Cancer Res Treat.  2014 Jan;46(1):65-73.

Clinical Implications of Systemic Inflammatory Response Markers as Independent Prognostic Factors in Colorectal Cancer Patients

• Paik KY
• Lee IK
• Lee YS
• Sung NY
• Kwon TS

Abstract

PURPOSE
Cancer-related inflammation affects many aspects of malignancy. We confirm the effects of early postoperative systemic inflammation on cancer prognosis.
MATERIALS AND METHODS
Six hundred consecutive patients underwent surgery for colorectal cancer from 2006 to 2009. Measurements of white blood cells, neutrophils, lymphocytes, monocytes, and platelet counts were performed preoperatively, daily until the fourth postoperative day, and subsequently every two days. Patients were divided into three groups based on the days spent on the leukocyte count to drop below 10,000/mm3 after surgery.
RESULTS
Preoperative white blood cell (WBC) counts correlated with stage of disease. In univariate survival analyses, tumor, node, metastasis (TNM) stage, and monocyte count were associated with cancer-free survival. In addition, cancer-free survival outcomes were worse in patients who required more than four days for the normalization of WBC count. A TNM stage greater than II and the neutrophil lymphocyte ratio were associated with the duration of overall survival. In a multivariate analysis of these significant variables, TNM stage, an interval longer than four days for normalization of WBC counts and monocyte count independently associated with cancer-free survival.
CONCLUSION
Postoperative early inflammatory phase and preoperative monocyte count correlate with poor colon cancer prognosis. We can conclude that preoperative and postoperative inflammatory response and period unfavorably affect the metastatic microenvironment.

Keyword

Colorectal neoplasms; Inflammation; Perioperative period; Prognosis

MeSH Terms

Colonic Neoplasms
Colorectal Neoplasms*
Humans
Inflammation
Leukocyte Count
Leukocytes
Lymphocytes
Monocytes
Multivariate Analysis
Neoplasm Metastasis
Neutrophils
Perioperative Period
Platelet Count
Prognosis

Figure

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  Fig. 1 Overall survival and cancer-free survival according to disease stage.

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  Fig. 2 Overall survival and cancer-free survival according to the three groups.

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  Fig. 3 Overall survival and cancer-free survival according to monocyte count (×109).

Reference

1. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420:860–867. PMID: 12490959.

2. Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res. 2006; 4:221–233. PMID: 16603636.

3. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008; 454:436–444. PMID: 18650914.

4. Lee IK, Vansaun MN, Shim JH, Matrisian LM, Gorden DL. Increased metastases are associated with inflammation and matrix metalloproteinase-9 activity at incision sites in a murine model of peritoneal dissemination of colorectal cancer. J Surg Res. 2013; 180:252–259. PMID: 22763216.

5. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009; 12:223–226. PMID: 19318937.

6. Leitch EF, Chakrabarti M, Crozier JE, McKee RF, Anderson JH, Horgan PG, et al. Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer. 2007; 97:1266–1270. PMID: 17923866.

7. Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol. 2005; 91:181–184. PMID: 16118772.

8. Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009; 197:466–472. PMID: 18639229.

9. Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, et al. AJCC cancer staging handbook: from the AJCC cancer staging manual. New York: Springer;2002.

10. Ishizuka M, Nagata H, Takagi K, Horie T, Kubota K. Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer. Ann Surg. 2007; 246:1047–1051. PMID: 18043109.

11. Crozier JE, Leitch EF, McKee RF, Anderson JH, Horgan PG, McMillan DC. Relationship between emergency presentation, systemic inflammatory response, and cancer-specific survival in patients undergoing potentially curative surgery for colon cancer. Am J Surg. 2009; 197:544–549. PMID: 18614139.

12. Okuse T, Chiba T, Katsuumi I, Imai K. Differential expression and localization of WNTs in an animal model of skin wound healing. Wound Repair Regen. 2005; 13:491–497. PMID: 16176457.

13. Rubin P, Constine L, Williams J. Late effects of cancer treatment. In : Perez CA, Brady LW, editors. Principles and practice of radiation oncology. Philadelphia: Lippincott-Raven;1998. p. 194–211.

14. Milsom JW, Senagore A, Walshaw RK, Mostosky UV, Wang P, Johnson W, et al. Preoperative radiation therapy produces an early and persistent reduction in colorectal anastomotic blood flow. J Surg Res. 1992; 53:464–469. PMID: 1434596.