Yijun Wang

Comparison of two different thermal techniques for the treatment of hepatocellular carcinoma

PURPOSE To compare the safety and efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) in treating hepatocellular carcinoma (HCC) while conforming to the Milan criteria. MATERIALS AND METHODS The study was approved by the Institutional Review Board, and informed consent was waived due to the retrospective study design. One hundred ninety-eight patients met the inclusion criteria and were included in the study. Eighty-five patients with 98 lesions received RFA, and 113 patients with 131 lesions underwent MWA. Complete ablation rates, local recurrence rates, disease-free survival rates, cumulative survival rates, and major complications were compared between the two treatment groups. RESULTS Complete ablation rates were 99.0% for RFA and 98.5% for MWA (P=1.000). Local recurrence rates were 5.2% for RFA and 10.9% for MWA (P=0.127). Disease-free survival rates at 1, 2, 3, and 4 years were 80.3%, 61.8%, 39.5%, and 19.0% in the RFA group and 75.0%, 59.4%, 32.1%, and 16.1% in the MWA group, respectively (P=0.376). Cumulative survival rates at 1, 2, 3, and 4 years were 98.7%, 92.3%, 82.7%, and 77.8% in the RFA group and 98.0%, 90.7%, 77.6%, and 77.6% in the MWA group, respectively (P=0.729). Major complication rates were 2.4% and 2.7% in the RFA group and the MWA group, respectively (P=1.000). There were no patient deaths due to treatment. CONCLUSION RFA and MWA have the same clinical value in treating HCC conforming to the Milan criteria. RFA and MWA are both safe and effective techniques for HCC as clinical application.

Tumor-Infiltrating FoxP3+ Tregs and CD8+ T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

Purpose: Tumor-infiltrating lymphocytes are considered to represent a host immune response against tumor. This study was carried out to analyze the effect of both FoxP3+ regulatory T cells (Tregs) and CD8+ T lymphocytes in prognostic value of hepatocellular carcinoma (HCC) patients. Methods: Expressions of FoxP3, CD4, CD8 and CD34 in patient-matched tumors and peritumoral tissues were assessed by immunohistochemistry for 54 HCC patients. The prognostic effect of groups with high and low numbers was evaluated by the Kaplan-Meier and Cox model analysis using median values as a cutoff. Results: Compared with the corresponding peritumoral tissue, the density of intratumoral Tregs was significantly higher, while the density of intratumoral CD8+ T cells was lower (p < 0.001 and p = 0.013, respectively). In addition, tumor-infiltrating Tregs were positively correlated with microvessel density in tumors (r = 0.334, p = 0.020). The high intratumoral Tregs density group showed a significantly lower survival rate (overall survival, p = 0.018; disease-free survival, p = 0.029). Multivariate Cox analysis revealed that intratumoral Tregs density was an independent prognostic factor for HCC. Conclusions: Tumor-infiltrating Tregs may promote HCC progression by fostering angiogenesis and decreasing CD8+ T cells. High tumor-infiltrating Tregs are thought to be an unfavorable prognostic indicator for HCC.

Aberrant DNA methylation profile of hepatocellular carcinoma and surgically resected margin.

Field cancerization currently described the theory of tumorigenesis and, until now, has been described in almost all organ systems except in liver. For this reason, we explore the presence of field cancerization in liver and its underlying clinical implication in hepatocellular carcinoma (HCC). In our study, methylation profile of HCC and surgically resected margin (SRM) were established by methylation‐specific PCR. Liver cirrhosis (LC), chronic hepatitis and normal liver were treated in the same way as the background control. The correlation analysis among the methylation profile of HCC, SRM and clinicopathological data of HCC patients was made respectively. Our results showed that methylation abnormities related to HCC, but not background disease existed in histologically negative SRM. Monoclonal and polyclonal models may coexist in field cancerization in liver. Patients with RIZ1 methylation in SRM had a shorter disease free survival. The local recurrence trend of early and later recurrence in HCC is potentially related to a second field tumor. From these results, we can suggest that field cancerization exists in liver. The study of field cancerization in liver plays an important role in hepatocarcinogenesis. Second field tumor derived form field cancerization may have important implications in HCC prognosis assessment that is worthy of further study. (Cancer Sci 2009; 100: 996–1004)

Foxp3+ regulatory T cells are associated with the natural history of chronic hepatitis B and poor prognosis of hepatocellular carcinoma

Recent studies have focused on regulatory T cells (Tregs) in chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) and they were also conducted independently of each other.

