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Aim Sirolimus (SRL) acts as a primary immunosuppressant or antitumor agent. The aim of the present study was to evaluate the influence of SRL on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) exceeding the Milan criteria. Materials and Methods We retrospectively examined 73 consecutive patients who underwent OLT for HCC exceeding the Milan criteria from March 2004 through December 2005. Among them, 27 patients were treated with SRL-based immunosuppressive protocols after OLT, and 46 patients by an FK506-based protocol. Statistical analysis was based on the intent-to-treat method. Results The 2 groups were comparable in all clinicopathologic parameters. The mean overall survival was 594 ± 35 days in the SRL group and 480 ± 42 days in the FK506 group ( P = .011); the mean disease-free survival period was 519 ± 43 days in the SRL group and 477 ± 48 days in the FK506 group ( P = .234). Multivariate analysis revealed Child's status ( P = .004) and immunosuppressive protocol ( P = .015) were the significant factors affecting overall survival. Only microvascular invasion ( P = .004) was significantly associated with disease-free survival. Among 24 surviving patient in the SRL group, 2 patients had SRL discontinued for toxicity; 10 had SRL monotherapy immunosuppression. Conclusion The SRL-based immunosuppressive protocol improved the overall survival of patients after OLT for HCC exceeding the Milan criteria, probably by postponing recurrence and with better tolerability.

Purpose: Cytokeratin 10 (CK10) was found to be expressed differently in human hepatocellular carcinoma (HCC) cell lines with different metastatic potentials in our previous research. The aim of this study was to assess the value of CK10 alone or in combination with cytokeratin 19 (CK19) in predicting tumor recurrence after curative resection in HCC patients. Experimental Design: CK10 expression in stepwise metastatic HCC cell lines and tumor tissues from 50 HCC patients was investigated using immunofluorescence assay, quantitative real-time reverse transcription-PCR, and Western blot analyses. Tumor tissue microarrays of 300 HCC patients who underwent curative resection between 1997 and 2000 were used to detect the expressions of CK10 and CK19. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Results: CK10 was overexpressed in the high metastatic HCC cell line and in tumor tissues of recurrent patients. Both univariate and multivariate analyses revealed that CK10 was a significant predictor for overall survival (OS) and disease-free survival, and that CK19 was a significant predictor for OS. CK10 expression was correlated with poor prognosis regardless of α-fetoprotein, tumor-node-metastasis stage, and vascular invasion. The 7-year OS and disease-free survival rates in CK10+ and/or CK19+ patients were 30.0% and 37.6%, respectively, which were significantly lower than that of CK10−/CK19− patients (56.1% and 60.0%, respectively; P < 0.001). Conclusion: CK10 is associated with HCC invasiveness. CK10 alone, or in combination with CK19, can be a novel predictor for poor prognosis of HCC patients after curative resection.

Objective To study severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. Methods Clinical records of severe and rare complications following TACE in 1348 cases of liver cancer from January 1997 to February 2004 were studied retrospectively. Results A total of 2012 TACE procedures were performed for 1348 patients. There were 3 cases of spontaneous rupture of liver cancer, 1 case of perforation of duodenum, 3 cases of liver abscess (1 of them was associated with sepsis), 1 case of pulmonary embolism, 1 case of spasm of the hepatic artery, 40 cases of hepatic artery occlusion, 3 cases of femoral nerve injury, 1 case of bilioma and 1 case of acute renal failure. Conclusion Although the severe complications of TACE are rare, the procedure should be done cautiously including super selection of hepatic artery, slow infusion of lipiodol, careful postoperative observations and early detection and management of complications.

Background/Aims: Recurrence after resection of hepatocellular carcinoma (HCC) is a frequent event. This study evaluated the effect of postoperative interferon α (IFN α) treatment on recurrence and survival in patients with hepatitis B virus (HBV)-related HCC. Method: Two hundred and thirty six patients were randomized after resection into IFN α treatment (5 mu i.m. tiw for 18 months) and control groups. Treatment was terminated if recurrence was diagnosed, and recurrence was managed the same way in both groups. Statistical analysis was based on the method of intent-to-treat. Results: The two groups were comparable in all clinicopathological parameters. The median overall survival was 63.8 months in the treatment group and 38.8 months in the control group (P=0.0003); the median disease-free survival period was 31.2 versus 17.7 months (P=0.142). Fever, leucocytopenia, and thrombocytopenia were adverse effects in the treatment group, but were mostly manageable. Conclusions: IFN α treatment improved the overall survival of patients with HBV-related HCC after curative resection, probably by postponing recurrence.

Early hepatic artery thrombosis (HAT) after orthotopic liver transplantation remains a significant cause of graft loss and patient death. The most effective treatment approach is still controversial. The purpose of this study was to assess the effect of continuous transcatheter arterial thrombolysis in the treatment of early HAT. Routine posttransplant color Doppler imaging (CDI) was performed to monitor hepatic artery blood flow. HAT was confirmed by arterial angiography in suspected cases. HAT was identified in 8 patients (8/287, 2.8%) which occurred on days 2 to 19 (mean, 5.2 days) after liver transplantation. Patients with HAT were treated with continuous transcatheter arterial thrombolysis using urokinase. Successful revascularization through thrombolysis was obtained in all eight cases. One patient died of a pulmonary infection at 2 months after liver transplantation. Another patient underwent retransplantation because of resistant allograft rejection and recurrence of HAT 6 months after the first operation, but died from multiple system organ failure 2 months later. The other six patients remained in good health during the follow-up period of 3 to 27 months. Our results demonstrate that CDI is an effective method to monitor the occurrence of early HAT after liver transplantation. Furthermore, continuous transcatheter arterial thrombolysis with urokinase could be a rational therapeutic approach to rescue the allograft following early HAT diagnosis confirmed by arterial angiography.

Objective The present study was designed to develop the “Three-Grade Criteria” for radical resection of primary liver cancer (PLC) and to evaluate its clinical significance.

