The Impact of Anaesthesia on Inflammation and NETosis in Hepatocellular Carcinoma Resection

Summary

According to recent literature, liver disease causes approximately 2 million deaths annually; 1 million are attributed to the complications of cirrhosis, while the remaining deaths are caused by hepatocellular carcinoma (HCC). The latter currently ranks 16th among the leading causes of death worldwide. Current research focuses on investigating novel therapeutic modalities, optimizing surgical and anesthetic practices, and identifying biological biomarkers to predict disease progression and severity. In this study, we address radiofrequency ablation (RFA) with the goal of improving periprocedural prognosis, recurrence rates, and overall survival. Specifically, we will quantify the expression of NETosis, a relatively novel biomarker with potential therapeutic and prognostic value in HCC progression. NETosis is a regulated form of cell death through which granulocytes release decondensed chromatin and various proteases into the extracellular space, forming a web-like meshwork known as neutrophil extracellular traps (NETs). These structures are actively involved in hepatic tumorigenesis by promoting tumor growth and metastasis. Recent clinical data reveal that NETs play a key role in: Local tumor progression The incidence of hepatic metastasis Direct modulation of the immune response Hepatic ischemia-reperfusion injury Several recent studies demonstrate that the in vivo blockade of NETosis reduces tumor recurrence, mitigates the pro-inflammatory state, and serves as a valuable prognostic indicator in advanced liver disease \[2,3,4\]. To suppress NETosis expression and ultimately lower recurrence rates, our protocol evaluates the intraprocedural administration of 1% lidocaine followed by a continuous postoperative intravenous lidocaine infusion.

Timeline

Start

2024-11-12

Primary completion

2026-03-31

Completion

2026-11-12

Publications

• Results Foo I, Macfarlane AJR, Srivastava D, Bhaskar A, Barker H, Knaggs R, Eipe N, Smith AF. The use of intravenous lidocaine for postoperative pain and recovery: international consensus statement on efficacy and safety. Anaesthesia. 2021 Feb;76(2):238-250. doi: 10.1111/anae.15270. Epub 2020 Nov 3.
• Results Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer. 2014 Mar;14(3):199-208. doi: 10.1038/nrc3672.
• Results Wee IJY, Moe FNN, Sultana R, Ang RWT, Quek PPS, Goh BKP, Chan CY, Cheow PC, Chung AYF, Jeyaraj PR, Koh YX, Mack POP, Ooi LLPJ, Tan EK, Teo JY, Kam JH, Chua JSS, Ng AWY, Goh JSQ, Chow PKH. Extending Surgical Resection for Hepatocellular Carcinoma Beyond Barcelona Clinic for Liver Cancer (BCLC) Stage A: A Novel Application of the Modified BCLC Staging System. J Hepatocell Carcinoma. 2022 Aug 17;9:839-851. doi: 10.2147/JHC.S370212. eCollection 2022.
• Results Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010 Feb;30(1):61-74. doi: 10.1055/s-0030-1247133. Epub 2010 Feb 19.
• Results McBrien M, Thomas ML. Unilateral renal dysplasia in the adult. Br J Urol. 1971 Aug;43(4):387-90. doi: 10.1111/j.1464-410x.1971.tb12057.x. No abstract available.
• Results Facciorusso A. Drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma: Current state of the art. World J Gastroenterol. 2018 Jan 14;24(2):161-169. doi: 10.3748/wjg.v24.i2.161.
• Results Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
• Results Papayannopoulos V. Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol. 2018 Feb;18(2):134-147. doi: 10.1038/nri.2017.105. Epub 2017 Oct 9.
• Results Itoh Y, Yamada M. Apolipoprotein E and the neuropathology of dementia. N Engl J Med. 1996 Feb 29;334(9):599-600. doi: 10.1056/NEJM199602293340913. No abstract available.

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