Intraoperative opioids are associated with decreased recurrence rates in colon adenocarcinoma: A retrospective observational cohort study Journal Article


Authors: Yuval, J. B.; Lee, J.; Wu, F.; Thompson, H. M.; Verheij, F. S.; Gupta, H. V.; Irie, T.; Scarpa, J. R.; McCormick, P. J.; Smith, J. J.; Shia, J.; Weiser, M. R.; Sánchez-Vega, F.; Tan, K. S.; Fischer, G. W.; Garcia-Aguilar, J.; Mincer, J. S.
Article Title: Intraoperative opioids are associated with decreased recurrence rates in colon adenocarcinoma: A retrospective observational cohort study
Abstract: Background: Opioid-induced immunomodulation may be important in colon adenocarcinoma, where tumour DNA mismatch repair (MMR) can determine the level of immune activation with consequences for therapeutic response and prognosis. We evaluated the relationship between intraoperative opioid exposure, MMR subtype, and oncological outcomes after surgery for colon adenocarcinoma. Methods: Intraoperative opioid use (standardised by calculating morphine milligram equivalents) during stage I–III colon adenocarcinoma resection was reviewed retrospectively. Tumours were classified as DNA mismatch repair deficient (dMMR) or proficient (pMMR) by immunohistochemistry. The primary outcome was local tumour recurrence, distant tumour recurrence, or both (multivariable analysis). The exposures of interest were intraoperative analgesia and tumour subtype. Opioid-related gene expression was analysed using The Cancer Genome Atlas Colon Adenocarcinoma transcriptomic data. Results: Clinical and pathological data were analysed from 1157 subjects (median age, 60 [51–70] yr; 49% female) who underwent curative resection for stage I–III colon adenocarcinoma. Higher intraoperative opioid doses were associated with reduced risk of tumour recurrence (hazard ratio=0.92 per 10 morphine milligram equivalents; 95% confidence interval [95% CI], 0.87–0.98; P=0.007), but not with overall survival. In tumours deficient in DNA MMR, tumour recurrence was less likely (HR=0.38; 95% CI, 0.21–0.68; P=0.001), with higher opioid dose associated with eightfold lower recurrence rates. Gene expression related to opioid signalling was different between dMMR and pMMR tumours. Conclusions: Higher intraoperative opioid dose was associated with a lower risk of tumour recurrence after surgery for stage I–III colon adenocarcinoma, but particularly so in tumours in which DNA MMR was deficient. © 2022 British Journal of Anaesthesia
Keywords: gene expression; dna mismatch repair; surgery; immunomodulation; opioids; colon adenocarcinoma
Journal Title: British Journal of Anaesthesia
Volume: 129
Issue: 2
ISSN: 0007-0912
Publisher: Oxford University Press  
Date Published: 2022-08-01
Start Page: 172
End Page: 181
Language: English
DOI: 10.1016/j.bja.2022.04.024
PUBMED: 35718564
PROVIDER: scopus
PMCID: PMC9465945
DOI/URL:
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Jinru Shia
    720 Shia
  2. Martin R Weiser
    538 Weiser
  3. Jesse Joshua Smith
    221 Smith
  4. Kay See   Tan
    241 Tan
  5. Gregory Walter Fischer
    40 Fischer
  6. Takeshi Irie
    14 Irie
  7. Fan Wu
    17 Wu
  8. Joshua Samuel Mincer
    23 Mincer
  9. Jonathan Benjamin Yuval
    37 Yuval
  10. Floris Stefanus Verheij
    36 Verheij
  11. Jasme Lee
    32 Lee