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Discover the most talked about and latest scientific content & concepts.

Concept: Bile duct

139

Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct. Most patients with CCA have an unresectable tumor at the time of diagnosis. In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries. A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection. Tests of serum, saliva and urine samples are also potentially diagnostic. The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas. The “liver fluke-cholangiocarcinoma” carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke’s antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke. A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas. Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas.

Concepts: Immune system, Digestive system, Liver, Hepatology, Bile duct, Gallbladder, Cholangiocarcinoma, Primary sclerosing cholangitis

136

We introduce a training porcine model for laparoscopic common bile duct (CBD) repair with T-tube insertion. The model could be the feasible training tool for a surgeon learning hepatobiliary surgery.

Concepts: Surgery, Bile duct, Common bile duct

29

Abstract Objective. Endoscopic sphincterotomy plus large-balloon dilatation (ESLBD) has an efficacy equal to or higher than that of endoscopic sphincterotomy alone for biliary lithiasis extractions. Our purpose was to evaluate the feasibility, efficacy and morbidity of large-balloon dilatation of the sphincter of Oddi after sphincterotomy or infundibulotomy for large or multiple common bile duct stones. Material and methods. Retrospective analysis. Results. A total of 64 ESLBD procedures were performed in 62 patients: 57 after sphincterotomy and 7 after infundibulotomy. The feasibility was 100%, and full clearance of the common bile duct was achieved in a single session without using mechanical lithotripsy in 95.3% of cases. Short-term complications were observed in 9 patients (14%). There were no perforations. The most frequent complication was delayed bleeding (7.8%). There was no significant difference of overall complications after sphincterotomy or after infundibulotomy (12.3% vs. 28.6%, p = 0.25). The incidence of acute pancreatitis was significantly higher after infundibulotomy than after sphincterotomy (28.6% vs. 0%, p = 0.01). Conclusions. ESLBD after endoscopic sphincterotomy or infundibulotomy is a simple, reproducible and effective technique, associated with a low morbidity rate and helps in avoiding mechanical lithotripsy in 95.3% of cases for the endoscopic extraction of large or multiple common bile duct stones.

Concepts: Digestive system, Bile, Bile duct, Endoscopic retrograde cholangiopancreatography, Common bile duct, Choledocholithiasis

28

Cholangiocytes, the cells lining bile ducts, are a heterogenous, highly dynamic population of epithelial cells. While these cells comprise a small fraction of the total cellular component of the liver, they perform the essential role of bile modification and transport of biliary and blood constituents. From a pathophysiological standpoint, cholangiocytes are the target of a diverse group of biliary disorders, collectively referred to as the cholangiopathies. To date, the cause of most cholangiopathies remains obscure. It is known, however, that cholangiocytes exist in an environment rich in potential mediators of cellular injury, express receptors that recognize potential injurious insults, and participate in portal tract repair processes following hepatic injury. As such, cholangiocytes may not be only a passive target, but are likely directly and actively involved in the pathogenesis of cholangiopathies. Here, we briefly summarize the characteristics of the reactive cholangiocyte and cholangiocyte responses to potentially injurious endogenous and exogenous molecules, and in addition, present emerging concepts in our understanding of the etiopathogenesis of several cholangiopathies.

Concepts: Digestive system, Epithelium, Liver, Tissues, Bile, Connective tissue, Bile duct, Gallbladder

28

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic, idiopathic liver disease characterized by fibro-obliterative inflammation of the hepatic bile ducts. In a clinically significant proportion of patients, PSC progresses to cirrhosis, end-stage liver disease, and in some cases, cholangiocarcinoma. Despite clinical trials of nearly 20 different pharmacotherapies over several decades, safe and effective medical therapy, albeit critically needed, remains to be established. PSC is pathogenically complex, with genetic, immune, enteric microbial, environmental and other factors being potentially involved and, thus, not surprisingly, it manifests as a clinically heterogeneous disease with a relatively unpredictable course. It is likely that this complexity and clinical heterogeneity are responsible for the negative results of clinical trials, but novel insights about and approaches to PSC may shift this trend. The authors herein provide a review of previously tested pharmacologic agents, discuss emerging fundamental concepts and present viewpoints regarding how identifying therapies for PSC may evolve over the next several years.

Concepts: Medicine, Cirrhosis, Liver, Therapy, Hepatology, Bilirubin, Bile duct, Primary sclerosing cholangitis

28

: In this review of the literature, we analyze the indications for preoperative drainage in jaundiced patients who are candidates for pancreaticoduodenectomy (PD) or major hepatectomy due to periampullary or proximal bile duct neoplasms.

