant was developed. C57BL/6J mice were immunized intra-dermally with the vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa 1–6 cells.Results: All of 15 nonimmunized control mice developed the hepatoma. Protection of mice immunized with fixed Hepa 1–6 cells and both of IL-2/GM-CSF microspheres or further mixed with TiterMax Gold reached 80% and 87%, respectively. Mass growth of the established tumors, vaccinated twice at 5 mm in diameter, the tumor of control animals continued to grow. However, 7–10 days after the second injection of the tumor vaccine, the tumor growth was suppressed in 9 of 10 mice and then markedly reduced. Complete tumor regression was observed in 60% (6/10) of mice. Splenocytes from the control mice were not able to lyse target Hepa 1–6 cells and other tumor cells. In contrast splenocytes from the vaccinated mice exhibited a 41% lytic activity against the Hepa 1–6 cells tested at an effector/target (E/T) ratio of 5, whereas they did not exhibited such activity against the melanoma cells (B16-F1), Lewis lung carcinoma cells (LLC), renal carcinoma cells (Renca), and bladder carcinoma cells (MBT-2). The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class I monoclonal antibodies but not with anti-CD4 and anti-MHC-class II antibodies. In the Phase-I clinical trial, vaccination of HCC patients with the autologous vaccine is a well-tolerated treatment and induces fixed tumor fragment-specific immunity.Conclusion: Fixed HCC vaccination elicited protective and therapeutic antitumor immunity against HCC. The tumor vaccine elicited antigen specific CTL response lysis of the target HCC was mediated by the typical MHC-class I restricted CD8+ T cells. Key words cancer vaccine - cytotoxic T lymphocyte - immunotherapy - hepatoma

Ascorbic Acid Promotes Arsenic-induced Cytotoxicity in Human Hepatocarcinoma Cells and Their Underlying Mechanisms

Objective: To study synergistic effect with Ascorbic acid(AA) on arsenic trioxide inducing human Hepatocarcinoma cell apoptosis, and provide theoretical basis for promoting human Hepatocarcinoma cell apoptosis induced by arsenic trioxide(AT). Methods: Human Hepatocarcinoma cell line BEL-7402 being cultured in vitro, the effect of AT and (or) AA on its growth inhibition and its two intracellular signal molecules was evaluated separately using MTT and Western blot. Results: AT at a few μmol/L concentration could suppress abnormal proliferation of human hepatocarcinoma cells, and initiate their apoptosis by activation of caspase-3, and activate extracellular-signal regulated kinases (ERKs), which were dependent on the dosage of AT conspicuously. The effect of AA on BEL-7402 was not significant; However, AA could effectively enhance AT-induced hepatocarcinoma cell apoptosis and lesion severity through activation of caspase-3 but not ERKs. Conclusion: Caspase-3 and ERKs proteins could involve in arsenic-induced hepatocarcinoma cell apoptosis and differentiation respectively as intracellular signaling molecules; The effect between AT and AA on hepatocarcinoma is synergistic, which further inhibits cell growth and induces apoptosis in human hepatocarcinoma cells through activation of caspase-3 but not ERKs.

Uptake of bacterial lipopolysaccharide and expression of tumor necrosis factor α mRNA in isolated rat intrahepatic bile duct epithelial cells *

AIM To study the uptake of bacterial lipopolysaccharides (LPS) and expression of tumor necrosis factor α mRNA (TNF α mRNA) with cultured rat intrahepatic bile duct epithelial cells.

Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells

AIM： To investigate the effect of hot water-extracted Lydurn barbarum （LBE） and Rehrnannia glutinosa （RGE） on cell proliferation and apoptosis in rat and/or human hepatocellular carcinoma （HCC） cells. METHODS： Rat （H-4-Ⅱ-E） and human HCC （HA22T/ VGH） cell lines were incubated with various concentrations （0-10 g/L） of hot water-extracted LBE and RGE. After 6-24 h incubation, cell proliferation （n = 6） was measured by a colorimetric method. The apoptotic cells （n = 6） were detected by flow cytometry. The expression of p53 protein （n = 3） was determined by SDS-PAGE and Western blotting. RESULTS： Crude LBE （2-5 g/L） and RGE （2-10 g/L） dose-dependently inhibited proliferation of H-4-Ⅱ-E cells by 11% （P 〈 0.05） to 85% （P 〈 0.01） after 6-24 h treatment. Crude LBE at a dose of 5 g/L suppressed cell proliferation of H-4-Ⅱ-E cells more effectively than crude RGE after 6-24 h incubation （P 〈 0.01）. Crude LBE （2-10 g/L） and RGE （2-5 g/L） also dose-dependently inhibited proliferation of HA22T/VGH cells by 14%-43% （P 〈 0.01） after 24 h. Crude LBE at a dose of 10 g/L inhibited the proliferation of HA22T/VGH cells more effectively than crude RGE （56.8% ＋ 1.6% vs 70.3% ＋ 3.1% of control, P = 0.0003 〈 0.01）. The apoptotic cells significantly increased in H-4-Ⅱ-E cells after 24 h treatment with higher doses of crude LBE （2-5 g/L） and RGE （5-10 g/L） （P 〈 0.01）. The expression of p53 protein in H-4-Ⅱ-E cells was 119% and 143% of the control group compared with the LBE-treated （2, 5 g/L） groups, and 110% and 132% of the control group compared with the RGE -treated （5, 10 g/L） groups after 24 h. CONCLUSION： Hot water-extracted crude LBE （2-5 g/L） and RGE （5-10 g/L） inhibit proliferation and stimulate p53-mediated apoptosis in HCC cells.

Tumor vaccine against recurrence of hepatocellular carcinoma

AIM: To investigate the effects of autologous tumor vaccine on recurrence of hepatocellular carcinoma (HCC). METHODS: Sixty patients with HCC who had undergone curative resection, were randomly divided into HCC vaccine group and control group. Three vaccinations at 2-wk intervals were performed after curative hepatic resection. Delayed-type- hypersensitivity (DTH) test was performed before and after vaccination. Primary endpoints were the time of recurrence. RESULTS: Four patients in control group and 6 patients in HCC vaccine group were withdrawn from the study. The vaccine containing human autologous HCC fragments showed no essential adverse effect in a phase II clinical trial and 17 of 24 patients developed a DTH response against the fragments. Three of 17 DTH-positive response patients and 5 of 7 DTH- negative response patients had recurrences after curative resection. After the operation, 1-, 2- and 3-year recurrence rates of HCC vaccine group were 16.7%, 29.2% and 33.3%, respectively. But, 1-, 2- and 3-year recurrence rates of the control group were 30.8%, 53.8% and 61.5%, respectively. The time before the first recurrence in the vaccinated patients was significantly longer than that in the control patients (P<0.05). CONCLUSION: Autologous tumor vaccine is of promise in decreasing recurrence of human HCC.

Significance and relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma tissues

AIM: To investigate the relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma (HCC) tissues and their clinicopathological features.METHODS: The paraffin-embedded specimens from 70 cases with HCC were stained using EliVision immunohistochemistry with mAbs against CD68, tryptase,and CD34. The counts of tumor-associated macrophage (TAM), mast cell (MC) and tumor microvessel (MV) were performed in the tissue sections.RESULTS: The mean counts of TAM, MC, and MV in HCC tissues were significantly higher than those in pericarcinomatous liver tissues (TAM: 69.31± 11.58 vs 40.23±10.36; MC: 16.74±5.67 vs 7.59±4.18; MV:70.11±12.45 vs 38.52± 11.16, P＜0.01). The MV count in the patients with metastasis was markedly higher than that with non-metastasis (P＜0.01). In addition, the MC count in the patients with poorly differentiated HCC was obviously higher than that with well differentiated HCC (P＜ 0.01). The correlation analysis showed that the TAM count was significantly correlated with the count of MV(r=0.712, P＜0.01), and the MC count was obviously correlated with the MV count (r= 0.336, P＜ 0.05).CONCLUSION: TAM and MC might be closely related to the enhancement of tumor angiogenesis. The MV count might be associated with tumor invasion and metastasis.Moreover, the MC count might be associated with tumor differentiation and prognosis of HCC.

