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Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography.

ABSTRACT: This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during the recovery phase. Monocyte cytokine responses to LPS, DC subsets and co-stimulatory molecule expression were compared with controls. Duodenal morphology and occludin expression were also assessed. Monocytes obtained before ERCP from jaundiced patients demonstrated reduced cytokine responses to endotoxin compared with controls (IL-1?: 2678 compared with 4631 pg/ml, P=0.04 and IL-6: 3442 compared with 6157 pg/ml, P=0.002). Monocytes from patients with malignancy had poorer responses to endotoxin than from those with benign OJ (IL-1?: 2025 compared with 3332 pg/ml, P=0.001). After ERCP, the secretion of inflammatory cytokines by monocytes obtained from jaundiced patients increased (IL-1?: 2150 compared with 2520 pg/ml, P=0.03 and IL-6: 2488 compared with 3250 pg/ml, P=0.01). Occludin expression (85 compared with 95%, P=0.004) and mean duodenal villus height (334 compared with 404 ?m, P=0.03) were lower in jaundiced patients. Before biliary drainage, patients with OJ had a higher percentage of myeloid dendritic cells (mDCs) and greater mDC expression of CD40 (P=0.04) and CD86 (P=0.04). Monocytes from patients with OJ had lower proinflammatory cytokine secretion in response to LPS, an effect reversed following biliary drainage.

SUBMITTER: Chowdhury AH

PROVIDER: S-EPMC4947925 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography.

Chowdhury Abeed H AH Camara Miguel M Martinez-Pomares Luisa L Zaitoun Abed M AM Eremin Oleg O Aithal Guruprasad P GP Lobo Dileep N DN

Clinical science (London, England : 1979) 20160601 17

This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood ...[more]

PMID: 27252406

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Project description:Background & aimsCholecystectomy (CCY) after an episode of choledocholithiasis requiring endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction reduces recurrent biliary events compared to expectant management. We studied practice patterns for performance of CCY after ERCP for choledocholithiasis using data from 3 large states and evaluated the effects of delaying CCY.MethodsWe conducted a retrospective cohort study using the ambulatory surgery, inpatient, and emergency department databases from the states of California (years 2009-2011), New York (2011-2013), and Florida (2012-2014). We collected data from 4516 patients hospitalized with choledocholithiasis who underwent ERCP. We compared outcomes of patients who underwent CCY at index admission (early CCY), elective CCY within 60 days of discharge (delayed CCY), or did not undergo CCY (no CCY), calculating rate of recurrent biliary events (defined as an emergency department visit or unplanned hospitalization due to symptomatic cholelithiasis, cholecystitis, choledocholithiasis, cholangitis, or biliary pancreatitis), mortality, and cost by CCY cohort. We also evaluated risk factors for not undergoing CCY. The primary outcome measure was the rate of recurrent biliary events in the 365 days after discharge from index admission.ResultsOf the patients who underwent ERCP for choledocholithiasis, 41.2% underwent early CCY, 10.9% underwent delayed CCY, and 48.0% underwent no CCY. Early CCY reduced relative risk of recurrent biliary events within 60 days by 92%, compared with delayed or no CCY (P < .001). After 60 days following discharge from index admission, patients with early CCY had an 87% lower risk of recurrent biliary events than patients with no CCY (P < .001) and patients with delayed CCY had an 88% lower risk of recurrent biliary events than patients with no CCY (P < .001). A strategy of delayed CCY performed on an outpatient basis was least costly. Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.ConclusionsIn a retrospective analysis of >4500 patients hospitalized with choledocholithiasis, we found that CCY was not performed after ERCP for almost half of the cases. Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of recurrent biliary event while waiting for a delayed CCY compared with patients who underwent early CCY. Delayed CCY is a cost-effective strategy that must be balanced against the risk of loss to follow-up, particularly among patients who are ethnic minorities or have little or no health insurance.

Dataset Information

Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography.

Publications

Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography.

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