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 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.
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.
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 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.
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.
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.
ObjectiveTo understand the progress and problems of liver transplantation standard for hepatocellular carcinoma. MethodsThe related articles regarding transplant criteria of hepatocellular carcinoma were reviewed and analyzed. ResultsSince Milan criteria were proposed by Mazzaferro in 1996, a number of criteria were porposed by many transplant centers. These criteria expanded Milan criteria. Compared with Milan criteria, these criteria expanded tumor size and (or) tumor number, or combined with some biological variables, or combined with some immunological variables. However, there are still some issues should be clarified. ConclusionDespite there are many transplant criteria of hepatocellular carcinoma, but a number of issues should be further investigated.
【Abstract】ObjectiveTo discuss the possibility and clinical significance of SSX-1 mRNA used as specific marker for examining HCC cells in peripheral blood of HCC patients. MethodsUsing the RT-PCR method, the SSX1 mRNA of the peripheral blood was examined in 25 cases of HCC patients and 20 non-HCC patients. The same method was used to detect the expression of SSX-1 mRNA in the tumor tissues, para-tumor tissues, cirrhosis tissues and normal hepatic tissues. A randomized sample was extracted for DNA sequencing from positive electrophoresis expression samples of SSX-1 to examine the reliability of results. ResultsThe expression rates of SSX-1 mRNA were 60%(15/25) and 40%（10/25） respectively in tumor tissues of HCC and the corresponding peripheral blood. SSX-1 mRNA were not expressed in para-tumor tissues,cirrhosis tissues and normal hepatic tissues. The DNA sequence -confirmed that the RTPCR products were true target cDNA. No relationships were found between the expression of SSX-1 gene and clinical characteristics, such as age, sex, tumor size, TNM stage， extent of differentiation and serum AFP level (Pgt;0.05). However, in 33%（3/9） patients with normal serum AFP (lt;20 μg/L), specific expression of SSX1 mRNA was observed. ConclusionHigh specific expression of SSX-1 mRNA is observed in the peripheral blood of patients with HCC, it suggests that applying it as a tumor marker to detect HCC cells in peripheral blood is an adjuvant diagnostic tool. The expression of SSX-1 mRNA in the peripheral blood is observed in the group HCC patients whose serum AFP (lt;20 μg/L) are normal, which suggests that applying both SSX-1 mRNA and AFP as tumor markers together might be useful to improve the diagnostic accuracy for HCC.