Purpose: To investigate the effects on sensitivity to fluoropyrimidine and endothelial cell (EC) migration by transfection with thymidine phosphorylase (TP) cDNA to a hepatocellular carcinoma (HCC) cell line SMMC-7721. Methods: SMMC-7721 was transfected with pcDNA3.1/zeo (+) with human TP cDNA. TP mRNA expression was determined by RT–PCR. Sensitivity to fluoropyrimidine was determined by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Induction of EC migration was detected by Boyden chamber assay. Results: The construction of pcDNA3.1/zeo(+)-TP was verified by digestion with restriction endonuclease Apa1. When comparison was made between SMMC-7721 cell clone transfected with pcDNA3.1/zeo(+)-TP (S-TP) and control clone transfected with pcDNA3.1/zeo(+) (S-vector), we found that TP mRNA expression level was much higher in S-TP, being 2.09±0.16 vs 0.48±0.06 in S-vector (P

Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. This paper summarized a decade's studies on HCC metastasis at the Liver Cancer Institute of Fudan University. We have established a stepwise metastatic human HCC model system, which included a metastatic HCC model in nude mice (LCI-D20), a HCC cell line with high metastatic potential (MHCC97), a relatively low metastatic potential cell clone (MHCC97L) and several stepwise high metastatic potential cell clones (MHCC97H, HCCLM3, and HCCLM6) from their parent MHCC97 cell. Endeavors have been made for searching human HCC metastasis-related chromosomes/proteins/genes. Monogene-based studies revealed that HCC invasion/metastasis was similar to that of other solid tumors, and the biological characteristics of small HCC were only slightly better than that of large HCC. Using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), genotyping, cDNA microarray, and 2-dimensional gel electrophoresis, we obtained some interesting results. In particular, in collaboration with the National Institute of Health (NIH) in the United States, we generated a molecular signature that can classify metastatic HCC patients, identified osteopontin as a lead gene in the signature, and found that genes favoring metastasis progression were initiated in the primary tumors. We also found that chromosome 8p deletion, particularly in the region of 8p23, was associated with HCC metastasis. Cytokeratin 19 was identified as one of the proteins, which was found in MHCC97H, but not in MHCC97L cells. Experimental interventions using the high metastatic nude mice model have provided clues for the prevention of HCC metastasis. Translation from workbench to bedside demonstrated that serum VEGF, microvessel density, and p53 scoring may be of value for the prediction of postoperative metastatic recurrence. Interferon alpha proved effective for the prevention of recurrence both experimentally and clinically. In conclusion, HCC metastasis that probably initiated in the primary tumor is a multigene-involved, multistep, and changing process. The further elucidation of the mechanism underlying HCC metastasis will provide a more solid basis for the prediction and prevention of the metastatic recurrence of HCC.

Large primary liver cancer (PLC) more than 10 cm in diameter is not infrequently encountered in clinical practice. This study evaluated the clinicopathological features and long-term results after surgery for large PLC.Comparison of clinicopathological data between patients with PLC/=10 cm ( n=1,227) and PLC10 cm ( n=2,349) during the same period.In comparison with patients with PLC10 cm, patients with PLC/=10 cm were significantly younger ( P0.01), had a lower incidence of asymptomatic tumors (9.1% vs 39.5%, P0.001), higher alpha-fetoprotein levels (400 ng/ml, 78.3% vs 49.2%, P0.001), higher gamma-glutamyl transpeptidase levels (6U, 87.7% vs 70.5%, P0.001), a lower incidence of a history of hepatitis (45.0% vs 61.4%, P0.001) and associated macronodular cirrhosis (cirrhotic nodules/=0.3 cm, 59.8% vs 66.6%, P0.001), poor differentiation of tumor cells (Edmondson grade 3-4, 24.3% vs 19.7%, P0.01), a lower percentage of single nodule tumors (59.9% vs 75.4%, P0.001) and well-encapsulated tumors (28.5% vs 62.1%, P0.001), a higher proportion of tumor emboli in the portal vein (20.5% vs 9.0%, P0.001), a lower resection rate (50.6% vs 86.8%, P0.001), a lower curative resection rate (54.8% vs 78.3%, P0.001), a higher operative mortality rate (4.5% vs 2.3%, P0.001), and less local resection (52.5% vs 80.2%, P0.001). The 5- and 10-year survival rates after resection were 26.2% and 17.5%, respectively, for patients with PLC/=10 cm ( n=621), and 54.3% and 39.5%, respectively, for patients with PLC10 cm ( n=2039) ( P0.01).Large PLC had specific clinicopathological features. Surgery is the first choice of treatment. In selected patients, resection is safe and offers the chance of long-term survival. Large PLC does not exclude the possibility of cure.

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies. Its high mortality rate is mainly a result of intra-hepatic metastases. We analyzed the expression profiles of HCC samples without or with intra-hepatic metastases. Using a supervised machine-learning algorithm, we generated for the first time a molecular signature that can classify metastatic HCC patients and identified genes that were relevant to metastasis and patient survival. We found that the gene expression signature of primary HCCs with accompanying metastasis was very similar to that of their corresponding metastases, implying that genes favoring metastasis progression were initiated in the primary tumors. Osteopontin, which was identified as a lead gene in the signature, was over-expressed in metastatic HCC; an osteopontin-specific antibody effectively blocked HCC cell invasion in vitro and inhibited pulmonary metastasis of HCC cells in nude mice. Thus, osteopontin acts as both a diagnostic marker and a potential therapeutic target for metastatic HCC.

Objective To report our experience of retrograde hepatectomy in 244 cases of difficultly resected liver cancer.

Recently, we found that chromosome 8p deletion might be associated with hepatocellular carcinoma (HCC) metastasis by analyzing the differences in chromosomal alterations between primary tumors and their matched metastatic lesions of HCC with comparative genomic hybridization (CGH) (Qin et al. 1999). To further confirm this interesting finding, the genomic changes of two models bearing human HCC with different metastatic potentials (LCI-D20 and LCI-D35), and the new human HCC cell line with high metastatic potential (MHCC97) were analyzed by CGH. Gains on 1q, 6q, 7p, and 8q, and losses on 13p, 14p, 19p, 21, and 22 were detected in both LCI-D20 and LCI-D35 models. However, high copy number amplification of a minimum region at 1q12-q22 and 12q, and deletions on 1p32-pter, 3p21-pter, 8p, 9p, 10q, 14q, and 15p were detected only in the LCI-D20 model. Gains on 1p21-p32, 2p13-p21, 6p12-pter, 9p, 15q, and 16q11-q21, and losses on 2p23-pter, 4q24-qter, 7q31-qter, 12q, 17p, and 18 were detected only in the LCI-D35 model. The chromosomal aberration patterns in the MHCC97 cell line were similar to its parent LCI-D20 model, except that gains on 19q and losses on 4, 5, 10q, and 13q were found only in the cell line. These results provide some indirect clues to the metastasis-related chromosomal aberrations of HCC and further support the finding that 8p deletion is associated with HCC metastasis. 1q12-22 and 12q might harbor a novel oncogene(s) that contributes to the development and progression of HCC. Amplification on 8q and deletions on 4q and 17p may be not necessary for HCC metastasis.

