[Theoretical study of the influence of different substituents on the electron-photon spectra of quinoline].

Different substituents result in different changes in electron-photon spectra, and to reveal the relationship between substituents and spectra, a theoretical investigation was elaborated via quantum chemical calculations. Density functional theory and single excitation configuration interaction were respectively employed in optimizing geometric and electronic structures of ground and excited states, and the absorption and emission spectra were studied by time-dependent density functional theory methods. The results show that all the different substituents bring on different geometric and electronic structures of ground and excited states, different energies of frontier molecular orbitals as well as different pi-conjugated systems, the spectra change with all the differences, and relationships are brought out in this paper, which gives theoretical reference for identifying different derivatives from electron-photon spectra.

Focal nodular hyperplasia of the liver in 86 patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial.

BACKGROUND/AIMS: Recurrence after resection of hepatocellular carcinoma (HCC) is a frequent event. This study evaluated the effect of postoperative interferon alpha (IFN alpha) 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 alpha treatment (5 micro 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 alpha treatment improved the overall survival of patients with HBV-related HCC after curative resection, probably by postponing recurrence.

Factors influencing survival in hepatocellular carcinoma patients with macroscopic portal vein tumor thrombosis after surgery, with special reference to time dependency: a single-center experience of 381 cases.

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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 (P<0.05). Multivariate analysis showed that portal vein infusion chemotherapy, serum alpha-fetoprotein > 20 mg/L and positive surgical margin were significant prognostic factors within 2 years after operation. In contrast, alanine aminotransferase > 80 U/L was the only significant factor beyond 2 years after operation. CONCLUSIONS: 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.

[Time dependency of factors influencing survival of hepatocellular carcinoma patients with portal vein tumor thrombosis after surgery].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 P < 0.05). Multivariate analysis showed that portal infusion chemotherapy, serum alpha-fetoprotein < 20 microg/L and negative surgical margin were significant favorable prognostic factors within 2 years after operation. Alanine aminotransferase > 80 U/L was the only significant unfavorable factor beyond 2 years after operation. CONCLUSION: 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.

The prognostic factor for outcome following second resection for intrahepatic recurrence of hepatocellular carcinoma with a hepatitis B virus infection background.

PURPOSE: Second resection has been proved to be a safe and effective treatment for patients with intrahepatic recurrent HCC after primary resection; however, preoperative prognostic factors for outcome following second resection in patients with a hepatitis B virus (HBV) infection background remains to be clarified. METHODS: Fifty-seven patients with intrahepatic recurrent an HCC and HBV infection background received second resection from 1997 to 2003 in our institute. All of them were negative for anti-hepatitis C virus (HCV) and positive regarding HBV profile. Patient and tumor factors were analyzed. RESULTS: At the time of preparing this paper, 31 had re-recurrence and 21 patients had died. No postoperative mortality was noted. The 1-, 3-, and 5-year overall survival after second resection were 69.9%, 61.2%, and 30.6%, respectively. Univariate and multivariate analysis showed that vascular invasion and time to recurrence were the independent prognostic factors for overall survival following second resection. The 3- and 4-year overall survival after second resection were 57.7% and 46.6% in patients with the presence of any of two risk factors (n = 46), and 100% and 100% in those with absence of both risk factors (n = 11, P = 0.008). CONCLUSIONS: Vascular invasion and time to recurrence were the prognostic factors for overall survival following second resection of intrahepatic recurrent HCC.

[The effects of portal vein microscopic and macroscopic tumor thrombi on post-operation patients with hepatocellular carcinoma].

OBJECTIVE: To evaluate the effects of portal vein microscopic and macroscopic tumor thrombi on post-operation patients with hepatocellular carcinoma (HCC). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Cryohepatectomy for liver cancer: preliminary evaluation of reducing postoperative recurrence].

OBJECTIVE: To determine whether cryohepatectomy is potentially beneficial in reducing the recurrence and prolonging survival for hepatocellular carcinoma (HCC). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Antisense Tcf inhibits the neoplastic growth of liver cancer cells.

