Colorectal cancer is the third leading cause of cancer-related mortality among both men and women [1]. Gastrointestinal tumor excision is the most common form of treatment among patients with this condition [1]. However, several studies indicate that the stress of surgery, as well as immunosuppressant and other metastasis-inducing effects of certain anesthetics, can promote cancer resurgence [1, 2]. It follows that a physician’s choice of anesthesia is a crucial factor in ensuring the long-term success of surgery for colorectal cancer patients [1].
Intravenous anesthetics have an uncertain association with colorectal cancer surgery resurgence [1]. Ketamine and thiopental can promote lung retention of circulating cancer cells (CTCs), which travel from the primary tumor and can reach the lymphatic or circulatory systems [1]. By doing so, they can promote cancer in other regions of the body [1]. Furthermore, ketamine and thiopental can also suppress the activity of natural killer (NK) cells, which are important in catching and destroying CTCs [1, 2]. However, not all intravenous anesthetics have potential cancer-promoting effects. Propofol has been associated with neither CTC promotion nor NK cell suppression [1]. Conversely, it may promote anti-inflammatory and anti-tumor activity [1].
Volatile anesthetics have similarly uncertain effects on metastatic behaviors. Halothane can operate similarly to ketamine and thiopental in suppressing natural killer cell circulation [3]. Isoflurane may also induce physiological changes that promote cancer in the long term, but it is not without its purported benefits as well [1]. Researchers have observed how exposure to the anesthetic can both promote the malignancy and growth of a carcinoma cell line in the kidneys, while also preventing colon cancer cells from engaging in metastasis [1]. On the other hand, desflurane and sevoflurane are more definitively helpful [1]. They can regulate signals which prevent ischemia-reperfusion (I/R) injury and diminish the invasive potential of colon cancer cells, impeding cancer recurrence [1].
While opioids are a central component of modern anesthesia techniques, they appear to have a detrimental impact on cancerous activity [1, 4]. Opioids may contribute to multiple cancer-promoting events, such as the recurrence, progression, and metastasis of malignant tumors [4]. One study found that morphine, when administered in clinically relevant doses, could initiate signaling events [4]. These events contributed to angiogenesis, tumor neovascularization, and, consequently, tumor growth [4]. As a result, anesthesia providers should aim to limit opioid use as much as possible [4].
Lastly, local and regional anesthesia can have uncertain effects on metastatic activity when administered to colorectal cancer patients. While epidural anesthesia has contributed to lower rates of cancer resurgence in the context of other operations, some research suggests that it does not appear to have an overall beneficial effect for colorectal cancer patients [5]. However, one study found that resurgence rates in patients aged 65 and older might benefit from epidural anesthesia in the place of opioids and inhaled anesthetics [2]. Meanwhile, lidocaine and ropivacaine were associated with inflammatory inhibition and blocked cancer cell activation, indicating that they may also serve as an alternative to agents associated with greater risk [1].
Ultimately, inhalation agents, epidural or regional blocks with general anesthesia, and local anesthesia paired with those blocks may contribute to lower rates of resurgence [6]. Meanwhile, opioids, ketamine, and thiopental may have the opposite effect [1, 6]. While the full extent of benefits and detriments conferred by anesthetic agents in this context is unknown, following these guidelines may contribute to lower rates of cancer resurgence in colorectal cancer patients.
References
[1] T. Piegeler et al., “Anesthesia and colorectal cancer – The perioperative period as a window of opportunity?,” European Journal of Surgical Oncology (EJSO), vol. 42, no. 9, p. 1286-1295, September 2016. [Online]. Available: https://doi.org/10.1016/j.ejso.2016.05.004.
[2] A. Gottschalk et al., “Association between Epidural Analgesia and Cancer Recurrence after Colorectal Cancer Surgery,” Anesthesiology, vol. 113, p. 27-34, July 2010. [Online]. Available: https://doi.org/10.1097/ALN.0b013e3181de6d0d.
[3] R. Melamed et al., “Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures,” Anesthesia & Analgesia, vol. 97, no. 5, p. 1331-1339, November 2003. [Online]. Available: https://doi.org/10.1213/01.ANE.0000082995.44040.07.
[4] K. Gupta et al., “Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth,” Cancer Research, vol. 62, no. 15, p. 4491-4498, August 2002. [Online]. Available: https://pubmed.ncbi.nlm.nih.gov/12154060/.
[5] A. Gupta et al., “Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: a retrospective analysis of data from 655 patients in Central Sweden,” British Journal of Anaesthesia, vol. 107, no. 2, p. 164-170, August 2011. [Online]. Available: https://doi.org/10.1093/bja/aer100
[6] Y. Karaman, “Anesthesia Practices in Colorectal Cancer Surgery,” in Colon Polyps and Colorectal Cancer, 2nd ed., Omer Engi, Ed. Switzerland: Springer, 2020, pp. 235-250.
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