Beta-catenin plays important roles in liver physiology and hepatocarcinogenesis. While studying the role of b-catenin in diet-induced steatohepatitis, we recently found that liverspecific b-catenin knockout (KO) mice exhibit intrahepatic cholestasis. This study was undertaken to further characterize the role of b-catenin in biliary physiology. KO mice and wild-type (WT) littermates were fed standard chow or a diet supplemented with 0.5% cholic acid for 2 weeks. Chow-fed KO mice had higher serum and hepatic total bile acid levels and lower bile flow rate than WT mice. Expression levels of bile acid biosynthetic genes were lower and levels of major bile acid exporters were similar, which therefore could not explain the KO phenotype. Despite loss of the tight junction protein claudin-2, KO mice had preserved functional integrity of tight junctions. KO mice had bile canalicular morphologic abnormalities as evidenced by staining for F-actin and zona occludens 1. Electron microscopy revealed dilated and tortuous bile canaliculi in KO livers along with decreased canalicular and sinusoidal microvilli. KO mice on a cholic acid diet had higher hepatic and serum bile acid levels, bile ductular reaction, increased pericellular fibrosis, and dilated, misshapen bile canaliculi. Compensatory changes in expression levels of several bile acid transporters and regulatory genes were found in KO livers. Conclusion: Liver-specific loss of b-catenin leads to defective bile canalicular morphology, bile secretory defect, and intrahepatic cholestasis. Thus, our results establish a critical role for b-catenin in biliary physiology. (HEPATOLOGY 2010;52:1410-1419 B eta-catenin, the primary effector of the canonical Wnt signaling pathway, plays critical roles in hepatocarcinogenesis and liver development. [1][2][3][4][5][6] However, its role in adult liver physiology is not well understood. Cytoplasmic levels and localization of bcatenin are tightly regulated (reviewed in MacDonald et al. 7 ). In the absence of Wnt signaling, b-catenin is bound in the cytoplasm by a multiprotein complex. Phosphorylation via the action of glycogen synthase kinase 3b and casein kinase 1 targets b-catenin for proteasomal degradation. In the presence of Wnt ligands, bcatenin remains unphosphorylated, translocates to the nucleus, and activates transcription of its target genes by binding to T cell factor/lymphoid-enhancing factor family of transcriptional activators. Through its association with E-cadherin at the cell membrane, where it links cadherins to the actin cytoskeleton, b-catenin also plays an important role in the formation of adherens junctions (reviewed in Hartsock and Nelson 8 ).We recently showed that liver-specific b-catenin knockout (KO) mice have increased susceptibility to developing

In neurosurgery and ear, nose and throat surgery the application of computerised navigation systems for guiding operations has been expanding rapidly. However, suitable models to train surgeons in using navigation systems are not yet available. We have developed a technique using an industrial, rapid prototyping process from which accurate spatial models of the cranium, its contents and pathology can be reproduced for teaching. We were able to register, validate and navigate using these models with common available navigation systems such as the Medtronic StealthStation S7®.

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Postoperative complications from gastrointestinal surgery can be associated with significant morbidity, and mortality especially if repeat surgery is needed to address these complications. There are wide array of endoscopic interventions and tools available for management of these complications using minimally invasive methods thus decreasing length of hospitalization, morbidity and leading to better patient outcomes. With the advent new tools like Overstitch device, Over the Scope Clip, fibrin glue, etc., these complications can be managed successfully with minimal morbidity. We provide an indepth discussion about available endoscopic options and their application in various scenarios in our article. Endoscopist should be familiar with these complications and endoscopic tools to promote use of these tools and techniques to achieve successful management of these complex conditions.

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