PURPOSE: T cell transcription factors are nuclear effectors of the Wnt signaling transduction pathway and play crucial roles in embryonic and malignant development. Our previous study showed increased expression level of Tcf mRNA in liver cancer. In the present paper, antisense Tcf RNA was used to explore the possible therapeutic effect on liver cancer cells by interrupting the abnormal Wnt pathway. METHODS: Antisense expression vectors containing the conserved sequence of Tcf cDNA were constructed and transfected into a human liver cancer cell line SMMC-7721. Tumorigenic potential was determined by cellular growth assay and tumor growth in nude mice. RESULTS: The stable transfection of anti-sense Tcf in SMMC-7721 cells significantly reduced Tcf expression at both mRNA and protein levels compared with parental and mock-transfected cells. Antisense-mediated suppression of Tcf inhibited the in vitro proliferation and in vivo tumor formation ability. Furthermore, the apoptosis rate of antisense transfected cells was significantly higher than that of control, indicating that antisense RNA suppressed malignant growth by induction of apoptosis. CONCLUSION: Our studies demonstrate the critical role of Wnt signaling pathway in the neoplastic growth of liver cancer cells and suggest that inhibition of Tcf activity with antisense Tcf RNA may be a potential new gene therapy method for liver cancer.

Surgery for large primary liver cancer more than 10 cm in diameter.

PURPOSE: 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. METHODS: Comparison of clinicopathological data between patients with PLC >/=10 cm ( n=1,227) and PLC <10 cm ( n=2,349) during the same period. RESULTS: In comparison with patients with PLC <10 cm, patients with PLC >/=10 cm were significantly younger ( P<0.01), had a lower incidence of asymptomatic tumors (9.1% vs 39.5%, P<0.001), higher alpha-fetoprotein levels ( >400 ng/ml, 78.3% vs 49.2%, P<0.001), higher gamma-glutamyl transpeptidase levels ( >6U, 87.7% vs 70.5%, P<0.001), a lower incidence of a history of hepatitis (45.0% vs 61.4%, P<0.001) and associated macronodular cirrhosis (cirrhotic nodules >/=0.3 cm, 59.8% vs 66.6%, P<0.001), poor differentiation of tumor cells (Edmondson grade 3-4, 24.3% vs 19.7%, P<0.01), a lower percentage of single nodule tumors (59.9% vs 75.4%, P<0.001) and well-encapsulated tumors (28.5% vs 62.1%, P<0.001), a higher proportion of tumor emboli in the portal vein (20.5% vs 9.0%, P<0.001), a lower resection rate (50.6% vs 86.8%, P<0.001), a lower curative resection rate (54.8% vs 78.3%, P<0.001), a higher operative mortality rate (4.5% vs 2.3%, P<0.001), and less local resection (52.5% vs 80.2%, P<0.001). 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 PLC <10 cm ( n=2039) ( P<0.01). CONCLUSIONS: 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.

A decade's studies on metastasis of hepatocellular carcinoma.

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.

Multimodality treatment of hepatocellular carcinoma.

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.

Pathological characteristics, PCNA labeling index and DNA index in prognostic evaluation of patients with moderately differentiated hepatocellular carcinoma.

AIM: To study the relationship between prognosis and pathological characteristics, proliferating cell nuclear antigen labeling index (PCNA-LI) and DNA index (DI) in patients with moderately differentiated hepatocellular carcinoma(HCC). METHODS: 51 cases of moderately differentiated HCC were analyzed with respect to the relation between their clinical follow-up data and pathological characteristics. Meanwhile, PCNA-LI of HCC cells was detected by immunohistochemistry assay and DI was measured by Feulgen staining and automatic image analysis technique. RESULTS: Patients with a single tumor nodule, less than 5 cm in diameter, no tumor emboli, no daughter nodules and necrosis had relatively better prognosis; patients with euploidy HCC had better prognosis than those with aneuploidy; among the aneuploidy patients those with DI<1.5 had better prognosis than the cases with DI>1.5; The higher the PCNA-LI, the worse would be the prognosis. The increase in DI was correlated with the increase in PCNA-LI, and both of them were correlated with the pathological changes of the tumor. CONCLUSION: A composite analysis of the pathological characteristics of tumor tissue, DI and PCNA-LI might be useful in predicting the prognosis of HCC patients.

Association of hTcf-4 gene expression and mutation with clinicopathological characteristics of hepatocellular carcinoma.

