Objective:

To explore the impact of sevoflurane and 5-fluorouracil on ACOD1/itaconate immune regulation in cancer patients undergoing anesthesia, highlighting the significance of these interactions in improving patient outcomes.

Key Findings:

• 5-fluorouracil (5-FU) generates fluoroacetate, which inhibits aconitase and depletes cis-aconitate for ACOD1, impacting immune regulation and potentially leading to adverse clinical outcomes.
• Sevoflurane metabolism may produce aconitase-inhibitory species, further disrupting itaconate synthesis and affecting immune responses.
• The perioperative period is critical for maintaining anti-tumor immune surveillance, which may be compromised by these agents, highlighting the need for careful anesthetic management.

Interpretation:

The concurrent use of sevoflurane and 5-FU may lead to a depletion of itaconate, resulting in both immune evasion at the tumor site and increased systemic inflammation, which could adversely affect patient recovery and outcomes.

Limitations:

• The specific downstream products of sevoflurane metabolism and their aconitase-inhibitory potential require further investigation through targeted metabolomic studies.
• Clinical implications of ACOD1/itaconate depletion in diverse patient populations need more comprehensive studies to understand the full impact on treatment outcomes.

Conclusion:

Pre-operative genotyping for DPYD and ACOD1 variants could guide anesthetic choices to mitigate adverse immunological effects in oncological surgeries, potentially improving patient outcomes.