To study the relationship between thrombomodulin (TM) plasma levels and the formation of portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma (HCC).Pre- and-postoperative plasma TM levels of 45 patients with HCC and six patients with benign liver-occupying lesion were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of TM in human HCC tissues was determined by immunohistochemistry assay.The preoperative plasma TM level of patients with HCC (10.2+/-5.7 ng/ml) was significantly higher than that of those patients with benign liver-occupying lesion (6.1+/-2.2 ng/ml) and that of normal controls (5.7+/-1.0 ng/ml), respectively (P0.05). The postoperative TM level of 40 patients with HCC whose tumors had been removed decreased significantly than the preoperative TM level (10.8+/-5.3 ng/ml versus 7.6+/-4.2 ng/ ml, P0.05), whereas there was no significant difference between the preoperative and postoperative TM level of six patients with benign liver-occupying lesion (6.1+/-2.2 ng/ml versus 5.9+/-1.8 ng/ml, P0.05). The preoperative plasma TM level of patients with single HCC (11.5+/-5.9 ng/ml) or no PVTT (11.4+/-5.6 ng/ml) was significantly higher than that of those patients with multiple HCC (8.1+/-4.6 ng/ml) or PVTT (6.9+/-4.5 ng/ ml), respectively (P0.05). The preoperative plasma TM level of the patients with HCC tissue that stained positive for TM was significantly higher than those with tissue that stained negative for TM (12.2+/-6.5 ng/ ml versus 8.7+/-4.6 ng/ml, P0.05). The postoperative plasma TM level showed no difference between the patients with HCC tissue stained positive and negative for TM (8.3+/-4.1 ng/ml versus 7.6+/-4.4 ng/ml, P0.05). There was also no significant difference between the plasma TM level and other clinicopathological futures.Plasma TM increases in patients with HCC and can be a biomarker of the formation of PVTT.

BACKGROUND Recently, the implementation of screening programs using α-fetoprotein (AFP) and ultrasonography in high risk populations has identified increasing numbers of patients with small hepatocellular carcinoma (small HCC). The aim of this study was to summarize the authors' experience in patients who underwent hepatectomy for small HCC and the factors that influence or improve long term survival. METHODS The study included 1000 patients who underwent hepatectomy for small HCC (≤ 5 cm) and compared them with 1366 patients who underwent hepatectomy for large HCC (> 5 cm) during the same period. A Cox proportional-hazards model was used for multivariate analysis of prognostic factors. RESULTS Comparison between patients with small HCC (n = 1000 patients) and patients with large HCC (n = 1366 patients) revealed that those with small HCC had a higher resection rate (93.6% [1000 of 1068 patients] vs. 55.7% [1366 of 2451 patients]; P 0.05). Reresection for subclinical recurrence or solitary pulmonary metastasis after small HCC resection was undertaken in 84 patients. CONCLUSIONS Resection is still the modality of first choice for the treatment of patients with small HCC. Minor resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality, and reresection for subclinical recurrence or solitary pulmonary metastasis was important approach to prolonging survival further. Cancer 2001;91:1479–86. © 2001 American Cancer Society.

Surgical resection has been accepted as the only curative therapy for primary liver cancer (PLC). Unfortunately, most patients are surgically unresectable when they seek treatment. An alternative therapeutic approach for some of these patients is transcatheter arterial chemoembolization. However, this is not curative by itself, and additional therapy is required to eradicate residual disease. This study investigates the approach of preoperative hepatic arterial chemoembolization followed by the combination of oral Furtulon (5'-deoxy-5-fluorouridine) as a radiosensitizer and external beam radiotherapy (RT). From July 1997 to December 1998, 25 patients with unresectable PLC were treated with hepatic arterial chemoembolization followed by limited-field radiotherapy plus oral Furtulon as a radiosensitizer. Hepatic arterial chemoembolization was performed with 5-fluorouracil 1 g, cisplatin 80 mg (DDP), mitomycin C (MMC) 10 mg, and arterial embolization with iodized oil-10 ml mixed with 10 mg MMC. Hepatic arterial chemoembolization was performed at regular intervals of 6 weeks, and the patients then received limited-field RT. Mean tumor dose was 4,600 cGy (range, 4,100-5,200 cGy) in daily 1.8-Gy fractions, 5 times a week. The toxicity and responses between RT and surgery were assessed. After surgical evaluation, resection was performed. The histopathologic study was also performed in the specimens of both normal and radiation-injured liver tissues from the patients who underwent resection. Seventeen of 25 patients (68%) showed an objective response. One patient with cholangiocarcinoma involving the portal lymph nodes attained a complete response. Eight patients (32%) underwent sequential resection. The most common toxicity was an increase in liver enzymes, which were less than twofold of the upper limit of normal. Follow-up computed tomography studies after treatment showed a low-attenuation area adjacent to the hepatic tumor in the target volume. On pathologic evaluation, the low-attenuation area revealed hyperemia, distended hepatic sinusoids packed with erythrocytes, and hepatic cell loss when examined with microscopy; "new-born" hepatocytes, hepatic cords in the process of forming, and endothelial cells have appeared on electronic microscopic examination. The combination of hepatic arterial chemoembolization and external radiotherapy is efficacious and a safe modality for unresectable primary liver cancers. Furtulon offers the potential for use as a clinical radiosensitizer. Radiation can significantly damage the liver tissue between 41 Gy and 52 Gy, but the new hepatocytes were forming within the radiation-injured liver after RT.

Purpose: Both platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) are known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We aimed at evaluating the gene expression of PD-ECGF and VEGF in hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). Patients and methods: Surgical specimens (28 HCC, 28 nontumorous liver tissues and 18 PVTT) were studied by Northern blot analysis. The levels of PD-ECGF mRNA and VEGF mRNA expression were measured by densitometric scanning of the autoradiographs, and they were normalized to the level of expression of an internal control (glyceraldehyde-phosphate dehydrogenase) mRNA. Results: The expression rates of PD-ECGF mRNA in PVTT, HCC and nontumorous liver tissues were 77.8% (14/18), 67.9% (19/28) and 35.7% (10/28), being 88.9% (16/18), 75.0% (21/28) and 17.9% (5/28) respectively for VEGF mRNA. The expressions of PD-ECGF mRNA and VEGF mRNA were higher in HCC with PVTT than when PVTT was absent (P

By 1996, 2898 patients with pathologically proven hepatocellular carcinoma (HCC) had been treated at the Liver Cancer Institute of Shanghai Medical University. The 5 year survival in the entire series was 36.2%, being increased from 4.8% in 1958-70, 12.2% in 1971-83, to 50.5% in 1984-96 and 274 patients had survived more than 5 years. The increase in the survival rate could be attributed to the decreasing mean tumour diameter (11.7, 10.5 and 9.5 cm, respectively) and multimodality treatment. In addition to small HCC resection (5 year survival 64.9%, n = 735) and large HCC resection (5 year survival 37.4%, n = 1050), the following deserves to be mentioned. First, the 5 year survival of unresectable HCC treated by palliative surgery increased from 0% to 7.2% to 20.0%, which was related to the increase in use of multimodality treatment, particularly in those followed by second-stage resection. Second, cytoreduction and sequential resection is a new field with a significant potential in the treatment of localized unresectable HCC in a cirrhotic liver. Cytoreduction can be achieved by surgery, such as hepatic artery ligation, cannulation, cryosurgery and their combination, and followed by intrahepatic arterial chemoembolization, targeting therapy or regional radiotherapy. Ninety of 647 patients with unresectable HCC so treated had marked shrinkage of tumour and received second-stage resection; the 5 year survival was 71.4%. Third, non-surgical cytoreduction was mainly achieved by transcatheter arterial chemoembolization (TACE); for 70 patients with second-stage resection following TACE, the 5 year survival was 56.0%. Finally, re-resection of subclinical recurrence of tumour after curative HCC resection was performed in 155 patients; the 5 year survival calculated from the first resection was 50.9%, which played an important role in increasing the 5 year survival in the resection group (from 13.0% to 29.5% to 56.2%). It is concluded that multimodality treatment with combined and sequential use of different modalities and repeated use of some modalities is of substantial benefit for localized unresectable HCC.

