PERSISTENT SYSTEMIC INFLAMMATORY RESPONSE AFTER STENT INSERTION IN PATIENTS WITH MALIGNANT BILE-DUCT OBSTRUCTION

Background-Surgery in patients with malignant bile duct obstruction is associated with high postoperative morbidity and mortality. Tumour ne crosis factor a (TNF-alpha) plays a key role in the pathogenesis of th ese complications. Aims-To determine the effect of biliary drainage on plasma concentrations of TNF-alpha, its soluble circulating receptors (sTNFr), and other proinflammatory cytokines. Methods-Plasma concentr ations of TNF-alpha, sTNFr-P75, interleukin 6 (IL-6), and IL-1 alpha w ere measured in 25 patients with malignant bile duct obstruction befor e and after endoscopic stent insertion. Results-Mean serum bilirubin w as 157 mu mol/l before stent insertion and 35.2 mu mol/l one week post stent insertion. There was complete relief of jaundice in 77% of pati ents by four weeks. Plasma concentrations of TNF-alpha and IL-1 alpha were below the detection limit of the assays in all samples. Median pl asma sTNFr-P75 in the cancer patients was 960 ng/l (range 400-6600) be fore stent insertion and remained unchanged at one and four weeks afte r stenting. Plasma sTNFr-P75 in cancer patients was significantly high er (p<0.01) than in healthy controls (250 (200-650) ng/l). Before sten t insertion, plasma IL-6 concentrations were detectable (above 5 ng/l) in 17 (68%) patients. After relief of biliary obstruction IL-6 levels fell from a prestent median of 13.2 to less than 5 ng/l at one week a fter stent insertion. Plasma concentrations of IL-6 were undetectable in 76% of patients at this time. Conclusion-Activation of the TNF/sTNF r complex is unchanged after biliary drainage in patients with maligna nt bile duct obstruction. This may explain why preoperative drainage d oes not influence the high morbidity and mortality associated with sur gery in these patients.