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Neutrophil Count, but Not Other Components of a White Cell Count, Reflects the Impact of the Systemic Inflammatory Response and Long Term Survival in Patients Following Elective Surgery for Colorectal Cancer
David G. Watt*, James H. Park, Michelle L. Ramanathan, Paul G. Horgan, Donald C. Mcmillan
Academic Unit of Colorectal Surgery, Glasgow Royal Infirmary, Glasgow, United Kingdom
Background
It has recently been reported that the magnitude of the post-operative systemic inflammatory response can be assessed by monitoring the concentrations of C-reactive protein (CRP) but not a white cell count (WCC). Although the majority of white cells are neutrophils, there are other cells that are included and these may respond differently following surgical intervention. Furthermore, pre-operative systemic inflammatory scoring systems such as the Neutrophil Lymphocyte Ratio (NLR) have been described in many solid organ cancers and shown to have prognostic value. However, different NLR thresholds have been reported for its clinical utility. Therefore, the aim of the present study was to determine which of the components of the WCC were involved in predicting short and long term outcomes in patients undergoing elective surgery for colorectal cancer (CRC).
Methods
Patients with histologically proven CRC who were considered to have undergone potentially curative resection were studied. 2 patient cohorts were examined. Short term outcomes (cohort 1) were examined in 378 patients and were performed using open (n = 291) or laparoscopic (n = 87) surgery. Daily blood samples to measure CRP and differential WCC were taken routinely in the perioperative period and patients were assessed for post-operative complications. Long term outcomes were examined in 508 patients (cohort 2). Pre-operative CRP and differential WCC were measured and their association with cancer-specific (CSS) and overall survival (OS) were examined.
Results
In cohort 1, only the neutrophil and monocyte count significantly increased following surgery (lymphocytes, eosinophils, basophils and platelets were lower), peaking on post-operative day 1 and were significantly different to pre-operative values (all p < 0.001). Laparoscopic surgery was associated with lower neutrophil counts but higher lymphocyte counts (both p < 0.01) compared with open procedures. Compared with no complications, infective complications were associated with greater neutrophil counts from post-operative day 3 (p < 0.01) but lymphocyte counts were not altered. In cohort 2, there were 172 cancer deaths and 120 non-cancer deaths. On Kaplan Meier analysis age, TNM stage, venous invasion, margin involvement, peritoneal involvement, tumour perforation, white cell and neutrophil count (all p<0.05) were associated with CSS. In those with node negative colon cancer (n=226), on multivariate analysis, age, venous invasion, and neutrophil count (all p<0.05) were independently associated with CSS.
Conclusions
Of the components of a WCC, only the neutrophil count reflected the impact of the magnitude of injury, development of infective complications and was independently associated with cancer-specific survival. Therefore, it is likely that the prognostic value of the NLR is mainly determined by the neutrophil count.
Table 1. The magnitude of the neutrophil count in patients undergoing open and laparoscopic procedures and developing infective and no complications following elective colorectal cancer resection
| Time after surgery (Days) | Open (median) | Laparoscopic (median) | p-value | | Neutrophil count (109/L) | | | | | Pre-op | 5.0 | 4.1 | 0.002 | | Day 1 | 9.1 | 8.4 | 0.086 | | Day 2 | 9.0 | 7.6 | 0.006 | | Day 3 | 7.3 | 6.6 | 0.100 | | Day 4 | 6.3 | 5.7 | 0.743 | | | | | | Time after surgery (Days) | No Complication
(median) | Infective Complication
(median) | p-value | | Pre-op | 4.6 | 4.8 | 0.755 | | Day 1 | 8.9 | 9.0 | 0.610 | | Day 2 | 8.6 | 8.8 | 0.112 | | Day 3 | 6.7 | 7.8 | 0.001 | | Day 4 | 5.9 | 6.9 | 0.005 |
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