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.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.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.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.

To clarify the clinicopathologic features of patients survivingor =20 years after resection for hepatocellular carcinoma (HCC).Between 1961 and 1987, a total of 396 patients underwent hepatic resection for HCC; 53 (13.4%) patients survivedor =20 years, and 343 (86.6%) patients survived20 years. A comparative study between the two groups was made.By March of 2007, 67.6% (36/53) patients are still alive, disease free; 5.7% (3/53) patients died of tumor recurrence or metastasis; 11.3% (6/53) patients died of liver failure; 5.7% (5/53) patients were lost during follow-up. The longest patient survived 43 years and 2 months. Five young patients got married after resection and have had babies. One patient with a tumor measuring 17 x 13 x 9 cm (largest tumor in this series) survived for 37 years after resection, still alive, free of disease. Reresection for recurrence was done in nine patients, mean survival being 26 years and 11 months. Reresection for solitary pulmonary metastasis was carried out in three patients, mean survival being 29 years and 2 months. In comparison with patients surviving20 years, patients survivingor =20 years were significantly younger (P = 0.031), had a higher incidence of asymptomatic tumors (56.6 vs. 34.4%, P = 0.002); lower gamma-glutamyl transpeptidase level (or =50 U/L, 64.2 vs. 25.9%, P0.000), lower proportion of liver cirrhosis (66.0 vs. 83.6%, P = 0.002); higher percentage of small tumors (or =5 cm, 62.3 vs. 29.9%, P0.000), single nodule tumors (90.6 vs. 62.9%, P0.000), and well-encapsulated tumors (86.8 vs. 43.6%, P0.000); lower proportion of tumor emboli in the portal vein (3.8 vs. 22.5%, P = 0.002), better differentiation of tumor cells (Edmondson grade I, 21.6 vs. 9.1%, P = 0.036), and higher curative resection rate (100 vs. 64.1%, P0.000).Early detection and curative resection are the principal factors improving long-term survival. Long-term follow-up after resection of HCC is very important, and should continue for the remainder of the patient's life. Reresection for recurrence and metastasis is important approach to improve prognosis.

To clarify clinicopathologic differences between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), and identify potential factors influencing survival after hepatectomy for ICC. Comparison of clinicopathologic data was made between patients who underwent hepatectomy for ICC (n = 272) and HCC (n = 5,829) during the same period. Twenty-five clinicopathologic variables were selected for univariate and multivariate analyses to evaluate their influence on prognosis of ICC. Compared with patients with HCC, ICC patients were more common in females and more elderly, had a lower proportion of asymptomatic tumors, lower serum alpha-fetoprotein, higher serum carcinoembryonic antigen, carbohydrate antigen 19–9 and alkaline phosphatase levels; lower incidence of hepatitis history, associated cirrhosis and serum hepatitis B surface antigen; lower proportion of small tumors, well-encapsulated tumors and tumor emboli in the portal vein; higher proportion of single tumor, perihila lymph node involvement and poor differentiation; and less frequency of limited resection (all, P

To identify the side population (SP) cells from four hepatocellular carcinoma (HCC) cell lines with stepwise metastatic potentials.SP cells were sorted from HCCLM3, MHCC97-H, MHCC97-L and Hep3B by flow cytometry, and then analyzed by differentiation study, clonogenic assay, chemoresistance study and tumorigenicity assay in vivo. The expression of ABCG(2) in SP cells was detected by immunocytochemistry, western blotting and real-time quantitative PCR, respectively.There was significant difference in SP proportion among HCCLM3, MHCC97-H, MHCC97-L and Hep3B (28.7 +/- 1.6%, 14.5 +/- 0.6%, 4.2 +/- 0.4%, 0.9 +/- 0.1%, respectively, P0.01). All the SP cells showed similar characteristics of self-renewal, high clonogenicity, remarkable chemo-resistance and high expression of ABCG(2). As low as 2,000 SP cells could initiate tumors in non-obese diabetic/severe combined immunodeficiency mice successfully.SP cells purified from HCC cell lines harbors cancer stem cell-like properties, and may be related to the metastatic potentials and therapeutic-resistance of HCC.

To investigate the characteristics of pulmonary infection and its risk factors after orthotopic liver transplantation (OLT).Clinical data of 250 cases having liver transplantations from April 2001 to August 2005 were retrospectively studied in order to analyse the differences between patients with and without pulmonary infection.Fifty-seven (57/250, 22.8%) recipients had 72 episodes of pulmonary infection after liver transplantation. Bacterial infection was the most common followed by fungal infection (13/72, 18.1%), and cytomegalovirus infection (12/72, 16.7%). There were 36 episodes of pulmonary infection caused by one kind of bacteria, 5 episodes by two kinds of bacteria and 6 episodes by multiple kinds of bacteria. Seven episodes of fungal infection were accompanied with bacterial infection, and three episodes of cytomegalovirus infection were accompanied with bacterial infection simultaneously. The 1-, 2- and 3- year survival rates were 71.9%, 61.4%, and 53.4% of the patients with pulmonary infection and 93.1%, 75.8%, and 67.2% of those without the infection. Logistic regression analysis suggested that preoperative infection, mechanical ventilation12 hours, a long duration of the operation, total volume of blood transfusion during operation1000 ml, reoperation after OLT, postoperative pleural effusion and the duration of stay in the intensive care unit were independent risk factors of pulmonary infection after OLT.Bacterial infections were the main pulmonary infection after OLT and the infections caused by multiple pathogens or multiple-antibiotic-resistant bacteria were seen more frequently. The risk factors of pulmonary infection should be controlled to decrease the infection rate after OLT. It is important to make a correct diagnosis for pulmonary infection after OLT and use appropriate antibiotics as soon as possible.

To identify the influence of tumor characteristics on the outcome of liver transplantation (LT) among patients with hepatocellular carcinoma (HCC).A retrospective analysis was performed on 251 consecutive patients with HCC who underwent LT between April 2001 and February 2006 at our institution. We compared the outcome of the patients classified by different tumor related factors. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression methods.Macroscopic vascular invasion, lymph node metastasis, Edmondson pathologic classification, microscopic tumor thrombosis, tumor location, satellite nodules and alpha-fetal protein (AFP) all significantly affected the overall survival and/or recurrence-free survival post-LT (P0.01 or P0.05). Pre-operative treatment and hepatitis background had no effect to the prognosis (P0.05). At multivariate Cox regression analysis, the factors associated with mortality or recurrence were macroscopic vascular invasion, microscopic tumor thrombosis and satellite nodules (P0.01 or P0.05).Edmondson grade III - IV, microscopic tumor thrombosis, left lobar or bilobar tumor, satellite nodules and AFPor = 300 microg/L were predictive factors of poor prognosis. Presence of macroscopic vascular invasion or lymph node metastasis should be contraindicated.

