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sTu1959

Effect of Pentadecapeptide BPC 157 on Liver Lesions Induced by BiliaryObstruction in RatsAnita Zenko Sever, Marko Sever, Domagoj Drmic, Zeljko Romic, Sven Seiwerth, PredragSikiric

Aim. Bile duct obstruction during longer period of time induces liver lesions which cancause liver cirrhosis. For pentadecapeptide BPC 157 hepatoprotective effect was shown onCCl4, alcohol (acute and chronic abuse)and NSAIDs induced liver lesions, thus we testedthat effect on liver lesions induced by biliary obstruction in rats. Methods. In this study weused 60 male Wistar rats. Biliary obstruction was surgically induced by bile duct ligation.Animals were randomized to control and pentadecapeptide BPC 157 μg group. BPC groupanimals got pentadecapeptide BPC 157 in drinking water (10μg/kg/day), control group gotequivalent water volume. After sacrifice (4,6 and 8 weeks after the bile duct ligation)blood samples for AST, ALT, bilirubin and albumin serum levels were taken. Macroscopicobservation, liver mass, bile duct diameter and microscopic observation were performed.Results. Since 3rd week significantly higher serum levels of bilirubin, AST, ALT, albuminand PT were found in control group compared to pentadecapeptide BPC 157 treated group.In control animals larger liver congestion with larger bile duct diameters (5x3cm) was foundcompared to BPC 157 treated rats (bile duct diameters 2x1cm). Microscopically larger liverportal spaces with significant bile ductules proliferation were found in controls comparedto BPC 157 treated rats. Conclusion.We can conclude that pentadecapeptide BPC 157 hashepatoprotective effect on long time biliary obstruction induced liver lesion. Key words:Pentadecapeptide BPC 157, biliary obstruction, liver lesion, bile duct ligation

Tu1960

Predictors of Effectiveness of ERCP Performed for Postoperative Bile LeaksShishira Bharadwaj, Tushar Gohel, Dhruv Mehta, Vennia Vasant, Rocio Lopez,Madhusudhan R. Sanaka, Mansour A. Parsi, Udayakumar Navaneethan

Background and aim: Bile leak (BL) is a rare, but significant complication post cholecystec-tomy and hepatobiliary surgeries (HBS). ERCP is effective for treating BL post cholecystec-tomy, however limited data exists on its effectiveness after HBS. The aim of this study is todetermine the predictors of effectiveness of ERCP for treating postoperative BLs. Methods:In this retrospective, institutional review board approved study, patients referred for ERCPtreatment for postoperative BLs between 1999 to 2013 were included. A multivariate analysisto assess predictors of ERCP effectiveness for BLs was performed Results: A total of 105patients who underwent ERCP for BLs post cholecystectomy and HBS between 1999 and2013 were identified. Ninety seven ( 92.4 %) patients out of 105 had resolution of BL.Eighty two (78.1 %) patients out of 105 had resolution of BL within 12 weeks. ERCP waseffective for resolution of BL in 95 (90.5%) of these patients. ERCP was effective for resolutionof BL within 12 weeks in 80 ( 76.2%) of 105 patients. In the multivariate model, ERCPperformed in the afternoon was 5 times more effective for resolution of BL within 12 weekswhen compared to ERCP performed in the morning (odds ratio [OR]= 4.6, 95% confidenceinterval [CI]: 1.7, 12.9; p=0.003). Also for every point increase in American Society ofAnesthesiologists (ASA) score, the likelihood of effectiveness of ERCP for BL within 12 weeksdecreased by 55 % (OR= 0.45, 95% CI: 0.21, 0.95; p=0.037). Conclusion: ERCP is effectivefor treating postoperative BLs in majority of the cases. The effectiveness of ERCP for BLresolution within 12 weeks is predicted by the time of the procedure and the preoperativeASA score.Table1: Multivariate analysis of factors associated with effectiveness of ERCP performed forpostoperative bileleaks

Tu1961

Microbial Analysis in High-Risk Patients With Acute Bacterial CholangitisTreated in a Tertiary Care Center in Mexico CityJose F. Castro-Gomez, Ignacio Garcia-Juarez, Juan F. Sanchez-Avila

Background: Acute bacterial cholangitis is a biliary tract infection that warrants an effectiveantibiotic treatment for proper resolution. In most cases, antimicrobial therapy selection isempirical. Epidemiological studies based on microbiological cultures and their resistancepattern leads us to choose the proper antibiotics. Methods: A retrospective review of 198cases classified as acute biliary tract infection thru January 1, 2000 to August 31, 2010 wasperformed. Only cases of acute bacterial cholangitis with positive bile culture and/or positiveblood culture were included. A microbial analysis including the prevalence of the bacteriacultured and its antibiotic susceptibility pattern was made. Etiology, clinical features andtreatment were also reviewed. Results: One hundred cases met our inclusion criteria. Themean age of the study population was 54 years. The most common etiology was iatrogenicbiliary injury (29%), followed by pancreatic adenocarcinoma (18%) and cholangiocarcinoma(16%). Previous history of bile duct manipulation was very common (80%) and 58 patientshad experienced one or more events of acute bacterial cholangitis. Blood culture was positivein 84 patients and bile culture in 21 cases. Five patients had a positive blood and bileculture. The cultures were mostly monomicrobial (72%). A total of 139 bacteria were isolated.The most frequent pathogens in blood and bile were E. coli (50.7%), Enterococcus spp(20.3%) and Pseudomonas spp (6.5%). E. coli showed highly resistant to third generationcephalosporins (30%) and quinolones (60%). The 28.5% (8/28) of the Enterococcus sppisolated were ampicillin resistant. In overall, the most effective antibiotics were amikacin,carbapenems and linezolid. Invasive treatment was merited in most of the patients (65%).

