Persistent systemic inflammatory response after stent insertionin patients with malignant bile duct obstruction

Background—Surgery in patients with malignantbile duct obstruction is associated with high postoperative morbidityand mortality. Tumour necrosis factor α (TNF-α) plays a key role inthe pathogenesis of these complications.
Aims—To determine the effect of biliary drainageon plasma concentrations of TNF-α, its soluble circulating receptors(sTNFr), and other proinflammatory cytokines.
Methods—Plasma concentrations of TNF-α,sTNFr-P75, interleukin 6 (IL-6), and IL-1α were measured in 25 patients with malignant bile duct obstruction before and afterendoscopic stent insertion.
Results—Mean serum bilirubin was 157 µmol/lbefore stent insertion and 35.2 µmol/l one week post stent insertion.There was complete relief of jaundice in 77% of patients by fourweeks. Plasma concentrations of TNF-α and IL-1α were below thedetection limit of the assays in all samples. Median plasma sTNFr-P75in the cancer patients was 960 ng/l (range 400-6600) before stent insertion and remained unchanged at one and four weeks after stenting. Plasma sTNFr-P75 in cancer patients was significantly higher(p<0.01) than in healthy controls (250 (200-650) ng/l).Before stent insertion, plasma IL-6 concentrations were detectable(above 5 ng/l) in 17(68%) patients. After relief of biliaryobstruction IL-6 levels fell from a prestent median of 13.2 to lessthan 5 ng/l at one week after stent insertion. Plasma concentrations ofIL-6 were undetectable in 76% of patients at this time.
Conclusion—Activation of the TNF/sTNFr complex isunchanged after biliary drainage in patients with malignant bile ductobstruction. This may explain why preoperative drainage does notinfluence the high morbidity and mortality associated with surgery inthese patients.

Keywords:jaundice; tumour necrosis factor α; biliarydrainage; pancreatic cancer