To investigate whether focal adhesion kinase (FAK) is involved in the progression of human hepatocellular carcinoma (HCC) and whether FAK mRNA expression has prognostic significance for HCC.Real-time PCR and immunohistochemistry were used to det4ec the mRNA and protein expression of FAK in 50 specimens of HCC obtained during operation. The correlation between FAK expression and clinicopathologic parameters was.The mRNA expression of FAK was significantly higher in the HCC specimens than in the corresponding non-cancerous liver tissues (P0.001), in the embolism than in the tumor tissue by the emboli of the same specimen (P0.05), and in the HCC with embolism than in the HCC without embolism (P = 0.003). Cox regression analysis showed that the FAK mRNA expression was correlated significantly with embolism (P = 0.003) and invasion (P = 0.020). Univariate and multivariate analyses revealed that FAK expression was an independent prognostic factor for survival.FAK plays an important role in HCC progression, especially in vascular invasion and FAK expression has prognostic significance for HCC.

To observe clinical therapeutic effect of head point-through-point electroacupuncture (EA) on poststroke depression (PSD) and to study the mechanism.One hundred and eight cases of PSD were randomly divided into a point-through-point EA group (n = 38), a non point-through-point group (n = 36) and a western medicine group (n = 34). After treatment of 28 days, their therapeutic effects, scores of HAMD depression scale and SDS self-rating scale, and plasma 5-HT contents were compared before and after treatment among the 3 groups.The effective rate of 86.84% in the point-through-point EA group was better than 63.89% in the non point-through-point group and 67.65% in the western medicine group (P0.05 or P0.01). Plasma 5-HT content in the point-through-point EA group increased significantly, with a very significant difference as compared with that of the non point-through-point group (P0.01).Head point-through-point therapy can obviously increase plasma 5-HT content of the patient with PSD, so as to cure poststroke depression, with a better therapeutic effect than other two groups.

Recurrence after resection of hepatocellular carcinoma (HCC) is frequent and is a major cause of a poor outcome. Most recurrence may occur from the spreading of the original lesion via the intrahepatic portal vein. Cryosurgery has been used for the treatment of various tumors for decades. The aim of this study was to determine whether cryohepatectomy is potentially beneficial in reducing the recuurence and prolonging survival.The study included 84 patients who underwent cryohepatectomy, cryosurgery with liquid nitrogen (-196 degrees C) followed by the resection of the frozen tumor by conventional technique, for HCC and were closely follow-up after surgery. Recurrence and survival rates were calculated by the life-table method.The postoperative course of cryohepatectomy in all of the 84 patients was uneventful, there being no operative mortality or severe complications. The 1-, 3-, and 5-year survival rates after cryohepatectomy were 98.7%, 83.9%, and 64.0%, respectively. The 1-, 3-, and 5-year recurrence rates after cryohepatectomy were 15.1%, 30.1% and 39.0%, respectively.Cryohepatectomy for HCC is a safe procedure and may be potentially beneficial in reducing recurrence and prolonging survival. More time is needed to further define whether this procedure will improve long-term survival as compared with conventional resection.

To investigate the surgical outcome of the hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) after surgery and the time-dependency of the factors influencing survival.The clinicopathological data of 382 HCC patients with macroscopic PVTT who had undergone resection of HCC were analyzed. The survival rte was calculated using Kaplan-Meier method. Stratified Cox model was used to identify the factors independently influencing the short- and long-term survival rates.The 1-, 2-, 3-, 5-, and 10-year survival rates of the 382 patients were 47%, 23%, 16%, 12%, and 6% respectively. The 1-, 3-, and 5-year survival rates re-calculated from the time of re-resection because of recurrence within 2 years after the first operation were 36%, 14%, and 0% 1 respectively. However, the 1-, 3-, and 5-year survival rates re-calculated from the time of re-resection because of recurrence 2 years after the first operation were 85%, 53%, and 32%, all significantly higher than those re-calculated from the time of re-resection within 2 years after the first operation (all P0.05). Multivariate analysis showed that portal infusion chemotherapy, serum alpha-fetoprotein20 microg/L and negative surgical margin were significant favorable prognostic factors within 2 years after operation. Alanine aminotransferase80 U/L was the only significant unfavorable factor beyond 2 years after operation.The prognosis of the patients with macroscopic PVTT who suffer from liver tumor recurrence occurring more than 2 years after the first operation is much better than those with the recurrence occurring within 2 years. Evaluation of the time-dependency of risk factors may have important clinical implication in determining the therapeutic strategy.

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

To investigate the effects of rapamycin (RPM) in inhibiting the growth and metastasis of hepatocellular carcinoma (HCC).Human HCC cells of the line MHCC97H with a high potential of metastasis were divided into 3 groups to be cultured with cyclosporine A (CsA) 100 ng/ml, RPM 10 ng/ml, or CsA + RPM for 48 hours. Flow cytometry was used to examine the apoptosis and cell cycle MTT method was used to examine the effect of RMP on the proliferation of the MHCC97H cells. RT-PCR was used to detect the mRNA expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hypoxia-inducible factor-1alpha (HIF-1alpha), and transforming growth factor b (TGFb). Another MHCC97H cells were cultured in complete medium without RPM for 48 hours, then the protein expression of VEGF in the supernatant was detected by ELISA. Twenty-eight nude LCI-D20 mice were inoculated with human HCC cells and then divided into 4 groups to be fed with CsA (25 mg/kg), RPM (2 mg/kg), CsA + RPM, and normal saline (0.2 ml, as control group) for 35 days. Then the mice were killed to take the weight of inoculated tumor, measure the blood drug concentration, calculate the lung metastasis rate and number of metastatic foci, and observe pathology of the lung.CsA showed no effect on the cycle of the MHCC97H cells. The MHCC97H cells of the RPM and CsA + RPM groups arrested at the stage G(0)/G(1) (both P = 0.000). MMT method also showed that the proliferation of the MHCC97H cells in the RPM and CsA + RPM groups were blocked (P = 0.003 and P = 0.002). However, CsA did not influence the proliferation of the MHCC97H cells. Flow cytometry showed that RPM did not promote the apoptosis of the MHCC97H cells. RT-PCR showed that RPM down-regulated the mRNA expression of VEGF and HIF-1alpha (both P0.05), however, did not influence the mRNA expression of bFGF, TGFb, and TGFb. The VEGF protein level in the supernatant of the culture fluid of MHCC97H cells of the RPM group was (890.3 +/- 25.1) pg/ml, significantly lower than that of the control group, (1583.7 +/- 17.3) pg/ml (P = 0.000). The tumor inhibiting rate of the RPM group was 63.7%, not significantly different from that of the RPM + CsA group (80.9%, P = 1.000). The metastatic rate of the CsA and control groups were both 100% with a higher number of metastatic tumors in the CsA group (P = 0.046).RPM significantly inhibits the growth and metastasis of HCC. RPM-based immunosuppressive regimen may be of value in HCC patients receiving liver transplantation.

