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Z Y Tang

Publications and source records attributed to Z Y Tang.

At least 55 records · Page 3Linked to original sources

Elevated activity of N-acetylglucosaminyltransferase V in human hepatocellular carcinoma.

Cell-surface glycoproteins are regarded as candidates for involvement in the spread of tumor cells. N-linked beta1-6 branched oligosaccharides may contribute directly to the malignant or metastatic phenotypes of tumor cells. Increased beta1-6 branching has been associated with an increased level of N-acetylglucosaminyltransferase V (GlcNAc transferase V), the glycosyltransferase that initiates the beta1-6 branching. In this report, 33 pathologically verified hepatocellular carcinoma (HCC) specimens, six non-cancerous tissues surrounding HCC and five normal liver specimens have been studied. We have quantified N-linked beta1-6 branched oligosaccharides indirectly by measuring GlcNac transferase V activity. The average GlcNac transferase V activities in hepatocellular carcinoma (HCC), noncancerous tissues surrounding HCC and normal liver tissues were 324.2 +/- 269.8, 84.8 +/- 20.7 and 7.0 +/- 6.2 pmol product h(-1) mg protein(-1) (P < 0.05) respectively. In addition, the activity was correlated with the TNM classification of HCC. The average activities of GlcNAc transferase V in stages T1, T2-3 and T4 were 77.6 +/- 57.8, 369.0 +/- 294.7 and 329.9 +/- 205.9 pmol product h(-1) mg protein h(-1) respectively (P < 0.05), showing that the activity of the enzyme in advanced HCC was higher than that in early HCC. Our preliminary results indicated that GlcNAc transferase V activity increased in human HCC and was correlated with its progression.

Adult↗

The expression of the mdm2 gene may be related to the aberration of the p53 gene in human hepatocellular carcinoma.

The relationship between mdm2 gene expression and p53 gene mutation in hepatocellular carcinoma (HCC) and their correlation with the invasiveness of the disease were investigated in this study. Either the expression level of the mdm2 gene or the mutation rate of the p53 gene was higher in HCC than in paratumor liver tissues. Studies on the relationship between mdm2 and p53 revealed that mdm2 gene expression in HCC without p53 mutation was higher than when there was p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was significantly lower than in HCC without mdm2 overexpression. Among 23 HCC with invasion, mdm2 gene overexpression was found in 6 patients while p53 mutation was found in the other 11 patients, and only 1 patient was found to have both mdm2 overexpression and p53 mutation. These results indicated that either mdm2 overexpression or p53 mutation may be related to the invasiveness of HCC. Considering that an autoregulatory feedback loop between the mdm2 and p53 genes may exist, wild-type P53 can induce the expression of mdm2 via a p53-binding site in the mdm2 gene, while MDM2 protein functions as a negative regulator of P53 protein. These results also suggest that mdm2 may be related to the high invasiveness of HCC through inactivating the tumor-suppressor function of the p53 gene.

Adult↗

Improved long-term survival for unresectable hepatocellular carcinoma (HCC) with a combination of surgery and intrahepatic arterial infusion of 131I-anti-HCC mAb. Phase I/II clinical trials.

