Cancer surgery: how may anesthesia influence outcome?

doi:10.1016/j.jclinane.2015.02.007

Journal of Clinical Anesthesia

Volume 27, Issue 3, May 2015, Pages 262-272

https://doi.org/10.1016/j.jclinane.2015.02.007 Get rights and content

Highlights

•
Surgery can promote local recurrence and distance spread of cancer.
•
Anesthetic agents might influence cancer cell proliferation.
•
Opioids promote angiogenesis and tumor progression.
•
Local anesthetics inhibit proliferation and stimulate apoptosis.
•
Perioperative pain management may influence long-time survival.

Abstract

Objective

To review the published literature regarding the effects of anesthesia on cancer surgery to prevent tumor cell proliferation/migration or induce apoptosis.

Background

Surgery is the main treatment for potentially curable solid tumors, but most cancer-related deaths in patients who have received previous surgical treatment are caused by metastatic disease. There is increasing evidence that anesthetic technique has the potential to affect long-term outcome after cancer surgery.

Methods

This work reviews the English published literature that was obtained by performing a search of the PubMed database up to January 2014. We selected articles that provided evidence or reviewed the possible actions of anesthetics on cancer cells or the influence of anesthesia in recurrence/outcome.

Results

Inhaled anesthetics induce immunosuppression and activate inflammatory cascade activation, whereas propofol has a protective action. Opioids might promote cancer recurrence and metastasis. In vitro and in vivo studies have demonstrated that local anesthetics inhibit proliferation and migration of cancer cells and induce apoptosis.

Conclusions

Anesthesiologists should follow current best clinical practice and include all strategies that effectively decrease pain and attenuate stress. Regional anesthesia and multimodal analgesia, adding anti-inflammatory drugs, play an unquestionable role in the control of perioperative pain and may improve recurrence-free survival.

Section snippets

Background

Cancer treatment is evolving as we learn more about the molecular basis of cancer and new therapeutic targets are discovered. However, despite the use of radical surgery, chemotherapy and radiotherapy, and new hormonal and immunological treatments, recurrences and metastases continue to appear.

Surgery, surgical stress, and cancer progression

Some authors, such as Demicheli et al [1], demonstrated that surgery itself plays a fundamental role in cancer progression and metastatic recurrence. Nearly a century ago, Tizzer [2] reported that surgery induced tumor growth in animals inoculated with cancer cells. Van der Bij et al [3] following their survey postulated that blood vessel integrity in the liver is compromised after abdominal trauma, resulting in enhanced extracellular matrix exposure, which enables tumor cell adhesion and

General anesthetics and cancer progression

Anesthetic and analgesic agents administered during surgery might influence cancer cell activity. Some specific techniques have been linked with tumor recurrence and long-term outcome [8]. Melamed et al [15] demonstrated in rat models that some anesthetics (eg, ketamine, thiopental, halothane, but not propofol) increase the probability of tumor metastasis, apparently by suppressing NK cell activity. Ketamine was the most deleterious, and its effects were prevented by peripheral blockade of

Perioperative opioids and cancer progression

Opioids are the primary drugs used in perioperative pain management, and their analgesic effect is beneficial in reducing pain and its consequent surgical stress. There is a growing interest in investigating the relationship between opioids and tumor progression, although the results obtained thus far are controversial.

Perioperative opioids may produce cellular and humoral immunosuppression. Research data have demonstrated that opioids have a suppressive effect on phagocytic, NK, B, and T cells

Local-regional anesthesia and cancer surgery

Combining regional and general anesthesia in major surgery has become common practice in many institutions and is expected to reduce the requirement for inhaled general anesthetics and opioids. Combined or given separately, regional anesthesia attenuates the neuroendocrine stress response to surgery and avoids perioperative immunosuppression.

An animal study demonstrated that regional anesthesia and analgesia reduced the metastatic burden in animals inoculated with adenocarcinoma cells after

Cellular effects of LAs: apoptosis activation, migration inhibition, and cancer cell proliferation

LAs have been shown to affect certain tumor cells' vital cycle and processes critical for metastasis, such as apoptosis, migration, and proliferation (Table 2).

Hollman and Durieux [81] have suggested that the antimetastatic effects of LAs are due to their systemic actions. LAs show pleiotropic effects that are unrelated to sodium channel blockade but include neuroprotective, anti-inflammatory, bronchodilator, antithrombotic, and anti-infectious activity. Yardeni et al [58], in a survey

Substance P and cancer

Substance P (SP) is a neuropeptide that belongs to the tachykinin family, facilitating pain through activation of the neurokinin 1 (NK-1) receptor. The NK-1 G protein-coupled receptor has widespread distribution in the central nervous system and in peripheral tissues. There are numerous studies suggesting that this receptor system could play an important role in the development of cancer. It is known that SP has a mitogenic action on several human cancer cell lines (eg, neuroblastoma, glioma,

Conclusion

We have reviewed how anesthesia may influence the outcome of cancer surgery. Inhaled anesthetics induce immunosuppression and activate the inflammatory cascade, whereas propofol has a protective action. Opioids might promote cancer recurrence and metastasis, as demonstrated in vitro and in animal studies. Some clinical retrospective publications also suggest an improvement in survival by procedures that reduce perioperative morphine dosing.

