Anesthesia and the Perioperative Care of the Cancer Patient

Myron Yaster MD and Lynne G. Maxwell MD

The April issue of Anesthesia and Analgesia is a themed issue featuring several articles on the “Perioperative Care of the Cancer Patient” and highlights critical topics for anesthesiologists and perioperative medicine specialists: cancer epidemiology; advances in cancer biology; microbiome and its role in health and cancer; perioperative implications of the emerging novel cancer therapeutics; role of prehabilitation in optimizing postoperative outcomes; the influence of anesthetic techniques and strategies, anemia, and blood transfusions on cancer outcomes; and managing acute postoperative pain conditions in patients with cancer.

As you all know, “cancer is a disease of bewildering and presently indecipherable complexity. The long-established treatments of surgery, radiotherapy, and chemotherapy retain their place at the forefront of modern-day cancer care. Despite frequently reducing tumor burden to undetectable levels, each comes with paradoxical risks of disease promotion.”¹ Indeed, have you ever wondered if surgery and anesthesia may actually worsen outcome by affecting cancer progression, tumor growth, and the development of metastases? I know I have and today’s article by Perry et al. shook me to my core. So that’s where we will start. To be honest though, much of the science discussed in this and many of the articles in this issue of A&A is way, way beyond my area of expertise and is discussed at a depth that is beyond the 5-6 minute reads of a PAAD. However, even though pediatric cancers are very different than adult cancers the issues raised in this themed issue are so important and game changing that I decided to pick a couple to review for you and I will do my best to discuss some of the highlights. So, over the next couple of weeks, expect to see reviews of several articles from this issue in the PAAD.

Finally, there weren’t any articles in this issue on how cancer may affect you personally as an anesthesiologist if, or more likely when, you get this diagnosis. We have an upcoming podcast entitled “Doctors as Patients” in which Dr. Allison Fernandez interviews Drs. Karla Castro-Frenzel, Katherine Keech, and Leelach Rothschild, who describe their journeys from cancer diagnosis to treatment. They talk about how they navigated their professional lives and maintained their careers while seeking treatment. As a result of their experience through illness, they have created a community with the Society for Pediatric Anesthesia (SPA) titled H2O- Helpers Healing Each Other. So, keep your eyes and ears open for it. Myron Yaster MD

Editorial

Gottumukkala, V. & Gan, T. (2025). Anesthesiology and Perioperative Care of the Cancer Patient: Enhancing Lives and Improving Outcomes. Anesthesia & Analgesia, 140 (4), 747-751. doi: 10.1213/ANE.0000000000007416.

Original article

Perry NJS, Jhanji S, Poulogiannis G. Cancer Biology and the Perioperative Period: Opportunities for Disease Evolution and Challenges for Perioperative Care. Anesth Analg. 2024 Dec 17. doi: 10.1213/ANE.0000000000007328. Epub ahead of print. PMID: 39689009.

“Cancer is a disease of bewildering and presently indecipherable complexity. Cancers subvert systems physiology and exploit endogenous programs involved in homeostatic control of metabolism, immunity, regeneration, and repair. Many such programs are engaged in the healing response to surgery which, together with other abrupt biochemical changes in the perioperative period, provide an opportunity for the macroevolution of residual disease. Today’s review relates contemporary perspectives of cancer as a systemic disease with the overlapping biology of host responses to surgery and events within the perioperative period. With a particular focus on examples of cancer cell plasticity and changes within the host, Perry et al. explore how perioperative inflammation and acute metabolic, neuroendocrine, and immune dyshomeostasis might contribute to cancer evolution within this contextually short, yet crucially influential time frame, and highlight potential therapeutic opportunities within to further surgical cancer care and its long-term oncological outcomes.”¹

“Perioperative factors contribute to cancer cell plasticity. Preoperative patient and treatment factors combine with surgery and anesthetic factors to disturb the tumor ecosystem and promote macroevolution. Survival, growth, and metastatic dissemination of residual disease is influenced by complex stromal interactions and metabolism within an inflammatory wound, resulting in epigenetic reprograming, altered gene expression, posttranslational modifications, metabolic rewiring, and phenotypic plasticity.”¹ “Surgical trauma elicits local and systemic inflammatory responses designed to reorganize inchoate tissue and restore integrity, architecture, cellularity, and function. However, cancers repeatedly demonstrate their capacity to subvert, exploit, and repurpose these physiological mechanisms of regeneration, leading to inevitable concerns that surgery offers an opportunity for disease to advance. Additionally, there are exposures to a variety of drugs and interventions that have themselves been implicated in disease progression, including anesthetics and blood transfusions. Patients can suffer complications ranging from wound breakdown to septic shock; endure pain, psychological stress, and disrupted sleep; and experience significant physical deconditioning due to changes in physical activity, nutrition, and systemic metabolism. Collectively, these physiological disturbances represent an abrupt change to the ecosystem of a developing cancer to promote the macroevolution of residual disease.”¹

