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Title: An investigation of the relationship between the systemic and local inflammatory responses and survival in patients with primary operable colorectal cancer
Author: Canna, Khalid
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2007
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Colorectal cancer remains the second commonest cause of cancer death in Western Europe and North America. Overall survival is poor. Even in those patients who undergo potentially curative resection more than one third will die within 5 years. It has long been recognised that disease progression in cancer patients is not solely determined by the characteristics of the tumour but also by the host response. One aspect of the host response, which has recently generated interest, is the non-specific systemic inflammatory response, associated with primary operable colorectal cancer. There is evidence that the systemic inflammatory response (as evidenced by C-reactive protein) predicts recurrence, and overall and cancer specific survival, independent of stage, in patients who have undergone curative resection for colorectal cancer. Another aspect of the host response is tumour lymphocytic infiltration, there is increasing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumours. In patients with colorectal cancer, there is good evidence that, on simple staining of tumour sections, the presence of a pronounced lymphocytic infiltration within the tumour is associated with improved survival. In the first research chapter of this thesis we assessed the value of combining Dukes stage and C-reactive protein to form a new prognostic score in patients undergoing apparently curative resection for colorectal cancer. The results suggest that this simple prognostic score, which reflects both the contribution of the tumour and the host response, appears to differentiate between low risk and high risk Dukes B and C tumours and may therefore be useful in selecting appropriate patients for adjuvant chemotherapy. In the second research chapter we examined the relationships between the systemic inflammatory response, tumour lymphocytic infiltration, tumour proliferative activity and cancer survival in patients with Dukes stage B and C colorectal cancer undergoing potentially curative resection. A poor tumour CD4+ and CD8+ T-lymphocyte infiltrate, an increased Ki-67 labelling index were associated with poorer cancer specific survival. Poor tumour CD4+ T-lymphocyte infiltrates, increased Ki-67 labelling index and increased tumour diameter were associated with an elevated circulating C-reactive protein. Multivariate survival analysis showed that both local (tumour CD8+ T-lymphocyte infiltrate) and systemic (C-reactive protein) inflammatory responses, but not tumour proliferation (Ki-67 labelling index), were significantly associated with cancer specific survival. That tumour proliferation is a relatively poor predictor of survival compared with the systemic inflammatory responses, possibly relates to the fact that tumour dissemination, rather than tumour proliferation, is the primary determinant of survival in patients with colorectal cancer. These results would suggest that local and systemic inflammatory responses are linked to tumour proliferation in patients with colorectal cancer and these responses are in turn linked to cancer specific survival, independent of tumour stage. This means that, both local and systemic inflammatory responses are intrinsically linked to cancer specific survival in patients who have undergone apparently curative surgery for colorectal cancer. Furthermore, these results would suggest that the presence of a systemic inflammatory response reflects increased tumour bulk and compromised cell mediated immunity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available