Although beyond the scope of this review, it is

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The perioperative period theoretically is a critical time of opportunity for the progression of pre-existing tumour micrometastasis. Therefore,the timing of introducing cancer therapies including chemotherapy, radiation therapy and immunotherapies in the postoperative period is important. A thorough exploration of the perioperative immune events at a cellular level in combination with an intricate review of available clinical rials was conducted to extrapolate the effects of oncological surgery on the perioperative immune milieu.This is timely in view of the recently published Checkmate-577 trial which demonstrated significant disease-free survival in carcinoma of the gastroesophageal junction with the use of adjuvant anti-programmed cell deathprotein 1(PD-1) immunotherapy.This review focusing in particular on perioperative immunosuppression, identifies potential modifiable factors, the effects of perioperative conditioning and optimisation, the most recent trials in the curative setting for Gastrointestinal malignancies and the new treatment avenues possible in the context of the combination of immunotherapy and major oncological gastrointestinal surgery.
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Citation Excerpt :
In addition to its inhibitory effects on immune system, surgery was experimentally and clinically found to be associated with increased angiogenesis and promoted metastasis.3 Anesthetics such as opioids were also found to suppress cell-mediated immunity21 and promote tumor development and metastasis.22 In a rat model, remifentanil was found to repress NK cell activity and proliferation of lymphocyte.23
To investigate whether the use of Pecs II block benefit patients with the respect to the immune functions.
Totally 196 patients were included in this study. These patients were randomized to two groups, general anesthesia alone group (G group) and Pectoral nerve (Pecs) II block under general anesthesia group (PG group).
It was found that remifentanil consumption was less in PG group than it in G group. PG group showed a higher proportion of NK cells in peripheral blood mononuclear cell (PBMC) and an improved killing activity than G groups after surgery. We also found that postoperative interleukin (IL)-2 concentration in the plasma of PG group was dramatically higher than it of G group. Interestingly, there was even no significant change between preoperative and postoperative IL-2 levels in PG group, suggesting the less inhibitory effect of Pecs II block on immune system of those patients.
In conclusion, these results indicate that Pecs II block use in patients may have an enhanced immunity compared with general anesthesia method.
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ReviewCancer surgery: how may anesthesia influence outcome?

Highlights

Abstract

Objective

Background

Methods

Results

Conclusions

Section snippets

Background

Surgery, surgical stress, and cancer progression

General anesthetics and cancer progression

Perioperative opioids and cancer progression

Local-regional anesthesia and cancer surgery

Cellular effects of LAs: apoptosis activation, migration inhibition, and cancer cell proliferation

Substance P and cancer

Conclusion

Ann Oncol

Br J Anaesth

J Clin Anesth

Br J Anaesth

Biochem Pharmacol

J Neuroimmunol

Eur J Pharmacol

Br J Anaesth

Br J Anaesth

Exp Cell Res

Biochem Pharmacol

Neurotoxicology

Br J Anaesth

Int J Biochem Cell Biol

J Biol Chem

Int J Biochem Cell Biol

J Biol Chem

J Biol Chem

Br J Anaesth

Peptides

J Endod

Factors in the production and growth of tumor metastases

J Med Res

Blocking alpha-2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth

Hepatology

Role of circulating tumour cells in predicting recurrence after excision of primary colorectal carcinoma

Br J Surg

Surgery-induced immunosuppresion and postoperative pain management

AACN Clin Issues

Clinical review: immunodepression in the surgical patient and increased susceptibility to infection

Crit Care

Combined spinal and general anesthesia attenuates liver metastasis by preserving TH1/TH2 cytokine balance

Anesthesiology

Inflammation and cancer

Nature

Impact of anesthesia for cancer surgery: continuing professional development

Can J Anaesth

Improving postoperative immune status and resistance to cancer metastasis: a combined perioperative approach of immunostimulation and prevention of excessive surgical stress responses

Ann Surg

Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis

Anesth Analg

The relationship of human wound vascular endothelial growth factor (VEGF) after breast cancer surgery to circulating VEGF and angiogenesis

Clin Cancer Res

Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer

Am J Hematol

Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanism and prophylactic measures

Anesth Analg

Anesthetics, immune cells, and immune responses

J Anesth

Anesthetic drugs accelerate the progression of postoperative metastases of mouse tumors

J Clin Invest

Cancer recurrence after surgery: direct and indirect effects of anesthetic agents

Int J Cancer

A comparison of the effect of total intravenous anaesthesia with propofol and remifentanil and inhalational anaesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy

Anaesth Intensive Care

Enhancement of anti-tumor immunity after propofol treatment in mice

Immunopharmacol Immunotoxicol

Propofol induced alterations in myocardial beta-adrenoceptor binding and responsiveness

Anesth Analg

Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells

Breast Cancer Res

Effects of propofol on the leukocyte nitric oxide pathway: in vitro and ex vivo studies in surgical patients

Naunyn Schmiedebergs Arch Pharmacol

Review
Cancer surgery: how may anesthesia influence outcome?