Objective To systematically review the efficacy and safety of laparoscopic hepatectomy (LH) and open hepatectomy (OH) for patients with hepatocellular carcinoma (HCC). Methods PubMed, EMbase, The Cochrane Library, CBM, WanFang Data, CNKI databases were electronically searched to collect the case-control studies about LH vs. OH for patients with HCC from inception to December, 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then meta-analysis was performed by using RevMan 5.3 software. Results A total of 28 studies involving 1 908 patients were included. The results of meta-analysis showed that: the LH group was superior to OH group on complications (OR=0.35, 95%CI 0.26 to 0.48, P<0.000 01), hospital stay (MD=–4.18, 95%CI (–5.08, –3.29),P<0.000 01), and five years overall survival rate (OR=1.65, 95%CI 1.23 to 2.19,P=0.000 7) and disease-free survival rate (OR=1.51, 95%CI 1.12 to 2.03, P=0.006). However, no significant differences were found in one year and three years overall survival rate, disease-free survival rate, and postoperative recurrence rate. Conclusion Current evidence shows that the LH is superior to OH for the treatment of HCC, and may be amenable to surgery because of its safety and longtime efficacy. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
Objective To evaluate the effect of methylation determination about the peripheral plasma DNA in diagnose of hepatocellular carcinoma （HCC） and select the highly sensitive and specific methylated cancer suppressor genes. Methods Methylation-specific PCR （MSP） was used to detect the degree of methylation about SLIT2 and DAPK genes in peripheral plasma and associated cancer tissues of 34 patients with HCC confirmed by pathology, then analyzed their relationship to clinicopathologic feature. Results The positive rate of the promoter methylation of SLIT2 and DAPK genes in cancer tissues in 34 cases were 70.6% （24/34） and 79.4% （27/34）, while the relevant promoter methylation rate in plasma were 44.1% （15/34） and 50.0% （17/34） correspondingly. The sensitivity of detection of DNA methylation about SLIT2 and DAPK genes in plasma was 62.5% and 63.0%, respectively；both of the specificity for them were 100%. The negative predicted value was 52.6% and 41.2%, respectively；while both of the positive predicted value were 100%. There were no significant correlation between the clinicopathologic features and the methylation rate in cancer tissues and plasma （P＞0.05）. In plasma of patients whose AFP＜400 μg/L, the positive rate of combined detection of DNA methylation of SLIT2 and DAPK was 61.1% （11/18）. Conclusions The detection rate of DNA methylation of SLIT2 and DAPK genes in plasma is higher, and there is a significant correlation between the DNA methylation in HCC tissue and plasma, based on MSP method. DNA methylation in plasma, as an non-invasive method, could be used to diagnose HCC, especially for the patients whose AFP is negative. HBV infection may be only associate with DNA methylation of part gene.
Objective To investigate the relationship between syndecan-1 protein and malignant phenotypes of hepatocellular carcinoma (HCC). Methods forty-seven formalin-fixed sections were obtained. The syndecan-1 was measured with immunohistochemistry assay (ABC method). Results Among 47 HCC tissues, 28 (59.6%) show negative staining, the syndecan-1 negative rate in HCC with poor differentiation was higher than those with good differentiation (78.3% vs 41.7%, Ｐ＜0.05), and negative rate in large HCC was higher than in small HCC (81.0% vs 42.3%, Ｐ＜0.01), and negative rate in HCC with the presence of tumor-cells in blood was greater than in those without tumor-cells in blood (84.2% vs 42.9%, P＜0.01). No correlation was found between syndecan-1 expression and serum AFP level and Child class. Conclusion Syndecan-1 expression is correlated with the growth, differentiation, invasiveness, metastasis and progression of HCC. It is possible that syndecan-1 is a negative regulator of these malignant phenotypes of HCC, can be regarded as suppressive gene.
