Short-medium- and long-term effect of ursodeoxycholic acid on cholesterol an bile acid synthesis in healthy humans

Short-medium- and long-term effect of ursodeoxycholic acid on cholesterol an bile acid synthesis in healthy humans

to quantitatethe biliary tree anatomy in a strain of Sprague-Dawleyrats (PCK) that spontaneously develops PKD and PLD with aging. METHODS:We used a te...

208KB Sizes 0 Downloads 8 Views

to quantitatethe biliary tree anatomy in a strain of Sprague-Dawleyrats (PCK) that spontaneously develops PKD and PLD with aging. METHODS:We used a technique involving a microCT scanner and novel software previously developedby us (GASTROENTEROLOGY116:A18, 1999). A silicone polymer was retrogradely injected through the common bile duct of 26week old PCK rats. Liver lobes were assessed by micro-CT scanning and 3D-images reconstructed using a modified Feldkamp'sbackprojectionalgorithm. A customizedsoftware package (ANALYZE)was then employedfor quantitativeanalysis. RESULTS:In PCK rats, liver weights and body/liver weight ratios were increased approximately four-fold compared to controls. The outer surface of livers of PCK rats was diffusely deformed by numerous cysts. Light microscopy showed that cysts varied in size and shape, were often surrounded by fibrosis tissue, and contained fluid. Three-dimensionalanalysis revealed major changes in PCK bile duct anatomy compared with controls; localizedand diffusely dilated bile ducts were spread along the entire biliary tree. The diameter of proximal bile duct segments increasedapproximately three-fold, and the total liver volume, total biliary tree volume and total biliary tree surface area were increased approximately four-fold compared to controls. CONCLUSION: Our study provides the first quantitative assessmentof the biUarytree anatomy in PCK rats. The data suggest that this pathological condition reflects a global distortion of the entire intrahepatic biliary tree.

method. RCTswere pooled and 12-month mortality rates, 6-month cholangitis rates and 6month stent occlusion rates were calculated. Relative risk reduction (RRR), absolute risk reduction (ARR) and number neededto treat (NNT) were derived. ManteI-Haenszelodds ratios (ORM.H)and/or crude OR were calculated for all end-points. Results: We identified 4 RCTs without significant heterogeneity(P = 0.18). After pooling, 165 patients had beenrandomized to metal stents and 203 to plastic. All RCTscompared mortality as a primary end-point. There was no significant difference in pooled 12-month mortality rates, which were 76.5% for metal and 77.1% for plastic stents; RRR = 1%; NNT = 159; OR,., = 0.98 [95% CI 0.57, 1.88]. 3 RCTsevaluatedcholangitis as a primary end-point. 6-month cholangifis rates were 27.2% for metal stents and 42.2% for plastic stents; RRR = 36%; ARR = 15%; NNT = 6.7; OR=. H= 0.56 [95% CI 0.33, 0.95]. Stent occlusion rates at 6 months were 22.0% for metal stents and 48.5% for plastic stents; RRR = 55%; ARR = 26.6%; NNT = 3.8; ORM-H= 0.30 [95% CI 0.18, 0.51]. Conclusions: Metal stent placement is associated with less. morbidity, and thus improved clinical outcomes, than plastic stent placementfor the palliation of malignant common bile duct obstruction. The benefit of this reduction in morbidity should be included in cost analysescomparing metal versus plastic stent placementin the palliation of malignant common bile duct obstruction.

1983

1980

Intmhepatic Ductal Hypoplnsia and Anomalous Junction of Panereatico-biliary Ouctal System as Causes of Choledocal Cysts. Dae Kun Yoon, Hallym Univ, Seoul South Korea; Ho Sung Han, Ehwa Univ, Seoul South Korea; Choong Ki Park, Hallym Univ, Seoul South Korea; James R. Gum, Jenny J L Ho, Young S. Kim, UCSF,San Francisco, CA; Bung Hwa Lee, Hallym Univ, Seoul South Korea

