The Influence of Opioids & Anesthesia on Cancer Survivorship

The Influence of Opioids & Anesthesia on Cancer Survivorship

Overview

How do anesthetics and analgesics interact with the immune system and angiogenesis in ways that influence tumor growth and metastasis?

Cancer pain affects millions of Americans. There are more than 14 million cancer survivors in the United States, and an estimated 40% of cancer survivors continue to experience persistent pain as a result of treatments such as surgery, chemotherapy, and radiation therapy

Dr. Monika Patel presents the latest information on:

• Mechanisms of angiogenesis and immunity
• How key targets involved in cancer development are affected by pharmaceuticals
• Research pearls of cancer progression with commonly used pain relieving pharmaceuticals
• Importance of anesthetic technique on cancer survivorship
• Gaps in research

Learning Objectives

As a result of participating in this activity, learners will be able modify their clinical algorithm for providing good pain control, by considering the type of cancer that a patient has, in order to:

• Mitigate undesired cancer proliferation
• Include NSAIDS concomitantly
• Determine when to utilize local vs. general anesthetics
• Choose between volatile vs. nonvolatile agents as a general anesthetic

Desirable Physician Attributes

• Patient Care [ACGME/ABMS] Provide care that is compassionate, appropriate and effective for the treatment of health problems and the promotion of health
• Medical Knowledge [ACGME/ABMS] about established and evolving biomedical, clinical, and cognate (e.g. epidemiological and social-behavioral) sciences and the application of this knowledge to patient care
• Employ Evidenced-based Practice [IOM] Integrate best research with clinical expertise and patient values for optimum care, and participate in learning and research activities to the extent feasible

Pain management domains and core competencies

2. Pain assessment and measurement: How is pain assessed and measured?

• Describes patient, clinician, and system factors that can facilitate or interfere with effective pain assessment and management
• Demonstrates use of proper patient assessment, including physical exam and history, when treating
  pain

3. Treatment: How is pain safely and effectively treated?

• Demonstrates knowledge of risk stratification, patient selection, and ongoing monitoring for pharmacological pain treatment
• Develops a treatment plan that takes into account the differences among acute pain, acute-on-chronic
  pain, chronic or persistent pain, and pain at the end of life
• Develops a pain treatment plan based on benefits and risks of available treatments

Accreditation & Designation

Release date: This activity was released 8/27/2021.

Termination date: The content of this activity remains eligible for CME Credit until 8/26/2024, unless reviewed or amended prior to this date.

Neurovations Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Neurovations Education designates this other activity (blended learning) for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Disclosure of Financial Relationships

Neither the presenter, reviewers nor any other person with control of, or responsibility for, the planning, delivery, or evaluation of accredited continuing education has, or has had within the past 24 months, any financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