Objective To construct the recombinant of hepatocellular carcinoma-targeting adenovirus containing r-Caspase-3 gene and provide the gene therapic strategy for hepatocellular carcinoma. Methods The pAdTrack-EAFP-PALB was constructed and the r-Caspase-3 gene was subcloned into the vector. The linearized shuttle plasmid was homogenously recombined with AdEasy-1 in BJ5183 cells. The candidate clone was analyzed by restriction endonuclease digestion and sequencing, and then pAdEasy-EAFP-PALB/r-Caspase-3 vector was digested with PacⅠand transfected into AD293 cells for packaging and amplifying, recombinant virus was constructed successfully. Infection titer and efficiency of recombinant virus were monitored by green fluorescent protein (GFP) expression. The expression of r-Caspase-3 in infected HepG2 cells was detected by RT-PCR and Western blot. The apoptosis of HepG2 cells was detected by SRB dyeing method. Results Shuttle vector pAdTrack-EAFP-PALB/r-Caspase-3 was correct after identification by restriction endonuclease analysis and sequencing. By PCR and PacⅠ restriction endonuclease analysis， the homologous recombinant of pAdEasy-EAFP-PALB/r-Caspase-3 was successful. The expression of GFP was observed when linearized pAdEasy-EAFP-PALB/r-Caspase-3 was transfected into AD293 cells. AD293 cells could be infected repeatedly by recombinant adenovirus. The expression of r-Caspase-3 gene on HepG2 cells was detected by RT-PCR and Western-blot methods respectively, which confirmed that the Ad-EAFP-PALB/r-Caspase-3 was constructed successfully. The specificity of Ad-EAFP-PALB/r-caspase-3 which targeting induced hepatocellular carcinoma cells was founded by SRB dyeing test. Conclusion The Recombinant of hepatocellular carcinoma-targeting adenovirus containing r-Caspase-3 gene was constructed successfully and which established the foundation of r-Caspase-3 gene therapy in future research to hepatocellular carcinoma.
Objective To introduce the possible effects and significances of angiogenesis and antiangiogenic in the development and treatment of hepatocellular carcinoma (HCC). Methods Recently relevant literatures were reviewed. Results Angiogenesis played a significant role in the development and therapy of HCC, and the development and metastasis of HCC could be effectively suppressed by antiangiogenic therapy. This might provide a new approach for the treatment of HCC. Conclusion Comprehending the molecular mechanism of angiogenesis and applying antiangiogenic therapy will contribute a lot for the prevention and treatment of HCC.
1术后生存41年，肝癌治疗史上的奇迹肝癌在我国是最常见的癌症之一，每年约10万人被夺去生命。此病进展迅速，预后很差，人们常将其称为“癌中之王”，或“不治之症”。 近年，肝癌研究不断取得突破进展，振奋人心。其中印象最深的是，复旦大学附属中山医院(原上海医科大学附属中山医院)在41年前为一肝癌患者成功施行了肝切除手术，至今已91岁高龄，仍健在。创造了肝癌外科治疗史上的奇迹。
ObjectiveTo explore the relationship between the expressions of fibronectin (FN) and phosphatase and tensin homology deleted on ehromosome ten (PTEN) in hepatocellular carcinoma (HCC) tissues and the clinical pathological features. MethodsThe expressions of FN and PTEN were detected by using Western blot and immunohistochemistry respectively in 83 HCC tissues and para-carcinoma tissues, 47 hepatic cirrhosis tissues and 11 normal hepatic tissues. The correlations between the expressions of FN and PTEN and the clinicopathologic features of HCC patients were analyzed. ResultsThe positive expression rate of FN protein in HCC tissues was significantly higher than those in para-carcinoma tissue, normal hepatic tissue, and liver cirrhosis tissues (P<0.05); meanwhile the expression of PTEN was opposite (P<0.05). The positive expression rate of FN protein in para-carcinoma tissues was also obviously higher than that liver cirrhosis tissues and normal hepatic tissues (P<0.05), meanwhile the expression of PTEN was opposite (P<0.05). The positive expression rate of FN protein was higher in HCC tissues with cancer embolus, lymphatic metastasis, positive AFP, and multiple tumor (P<0.05), but there were no statistically significant differences in FN protein expression, gender, age, HBsAg, degree of tumor differentiation, and size of tumor (P>0.05). The positive expression rate of PTEN was lower in HCC tissues with high-medium differentiation, cancer embolus, positive AFP, lymphatic metastasis, and tumor diameter ≥2 cm (P<0.05), there were no statistically significant differences in PTEN expression, gender, age, HBsAg, and the number of tumor (P>0.05). ConclusionsThe abnormal expressions of FN and PTEN in HCC tissues which may play a role in promoting or inhibiting occurrence, development, invasion, and metastasis of HCC. The abnormal expressions of both can be used as molecular biological markers for the malignant degree, invasion, and metastasis of HCC.
