Schweizerisches Medizin-Forum

Swiss Medical Forum

Forum Médical Suisse20.8.2008

Jahreskongress

SGG Schweizerische Gesellschaft für Gastroenterologie

SGVC Schweizerische Gesellschaft für Viszeralchirurgie

SASL Swiss Association for the Study of the Liver

Interlaken, 28.–29. August 2008

Supplementum 41ad Swiss Medical Forum2008;8(34)

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INHALT Schweiz Med Forum 2008;8(Suppl. 41) 1 S

1–35 Oral presentations 2 S

P1–P47 Posters 12 S

Autorenverzeichnis 24 S

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I M P R E S S U M Offizielles Fortbildungsorgan der Schweizerischen Gesellschaft für Innere Medizin

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1HBV-HCV Coinfection: Insights from a Novel Model System Pantxika Bellecave1, Jérôme Gouttenoire1, Markus Gajer2, VolkerBrass2, George Koutsoudakis3, Hubert E. Blum2, Michael Nassal2, Ralf Bartenschlager3 and Darius Moradpour1

1 Division of Gastroenterology and Hepatology, Centre HospitalierUniversitaire Vaudois, University of Lausanne, CH-1011 Lausanne,Switzerland, 2 Department of Medicine II, University of Freiburg, D-79106 Freiburg, Germany and 3 Department of Molecular Virology,University of Heidelberg, D-69120 Heidelberg, Germany Background: Coinfection with hepatitis B virus (HBV) and hepatitisCvirus (HCV) has been associated with severe liver disease and frequent progression to liver cirrhosis and hepatocellular carcinoma.Clinical evidence suggests reciprocal replicative suppression of thetwo viruses (‘viral interference’). However, virtually nothing is knownabout molecular interactions between HBV and HCV due to the lackof appropriate model systems. Methods: A tetracycline-regulated gene expression system was usedto generate a panel of stable Huh-7 cell lines inducibly replicatingHBV. These cell lines and control Huh-7 cell lines inducibly expressingthe green fluorescent protein (GFP) were transfected with selectableHCV replicons or infected with cell culture-derived HCV (HCVcc). Results: Three successive transfection and selection steps allowedthe establishment of Huh-7 cells inducibly replicating HBV and constitutively replicating subgenomic HCV RNA. In these cell lines,it is possible to regulate the expression of HBV proteins, HBVgenome replication, and infectious viral particle formation by theconcentration of tetracycline in the culture medium while HCV proteins are expressed and HCV RNA replicated constitutively. Thepresence or absence of replicating HBV did not influence the antiviraleffect of interferon-alpha against HCV. In addition, specific inhibitionof one virus did not significantly affect gene expression, replicationand release of the other. Experiments using HCVcc did not reveal anysignificant superinfection exclusion of HCV by HBV. Finally, cell cul-ture-adapted HCVcc isolated from long-term cultures did not displayany HBV-specific adaptation. Conclusion: HBV and HCV can replicate in the same cell without anysignificant direct interaction. Therefore, the viral interference observedin vivo in coinfected patients is likely due to innate and/or adaptivehostimmune responses. These findings provide new insights into thepathogenesis of HBV-HCV coinfection and may contribute in thefuture to its clinical management.

2Inactivation of Cardif, an Essential Adaptor Protein in the RIG-I Antiviral Pathway, in Patients with Hepatitis C Pantxika Bellecave1, Magdalena Sarasin-Filipowicz2, Olivier Donzé3,Jérôme Gouttenoire1, Etienne Meylan4, Jürg Tschopp4, ChristophSarrazin5, Thomas Berg6, Markus H. Heim2 and Darius Moradpour1

1 Div. of Gastroenterology and Hepatology, CHUV, CH-1011Lausanne, 2 Dept. of Biomedicine and Div. of Gastroenterology andHepatology, University Hospital Basel, CH-4031 Basel, 3 ApotechCorp., CH-1066 Epalinges, 4 Dept. of Biochemistry, University ofLausanne, CH-1066 Epalinges, 5 Dept. of Medicine I, J. W. GoetheUniversity Hospital, D 60590 Frankfurt a. M., 6 Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Campus Virchow-Klinikum, D-13353 Berlin Background: Hepatitis C virus (HCV) has evolved various strategiesto counteract the host immune response and to establish persistentinfection. The HCV NS3-4A serine protease blocks interferon pro -duction by cleaving and thereby inactivating the essential adaptormolecule Cardif in the RIG-I antiviral pathway. The aim of this studywas to extend these experimental observations to patients with hepatitis C. Methods: Polyclonal and monoclonal antibodies against Cardif wereestablished. A panel of 118 well-characterized liver biopsies frompatients with chronic hepatitis C was analyzed by immunoblot andreal time RT-PCR. Biopsies from 51 patients with other liver diseasesserved as controls. Results: Cardif is cleaved to varying degrees specifically in patientswith hepatitis C but not in controls. We found a significant inversecorrelation between viremia and the amount of full-length Cardif in the liver. In addition, the amount of full-length Cardif was significantlylower in easy-to-treat genotypes 2 and 3 as compared to difficult- to-treat genotypes 1 and 4. The amount of full-length or cleavedCardif did not correlate with Cardif mRNA levels, necro-inflammatoryactivity, fibrosis stage or treatment outcome.

