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Objective: To evaluate the relationship between PAR1 (Protease-Activated Receptor 1) expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection., Methods: Real-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage. Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated., Results: Peritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P < 0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P < 0.05). Kaplan-Meier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival (OS) (P < 0.05) of HCC patients and the time to recurrence (TTR) (P < 0.05). The 1, 3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue., Conclusions: Peritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.

Osteopontin (OPN) has close relationship with metastasis in hepatocellular carcinoma but its downstream signal pathways have not been well defined in hepatocellular carcinoma. The object of this study is to identify the associated signal pathways in human HCC tissues. The expressions of OPN, intergrin aV, CD44v6, P-FAK, FAK, P-Src, Src, P-ERK and P-AKT were assayed using TMA analysis. The relationship of OPN with P-ERK, P-Src and P-AKT were explored and the role in HCC metastasis was analysed. The expression levels of OPN, intergrin aV, CD44v6, P-FAK, P-Src, Src, P-ERK and P-AKT in HCC tissue were significantly higher than that in normal tissue (P value is less than 0.05). No significant difference was found between the expression levels of FAK in HCC tissue and normal tissue (P value is more than 0.05). OPN expression was significantly associated with Integrin av (P value is less than 0.01), CD44V6 (P value is less than 0.01) and P-ERK (P value is less than 0.05) but not with P-Src, P-FAK and P-AKT (P value is more than 0.05). The expressions of P-FAK (P value is less than 0.05), P-Src (P value is less than 0.01) and P-AKT (P value is less than 0.05) were significantly associated with Integrin av and the P-FAK expression was also significantly associated with CD44V6 (P value is less than 0.01). OPN promotes HCC metastasis though Integrin av/CD44V6/MAPK pathway in human HCC.

Background & Aims: Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis mainly due to metastasis. MicroRNAs are endogenous small noncoding RNAs that regulate cellular gene expression and are functionally linked to tumourigenesis. Using microarray analysis, we recently identified 20 miRNAs associated with HCC metastasis. Here, we carried out further analyses on one of these microRNAs, let-7g, to determine whether it is functionally linked to HCC metastasis., Methods: Quantitative real-time polymerase chain reaction was used to determine the level of mature let-7g transcript in HCC clinical specimens and its correlation with patient survival. Ectopic expression of let-7g was carried out in HCC cell lines to assess its influence on cell growth, migration, and invasion., Results: We confirmed that the level of let-7g was significantly lower in metastatic HCCs compared to metastasis-free HCCs. Moreover, low let-7g expression in a tumour was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of let-7g significantly inhibits HCC cell migration and cell growth. In-silico analysis revealed members of soluble collagens as potential targets of let-7g. Consistently, the levels of type I collagen alpha2 (COL1A2) and let-7g were inversely correlated in HCC clinical specimens. COL1A2 was experimentally validated as a direct target of let-7g. Moreover, addition of COL1A2 counteracted the inhibitory effect of let-7g on cell migration., Conclusions: These results suggest that let-7g may suppress HCC metastasis partially through targeting COL1A2., (Copyright (c) 2010. Published by Elsevier B.V.)

Objective: To investigate the clinicopathologic features, diagnosis and treatment of hepatic angiomyolipoma (HAML)., Methods: The clinical, histopathological, treatment and prognosis data of 51 patients treated for HAML from October 1998 to October 2007 were retrospectively analyzed., Results: HAML had a female predilection (female/male = 41/10) and the mean age was 44 years old. The main symptoms were abdominal mass (33 cases) and abdominal pain or discomfort (15 cases), the other 2 cases presented as fever. Histopathologically, HAML was composed of a heterogeneous mixture of blood vessels, smooth muscle, and adipose cells. Immunohistochemical staining showed relatively high positive rate of HMB-45 (50/51), SMA (47/49) and S-100 (39/42). All 51 patients underwent partial hepatectomy. The mean hospital stay was 13.8 days and mean intraoperative blood loss was 263 ml. There was no recurrence or metastasis after a mean follow-up of 55.4 months., Conclusions: HAML is a rare benign mesenchymal tumor of the liver. Definitive diagnosis of HAML depends on the pathohistological findings and HMB-45 positive myoid cell is an important diagnostic marker. Complete surgical resection is the optimal treatment for HAML with favorable prognosis.