Resectional therapy has been accepted as the only curative therapy for hepatocellular carcinoma (HCC). Unfortunately, it is estimated that only 10% of HCC are resectable at the time of diagnosis. Cytoreduction and sequential resection offer a new hope for patients with unresectable HCC. Radioimmunotherapy (RIT) is an attractive approach for cytoreduction. We have previously shown that intrahepatic arterial 131I-labelled anti-HCC monoclonal antibody (131I-Hepama-1 mAb) could be used safely in combination with hepatic artery ligation for treatment of unresectable HCC, and encouraging results have been achieved. In this paper, the long-term survival and the prognostic factors in HCC patients treated with radioimmunotherapy will be analysed. Sixty-five patients with surgically verified unresectable HCC were treated with hepatic artery ligation plus hepatic artery cannulation and infusion from 1990 to 1992. Thirty-two patients were enrolled in a phase I-II clinical trial with infusion of 131I-radiolabelled anti-HCC monoclonal antibody (Hepama-1 mAb) via the hepatic artery (the RIT group). Another 33 patients formed the group treated with intrahepatic-arterial chemotherapy (the non-RIT group). T cell subsets were measured in 24 patients and human anti-(murine Ig) antibody (HAMA) were monitored in the RIT group. The 5-year survival rate was significantly higher in the RIT group than in the chemotherapy group, being 28.1% compared to 9.1% (P < 0.05); this was mainly a result of better cytoreduction and a higher sequential resection rate (53.1% compared to 9.1%). Significant prognostic factors in the RIT group included tumour capsule status and the number of tumour nodules. HAMA incidence and CD4+ T lymphocytes influenced short-term, but not long-term survival. It is suggested that intrahepatic-arterial RIT, using 131I-Hepama-1 mAb, combined with hepatic artery ligation might be an effective approach to improve long-term survival in some patients with unresectable HCC, which may successfully be made resectable by intra-arterial infusion of 131I-Hepama-1 mAb.

Adult↗

Treatment of hepatocellular carcinoma.

Treatment of hepatocellular carcinoma (HCC) remains a critical issue particularly in the endemic areas. This paper summarizes the literature in the recent 4 years and the author's data. Substantial progress has been found in the treatment of HCC during the recent decades, which was mainly a result of advances in medical imaging, aggressive surgical approach, regional cancer therapies and multidisciplinary approach. Surgical approaches that resulted in significant prolonged survival included: resection (particularly small HCC resection), re-resection for subclinical recurrence, cytoreduction and sequential resection for initially unresectable HCC, and liver transplantation for small HCC. In nonsurgery, regional cancer therapy has been a new trend, which includes transcatheter arterial chemoembolization, percutaneous ethanol injection for small HCC, and others. As a result of multimodality combination treatment and changing concepts in surgical oncology, the role of surgery in the treatment of HCC has become bigger. However, the inadequacy of regional cancer therapies, its multicentric origin and tumor invasiveness remain major targets to be studied for a curative treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Improved survival with resection after transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma.

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

Adult↗

Significance of vascular endothelial growth factor mRNA expression in invasion and metastasis of hepatocellular carcinoma.

Vascular endothelial growth factor (VEGF) is an important mediator of vascular development in tumors. We aimed at clarifying the relationship between VEGF mRNA expression and invasion or metastasis of hepatocellular carcinoma (HCC). Reverse transcript-polymerase chain reaction (RT-PCR) was carried out on surgical specimens of 48 patients with HCC. The relative levels of VEGF mRNA expression were measured by determining a ratio between PCR products of VEGF and the endogenous internal standard gene beta-actin. Expression of VEGF mRNA in tumor was found in 76.5% (39/51) of patients, whereas it was 21.69% (11/51) in non tumorous liver. The levels of VEGF mRNA expression in tumors with tumorous emboli and in poor-encapsulated tumors were higher than that without tumorous emboli and in well-encapsulated tumors respectively (p < 0.05 t test). There was no significance in the expression of VEGF mRNA between large HCC (diameter > 5cm) and small HCC (diameter < or = 5cm) (p > 0.05). VEGF may play an important role in the invasion and metastasis of HCC. Angiogenesis in tumor correlates with progression of HCC.

Adult↗

Progress and prospects in hepatocellular carcinoma surgery.