Conclusions: Cardif is cleaved and thereby inactivated specificallyinpatients with chronic hepatitis C. Increased Cardif cleavage inpatients infected with HCV genotypes 2 and 3 may be related to theless frequent preactivation of interferon stimulated genes recentlyreported in these patients. However, a significant correlation withtreatment outcome was not observed at the sample size examined in this study. Therefore, Cardif cleavage in the liver reveals insightsinto the pathogenesis of hepatitis C but does not provide an easily applicable predictor of treatment response.

3Modulation of the inflammatory reaction by granulocyte -macrophage colony-stimulating factor improves mucosal repair in a mouse model of acute colitis Eric Bernasconi1, Laurent Favre1, Daniel Bachmann1, HanifaBouzourene2, Ed Croze3, Sharlene Velichko3, John Parkinson3, RetoSchwendener4, Pierre Michetti1, and Dominique Velin1

1 Department of Gastroenterology and Hepatology, 2 Institute ofPathology, CHUV, Lausanne, 3 Department of Immunology, BerlexBiosciences, Richmond, United States, 4 Institute of MolecularCancer Research, University of Zurich, Zurich Background: Innate immune cell subsets infiltrating inflamed andsevered tissues exert complementary, pro-and anti-inflammatoryfunctions, aiming at regenerating damaged tissues and reestablishingimmune homeostasis. We tested the hypothesis that granulocyte -macrophage colony-stimulating factor (GM-CSF) treatment may exertbeneficial effects during acute colitis by reinforcing recruitment ofCD11b-positive granulocytes and macrophages (GM). Methods: Mice were exposed for 7 days to 4% dextran sulfatesodium (DSS) to induce colitis. Kinetic analyses of the inflammatorycell infiltrate, inflammatory mediator release and mucosal repairprocesses were comparatively assessed in untreated wild-type miceversus phagocyte-depleted wild- type mice or mice deficient for GM-CSF receptor. Moreover, the impact of GM-CSF administrationon colitis was evaluated. Results: Dysregulation of GM recruitment in phagocyte-depletedwild-type mice or mice deficient for GM-CSF receptor exacerbatedulcer numbers and fecal blood during DSS colitis. In contrast, adop-tive transfer of CD11b- positive GM isolated from the spleen of GM-CSF-treated mice was protective. GM-CSF therapy elicitedrecruitment of anti-inflammatory monocytes and promoted prorepairfactor expression. This resulted in reduced late inflammatory reac-tions, prevention of body weight loss and diarrhea, and a clear acceleration of ulcer healing. Conclusions: Our study shows that CD11b-positive GM-CSF-responsive GM are critically involved in ulcer repair during DSS colitis and, by extension, suggests that enhanced mucosal healingmight contribute to the mechanisms of action of GM-CSF treatmentin Crohn’s disease.

4Dysregulation of glucose homeostasis in chronic hepatitis C: The role of Protein Phosphatase 2A Christine Bernsmeier, François Duong and Markus HeimHepatology Laboratory, Department of Biomedicine, UniversityHospital Basel Background: Insulin resistance development and type 2 diabetesmellitus are metabolic disorders induced by the hepatitis C virus. They are considered as risk factors for fibrosis progression and non -response to antiviral therapy in chronic hepatitis C. The molecularmechanisms of insulin resistance development in HCV remain to beelucidated. Glucose homeostasis is tightly regulated by differentsignalling pathways that regulate glycogensynthesis and gluconeoge-nesis. We have shown that protein phosphatase 2A (PP2A) is overex-pressed in HCV transgenic mice and in liver biopsies from patientswith CHC and that PP2A overexpression inhibits insulin signalling andAMPK phosphorylation. We therefore tested if HCV induced hepaticPP2A overexpression interferes with gluconeogenesis and therebyinducesan insulin resistant phenotype.Methods: Insulin sensitivity was studied in HCV transgenic (B6HCV) and in control mice by measuring fasting glucose and insulinlevels (for calculation of HOMA) and by glucose and insulin tolerancetests. Expression levels of gluconeogenetic key enzymes such as

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PEPCK, G6Pase, PGC1a were measured in cells that overexpressPP2A, inHCV transgenic mice and in liver biopsies from control andHCV patients.Results: B6HCV mice were insulin resistant, and hepatic expression-levels of PEPCK, G6Pase, PGC1a were increased. Overexpression ofPP2A in Huh7 cells also increased PEPCK, G6Pase, PGC1a expres-sion levels when cells were cultured in high glucose medium. In liverbiopsies from HCV patients we observed an upregulation of PGC1a. Conclusion: PP2A overexpression in HCV infected cells leads to aninappropriate inhibition of gluconeogenesis, thereby inducing aninsulin resistance phenotype.