Objective: To identify the metastasis-related miRNAs in hepatocellular carcinoma (HCC) cell lines., Methods: A qRT-PCR method was established and optimized., Results: All candidate metastasis associated miRNAs except miR-124a were expressed in high metastasis cell line MHCC97H and low metastasis cell line MHCC97L, while some miRNAs were differentially expressed between liver cancer cell line (HepG2) and hepatic cell line (L02) (P less than 0.05), these miRNAs include: miR-148b (1.96+/-0.51 vs 3.76+/-0.28), miR-9 (-4.38+/-0.86 vs -1.10+/-0.53), miR-30c (8.41+/-0.40 vs 6.82+/-0.29), miR-338 (3.14+/-0.29 vs -2.36+/-0.32), miR-34a (0.71+/-0.40 vs -2.95+/-0.26), Let-7g (-4.07+/-0.55 vs -6.98+/-0.56). miR-148b expression was about 4 times higher than miR-148a [5.46 (IQR 4.25-6.67) vs 1.29 (IQR 0.94-1.64)] in all cell line tested (Z=-5.097, P=3x10(-7))., Conclusion: This study may help to understand the biological significance of miRNAs in HCC metastasis.

Objective: To assess the feasibility, safety and outcome of anatomical laparoscopic left lateral hepatic lobectomy for benign and malignant liver tumors., Methods: From April 2005 to May 2008, 11 patients (7 male, 4 female; mean age 51.7 years) underwent anatomical laparoscopic left lateral hepatic lobectomy. Four patients presented with hepatocellular carcinoma and cirrhosis, while 1 patient had metastatic liver tumors from postoperatively colon cancer, five patients had hemangioma (2 cases with gallstones underwent cholecystectomy), 1 patient had a huge symptomatic angiolipoleiomyoma. Mean tumor size was 5.8 cm (range 2.1 to 12.0 cm). All the lesions were localized in the anatomical left lateral lobe (segments II to III)., Results: The mean operative time was 147 min (range 120 to 180 min). There were no intraoperative or postoperative complications, and blood transfusions were not required. The mean postoperative hospital stay was 5.9 days., Conclusions: Anatomical laparoscopic left lateral hepatic lobectomy are feasible and safety.

Objective: To evaluate the efficacy of radiofrequency ablation for the treatment of postoperative recurrence of hepatocellular carcinoma and whether radiofrequency ablation can be used as first line treatment for recurrent hepatocellular carcinoma., Methods: There were 213 patients with small recurrent hepatocellular carcinoma (tumor size of 3 cm or less and no more than 3 nodules) who treated in Liver Cancer Institute, Fudan University from January 2000 to December 2005. Among these patients 68 were treated with radiofrequency ablation and 145 were treated with repeated surgical resection. Kaplan-Meier method was used to evaluate the overall survival or disease free survival. Log-rank used to determine the survival difference between groups and COX proportional hazard was used for multivariate analysis to evaluate the risk factors for prognosis. The overall survival or disease free survival was calculated from the time treated with radiofrequency or repeated surgical resection., Results: The 1-, 3-, 5-years overall survival rates were 94.7%, 65.1%, 37.3% and 88.1%, 62.6%, 41.0% in radiofrequency ablation group and surgical repeated resection group, respectively. There was no significant difference between two groups (P = 0.693). However, the disease free survival was better in repeated surgical resection than in radiofrequency ablation, which were 79.4%, 48.1%, 34.4% and 58.0%, 27.8%, 12.4% in repeated surgical resection and radiofrequency ablation, respectively (P = 0.001). The interval between recurrence and initial hepatectomy with more than 2 years was independent factor favor to good prognosis., Conclusions: Radiofrequency ablation seems to be as effective as repeated surgical resection owing to comparable overall survival and can be considered as alternative therapy for surgical resection treatment of small recurrent hepatocellular carcinoma.