Hepatocellular carcinoma (HCC), the second cause of cancer death in China, is responsible for 130,000 deaths every year. However, as a result of efforts in early detection and small HCC resection, re-resection for subclinical recurrence, cytoreduction and second-stage resection for unresectable HCC, and aggressive palliative surgery other than resection (hepatic artery ligation/cannulation, cryosurgery, etc.), and encouraging improvemental of long-term survival of inpatients has been observed in the authors' institution. In the entire series of 2672 HCC inpatients, the 5-year survival was 4.8% in 1958-70, 12.2% in 1971-83, and 46.7% in 1984-95. The 5-year survival rates were: 61.3% for small HCC resection (n = 645), 33.6% for large HCC resection (n = 950), 48.9% for re-resection (n = 147) calculated from the first resection, 67.9% for second-stage resection (n = 73), and 19.8% for palliative surgery (n = 574, including 73 with second-stage resection). By 1995, 239 HCC patients survived for more than 5 years. Recurrence and metastasis remained the major obstacles to more prolonged survival after HCC surgery. Molecular studies of HCC invasiveness, experimental intervention in the newly established highly metastatic model of human HCC in nude mice in the authors' institution have also been delineated. It is concluded that early detection and small HCC resection remain the major approach to improve survival. Aggressive surgical treatment, such as re-resection and second-stage resection, are also important, and invasiveness-related recurrence will be the next target to be studied.

Animals↗

KAI1 gene expression in hepatocellular carcinoma and its relationship with intrahepatic metastases.

KAI1 gene is a novel metastasis suppressor gene. Its transcription level has been reported to be related with metastases in several kinds of tumors. The Authors used RT-PCR method to investigate the expression levels of KAI1 gene in hepatocellular carcinoma (HCC) tissues from 42 patients. The results demonstrated that 57.1% of tumor tissues were positive in KAI1 expression. There was no statistically significant difference on KAI1 gene expression rate between large (>5 cm) and small (<=5 cm) tumors, encapsulated and non-capsulated tumors, as well as alpha-fetoprotein (AFP) positive (>20 ug/ml) and negative (<=20 ug/ml) tumors; however, the expression rate was higher in tumors without intrahepatic metastasis than in those with intrahepatic metastasis (63.9% vs. 16.7%, P<0.05). It is suggested that KAI1 gene expression may be related to the metastases of hepatocellular carcinoma.

Adult↗

The abundance of NM23-H1 mRNA is related with in situ microenvironment and intrahepatic metastasis in hepato-cellular carcinoma.

In HCC specimens from 25 patients, the levels of nm23-H1 and H-ras mRNA were analyzed by quantitative reverse transcription-polymerase-chain reaction (RT-PCR). Tumor microvessel density (MDV), the essential factor of microenvironment and proliferating cell nucleus antigen (PCNA), indexes as tumor cell proliferating in its microenvironment are also analyzed by immunohistochemical methods using antibodies against endothelial protein factor VIII related antigen (F8RA) and antibody PC-10. Results show that The MDV and PCNA index in the group with intrahepatic metastasis is remarkably higher than that in without one (p<0.01), but the abundance of nm23-H mRNA is opposite (p<0.01). The abundance of H-ras mRNA shows little difference (p>0.05). MDV index shows directly relationship with PCNA index (p<0.01), the abundance of nm23-H1 mRNA show an inverse one with PCNA index (p<0.05). We conclude that in HCC, tumor in situ microenvironment, especially a deteriorative one, plays an important selective role. The decline of nm23-H1 mRNA abundance implies the increase of highly potential metastatic cancer cells which adapt to their microenvironment.

Biomarkers, Tumor↗

Apoptosis of human BEL-7402 hepatocellular carcinoma cells released by antisense H-ras DNA--in vitro and in vivo studies.

