Anastomotic leakage (AL) after colorectal surgery constitutes a dreaded complication after colorectal surgery [
1]. Depending on the anatomical localization, insufficiency rates of about 3% after colon surgery and between 3 and 19% after colorectal surgery are described [
2‐
4]. Even in high-volume centers, a portion of patients develops an anastomotic leakage. However, high-volume centers reveal less in-hospital mortality rates of patients with anastomotic leakage [
5] . Consensus definition states anastomotic leakage as a communication between the intra- and extraluminal compartments resulting from a defect in the integrity of the intestinal wall at the anastomosis. Leakages originating from the suture or staple line of a neorectal reservoir, as well as a pelvic abscess in the proximity of the anastomosis, are also considered an anastomotic leakage [
6,
7]. Defined by the International Study Group of Rectal Cancer, three grades of AL exist ranking the AL due to its clinical severity. Grade A is called a radiologic leakage meaning the patient has no clinical symptoms or increased infectious values in the blood test. This kind of anastomotic leakage entails no active therapeutic intervention. Grade B patients present with leukocytosis, an increase of CRP, abdominal pain, and distension and require an active therapeutic intervention in terms of antibiotics or an interventionally placed pelvic drain. But there is no need for relaparotomy. Grade C AL includes the symptoms as Grade B together with an ensuing peritonitis or sepsis. Patients with Grade C AL require a relaparotomy which is often associated with Hartmann’s procedure [
6,
7]. The mean occurrence of colorectal anastomotic leakage (CAL) has been described for the eighth postoperative day (POD), with an interval between the sixth and thirteenth POD [
8,
9]. Preoperative and intraoperative risk factors for CAL are male sex, distal anastomosis, advanced tumor stage, emergency surgery, duration of surgery, or amount of blood loss [
1,
10‐
16]. Nevertheless, CAL rates remain stable over the past years [
17]. AL after colon or colorectal resection is associated with a prolonged hospital stay, substantial negative impact on morbidity and mortality rates, as well as higher cancer recurrence frequency [
1,
3,
18,
19]. Therefore, an objective of utmost importance is the early detection of AL to limit the negative postoperative outcome to a minimum. Occurrence of an anastomotic leakage is associated with a local inflammation at this site. Moreover, an upregulation of inflammatory cytokines and chemokines in case of inflammation is commonly known [
20]. As acute-phase proteins, cytokines or chemokines, respectively, were synthesized in the liver and at the site of inflammation, protein levels taken from pelvic drain fluid represent the local milieu and could be more specific for the detection of an anastomotic leakage [
21]. To investigate markers for AL, we analyzed a panel of inflammatory markers in sera and peritoneal fluid from the abdominal drain on the third postoperative day from patients with and without CAL after colorectal surgery due to colorectal cancer. CCL-1/I-309 (C-C motif ligand 1), CCL8/MCP-2 (monocyte chemotactic protein-2), CCL13/MCP-4 (monocyte chemotactic protein-4), CXCL5/ENA-78 (epithelial neutrophil-activating peptide), LIF (leukemia inhibitory factor), IL-16 (interleukin-16), and IL-21 (interleukin-21) were chosen for analysis. Selected markers were chosen based on a literature research because of their known role in inflammatory processes. CCL-1/I-309 is produced mostly by T
regs at the site of inflammation [
22]. CCL8/MCP-2 activates immune cells like natural killer cells as a proinflammatory mediator [
23]. CCL13/MCP-4 carries out proinflammatory actions through chemotaxis of monocyte-derived macrophages, lymphocytes, and basophils [
24]. CXCL5/ENA-78 is detected in inflamed intestinal mucosa. Il-16 is produced by T lymphocytes, eosinophils, mast cells, and macrophages during inflammatory responses and is recruited if cell necrosis occurs [
25,
26]. Il-21 expression is induced by other cytokines, e.g., Il-6, and it regulates the proliferation and function of numerous immune cells like natural killer cells [
27]. And LIF promotes recruitment of inflammatory cells to the area of damage [
28].Moreover, until now no study investigated the influence of these inflammatory markers in anastomotic leakage after colorectal surgery. We hypothesize that the above named inflammatory markers - measured in the peritoneal fluid - could predict the occurrence of an anastomotic leakage after colorectal surgery already on the third postoperative day, prior to the mean occurrence at the eight postoperative day.