Objective: To evaluate the usefulness of serum alpha-fetoprotein (AFP) in clinical diagnosis and screening for hepatocellular carcinoma (HCC)., Methods: Totally 290 HCC patients, 48 liver cirrhosis patients, and 49 healthy subjects were enrolled in this study. Serum AFP analysis was performed to investigate the correlation between the serum AFP level in HCC and the clinical or biochemical parameters of the disease, which included the size and number of tumor and the TNM stage. Sensitivities and specificities of AFP in HCC prediction at different cut-off levels were determined., Results: The serum AFP level was significantly higher in HCC patients than in liver cirrhosis patients (P = 0.0274) and healthy subjects (P = 0.0001). Among 290 HCC patients, 95 patients (32.8%) were AFP-negative (AFP < 20 microg/L), 195 (67.2%) were AFP-positive (AFP > or =20 microg/L). Sensitivity and specificity of AFP at 20 microg/L cut-off was 67.2% and 29.2%, respectively, and the positive and negative predictive value was 85.2% and 12.8%, respectively. Sensitivity of AFP at 400 microg/L cut-off was only 42.8%. Serum AFP levels were significantly different among HCC with different tumor size (P = 0.0009), tumor number (P = 0.0001), and TNM stage [TNM I vs. TNM III-IV (P = 0.0001); TNM II vs. TNM III-IV (P = 0.0003)]., Conclusions: Increased serum AFP level is highly suggestive in HCC diagnosis. Combined with other imaging examinations, AFP level can be used for the screening of high risk population and for the follow-up of AFP-positive patients.

Purpose: Our previous studies have shown that chromosome 8p deletion correlates with metastasis of hepatocellular carcinoma (HCC). This study was to determine whether 8p deletion could be used in predicting the prognosis of patients with HCC, particularly in those with early stage of HCC., Experimental Design: A total of 131 patients with tumor-node-metastasis (TNM) stage I of HCC who underwent curative liver resection were enrolled. Loss of heterozygosity (LOH) was examined using 10 microsatellite markers at chromosome 8p, as well as 14 microsatellites at chromosome 1p, 17p, 4q, 13q, and 16q, and their association with 5-year overall survival (OS) and disease-free survival (DFS) of patients was analyzed., Results: In the entire cohort of patients, the mean LOH frequency at these 24 loci was 43.2%; LOH frequencies at D8S298 and D1S199 were 31.5% and 33.7%, respectively. LOH at D8S298 was associated with a worse 5-year OS (P = 0.008) and DFS (P = 0.038) in patients with TNM stage I of HCC. Likewise, the patients with LOH at D1S199 had a worse 5-year OS (P < 0.001) and DFS (P = 0.014) compared with those without LOH at D1S199. In multivariate analyses, LOH at D8S298 was an independent predictor of decreased DFS (hazard ratio, 0.372; 95% 95% confidence interval, 0.146-0.948; P = 0.038), whereas LOH at D1S199 was an independent predictor of decreased OS (hazard ratio, 0.281; 95% confidence interval, 0.123-0.643; P = 0.003)., Conclusions: LOH at D8S298 and D1S199 is independently associated with a worse survival in patients with TNM stage I of HCC after curative resection and could serve as novel prognostic predictors for this subgroup of patients.

Objectives: To detect the loss of heterozygosity (LOH) of circulating DNA in the plasma of patients with hepatocellular carcinoma (HCC), and to assess its potential as a clinical predictive marker., Methods: Three high-polymorphic microsatellite markers D8S277, D8S298 and D8S1771 located at chromosome 8p were selected to detect LOH in plasma DNA of 62 HCC patients. The associations between LOH and its clinicopathological features, including HBsAg, liver cirrhosis, serum AFP level, tumor size, tumor cell differentiation, and intrahepatic metastasis were also examined., Results: In plasma DNA of the 62 HCC patients, LOH was found at one or several loci in 36 (58.1%), and heterozygosity at D8S277, D8S298, and D8S1771 loci was 74.2% (46/62), 75.8% (47/62), and 69.4% (43/62), respectively. LOH frequency at D8S277, D8S298 and D8S1771 was 32.6% (15/46), 44.7% (21/47), and 46.5% (20/43), respectively. LOH in plasma DNA was more frequently detected in the patients with intrahepatic cancer metastasis than those without metastasis (62.5 percent vs. 26.1 percent, P < 0.05); however, no statistically significant correlations were observed between LOH at these loci and other clinicopathological features analyzed in this study., Conclusions: LOH at D8S298 in plasma DNA may be a potential predictive marker of intrahepatic metastatic recurrence after surgical resection of the HCC.

