Systemic inflammatory markers and outcome in patients with locally advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction.

BACKGROUND: Raised levels of systemic inflammatory markers are associated with poor survival in patients with cancer. The aim of this study was to assess the prognostic value of markers of systemic inflammation in patients with adenocarcinoma of the oesophagus or gastro-oesophageal junction. METHODS: Data from a consecutive series of patients undergoing transthoracic oesophagectomy following neoadjuvant therapy at a single centre were analysed. Fibrinogen, albumin, C-reactive protein, leucocyte differential and platelet counts were measured before surgery. The upper quartile (75th percentile) was used as a cut-off for dichotomization. Multivariable regression analysis was performed to identify independent prognostic factors. RESULTS: A series of 199 patients underwent transthoracic oesophagectomy following neoadjuvant therapy. Univariable analysis indicated that reduced median survival was associated with a raised platelet : lymphocyte ratio (158 or above; 25.6 versus 44·4 months for patients with a normal ratio, P = 0·038) and increased fibrinogen levels (4·9 g/l or above; 22·8 versus 59·9 months for those with a normal level, P = 0·005). On multivariable analysis a combination of one or more markers of systemic inflammation was associated with poorer overall survival (hazard ratio 2·12, 95 per cent c.i. 1·20 to 3·74; P = 0·010). CONCLUSION: Preoperative markers of systemic inflammation predict poor outcome in patients undergoing curative treatment for locally advanced oesophageal and gastro-oesophageal adenocarcinoma.

Characterisation of fractalkine/CX3CL1 and fractalkine receptor (CX3CR1) expression in abdominal aortic aneurysm disease.

OBJECTIVES: Fractalkine (CX3CL1) promotes adhesion and extravasation of leucocytes through interactions with fractalkine receptor (CX3CR1) expressed on CD56+/CD16+ NK cells and CD8+ T cells. The current study aims to test the hypothesis the CX3CL1-CX3CR1 interaction contributes to the inflammatory infiltrate in AAA tissue. DESIGN AND METHODS: Immunohistochemistry (IHC) was used to define expression of CX3CR1 in AAA tissue. Multi-parametric flow cytometry (FC) was used to determine CX3CR1 expression on T-cells (CD3+) and NK cells (CD56+) from AAA tissue and peripheral blood of AAA patients and healthy controls. Regulation of CX3CL1 expression by vascular endothelial (vEC) and smooth muscle cells (vSMC) was examined in vitro using primary cell cultures. RESULTS: CX3CR1+ cells were detected in 19/28 AAA tissue samples and predominately localised in the adventitia. PBMCs from patients with AAA demonstrated higher percentages of CX3CR1+ NK cells (60.0-88.6%) and T cells (7.5-39.4%) compared with healthy controls. Furthermore, the frequency of CX3CR1+ NK cells (91%) and T cells (94%) in inflammatory AAA tissue were higher than in atherosclerotic AAA tissue. The pro-inflammatory cytokine TNFalpha increased expression of fractalkine by vSMC and vEC. CONCLUSION: CX3CL1+ and CX3CR1+ cells are present in AAA disease and their interaction may contribute to the recruitment of inflammatory cells seen in AAA tissue.

Intra-operative Doppler flow measurement do not predict 'at-risk' status of infrainguinal bypass grafts.

AIMS: Patients undergoing infrainguinal arterial reconstruction using vein conduits, frequently undergo intra-operative Doppler flow measurements to determine technical adequacy. The aim of this study was to determine the proportion of vein grafts with normal intra-operative haemodynamic parameters that were subsequently discovered to be 'at risk' on post-operative duplex surveillance scanning. METHODS: We prospectively collected data on 82, primary infrainguinal vein bypass grafts. Post papaverine graft flow and peripheral resistance were measured using the Scimed Opdop intra-operative Doppler machine. All grafts were determined to be technically adequate on the basis of measured peripheral resistance units (mPRU) being < or =1. At 1 week, a post-operative duplex surveillance scan was performed. At risk status was determined and compared to the intra-operative Doppler flow measurement. Statistical analysis was performed using the Mann-Whitney U-test. RESULTS: The post-operative duplex scan demonstrated that 53 (65%) of the 82 vein bypass grafts were diagnosed as being 'not at risk'; and 29 (35%) were regarded as at risk. When the groups were compared, there was no significant difference in intra-operative haemodynamic parameters between those not at risk and those at risk (P=0.19, Mann-Whitney U-test). The 1 month primary patency rate was 79% with a secondary patency rate of 100%. CONCLUSION: Despite normal intra-operative Doppler flow measurements, 35% of vein grafts were regarded as being at risk at the 1 week post-operative duplex surveillance scan. No single value may be universally applicable for identifying at risk grafts intraoperatively. Indeed, graft failure appears to be a multifactorial process.