5Restoration of HBV-Specific T Cell Responses in LamivudineLong Term Responder Florian Bihl1, Elisabetta Loggi2, Cinzia Fortini2, Carmela Cursaro2,Elena Grandini2, Lorenzo Micco2, Christian Brander3 and PietroAndreone2

1 Service de Gastroentérologie et Hépatologie, HôpitauxUniversitaires de Genève 2 Dipartimento di Medicina Interna etEpatologia Ospedale S. Orsola-Malpighi, Universita’ degli Studi di Bologna, Italy 3 Partners AIDS Research Center, MassachusettsGeneral Hospital, Harvard Medical School, Boston, USABackground: HBV-specific T cell responses play a crucial role inHBVinfection control and disease outcome. The benefit of antivirals suchas Lamivudine (LAM) is compromised by progressively increasingemergence of drug-resistant strains (up to 70% after 5 years). How-ever, 20–30% of patients do not develop resistance despite long-termtherapy. While LAM has been shown to induceearly but only transientrestoration of HBV-specific T cell responses, the immunological pro-file of LAM long-term responders (LAM-LTR) defined by sustainedHBV-DNA suppression during prolonged LAM administration, has notyet been analyzed.Methods: Seven LAM-LTR treated for a median time of 9 years(range: 7–11) and 13 LAM treated patients with viral breakthrough(LAM-R), were tested with a panel of overlapping peptides (18mers) spanning the entire HBV sequence. The frequency and magnitudeof HBV-specific T cell responses was assessed by IFN-gELISPOT and ICS in vivo and in vitro stimulation and positiveresponses were characterized by functional analyses (PD-1, CD107a)Results: HBV-specific immune responses were detected in all LAM -LTR (100%) and in eight of the 13 subjects with LAM-R (61%). Thefrequency of HBV-specific T cell responses was higher in LAM-LTRcompared to LAM-R (median 5 vs 1, respectively, p=0.001). LAM LTRpresented stronger IFN-g responses (median: 2’793 vs 1’740SFC/106PBMC, p=0.03). Polymerase-specific responses dominat-edthe T cell repertoire in both groups of patients, although LAM-LTRpresented multiple responses to all four HBV proteins. Conclusions: LAM-LTR are characterized by a multi-specific patternof HBV-specific T cell responses. The HBV-specific cellularimmunerepertoire restores in terms of both frequency and magnitudeinLAM-LTR.

6Hyperimmune anti-HBs plasma for the prevention of HBVrecurrence after liver transplantation: efficacy, safety, kineticsand economics in 21 patients during a 13-year experience of two centers Florian Bihl1, Stefan Russmann2, Vanina Gurtner3, Loriana DiGiammarino Bihl4, Loredana Pizzi-Bosman5,Andreas Cerny6, PietroMajno7, Antoine Hadengue1, Emiliano Giostra1, Damiano Castelli3,Gilles Mentha7

1 Dep. of Gastroenterology and Hepatology, HUG; 2 ClinicalPharmacology, USZ; 3 Transfusion Service, Lugano; 4 Dep. ofGastroenterology and Hepatology, CHUV; 5 Transfusion Service,Geneva; 6 Clinica Moncucco, Lugano; 7 Transplantation Unit, HUG Background: Commercial hepatitis B immune globulin (HBIG) prod-ucts in combination with nucleos(t)ide analogues (NA) are effectivelyused for the prevention of HBV recurrence after livertransplantation(LT). However, associated treatment costs are exceedingly high.Methods: Hyperimmune anti-HBs plasma (HIP) is obtained fromblood donors vaccinated against HBV with high anti-HBs titer(>15’000IU/L). 21 HBV-related LT recipients received HIP starting attransplantation, followed by long-term treatment in combination withNA.

