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Review
. 2020 Jan 23;2(2):57-69.
doi: 10.1016/j.sopen.2019.12.005. eCollection 2020 Apr.

Does postoperative inflammation or sepsis generate neutrophil extracellular traps that influence colorectal cancer progression? A systematic review

Georgia M Carroll  1   2   3 , Grace L Burns  3   4 , Joel A Petit  1   2   3 , Marjorie M Walker  2   3 , Andrea Mathe  3   4 , Stephen R Smith  1   2 , Simon Keely  3   4 , Peter G Pockney  1   2
Affiliations
Review

Does postoperative inflammation or sepsis generate neutrophil extracellular traps that influence colorectal cancer progression? A systematic review

Georgia M Carroll et al. Surg Open Sci. .

Abstract

Background: Colorectal cancer is the third most common cancer worldwide. Almost half of those that have a potentially curative resection go on to develop metastatic disease. A recognized risk for recurrence is perioperative systemic inflammation and sepsis. Neutrophil extracellular traps have been implicated as promotors of tumor progression. We aimed to examine the evidence in the literature for an association between neutrophil extracellular traps and postoperative metastasis in colorectal cancer.

Materials and methods: Studies published between 2000 and December 2018 that examined the role of neutrophil extracellular traps in sepsis and inflammation in colorectal cancer and in relation to tumor-related outcomes were identified through a database search of Cochrane, CINAHL, and MEDLINE. Quality and bias assessment was carried out by 2 reviewers.

Results: Of 8,940 screened and of the 30 studies included, 21 were observational, 5 were in vivo experimental, 1 was in vitro, and 3 used a combination of these approaches.

Conclusion: There is clear evidence from the literature that presence of a preoperative systemic inflammatory response predicts cancer recurrence following potentially curative resection, but the evidence for association of sepsis and progression is lacking. There is robust experimental evidence in murine models showing that neutrophil extracellular traps are present in sepsis and are associated with cancer progression. Some human observational studies corroborate the prognostic significance of neutrophil extracellular traps in progression of colorectal cancer. Further human studies are needed to translate the experimental evidence and to definitively associate sepsis and neutrophil extracellular traps with poor colorectal cancer-specific outcomes.

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Figures

Fig. 1
Fig. 1
A, NETosis is induced by surgical stress and postoperative infection, and NETs are released into systemic circulation; (B) concurrently, there are circulating viable tumor cells being shed by the primary tumor, (C) circulating tumor cells and circulating NETs interact, (D) tumor cells are trapped by NETs and embedded on endothelium in sites distant to the original tumor, and (E) metastatic deposits develop.
Fig. 2
Fig. 2
PRISMA flow diagram.
See this image and copyright information in PMC

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