Additional Reading

• Kim, R. (2017). Anesthetic technique and cancer recurrence in oncologic surgery: unraveling the puzzle. Cancer and Metastasis Reviews, 36(1), 159-177.
• Shakhar, G., & Ben-Eliyahu, S. (2003). Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients?. Annals of Surgical Ocology, 10(8), 972-992.
• Ash, S. A., & Buggy, D. J. (2013). Does regional anaesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence. Best Practice & Research Clinical Anaesthesiology, 27(4), 441-456.
• Tedore, T. (2015). Regional anaesthesia and analgesia: relationship to cancer recurrence and survival. BJA: British Journal of Anaesthesia, 115(suppl_2), ii34-ii45.
• Shavit, Y., Lewis, J. W., Terman, G. W., Gale, R. P., & Liebeskind, J. C. (1984). Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science, 223(4632), 188-190.
• Boland, J. W., & Pockley, A. G. (2018). Influence of opioids on immune function in patients with cancer pain: from bench to bedside. British Journal of Pharmacology, 175(14), 2726-2736.
• Doornebal, C. W., Vrijland, K., Hau, C. S., Coffelt, S. B., Ciampricotti, M., Jonkers, J., ... & Hollmann, M. W. (2015). Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2+ breast cancer. Pain, 156(8), 1424-1432.
• Doornebal, C. W., Klarenbeek, S., Braumuller, T. M., Klijn, C. N., Ciampricotti, M., Hau, C. S., ... & de Visser, K. E. (2013). A preclinical mouse model of invasive lobular breast cancer metastasis. Cancer Research, 73(1), 353-363.
• Page, G. G. (2005). Immunologic effects of opioids in the presence or absence of pain. Journal of Pain and Symptom Management, 29(5), 25-31.
• Melamed, R., Bar-Yosef, S., Shakhar, G., Shakhar, K., & Ben-Eliyahu, S. (2003). 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, 97(5), 1331-1339.
• Yuki, K., Astrof, N. S., Bracken, C., Soriano, S. G., & Shimaoka, M. (2010). Sevoflurane binds and allosterically blocks integrin lymphocyte function-associated antigen-1. The Journal of the American Society of Anesthesiologists, 113(3), 600-609.
• Loop, T., Dovi-Akue, D., Frick, M., Roesslein, M., Egger, L., Humar, M., ... & Pannen, B. H. (2005). Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. The Journal of the American Society of Anesthesiologists, 102(6), 1147-1157.
• Wei, H., Liang, G., Yang, H., Wang, Q., Hawkins, B., Madesh, M., ... & Eckenhoff, R. G. (2008). The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1, 4, 5-trisphosphate receptors. The Journal of the American Society of Anesthesiologists, 108(2), 251-260.
• Huitink, J. M., Heimerikxs, M., Nieuwland, M., Loer, S. A., Brugman, W., Velds, A., ... & Kerkhoven, R. M. (2010). Volatile anesthetics modulate gene expression in breast and brain tumor cells. Anesthesia & Analgesia, 111(6), 1411-1415.
• Tavare, A. N., Perry, N. J., Benzonana, L. L., Takata, M., & Ma, D. (2012). Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. International Journal of Cancer, 130(6), 1237-1250.
• Moudgil, G. C., & Singal, D. P. (1997). Halothane and isoflurane enhance melanoma tumour metastasis in mice. Canadian Journal of Anaesthesia, 44(1), 90-94.
• Biki, B., Mascha, E., Moriarty, D. C., Fitzpatrick, J. M., Sessler, D. I., & Buggy, D. J. (2008). Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. The Journal of the American Society of Anesthesiologists, 109(2), 180-187.
• Chen, Z., Zhang, P., Xu, Y., Yan, J., Liu, Z., Lau, W. B., ... & Zhou, S. (2019). Surgical stress and cancer progression: the twisted tango. Molecular cancer, 18(1), 1-11.
• Cummings, K. C., Xu, F., Cummings, L. C., & Cooper, G. S. (2012). A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy: a population-based study. The Journal of the American Society of Anesthesiologists, 116(4), 797-806.
• Deegan, C. A., Murray, D., Doran, P., Moriarty, D. C., Sessler, D. I., Mascha, E., ... & Buggy, D. J. (2010). Anesthetic technique and the cytokine and matrix metalloproteinase response to primary breast cancer surgery. Regional Anesthesia & Pain Medicine, 35(6), 490-495.
• Cassinello, F., Prieto, I., del Olmo, M., Rivas, S., & Strichartz, G. R. (2015). Cancer surgery: how may anesthesia influence outcome?. Journal of Clinical Anesthesia, 27(3), 262-272.
• Müller-Edenborn, B., Roth-Z'graggen, B., Bartnicka, K., Borgeat, A., Hoos, A., Borsig, L., & Beck-Schimmer, B. (2012). Volatile anesthetics reduce invasion of colorectal cancer cells through down-regulation of matrix metalloproteinase-9. The Journal of the American Society of Anesthesiologists, 117(2), 293-301.
• Fleischmann, E., Marschalek, C., Schlemitz, K., Dalton, J. E., Gruenberger, T., Herbst, F., ... & Sessler, D. I. (2009). Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial. BMC Anesthesiology, 9(1), 1-9.
• Ohta, N., Ohashi, Y., & Fujino, Y. (2009). Ketamine inhibits maturation of bone marrow-derived dendritic cells and priming of the Th1-type immune response. Anesthesia & Analgesia, 109(3), 793-800.
• Beilin, B., Rusabrov, Y., Shapira, Y., Roytblat, L., Greemberg, L., Yardeni, I. Z., & Bessler, H. (2007). Low-dose ketamine affects immune responses in humans during the early postoperative period. British Journal of Anaesthesia, 99(4), 522-527.
• Forget, P., Collet, V., Lavand'homme, P., & De Kock, M. (2010). Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages. European Journal of Anaesthesiology| EJA, 27(3), 233-240.
