Progress in the molecular mechanism and the prediction of postoperative recurrence of hepatocellular carcinoma / 中国实用外科杂志

The radical resection is the most important treatment for primary liver cancer, but the high recurrence rate is the main obstacle to the survival of postoperative patients.According to the time of tumor recurrence, the postoperative recurrence of liver cancer is divided into the early recurrence and late recurrence. The former is mainly related to the invasion and metastasis of liver cancer, and the latter is mainly caused by multicenter tumor occurrence based on the background of liver disease. The early prediction of postoperative recurrence risk contributes to the timely and effective intervention and improved the prognosis of the patients. In the past ten years, the clinical research on the recurrence of liver cancer has been systematically studied. The molecular mechanism of the metastasis and recurrence has been newly recognized: the metastatic potential of liver cancer begins in the early stage of primary tumor; the imbalance of micro-environmental inflammatory response promotes the metastasis of cancer. At the same time, a variety of molecular markers for predicting the recurrence of liver cancer were identified, and a molecular prediction model for the metastasis of liver cancer was created and optimized. These research results lay the foundation for more accurately understanding of the recurrence and metastasis of liver cancer and developing the more precise prevention and treatment strategies.

High expression of thrombin receptor PAR1 in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma in early stage / 中华肝脏病杂志

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

A clinicopathologic study of hepatic angiomyolipoma / 中华外科杂志

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

Prognostic analysis of 669 liver metastasis of colorectal cancer cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the relation between different therapy and survival rate of liver metastasis of colorectal cancer (LMCC).</p><p><b>METHODS</b>Clinical data of 669 LMCC patients,collected from Fudan University Zhongshan Hospital from January 2000 to July 2008, were analyzed retrospectively.</p><p><b>RESULTS</b>Of the 669 cases, 379 cases were synchronous liver metastases(SLM) and 290 cases were metachronous liver metastases(MLM). There were no significant differences in age, gender and position of primary tumor between SLM and MLM groups(P>0.05), but as to liver metastasis characteristics(liver lobe involved, focus number and maximal focus diameter) and CEA, CA19-9 before therapy,there were significant differences(P<0.05). Two hundred and fifty-three cases underwent curative hepatic resection, including 123 cases in SLM and 130 cases in MLM. Until October 31, 2008, all the cases were followed up. The median survival time of SLM was(11+/-1) months and of MLM(23+/-2) months(P<0.01). Five-year survival rate of SLM was 6.4% and of MLM 11.4%(P<0.01). As to different treatments, median survival time and 5-year survival rate of curative hepatic resection group were 37 months and 35.6%, and of non-operation groups(i.e. intervention, chemotherapy, radiofrequency therapy and percutaneous ethanol injection) were 5 to 26 months and 0 to 3.6% respectively(P<0.05).</p><p><b>CONCLUSIONS</b>Curative hepatic resection is the first choice of liver metastasis of colorectal cancer, which can improve the survival rate. Resection rate and survival of MLM are better than those of SLM.</p>

Identification of metastasis-related microRNAs of hepatocellular carcinoma in hepatocellular carcinoma cell lines by quantitative real time PCR / 中华肝脏病杂志

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

Application of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma / 中国医学科学院学报

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

Treatment of postoperative recurrence of hepatocellular carcinoma with radiofrequency ablation comparing with repeated surgical resection / 中华外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Primary experience of the anatomical laparoscopic left lateral hepatic lobectomy procedure for benign and malignant liver tumors / 中华外科杂志

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

Diagnosis and treatment of primary hepatic carcinoid tumor / 中华外科杂志

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

Therapeutic effects of hepatic resection in liver metastasis of colorectal cancer / 中华外科杂志