Objective: To discuss the diagnosis and treatment of primary hepatic carcinoid tumor (PHCT)., Methods: Report one case of huge PHCT treated in February 2004, and search the other 19 cases which were published from January 1994 to December 2006 in the Chinese biological and medical literature database. The clinical manifestation, pathological findings, diagnosis and treatment of these 20 PHCT patients were analyzed retrospectively., Results: The main symptoms were abdominal pain or discomfort (8 cases) and abdominal mass (7 cases), cases with typical carcinoid syndrome were rare (3 cases). Immunohistochemical staining was positive for neuron-specific enolase, chromogranin A and synaptophysin in most cases. Sixteen cases received operation, among which there were 13 removed completely, other 4 cases were treated by transcatheter arterial chemoembolization (TACE)., Conclusions: The definite diagnosis of PHCT depends on pathological and histochemical findings. Complete surgical resection is the best treatment for PHCT with favourable prognosis. TACE is also effective for nonoperative cases.

Aim: To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) and to evaluate its prognostic value., Methods: Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated., Results: Compared with the healthy volunteers (17.6 +/- 9.5 ng/mL), a significant higher circulating DNA level was found in the patients with HCC (47.1 +/- 43.7 ng/mL, P = 0.000) or with liver cirrhosis (30.0 +/- 13.3 ng/mL, P = 0.002). The circulating DNA level was closely associated with tumor size (P = 0.008) and TNM stage (P = 0.040), negatively associated with the 3-year disease-free survival (DFS) (P = 0.017) and overall survival (OS) (P = 0.001)., Conclusion: Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.

Objective: To explore the features of microsatellite alterations of circulating DNA in the plasma of patients with hepatocellular carcinoma (HCC) and whether they are in concordance with those in the carcinoma tissues., Methods: Peripheral blood samples were collected from 62 HCC patients and the corresponding tumor tissues were obtained during operation. Three high-polymorphic microsatellite markers located at chromosome 8p, D8S277, D8S298, and D8S1771, were selected to be used to detect the loss heterozygosity (LOH) and microsatellite instability (MSI) by PCR and sequencing., Results: Joint detection showed that 39 out of the 62 tissue samples showed LOH at all the 3 loci, and the same alterations at the same loci were seen in 33 matched plasma samples with a concordance rate of 84.6%. Nineteen tissue samples showed MSI at all 3 loci, and the same alterations were shown in 14 matched plasma samples with a concordance rate of 73.3%. The rate of LOH for at least one locus in the plasma DNA was 58.1% (36/62), significantly higher than the rate of MSI at at least one locus in the plasma samples (29.0%, 18/62, P < 0.01). The MSI positive rate in the loci D8S277 of the plasma DNA was 22.6%, significantly higher than those of the other 2 loci (4.8% and 4.8% respectively, both P < 0.05). The MSI positive rate at the loci D8S277 of the cancer tissue was 46.8%, significantly higher than those of the other 2 loci (38.7% for D8S298 and 37.1% for D8S1771, both P < 0.05)., Conclusion: Microsatellite alterations show a high concordant pattern between the tissue and plasma DNA in HCC, which indicates that the microsatellite alterations of tumor tissue are reflected by plasma DNA, LOH may play an important role in hepatocarcinogenesis whereas MSI may also contribute to this progress in a less significant way, and D8S277 is a sensitive locus to MSI in HCC.

Objective: To study the effect of osteopontin (OPN) expression down-regulated by RNA interference (RNAi) on the invasiveness of hepatocelluar carcinoma cell line HCC-LM3., Methods: HCC-LM3 cells were transfected with the chemically synthesized small interfering RNA (siRNA) formulated by lipofectamine 2000. Wild type HCC-LM3 and HCC-LM3 cells transfected with non-specific siRNA served as controls. Real-time PCR and Western blotting were used to quantify the mRNA and OPN protein levels. The malignant phenotypes of transfected HCC-LM3 cells including cellular growth rate, colony formation and Matrigel invasion activities were analyzed., Results: Sequence-specific siRNAs targeting OPN suppressed OPN RNA expression by 79% and also decreased OPN protein level by 81% in HCC-LM3 cells. The number of formed colonies and migrating numbers in vitro were decreased in HCC-LM3 cells transfected using sequence-specific siRNAs targeting OPN relative to controls (P < 0.05)., Conclusion: This study demonstrated that specific siRNA is able to reduce OPN at both the mRNA and protein levels and significantly diminishes the invasiveness of hepatocellular carcinoma cells.

