Excessive inflammation portends complications: Wound cytokines and head and neck surgery outcomes
Amy Anne D. Lassig MD, MS, FACS  Bruce R. Lindgren MS  Ridwan Itabiyi BS  Anne M. Joseph MD, MPH  Kalpna Gupta PhD
First published: 09 January 2019 https://doi.org/10.1002/lary.27796
The authors gratefully acknowledge the financial support of the Triological Society for its generous funding of this work.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.

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Abstract
Objectives/Hypothesis
Postoperative wound‐healing complications can be devastating after head and neck surgery. Whereas many patients are expected to have more complications, few objective indicators predict these poorer outcomes. We evaluated wound healing in this population by studying the association between biomarkers and surgical outcomes.

Study Design
Prospective cohort study.

Methods
A study was performed of head and neck surgery patients at our tertiary care center, from 2012 to 2015. Postsurgical drain fluid was collected 24 hours postoperatively. Biomarkers of wound healing were assayed. These included interleukin (IL)‐1, ‐6, and ‐8; tumor necrosis factor (TNF)‐α; transforming growth factor β; epidermal growth factor; fibroblast growth factor; C‐reactive protein (CRP); vascular endothelial growth factor (VEGF); soluble fms‐like tyrosine kinase‐1; and placental growth factor. Patient characteristics and clinical outcomes were recorded. Two‐sample, two‐sided t tests evaluated differences in cytokine levels by clinical outcomes.

Results
Twenty‐eight patients were enrolled with drain fluid collection. IL‐1β, IL‐8, and matrix metalloproteinase (MMP)‐9 were significantly higher in the wound fluid of subjects with complications. Patients with longer length of stay in days had statistically higher levels of TNF‐α (P = .011), IL‐6 (P = .021), IL‐8 (P = .004), IL‐1β (P = .004), MMP‐1 (P = .002), MMP‐2 (P = .022), VEGF‐A (P = .038), and CRP (P < .001), and longer length of stay was associated with malignancy. There were no statistically significant associations between baseline clinical characteristics and post‐operative complications.

Conclusions
In this head and neck surgical cohort, higher IL‐1β, IL‐8, and MMP‐9 levels in wound fluid were associated with postoperative complications, and elevation of multiple proinflammatory cytokines was associated with longer length of stay. These findings suggest excessive inflammation in early wound healing may portend poorer clinical outcomes after head and neck surgery.

Level of Evidence
2b

Laryngoscope, 129:E238–E246, 2019