Results: Patients received on average 8.2 HIP transfusions per year(range 5.8-11.4). Anti-HBs terminal elimination half-life after HIPadministration was determined in 5 patients with amean of 20.6 days,which is comparable to commercial HBIG products. All patientsremained free of HBV recurrence during follow-up. Seven patientsdeveloped reversible mild transfusion reactions and were switched tocommercial HBIG. Any transfusion-transmitted infection or otherserious transfusion complication was observed. The cost for one HIPunit is 140 US$ with an average yearly treatment costs of 1’148 US$per patient, which compares to 25’000–100’000 US$ for treatmentwith commercial HBIG. Conclusions: HIP is an effective, safe and inexpensive treatment forthe prevention of HBV recurrence after LT. It can be easily producedand may be an attractive alternative to commercial HBIG products.

7Esophageal dysfunction induced by gastric banding –bolus transit and manometric abnormalitiesBorovicka, Jan; van der Weg, Boudewijn;Thurnheer, Martin; Schultes,Bernd; Grübel, Claudia; Kuenzler, Patrizia; Pohl, Daniel; Fried,Michael; Meyenberger, Christa; Tutuian, Radu Division of Gastroenterology Kantonsspital St.Gallen; Department of Surgery, Kantonsspital St. Gallen; Division of GastroenterologyUniversity of Zurich Background: Recent studies report on esophageal motility disordersinduced by gastric banding, on occasions severe enough to mimicpseudoachalasia. The effect of gastric banding on esophageal bolustransport is underinvestigated. Aim: Evaluate changes in esophageal symptoms, peristalsis, bolustransit and clearance in patients with gastric banding. Methods: Obese patients who previously underwent gastric bandingwere evaluated. Clinical assessment included 7-point Likert scalerating of dysphagia, heartburn, regurgitation and chest pain. Patientswere asked to rate these symptoms during times when the band wasinflated and deflated. Esophageal persistalsis and bolus transit wereassessed using combined impedance-manometry. Esophageal emptying was assessed using a modified timed barium swallow. Results: Thirty-three patients (28 F, mean age 43.4, range 27-61years) underwent esophageal evaluations. When the gastric bandwas inflated patients experienced more symptoms. Esophagealmanometry was abnormal in 48.5% patients (14 ineffectiveesophageal manometry, 2 esophageal spasms) while esophagealimpedance testing found abnormal bolus transit in 72.2% patients.Esophageal clearance (barium swallow) and bolus transit (impedance)agreed on normal vs. abnormal esophageal function in 21/23 patients(kappa 0.775; p’ZO.O1). Conclusions: Assessing esophageal bolus transit/clearance complements esophageal manometry in assessing the degree ofesophageal dysfunction induced by gastric banding. Impedancemeasurements allow a better understanding of abnormal motility inthe obstructed esophagus. Improved symptoms when the gastricband is deflated gives hope that these changes are reversible. Ongoing studies evaluate the reversibility of esophageal dysfunctioninduced by gastric banding.

8Benefit of baseline cytometry as add-on to standard histology on surveillance in patients with Barrett! esophagus Vogt, Nicole; Schönegg, René; Gschossmann, Juergen M.; Borovicka, Jan Division of Gastroenterology, Kantonsspital St. Gallen. Institute of Pathology, Kantonsspital St. Gallen. Division of Gastroenterology,University Hospital Bern Background and Aims: The current gold standard in the surveillance ofBarrett’s esophagus (BE) is the Seattle four quadrant biopsies protocol(4-QB) every 1 to 2 cm. Using endoscopic brush cytology we studiedprospectively whether digital image cytometry (DICM) is of additionalbenefit to regular histology as a predictor for progression to high-gradedysplasia (HGD) or cancer during a surveillance of at least 3 years. Methods: In this prospective cohort we included 74 patients (65% male)with BE and baseline endoscopies with at least one DICM in additionto 4-QB. A minimal endoscopic surveillance follow-up of at least 3 years at the time of analysis was requested. HGD and adenocarci-noma (AC) were defined as primary endpoints. DNA patterns weredefined as diploid (2c), intermediate and aneuploid.

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Results: 8 of 74 patients with diagnosis of HGD or AC at baselineendoscopy were excluded from follow-up analysis. 66 patients wereanalyzed after a mean follow-up time of 44 months (range 36-72). Ten of 66 patients (15%) had low-grade dysplasia (LGD) at baselinehistology: One of two patients with LGD and aneuploid DICM showedHGD on follow-up whereas none of 8 patients with LGD and diploidDICM developed HGD. 56 of 66 patients (85%) had either no dyspla-sia (49) or indefinite for dysplasia (5) at baseline histology. One of 6 patients with no dysplasia and intermediate/aneuploid DICM devel-oped HGD. None of those with negative or indefinite for dysplasiaand diploid DICM had HGD on follow-up, at baseline and no patientwith diploid DICM developed HGD. Conclusion: DICM from brush cytology as add on to histology appearsto be of additional benefit during surveillance of BE. While aneuploidywarrants an early re endoscopy a diplod result of DICM underscoresthe low-risk status in patients with low-grade dysplasia. Studies withlarger Datient arous at low-risk are therefore encouraged.

9Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients Philip Bruggmann1, Luis Falcato1, Beat Helbling2, Olivia Keiser3,Francesco Negro4, Daniel Meili1 on behalf of the Swiss Hepatitis CCohort Study 1 ARUD Zurich, 2 Department of Gastroenterology and Hepatology,Stadtspital Waid, Zurich, 3 SCCS Cohortcenter Lausanne, 4Department of Gastroenterology and Hepatology HUG, Geneva Background: Reluctance has been expressed about treating hepa -titis C (HCV) in active IV drug users in both guidelines and clinicalpractice. IV drug users make up the largest risk group in HCVpatients. The literature affords no evidence for a general exclusion ofthis high risk group. The aim of this study was to evaluate the directinfluence of active IV drug use on the efficacy of HCV treatment.Methods: In this retrospective study 2535 patients were analysed. Tostudy the direct influence of IV drug use on treatment outcome weselected only patients adherent enough to have their serum HCV RNAtested 6 months after the end of treatment and to attend at least onecohort follow-up visit during HCV therapy, documenting the drug usestatus. Type of anti HCV medication and the cumulative dose ofinterferon and ribavirin were assessed for all patients. Results: The proportion of patients with a sufficient antiviral drugexposure (>80% of the scheduled cumulative dose) and treatmentduration (>80% of the scheduled duration) was comparable in thetwo groups: 66% of the patients with active IVDU during therapy and 60.5% in non-IVDU group. The SVR rate was 69.3% in the IVDUgroup and 59.8% in the non-IVDU group. The multiple logistic regres-sion analysis showed that the only independent predictors of SVRwere HCV genotype and age whereas active IVDU during therapy didnot have a significant influence on treatment outcome. Conclusions: IV drug use does not have a negative direct influence onthe efficacy of HCV treatment in patients adherent to antiviral therapy.Our study results should encourage physicians not to exclude IVDUper se from HCV treatment. Based on our experience adherence in IVdrug users can be improved by a comprehensive care setting and byinterfacing opioid maintenance treatment with HCV therapy.

10Alcohol consumption during Hepatitis C therapy in patients of the Swiss hepatitis C cohort study Philip Bruggmann, Magdalena Dampz, Luis Falcato ARUD Zurich Background: Usually clinicians demand complete abstinence for atleast 6 months before treating alcoholics for hepatitis C (HCV). Thereis only few data on the effect of ethanol consumption during HCVtherapy. This evaluation uses the data of the Swiss hepatitis C cohortstudy (SCCS) to examine the effect of ongoing alcohol intake onsustained virological response (SVR).

Methods: Patients were eligible for the study if they had their HCVRNA tested 6 months after the end of treatment and at least onecohort follow-up visit during HCV therapy, documenting the con-sumed amount of alcohol. They were assigned to three groups: abstinence, 1 24g alcohol per day and 25g and more per day. Thetype of interferon and the cumulative dose of interferon and ribavirinwere assessed additionally. Results: At the time of the analysis, 2535 people were included in theSCCS. 368 patients were included, 236 (64%) indicating no alcoholconsumption during HCV therapy, 100 (27%) with 1-24g/d and 32(9%) with 25g and more ethanol a day. Neither the type of interferonused nor the rate of patients with at least 80% of the scheduledcumulative dose (59.5% vs. 65.7% vs 59.4%) did significantly differbetween the three groups. 93% of all patients were treated withpeginterferon. The SVR rate for non drinker group was 64%, for the1-24g group 61% and ≥25g/d group 50%. No significant negativeinfluence of alcohol consumption during therapy was observed in themultiple regression analysis for treatment success (OR 1.16 for>24g/d, 95% CI 0.72-3.66). Conclusion: Alcohol seems not to have a relevant direct influence onthe efficacy of anti HCV drugs, as drinkers reached similar rates ofSVR and sufficient cumulative doses to non drinkers. Previous stud-ies described a negative influence of a recent history of alcoholism onthe compliance to HCV therapy, a factor which was not studied in thisevaluation. Future efforts in care of patients not able to abstain com-pletely from alcohol should attempt to improve compliance. Thiscould be reached for example by comprehensive care with high fre-quency contact settings during HCV treatment.

