Exploiting the critical perioperative period to improve long-term cancer outcomes

Horowitz, Maya; Neeman, Elad; Sharon, Eran; Ben-Eliyahu, Shamgar

doi:10.1038/nrclinonc.2014.224

Cited by 487Cancer, Stress, Anesthesia, and Immune ResponseEnhanced Recovery After SurgeryCancer Cells and Metastasis

Exploiting the critical perioperative period to improve long-term cancer outcomes

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Horowitz, Maya, Neeman, Elad, Sharon, Eran, Ben-Eliyahu, Shamgar·2015·Nature Reviews Clinical Oncology

DOI 10.1038/nrclinonc.2014.224PMC PMC5497123

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Abstract

Evidence suggests that the perioperative period and the excision of the primary tumour can promote the development of metastases—the main cause of cancer-related mortality. This Review first presents the assertion that the perioperative timeframe is pivotal in determining long-term cancer outcomes, disproportionally to its short duration (days to weeks). We then analyse the various aspects of surgery, and their consequent paracrine and neuroendocrine responses, which could facilitate the metastatic process by directly affecting malignant tissues, and/or through indirect pathways, such as immunological perturbations. We address the influences of surgery-related anxiety and stress, nutritional status, anaesthetics and analgesics, hypothermia, blood transfusion, tissue damage, and levels of sex hormones, and point at some as probable deleterious factors. Through understanding these processes and reviewing empirical evidence, we provide suggestions for potential new perioperative approaches and interventions aimed at attenuating deleterious processes and ultimately improving treatment outcomes. Specifically, we highlight excess perioperative release of catecholamines and prostaglandins as key deleterious mediators of surgery, and we recommend blockade of these responses during the perioperative period, as well as other low-risk, low-cost interventions. The measures described in this Review could transform the perioperative timeframe from a prominent facilitator of metastatic progression, to a window of opportunity for arresting and/or eliminating residual disease, potentially improving long-term survival rates in patients with cancer.

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The resulting physiological changes can create a protumorigenic or prometastatic environment, potentially facilitating cancer progression or recurrence.
“The resulting physiological changes can create a protumorigenic or prometastatic environment, potentially facilitating cancer progression or recurrence [7].”
From Pancreatic resection with perioperative drug repurposing of propranolol and etodolac – the phase II randomized controlled PROSPER trial (2025) · cites this paper as [7]

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Authors: Horowitz, M., Neeman, E., Sharon, E., & Ben-Eliyahu, S.
Affiliations: Tel Aviv University (IL)
Rabin Medical Center (IL)
ORCID: Neeman, Elad
Sharon, Eran
Venue: Nature Reviews Clinical Oncology
Publisher: Springer Science and Business Media LLC
Published: 2015-01-20
Volume: 12
Issue: 4
Pages: 213-226
ISSN: 1759-4774 (ISSN-L)
1759-4782
DOI: 10.1038/nrclinonc.2014.224
PMC: PMC5497123
OpenAlex: W2078505577
Semantic Scholar: e262754c5c3cffc0898230df898629f73cd9a8d0
Cited by: 487
References: 228
Citations by year: 2026: 36 · 2025: 33 · 2024: 39 · 2023: 48 · 2022: 60 · 2021: 60 · 2020: 55 · 2019: 40 · 2018: 42 · 2017: 38 · 2016: 22 · 2015: 14
FWCI: 5.32
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA172138)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
Health Sciences › Medicine › Surgery › Enhanced Recovery After Surgery
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: perioperative period, metastasis, surgical stress response, catecholamines, prostaglandins, anesthesia, analgesia, hypothermia, blood transfusion, tissue damage, sex hormones, nutritional status, paracrine signaling, neuroendocrine response, residual disease, cancer survival
MeSH terms: Humans, Immune Tolerance, Neoplasm Metastasis, Neoplasms, Nutritional Status, Prognosis, Recurrence, Stress, Physiological, Stress, Psychological, Treatment Outcome, Perioperative Care, Perioperative Period

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