AIM: Hepatocellular carcinoma(HCC) is a significant health problem in China. But the molecular mechanisms of HCC remains unclear. APC/beta-Catenin/Tcf signaling pathway, also known as Wnt pathway, plays a critical role in the development and oncogenesis. As little is known about the alteration of human T-cell transcription factor-4 (hTcf-4) gene in HCC, it is of interest to study the expression and mutation of hTcf-4 gene in HCC and the relationship between hTcf-4 gene and progression of HCC. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the expression of hTcf-4 mRNA in 32 HCC and para-cancerous tissues and 5 normal liver tissues. PCR-single strand conformation polymorphism (PCR-SSCP) method was used to detect the mutation of hTcf-4 exons 1, 4, 9 and 15 in HCC. The correlation of expression and mutation of the hTcf-4 gene with clinicopathological characteristics of HCC was also analyzed. RESULTS: RT-PCR showed that the expression rate of hTcf-4 mRNA in HCC, para-cancerous tissues and normal liver tissues was 90.6 %, 71.9 % and 80 %, respectively. The gene expression level in tumor was 0.71+/-0.13, much higher than that in para-cancerous liver 0.29+/-0.05 and normal liver 0.26+/-0.05 (P<0.001), although there was no significant difference in gene expression level between para-cancerous tissues and normal liver (P>0.05). Furthermore, hTcf-4 gene expression was closely associated with tumor capsule status and intrahepatic metastasis of HCC. On SSCP, 2 of 32 cases of HCC (6.25 %) displayed characteristic mutational mobility shifts in exon 15 of the hTcf-4 gene. No abnormal shifting bands were observed in para-cancerous tissues. CONCLUSION: The high expression level of hTcf-4 in HCC, especially in tumors with metastasis, suggests that the over-expression of hTcf-4 gene may be closely associated with development and progression of HCC, but the mutation of this gene seemed to play less important role in this respect.

Diagnosis and surgical treatments of hepatocellular carcinoma with tumor thrombosis in bile duct: experience of 34 patients.

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.

P53 immunohistochemical scoring: an independent prognostic marker for patients after hepatocellular carcinoma resection.

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.

Recurrence and metastasis of hepatocellular carcinoma: progress and prospects.

BACKGROUND: Recurrence after resection of hepatocellular carcinoma (HCC) is a major obstacle to improve prognosis. Therefore, further improvement of long-term survival may depend on prevention and treatment of the recurrent tumor. OBJECTIVE: To evaluate the progress of surgery for HCC, the risk factors for recurrence, and clinical and basic studies on the prevention and management of recurrence and metastasis after resection of HCC. DATA SOURCES: A review of currently available data in the mentioned areas. DATA SYNTHESIS: Encouraging changes in the prognostic pattern were observed when the primary liver cancer (PLC) data of 1958-1967 (n=118), 1968-1977 (n=356), 1978-1987 (n=715) and 1988-1997 (n=2038) were compared. The 5-year survival was 2.8%, 7.3%, 27.1% and 52.5%, respectively, and the 10-year survival 2.8%, 4.3%, 19.8% and 39.9%, respectively. Risk factors for recurrence included symptomatic patient, high gamma-glutamyl-peptidase (gamma-PGT), large tumor size, portal vein embolus, advanced tumor stage, etc. Active hepatitis activity in the nontumorous liver and perioperative transfusion enhanced the recurrence. Molecular research into the invasiveness of HCC identified some factors positively related to invasiveness, P16 and P53 mutation, H-ras, c-cerbB2, mdm2, transforming growth factor (TGF), epidermal growth factor receptor (EGF-R), matrix metalloproteinase-2 (MMP-2), urokinasetype plasminogen activator (uPA), its receptor (uPA-R) and inhibitor (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF). In contrast, some factors were negatively related to HCC invasiveness: nm23-H1, Kai-1, tissue inhibitor of metalloproteinase-2 (TIMP-2), integrin 5, and E-cadherin. Re-resection of subclinical recurrence yielded a 5-year survival of 56.0% calculated from the first resection (n=202). Postoperative transarterial chemoembolization (TACE, n=103), hepatic artery cannulation during operation (n=105), postoperative biotherapy (n=49), and cryohepatectomy (cryosurgery followed by immediate resection of the frozen tumor, n=84) might decrease the recurrence rate, and the 3-year recurrence rate was 7.6%, 18.0%, 11.1%, and 30.1%, respectively. Minimal intraoperative blood loss and transfusion could reduce postoperative recurrence, although the exact mechanism remains to be elucidated. CONCLUSIONS: HCC invasiveness is the major topic to be studied, particularly in the molecular level. Anti-angiogenesis, biotherapy, novel approach based on molecular findings, and multidisciplinary interventions might also be important for HCC.

Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cryohepatectomy for hepatocellular carcinoma--results in 84 patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Three-grade criteria of curative resection for primary liver cancer].

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.