Recent findings suggest that over-expression of activated H-ras inhibited apoptotic cell death by blocking the activity of apoptotic endonuclease(s). This study was designed using antisense H-ras oligodeoxynucleotides (ODN) to evaluate whether alterations of H-ras expression in BEL-7402 human hepatocellular carcinoma cells could influence the induction of apoptosis in vitro and in vivo. We found that, in vitro, continuous suppression of H-ras expression could decrease the proliferation of BEL-7402 cells and inhibit H-ras-induced entry into S phase. In situ end labeling showed that a large number of cells underwent apoptotic cell death after treatment with antisense H-ras ODN (P < 0.01), and gel electrophoresis of DNA extracted from these cells demonstrated a typical DNA ladder, characteristic of apoptosis. In vivo study indicated that pretreatment with antisense H-ras significantly retarded tumor growth in comparison with the untreated controls or tumors treated with non-specific ODN (P < 0.01, P < 0.01). In situ end-labeling revealed that pronounced apoptotic nuclei were also present in the tissue treated with antisense H-ras ODN (P < 0.01). Immunocyto-histochemical study showed that expression of p21H-ras was significantly decreased after treatment with antisense H-ras. These results indicate that suppression of H-ras over-expression by antisense ODN could effectively inhibit tumor growth and revive the apoptotic pathway by releasing the activity of apoptotic endonuclease(s). The data also suggest the need for further studies to elucidate molecular events involved in antisense H-ras-released apoptosis and evaluate its therapeutic implications.

Animals↗

Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma.

The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma-LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 nude mice; the mice were then randomized into two groups. To one group, TNP-470 30 mg/kg was given as a subcutaneous injection every other day from day 1 to day 15 and the mice were sacrificed on day 26. An antitumor effect of TNP-470 was clearly demonstrated by tumor weight (0.97 +/- 0.34 g compared to 2.04 +/- 0.34 g, P < 0.001) and alpha-Fetoprotein value (93 +/- 59 micrograms/L compared to 769 +/- 282 micrograms/L, P < 0.001). There was also an anti-metastatic effect of TNP-470. Lung metastases developed in only 1 of 12 mice in the treated group, while they developed in 6 of mice of the control group. No severe side-effect of TNP-470 was found in this study. In vitro study revealed that the purified hepatoma cells were insensitive to TNP-470 (the 50% inhibitory concentration was 43 micrograms/ml). These results suggest that the angiogenesis inhibitor TNP-470 has both strong antitumor and anti-metastatic effects on a human hepatocellular carcinoma model in nude mice.

Animals↗

High-intensity focused ultrasound in the treatment of experimental liver tumour.

This project aimed to determine the adequacy and accuracy of high-intensity focused ultrasound (HIFU) for ablating experimental liver tumour, and to assess imaging methods for monitoring the therapeutic results. The rabbit liver pseudotumour model was established by injection of Freund's complete adjuvant into the liver; the animals then received HIFU therapy via laparotomy at the focal point of the beam (1.1 MHz, 500 W/cm2, 20 s). The rabbits were sacrificed at scheduled times after treatment and liver tumours were examined histologically. Sequential imaging of the liver tumour was performed before and after HIFU treatment. HIFU accurately destroyed the rabbit liver tumour and induced coagulation necrosis 24 h later. Sonographic imaging studies revealed that characteristic changes occurred. A hyperechoic mass turned to a hypoechoic lesion with no Doppler signal, and a high echogenic rim appeared 24 h after HIFU treatment, correlating well with the pathological changes of a sonoablated lesion. These results verify that HIFU has the power to ablate liver tumour quite adequately and accurately, and that sonography is useful for monitoring sonoablated liver tumour.

Animals↗

Expression of the integrin alpha5 subunit and its mediated cell adhesion in hepatocellular carcinoma.

