Using taurolidine to attenuate the surgically-induced endotoxaemia and the subsequent inflammatory response in patients with primary non-metastatic colon cancer

INTERVENTION: Amended as of 25/11/2008: From induction of anaesthesia, patients will be administered 250 ml of 2% taurolidine or normal saline four times daily intravenously for four days. Initial information at time of registration: From induction of anaesthesia, patients will be administered 250 ml of 2% taurolidine or the same volume of normal saline intravenously three times a day for three days. CONDITION: Colon cancer ; Cancer ; Colon cancer PRIMARY OUTCOME: Amended as of 25/11/2008: ; 1. Percent change in taurolidine as compared to control group in mean day 1 IL‐6 relative to mean baseline IL‐6. Mean day‐1 lL‐6 defined as mean of available values from (+3, +6, +24 hours post‐induction). Mean baseline defined as mean of available pre‐op IL‐6 levels.; ; Initial information at time of registration:; The following will be measured twice pre‐operatively and at 4 hours, 24 hours, 48 hours, 3 days and 5 days post‐operatively: ; 1. Pro‐inflammatory cytokine levels (Interleukin‐6 [IL‐6], Interleukin‐1‐beta [IL‐1beta], Tumour Necrosis Factor‐alpha [TNF‐alpha], Vascular Endothelial Growth Factor [VEGF]); 2. Anti‐inflammatory cytokine levels (Interleukin‐1‐Receptor Antagonist [IL‐1RA], Interleukin‐10 [IL‐10]); 3. C‐Reactive Protein (CRP); 4. Endotoxin/Lipopolysaccharides (LPS) level; ; The following will be measured twice pre‐operatively and at 24 hours and 5 days post‐operatively: ; 5. Natural Killer (NK) Cell and Cytotoxic T‐Lymphocyte (CTL) cytotoxic activity ; 6. Neutrophil/monocyte receptor expression (CD11b, CD14, Toll‐Like Receptor‐4 [TLR4]) INCLUSION CRITERIA: Initial information at time of registration: 1. Patients of both genders who are 18 to 75 years of age 2. Patients with a solitary, non‐metastatic extraperitoneal colonic tumour that already has been histologically confirmed 3. Patient has given full written informed consent 4. Elective setting Added as of 25/11/2008: 5. Negative pregnancy test in women of childbearing age SECONDARY OUTCOME: Amended as of 25/11/2008: ; 1. Laboratory endpoints:; 1.1. Percent change in taurolidine as compared to control group in mean day 2 and day 3 IL‐6 relative to mean baseline Il‐6. Mean day 2/day 3 defined as available IL‐6 from 48 and 72 hours post‐induction.; 1.2. Percent change in taurolidine as compared to control group in mean available day 1 to day 3 versus mean baseline IL‐10, endotoxin level, and C‐reactive protein (CRP); 2. Clinical endpoints:; 2.1. Comparison of Taurolidine with control group with regard to occurrence and severity of post‐operative infections over 10 days post‐operatively or until hospital discharge; 2.2. Time to bowel functional recovery defined as time to first flatus or return of bowel sounds; 2.3. Comparison of taurolidine with control group with regard to analgesic requirements (using ordinal ranking scale) and self assessed pain control using visual analogue scale at 24 and 72 hours post‐induction; 2.4. Percent tumour recurrence at 12 months following operation in taurolidine as compared to control group; ; Tertiary outcomes:; Percent change in taurolidine compared to control group in mean available day 1 ‐ day 3 versus mean baseline:; 1. Inflammatory cytokine levels (tumour necrosis factor alpha [TNF‐a], vascular endothelial growth factor [VEGF], interleukin‐1 receptor antagonist [IL‐1ra], IL‐1beta); 2. Natural Killer (NK) cell and cytotoxic T‐lymphocyte (CTL) cytotoxic activity ; 3. Neutrophil/monocyte receptor expression (cluster of differentiation‐14 [CD14], cluster of differentiation‐11b [CD11b], toll‐like receptor‐4 [TLR4]) ; ; Safety endpoints:; Comparison of routine haematological and biochemical data at day 1, 2, 3, 5, hospital discharge, and 1 month. Clinical status at hospital discharge, 1, 6 and 12 months.; ; Initial information at time of registration:; 1. Post‐operative pain scores (Visual Analogue Scales [VAS]); 2. Post‐operative GI function (time to first flatus and to bowel sounds); 3. Post‐operative respiratory function/infections (clinical); 4. Clinical wound infection rate; 5. Length of hospital stay; 6. Survival at 1 and 2 years ; 7. Time to tumour recurrence (radiological)