Objective: To investigate the enhanced predictive activity of preoperative plasma osteopontin (OPN) level in combination with intercellular adhesion molecule-1 (ICAM-1) for recurrence and prognosis of patients after resection of hepatocellular carcinoma (HCC)., Methods: A total of 75 patients received liver resection for HCC from August 2001 to December 2001 in authors' institute were enrolled in this study. The preoperative plasma levels of OPN and ICAM-1 were detected by ELISA, and the association of them combination with the recurrence and prognosis of HCC patients was analyzed., Results: OPN and ICAM-1 could be detected in all of the plasma samples of the tested patients. A significantly higher OPN level and ICAM-1 level were found in plasma of patients who were found to have HCC recurrence during the follow-up time compared with those without recurrence (210.40 vs. 154.86 ng/ml, P = 0.001; 1011.23 vs. 747.49 ng/ml, P = 0.027). A significant difference of OS and DFS were found in different subgroups with higher or lower level of OPN (625 vs. 808 days, P = 0.0006; 433 vs. 674 days, P = 0.0003); and a similar situation was found in patients of high- and low- ICAM-1 levels (651 vs. 794 days, P = 0.0269; 489 vs. 642 days, P = 0.0248). The 2-year recurrence rates of the patients with higher and lower plasma levels of both OPN and ICAM-1 were 87.50% and 28.00% (P < 0.001), respectively; and the 2-year OS rates were 37.50% and 88.00% (P = 0.001), and the 2-year DFS rates were 12.50%, and 76.00 (P = 0.001), respectively., Conclusions: The evaluation of preoperative plasma level of OPN or ICAM-1 may be helpful to predict the recurrence and prognosis of HCC patients in advance. The assessment of OPN level in combination with ICAM-1 could stratify patients into groups with different potentials of HCC recurrence and different outcomes more accurately than OPN or ICAM-1 individually.

Aim: To evaluate the effect of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on the prognosis of hepatocellular carcinoma (HCC) patients with or without risk factors for the residual tumor., Methods: From January 1995 to December 1998, 549 consecutive HCC patients undergoing surgical resection were included in this research. There were 185 patients who underwent surgical resection with adjuvant TACE and 364 patients who underwent surgical resection only. Tumors with a diameter more than 5 cm, multiple nodules, and vascular invasion were defined as risk factors for residual tumor and used for patient stratification. Kaplan-Meier method was used to analyze survival curve and Cox proportional hazard model was used to evaluate the prognostic significance of adjuvant TACE., Results: In the patients without any risk factors for the residual tumor, the 1-, 3-, 5-year survival rates were 93.48%, 75.85%, 62.39% in the control group and 97.39%, 70.37%, 50.85% in the adjuvant TACE group, respectively. There was no significant difference in the survival between two groups (P = 0.3956). However, in the patients with risk factors for residual tumor, postoperative adjuvant TACE significantly prolonged the patients' survival. There was a statistically significant difference in survival between two groups (P = 0.0216). The 1-, 3-, 5-year survival rates were 69.95%, 49.86%, 37.40% in the control group and 89.67%, 61.28%, 44.36% in the adjuvant TACE group, respectively. Cox proportional hazard model showed that tumor diameter and cirrhosis, but not the adjuvant TACE, were the significantly independent prognostic factors in the patients without risk factors for residual tumor. However, in the patients with risk factors for residual tumor adjuvant TACE, and also tumor diameter, AFP level, vascular invasion, were the significantly independent factors associated with the decreasing risk for patients' death from HCC., Conclusion: Postoperative adjuvant TACE can prolong the survival of patients with risk factors for residual tumor, but can not prolong the survival of patients without risk factors for residual tumor.