Comparison of microwave ablation and surgical resection for treatment of hepatocellular carcinomas conforming to Milan criteria

To compare the efficacy of microwave ablation (MWA) and surgical resection (RES) in the treatment of hepatocellular carcinoma (HCC) conforming to Milan criteria.

Intrahepatic interleukin-17+ T cells and FoxP3+ regulatory T cells cooperate to promote development and affect the prognosis of hepatocellular carcinoma.

Recent studies have shown that imbalance between tumor‐infiltrating interleukin (IL)‐17+ T cells and regulatory T cells (Tregs) is an important regulator of progression in various cancers, but little is known regarding this imbalance in hepatocellular carcinoma (HCC). This study explored the role of imbalance between IL‐17+ T cells and Tregs in the immunopathogenesis of HCC in patients with chronic hepatitis B (CHB) infection.

Enhanced specificity of real-time PCR for measurement of hepatitis B virus cccDNA using restriction endonuclease and plasmid-safe ATP-dependent DNase and selective primers

The persistence of covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) in hepatocytes plays a key role in viral persistence and resistance to therapy. Therefore, quantitative cccDNA measurement is of clinical importance for evaluating the efficacy of antiviral drugs, selecting an appropriate treatment strategy, and predicting the prognosis. Current established methods for measurement of cccDNA need further improvement. A modified method was developed using digestion with restriction endonucleases that do not recognize sites in the HBV DNA and plasmid-safe ATP-dependent DNase (PSAD), and using a cccDNA-specific primer set in a real-time PCR reaction. The cccDNA-specific primer has a similar amplification efficiency as a commercial kit. Treatment of samples with restriction endonuclease followed by PSAD digestion increased significantly the specificity of a cccDNA-selective primer set compared with other treatments (P<0.05). Analysis of 35 serum and liver DNA samples from patients with hepatocellular carcinoma demonstrated that the amount of serum cccDNA is beyond the minimum detection limit and that the liver cccDNA quantity is about 0-49.2 copies/cell, consistent with previous reports. Taken together, this method has the potential for evaluating the efficacy of antiviral drugs.

Differential Diagnostic Value of GPC3-CD34 Combined Staining in Small Liver Nodules With Diameter Less Than 3 cm

The diagnostic value of combining glypican-3 (GPC3) and CD34 staining for small nodules in liver biopsy specimens has not been evaluated. In this study, 201 thin-core biopsy specimens were assessed using GPC3 and CD34 immunochemical staining, including 33 cirrhotic regenerative nodules, 31 high-grade dysplastic nodules, 70 hepatocellular carcinomas (HCCs) with nodules 3 cm or smaller, and 67 HCCs with nodules larger than 3 cm. The results showed that the accuracy of GPC3 staining (90.3%) among liver nodules 3 cm or smaller was better than its use among all nodules (P = .045). Furthermore, the positive expression rate of costaining was significantly greater than that observed for GPC3 or CD34 single staining (P < .001 and P = .002, respectively). These data demonstrate that GPC3 staining is more accurate for the diagnosis of HCC on thin-core biopsy specimens in nodules 3 cm or smaller compared with its use in all nodules, while GPC3 and CD34 costaining has better diagnostic value than does single staining.

Gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma correlates with prognosis of patients.

Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters.

Extracellular domain of human 4-1BBL enhanced the function of cytotoxic T-lymphocyte induced by dendritic cell.

Interaction of costimulatory molecules and their receptors is crucial for tumor lysate-pulsed dendritic cells (sensitized DC, sDC) to promote T cell activation, clonal expansion and its antitumor immunity. To augment the costimulatory signal may regulate the interaction between DC and cytotoxic T lymphocyte (CTL) and consequently enhance the antitumor response. The costimulatory ligand and receptor pair of 4-1BB/4-1BBL is one of the main factors in the costimulation of CTL. We explored the adjuvant role of a recombinant human 4-1BBL extracellular domain (ex4-1BBL) in modulating CTL activation induced by HepG2 antigen-loaded DC (sDC). The augment effects of sDC in combination with ex4-1BBL on the proliferation, activation, cell survival and cytotoxicity against HepG2 cells of CTL were examined. In the presence of ex4-1BBL, sDC exhibited markedly augmented effects on the above four functions of CTL. These results demonstrate that ex4-1BBL plays an important role in the costimulation pathway for DC-mediated CTLs activation, which might be a useful adjuvant factor for DC-based cancer biotherapy.