Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases

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Abstract

Background

The neutrophil–lymphocyte ratio (NLR) provides an indicator of inflammatory status. An elevated NLR has been shown to be a prognostic indicator in primary colorectal malignancy. The aim of this study was to establish whether NLR predicts outcome in patients undergoing resection for colorectal liver metastasis.

Design

Retrospective analysis of the white cell and differential counts for 440 patients undergoing liver resections for colorectal liver metastasis between January 1996 and January 2006. An NLR  5 was considered to be elevated.

Results

Two hundred and eighty-nine males and 151 females were included. Seventy-eight patients (18%) had an elevated NLR, 55 of whom died, giving elevated NLR a positive predictive value (PPV) for death of 71%. Sixty of the 78 patients had recurrent disease giving raised NLR an PPV for recurrence of 78%. The 5-year survival for patients undergoing resection with high NLR was significantly worse than that for patients with normal NLR (22% vs. 43%, p < 0.0001). Univariate analysis of factors affecting survival revealed raised NLR, number of metastases >8, tumour size >5 cm and age >70 significantly affected outcome. All factors except tumour size remained significant predictors of term survival on multivariate analysis (NLR:HR = 2.261, CI = 1.654–3.129, p < 0.0001, metastases >8:HR = 1.611, CI = 1.006–2.579, p = 0.047, age >70:HR = 1.418, CI = 1.049–1.930, p = 0.027). Elevated NLR was found to be the sole positive predictor of recurrence on univariate analysis (HR = 4.521, CI = 2.475–8.257, p < 0.0001).

Conclusion

Elevated NLR increases both risk of death and the risk of recurrence in patients who undergo surgery for CRLM. Preoperative NLR measurement may therefore provide a simple method of identifying patients with a poorer prognosis.

Introduction

Liver resection is the primary mode of treatment for patients with CRLM, offering the only potential for disease eradication and therefore cure. Five-year survival approaches 45–50% in some centres,1, 2, 3, 4, 5, 6 however, cure from CRLM after surgery only occurs in 15–20% of patients. In addition, both intra- and extra-hepatic tumour recurrence rates remain high at around 60–65%.7, 8 The identification of patients more likely to have recurrence or poor outcome after surgery is therefore important and useful in guiding treatment.

Several studies have searched for prognostic indicators of outcome for CRLM patients. Potential prognostic indicators include primary tumour stage and grade, size, distribution and number of liver metastases, extra-hepatic disease, resection margins and lymph node status.4, 9, 10, 11, 12, 13 Although these histological and surgical prognostic indicators are valuable, they have not been widely applied and little exists by way of a consensus for selecting patients who would benefit most from surgery and adjuvant chemotherapy. More recently, there has been growing interest in the host's inflammatory response to tumour, and the systemic effects exerted by tumours in causing upregulation of the inflammatory process, thereby increasing propensity to metastasise through the inhibition of apoptosis, promotion of angiogenesis and damage of DNA.14, 15, 16, 17, 18

The most widely studied measure of inflammation is C-reactive protein (CRP), levels of which have been shown to independently predict survival in patients who undergo curative resection for colorectal cancer.19, 20 Recently, our group has identified CRP as a prognostic indictor in patients undergoing surgery for CRLM.21 A further marker of inflammation that is increasingly used to assess outcome in critically ill surgical patients is the neutrophil to lymphocyte ratio (NLR). An elevated NLR has been shown to be an indictor of poor outcome in vascular and cardiovascular patients undergoing intervention.22, 23 Walsh et al.24 have also shown an NLR  5 to be a marker of survival in colorectal cancer patients. We therefore hypothesise that an elevated NLR may be used as a preoperative prognostic indictor of both outcome and recurrence in CRLM patients undergoing curative hepatic resection.

Section snippets

Calculation of NLR

Patients undergoing resection for colorectal liver metastases had neutrophil and lymphocyte counts measured preoperatively as part of the routine work up. All white cell and differential counts were taken on the day before surgery with none of the patients showing clinical signs of sepsis. The NLR was calculated from the differential count by dividing the neutrophil measurement by the lymphocyte measurement. An NLR  5 was considered elevated. Patients were excluded if preoperative full blood

Results

A total of 440 patients were included in this study. Of these patients 289 (65%) were males and 151 (35%) females. The mean age of patient at time of surgery was 64 years (range 32–88 years; S.D. 10.7 years). All patients underwent liver resection. A total of 266 patients (61%) had a “major” (three or more Couinaud's segments) resection performed. The in-hospital mortality rate was 2.5%, overall (long term) mortality was 42% and 52% of patients developed recurrence.

Inflammation, elevated NLR and malignancy

The first casual link between cancer and inflammation was described over one and a half centuries ago by Rudolf Virchow, when he observed that leucocytes existed in neoplastic tissue.14 It is only in the past decade, however, that the complexities of the tumour inflammatory microenvironment, and the host's response to tumour induced inflammatory pathways are beginning to be understood, resulting in an improved ability to prevent and treat malignancy.

Inflammation has been shown to play an

Conclusion

In summary, elevated preoperative NLR increases both risk of death and the risk of recurrence in patients who undergo surgery for colorectal liver metastases. Preoperative NLR measurement in such patients may provide a simple method of identifying patients with a poorer prognosis and aid in guiding treatment effectively. Although no specific therapy for such patients exists at present, pre- and post-operative inflammatory and immune modulation may prove beneficial in improving their long term

Acknowledgements

The authors would like to acknowledge Mr. Anthony Kaye (Department of Haematology) for providing access to patients' blood results.

References (40)

  • G. Fegiz et al.

    Hepatic resections for colorectal metastases: the Italian multicenter experience

    J Surg Oncol

    (1991)
  • P.C. Simmonds et al.

    Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies

    Br J Cancer

    (2006)
  • Finch RJB, Malik HZ, Hamady ZZR, et al. Outcome following liver resection for colorectal liver metastases: effect of...
  • J. Yamamoto et al.

    Factors influencing survival of patients undergoing hepatectomy for colorectal metastases

    Br J Surg

    (1999)
  • K.S. Hughes et al.

    Resection of the liver for colorectal carcinoma metastases: a multiinstitutional study of patterns of recurrence

    Surgery

    (1986)
  • B. Nordlinger et al.

    Hepatic resection for colorectal liver metastases. Influence on survival of preoperative factors and surgery for recurrences in 80 patients

    Ann Surg

    (1987)
  • K. Tanaka et al.

    Pre-hepatectomy prognostic staging to determine treatment strategy for colorectal cancer metastases to the liver

    Arch Surg

    (2004)
  • Y. Fong et al.

    Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases

    Ann Surg

    (1999)
  • J.K. Seifert et al.

    Prognostic factors following liver resection for hepatic metastases from colorectal cancer

    Hepatogastroenterology

    (2000)
  • L.M. Coussens et al.

    Inflammation and cancer

    Nature

    (2002)
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