A key feature of cancer survival is the development of metastasis. In the figure below, Perry et al.¹ review the mechanisms of postoperative metastasis. “A: Systemic inflammation and altered metabolism help to prime the premetastatic niche in future organs of metastasis. Endothelial activation increases vascular permeability, whereas recruitment of inflammatory immune cells remodels the stroma and ECM to favor colonization. Circulating tumor cells (CTCs) disseminated during and in the days after surgery form aggregates with activated platelets and NETs. This offers protection from physical and oxidative stress and from circulating effector immune cells, and facilitates margination, adhesion and arrest in distant organ capillaries. B: Subclinical/ dormant metastatic disease from early (preoperative) dissemination may be restricted by competent immunosurveillance. The systemic inflammatory response to surgery and/or postoperative complications disrupts immune equilibrium, resulting in apoptosis, exhaustion, and impaired cytotoxicity of effector immune cells and mobilization and recruitment of bone marrow-derived cells and regulatory T cells to cooperate in immune evasion.”¹

Next, “the autonomic nervous system extensively contributes to tumor progression and metastasis in numerous cancers and by various mechanisms, leading to an emerging appreciation of the intersection of neurobiology with many cancer hallmarks. Moreover, these observations have formed the rationale for recent attempts to block this potential axis of disease progression within the perioperative period, when psychological and physiological stress often reach a peak, through the repurposing of β-blockers and anesthetic adjuncts.”¹

Finally, “evading immune destruction is a hallmark of cancer, with CD8 + cytotoxic T lymphocytes, CD4 + T h 1 helper T cells, and NK cells occupying particularly important roles in immune surveillance and cancer cell eradication. Several factors within the perioperative period are known to compromise these host defenses, potentially leaving patients vulnerable to the opportunistic advance of newly disseminated or quiescent disease. For instance, anesthetics have long been suspected to contribute to postoperative immunosuppression, with numerous laboratory studies demonstrating impairment of cell-mediated immunity after exposure to inhalational agents, as well as certain intravenous agents such as ketamine.^2-4 These effects appear to be spared by propofol, adding further rationale to the debate that total intravenous anesthesia (TIVA) with propofol offers an oncological advantage. Exogenous opioids have also been suspected to promote disease progression, in part by attenuating innate and adaptive immunity.⁵ This has and will remain difficult to definitively assess, since inadequate pain control is itself an influential driver of disease progression through sympathetic signaling, whilst variable tumor expression of opioid receptors and the wide range of opioid drug types in use further confound the picture. Accordingly, clinical data on the role of opioids in oncological outcomes is inconsistent,⁶ with recent examples suggesting that the direction of any oncological response to intraoperative opioids may be determined by expression patterns of pro- or antitumor opioid receptors in specific cancer types and immune cell subset.”¹

There is much more in this article that I can give justice to. Please read and discuss it with your colleagues and students. Send your thoughts to Myron who will post in a Friday reader response.

References

1. Perry NJS, Jhanji S, Poulogiannis G. Cancer Biology and the Perioperative Period: Opportunities for Disease Evolution and Challenges for Perioperative Care. Anesthesia and analgesia 2024 (In eng). DOI: 10.1213/ane.0000000000007328.

2. Stollings LM, Jia LJ, Tang P, Dou H, Lu B, Xu Y. Immune Modulation by Volatile Anesthetics. Anesthesiology 2016;125(2):399-411. (In eng). DOI: 10.1097/aln.0000000000001195.

3. Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. 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 and analgesia 2003;97(5):1331-1339. (In eng). DOI: 10.1213/01.Ane.0000082995.44040.07.

4. Tazawa K, Koutsogiannaki S, Chamberlain M, Yuki K. The effect of different anesthetics on tumor cytotoxicity by natural killer cells. Toxicol Lett 2017;266:23-31. (In eng). DOI: 10.1016/j.toxlet.2016.12.007.

5. Plein LM, Rittner HL. Opioids and the immune system - friend or foe. British journal of pharmacology 2018;175(14):2717-2725. (In eng). DOI: 10.1111/bph.13750.

6. Montagna G, Gupta HV, Hannum M, et al. Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer. British journal of anaesthesia 2021;126(2):367-376. (In eng). DOI: 10.1016/j.bja.2020.10.021.