Tumor invasion and metastasis are complex processes, requiring the ability of tumor cells to interact with proteins of the extracellular matrix through cell-adhesion molecules on the cell surface. Integrins are heterodimeric membrane glycoproteins, consisting of alpha and beta subunits, which enable cells to recognize adhesive substrates in the extracellular matrix. The roles of the integrin alpha5beta1 in tumor invasion are highlighted by finding that some tumor cells have lost or reduced alpha5beta1 expression. It therefore functions as a negative signaling regulator. Expression of alpha5beta1 and its mediation of cell adhesion in hepatocellular carcinoma (HCC) have not been elucidated. In surgical specimens of HCC we found, by immunohistochemistry and Northern blot analysis, that the alpha5-positive rates in cancerous tissues were lower than the corresponding rates in non-cancerous tissues. Reduced expression of the integrin alpha5 occurred more frequently in HCC with more malignant phenotypes, such as poor differentiation, large size (more than 10-cm in diameter), absence of capsule and high invasion. Reverse transcription/polymerase chain reaction, a more sensitive assay, was used to detect the alpha5 mRNA level in LCID20, a highly metastatic model of human HCC, and LCID35, a low-metastasis model. The results showed that integrin alpha5 was negative in the former and positive in the latter. Cell adhesion assays showed the maximal percentage inhibition of anti-alpha5 mAb on SMMC 7721 cell adhesion to fibronectin to be 68.9 +/- 4.9% at the saturation concentrations of each antibody (200 microg/ml). If anti-alpha5 mAb was combined with anti-beta1 mAb, the inhibition was 74.1 +/- 11.1%. It is concluded that reduced expression of the integrin alpha5 subunit is correlated with more malignant phenotypes of human HCC. Any change in the adhesion of hepatocellular carcinoma cells to fibronectin is mainly dependent upon the function of the integrin alpha5beta1.

Antigens, CD↗

Reconstruction and expression of chimeric anti-HBx antibody in Escherichia coli.

The variable regions of murine monoclonal anti-HBx immunoglobulin and the constant region of human antibody were cloned by reverse transcript-polymerase chain reaction (RT-PCR). The heavy-chain and light-chain variable regions were connected and coexpressed with human constant region C-r3 and C-k3 in the reconstructed vector of E. coli. The products showed high specificity and binding ability with HBx. Which is closely associated with hepatocarcinogenesis. This makes it possible to humanize the mouse monoclonal antibodies and express the fusion protein in E.coli for potential radioimmunotherapy in patients with hepatocellular carcinoma.

Animals↗

Expression and purification of single-chain anti-HBx antibody in Escherichia coli.

Monoclonal antibodies have been widely used in tumor targeting studies with promising results. However, their clinical application has been limited by heterogeneity and macro-molecular movement of murine antibody. In this study, the variable-region (heavy- and light-chain) fragments of anti-HBx monoclonal antibody were enriched by the polymerase chain reaction. The expression vector, which included a 6x histidine sequence in the 3' terminus of the HBx single-chain antibody (sFv) was recombined with a linker sequence (KLGGGGFSGA) between the variable regions. The expression product from Escherichia coli fused with 6xHis was purified by nickel (Ni2+) nitrilotriacetate chelating resin. The results of enzyme-linked immunosorbent assay and Western blotting showed that sFv had binding affinity with HBxAg, suggesting that it could become a novel targeting carrier in clinical trials.

Animals↗

Iodized oil enhances the thermal effect of high-intensity focused ultrasound on ablating experimental liver cancer.

The influence of the biological medium on high-intensity focused ultrasound (HIFU) therapy for ablating experimental liver cancer was studied. In study 1, the temperature rise in the focal zone in the presence of iodized oil or castor oil was observed in vitro. The results showed that HIFU with iodized oil produced a higher and faster temperature rise than did HIFU with castor oil, whether high-power (500 W/cm2) or relatively low-power (136 W/cm2) conditions were used (P = 0.0008 and P = 0.0004 respectively). With the excised liver samples, the temperature also rose higher and more rapidly after injection of iodized oil into the liver than when castor oil was injected (P = 0.0239), and the target liver tissue revealed more radically and extensive destruction with iodized oil than with castor oil. In study 2, 48 nude mice, bearing primary liver cancer LTNM4 implanted subcutaneously, were randomly divided into four groups. Group I (n = 12) were the controls, group II (n = 12) were injected with iodized oil alone, group III (n = 12) received HIFU treatment, and group IV (n = 12) were exposed to HIFU after iodized oil injection. Significant inhibition of tumor growth was seen in groups III and IV as compared with group I or group II (P < 0.05), the tumor growth inhibition rate on the 28th day after treatment being 87% and 93% respectively. Significantly improved survival was noted in groups III and IV compared with groups I and II (P < 0.05). Histologically, group IV showed more complete tumor necrosis than did group III. These data suggest that HIFU combined with iodized oil might have achieve of synergism, location and targeting in the treatment of liver cancer.

