Abstract
BackgroundInflammation-induced endothelial precursor cell recruitment and angiogenesis are thought to be associated with CXCL16-CXCR6 pair activity. This study’s main purpose was to determine plasma CXCL16 levels after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC); an adjunct study assessed wound fluid (WF) and plasma CXCL16 levels in a separate group of CRC patients.MethodsCRC patients who had MICR and for whom plasma was available in a tissue bank were eligible. Plasma samples were collected preoperatively from all patients. Samples were also collected on postoperative days (POD) 1 and 3 and at various late postoperative time points (POD 7–34). In a separate study, blood and intra-abdominal wound fluid (WF) samples were collected from CRC MICR patients (pts). Samples were stored at − 80 °C. CXCL16 levels were determined via ELISA. The Wilcoxon signed-rank and Mann and Whitney tests were used for analysis.ResultsMain study: 86 CRC pts. were included. The mean preoperative plasma CXCL16 level was 2.36 ± 0.57 ng/ml. Elevated mean plasma levels (p < 0.0001 × first 4 time points) were noted on POD 1 (2.82 ± 0.81, n = 86), POD 3 (3.12 ± 0.77, n = 82), POD 7–13 (3.28 ± 0.88, n = 64), POD 14–20 (3.03 ± 0.62, n = 24), POD 21–27 (3.06 ± 0.67, n = 20, p = 0.0003), and POD 28–34 (3.17 ± 0.43, n = 11, p = 0.001) vs. preop levels. WF study: In the adjunct study, plasma and WF CXCL16 levels were determined for 23 CRC MICR pts. WF levels at all time points were significantly elevated over plasma levels.ConclusionPlasma CXCL16 levels were elevated for 4 weeks after minimally invasive colorectal resection for cancer. Also, WF CXCL16 levels were 3–10 times greater than the corresponding plasma concentrations. The source of the late plasma elevations may be the healing wound. Increased plasma CXCL16 levels may promote tumor angiogenesis in the first month after MICR.
Highlights
Inflammation-induced endothelial precursor cell recruitment and angiogenesis are thought to be associated with CXCL16-CXCR6 pair activity
As regards study B, colorectal cancer (CRC) patients who met the following criteria were eligible: had enrolled in the abovementioned tissue and data collection protocol, underwent minimally invasive colorectal resection (MICR) during which a Jackson-Pratt drain was placed in the pelvis, agreed postoperatively to enter the IRB-approved wound fluid study (IRB of the Mount Sinai Icahn School of Medicine, New York; IRB reference NO: GCO#1: 16-1863), and IRB-approved (Institutional Review Board of the Mount Sinai School of Medicine, New York NY; IRB reference NO: GCO#16-1863) informed consent for participation in the study was obtained from all participants
Study A Preoperative and one or more late postoperative plasma sample were available for 86 CRC patients who underwent MICR for plasma CXCL16 study
Summary
Inflammation-induced endothelial precursor cell recruitment and angiogenesis are thought to be associated with CXCL16-CXCR6 pair activity. Despite surgery and, where indicated chemo- and radiotherapy, recurrence develops in a substantial percentage of patients. There is both human and experimental evidence that colon resection-related surgical trauma and surgical trauma in general are linked to tumor establishment and tumor growth after [2,3,4,5,6]. Proposed mechanisms leading to stimulated tumor growth and metastasis after surgery include immunosuppression, tissue trauma-associated adrenergic response, and the wound bed environment that can directly illicit an inflammatory cascade linked to tumor initiation, invasion, and metastasis [2,3,4, 13,14,15]. There is an enlarging body of evidence that colorectal resection in humans is linked to changes in plasma composition that render it pro-angiogenic for 3–5 weeks after surgery
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