• Inada, T., Kubo, K., & Shingu, K. (2011). Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol. Journal of Anesthesia, 25(4), 569-575.
• Enlund, M., Berglund, A., Andreasson, K., Cicek, C., Enlund, A., & Bergkvist, L. (2014). The choice of anaesthetic—sevoflurane or propofol—and outcome from cancer surgery: a retrospective analysis. Upsala Journal of Medical Sciences, 119(3), 251-261.
• Lee, J. H., Kang, S. H., Kim, Y., Kim, H. A., & Kim, B. S. (2016). Effects of propofol-based total intravenous anesthesia on recurrence and overall survival in patients after modified radical mastectomy: a retrospective study. Korean Journal of Anesthesiology, 69(2), 126.
• Sekandarzad, M. W., van Zundert, A. A., Lirk, P. B., Doornebal, C. W., & Hollmann, M. W. (2017). Perioperative anesthesia care and tumor progression. Anesthesia & Analgesia, 124(5), 1697-1708.
• Mammoto, T., Higashiyama, S., Mukai, M., Mammoto, A., Ayaki, M., Mashimo, T., ... & Akedo, H. (2002). Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF). Journal of Cellular Physiology, 192(3), 351-358.
• Sakaguchi, M., Kuroda, Y., & Hirose, M. (2006). The antiproliferative effect of lidocaine on human tongue cancer cells with inhibition of the activity of epidermal growth factor receptor. Anesthesia & Analgesia, 102(4), 1103-1107.
• Yoon, J. R., Whipple, R. A., Balzer, E. M., Cho, E. H., Matrone, M. A., Peckham, M., & Martin, S. S. (2011). Local anesthetics inhibit kinesin motility and microtentacle protrusions in human epithelial and breast tumor cells. Breast Cancer Research and Treatment, 129(3), 691-701.
• Lirk, P., Berger, R., Hollmann, M. W., & Fiegl, H. (2012). Lidocaine time-and dose-dependently demethylates deoxyribonucleic acid in breast cancer cell lines in vitro. British Journal of Anaesthesia, 109(2), 200-207.
• Ying, B., Huang, H., Li, H., Song, M., Wu, S., & Ying, H. (2017). Procaine inhibits proliferation and migration and promotes cell apoptosis in osteosarcoma cells by upregulation of microRNA-133b. Oncology Research, 25(9), 1463.
• Villar-Garea, A., Fraga, M. F., Espada, J., & Esteller, M. (2003). Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Research, 63(16), 4984-4989.
• Castellano, S., Kuck, D., Sala, M., Novellino, E., Lyko, F., & Sbardella, G. (2008). Constrained analogues of procaine as novel small molecule inhibitors of DNA methyltransferase-1. Journal of Medicinal Chemistry, 51(7), 2321-2325.
• Perez-Castro, R., Patel, S., Garavito-Aguilar, Z. V., Rosenberg, A., Recio-Pinto, E., Zhang, J., ... & Xu, F. (2009). Cytotoxicity of local anesthetics in human neuronal cells. Anesthesia & Analgesia, 108(3), 997-1007.
• Werdehausen, R., Fazeli, S., Braun, S., Hermanns, H., Essmann, F., Hollmann, M. W., ... & Stevens, M. F. (2009). Apoptosis induction by different local anaesthetics in a neuroblastoma cell line. British Journal of Anaesthesia, 103(5), 711-718.
• Chang, Y. C., Liu, C. L., Chen, M. J., Hsu, Y. W., Chen, S. N., Lin, C. H., ... & Hu, M. C. (2014). Local anesthetics induce apoptosis in human breast tumor cells. Anesthesia & Analgesia, 118(1), 116-124.
• Chang, Y. C., Hsu, Y. C., Liu, C. L., Huang, S. Y., Hu, M. C., & Cheng, S. P. (2014). Local anesthetics induce apoptosis in human thyroid cancer cells through the mitogen-activated protein kinase pathway. PloS One, 9(2), e89563.
• Fraser, S. P., Foo, I., & Djamgoz, M. B. A. (2014). Local anaesthetic use in cancer surgery and disease recurrence: role of voltage-gated sodium channels?.
• Piegeler, T., Votta-Velis, E. G., Liu, G., Place, A. T., Schwartz, D. E., Beck-Schimmer, B., ... & Borgeat, A. (2012). Antimetastatic potential of amide-linked local anesthetics: inhibition of lung adenocarcinoma cell migration and inflammatory Src signaling independent of sodium channel blockade. The Journal of the American Society of Anesthesiologists, 117(3), 548-559.
• Melamed, R., Rosenne, E., Shakhar, K., Schwartz, Y., Abudarham, N., & Ben-Eliyahu, S. (2005). Marginating pulmonary-NK activity and resistance to experimental tumor metastasis: suppression by surgery and the prophylactic use of a β-adrenergic antagonist and a prostaglandin synthesis inhibitor. Brain, Behavior, and Immunity, 19(2), 114-126.
• Farooqui, M., Li, Y., Rogers, T., Poonawala, T., Griffin, R. J., Song, C. W., & Gupta, K. (2007). COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia. British Journal of Cancer, 97(11), 1523-1531.
• Exadaktylos, A. K., Buggy, D. J., Moriarty, D. C., Mascha, E., & Sessler, D. I. (2006). Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?. The Journal of the American Society of Anesthesiologists, 105(4), 660-664.
• Koonce, S. L., Mclaughlin, S. A., Eck, D. L., Porter, S., Bagaria, S., Clendenen, S. R., & Robards, C. B. (2014). Breast cancer recurrence in patients receiving epidural and paravertebral anesthesia: a retrospective, case-control study. Middle East Journal of Anaesthesiology, 22(6), 567-571.
• Ramirez, M. F., Gorur, A., & Cata, J. P. (2021). Opioids and cancer prognosis: a summary of the clinical evidence. Neuroscience Letters, 135661.
• Smith, N. K., Demaria Jr, S., Katz, D., Tabrizian, P., Schwartz, M., Miller, J. C., ... & Zerillo, J. (2019, September). Intrathecal morphine administration does not affect survival after liver resection for hepatocellular carcinoma. In Seminars in cardiothoracic and vascular anesthesia (Vol. 23, No. 3, pp. 309-318). Sage CA: Los Angeles, CA: SAGE Publications.