S-882AGA Abstracts

Endoscopic drainage was used in 36 of 65 (55.3%) patients, followed percutaneous drainagein 24 of 65 patients (36.9%) and surgery in 20 of 65 patients (30.7%). Conclusions: Ourhospital is a national referral center for biliary tract disease including iatrogenic injuries andbiliary/pancreatic cancer. This could explain the low prevalence of "Naive" biliary tract inour population and a high prevalence of Enterococcus spp. This study encourages the needfor a well design local epidemiological study that could redefine the antibiotic selection inour center.

Tu1962

Therapeutic ERCP in Cholelithiasis - Results After a Ten-Year Experience of aSingle CenterMarcel Tantau, Voicu Mercea, Dana Crisan, Alina Tantau, Gabriela M. Mester, StefanCristian Vesa

Background: Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is the standardmethod of treatment of choledocholithiasis. ERCP entails certain risks, which increase withthe complexity of the procedure and the severity of patient disease. Aim: To evaluate theoutcomes and complications of therapeutic ERCP for bile duct stones. Method: A total of3097 consecutive ERCPs were performed in 2986 patients during a 10-year period (2002-2011) in our endoscopy department. The analysis of the results of therapy was performeddepending on anatomic variants, age and opacification of the Wirsung duct. Short-timecomplications were assessed in 847 patients enrolled in the last 3 years. Results: The rateof successful cannulation was 98%. The patient's age and the diameter of the common bileduct were the factors influencing the probability of finding a gallstone (age over 74 years,AUC=0.547; p<0.001) and a CBD diameter larger than 12 mm (AUC=0.735, p<0.001).Stone removal was unsuccessful in 2.3%. Factors associated independently with unsuccessfulextraction were previous surgical sphincteroplasty, stone size and Billroth I anastomosis.The prevalence of pancreasum divisum in 866 patients with pancreatography was of 3.0%.Of the subgroup enrolled in the last 3 years, the overall complications rate was 5.19% (44patients): pancreatitis in 21 patients (2.47%), hemorrhage in 11 (1.29%), cholangitis in 4(0.47%), perforation during ES in 5 (0.59%), and cholecystitis in 3 (0.35%). In multivariateanalysis, the following risk factors were significantly associated with complications: forpancreatitis, age and pancreatic ductal opacification, while for hemorrhage - acute cholangytisand coagulopathy. Conclusions: The endoscopic treatment of choledocholithiasis is highlyeffective and with low rate of complications, especially in the hands of a high experiencedoperator. The knowledge of complications and of factors favouring their occurance, allowsthe gastroenterologist to promptly recognize these risks and institute appropriate preven-tive measures.

Tu1963

The Bile Acid Receptor TGR5 Sensitizes the TRPA1 Channel to InduceCholestatic ItchTinaMarie Lieu, Gihan Jayaweera, Peishen Zhao, Daniel P. Poole, Dane D. Jensen, MeganS. Grace, Romke Bron, Peter McIntyre, Nigel W. Bunnett

Patients with cholestatic liver disease have elevated systemic concentrations of bile acids(BAs) and exhibit profound pruritus. The BA receptor TGR5 is expressed by nociceptiveneurons of dorsal root ganglia (DRG), where activation induces hyperexcitability and scratch-ing behavior in mice by unknown mechanisms. We evaluated the contribution of transientreceptor potential ankyrin 1 (TRPA1) to BA-evoked, TGR5-dependent pruritus. Using retro-grade tracing, single cell RT-PCR, immunofluorescence and in situ hybridization, we detectedTGR5 in a subpopulation of DRG neurons innervating the mouse skin. TGR5 and TRPA1were coexpressed in retrogradely-labeled small diameter neurons. In HEK cell lines expressingTGR5 and TRPA1, and in mouse DRG neurons in culture, pre-incubation with the BAsdeoxycholic acid (DCA) and taurolithocholic acid (TLCA) magnified TRPA1-dependent Ca2+signals, indicating channel sensitization. TRPA1 antagonism or deletion or inhibition ofprotein kinase A all prevented BA-evoked sensitization of TRPA1. Moreover, BAs stimulatedgeneration of cAMP and activation of ERK1/2 in DRG neurons from wild-type but not TGR5knockout mice, confirming the capacity of BAs to signal to sensory neurons by activatingTGR5. Intradermal injection of DCA or TLCA induced scratching behavior in mice andstimulated fos expression in spinal neurons. TRPA1 antagonism or deletion prevented BA-evoked scratching and activation of spinal fos, whereas antagonism of TRPV1 had no effect.TGR5 transgenic mice demonstrated enhanced spontaneous scratching that was attenuatedby feeding the BA sequestrant colestipol and is thus dependent on endogenous BAs. Antago-nism of TRPA1 also suppressed spontaneous scratching in TGR5 transgenic mice. Thus,TGR5 is coexpressed with TRPA1 by a subpopulation of DRG neurons that innervate theskin. TGR5 causes protein kinase A-dependent sensitization of TRPA1, which is requiredfor the pruritogenic actions of exogenous and endogenous BAs. This mechanism may contrib-ute to cholestatic pruritus in patients with elevated systemic concentrations of BAs.