Concepts: Digestive system, Liver, Hepatology, Bile, Pancreatic cancer, Bile duct, Cholangiocarcinoma, Gallstone

28

Patients with primary sclerosing cholangitis (PSC) are at increased risk of bacterial cholangitis due to biliary strictures and bile stasis. A subset of PSC patients suffer from repeated episodes of bacterial cholangitis, leading to frequent hospitalizations and impaired quality of life. Although PSC waitlist candidates with bacterial cholangitis frequently receive exception points, and/or are referred for living donor transplantation, the impact of bacterial cholangitis on waitlist mortality is unknown. We performed a retrospective cohort study of all adult PSC waitlist candidates listed for initial transplantation from February 27, 2002 to June 1, 2012 at the University of Pennsylvania and the University of Colorado-Denver. Over this period, 171 PSC patients were waitlisted for initial transplantation. Prior to waitlisting, 38.6% (66/171) of patients had a history of bacterial cholangitis, while 28.0% (44/157) of those with at least one MELD update experienced cholangitis on the waitlist. During follow-up, 30 (17.5%) patients were removed from the waitlist for death or clinical deterioration, with 46.7% (14/30) developing cholangiocarcinoma. Overall, 12/82 (14.6%) waitlist candidates who ever had an episode of cholangitis were removed for death or clinical deterioration, compared with 18/89 (20.2%) without cholangitis (P=0.34 comparing two groups). No patients were removed due to bacterial cholangitis. In multivariable competing risk models, a history of bacterial cholangitis was not associated with an increased risk of waitlist removal for death or clinical deterioration (subhazard ratio=0.67; 95% CI: 0.65-0.70, P<0.001). In summary, PSC waitlist transplant candidates with bacterial cholangitis do not have an increased risk of waitlist mortality. The data call into question the systematic granting of exception points or referral for living donor transplantation due to a perceived risk of increased waitlist mortality. © 2012 American Association for the Study of Liver Diseases.

Concepts: Cohort study, Actuarial science, Cirrhosis, Liver disease, Bile duct, Cholangiocarcinoma, Primary sclerosing cholangitis, Ascending cholangitis

27

Studies to date have not investigated whether body mass index (BMI) affects the sensitivity and specificity of magnetic resonance cholangiopancreatography (MRCP). The purpose of this study was to investigate the effect of BMI and also concomitant pancreatitis, cholecystitis and cholelithiasis on the sensitivity and specificity of MRCP.

Concepts: Sensitivity and specificity, Body mass index, Bile duct, Common bile duct, Choledocholithiasis

27

BACKGROUND: There is no doubt that urgent biliary decompression needs to be done in case of severe acute cholangitis. However, it remains to be determined how early biliary decompression should be performed and elective intervention would be comparable to urgent intervention, in case of mild to moderate choledocholithiasis associated cholangitis. METHODS: One hundred ninety-five patients were enrolled who were diagnosed with mild to moderate cholangitis with common bile duct (CBD) stones between January 2006 and August 2010. They were divided into two groups according to door to intervention time, and urgent (≤24 h, n = 130) versus elective (>24 h, n = 82). Primary outcomes of this study were technical success rate (CBD stones removal) and clinical success rate (improvement of cholangitis) between the two groups. Hospital stay and intervention-related complications were also evaluated. RESULTS: There was no statistically significant difference in technical, clinical success rate and intervention-related complications between the urgent and elective groups (P = 0.737, 0.285, 0.398, respectively). Patients in the urgent group had significantly shorter hospitalization than in the elective group (6.8 vs. 9.2 days, P < 0.001), and furthermore, intervention to discharge time was also significantly shorter by 1.1 days in the urgent group (P = 0.035). In terms of laboratory parameters, initial CRP level was the only factor correlated with hospital stay and intervention to discharge time. CONCLUSIONS: This study demonstrates that urgent ERCP would be recommended in the management of patients with CBD stone-related mild to moderate acute cholangitis because of the advantage of short hospital stay and intervention to discharge time.

Concepts: Statistical significance, Digestive system, Hepatology, Bile duct, Ascending cholangitis, Common bile duct, Gallstone, Choledocholithiasis

27

Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease of the liver of unclear etiology, characterized by chronic inflammation and fibrosis of bile ducts. It primarily affects middle aged men, and is associated with 4-fold increased mortality as compared to age- and gender-matched population. Progressive biliary and hepatic damage results in portal hypertension and hepatic failure in a significant majority of patients over a 10-15 year period from initial diagnosis. In addition, PSC confers a markedly increased risk of hepatobiliary cancer, including cholangiocarcinoma and gallbladder cancer as compared to the general population, and cancer is the leading cause of mortality in patients with PSC. It is associated with inflammatory bowel disease in 70% patients, and increases the risk of colorectal cancer almost 10-fold. Despite significant research efforts in this field, the pathogenic mechanisms of PSC are still incompletely understood, although growing evidence supports the role of genetic and immunologic factors. There are no proven medical therapies that alter the natural course of the disease. Thus, liver transplantation is the only available treatment for patients with advanced PSC, with excellent outcomes in this population.

Concepts: Medicine, Cirrhosis, Liver, Ulcerative colitis, Hepatology, Bile, Bile duct, Primary sclerosing cholangitis