<p><b>OBJECTIVES</b>To evaluate therapeutic effects of hepatic resection in liver metastasis of colorectal cancer (LMCC).</p><p><b>METHODS</b>The clinical data of 133 cases of LMCC received hepatic resection from January 1, 2000 to December 31, 2005 in Zhongshan Hospital were analyzed retrospectively. The relationship between hepatic resection and survival rate was also concerned.</p><p><b>RESULTS</b>One hundred and thirty-three cases received curative hepatic resection in all 470 LMCC cases, of which 30 cases from synchronous liver metastasis (SLM) group (totaled 196 cases) and 103 cases from metachronous liver metastasis (MLM) group (totaled 274 cases). Mortality rate during operation was 3.3% in SLM and 1.9% in MLM (P < 0.05). All patients were followed-up till June 31, 2006, the 1, 3, 5 year survival rates and median survival time of SLM were similar to those of MLM, but its recurrence rate was higher (36.7% vs 20.4%, P = 0.030). The 1, 3, 5 year survival rate in the 49 patients who were operable but received non-operation treatment were significantly lower than those in operated patients (P = 0.003). In 30 SLM cases, 22 received I stage resection of their primary and liver metastasis tumor and 8 received liver metastasis resection after the primary surgery (II stage operation), 1, 2, 3 year survival and the median survival time were similar in the two groups. With COX multivariate analysis, incision margin > or = 1 cm (P = 0.036) and reoperation after recurrence (P = 0.041) were protective survival factors, and post-operation recurrence (P = 0.023) was survival risk factor.</p><p><b>CONCLUSIONS</b>Curative hepatic resection is the first choice of therapy in liver metastasis of colorectal cancer and it can improve survival.</p>

Loss of heterozygosity of plasma circulating DNA from hepatocellular carcinoma patients and its clinical significance / 中华肝脏病杂志

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

Survival of patients with liver metastasis from colorectal cancer by different modes of therapy: a report of 363 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the correlation between different therapies and survival of liver metastasis from colorectal cancer ( LMCC) , and to compare the clinical outcome of synchronous liver metastasis (SLM) with that of metachronous liver metastasis (MLM).</p><p><b>METHODS</b>The clinical data of 363 patients with LMCC were retrospectively reviewed with focus on the correlation between different therapy and survival.</p><p><b>RESULTS</b>Of these 363 patients, 160 had SLM and 203 had MLM. Between the SLM and MLM group, there was no significant difference in age, or gender or primary cancer site (P > 0. 05 ), but significant differences were observed in condition of liver metastasis including liver lobe involved, focus number, maximum focus diameters and level of serum CEA and CA199 before therapy(P <0. 05). Ninety-one patients underwent curative hepatic resection, 22 of them in the SLM group and 69 in the MLM group. Mortality rate related to operation was 4. 5% (1/22) in SLM group and 2. 9% (2/69) in MLM group( P < 0.05). All patients were followed until 31/6/2005. The 3-year survival rate was 5. 2% with a median survival time of 10 +/- 1 months for the SLM group, and it wasl6. 4% and 17 +/- 1 months for the MLM group (P<0.01). Regarding to the treatment modalities, the 3-year survival rate was 30. 2% with a median survival time of 26 months for curative hepatic resection group, and it was 0% - 16. 7% and 10 - 17 months for non-operation groups treated by intervention, chemotherapy, radiofrequency therapy, percutaneous ethanol injection and Chinese traditional drugs (P <0. 05, P <0. 01 ).</p><p><b>CONCLUSION</b>Curative hepatic resection is still the first choice for liver metastasis from colorectal cancer improving the survival significantly. Other non-operative methods also can improve phase II resection rate. Metachronous liver metastasis has higher resection rate and better survival than the synchronous liver one.</p>

Knocking down osteopontin expression by specific siRNA reduces the in vitro invasiveness of human hepatocellular carcinoma cells / 中华肿瘤杂志

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

The investigation of the technology of microcell mediated chromosome transfer for functional localization of metastasis suppressor genes for liver cancer on human chromosomes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>In order to seek the functional evidence that there could be metastatsis suppressor gene for liver cancer on human chromosomes, the objective of this study is to establish a method of microcell mediated chromosome transfer (MMCT).</p><p><b>METHODS</b>Human chromosome 8 randomly marked with neo gene was introduced into highly metastatic rat liver cancer C5F cell line by treating the single human chromosome donor cells with sequential steps of micronucleation, enucleation and microcell fusion. Double selections of G418 and HAT were applied to screen positive microcell hybrids, which were cloned by single cell isolation. Microcell hybrid clones were confirmed by STS-PCR and WCP-FISH.</p><p><b>RESULTS</b>Microcell hybrids resistant to HAT and G418 were obtained, from which 15 clones were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that human chromosome 8 had been successfully introduced into rat liver cancer cell line C5F. The human chromosome 8 introduced into C5F was found to have random loss of chromosome fragments by STS-PCR and consistent recombination with rat chromosome by WCP-FISH.</p><p><b>CONCLUSION</b>The successfulls introduction of human chromosome into highly metastatic rat liver cancer cell line has established the technical basis for functional localization of metastasis suppressor gene(s) for liver cancer on human chromosomes.</p>