11Prognostic influence of immunohistochemically detected lymph node micrometastasis and histological subtype in pN0 oesophageal cancer M. Busch3, U. Zingg1, M. Montani2, U. Metzger3, P. Went2, D. Oertli11 Department of Surgery, University Hospital Basel, 4031 Basel,Switzerland, 2 Department of Pathology, Triemli Hospital Zurich, 8063 Zurich, Switzerland, 3 Department of Surgery, Triemli HospitalZurich, 8063 Zurich, SwitzerlandIntroduction: Differences in frequency and clinical impact of lymphnode micrometastasis between histological subtypes of oesophagealcancer have not been determined. Methods: 1204 lymph nodes from 32 squamous cell carcinomas and54 adenocarcinomas with complete resection and pN0 status werere-evaluated using a serial sectioning protocol including immunohis-tochemistry. Intra-nodal tumor cells were classified as micrometas-tases (0.2–2 mm) or isolated tumor cells (<0.2 mm). Results: No significant difference in the frequency of micrometas-tases between adenocarcinoma and squamous cell carcinoma(11.3% vs. 3.1%, p=0.247) occurred. Kaplan-Meier curves showed a significantly prolonged 5-year survival (p=0.017) and disease freeinterval (p=0.006) in immunohistochemically negative patients withsquamous cell carcinoma. In adenocarcinoma, no difference (p=0.404and p=0.092, respectively) was seen. Patients without pre-treatmentand adenocarcinoma showed a significant 5-year survival (65% vs. 53%; p=0.029) and disease free interval (83% vs. 58%; p=0.048)advantage compared to squamous cell carcinoma. After pre-treat-ment, no difference between the histological subtypes could bedetected. Regression analysis showed no factor influencing overallsurvival significantly in this nodal negative collective, whereas fourfactors influenced disease free interval significantly: pre treatment (HR 3.3 [95% CI 1.2-9.1], p=0.020); micrometastasis (HR 5.3 [95% CI 1.4-19.7], p=0.012); UICC stage II vs. 0/I (HR 2.2 [95% CI 1.1-4.4],p=0.032); adenocarcinoma (HR 0.3 [95% CI 0.1-0.9], p=0.028). Conclusion: The differences in frequency and clinical impact ofimmunohistochemically detected micrometastasis may indicate thatadenocarcinoma and squamous cell carcinoma should not be treatedas one entity.

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12The Hepatitis C Virus Core Protein of different Genotypes Down- Regulates Insulin Receptor Substrate 1 via Genotype -Specific Mechanisms Sophie Clément1, Stéphanie Pascarella1, Valerio Pazienza1, KévinGuilloux1, Stéphanie Conzelman1 and Francesco Negro1,2

1 Divisions of Clinical Pathology and of 2 Gastroenterology andHepatology, University Hospital, University of Geneva School ofMedicine, Geneva Background: HCV is now considered as one of the causes of insulinresistance as it increases the homeostasis model assessment(HOMA) score in patients even in the early stage of liver disease,while HCV clearance leads to a decrease of the HOMA score. HCVleads mainly to insulin resistance through the down regulation of IRS 1via mechanisms that seem to be specific for each HCV genotype. Infact, IRS 1 down regulation occurs through a decrease of the peroxi-some proliferator activated receptor (PPAR ) and the up regulation ofsuppressor of cytokine signaling (SOCS) 7 in genotype 3a, andthrough the activation of mTOR for genotype 1b. Our goal in thisstudy was double: (1) to study the mechanism leading to insulinresistance in other genotypes (namely 2a, 4h) and (2) to compare and analyze the sequence of the core protein of different genotypes in order to identify the amino acid residues responsible for insulin resi stance. Methods: Using a lentiviral system, we expressed the HCV coreprotein of genotypes 2a, 4h and chimeric constructs and we meas-ured the expression levels of IRS 1 and several SOCS family mem-bers, involved in the insulin signal pathway in a human hepatoma cell line (Huh 7). Results and Conclusions: Our results show that while HCV coreproteins of all genotypes induced downregulation of IRS 1, mecha-nisms involved different actors and pathways in each case. In addi-tion, investigations with chimeric constructs give the first indicationsregarding the sequence involved in these processes.

13Monocyte Chemoattractant Protein 1 Secreted By Adipose Tissue Induces Direct Lipid Accumulation In Hepatocytes Sophie Clément1, Cristiana Juge- Aubry5, Antonino Sgroi3, StéphanieConzelmann1, Valerio Pazienza1, Brigitte Pittet -Cuenod4, Christoph A.Meier5,6 and Francesco Negro1,2

