Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, the process of formation of new blood vessels, is required for cancer cells to obtain nutrients and oxygen. HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth, progression, invasion, and metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR), and are considered effective strategies for HCC, particularly advanced HCC. However, because the survival benefits conferred by these anti-angiogenic therapies are modest, new anti-angiogenic targets must be identified. Several recent studies have determined the underlying molecular mechanisms, including pro-angiogenic factors secreted by HCC cells, the tumor microenvironment, and cancer stem cells. In this review, we summarize the roles of pro-angiogenic factors; the involvement of endothelial cells, hepatic stellate cells, tumor-associated macrophages, and tumor-associated neutrophils present in the tumor microenvironment; and the regulatory influence of cancer stem cells on angiogenesis in HCC. Furthermore, we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC. A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research.

Hepatocellular carcinoma (HCC) remains an important disease for health care systems in view of its high morbidity, mortality, and increasing incidence worldwide. Radiofrequency ablation (RFA) is preferred to surgery as a local treatment for HCC because it is safer, less traumatic, less painful, better tolerated, causes fewer adverse reactions, and allows more rapid postoperative recovery. The biggest shortcoming of RFA when used to treat HCC is the high incidence of residual tumor, which is often attributed to the vascular thermal deposition effect, the wide infiltration zone of peripheral venules, and the distance between satellite foci and the main focus of the cancer. Recurrence and progression of the residual tumor is the most important determinant of the prognosis. Therefore, it is important to be aware of the risk of recurrence and to improve the efficacy of RFA. This review summarizes the relevant literature and the possible mechanisms involved in progression of HCC after RFA. Current studies have demonstrated that multimodal treatments which RFA combined with other anti-cancer approaches can prevent progression of HCC after RFA.

Complications of Radiofrequency Ablation for Hepatic Hemangioma: A Multicenter Retrospective Analysis on 291 Cases.

PURPOSE: To report the complications of radiofrequency ablation (RFA) for hepatic hemangioma. PATIENTS AND METHODS: Investigators from six centers performed RFA for hepatic hemangioma and used a standardized follow-up protocol. Data were collected from 291 patients, including 253 patients with hepatic hemangioma 5 to 9.9 cm in diameter (group A) and 38 with hepatic hemangioma ≥ 10 cm (group B). Technical success, complete ablation, and complications attributed to the RFA procedure were reported. Analysis of variance was used to determine whether the major complication rate was related to tumor size or clinical experience. RESULTS: A total of 304 lesions were treated in 291 patients. Technical success was achieved without adverse events in all cases. A total of 301 lesions were completely ablated, including 265 of 265 (100%) lesions in group A, and 36 of 39 (92.31%) in group B. The rate of technology-related complications was similar in groups A and B (5.14% (13/253) and 13.16% (5/38), respectively; P = 0.121). Moreover, all technology-related complications occurred during the early learning curve period. The rate of hemolysis-related complications in two groups were 83.40% (211/253) and 100% (38/38) (P =0.007) and the systemic inflammatory response syndrome-related complications in two groups were 33.99% (86/253) and 86.84% (33/38) (P<0.001). There were no delayed complications in either group. CONCLUSION: RFA is minimally invasive, safe, and effective for hepatic hemangiomas 5 to 9.9 cm in diameter. More clinical data are needed to confirm the safety of RFA for hepatic hemangiomas ≥ 10 cm.