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Megan Sulciner, MD

Pronouns

She/Her/Hers

Job Title

General Surgery Resident, Research Fellow

Academic Rank

Research Fellow

Department

Anesthesiology, Perioperative and Pain Medicine, Surgery, Therapeutics & Reperfusion Injury

Authors

Megan L. Sulciner, Kimmie Ng, William L. Tan, Lauren K. Brais, Chandrajit P. Raut, Charles N. Serhan

Principal Investigator

Charles N. Serhan

Research Category: Cancer

Tags

Evaluating Failed Resolution of Inflammation Mechanisms as Potential Novel Risk Determinants for Stage 3 Colon Cancer Recurrence in Humans

Scientific Abstract

Background: Resolution of inflammation is the active process of returning to homeostasis after inflammatory insult, mediated by endogenous specialized pro-resolving mediators (SPMs). Failed resolution of inflammation secondary to surgery contributes to tumor recurrence in animal models. We sought to characterize a comprehensive inflammatory profile in patients after primary tumor resection.

Methods: Plasma collected postoperatively from primary resection of stage 3 colon cancer patients was obtained. Mediator levels were quantified via ELISA. Patient characteristics, oncologic outcomes, and surgical outcomes were analyzed.

Results: Of 19 patients included, 9 developed recurrence after primary resection (cohort 1) and 10 did not (cohort 2) at a median follow-up of 3.4 years. Mean plasma SPM resolvin D2 was 73.9 pg/ml in cohort 1 and 206.3 pg/ml in cohort 2 (p=0.04). Mean levels of other SPMs resolvin D1 (90.2 pg/ml v. 103.2 pg/ml), and lipoxin A4 (226.3 pg/ml v. 279.0 pg/ml), and pro-inflammatory leukotriene B4 (32.7 pg/ml v. 29 pg/ml) and CRP (3.6 ug/ml v. 4.7 ug/ml) were similar. Mean interleukin-6 was 8.1 pg/ml in cohort 1 and 0.5 pg/ml in cohort 2 (p=0.36).

Conclusions: Patients with stage 3 colon cancer that recurred after primary resection had lower plasma levels of the SPM resolvin D2. Trends noted with other SPMs and pro-inflammatory mediators need further investigation.

Lay Abstract

Background: Persistent inflammation after surgical removal of a tumor has been implicated in contributing to cancer recurrence. Markers of inflammation have been correlated with recurrence risk. We sought to characterize a comprehensive inflammatory profile, inclusive of both inflammatory markers and markers that demonstrate the resolution of inflammation, in cancer patients after tumor resection.

Methods: Levels of inflammatory (leukotriene B4, c-reactive protein, interleukin-6) and resolution of inflammation markers (term specialized pro-resolving mediators; resolvin D2, resolving D1, lipoxin A4) were measured in plasma collected postoperatively from patients with stage 3 colon cancer.

Results: Of 19 patients included, 9 patients developed tumor recurrence after primary resection (cohort 1) and 10 did not (cohort 2). The mean level of interleukin-6 was higher in cohort 1, though not statistically significant. The mean level of leukotriene B4 and c-reactive protein were similar between cohorts. Mean level of resolvin D2 was significantly lower in cohort 1 compared to cohort 2. Mean levels of resolvin D1 and lipoxin A4 were similar.

Conclusions: Patients with stage 3 colon cancer that recurred after primary resection had lower plasma levels of a marker that would indicate inflammation has resolved. Trends noted with these mediators need further investigation.

Clinical Implications

The findings in this translational study hold the potential to shift the paradigm in which failure of the resolution of inflammation contributes to the pathophysiology, diagnosis, and treatment of tumor recurrence.