Review
C-reactive protein in liver cancer surgery

https://doi.org/10.1016/j.ejso.2008.01.016Get rights and content

Abstract

Aims

The aim of this article is to review the current state of knowledge with regard to the importance of C-reactive protein (CRP) in patients undergoing hepatic resection for malignancy both in terms of its role as an acute phase reactant and predictor of outcome.

Methods

An electronic search was performed of the medical literature using the MEDLINE database to identify relevant articles that included the search terms: C-reactive protein; CRP; hepatocellular carcinoma; colorectal liver metastases; hepatic resection; and liver resection.

Results

The limited published data in relation to CRP and liver resection is contradictory. There are studies correlating an acute phase reactant-type postoperative rise in CRP with both good and poor outcome following colorectal liver metastases resection. In relation to prognosis, the only available publication indicates that a high preoperative CRP is a poor prognostic indicator in relation to patient survival. Data for CRP and resection of HCC is equally as limited with early evidence suggesting a correlation between CRP and stage of disease, and documenting an acute temporary elevation in CRP following resection.

Conclusions

The importance of CRP as a marker of both early postoperative outcome and long-term prognosis in patients with hepatic malignancies is at present unclear. Further studies are required to clarify the changes and more accurately define the mechanism by which CRP is being up-regulated.

Introduction

The concept of inflammation being important in the pathogenesis of cancer is not new. Indeed, as early as 1863, Virchow suggested that cancers had an inflammatory origin.1 In the later half of the 20th century, much work was performed on the subject and a clear understanding now exists as regards the role of inflammation in the pathogenesis of many cancers, including: Helicobacter pylori and gastric cancer, and inflammatory bowel disease and colonic adenocarcinoma.

Section snippets

C-reactive protein

C-reactive protein (CRP) the archetypal acute phase reactant was first identified in 19302 in a patient with Streptococcus pneumoniae infection when it was named C-reactive substance. It has since been shown to be elevated in a number of acute and chronic inflammatory conditions. CRP is synthesised by the liver and is primarily regulated in response to interleukin-6 (IL-6) whose synthesis is enhanced synergistically by IL-1β.3, 4

CRP and cancer

Given the link between inflammation and cancer, it was not surprising when evidence for the importance of a systemic inflammatory response, as indicated by an elevated CRP was identified in patients undergoing resection of colorectal cancer.5 McMillan and colleagues reported a relationship between CRP and Duke stage of the tumour and in subsequent studies, the Glasgow-based research group demonstrated that the presence of a perioperative elevation in CRP measured either pre- or post-operatively

Importance of CRP in cancer

It has recently been demonstrated in colorectal cancer that tumour infiltration with CD4+ lymphocytes carries a good prognostic outcome11 and that plasma CRP levels are inversely related to infiltration of the tumour microenvironment by CD4+ lymphocytes and this in turn carries a poor prognosis.12 The CD4+ T cells also known as helper T cells can express one of two cytokine patterns, the so-called Th1 (Interferon gamma, Tissue necrosis factor) and Th2 (Interleukins 4, 5, 6, 10 and 13)

CRP and resection of colorectal liver metastases

There is surprisingly little data. De Jong and colleagues compared perioperative changes in CRP in 24 patients undergoing hepatectomy with nine patients undergoing laparotomy (unresectable tumour) alone. They noted a significant elevation on day 1 in keeping with an acute phase response but this settled back towards normal by the fourth postoperative day.15 Furthermore, they found that the CRP response was greater in the laparotomy than the resection group and that the size of the CRP response

CRP and resection of hepatocellular cancer

Hashimoto and colleagues examined the relationship between baseline CRP and outcome in 141 patients undergoing resection of a hepatocellular carcinoma. They divided their patients into CRP negative (<1 mg/dL; n = 119) and CRP positive (>1 mg/dL; n = 22) and noted that the CRP correlated with tumour size, portal vein invasion, recurrence and long-term survival.23

Lan et al. looked at the acute phase response to hepatectomy in patients with hepatocellular carcinoma (n = 7) and in a cohort of patients

Conclusion

CRP is probably a lot more than just an acute phase reactant and may prove to be an important prognostic indicator; however, at present the data is simply not present to define at risk populations. Further studies are required for patients with colorectal metastases and hepatocellular carcinoma using high sensitivity assays and with careful documentation of concurrent medical disease. Additional studies are also required to define the pathways leading to activation of CRP in hepatic

Conflict of interest

Mr. Gareth Morris-Stiff, Mr. Dhanwant Gomez and Mr. K. Rajendra Prasad declare no conflict of interest in relation to this manuscript.

References (24)

  • S.M. Zhang et al.

    C-reactive protein levels are not associated with increased risk for colorectal cancer in women

    Ann Intern Med

    (2005)
  • Y. Ito et al.

    Colorectal cancer and serum C-reactive protein levels: a case–control study nested in the JACC study

    J Epidemiol

    (2005)

    • Cited by (75)

    View all citing articles on Scopus
    View full text
    Copyright © 2008 Elsevier Ltd. All rights reserved.