A study led by researchers at Stony Brook University Cancer Center in New York has added to the growing body of evidence that the type of general anesthetic administered to cancer patients during tumor surgical resection may significantly affect cancer outcomes.
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In a mouse model, the team found differences in how two anesthetics affected cancer metastasis in the lung following surgical resection of breast tumors.
Stress and inflammation responses during the perioperative period
Surgery and pain are known to trigger stress responses and inflammation during the perioperative period that may significantly influence the risk of metastatic recurrence.
A growing body of evidence suggests that the stress and inflammatory responses induced by surgery, pain, and anesthesia may disrupt cellular and physiological systems in ways that could determine the fate of any cancer remaining after tumor resection
Any residual cancer that persists following surgery may be the result of incomplete surgical removal, the introduction of cancerous cells to blood or lymph fluid or micrometastasis that was already present before surgery.
Surgical resection is the main and most effective approach to removing primary tumors and any lymph nodes cancer may have spread to.
However, cancerous cells that either go undetected or get dislodged during surgery can persist postoperatively. Whether these cells die, lie dormant, or multiply and spread depends on the involvement of various immunologic and microenvironmental factors.
Researchers in the field of onco-anesthesia have long speculated that the choice of perioperative anesthetic could influence immune and stress responses in ways that influence tumor growth, metastasis risk and patient survival following surgery.
Differences between inhaled and IV anesthetics
Importantly, differences have been observed between two different groups of general anesthetics administered in the clinic today. These are the fluorinated hydrocarbons administered through inhalation such as or sevoflurane, and the intravenously-administered anesthetics such as propofol.
Inhaled anesthetics account for almost all anesthetics currently used, but studies have demonstrated that they promote angiogenesis and the proliferation and spread of various types of cancer cells.
They are also thought to impede the immune cell function required for tumor cell monitoring and clearance, thereby decreasing cancer cell destruction and promoting metastasis. Clinical studies have also demonstrated a link between the use of inhalational anesthetics and decreased long-term or recurrence-free survival among cancer patients.
The intravenously infused propofol, on the other hand, has been demonstrated to disrupt cancer cell signaling pathways, tumor cell migration, and metastasis through its effects on metalloproteinases and cell motility.
However, whether the choice of anesthetic intervention affects the risk of cancer recurrence or cancer-related mortality remains undecided.
What did the current study find?
As reported in the journal Nature Communications, the Stony Brook researchers found that breast cancer metastasis is influenced by the effects that a chosen anesthetic has on cytokines and the tumor microenvironment.
Jun Lin from the university’s Department of Anesthesiology and team found that mice anesthetized with sevoflurane during surgery for primary breast tumors developed significantly more metastatic disease than mice that were anesthetized with propofol.
The researchers say their study provides the preclinical evidence informing the distinct effects of anesthetics on metastasis of breast cancers through a change of cytokines and the tumor microenvironment.
Our study not only unravels the mechanism underlying sevoflurane-promoted cancer metastasis but also offers a promising intervention to overcome the risk of general anesthesia,”
Choice of anesthesia may affect breast cancer metastases. EurekAlert! 2020. Available at: https://www.eurekalert.org/pub_releases/2020-01/sbu-coa012920.php
Lin J et al. Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models. Nature Communications 2020;11, 642 https://doi.org/10.1038/s41467-019-14065-6
Daqing M et al. Can Anesthesia Influence Cancer Outcomes After Surgery? JAMA Surgery 2019;154(4):279-280. doi:10.1001/jamasurg.2018.4619
Kim R. Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence. J Transl Med 2018;16:8 https://doi.org/10.1186/s12967-018-1389-7