Animals↗

Management of hepatocellular carcinoma: long-term outcome in 2639 cases.

This paper reports the progress of management in 2639 patients with pathologically proven primary liver cancer (PLC) over the past three decades, and the factors improving long-term outcome. The 5-, and 10-year survival after resection of PLC was 45.9% and 34.8%, respectively, for the whole series (n = 1826), and 61.3% and 45.7%, respectively, for patients with small PLC (< = 5 cm, n = 645). The 5-year survival after cryosurgery was 37.9% for the whole series (n = 191), and 53.1% for patients with small PLC (n = 56). The 5-year survival of 73 patients receiving sequential resection after cytoreduction therapy was 67.8%. The 5-year survival after re-resection for recurrence tumor (n = 148) was 34.5%; 239 patients survived more than 5 years; 124 of these patients (51.9%) were small PLC, and 63 patients survived more than 10 years. Encouraging changes in the prognostic pattern were observed when the PLC data of 1958-1970 (n = 178), 1971-1982 (n = 582) and 1983-1994 (n = 1879) were compared; the 5-year survival being 4.8%, 11.2% and 45.4%, respectively, and the 10-year survival being 4.2%, 7.5% and 34.6%, respectively. Some aspects to prolong survival further were discussed.

Adolescent↗

Three decades' experience in surgery of hepatocellular carcinoma.

In the author's institution, 2254 patients with hepatocellular carcinoma (HCC) have been treated during 1958-1994. The overall 5-year survival increased from 5.4% (1958-1970), to 11.9% (1971-1982), to 46.2% (1983-1984), which correlated well with the increasing proportion of small HCC in the series (2.6%, 12.1%, and 33.4%, respectively); with the increasing percentage of limited resection (3.1%, 32.2%, and 58.3%); with the increasing number of re-resections for recurrence (0, 27, and 114 patients); and with the increasing number of second stage resections (0, 5, and 67 patients). In our institution, surgical approaches that resulted in significantly prolonging survival included: small HCC resection, re-resection, and cytoreduction followed by sequential resection for initially unresectable HCC. Experience in these 3 aspects suggests: (a) Small HCCs are mainly found by screening using AFP and ultrasonography (US) in a high risk population, and limited resection is the best treatment in patients with compensated liver cirrhosis, the 5-year survival after resection being 62.9% (n = 549). (b) Postoperative monitoring using AFP/US every 2-3 months for 5-10 years after curative resection is needed to detect subclinical recurrence. Limited re-resection is indicated for liver recurrence less than 3 nodules, and lung lobectomy is of proven merit to prolong survival for solitary lung metastasis. Re-resection of subclinical recurrence has resulted in a 10-20% further increase in 5-year survival after curative resection. (c) Palliative surgery other than resection such as hepatic artery ligation (HAL) and cannulation with arterial infusion (HAI), cryosurgery, etc. are superior to palliative resection with residual cancer. (d) Cytoreduction and sequential resection have provided hope for localized unresectable HCC, particularly in the right cirrhotic liver. Multimodality combination treatments such as HAL+HAI+radioimmunotherapy/regional radiotherapy are acceptable cytoreductive therapies. Repeated transcatheter hepatic arterial chemoembolization (TACE) is an alternative nonsurgical approach. Sequential resection is important to eradicate residual cancer after cytoreduction. The 5-year survival of 72 patients with cytoreduction and sequential resection for initially unresectable HCC was 62.1% and resulted in improving 5-year survival in the entire series of unresectable HCC over the 3 periods from 0% to 7.4% to 25.7%, respectively. However, multicentric origin and tumor invasiveness are two major targets to be studied in the control of recurrence and metastasis.

Carcinoma, Hepatocellular↗