Download Thermo Combined-20 - Outcomes Research Consortium

Department of OUTCOMES RESEARCH
Regional Analgesia & Cancer Recurrence
Daniel I. Sessler, M.D.
Michael Cudahy Professor and Chair
Department of OUTCOMES RESEARCH
The Cleveland Clinic
No personal financial interests
related to this presentation
Providing the evidence for evidence-based medicine©
Objectives
Mechanistic evidence for regional analgesia and
cancer recurrence
Animal evidence that regional analgesia
ameliorates tumor progression
Human evidence regarding regional analgesia and
cancer recurrence
Causes of Long-term Mortality
≈10% one-year
mortality in
patients ≥65 yrs
Cause of Death
Monk, A&A 2005
%
Cancer
52%
Cardiovascular
17%
Renal/Liver Failure
5%
Respiratory Failure
4%
Pulmonary Emboli
2%
Sepsis/Infection
2%
Cancer Surgery
Cancer recurrence is usually lethal
Surgery remains primary treatment
• Releases tumor cells into blood stream
• There is always minimal residual disease
Natural killer (NK) cells are major defense
• Spontaneously recognize and kill tumor cells
Surgery and anesthesia impair NK Cell function
• Neuroendocrine stress response to surgery
• Volatile anesthetics
• Opioids
Regional Analgesia Protective?
Regional anesthesia & analgesia
• Reduces stress response to surgery
• Reduces or eliminates general anesthetics
• Obviates need for postoperative opioids
All three help preserve NK cell function
Hypothesis:
• Regional anesthesia & analgesia reduces risk of
cancer recurrence
Natural Kill Activity
Surgery in Rats
Reduced NK Activity
• In blood
• In the spleen
Increased lung metastases
Ben-Eliyahu, Int J
Cancer 1999
Anesth Increases Tumor Retention
Melamed, A&A 2003
Moudgil, CJA 1997
Opioids are Immunosuppressant
Lung tumor retention
Central pathway
• Glucocorticoid release
Peripheral pathways
• Reduced NK cell activity
• Impaired antibody production
• Decreased cytokine release
Shavit, Neuroimmunomodulation 2004
Rats: Bar-Yusof, Anesthesiology 2001
Paravertebrals & Breast Cancer
Retrospective analysis of 129 mastectomies for CA
• 50 had combined general & paravertebral analgesia
• 79 had general and morphine analgesia
% Recurrence-free
100
Paravertebral
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90
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80
General
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70
P = 0.012
0
0
12
24
Time (mo)
36
Exadaktylos,
Anesthesiology 2006
Epidurals & Prostate Cancer
Retrospective analysis of 225 prostatectomies for CA
• 102 had combined general & epidural analgesia
• 123 had general and morphine analgesia
% Recurrence-free
100
Epidural/
General
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90
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80
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70
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General/
Morphine
60
Epidurals associated
with 57% [17-78%]
less recurrence
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50
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P < 0.0001
0
0
2
4
6
Time (yr)
8
10
Biki, Anesthesiology
2008
Epidurals & Prostate Cancer
Scavonetto, BJA, in press
Spinals & Melanoma
Retrospective analysis of patients for melanoma surgery
• 52 well-matched pairs
Spinal
P = 0.09
General
Gottschalk,
BJA 2012
Negative Retrospective Results
Ismail et al: BJA 2010
• Brachytherapy for cervical cancer
– 63 neuraxial vs. 69 general anesthesia
Gottschalk et al: Anesthesiology 2010
• Colectomy for colon cancer
– 256 epidural vs. 253 general anesthesia
Tsui et al: CJA 2010
• Epidural analgesia for prostate cancer
– 49 epidural vs. 50 general anesthesia
Forget et al: EJA 2011
• Epidural analgesia for prostate cancer
– 578 epidural vs. 533 general anesthesia
Day et al: BJA 2012
• Laparoscopic colectomy
• 107 epidural; 144 spinal; and 173 general alone
Etc.
MASTER Trial Follow-up
Myles, BMJ, 2011
Epidural (n=230)
Also negative:
Tsui 2010
Christopherson 2008
General (n=215)
Binczak, et al 2013 (n=132)
Summary
Three compelling mechanisms protect NK function
• Reduced surgical stress response
• Decreased need for volatile anesthetics
• Decreased Opioid use
Results in rodents are convincing
Human results equivocol
• Retrospective studies mostly negative
• Only randomized trials negative
–But all small and designed for other purposes
Randomized trials needed — and in progress
Department of OUTCOMES RESEARCH