Objective To clarify relationship between signal heterogeneity on hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI and prognosis of hepatocellular carcinoma (HCC). Methods From January 2014 to January 2017 in the First Affiliated Hospital of Chongqing Medical University, a total of 77 patients with the pathologically proved HCC underwent Gd-EOB-DTPA-enhanced MRI prior to surgery were included in this study. On the basis of the signal heterogeneity in the hepatobiliary phase, the included patients were designed to homogeneous hypointensity group and heterogeneous hyperintensity group. The disease-free survival time were compared between the 2 groups and it’s influencing factors were analyzed. Results Seventy-seven patients with HCC were included, including 45 cases of homogeneous hypointensity and 32 cases of heterogeneous hyperintensity. There were no significant differences in the age, gender, etiology, liver function, alpha-fetoprotein, differentiated degree, Child-Pugh grade, lesion diameter, lesion border, and number of lesions between the 2 groups (P>0.05). However, the HCC patients with heterogeneous hyperintensity had a later BCLC staging (P=0.001). The disease-free survival time of the patients with homogeneous hypointensity and heterogeneous hyperintensity was (17.0±9.8) months and (12.4±10.4)months, respectively. The Kaplan-Meier survival curve showed that the disease-free survival time in the patients with homogeneous hypointensity was significantly better than that in the patients with heterogeneous hyperintensity (P=0.020). The results of univariate analysis showed that the other confounding factors had no effect on the disease-free survival time of patients with hepatocellular carcinoma (P>0.05) except for the signal of hepatobiliary phase (P<0.05). Furthermore, the hepatobiliary phase signal, BCLC stage, and degree of differentiation, which might be clinically considered as potentially influencing for the prognosis of patients with HCC, were included in the Cox multivariate proportional hazard regression model and found that the heterogeneous hyperintensity was still the risk factor of the disease-free survival rate in patients with HCC (P=0.047). Conclusion Signal heterogeneity on hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is related to prognosis of patients with HCC, heterogeneous hyperintensity may indicate a lower disease-free survival rate.
In recent years, the diagnosis and treatment of hepatocellular carcinoma (HCC) has entered a brand-new era due to the advancement of diagnosis methods and the emergence of targeted drugs and immunotherapy drugs. The author described and summarized in detail the screening program, diagnostic thought and procedure, clinical staging, mechanism of targeted and immune therapy and application range of HCC.
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.
【Abstract】Objective To construct a recombinant adenoviral vector carrying antisense matrix metalloproteinase2 (MMP2) for use in the gene therapy to inhibit the invasiveness and migratory capacity of hepatocellular carcinoma (HCC) cell line HepG2 in vitro and in vivo models. Methods Total RNA was extracted from HCC, and then a 500 bp fragment at the 5′ end of human MMP2 cDNA was synthesized by polymerase chain reaction (PCR) and was reversely inserted into the multiclone site (MCS) of the shuttle plasmid pAdTrack-CMV,with the resultant plasmid and the backbone plasmid pAdEasy-1,the homologous recombination took place in the E.coli BJ5183 and the recombinant adenoviral plasmid carrying the antisense MMP2 gene was constructed and generated. The adenoviruses(Ad-MMP2AS) were packaged and amplified in the HEK 293 cells.Then the viral titer was checked by GFP. Results The recombinant adenovirus vector carrying antisense MMP2 was constructed successfully, the b green fluorescence was observed in HEK 293 cells under a fluorescence microscopy. The viral titer was 1×108/ml. Conclusion The recombinant adenovirus Ad-MMP2AS constructed by us could introduce the antisense MMP2 into HepG2 effectively,which would provide experimental basis for reversing the overexpression of MMP2 in HCC and for inhibiting the invasiveness and migratory capacity of HepG2 in vitro and in vivo models.
ObjectiveTo investigate the expression of IQ motif-containing GTPase activating protein 1 (IQGAP1) in hepatocellular carcinoma (HCC) tissues, and to analyze the relationship of IQGAP1 and patient's clinical characteristics and prognosis after liver resection. MethodsData of 79 patients who received liver resection between 2007 and 2009 in our hospital were collected. The expression of IQGAP1 was examined by immunohistochemical tests. The clinical characteristics and prognosis were compared. ResultsIQGAP1 was detected in 43 patients (54.4%). Patients with IQGAP1 expression had more poor differentiation and microvascular invasion. The cumulative recurrence-free rate and overall survival rate in 1-, 3-, and 5-year after operation of patients with IQGAP1 expression (cumulative recurrencefree rate:67.4%, 39.5%, and 23.3%; cumulative overall survival rate:97.7%, 71.5%, and 53.3%) were poor than patients without IQGAP1 expression (cumulative recurrence-free rate:100%, 94.4%, and 83.3%; cumulative overall survival rate:1007%, 97.2%, and 88.9%), P < 0.001. ConclusionsHCC patients with IQGAP1 expression had a poor prognosis after liver resection. IQGAP1 may be a prognostic indicator for hepatocellular carcinoma.
