Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis i...Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Mthough being used for decades, Lipiodol~ (Lipiodol~ Ultra Fluid~, Guerbet, France) remains important as a tumor-seeking and radio-opaque clrug delivery vector in intervendonal oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem~ (CeloNova Biosciences Inc., USA), DC-Beads~ (BTG, UK) and HepaSphere~ (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres~ (Sirtex Medical Limited, Australia) and TheraSphere~ (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical tria展开更多
Objective:To compare radiofrequency ablation (RFA) or microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) with RFA or MWA monotherapy in hepatocellular carcinoma (HCC).Methods:A pros...Objective:To compare radiofrequency ablation (RFA) or microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) with RFA or MWA monotherapy in hepatocellular carcinoma (HCC).Methods:A prospective,randomized,controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery,the Second Affiliated Hospital of Southeast University.The patients were randomly assigned into the TACERFA or TACE-MWA (combined treatment group) and the RFA-alone or MWA-alone groups (control group).The primary end point was overall survival.The secondary end point was recurrence-free survival,and the tertiary end point was adverse effects.Results:Until the time of censor,17 patients in the TACE-RFA or TACE-MWA group had died.The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months (range,29 to 62 months).The 1-,3-and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6%,68.1% and 61.7%,respectively.Twenty-five patients in the RFA or MWA group had died.The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months (range,28 to 62 months).The 1-,3-and 5-year overall survival for the RFA or MWA group was 85.1%,59.6% and 44.7%,respectively.The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio (HR),0.526; 95% confidence interval (95% CO,0.334-0.823; P=0.002],and showed better recurrence-free survival than the RFA or MWA group (HR,0.582; 95% CI,0.368-0.895; P=0.008).Conclusions:RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.展开更多
Objective: IL-22-producing CD4+ T helper cells (Th22 cells) have been identified as major inducers of tissue inflammation and immune responses. Currently, no previous study explored the role of Th22 cells in the p...Objective: IL-22-producing CD4+ T helper cells (Th22 cells) have been identified as major inducers of tissue inflammation and immune responses. Currently, no previous study explored the role of Th22 cells in the pathogenesis of hepatocellular carcinoma (HCC). The study aimed to determine the biological function of Th22 cells and its effector IL-22 in HCC patients. Methods: Forty-five HCC patients and 19 healthy controls were recruited and their peripheral blood was collected. The flesh HCC tissues, adjacent HCC tissues and ten normal liver tissues were also collected. Flow cytometry analysis was used to determine the frequencies of circulating Th22 cells and Thl7 cells. Serum IL-22 levels were tested by enzyme-linked immtmosorbent assay (ELISA). Immunohistochemical staining and real-time polymerase chain reaction (PCR) were used to detect IL-22 protein and mRNA in tissues specimens, respectively. Results: Circulating Th22 cells, Thl7 cells and serum IL-22 levels were significantly elevated in HCC patients compared with those of healthy controls (P〈0.001). Th22 cells were showed to be positively correlated with IL-22 in HCC patients (P〈0.05), but not in healthy controls. No significant differences were found in HCC patients with HBeAg positivity or negativity in term of Th22 cells and serum IL-22 levels. The expression of IL-22 protein and mRNA was highest in HCC tissues, followed by adjacent HCC tissues and normal liver tissues. Furthermore, Th22 cells, serum IL-22 levels and IL-22 mRNA were elevated at stage III-IV compared with stage I-II of HCC (P〈0.05). Conclusions: Elevation of circulating Th22 cells and IL-22 may be implicated in the pathogenesis of HCC, and potentially be cellular targets for therapeutic intervention.展开更多
Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of mult...Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or inactivation of tumor suppressor genes. HCC is characterized with multiple cancer hallmarks including their ability to proliferate, anti-poptosis, invade, metastasis, as well as the emerging features such as stem cell properties and energy metabolic switch. The irreversible alterations at genetic level could be detected as early as in the pre-neoplastic stages and accumulate during cancer progression. Thus, they might account for the cancer initiating steps and further malignant transformation. In addition to genetic alterations, epigenetic alterations can affect the cancer transcriptome more extensively. Alterations in DNA methylation, histone modification, miRNAs, RNA editing, and IncRNAs might result in disrupted gene regulation networks and substantially contribute to HCC progression. In this review, the genetic and epigenetic alterations which significantly contribute to the malignant capabilities of HCC will be updated and summarized in detail. Further characterization of those critical molecular events might better elucidate the pathogenesis of HCC and provide novel therapeutic targets for treatment of this deadly disease.展开更多
