Ablative and locoregional treatment options, such as radiofrequency, ethanol injection, microwave, and cryoablation, as well as irreversible electroporation, are effective therapies for early-stage hepatocellular carcinoma (HCC). Hepatocyte death caused by ablative procedures is known to increase the release of tumor-associated antigen, thus enhancing tumor immunogenicity. In addition, the heat ablative resection induces pyroptotic cell death accompanied by the release of several inflammatory factors and immune-related proteins, including damage-associated molecular patterns (DAMPs), heat shock proteins (HSPs), ficolin 3, ATP, and DNA/RNA, which potentiate the antitumoral immune response. Surgical approaches that enhance tumor necrosis and reduce hypoxia in the residual liver parenchyma have been shown to increase the disease-free survival rate by reducing the host’s immunosuppressive response. Scalpel devices and targeted surgical approach combined with immune-modulating drugs are an interesting and promising area to maximize therapeutic outcomes after HCC ablation.
Hepatocellular carcinoma constitutes an ongoing challenge due to its incidence and the high mortality related to it. Metastases and relapses even after treatment with curative intent are frequent. The liver is a common site for metastasis because of anatomical and physiological reasons; its position, the particular cytoarchitecture and cell populations, and its peculiar immunologic properties make it a favorable and tolerogenic environment; the inflammatory state with the alteration of the cytoarchitecture and of the microcirculation associated, and gut permeability and metabolic diseases cause the development of a liable site to progression of hepatocellular carcinoma. The difficulty of always having an early diagnosis and the lack of therapeutic flow charts including the biological behavior of the disease have always posed great difficulties in dealing with it. In the last few years, mechanisms involved in the onset and in the progression of hepatocellular carcinoma are a source of great interest; the discovery of pro-neoplastic and pro-metastatic conditions, of the cross talk between organs and cells, of progression pathways, of mediators contributing to proliferation and metastasis and of modular check points, of miRNAs, all potential therapeutic targets, appear promising for transforming the approach to hepatocarcinoma, offering the possibility of earlier diagnosis, customizable treatments, and better outcome.
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