Aim: Hepatocellular carcinoma (HCC) with bile duct tumor thrombosis (BDT) is a rare event. The prognosis of this type of patients is very dismal. The aim of this study was to share the experience in the diagnosis and treatment of HCC with BDT, to further improve the prognosis of these patients., Methods: Thirty-four patients of HCC with BDT received surgical treatment in authors' institute from July 1987 to January 2003 were reviewed retrospectively. The experience in the diagnosis and treatment, and the outcome of this type of HCC patients were summarized., Results: Thirty of the 34 patients (88.2%) were positive for alpha-fetoprotein (AFP) (>20 microg/L), and 12 patients (35.3%) were found having obstructive jaundice before operation, 18 cases were suspected of "obstruction of bile duct" preoperatively. The primary tumors were frequently located at the left medial (13 cases) or right anterior lobe (14 cases). Thirty-one patients received liver resections and removal of BDT, while the other 3 patients received removal of BDT combined with hepatic artery ligation and cannulation (HAL+HAI), or only removal of BDT because their liver function reservation and general condition could not tolerate the primary tumor resection. The 1-year survival rate was 71.4%(20/28). The longest disease-free survival was over 15 years. The intrahepatic tumor recurrence within 1 year after operation was found in 14 patients (14/28, 50.0%)., Conclusion: Surgical removal of primary tumors and BDT is safe and beneficial to the HCC patients with BDT. Early detection, diagnosis, and surgical treatment are the key points to prolong the survival time of patients.

Objective: To evaluate the effect of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC) patients with residual tumor., Methods: The patients were classified into intervention group (with adjuvant TACE) and control group (without adjuvant TACE) who were further stratified to those with high risk (patients with single tumor > 5 cm in diameter, or with multiple tumors, invasion to blood vessels), and low risk factors. Univariate analysis and Cox model were used to analyse prognostic factors., Results: In low risk patients with residual tumor, the 1-, 2-, 3-, 4-year survival rate was 97.2%, 78.0%, 66.5% and 66.5% in the intervention group, and 91.2%, 81.4%, 70.3% and 54.4% in the control group, respectively. There was no statistical difference between the two groups in survival (log-rank P = 0.7667). Comparing with the control group, the 1-, 2-, 3-, 4-year survival rate was 89.5%, 73.4%, 59.2% and 53.8% in the intervention group, and 70.5%, 61.9%, 46.8% and 46.8% in the control group, respectively. Postoperative adjuvant TACE significantly prolonged the survival in high risk patients with residual tumor (P = 0.0029). Cox model revealed that the benefit of adjuvant TACE was significantly increased by the high risk factors in HCC patients with residual tumor., Conclusion: The beneficial effect of postoperative TACE was only observed in high risk patients with residual tumor but not in the low risk patients with residual tumor.

Objective: To clarify three-grade criteria of curative resection for primary liver cancer (PLC) and evaluate their clinical significance., Methods: Criteria of curative resection of PLC were summed up to three grades. Grade I: complete removal of all gross tumors with no residual tumor at the excision margin. Grade II: on the basis of Grade I, there was no extrahepatic metastasis, no hilar lymph node metastasis, no tumor thrombus in the main trunks and their primary tributaries of the portal vein, common hepatic duct, hepatic vein and vena cava inferior, and the tumor was not more than two in number. Grade III: in addition to the above criteria, AFP dropped to normal level (in patients with elevated AFP before surgery) within 2 months after operation, and no residual tumor upon diagnostic imaging. A total of 354 cases with PLC who had their liver resected was reviewed. Patients in each grade were divided into two portions depending on whether the treatment was curative or palliative., Results: The survival of patients receiving curative treatment was better than those receiving palliative treatment (P < 0.01). This was true for patients whose treatment belonged to anyone of the three-grade criteria. The survival was improved along with the promotion of curative criteria used. The 5-year survival rate of Grade I, II and III patients undergone curative resection was 43.2%, 51.2% and 64.4%, respectively (P < 0.01)., Conclusion: 1. The three-grade criteria may be used for judging the radicality of tumor resection for PLC. 2. The more stringent the criteria used, the better the survival would be. 3. Adopting high-grade criteria to select cases, to guide operation and postoperative follow-up would improve the results of liver resection for PLC.

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 (<10% -, 10-30% +, 31-50% ++, >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 predicting prognosis of patients after HCC resection than the common qualitative analysis.