Radical gastric cancer surgery results in widespread upregulation of pro-tumourigenic intraperitoneal cytokines

Andrew J. Long, Paul R. Burton, Michael J. De Veer, Geraldine J. Ooi, Cheryl P. Laurie, Peter D. Nottle, Matthew J. Watt, Wendy A. Brown

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Background: Radical surgical resection is the mainstay of curative treatment for oesophagogastric malignancy. However, survival and recurrence rates remain poor. Theoretical data suggests that the inflammatory response to surgery can promote tumour recurrence. The local and systemic inflammatory response to radical oesophagogastric cancer surgery has not been fully characterized. We aimed to measure this response, particularly factors associated with tumour implantation. Methods: Consecutive patients undergoing radical junctional or gastric cancer resection over 12 months were recruited. Repeated serum and adipose tissue were collected intra-operatively. Adipose tissue was collected adjacent and remote to the tumour, and cytokine messenger RNA (mRNA) expression was measured. Post-operatively, daily serum was collected for 7 days, and analysed for inflammatory cell profile and cytokine concentration. Results: There were nine patients recruited (67.1 ± 2.1 years). mRNA expression of interleukin-6 (IL-6), CC-chemokine ligand-2 and IL-1β increased in adipose tissue intra-operatively (P < 0.05), equally both adjacent and remote from the tumour site. Serum IL-6 concentration increased from 23.3 pg/mL to 161.8 pg/mL intra-operatively (P < 0.05) before falling steadily to 35.7 pg/mL post-operatively (P < 0.05). Serum tumour necrosis factor-α was elevated throughout, and IL-1β levels were unaffected. Leukocyte and neutrophil populations increased, while T-cell and dendritic cell populations decreased intra-operatively (P < 0.05). Conclusion: Radical surgery dramatically upregulates the expression of pro-tumourigenic cytokines in the peritoneum. There is also a marked systemic immune and inflammatory response to surgery, including downregulation of T-cell and dendritic cell populations. This offers two potential pathways that may facilitate tumour progression – local inflammation promoting peritoneal adherence and implantation, and secondary suppression of immunosurveillance due to circulating inflammatory response.

Original languageEnglish
Pages (from-to)E370-E376
Number of pages6
JournalANZ Journal of Surgery
Volume88
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • adipose tissue
  • cytokine
  • immune cell
  • inflammation
  • neoplasm recurrence
  • oesophageal neoplasm
  • stomach neoplasm

Cite this

@article{936ec061ed73427eb6c465325709583d,
title = "Radical gastric cancer surgery results in widespread upregulation of pro-tumourigenic intraperitoneal cytokines",
abstract = "Background: Radical surgical resection is the mainstay of curative treatment for oesophagogastric malignancy. However, survival and recurrence rates remain poor. Theoretical data suggests that the inflammatory response to surgery can promote tumour recurrence. The local and systemic inflammatory response to radical oesophagogastric cancer surgery has not been fully characterized. We aimed to measure this response, particularly factors associated with tumour implantation. Methods: Consecutive patients undergoing radical junctional or gastric cancer resection over 12 months were recruited. Repeated serum and adipose tissue were collected intra-operatively. Adipose tissue was collected adjacent and remote to the tumour, and cytokine messenger RNA (mRNA) expression was measured. Post-operatively, daily serum was collected for 7 days, and analysed for inflammatory cell profile and cytokine concentration. Results: There were nine patients recruited (67.1 ± 2.1 years). mRNA expression of interleukin-6 (IL-6), CC-chemokine ligand-2 and IL-1β increased in adipose tissue intra-operatively (P < 0.05), equally both adjacent and remote from the tumour site. Serum IL-6 concentration increased from 23.3 pg/mL to 161.8 pg/mL intra-operatively (P < 0.05) before falling steadily to 35.7 pg/mL post-operatively (P < 0.05). Serum tumour necrosis factor-α was elevated throughout, and IL-1β levels were unaffected. Leukocyte and neutrophil populations increased, while T-cell and dendritic cell populations decreased intra-operatively (P < 0.05). Conclusion: Radical surgery dramatically upregulates the expression of pro-tumourigenic cytokines in the peritoneum. There is also a marked systemic immune and inflammatory response to surgery, including downregulation of T-cell and dendritic cell populations. This offers two potential pathways that may facilitate tumour progression – local inflammation promoting peritoneal adherence and implantation, and secondary suppression of immunosurveillance due to circulating inflammatory response.",
keywords = "adipose tissue, cytokine, immune cell, inflammation, neoplasm recurrence, oesophageal neoplasm, stomach neoplasm",
author = "Long, {Andrew J.} and Burton, {Paul R.} and {De Veer}, {Michael J.} and Ooi, {Geraldine J.} and Laurie, {Cheryl P.} and Nottle, {Peter D.} and Watt, {Matthew J.} and Brown, {Wendy A.}",
year = "2018",
month = "5",
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language = "English",
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pages = "E370--E376",
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}

Radical gastric cancer surgery results in widespread upregulation of pro-tumourigenic intraperitoneal cytokines. / Long, Andrew J.; Burton, Paul R.; De Veer, Michael J.; Ooi, Geraldine J.; Laurie, Cheryl P.; Nottle, Peter D.; Watt, Matthew J.; Brown, Wendy A.