ObjectiveTo identify the risk factors of postoperative recurrence and survival for patients with hepatocellular carcinoma within Milan criteria following liver resection. MethodsData of 267 patients with hepatocellular carcinoma within Milan criteria who received liver resection between 2007 and 2013 in our hospital were retrospectively analyzed. ResultsAmong the 267 patients, 123 patients suffered from recurrence and 51 patients died. The mean time to recurrence were (16.9±14.5) months (2.7-75.1 months), whereas the mean time to death were (27.5±16.4) months (6.1-75.4 months). The recurrence-free survival rates in 1-, 3-, and 5-year after operation was 76.8%, 56.3%, and 47.6%, respectively; whereas the overall survival rates in 1-, 3-, and 5-year after operation was 96.6%, 82.5%, and 74.5%, respectively. Multivariate analyses suggested the tumor differentiation, microvascular invasion, and multiple tumors were independent risk factors for postoperative recurrence; whereas the tumor differentiation, positive preoperative HBV-DNA load, and preoperative neutrophil-to-lymphocyte ratio adversely influenced the postoperative survival. ConclusionsFor patients with hepatocellular carcinoma within Milan criteria after liver resection, the tumor differentiation, microvascular invasion, and multiple tumors contribute to postoperative recurrence; whereas the tumor differentiation, positive preoperative HBV-DNA load, and preoperative neutrophil-to-lymphocyte ratio adversely influence the postoperative survival.
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 investigate immunological therapeutic effect and safety of dendritic cells (DCs) combined with heat shock protein 70 (HSP70)-peptide complex (PC) derived from autogeneic hepatoma tissue. Methods Thirty patients with hepatocellular carcinoma from February 2010 to February 2015 in the Gaochun People’s Hospital of Nanjing and The Third Affiliated Hospital of Nantong University were studied, and subsequently were divided into an immunotherapy group (treated with HSP70-PC/DCs vaccine,n=15) and a chemotherapy group (n=15) according to the prescribed postoperative treatment methods. The levels of T lymphocyte subtypes were assayed by FACS. The toxicity adverse reactions, alpha-fetoprotein (AFP), CA19-9, hepatic tumor recurrence rate, survival rate, and KPS of two groups patients were evaluated and compared between these two groups. Results ① The values of CD3+, CD4+, CD4+/CD8+, and CD3CD56 had no significant differences between the immunotherapy group and the chemotherapy group before treatment (P>0.05), which in the immunotherapy group were significantly higher than those in the chemotherapy group after treatment (P<0.05), and which were significantly higher in the immunotherapy group after treatment as compared with the levels before treatment (P<0.05), and which had no significant differences in the chemotherapy group between after treatment and before treatment (P>0.05). ② Before treatment, the levels of AFP and CA19-9 had no significant differences between the immunotherapy group and the chemotherapy group (P>0.05), which in the immunotherapy group were significantly lower than those in the chemotherapy group after treatment (P<0.05). In the immunotherapy group, the levels of AFP and CA19-9 after treatment were significantly lower than those before treatment (t=2.564，P=0.021；t=2.011，P=0.041), which in the chemotherapy group before treatment were decreased as compared with the levels before treatment (t=2.221,P=0.036;t=2.487,P=0.066). ③ The patients treated with the HSP-PC/DCs vaccines was well tolerated and no obvious toxicity was appeared. ④ All the patients were followed up 5–19 months with median follow-up time of 9 months. The median survival time was 560 d and 436 d in the immunotherapy group and the chemotherapy group, respectively. After treatment, KPS score was significantly higher and recurrence rate was significantly lower in the immunotherapy group as compared with the chemotherapy group (P<0.05). The total survival had no significant difference between the immunotherapy group and the chemotherapy group (P>0.05). Conclusions The preliminary results of limited cases in this study show that HSP70-PC/DC vaccination is safe and effective in treatment of hepatocellular carcinoma, the pulsed DCs are effective in activating specific T-cell responses against hepatocellular carcinoma cells. HSP70-PC/DC vaccine might improve immunity and prevent postoperative recurrence of hepatocellular carcinoma.
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.
Objective To investigate the expressions of vascular endothelial growth factor-C (VEGF-C) and its receptor Flt-4 in hepatocellular carcinoma (HCC), in order to analyze the relationships among their expressions, angiogenesis, lymph-genesis, and clinicopathologic features of HCC. Methods Sixty-two cases of HCC and 15 cases of normal hepatic tissue were studied with immunohistochemical method in order to inspect the expressions of VEGF-C and Flt-4, and to calculate the microvessel density (MVD) marked by CD34 and the lymphatic vessel density (LVD) marked by Flt-4. Besides their correlations, their relations with clinicopathologic features of HCC were further analyzed. Results The positive rates of VEGF-C and Flt-4 were obviously higher in HCC than those in normal hepatic tissue (Plt;0.05, Plt;0.01). The expression of VEGF-C in HCC was remarkably related with portal vein tumor emboli, histological differentiation of HCC, and postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). The expression of Flt-4 in HCC was also related with histological differentiation and postoperative recurrence (Plt;0.05, Plt;0.01). MVD was related with tumor size, TNM clinical stage, histological differentiation, portal vein tumor emboli, and postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). LVD was related with histological differentiation, postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). Additionally, there was positive correlation between VEGF-C and Flt-4, MVD or LVD, Flt-4 and MVD or LVD, MVD and LVD, respectively (Plt;0.01). Conclusions VEGF-C and Flt-4 are highly expressed in HCC, and are related with postoperative recurrence, are positive correlated with MVD and LVD. It suggests that VEGF-C/Flt-4 might has an effect on progression and prognosis of HCC through promoting angiogenesis and lymph-genesis.