To evaluate the effects of different selection criteria on the prognosis of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) and to explore the new criteria adapted for Chinese National Situation.A retrospective analysis was performed on 251 consecutive patients with HCC who underwent LT between April 2001 and January 2006 at our institution. We compared the outcome of the patients meeting different criteria such as milan, UCSF and the Pittsburgh modified TNM criteria. Survival rates were calculated using the Kaplan-Meier method, and differences between the curves were assessed by log-rank test.There was no significant difference in 1, 2, 3-year survival rates and recurrence-free survival rates between milan criteria (n = 93; 86%, 77%, 77% and 91%, 86%, 86%) and UCSF criteria (n = 131; 90%, 83%, 83% and 92%, 89%, 89%). According to Pittsburgh criteria (n = 207), the 1, 2, 3-year survival rates and recurrence-free survival rates were 84%, 74%, 67% and 85%, 83%, 73%, respectively. For advanced tumors (over all the criteria), the survival rates and recurrence-free survival rates decreased significantly (n = 44; 65%, 43%, 43% and 47%, 43%, 43% respectively). When criteria (named as Shanghai Fudan Criteria) were expanded to HCC patients with solitary lesionsor = 9 cm in diameter, or no more than 3 lesions, the largestor = 5 cm, with a total tumor diameteror = 9 cm, there was no significant difference in 1, 2, 3-year survival rates and recurrence-free survival rates (n = 151; 88%, 80%, 80% and 90%, 88%, 88%, respectively) as compared with milan criteria, but more patients using Shanghai Fudan Criteria could undergo liver transplantation.Shanghai Fudan Criteria, which expanded the tumor size limits, does not adversely impact survival of HCC patients after LT.

To analyze the risk factors influencing the prognosis of orthotopic liver transplantation for hepatocellular carcinoma (HCC) and sum up the relevant clinical experience in diagnosis and treatment of HCC.The clinical data of 198 HCC patients, 177 males and 21 females, aged 49 (24-83), were analyzed.The 0.5-, 1-, and 2-year survival rates were 89%, 78%, and 65 respectively. The rates of disease-free survival (DFS) were 85%, 73, and 67% respectively. Univariate analysis revealed that tumor size, presence of vascular invasion, Edmondson grade, TNM classification, and preoperative alpha-fetoprotein (AFP) were significantly related to DFS, and the 4 foregoing factors were also related to the survival rate. Cox regression analysis suggested that presence of vascular invasion was an independent prognostic factor of survival rate and DFS.Vascular invasion plays a leading role in evaluating the prognosis of orthotopic liver transplantation for HCC. It is important to discover the micro-metastasis and explore more effective approaches to prevent recurrence after transplantation.

The prognosis ofhepatocellular carcinoma with macroscopic portal vein tumor thrombosis is extremely poor. The risk factors may differ at different postoperative intervals. This study was undertaken to clarify the surgical outcome and time dependency of factors influencing survival in these patients.We analyzed clinicopathological variables of 381 hepatocellular carcinoma patients with macroscopic portal vein tumor thrombosis who underwent hepatic resection. Survival rates were calculated using Kaplan-Meier method. The stratified Cox models were used to identify factors independently influencing short- and long-term survival, respectively.The cumulative 1-, 2-, 3-, 5-, and 10-year survival rates in 381 patients were 47%, 23%, 16%, 12%, 6%, respectively. The 1-, 3-, and 5-year survival rates calculated from time of re-resection were 36%, 14% and 0% in patients undergoing re-resection for intrahepatic recurrence within 2 years after first operation, and 85%, 53% and 32% in those more than 2 years after first operation (P0.05). Multivariate analysis showed that portal vein infusion chemotherapy, serum alpha-fetoprotein20 mg/L and positive surgical margin were significant prognostic factors within 2 years after operation. In contrast, alanine aminotransferase80 U/L was the only significant factor beyond 2 years after operation.The survival of hepatocellular carcinoma patients with macroscopic portal vein tumor thrombosis was poor, but the prognosis of patients who had tumor recurrence more than 2 years after operation was much better than those with tumor recurrence within 2 years. Evaluation of time-dependency of risk factors may have important clinical implication in determining the therapeutic strategy.

To further study the impact of interferon-alpha (IFN-alpha) on thymidine phosphorylase (TP) expression and angiogenesis.Human hepatocellular carcinoma cells of the line SMMC-7721 were cultured and added with IFN-alpha of different doses: 0 (as control group), 1000, 5000 and 10,000 U/ml. Twenty-four hours later RT-PCR was used to detect the TP mRNA expression. Boyden chamber method was used to examine the endothelial cells migration. Suspension of SMMC-7721 cells was inoculated subcutaneously into 30 male BALB/c-nu/nu mice, the mice were randomly divided into 5 equal groups to be subcutaneously injected with IFN-alpha of different doses: 0 (as control group), 1.0 x 10(6), 3.0 x 10(6), 9.0 x 10(6), and 1.5 x 10(7) U.kg(-1).d(-1) for 3 weeks. The eating behavior, activity, body weight, and tumor size were observed. The rats were killed 2 days after the drug injection was stopped. The subcutaneous tumors were taken out to undergo histological examination and TP protein expression by ELISA. The microvessel density (MVD) was detected using anti-CD34 monoclonal antibody.The TP mRNA expression of the SMMC-7721 cells induced by IFN-alpha of the doses of 5000 U/ml and 10,000 U/ml significantly increased in comparison with the un-treated SMMC-7721 cells (0 U/ml, P0.05). The endothelial cell migration significantly increased in the IFN-alpha 1000 U/ml group compared with the control group (P0.001), and then decreased along with the increase of IFN-alpha dose; there were no significant differences in the epithelial migration among the groups of 0, 5000, and 10,000 U/ml IFN-alpha doses (all P0.05). The TP protein expression levels of the tumor in the rats treated with IFN-alpha of the doses of 9.0 x 10(6), and 1.5 x 10(7) U.kg(-1).d(-1) were 48 ng/mg +/- 24 ng/mg and 60 ng/mg +/- 6 ng/mg respectively, 1.9 and 2.4 times that of the control group (both P0.01). The MVD of the tumors was 6.0 +/- 1.8 in the 9.0 x 10(6) U.kg(-1).d(-1) IFN-alpha group, significantly higher than that of the control group (P0.01); and was 4.0 +/- 1.5 in the 1.5 x 10(7) U.kg(-1).d(-1) group, significantly lower than that of the 9.0 x 10(6) U.kg(-1).d(-1) group (P0.05) and not significantly different from that of the control group. The tumor inhibiting rate of the 1.5 x 10(7) U.kg(-1).d(-1) IFN-alpha group was 68%, significantly higher than that of the untreated group (P0.05).IFN-alpha of certain doses up-regulate the TP expression, and inhibit the angiogenesis induced by TP as well.