In: ANZ Journal of Surgery, Vol. 88, No. 5, 01.05.2018, p. E370-E376.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Radical gastric cancer surgery results in widespread upregulation of pro-tumourigenic intraperitoneal cytokines

AU - Long, Andrew J.

AU - Burton, Paul R.

AU - De Veer, Michael J.

AU - Ooi, Geraldine J.

AU - Laurie, Cheryl P.

AU - Nottle, Peter D.

AU - Watt, Matthew J.

AU - Brown, Wendy A.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background: Radical surgical resection is the mainstay of curative treatment for oesophagogastric malignancy. However, survival and recurrence rates remain poor. Theoretical data suggests that the inflammatory response to surgery can promote tumour recurrence. The local and systemic inflammatory response to radical oesophagogastric cancer surgery has not been fully characterized. We aimed to measure this response, particularly factors associated with tumour implantation. Methods: Consecutive patients undergoing radical junctional or gastric cancer resection over 12 months were recruited. Repeated serum and adipose tissue were collected intra-operatively. Adipose tissue was collected adjacent and remote to the tumour, and cytokine messenger RNA (mRNA) expression was measured. Post-operatively, daily serum was collected for 7 days, and analysed for inflammatory cell profile and cytokine concentration. Results: There were nine patients recruited (67.1 ± 2.1 years). mRNA expression of interleukin-6 (IL-6), CC-chemokine ligand-2 and IL-1β increased in adipose tissue intra-operatively (P < 0.05), equally both adjacent and remote from the tumour site. Serum IL-6 concentration increased from 23.3 pg/mL to 161.8 pg/mL intra-operatively (P < 0.05) before falling steadily to 35.7 pg/mL post-operatively (P < 0.05). Serum tumour necrosis factor-α was elevated throughout, and IL-1β levels were unaffected. Leukocyte and neutrophil populations increased, while T-cell and dendritic cell populations decreased intra-operatively (P < 0.05). Conclusion: Radical surgery dramatically upregulates the expression of pro-tumourigenic cytokines in the peritoneum. There is also a marked systemic immune and inflammatory response to surgery, including downregulation of T-cell and dendritic cell populations. This offers two potential pathways that may facilitate tumour progression – local inflammation promoting peritoneal adherence and implantation, and secondary suppression of immunosurveillance due to circulating inflammatory response.

AB - Background: Radical surgical resection is the mainstay of curative treatment for oesophagogastric malignancy. However, survival and recurrence rates remain poor. Theoretical data suggests that the inflammatory response to surgery can promote tumour recurrence. The local and systemic inflammatory response to radical oesophagogastric cancer surgery has not been fully characterized. We aimed to measure this response, particularly factors associated with tumour implantation. Methods: Consecutive patients undergoing radical junctional or gastric cancer resection over 12 months were recruited. Repeated serum and adipose tissue were collected intra-operatively. Adipose tissue was collected adjacent and remote to the tumour, and cytokine messenger RNA (mRNA) expression was measured. Post-operatively, daily serum was collected for 7 days, and analysed for inflammatory cell profile and cytokine concentration. Results: There were nine patients recruited (67.1 ± 2.1 years). mRNA expression of interleukin-6 (IL-6), CC-chemokine ligand-2 and IL-1β increased in adipose tissue intra-operatively (P < 0.05), equally both adjacent and remote from the tumour site. Serum IL-6 concentration increased from 23.3 pg/mL to 161.8 pg/mL intra-operatively (P < 0.05) before falling steadily to 35.7 pg/mL post-operatively (P < 0.05). Serum tumour necrosis factor-α was elevated throughout, and IL-1β levels were unaffected. Leukocyte and neutrophil populations increased, while T-cell and dendritic cell populations decreased intra-operatively (P < 0.05). Conclusion: Radical surgery dramatically upregulates the expression of pro-tumourigenic cytokines in the peritoneum. There is also a marked systemic immune and inflammatory response to surgery, including downregulation of T-cell and dendritic cell populations. This offers two potential pathways that may facilitate tumour progression – local inflammation promoting peritoneal adherence and implantation, and secondary suppression of immunosurveillance due to circulating inflammatory response.

KW - adipose tissue

KW - cytokine

KW - immune cell

KW - inflammation

KW - neoplasm recurrence

KW - oesophageal neoplasm

KW - stomach neoplasm

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U2 - 10.1111/ans.14267

DO - 10.1111/ans.14267

M3 - Article

VL - 88

SP - E370-E376

JO - ANZ Journal of Surgery

JF - ANZ Journal of Surgery

SN - 1445-1433

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ER -