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

Abstract

Background: Surgery in patients with malignant bile duct obstruction is associated with high postoperative morbidity and mortality. Tumour necrosis factor alpha (TNF-alpha) plays a key role in the pathogenesis of these 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 concentrations of TNF-alpha, sTNFr-P75, interleukin 6 (IL-6), and IL-1 alpha were measured in 25 patients with malignant bile duct obstruction before and after endoscopic stent insertion.

Results: Mean serum bilirubin was 157 mumol/l before stent insertion and 35.2 mumol/l one week post stent insertion. There was complete relief of jaundice in 77% of patients by four weeks. Plasma concentrations of TNF-alpha and IL-1 alpha were below the detection limit of the assays in all samples. Median plasma sTNFr-P75 in 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 biliary obstruction IL-6 levels fell from a prestent median of 13.2 to less than 5 ng/l at one week after stent insertion. Plasma concentrations of IL-6 were undetectable in 76% of patients at this time.

Conclusion: Activation of the TNF/sTNFr complex is unchanged after biliary drainage in patients with malignant bile duct obstruction. This may explain why preoperative drainage does not influence the high morbidity and mortality associated with surgery in these patients.

Figure 1

Effect of stent insertion on plasma sTNFr concentrations. Patients who had blood taken at each assessment are represented by open circles; patients who had only a single sample taken before stent insertion are represented by closed circles; and patients who had blood samples before stent insertion and at the one week assessment are represented by closed triangles.

Figure 2

Effect of stent insertion on plasma IL-6 concentrations. Patients who had blood taken at each assessment are represented by open circles; patients who had only a single sample taken before stent insertion are represented by closed circles; and patients who had blood samples before stent insertion and at the one week assessment are represented by closed triangles.