To investigate the measures to further improve the therapeutic efficacy of liver transplantation.The clinical data of 203 consecutive cases of orthotopic liver transplantation (OLT) performed in Zhongshan Hospital, Fudan University April 2001 to October 2004, with the indications for considering OLT of hepatocellular carcinoma (HCC) (142 cases), liver cirrhosis (36 cases), fulminant hepatic failure (7 cases), Wilson's disease (6 cases), and other end-stage liver diseases (12 cases), including 199 cases of cadaveric OLT, inclusive of 2 cases of reduced-size and 1 case of splitting liver transplantation, and 4 cases of living-donor liver transplantation, were retrospectively analyzed. Multivariate analysis using Cox proportional hazards regression model was applied to determine the risk factors predicting liver transplantation prognosis for HCC.For the whole group of the 201 patients, the 1-year and 2-year cumulative survival rates were 85.0% and 82.4% respectively and the rejection rate was 12.3%. In the HCC group the 1- and 2-year cumulative survival rates were 80.2% and 78.4%, and the 1- and 2-year disease-free survival (DFS) rates were 85.3% and 80.3% respectively. HCC recurrence was observed in 20 patients after OLT with a recurrence rate of 14.1%. Multivariate analysis revealed that the tumor size and portal vein tumor thrombus were the most independent and statistically significant factors affecting the DFS.OLT may be the most effective treatment option for patients with end-stage liver diseases and may also provide the opportunity of curative treatment or survival improvement for selected patients with hepatic malignancies.

To explore the diagnosis and management of early hepatic artery thrombosis (HAT) after liver transplantation.Routine examination of Color Doppler Imagine (CDI) was used to detect hepatic artery flow after liver transplantation in 220 cases from April 2001 to November 2004. Suspected patients were further confirmed by immediate hepatic artery angiography, and continuous infusion of urokinase through hepatic artery with catheter was performed to the patients with HAT.HAT was identified in 6 patients (2.7%), occurring 5.5 days (2 - 19 days) after liver transplantation. Hepatic artery recanalization was obtained in 6 cases. One patient died from lung infection 2 months after liver transplantation. One patient underwent the second liver transplantation because of the recurrence of HAT 6 months after the first transplantation, but died from multiple system organ failure 2 months after the operation. The other 4 cases have been surviving well disease-freely.CDI is useful for the diagnosis of early HAT after liver transplantation. Contributes to recovery of the hepatic artery flow, continuous infusion of urokinase through hepatic artery with catheter may be the first choice of the therapy for early HAT.

Liver resection is still a complicated operation with a high risk of postoperative morbidity. This study was undertaken to analyze the risk factors for postoperative complications after liver resection.From 2001 to 2004, a total of 146 patients underwent liver resection for malignant or benign lesions. Postoperative complications after the resection were classified as surgical and medical, their incidences were analyzed retrospectively. The risk factors for both surgical and medical complications were analyzed. To increase the safety of liver resection, surgical techniques were modified after April 2003, including control of inflow or outflow and intra-operative test with methylene blue.Before April 2003, a series of 58 patients received liver resection. Modified surgical techniques were used in liver resections for 88 patients after April 2003. A total of 36 patients (24.7%) had postoperative complications. Surgical and medical complications occurred in 24 and 13 patients respectively (One patient had both surgical and medical complications). Perioperative blood transfusion was related to a higher risk of surgical complications (P0.05). Patients with diabetes mellitus were associated with a higher risk of medical complications (P0.05). Surgical complications and postoperative hospitalization were decreased after the use of modified surgical techniques (P0.05).Postoperative surgical complications can be decreased by modified surgical techniques, and careful selection of patients for liver resection may help to decrease postoperative medical complications also.

Aim: To elucidate the relationship between local immunocompetent cells and prognosis of human hepatocellular carcinoma (HCC) after resection. Methods: HE staining and immunohistochemical study were carried out on specimens from patients underwent surgical resection. Local immunocompetent cells, such as dendritic cells (DCs), memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes, were counted and their relationships with tumor-free survival rate were analyzed by grouping DCs with the T lymphocytes retrospectively. Results: The number grade of infiltrating immunocompetent cells in HCC nodules and pericancerous tissues under HE staining had no significant correlation with tumor-free survival time (P=0.054, 0.071, respectively). DCs were mainly among tumor cells, encircling tumor cells with their pseudopodia and were in contact with T lymphocytes. A certain number of DCs in HCC nodules (≥25/10HPF) statistically correlated to tumor-free survival time (P=0.005), while a certain number of DCs in pericancerous tissues (≥28/10HPF) had no correlation with tumor-free survival time (P=0.329). The number of memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes in HCC nodules strongly correlated to tumor-free survival time (P=0.003, 0.005, 0.037, respectively). The tumor-free survival rate curves revealed that the more DCs or together with memory T cells/CD3+ T lymphocytes or that the more CD8+ T lymphocytes were detected in HCC nodules, the better the prognosis would be. Conclusions: Marked infiltration of DCs in HCC nodules was closely related to the prognosis of HCC after surgical resection and can be served as a predictive index for recurrence and metastasis of HCC.

Selection of patients with hepatocellular carcinoma (HCC) for orthotopic liver transplantation (OLT) remains controversial. Since there is a trend to expand the transplant criteria for HCC patients, we reviewed the data of patients with HCC who had received OLT at our institute to determine their survival and prognostic factors.A total of 67 patients with HCC who had undergone OLT from April 2001 through December 2003 were reviewed retrospectively. Selection OLT candidates with HCC was dependent on the anatomical characteristics and/or the severity of underlying liver cirrhosis. The 67 patients were followed up for more than 6 months after transplantation. Their survival rate was calculated by the Kaplan-Meier method. Univariate and multivariate analyses using the Cox proportional hazards regression model were performed to reveal the factors affecting the survival rate.No perioperative death occurred in this series. The 1- and 2-year cumulative survival rates were 90.0% and 65.6%, and the disease-free survival (DFS) rates were 77.5% and 62.5% respectively. Univariate analysis revealed the tumor size, portal vein tumor thrombus (PVTT), serum alpha-fetoprotein level, bilobular distribution of tumors, pTNM stage and histological differentiation were statistically significant factors affecting the DFS (P0.05). Multivariate analysis showed tumor size and PVTT were independent and statistically significant factors affecting the DFS (P = 0.005 and 0.010, respectively). In this series, all but 2 received systemic chemotherapy, among them 13 had tumor recurrence within 8 months after OLT.OLT is indicated for patients with HCC, even for some patients with end-stage liver disease who may survive longer without tumor recurrence. Adjuvant chemotherapy may decrease the recurrence of HCC after OLT.

