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Title: An investigation of the relationship between patient physiology, inflammatory response and outcome in patients with oesophageal and gastric cancer
Author: Dutta, Sumanta
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2013
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Abstract:
Upper gastrointestinal tract cancers originating from oesophagus, oesophago-gastric junction or stomach constitute a major health problem around the world as well as in UK. Chapter 1 of the thesis describes the incidence, mortality, aetiology, staging, treatment and outcome of patients with oesophageal and gastric cancer. Each year approximately 8,000 people are diagnosed with oesophageal cancer and a similar number of people diagnosed with gastric cancer in UK. Early detection and surgery confers the greatest chance of long-term cure in oesophageal and gastric cancer. However, upper GI cancer surgery is associated with considerable morbidity and mortality. Postoperative mortality following gastro-oesophageal cancer resection is significant and has been reported as varying from 1%–23%. Therefore, preoperative surgical risk assessment is a vital part of modern surgical practice. Pathological TNM staging by American Joint Committee on Cancer (AJCC) is an established factor in predicting long term survival following resection of oesophageal and gastric cancer. However, it is increasingly recognised that, not only the intrinsic properties of tumour cells determine tumour spread but also the host inflammatory response has a vital role. Indeed, the systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, prior to surgery, has previously been shown to have independent prognostic value in patients with resectable gastro-oesophageal cancer. The overall aim of the thesis was to examine the inter-relationships between patient physiology, local and systemic inflammatory response and outcome (both short and long term), in patients undergoing resection for oesophageal and gastric cancer. Chapter 2 compared the POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) and mGPS (modified Glasgow prognostic score) models in prediction of post-operative outcome, both short and long term, in 121 patients undergoing resection of oesophago-gastric cancer. The results in this chapter demonstrated that, the POSSUM physiological score was an independent predictor of post-operative complications. On the other hand, elevated systemic inflammatory response as evidenced by the mGPS and not, patient physiology or post-operative complications, was independently associated with poor cancer specific survival. Therefore, results of the present study suggested that, pre-operative host related factors were important in determining both short and long term outcome following potentially curative resection of oesophago-gastric cancer. Chapter 3 examined the value of serial daily post-operative markers of systemic inflammatory response such as white cell count, albumin and C-reactive protein concentrations in the prediction of post-operative infectious complications in 136 patients following resection of oesophago-gastric cancer. The results showed that the magnitude of the systemic inflammatory response, in particular C reactive protein, following resection of oesophago-gastric cancer was associated with the development of post operative complications, in particular surgical site infections and anastomotic leak. Furthermore, C reactive protein threshold of 180mg/l on post operative days 3 and 4 was shown to predict surgical site infection and anastomotic leak with good and very good diagnostic accuracy respectively. Chapter 4 compared the prognostic value of selected markers of systemic inflammatory response such as white cell count, neutrophil count, lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet- lymphocyte ratio (PLR) and mGPS in 112 patients undergoing potentially curative resection of oesophageal cancer. The result demonstrated that, only mGPS was significantly associated with cancer specific survival and had prognostic value independent of pathological TNM stage. Therefore, an acute-phase protein-based prognostic score, the mGPS, was established to have the superior predictive value, compared to cellular components of the systemic inflammatory response in predicting survival in oesophageal cancer. Chapter 5 compared the prognostic value of selected markers of systemic inflammatory response such as white cell count, neutrophil count, lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet- lymphocyte ratio (PLR) and mGPS in 120 patients undergoing potentially curative resection of gastric cancer. The result showed that, only mGPS was significantly associated with cancer specific survival and had prognostic value independent of pathological TNM stage. Therefore, an acute-phase protein-based prognostic score, the mGPS, was established to have the superior predictive value, compared to cellular components of the systemic inflammatory response in predicting survival in gastric cancer. Chapter 6 examined the relationship between tumour necrosis, tumour proliferation, local and systemic inflammatory response, microvessel density and survival in 98 patients undergoing potentially curative resection of oesophageal adenocarcinoma. The results suggested that, among the tissue based factors, tumour macrophage infiltration appeared to play a central role in the proliferative activity and coordination of the inflammatory cell infiltrate and was also independently associated with poor outcome in patients with oesophageal adenocarcinoma. There was no direct relationship between local and systemic inflammatory response, tumour necrosis and angiogenesis; suggesting that the mechanisms underlying the relationship between local and systemic inflammatory responses and cancer-specific survival are likely to be complex. Chapter 7 examined the relationship between tumour necrosis, tumour proliferation, local and systemic inflammation, microvessel density and survival in 104 patients undergoing potentially curative resection of gastric cancer. The results suggested that, local peritumoural inflammatory infiltrate and intra tumoural necrosis appeared to play a role in tumour proliferation and poor outcome in patients with gastric cancer. There was no direct relationship between local and systemic inflammatory responses, tumour necrosis and angiogenesis; suggesting that the mechanisms underlying the relationship between local and systemic inflammatory responses and cancer-specific survival are likely to be complex. In summary, preoperative patient’s physiological status (as measured by POSSUM model) has been shown to be a good predictor of short term outcome i.e. postoperative morbidity and mortality following resection of oesophago-gastric cancer. Moreover postoperative serial measurements of C-reactive protein have been shown to be a useful tool to predict infectious complications. An elevated systemic inflammatory response (as evidenced by the mGPS) preoperatively has been established to be a predictor of poor survival, independent of tumour stage in both oesophageal and gastric cancer. Therefore, these results suggest that measurement of the mGPS should be performed routinely as part of preoperative clinical staging, to improve stratification of patients and therefore enable clinicians to optimise the treatment of patients with oesophageal and gastric cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.586789  DOI: Not available
Keywords: RD Surgery
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