The relationship between tumour necrosis, tumour proliferation, local and systemic inflammation, microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma.

BACKGROUND: There is increasing evidence that the local and systemic inflammatory responses are associated with survival in oesophageal cancer. The aim of this study was to examine the relationship between tumour necrosis, tumour proliferation, local and systemic inflammation and microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma. METHODS: The interrelationship between tumour necrosis, tumour proliferation, local inflammatory response (Klintrup-Makinen criteria, intra-tumoural CD8+ lymphocyte and macrophage infiltration), systemic inflammatory response (modified Glasgow Prognostic score (mGPS)), and microvessel density was examined in 121 patients undergoing potentially curative resection for oesophageal adenocarcinoma (including type I and II tumours of the gastro-oesophageal junction). RESULTS: Tumour necrosis was not significantly associated with any tumour measure other than the degree of differentiation. On multivariate analysis, only age (HR 1.93, 95% CI 1.23-3.04, P=0.004), mGPS (HR 2.91, 95% CI 1.51-5.62, P=0.001), positive to total lymph node ratio (HR 2.38, 95% CI 1.60-3.52, P<0.001) and macrophage infiltration (HR 1.49, 95% CI 1.02-2.18, P=0.041) were independently associated with cancer-specific survival in oesophageal adenocarcinoma. Intra-tumoural macrophages were associated with tumour proliferation (P<0.001) and CD8+ lymphocytes infiltration (P<0.01). CONCLUSION: The results of this study suggest that tumour necrosis does not link local and systemic inflammatory responses and is not significantly associated with survival. In contrast, tumour macrophage infiltration appears to have a central role in the proliferative activity and the coordination of the inflammatory cell infiltrate and is independently associated with poorer survival in patients with oesophageal adenocarcinoma.

An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of tumours. The aim of the present study was to examine the relationship between clinico-pathological status, preoperative C-reactive protein concentration and cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. One hundred and twenty patients attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow, who were selected for potentially curative surgery, were included in the study. Laboratory measurements of haemoglobin, white cell, lymphocyte and platelet counts, albumin and C-reactive protein were carried out at the time of diagnosis. All patients underwent en-bloc resection with lymphadenectomy and survived at least 30 days following surgery. On multivariate analysis, only the positive to total lymph node ratio (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.44-2.84, P<0.001) and preoperative C-reactive protein concentration (HR 3.53, 95% CI 1.88-6.64, P<0.001) were independent predictors of cancer-specific survival. The patient group with no evidence of a preoperative systemic inflammatory response (C-reactive protein < or =10 mg l(-1)) had a median survival of 79 months compared with 19 months in the elevated systemic inflammatory response group (P<0.001). The results of the present study indicate that in patients selected to undergo potentially curative resection for gastro-oesophageal cancer, the presence of an elevated preoperative C-reactive protein concentration is an independent predictor of poor cancer-specific survival.

Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of the present study was to examine whether an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was associated with survival, in patients with inoperable gastro-oesophageal cancer. Patients diagnosed with inoperable gastro-oesophageal carcinoma and who had measurement of albumin and C-reactive protein concentrations, at the time of diagnosis, were studied (n=258). Clinical information was obtained from a gastro-oesophageal cancer database and analysis of the case notes. Patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. On multivariate survival analysis, age (hazard ratio (HR) 1.22, 95% CI 1.02-1.46, P<0.05), stage (HR 1.55, 95% CI 1.30-1.83, P<0.001), the GPS (HR 1.51, 95% CI 1.22-1.86, P<0.001) and treatment (HR 2.53, 95% CI 1.80-3.56, P<0.001) were significant independent predictors of cancer survival. A 12-month cancer-specific survival in patients with stage I/II disease receiving active treatment was 67 and 60% for a GPS of 0 and 1, respectively. For stage III/IV disease, 12 months cancer-specific survival was 57, 25 and 12% for a GPS of 0, 1 and 2, respectively. In the present study, the GPS predicted cancer-specific survival, independent of stage and treatment received, in patients with inoperable gastro-oesophageal cancer. Moreover, the GPS may be used in combination with conventional staging techniques to improve the prediction of survival in patients with inoperable gastro-oesophageal cancer.