Introduction: Cold-inducible RNA-Binding Protein (CIRP) is primarily located in the nucleus where it regulates transcription. Under stress, CIRP migrates to the cytoplasm where it impacts translation; a proportion leaves the cell altogether and becomes extracellular CIRP (eCIRP). eCIRP is a damage-associated molecular pattern (DAMP) molecule that stimulates inflammatory responses including TNF-alpha, IL-6, and HMGB production. Surgery activates lymphocytes, PMN’s, and macrophages that may generate eCIRP. Blood levels of eCIRP after MICR for colorectal cancer were shown to be elevated for 1 month and may impact macrophage function and/or induce immune tolerance that may promote tumor progression. It is unclear if those eCIRP elevations are related to the cancer diagnosis and if similar changes occur after MICR for benign pathology (BP). The objective of this study was to analyze plasma eCIRP levels before and during the first month following MICR for BP.
Methods: Patients undergoing MICR for benign indications who participated in a tissue and data bank program for whom sufficient plasma samples were accessible (Preop, Postoperative day (POD) 1, 3 and at least 1 later sample) were eligible for this study. Late samples were bundled into 7 day time blocks (POD 7-13, 14-20, 21-27, and 28-41) and treated as separate time points. Samples were stored frozen until analysis. eCIRP levels were determined, in duplicate, via ELISA. The Wilcoxon paired t-test was utilized for data analysis.
Results: A total of 88 patients (mean age 60.3±11.61) who underwent MICR (laparoscopic, 64; hand-assisted laparoscopic, 24) for benign issues (diverticulitis, 44; benign polyps: 36, other: 8) were assessed. The average incision length was 7.1± 2.8cm and the mean length of stay was 5.5± 1.8 days. The mean PreOp eCIRP level was 948.7± 481.7pg/ml; vs preop levels, significant increases (p=<0.001) in mean levels were noted at the following time points: POD 1, 2613± 3709pg/ml (n= 88); POD3, 2232± 1435pg/ml (n= 76); POD7-13, 1494± 831.9pg/ml (n=55); POD14-20, 1677± 839.7pg/ml (n=33); and POD 21-27, 1674± 718.4pg/ml (n= 12, p=0.03). The POD 28-41 changes were not significant. No significant correlation was found between incision length and post eCIRP levels at any time point.
Conclusion: Similar to cancer patient results, after MICR for BP plasma eCIRP levels remain elevated for a month; thus, these changes are not related to the surgical indication. The percent change from baseline ranges from 43-175 % and peaks on POD1. The initial rise may be related to the acute inflammatory response while later increases may be associated with tissue remodeling and wound healing. The clinical import of these changes is uncertain. Of note, MICR for BP is also associated with other proangiogenic plasma changes akin to those observed in cancer patients. Further research is necessary.