Objective To investigate whether the growth of the human experimental hepatocellular carcinoma (HCC) can be suppressed by the antibody against vascular endothelial growth factor (VEGF). MethodsThe monoclonal antiVEGF antibody was injected to nude mice nearby the xenograft tumour foculs of the human SMMC7721 HCC. The changes of the tumour size were measured at different times. The intratumoural microvessels were showed by immunohistochemical staining of CD31 antigen; the apoptotic cells in the tumour tissues were detected in situ by terminal deoxynucleotidyl transferasemediated dUTPbiotin nick end labeling (TUNEL) assay. ResultsIn the first and second week after finishing the injection procedure, the tumour sizes were compared as the length (mm) multiplying width (mm) between the two groups, the tumour sizes as the test group vs the control group were (26.46±19.81) mm2 vs (105.77±17.40) mm2 (P＜0.001) and (45.20±23.02) mm2 vs (150.77±77.41) mm2 (P＜0.05), respectively. After 2 weeks the intratumoural microvessel density (iMVD) and the apoptotic index (AI) were compared between two groups with iMVD being (2 311±120)/mm2 vs (3 900±328)/mm2(P＜0.001 ) and AI being (15.31% vs 6.83%), P＜0.005. Conclusion The antiVEGF antibody can suppress the xenograft tumour growth of the human SMMC7721 HCC by antiangiogenesis.In fact, its antitumour effect is produced by elevating the incidence of apoptosis in tumour tissues.
ObjectiveTo summarize the biomarkers related to the efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC).MethodReviewed and summarized the literatures on the basic and clinical application of biomarkers related to programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and their combination with targeted therapy.ResultsThe combination of immunotherapy and targeted therapy had brought great hope for the treatment of patients with advanced HCC, but there were still some patients who could not benefit from it. Recent studies had shown that expression of PD-L1 in tumor tissue, tumor mutational burden, tumor-infiltrating lymphocytes, peripheral immune cells, circulating tumor DNA, gut microbiome, and so on, could predict the efficacy of immunotherapy or targeted therapy combined with immunotherapy for HCC.ConclusionsThere is no specific biomarker to predict the efficacy of immunotherapy and its combination regimen for HCC. More prospective studies are needed to confirm the predictive value of these biomarkers and to establish a multi-factor predictive model or immune score to screen patients who may benefit, which is of great significance for precise immunotherapy of HCC.
ObjectiveTo explore the relationship between the signal intensity on hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI and the degree of differentiation of hepatocelluar carcinoma (HCC). MethodsForty-eight cases of HCC with Gd-EOB-DTPA-enhanced MRI images in our hospital were retrospectively included. The signal to noise ratio (SNR), contrast ratio (CR), enhancement ratio of signal to noise ratio (%EnhancementSNR), enhancement ratio of the contrast ratio (%EnhancementCR), enhancement ratio (ER), and relative enhancement ratio (RER) were calculated, respectively. Then comparisons of these signal values among different differentiations of HCC were performed. ResultsAmong the 48 cases of HCC, there were 6 cases of well differentiated, 24 cases of moderately differentiated, and 18 cases of poorly differentiated. There were 37 cases of Child-Turcotte-Pugh (CTP)A classification and 11 cases of B classification, respectively. Neither in all cases nor in cases of CTP A classification, there was no statistically significant difference in SNR, CR, %EnhancementSNR, %EnhancementCR, ER, and RER among cases of different differentiation (P > 0.05). ConclusionThe signal intensity on hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI has limited value in predicting the degree of differentiation of HCC.