Knockdown of survivin gene expression by RNAi induces apoptosis in human hepatocellular carcinoma cell line SMMC-7721

AIM: To investigate the survivin gene expression in human hepatocellular carcinoma cell line SMMC-7721 and the effects of survivin gene RNA interference (RNAi) on cell apoptosis and biological behaviors of SMMC-7721 cells. METHODS: Eukaryotic expression vector of survivin gene RNAi and recombinant plasmid pSuppressorNeo-survivin (pSuNeo-SW), were constructed by ligating into the vector, pSupperssorNeo (pSuNeo) digested with restriction enzymes Xba I and Sail and the designed double-chain RNAi primers. A cell model of SMMC-7721 after treatment with RNAi was prepared by transfecting SMMC-7721 cells with the lipofectin transfection method. Strept-avidin-biotin-complex (SABC) immunohistochemical staining and RT-PCR were used to detect survivin gene expressions in SMMC-7721 cells. Flow cytometry was used for the cell cycle analysis. Transmission electron microscopy was performed to determine whether RNAi induced cell apoptosis, and the method of measuring the cell growth curve was utilized to study the growth of SMMC-7721 cells before and after treatment with RNAi. RESULTS: The eukaryotic expression vector of survivin gene RNAi and pSuNeo-SW, were constructed successfully. The expression level of survivin gene in SMMC-7721 cells was observed. After the treatment of RNAi, the expression of survivin gene in SMMC-7721 cells was almost absent, apoptosis index was increased by 15.6%, and the number of cells was decreased in G2/M phase and the cell growth was inhibited. CONCLUSION: RNAi can exert a knockdown of survivin gene expression in SMMC-7721 cells, and induce apoptosis and inhibit the growth of carcinoma cells.

Gli-1 siRNA induced apoptosis in Huh7 cells

AIM： To investigate the effects of Gli-1 small interference RNA （siRNA） on Huh7 cells, and the change of Bcl-2 expression in Huh7 cells. METHODS： Human hepatocellular carcinoma cells Huh7 were used. Cell viability was analyzed by 3-（4, 5-Dimethylthiazol-2-yl）-2, 5-diphenyl tetrazolium bromide （MTT） assay. The expressions of Gli-1 and Bcl-2 family members were detected by RT-PCR and Western blot. Apoptosis was detected by Flow cytometry using propidium iodide, measured by Hoechst 33258 staining using Advanced Fluorescence Microscopy and caspase-3 enzymatic assay. Cell growth was analyzed after treatment with Gli-1 siRNA and 5-fluorouracil （5-Fu）. RESULTS： Inhibition of Gli-1 mRNA in Huh7 cells through Gli-1 siRNA reduced cell viability. Gli-1 siRNA treatment also induced apoptosis by three criteria, increase in the sub-G1 cell cycle fraction, nuclear condensation, a morphologic change typical of apoptosis, and activation of caspase-3. Gli-1 siRNA was also able to down-regulate Bcl-2. However, Gli-1 siRNA resulted in no significant changes in Bcl-xl, Bax, Bad, and Bid. Furthermore, Gli-1 siRNA increased the cytotoxic effect of 5-Fu on Huh7 cell. CONCLUSION： Down-regulation of Bcl-2 plays an important role in apoptosis induced by Gli-1 siRNA in HCC cells. Combination Gli-1 siRNA with chemotherapeutic drug could represent a more promising strategy against HCC. The effects of the strategies need further investigation in vivo and may have potential clinical application.

