Urinary Elimination of Coproporphyrins Is Dependent on ABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III)). Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III) ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III) ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (P = .04) than those carrying the C allele. This higher UCP I/(I + III) ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III) ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient

LES TUMEURS PSEUDO-PAPILLAIRES ET SOLIDES DU PANCREAS

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mo1806 Natural History of Perianal Crohn's Disease: Long-Term Follow-Up on a Population-Based Cohort

International audienceno abstrac

Impact of age over 75 years on outcomes after pancreaticoduodenectomy.

International audienceBACKGROUND: The risks associated with pancreaticoduodenectomy (PD) in elderly patients continue to be debated. The aim of our study was to assess the incidence of death and postoperative complications following PD and identify the risk factors in patients >75 y. STUDY DESIGN: All patients who underwent PD between January 2000 and September 2009 were analyzed retrospectively. Patients were divided into two groups according to age (Group 1: patients aged 75 y proved to be predictive factors for mortality (OR 11.04, IC95% [2.57; 47.49], P = 0.001). When compared with Group 1, Group 2 was associated with increased postoperative deaths (24.4% versus 3.66%, P < 0.001) and pancreatic fistulas (26.8% versus 13.2%, P = 0.041), in particular, Grade C fistulas (14.6% versus 4.4%, P = 0.023). In multivariate analysis, only PH proved to be an independent predictive factor for mortality (OR 12.9, IC95% [1.07; 155.5], P = 0.04). CONCLUSIONS: PD in elderly patients aged over 75 y appears to be associated with an increased risk of postoperative death and pancreatic fistula. No single preoperative factor made it possible to predict this risk