Crozier, Joseph E M
An investigation of the systemic inflammatory response in the peri-operative period in patients undergoing potentially curative surgery for colorectal cancer.
MD thesis, University of Glasgow.
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Colorectal cancer remains the second commonest cause of cancer death in Western Europe and North America. Each year in the UK, there are approximately 35,000 new cases and 16,000 deaths attributable to the disease. Despite a trend towards earlier presentation and improvements in the quality of surgery many patients still die of their disease. Overall about a third of patients undergoing surgery for potentially curative disease will die within five years.
Recent work has meant that it is now recognised that it is not only the tumour characteristics that are responsible for cancer specific survival but also the host immune response. Part of this host response is the non-specific systemic inflammatory response. There is now a body of work examining the relationship between the systemic inflammatory response and cancer specific survival. Indeed, there is evidence that the systemic inflammatory response, as evidenced by an elevated C-reactive protein, predicts overall and cancer specific survival independent of tumour stage in a number of solid tumours including colorectal cancer.
The aim of this thesis was to investigate the following in patients undergoing potentially curative surgery for colorectal cancer:
1. To establish the prognostic value of the pre-operative compared with the post-operative systemic inflammatory response in patients undergoing potentially curative surgery for colorectal cancer.
2. To examine the pre-operative inflammatory response in patients undergoing potentially curative surgery for colorectal cancer.
3. To examine the utility of the systemic inflammatory response as a guide to treatment in patient undergoing potentially curative surgery for colorectal cancer.
Chapter 3 examines the relationship between the systemic inflammatory response in the preoperative period and the immediate post operative period. This chapter confirmed that an elevated C-reactive protein concentration, prior to but not immediately after surgery, was associated with poor cancer specific survival in patients undergoing curative open resection for colorectal cancer. This might suggest that approaches that focus on reducing the magnitude of the immediate post-operative systemic inflammatory response are unlikely to improve long term outcomes.
Chapter 4 examines the relationship between the tumour size and the systemic inflammatory response. This chapter shows that the maximal tumour diameter is associated with an elevated pre-operative C-reactive protein concentration but not survival in patients with primary operable colorectal cancer. This would suggest that the direct relationship between CRP and tumour diameter may be due to a compromised immune response promoting tumour growth.
Chapter 5 examines how the patients presented for their surgery. The results of this study suggest that as well as being prognostic in patients undergoing elective surgery C-reactive protein and the modified Glasgow prognostic score (mGPS) are prognostic in patients who present as an emergency which is the first time this has been shown.
Chapter 6 examines the relationship between the systemic inflammatory response, interleukin-6 and 10 and lymphocyte subpopulations in patients with colorectal cancer. The results of this study suggest that the presence of a systemic inflammatory response is associated with upregulation of immunomodulatory cytokines but not with down regulation of lymphocyte derived immune status.
Chapter 7 examines the relationship between the systemic inflammatory response and outcome in those patients receiving post-operative adjuvant chemotherapy. This shows that the presence of a systemic inflammatory response appears to be an independent predictor of poor outcome in patients receiving adjuvant 5FU-based chemotherapy following potentially curative resection for colorectal cancer.
Chapter 8 is a pilot study examining the relationship between node negative colon cancer patients and the systemic inflammatory response. This chapter suggests that an elevated C-Reactive protein might predict cancer specific survival, independent of recommended pathological criteria, in patients undergoing resection for node negative colon cancer. However this does need a further, much larger study to confirm this trend.
Taken together, the studies in the present thesis would indicate that an elevated pre-operative systemic inflammatory response is a prognostic factor independent of stage of disease.
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