Inhibitory effect of tumor suppressor p33^(ING1b) and its synergy with p53 gene in hepatocellular carcinoma

AIM: To investigate the inhibitory effect of tumor suppressor p33ING1b and its synergy with p53 gene in hepatocellular carcinoma (HCC).METHODS: Recombinant sense and antisense p33ING1b plasmids were transfected into hepatoma cell line HepG2 with lipofectamine. Apoptosis, G0/G1 arrest, cell growth rate and cloning efficiency in soft agar of HepG2 were analyzed after transfection. In three hepatoma cell lineswith different endogenous p53 gene expressions, the synergistic effect of p33ING1b with p53 was analyzed by flow cytometry and luciferase assay was performed to detect the activation of p53 downstream gene p21WAF1/CIP1. In addition, the expression and mutation rates of p33ING1b in HCC tissues were measured by immunohistochemistry and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP).RESULTS: Overexpression of p33ING1b inhibited cell growth of HepG2, induced more apoptosis and protected cells from growth in soft agar. Combined transfer of p33ING1b and p53 gene promoted hepatoma cell apoptosis, G0/G1 arrest and elevated expression of p21WAF1/CIP1. Immunostaining results showed co-localized P33ING1b with P53 protein in HCC tissues and there was a significant relation between protein expression rates of these two genes (P＜0.01).Among 28 HCC samples, p33ING1b presented a low gene mutation rate (7.1%).CONCLUSION: p33ING1b collaborates with p53 in cell growth inhibition, cell cycle arrest and apoptosis in HCC. Loss or inactivation of p33ING1b normal function may be an important mechanism for the development of HCC retaining wildtype p53.

The value and limitation of transcatheter arterial chemoembolization in preventing recurrence of resected hepatocellular carcinoma

AIM: To evaluate the value and limitation of postoperative transcatheter arterial chemoembolization (TACE) in preventing recurrence of hepatocellular carcinoma (HCC). METHODS: In the first group, 987 postoperative patients with HCC, who did not have any evidence of recurrence in the first preventative TACE but were found to have recurrence at different times during the follow-up survey, were analyzed. In the second group, 643 postoperative patients with HCC had no TACE for compared study. To study the relationship between the recurrence time and the number of TACE treatments was analyzed. RESULTS: The 6-, 12-, and 18-mo recurrence rates in the first and second groups were 22.2% (210 cases) vs 61.6% (396 cases), 78.0% (770 cases) vs74.7% (480 cases) and 88.6% (874 cases) vs80.1% (515 cases). There were significant differences between the recurrence rates of the two groups at 6 mo (P＜0.0001).CONCLUSION: The principal role of TACE after HCC operation is to suppress, detect early and treat micrometastasis. It has a good effect of preventing recurrence of HCC in 6 mo, but such an effect is less satisfactory in a longer period. When it is uncertain whether HCC is singlecentral or multi-central and if there is cancer residue or metastasis after operation, TACE is valuable to prevent recurrence.

Long-term outcomes of hepatectomy vs percutaneous ablation for treatment of hepatocellular carcinoma≤4 cm

AIM： To determine which treatment modality - hepatectomy or percutaneous ablation - is more beneficial for patients with small hepatocellular carcinoma （HCC） （≤4 cm） in terms of long-term outcomes. METHODS： A retrospective analysis of 149 patients with HCC ≤ 4 cm was conducted. Eighty-five patients underwent partial hepatectomy （anatomic in 47 and nonanatomic in 38） and 64 underwent percutaneous ablation （percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6）. The median follow-up period was 69 mo. RESULTS： Hepatectomy was associated with larger tumor size （P〈0.001）, whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy （P〈0.0001）. Survival was better following hepatectomy （median survival time： 122 mo） than following percutaneous ablation （median survival time： 66 mo; P= 0.0123）. When tumor size was divided into ≤ 2 cm vs 〉 2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors 〉2 cm （P= 0.0001）. The Cox proportional hazards regression model revealed that hepatoctomy （P= 0.006） and tumors ≤ 2 cm （P=0.017） were independently associated with better survival. CONCLUSION： Hepatectomy provides both better local control and better long-term survival for patients with HCC ≤4 cm compared with percutaneous ablation. Of the patients with HCC ≤4 cm, those with tumors 〉 2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.