文摘Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Mthough being used for decades, Lipiodol~ (Lipiodol~ Ultra Fluid~, Guerbet, France) remains important as a tumor-seeking and radio-opaque clrug delivery vector in intervendonal oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem~ (CeloNova Biosciences Inc., USA), DC-Beads~ (BTG, UK) and HepaSphere~ (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres~ (Sirtex Medical Limited, Australia) and TheraSphere~ (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical tria
文摘Objective:To compare radiofrequency ablation (RFA) or microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) with RFA or MWA monotherapy in hepatocellular carcinoma (HCC).Methods:A prospective,randomized,controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery,the Second Affiliated Hospital of Southeast University.The patients were randomly assigned into the TACERFA or TACE-MWA (combined treatment group) and the RFA-alone or MWA-alone groups (control group).The primary end point was overall survival.The secondary end point was recurrence-free survival,and the tertiary end point was adverse effects.Results:Until the time of censor,17 patients in the TACE-RFA or TACE-MWA group had died.The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months (range,29 to 62 months).The 1-,3-and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6%,68.1% and 61.7%,respectively.Twenty-five patients in the RFA or MWA group had died.The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months (range,28 to 62 months).The 1-,3-and 5-year overall survival for the RFA or MWA group was 85.1%,59.6% and 44.7%,respectively.The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio (HR),0.526; 95% confidence interval (95% CO,0.334-0.823; P=0.002],and showed better recurrence-free survival than the RFA or MWA group (HR,0.582; 95% CI,0.368-0.895; P=0.008).Conclusions:RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.
基金supported by research funding from the National Natural Science Foundation (No. 81260083) and National Natural Science Foundation (No. 31360221)
文摘Objective: IL-22-producing CD4+ T helper cells (Th22 cells) have been identified as major inducers of tissue inflammation and immune responses. Currently, no previous study explored the role of Th22 cells in the pathogenesis of hepatocellular carcinoma (HCC). The study aimed to determine the biological function of Th22 cells and its effector IL-22 in HCC patients. Methods: Forty-five HCC patients and 19 healthy controls were recruited and their peripheral blood was collected. The flesh HCC tissues, adjacent HCC tissues and ten normal liver tissues were also collected. Flow cytometry analysis was used to determine the frequencies of circulating Th22 cells and Thl7 cells. Serum IL-22 levels were tested by enzyme-linked immtmosorbent assay (ELISA). Immunohistochemical staining and real-time polymerase chain reaction (PCR) were used to detect IL-22 protein and mRNA in tissues specimens, respectively. Results: Circulating Th22 cells, Thl7 cells and serum IL-22 levels were significantly elevated in HCC patients compared with those of healthy controls (P〈0.001). Th22 cells were showed to be positively correlated with IL-22 in HCC patients (P〈0.05), but not in healthy controls. No significant differences were found in HCC patients with HBeAg positivity or negativity in term of Th22 cells and serum IL-22 levels. The expression of IL-22 protein and mRNA was highest in HCC tissues, followed by adjacent HCC tissues and normal liver tissues. Furthermore, Th22 cells, serum IL-22 levels and IL-22 mRNA were elevated at stage III-IV compared with stage I-II of HCC (P〈0.05). Conclusions: Elevation of circulating Th22 cells and IL-22 may be implicated in the pathogenesis of HCC, and potentially be cellular targets for therapeutic intervention.
基金ACKNOWLEDGEMENTS This work was supported by Hong Kong Research Grant Council (RGC) General Research Fund (HKU/7668/11M), RGC Collaborative Research Funds (HKU7/CRG/09, HKBU5/CRG/10 and HKU3/ CRF/11R), Hong Kong Theme-based Research Scheme fund (T12- 403/11), and grants from National Basic Research Program (973 Program) (No. 2012CB967001) and the National Natural Science Foundation of China (Grant Nos. 81272416 and 81172338).
文摘Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or inactivation of tumor suppressor genes. HCC is characterized with multiple cancer hallmarks including their ability to proliferate, anti-poptosis, invade, metastasis, as well as the emerging features such as stem cell properties and energy metabolic switch. The irreversible alterations at genetic level could be detected as early as in the pre-neoplastic stages and accumulate during cancer progression. Thus, they might account for the cancer initiating steps and further malignant transformation. In addition to genetic alterations, epigenetic alterations can affect the cancer transcriptome more extensively. Alterations in DNA methylation, histone modification, miRNAs, RNA editing, and IncRNAs might result in disrupted gene regulation networks and substantially contribute to HCC progression. In this review, the genetic and epigenetic alterations which significantly contribute to the malignant capabilities of HCC will be updated and summarized in detail. Further characterization of those critical molecular events might better elucidate the pathogenesis of HCC and provide novel therapeutic targets for treatment of this deadly disease.