The prognostic significance of preoperative plasma level of osteopontin in combination with intercellular adhesion molecule-1 for patients with hepatocellular carcinoma / 中华外科杂志

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

The effects of portal vein microscopic and macroscopic tumor thrombi on post-operation patients with hepatocellular carcinoma / 中华外科杂志

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

Screening hepatocellular carcinoma autoantibodies by serological proteome analysis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To screen hepatocellular carcinoma (HCC) autoantibodies as diagnostic biomarkers or therapy targets by serologic proteome analysis (SERPA).</p><p><b>METHODS</b>Total proteins extracted from human HCC cell line HCCLM3 were separated by two-dimensional electrophoresis (2-DE) and then transferred onto PVDF membranes, which were subsequently incubated with sera from HCC, hepatitis B virus (HBV) infected patients or healthy volunteers. All immuno-reactive protein spots on blot films were matched to those on 2-DE gel maps by image analysis and identified by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS/MS).</p><p><b>RESULTS</b>2-DE gel maps of HCCLM3 and corresponding blot films of good quality and reproducibility were established. The number of spots on HCCLM3 2-DE reference gel totaled 603 and those on HCC, HBV and healthy sera blotted films were 70.75+/-24.25, 68.5+/-23.44 and 41.38+/-15.05, respectively. Blot films of HCC and HBV groups had more spots than those of the healthy group (P < 0.05) while no significance was found between films of HCC and HBV groups. By identification, those HCC autoantibodies could be classified as nuclear proteins, cytoskeleton proteins, heat shock proteins and metabolic enzymes.</p><p><b>CONCLUSION</b>Serological proteome analysis is a high throughput technique for screening tumor autoantibodies. Those newly identified HCC associated tumor antigens and corresponding autoantibodies can be used in the early diagnosis or immuno-therapy of HCC.</p>

Effect of postoperative transcatheter arterial chemoembolization on hepatocellular carcinoma patients with residual tumor / 中华肿瘤杂志

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

Three-grade criteria of curative resection for primary liver cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To clarify three-grade criteria of curative resection for primary liver cancer (PLC) and evaluate their clinical significance.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Study on the relationship between serum cytokeratin 19 level in hepatocellular carcinoma patients and the clinico-pathologic characteristics / 中华肝脏病杂志

<p><b>OBJECTIVE</b>As our previous comparative proteomics study on high and low metastasis human hepatocellular carcinoma (HCC) cell strains revealed that cytokeratin 19 (CK19) was related to higher metastasis potential, we further investigated the relationship between serum CK19 level in HCC patients and their clinico-pathologic characteristics.</p><p><b>METHODS</b>Serum CK19 levels of 101 normal controls and 108 pathology-proven HCC patients were determined using radioimmunoassay, and the their correlation with clinico-pathologic parameters were studied.</p><p><b>RESULTS</b>The upper limit of one-side 98% confidence interval of normal serum CK19 level was 2.3 microg/L. Among 108 HCC patients, 24 (22.2%) had increased serum CK19 level, ranging from 2.4 to 45.5 microg/L. There were 12 patients (11.1%) with increased CK19 level but normal AFP level. The percentage of poor differentiated tumor was higher in CK19 increased cases (37.5%, 9/24) than in CK19 normal cases (20.2%, 17/84). Moreover, the presence of portal vein tumor emboli was significantly higher in CK19 increased cases (25.0%, 6/24) than in CK19 normal cases (6.0%, 5/84). (Chi-square = 7.403, P < 0.01) In addition, the percentage of TNM stage III/IV tumor was significantly higher in CK19 increased patients (54.2%, 13/24) than in CK19 normal cases. (chi-square = 13.300, P < 0.005)</p><p><b>CONCLUSION</b>Some HCC patients do have increased serum CK19 level, which could be related to portal vein tumor emboli, poor tumor differentiation and advanced tumor stages.</p>