1 Div. of Clinical Pathology and of 2 Gastroenterology andHepatology, 3 Surgical Research Unit, 4 Div. of Plastic andReconstructive Surgery, HUG, 5 Lab. of Molecular Endocrinology, Dpt of Cellular Physiology and Metabolism, Uni. of Geneva 6 Dpt ofMedicine, Triemli Hospital, Zurich Background: Since the discovery that adipocytes may secrete a variety of bioactive molecules (hormones, chemokines andcytokines), an endocrine and paracrine role for white adipose tissue in the regulation of energy balance and other physiological processeshas been established, particularly with regard to brain and muscle. In contrast, little is known about the interactions of white adiposetissue with liver. Hence, we examined the effect of the secretoryproducts of white adipose tissue on hepatocytes. Results: Conditioned medium of human white adipose tissueexplants induced significant steatosis in hepatocyte cell lines. Factor(s) responsible for the conditioned medium induced steatosiswere screened by a battery of blocking antibodies against differentcytokines/chemokines shown to be secreted by white adipose tissue. In contrast to interleukin-8 and - 6, the monocyte chemoat-tractant protein -1 was capable of inducing steatosis in hepatocytes ina time -dependent manner at concentrations similar to those found inconditioned medium. Incubation of conditioned medium with anti-monocyte chemoattractant protein -1 antibodies prevented triglyc-erides accumulation. Investigation of the mechanism leading to the triglyceride accumulation showed that both a diminution ofapolipoprotein B secretion and an increase in phosphoenolpyruvatecarboxykinase mRNA may be involved. Conclusions: The monocyte chemoattractant protein -1 secreted byadipose tissue may induce steatosis not only recruiting macrophagesbut also acting directly on hepatocytes.

14Sorafenib treatment for advanced HCC prior to surgery: Should we stop? JF. Dufour1, P. Romanque1,3, S. Wilhelm2

Institute of Clinical Pharmacology, Bern University 1, Switzerland,Bayer HealthCare Pharmaceuticals, Inc. USA 2. Medicine Faculty,University of Chile, Santiago, Chile 3 Background: HCC is the third most common cause of cancer relateddeath. Therapeutic options depend on the stage of the tumour, butonly patients with small HCCs are amenable to curative treatments.Sorafenib is a multiple kinase inhibitor which blocks the receptortyrosine kinases VEGFR, KIT and PDGFR-b and the ser/thr kinaseRAF. Sorafenib has been approved by the EMEA and the US FDA forthe treatment of unresectable HCC. Another potential indication forNexavar® is neoadjuvant therapy for patients with advanced disease,who are candidates for surgery. No preclinical studies of sorafenib onliver regeneration have been conducted, which was our aim. Methods: C57BL6 mice received oral BAY 54-9085, sorafenib tosylate, 30 mg/kg/day or its vehicle for 14 days before undergoing2/3 hepatectomy. Treatment was stopped the day before surgery(group B) or given continuously for up to 120h post hepatectomy(group C). For both groups the time points 24, 72 and 120 hours afterhepatectomy were investigated. Liver, scar tissue and blood sampleswere taken at endpoints. Results are presented as Mean ± SD.Results: When animals received continuous sorafenib treatment(group C) impaired liver regeneration was observed at 120h, whichwas statistically significant compared to control groups. (C=0.52±0.06,n=8 vs. vehicle=0.072±0.1, n=4 p<0.001, One way ANOVA and New-man Keuls). No significant differences in liver weight at the endpointwere observed when the treatment is stopped the day before surgery.Side effects such as diarrhoea, wound healing complications andbleeding during surgery were observed in few cases. Weight loss of about 10% occurred in animals treated with the drug. Additionalstudies to examine the effects of sorafenib treatment on BrdU incorporation and growth factor expression in this liver regenerationpreclinical model are ongoing. Conclusion: Our study indicates that when administered beforesurgery sorafenib therapy should be stopped before the resection.

15Laparoscopic vs. open sigmoid colectomy for diverticulardisease. A prospective randomized single-blind trial Pascal Gervaz, Ihsan Inan, Eduardo Schiffer, Philippe MorelDepartments of Surgery, University Hospital Geneva Background: Potential advantages for a laparoscopic approach tosigmoid resection include a reduction in postoperative pain and ashortened duration of hospital stay. The aim of this study was tocompare open (OP) vs. laparoscopic (LAP) sigmoidectomy for diver-ticular disease with the patient blinded to the surgical approach. Methods: 100 patients (median age 60 [range 34-84] years) scheduledfor an elective sigmoid resection for diverticular disease were random-ized to receive either a traditional open (47 patients) or a laparoscopic(53 patients) approach. Postoperatively, an opaque wound dressingwas applied and left in place for 4 days, and patients from both groupswere managed similarly. The primary endpoints for analysis were; 1)postoperative pain; 2) duration of postoperative ileus; and 3) durationof hospital stay. Results: Median duration of the procedure was 115 (range 85-210)minutes in the OP group and 165 (range 120-285) minutes in the LAPgroup (p<0.0001). The median delay between surgery and passing offlatus and stool were 28 and 80 hours in the LAP group versus 47 and102 hours in the OP group (p=0.0002). The median Visual AnalogScores (VAS) for pain on postoperative days I to IV were 3, 2, 2 and 1 inthe LAP group and 4, 3, 2 and 1 in the OP group (p=NS). Similarly, themedian dose of systemic opiates administrated was 2.5 (range 0 32)MG in the LAP group vs. 7.5 (range 0-60) MG in the OP group (p=0.08).Finally, the median duration of hospital stay was 5.5 [range 4-44] daysin the LAP group vs. 7 (range 5-17) days in the OP group (p=0.0003). Conclusion: Laparoscopic sigmoid resection is longer to perform, butis associated with a significant reduction in the duration of postopera-tive ileus, and hospital stay; however, neither postoperative pain, northe dose of systemic opiates were significantly reduced in the LAPgroup. These results confirm the benefit of a laparoscopic approachfor sigmoid resection, but also prove that its magnitude, when thepatient is blinded to the surgical approach, is less than expected.

