The recurrence of hepatocellular carcinoma (HCC) after minimally invasive therapy is frequent. Adoptive immunotherapy is thought to be an effective method to lower recurrence and metastasis rates of malignant tumors. Therefore, 85 HCC patients after transcatheter arterial chemoembolization and radiofrequency ablation therapy were randomized to immunotherapy group and no adjuvant therapy group. Autologous cytokine-induced killer (CIK) cells were transfused via hepatic artery to the patients. The alteration of levels of lymphocyte subsets in peripheral blood of patients was examined by flow cytometry. All patients were screened by computed tomography every 2 months to observe the tumor recurrent conditions. After CIK cell infusions, the percentages of CD3+, CD4+, CD56+, CD3+CD56+ cells, and CD4+/CD8+ ratio increased from 68.6+/-11.0%, 31.1+/-9.0%, 15.6+/-7.9%, 5.2+/-3.1%, and 1.1+/-0.5 to 70.7+/-10.1%, 33.5+/-8.0%, 18.4+/-9.4%, 5.9+/-2.8%, and 1.3+/-0.7, respectively (P<0.05); whereas the percentage of CD8 cells decreased from 31.1+/-7.8% to 28.6+/-8.3% (P<0.05). The 1-year and 18-month recurrence rates of the study group were 8.9% and 15.6%, compared with 30.0% and 40.0% of the control group (both P value<0.05). The data suggest that CIK cell transfusion is an effective treatment. It can boost the immunologic function in HCC patients and plays an important role in reducing the recurrence rate of HCC.

Targeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC) remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05). In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets.

Postoperative immunotherapy with CIK cell transfusion may be an effective adjuvant treatment for improving the outcomes of HCC patients; >8 cycles of CIK cell transfusion may ensure that patients derive maximal benefits. Moreover, patients with large tumors might benefit more from CIK cell adjuvant treatment than patients with small tumors.

This study evaluated the clinical efficacy of autologous cytokine-induced killer (CIK) cell transfusion in combination with transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA), compared to sequential therapy with TACE and RFA, for the treatment of hepatocellular carcinoma (HCC). We retrospectively studied 2 groups of HCC patients: 85 patients in the TACE+RFA+CIK group were treated with adoptive autologous CIK cell transfusion in combination with minimally invasive therapy, 89 patients in the TACE+RFA group were treated with minimally invasive therapy alone. The overall response rate was 76.5% in the TACE+RFA+CIK group and 79.8% in the TACE+RFA group. The disease control rate was higher in the TACE+RFA+CIK group than that in the TACE+RFA group (95.3% vs. 88.8%), but the difference was not significant (P=0.113). Kaplan-Meier analysis showed that the patients in the TACE+RFA+CIK group had significantly longer overall survival (56 vs. 31 mo, P=0.001) and progression-free survival (17 vs. 10 mo, P=0.001) than those in the TACE+RFA group. No severe side effects occurred in the CIK cell transfusion patients. In conclusion, CIK cell immunotherapy may be a valuable therapeutic strategy to prevent recurrence and metastasis in HCC patients after TACE and RFA, and to improve patient prognosis and quality of life. Combined CIK immunotherapy and minimally invasive therapies represent a safe, potential treatment modality for HCC. However, because patient assignment to the 2 treatments was not randomized, any conclusions concerning improvements in survival must be interpreted with great caution.

AIM:To analyze the local and systemic complications of high intensity focused ultrasound (HIFU) for patients with recurrent and metastatic abdominal tumors. METHODS:From Aug 2001 to Aug 2004, 17 patients with recurrent and metastatic abdominal tumors were enrolled in this study. Real-time sonography was taken, and vital signs, liver and kidney function, skin burns, local reactions, and systemic effects were observed and recored before, during, and after HIFU. CT and MRI were also taken before and after HIFU. RESULTS:All 17 patients had skin burns and pain in the treatment region; the next common complication was neurapraxia of the stomach and intestines to variable degrees. The other local and systemic complications were relatively rare. Severe complications were present in two patients; one developed a superior mesenteric artery infarction resulting in necrosis of the entire small intestines, and the other one suffered from a perforation in terminal ileum due to HIFU treatment. CONCLUSION:Although HIFU is a one of noninvasive treatments for the recurrent and metastatic abdominal tumors, there are still some common and severe complications which need serious consideration.