The Effects of PaclitaxeI-Coated Nylon Thread for the Proliferative Cholangitis in a Rat Seon Mee Park, Dongwoon Kim, Ro Hyun Sung, Jae-Woon Choi, Chungbuk National Univ, Cheongju South Korea Background: Proliferative cholangifis(PC) leads to biliary stricture, and is the main cause of hepatolithiasis, recurrent cholangitis, and biliary cirrhosis. We recently showed that local delivery of paclitaxel dissolved solution supressed bile duet proliferation in a rat. We tested whether paclitaxel-coatednylon thread prevents biliary stricture in a PC model of rat. Materials and Methods: Paclitaxel-coated5-0 nylon threads(1.8_+O.5/.~gtthread,measured by HPLC) were made by immersion of ethanolic paclitaxel(5Omg/ml)and evaporation of the solvent. Nylon threads were inserted into the bile duct of male Sprague-Dawleyrats weighing 200250g. Paclitaxel(n = 10) and control (n = 10) groups were divided with or without paclitaxelcoating procedure. The paclitaxel effects were assessed by histomorphological examination one week after thread implantation. Results:The bile duct wall thicknesses of pactitaxetgroup decreased by 32% (p=O.04, 273(31),u.m vs 404(48)/.~m, paclitaxel vs control). In paclitaxel group, the luminal perimeter and the ratio of lumen to bile duct cross sectional area increased by 90% (p=O.01, 1893(270)/~m vs 996(164)/Lm) and by 200% (p=O.O01, 0.18(0.02) vs 0.06(0.01)), respectively,versus control. Conclusion: Paclitaxel-coatednylon thread into bile duct was effectivefur the suppressionof luminal stenosis, and may offer a therapeuticoption for biliary stricture and biliary stricture associateddisease.

Background and Aim: Anomalous Junction of pancrcaticobiliary ductal system(AJPBD)was frequently observedin the patients with choledochalcyst. The aim of this study is to determine the conditions of AJPBD in the 32 cases of choledochal cysts which were diagosed between 1993 and 1999, and which were also confirmed with intraoperativecholangiography.Method: We measuredthe length of AJPBDin eachcasewith MRCP,and intraoperativecholangiography. Intraoperativeductal hypoplasiawas defined as decreaseof the diameter of intrahepatieduct and number of segementalbile ducts, which was observed by two radiologists, subsequently. The histopathology of each cyst was classified into two types; glandular and fibrotic. 27 were female and 5 were male. Mean age was 25.9 years old (Range; 8months - 70 years). With the Todanrs criteria, the type I and the type IVa were in 59.4% and 40.6%, exclusively. Results: Long common channels (over 15 mmm, AJPBD) were in 59.4%. Borderline (6-15 mm) and noncommon (1-6 mm) channels were 37.5% and 3.1%, respectively.We could classify into p-c type (57.9%) and c-p type (42.1%) on the basis of Ono's classification. Intrahepatic Ductal Hypoplasiawas observed in 53.1%. The length of common channel and the type of junction were not significantly affected by the intrahepatic ductal hypoplasia(p = 0.130). The histopathology of the walls of choledochal cysts were glandular type in 43.8% and fibrotic type in 56.2%. The pathology of the cysts was not changed in the presence of long channel or other types. Conclusion: In choledochalcyst, anomalousjuction of pancreaticobiliaryduct and intrahepatic ductal hypoplasia was observed more than half case, but clinical and patholgical parameters of choledochal cyst did not changed according to the types of AJPBD.

1981 The Diagnostic And Therapeutic Role Of Endoscopic Retrograde Cholangiopancreatagraphy (ERCP) In Biliary And Pancreatic Disorders in Children Rodolfo Rocca, MAURIZIANOHosp, Turin Italy; Cristiana Barbera, OIRM Hosp, Turin Italy; Francesca Castellino, Masoero Guya, Raffaello Sostegni, Franco Coppola, MAURIZlANO Hosp, Turin Italy; Luigi Calvo, OIRM Hosp, Turin Italy; Cristiana Laudi, Marco Daperno, Patrizia Della Monica, Angelo Pera, MAURIZlANO Hosp, Turin Italy

1984 Short- Medium- and Long-term Effect of UmodeoxycholicAcid on Cholesterol and Rile Acid Synthesis in Healthy Humans ~i Tifiessen, Gerd Sautar, Kiaus Georg Parhofer, Dieter Juengst, Oven Fischer, Clin Grosshadem, Munich Germany

