Surgical Complications and Long-Term Outcome of Different Biliary Reconstructions in Liver Transplantation for Primary Sclerosing Cholangitis—Choledochoduodenostomy versus Choledochojejunostomy

Choledochojejunostomy (CJS) is commonly used for biliary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC). We alternatively performed choledochoduodenostomy (CDS) and side-to-side choledochodocholedochstomy in a large cohort of patients. Fifty-one patients with PSC, transplanted between 1988 and 2000, were analyzed retrospectively. Biliary reconstruction was CDS in 25 (49%), CJS in 20 (39%) and CC in 6 transplantations (12%). Biliary leaks occurred in the early follow-up (< or =41 days) only in CDS patients (20%). However, in the late follow-up (>4 months), stricturing of anastomosis was found once in CDS (4%) and CJS (5%). Later (>9 months), intrahepatic bile duct strictures were diagnosed in four CDS (16%), one CJS (5%) and one CC (17%) patient(s). In 48% of CDS (12/25), 60% of CJS (12/20) and 17% of CC (1/6) at least one incidence of cholangitis was observed. Overall, biliary complication rates were significantly higher in CDS (40%) than CJS (10%) and CC (17%); of those none in CC and 12% in CDS were anastomosis-related. Graft/patient survival showed no significant differences among groups. Based on our results we consider CJS the standard method for biliary reconstruction in PSC; however, in selected cases where CJS is difficult to accomplish because of previous surgery or for retransplantation, CDS may present an alternative technique.     

Analysis of insulin signaling pathways through comparative genomics. Mapping mechanisms for insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus.

The precise molecular cause of insulin resistance has not yet been elucidated. Resistance to the normal action of insulin contributes to the pathogenesis of a number of common human disorders, including type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus, hypertension, and the Metabolic Syndrome X, thus constituting a major public health problem. A disease program aimed at combating this disorder should focus on the identification of targets for therapeutic intervention which may overcome insulin resistance and hence the associated metabolic consequences characteristic of the Metabolic Syndrome. Although the primary defect in the pathogenesis of type 2 diabetes is unknown, genetic and environmental factors are likely to contribute to the manifestation of this progressive metabolic disorder, which is usually not clinically apparent until mid-life. Defects at the level of glucose uptake/phosphorylation characterize insulin resistance in skeletal muscle of type 2 diabetic patients. Identification of putative components of the insulin receptor-signaling pathway may offer insights into mechanisms involved in insulin resistance. Enhanced flux of free fatty acids due to impaired lipid metabolism may contribute to impaired insulin secretion and peripheral insulin resistance. Genes regulating lipolysis are prime candidates for susceptibility towards the metabolic syndrome. Here we describe pathways constituting complex interactions that control glucose homeostasis. We will be considering (1) regulation of glucose uptake by the insulin receptor signaling pathway, and (2) control of adipogenesis and insulin sensitivity by the sterol response element binding protein (SREBP) pathway.