Liang Lijian

Fixed-Tumor Vaccine: A Practical Formulation with Cytokine-Microspheres for Protective and Therapeutic Antitumor Immunity

Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragments combined with sustained-releasers of cytokines and a non-toxic adjuvant was developed. C57BL/6J mice were immunized intra-dermally with the vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa 1–6 cells.Results: All of 15 nonimmunized control mice developed the hepatoma. Protection of mice immunized with fixed Hepa 1–6 cells and both of IL-2/GM-CSF microspheres or further mixed with TiterMax Gold reached 80% and 87%, respectively. Mass growth of the established tumors, vaccinated twice at 5 mm in diameter, the tumor of control animals continued to grow. However, 7–10 days after the second injection of the tumor vaccine, the tumor growth was suppressed in 9 of 10 mice and then markedly reduced. Complete tumor regression was observed in 60% (6/10) of mice. Splenocytes from the control mice were not able to lyse target Hepa 1–6 cells and other tumor cells. In contrast splenocytes from the vaccinated mice exhibited a 41% lytic activity against the Hepa 1–6 cells tested at an effector/target (E/T) ratio of 5, whereas they did not exhibited such activity against the melanoma cells (B16-F1), Lewis lung carcinoma cells (LLC), renal carcinoma cells (Renca), and bladder carcinoma cells (MBT-2). The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class I monoclonal antibodies but not with anti-CD4 and anti-MHC-class II antibodies. In the Phase-I clinical trial, vaccination of HCC patients with the autologous vaccine is a well-tolerated treatment and induces fixed tumor fragment-specific immunity.Conclusion: Fixed HCC vaccination elicited protective and therapeutic antitumor immunity against HCC. The tumor vaccine elicited antigen specific CTL response lysis of the target HCC was mediated by the typical MHC-class I restricted CD8+ T cells.

Hepatic Resection Provides Survival Benefit for Selected Intermediate-Stage (BCLC-B) Hepatocellular Carcinoma Patients

Purpose The intermediate stage of hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B) comprises a highly heterogeneous population, and the treatment strategy is still controversial. Because of the heterogeneity, a subclassification of intermediate-stage HCCs was put forward by Bolondi according to the ‘beyond Milan and within up-to-7’ criteria and Child-Pugh score. In this study, we aim to analyze the prognosis of BCLC-B stage HCC patients who received hepatic resection according to the Bolondi’s subclassification. Materials and Methods One thousand and one hundred three patients diagnosedwith HCC and treatedwith hepatic resectionwere enrolled in our hospital between 2006 and 2012. According to Bolondi’s subclassification, the BCLC-B patients were divided into four groups. Recurrence-free survival (RFS) and overall survival (OS) were analyzed. Results According to Bolondi’s subclassification, the BCLC-B patients were divided into four groups: B1 (n=41, 18.7%), B2 (n=160, 73.1%), B3 (n=11, 5.0%), and B4 (n=7, 3.2%). Significant difference was observed between B1 and other groups (B1 vs. B2, p=0.022; B1 vs. B3, p < 0.001; B1 vs. B4, p < 0.001), but no difference for B2 vs. B4 (p=0.542) and B3 vs. B4 (p=0.542). In addition, no significant differences were observed between BCLC-A and BCLC-B1 group for both RFS (p=0.087) and OS (p=0.643). In multivariate analysis, BCLC-B subclassification was not a risk factor for both OS (p=0.263) and RFS (p=0.892). Conclusion In our study, HCC patients at B1 stagewere benefited from hepatic resection and had similar survival to BCLC-A stage patients. Our study provided rationality of hepatic resection for selected BCLC-B stage HCC patients instead of routine transarterial chemoembolization.

Two-stages resection for advanced hepatocellular carcinoma

We performed two-stage resection for sixteen patients with advanced hepatocellular carcinoma from January, 1987 to July, 1991. All patients underwent various surgical therapies prior to resection which included gauze packing hemostasis in 1 case, hyperthermia plus radiotherapy in 1, hepatic arterial ligation in 2, operative hepatic arterial embolization in 3, and transcatheter embolization in 9. The median interval between the first therapy and tumour resection was 59 days with a range of 29--769 days, and the median diameter of tumours decreased from 10.5 cm to 7.5 cm. The majority of precedures on two-stage resection were irregular hepatectomy or Iobectomy under occlusion of porta hepatis. Regular hepatectomies were done in 4 cases. Pathalogical examination showed complete coagulation necrosis in 3 specimens. However, in the others were still found residual viable tumours. Survival periods of the patients who received two-stage resection were from 4 months to 4 years except 2 operative death. The significance, possibility as well as methods of two-stage resection were discussed.We performed two-stage resection for sixteen patients with advanced hepatocellular carcinoma from January, 1987 to July, 1991. All patients underwent various surgical therapies prior to resection which included gauze packing hemostasis in 1 case, hyperthermia plus radiotherapy in 1, hepatic arterial ligation in 2, operative hepatic arterial embolization in 3, and transcatheter embolization in 9. The median interval between the first therapy and tumour resection was 59 days with a range of 29--769 days, and the median diameter of tumours decreased from 10.5 cm to 7.5 cm. The majority of precedures on two-stage resection were irregular hepatectomy or Iobectomy under occlusion of porta hepatis. Regular hepatectomies were done in 4 cases. Pathalogical examination showed complete coagulation necrosis in 3 specimens. However, in the others were still found residual viable tumours. Survival periods of the patients who received two-stage resection were from 4 months to 4 years except 2 operative death. The significance, possibility as well as methods of two-stage resection were discussed.