BACKGROUND. Although ERCP has been used with increasing frequency in the pediatric populationto investigatebiliopancreaticdiseases,it is still an uncommon procedurein children. Major limitations are relatedto low incidenceof thesedisease,to equipment(sizeof endoscopes and devices)and endoscopistsexperience.MATERIALSAND METHODS.Between1996-2000, we performed36 ERCPin 30 children aged4 weeksto 16 yearsas part of diagnostic evaluation for suspected pancreatic or biliary tract disease or as therapeutic procedures. ERCP was performed under general anesthesia, using prototype paediatric duodenoscopes (Olympus PJF 7.5) in children younger than 18 months and standard endoscopesin those older than 2 years. RESULTS.The indications to performe ERCPwere common bile duct stones (CBDS) in 12 children, biliopancreaUcabnormalities in 9, extrahepatic biliary etresia in 3, recurrent pancreatiUs in 3, hereditary pancreetitis in 2, sclerosing cholangitis in 2, Alagille syndrome in 1, biliary leackageafter VLC in 1 and traumatic Wirsung disruption in 1. One third of children with CBDS presented initially with acute pancreatitis. Cannuletion was successful in all patients; biliary tracts opacification was achievedin all patients exceptthose with extrahepatic biliary atresia. Sphincterotomy together with either stone extraction or stent insertion, according to the underlying disease, was performed in 21 out of 30 patients. Immediate complications included two post- sphincterotomy bleedingtreated conservatively.Long- term complication was recurrent CBD stones at 2 years in one patient, treated by repeat ERCPand stone extraction.CONCLUSIONS.ERCPhas an invaluablerole in the diagnostic and therapeutic management of biliopancreaticdiseasesalso in childhood. Indications, endoscopictecniques and complications are similar to those reported for adult patients. ERCPis a safe procedure when performed by experiencedendoscopists.

BACKGROUNDANDAIMS: Gallbladderbile is efficientlydeseturetedin cholesterolby ursodeoxycholic acid (UDCA).To evaluatethe mechanismswhich may lead to a reduced hepaticoutput of biliary cholesterol we analysedthe two key enzymesof cholesterol metabolism HMG CoA reductase and cholesterol 7~hydroxylase. STUDYDESIGNAND METHODS:UDCAwas given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) for 46 (Jays in a single dose of 10-15 mg/kg body weight. Blood was drawn and 12h-urine collected overnight on days 1,3,5,10,20,30,40. For control values blood and urine were collectedbefore and after ingestion of UDCA.Urinary mevalonicacid (MVA, p~/g creetinine)was assayedas marker of cholesterol synthesis by combined gas chromatography-massspectrometry. 7a-hydroxy-4-choleeten-3one (7a-HC, xlg/ml was analysed in serum by HPLC as a marker for bile acid synthesis. RESULTS AND CONCLUSIONS:Our results suggest a decline of cholesterol and bile acid synthesis after short-term treatment with UDCA (Fig.1 and Fig.2). During medium-and longterm UDCA ingestion, bile acid and cholesterol synthesis reached pre-treetment levels as determined by MVA and 7e-HC. Thus, the course of both MVA and 7~-HC indicates an initial suppression of cholesterol and bile acid synthesis which is counterregulatedduring further treatment. Due to interindividual variation, the short-, medium- and long-term changes in cholesterol and bile acid synthesis are trends and do not reach statistical significance.

1982 Meta-Analysis Of Randomized Controlled Trials Comparing Plastic And Metal Stents For Palliation Of Malignant Obstructive Jaundice Patrick Okolo III, Willis G. Parsons, Colin W. Howden, Northwestern Univ, Chicago, IL

Fig, 1: Chok~u~-ol syml~sl as ~ m a t c d by m'inmy ~r~'tion of Movalooz~. As fc~ tl~ key e~ym= I-~G CoA ~ MVA assay~l by oombined 8as ohrmato~-'aphy-mms sp~muom~-,y.

Background: Palliationof malignant obstructivejaundice by stent placementis now considered the standard of care. Metal stents have higher acquisition costs than plastic stents but may be associatedwith superior clinical outcomes.Aims: To assess,by mete-analysisof randomized controlled trials (RCTs), the relative efficacy of metal and plastic stents in the palliation of malignant common bile duct obstruction. Methods: Recursive literature search for RCTs comparing metal and plastic stents in the palliation of obstructive jaundice resulting from malignant common bile duct obstruction. Homogeneitywas assessed using the Breslow-Day

A-387

Fi$,2: Cholmtm~c (ngJral) w~s amlys~ ia sm'~m by ~ ~ mm'kcr for bile az/d syathesis,