To determine whether cryohepatectomy is potentially beneficial in reducing the recurrence and prolonging survival for hepatocellular carcinoma (HCC).The study included 84 patients who underwent cryohepatectomy, cryosurgery with liquid nitrogen (-196 degrees C) followed by the resection of the frozen tumor by conventional technique, for HCC and were closely follow-up after surgery. Recurrence and survival rates were calculated by the life-table method.The postoperative course of cryohepatectomy in all of the 84 patients was uneventful, there being no operative mortality or severe complications. The 1-, 3-, and 5-year survival rates after cryohepatectomy were 98.7%, 83.9% and 64.0%, respectively. The 1-, 3-, and 5-year recurrence rates after cryohepatectomy were 15.1%, 30.1% and 39.0%, respectively.Cryohepatectomy for HCC is a safe procedure and may be potentially beneficial in reducing recurrence and prolonging survival. More time is needed to further define whether this procedure will improve long-term survival as compared with conventional resection.

To evaluate the effects of portal vein microscopic and macroscopic tumor thrombi on post-operation patients with hepatocellular carcinoma (HCC).Three thousand three hundred and forty eight HCC patients were retrospectively reviewed, which were divided into no portal vein tumor thrombi (PVTT), microscopic PVTT and macroscopic PVTT groups according to the pathology, effects of portal vein microscopic and macroscopic tumor thrombi on post-operation patients's survival were studied by univariate analysis and overall survival was evaluated in each group.Hazard ratio (HR) of portal vein microscopic tumor thrombi and macroscopic tumor thrombi was 1.421 and 3.136 respectively; The overall 1-, 3-, 5- and 10-year cumulative survival rate was 85.97%, 62.78%, 49.88% and 35.42% respectively, and mean time for survival was 59.7 months in group without PVTT, while 74.42%, 51.66%, 39.25% and 27.28% respectively and mean time for survival 39.1 months in group with microscopic PVTT, 52.59%, 25.97%, 20.42% and 11.33% respectively and mean time for survival 13.5 months in group with macroscopic PVTT.PVTT was an important prognostic factor for survival in post-operation patients with HCC while macroscopic PVTT was more danger than microscopic PVTT. The period of microscopic PVTT was the landmark affecting post-operation survival.

To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and investigate factors influencing prognosis.One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study. They were divided into four groups and underwent different treatments: conservative treatment group (n = 18), chemotherapy group (n = 53), surgical resection group (n = 24) and surgical resection with postoperative chemotherapy group (n = 84). Survival rates of the patients were analyzed by the Kaplan-Meier method. A log-rank analysis was performed to identify group differences. Cox's proportional hazards model was used to analyze variables associated with survival.The mean survival periods of the patients in four groups were 3.6, 7.3, 10.1, and 15.1 mo respectively. There were significant differences in the survival rates among the groups. The survival rates at 0.5-, 1-, 2-, and 3-year in surgical resection with postoperative chemotherapy group were 55.8%, 39.3%, 30.4%, and 15.6% respectively, which were significantly higher than those of other groups (P0.001). Multivariate analysis revealed that the strategy of treatment (P0.001) and the number of chemotherapy cycles (P = 0.012) were independent survival predictors for patients with HCC and PVTT.Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation. Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve.

Curable outcome of unresectable hepatocellular carcinoma (HCC) was seldom encountered in the past. This study was designed to assess the role of downstaging followed by resection (downstaging-resection) in the improvement of prognosis of unresectable HCC.During the period of 1958-2003, a total of 1085 patients were verified surgically to be unresectable. Of these patients, 139 received downstaging-resection, with a rate of 84.2% for coexisting cirrhosis and a median tumor diameter of 11.1 cm. Resection of the right lobe, hepatic hilum and bilateral cancer accounted for 97.8% of the patients. Downstaging including hepatic artery ligation (HAL)+hepatic artery chemo-infusion (HAI) was performed in 65.5% of the patients, HAL+HAI+radiotherapy/radioimmunotherapy in 29.5%, and HAL or HAI alone in 5.0%. Retrospective analysis was made of the survival of patients with unresectable HCC, downstaging-resection rate and treatment pattern.In the 139 patients with downstaging-resection, the median interval between the first and second operation was 7.2 months and the 5-year survival rate calculated from the first operation was 48.7%. In the 1085 patients with unresectable HCC, their 5-year survival was 0% in the period of 1958-1973, 11.5% in the period of 1974-1988 and 19.3% in the period of 1989-2003. These figures were correlated with the increasing downstaging-resection rate from 0%, 9.0% to 15.6%, and the increasing percentage of triple or double combination treatment from 32.2%, 60.4% to 69.7%. The 5-year survival in triple treatment group was 24.9%, double treatment 15.2%, and single treatment only 10.9%, which was also correlated with the downstaging-resection rate of 34.6%, 16.2% and 1.8% respectively.Downstaging-resection plays a role in improving prognosis of unresectable HCC. Triple and double treatments provide a higher downstaging-resection rate and may result in better prognosis.

To report the procedure of segmentectomy for hepatoma located in segment IX.11 cases of hepatoma originated from segment IX were treated by segmentectomy without interruption of blood flow of the liver. Among total 11 cases, 10 cases were primary liver cancer, the other one was secondary liver cancer.Tumor diameters from 6 to 14 cm (median 9.2 cm), no perioperative death occurred in this group. Intraoperative blood losses were 200-600 ml (median 350 ml) without severe postoperative complications. Postoperative hospitalization time were 9-14 days (median 11 days). Transhepatic artery chemoembolization (TACE) was given at 4-6 weeks after operation and repeated at intervals of 2 to 4 months for 1 year. During the follow up time of 5-29 months (media 17 months), 10 patients were tumor-free and 1 patient developed an intrahepatic metastasis.Segmentectomy without interruption of blood flow of the liver is safe and practical for hepatoma located in segment IX.

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.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.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%).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.

To compare the clinical effects of different therapies on hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT), and to study the factors that affected the prognosis.One hundred and thirty eight HCC with PVTT patients, whose liver function was compensatory and both tumor and PVTT could probably be resected together as evaluated by preoperative examinations, were divided into four groups: 1. conservative treatment group (n = 14); 2. chemotherapy group (n = 41); 3. surgical resection group (n = 19); 4. surgical resection with postoperative chemotherapy group (n = 64).The median survival periods in four groups were 3.5, 7.1, 10.1 and 13.4 months, respectively. The half a year-, 1-, 2-, 3-year survival rates in the surgical resection with postoperative chemotherapy group were 53.7%, 37.6%, 30.7% and 14.0%, respectively, which were significantly higher than those of the other three groups (P0.05). Univariate and multivariate analysis both revealed that the number of chemotherapy courses affected the effect of surgical resection.1. If patients' liver function is compensatory and tumors with PVTT can be removed together, exploration should be done. Surgical resection followed by postoperative chemotherapy would produce the best clinical result. 2. If patients' liver function is permissible, multiple chemotherapeutic courses should be given after resection of HCC with PVTT.