Abstract
Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC). We investigated whether peritoneal immune cytokines can predict PR. Cytokine concentrations of peritoneal fluid from CRC patients were measured. Patients were grouped according to peritoneal cancer burden (PCB): no tumor cells (≤ pT3), microscopic tumor cells (pT4), or gross tumors (M1c). Cytokine concentrations were compared among the three groups and the associations of those in pT4 patients with and without postoperative PR were assessed. Of the ten cytokines assayed, IL6, IL10, and TGFB1 increased with progression of PCB. Among these, IL10 was a marker of PR in pT4 (N = 61) patients based on ROC curve (p = 0.004). The IL10 cut-off value (14 pg/mL) divided patients into groups with a low (7%, 2 of 29 patients) or high (45%, 16 of 32 patients) 5-year PR (p < 0.001). Multivariable analysis identified high IL10 levels as the independent risk factor for PR. Separation of patients into training and test sets to evaluate the performance of IL10 cut-off model validated this cytokine as a risk factor for PR. Peritoneal IL10 is a prognostic marker of PR in pT4 CRC. Further research is necessary to identify immune response of intraperitoneal CRC growth.
Highlights
Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC)
CRC was one of the earliest cancers for which prognosis was shown to be influenced by the immune s ystem[9], and the ‘Immunoscore’ was validated in an international s tudy[10]; anti-PD-1 agents are ineffective for most CRC cases[11]
Because there was a large number of patients with ≤ pT3, we did not collect ascites from patients in clinical stage T1 or T2 since February 1, 2014
Summary
Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC). We investigated whether peritoneal immune cytokines can predict PR. Numerous studies have attempted to predict postoperative peritoneal recurrence (PR) to facilitate early detection and the administration of relevant adjuvant therapy to high-risk patients. Most of these studies aimed to detect and quantify free peritoneal cancer cells using cytological or molecular methods[5,6]; the effectiveness of using free peritoneal cancer cells to predict PR is u nclear[7]. We can specify immune characteristics according to the stages of peritoneal cancer burden based on pathological results as follows: no tumor cells (pT3 or lower; ≤ pT3), microscopic tumor cells (pT4), and gross tumors (M1c). Because the peritoneal cavity is substantially sterile, unless bowel perforation or intraperitoneal abscess occurs, this model is free from interference by immune responses to commensal bacteria, which is impossible in primary tumors
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