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16Stage IV colorectal cancer treated with neoadjuvantchemotherapy: a comparison of histological response in livermetastases, primary tumors and regional lymph nodes Background: We report herein the histopathological results of a novel“inversed” strategy designed to manage CRC patients presentingwith synchronous liver metastases using chemotherapy first, liversurgery second, and resection of the primary tumor as a final step.The aim of this study was to assess and to compare the response tochemotherapy in the resected liver metastases, in the primary tumorand in the locoregional lymph nodes. Methods: 27 patients with stage IV CRC were initially treated with acombination of oxaliplatin, irinotecan, 5-fluorouracil and leucovorin(OCFL) for 3-4 months. Histological response to chemotherapy wasassessed using a tumor regression grading (TRG) score based on the presence of residual tumor cells and the extent of fibrosis. TRG1corresponded to absence of tumor cells replaced by abundant fibrosis; TRG2 to rare residual tumor cells scattered throughout abundant fibrosis; TRG3 to more residual tumor cells throughout apredominant fibrosis; TRG4 to large amount of tumor cells predo -minating over fibrosis; and TRG5 most exclusively to tumor cells without fibrosis. Results: Median age of patients was 56 (range 37-69) years. Primarytumor location was: right colon (4); left colon (7); and rectum (16 patients). Median number of liver metastases was 5 (range 1-21).The median delay between liver surgery and resection of the primarywas 45 (range 0-280) days. Complete tumor response (pT0N0M0)was achieved in 2 patients. The majority of patients (81%) demon-strated identical (48%) or better (33%) response in the liver metas-tases than in the primary tumors. Complete absence of response(TRG5) was documented in the lymph nodes of 3 out of 19 (16%)patients with N+ tumors. Conclusion: Colorectal cancer is chemosensitive, whether it is primary or metastatic to the liver. Complete pathologic response,however, rarely occurs, and the most chemoresistant locationappears to be the locoregional lymph nodes. These data indicate that oncologically adequate lymph node and primary tumor resectionis still warranted after OCFL neoadjuvant chemotherapy for meta -static CRC.

17Carbon dioxide insufflation in routine colonoscopy: safe and more comfortable Geyer M1, Beglinger Ch2

1 Gastroenterologie Wettingen, 2 Dept. of Gastroenterology,University Hospital, Basel Background: Many patients experience pain and discomfort aftercolonoscopy. Preliminary studies indicate that insufflation of carbondioxide (CO2) can reduce periprocedural pain although air insufflationhas remained the standard procedure. It is therefore of interest todevelop methods that can reduce patient discomfort. Methods: 200 consecutive patients undergoing colonoscopy in aprivate GI practice will be enrolled in this study. Patients are randomlyassigned to either CO2 or air insufflation (double blind procedure).Pain and bloating and overall satisfaction are assessed on a 10 pointVAS scale during and after the examination at 1, 3, 6 and 24 hours.Transcutaneous CO2 is continuously measured with a Capnograph,as CO2 insufflation might lead to CO2 retention. Results: Up to now a total of 147 patients have been enrolled. 75 patients were randomized to CO2 (group 1) and 72 to normal air(group 2). The baseline characteristics were similar in both groupswith respect to age, gender and bmi. The mean propofol dose was132 ± 54 mg vs 115 ± 50 mg, respectively. The time to reach the ileumand the withdrawal time were 7.8 ± 4.4 and 13.1 ± 5.1, respectively(group 1) and 6.4 ± 4.2 and 12.5 ± 4.8 min (group 2, ns). pCO2 at theend of procedure was 35.6 ± 4.4 mm Hg (in group 1) versus 36.0 ± 6.3 mm Hg (group 2, ns). No significant respiratory distress and norelevant complication occurred. In the post procedure recovery periodin the office there was a strong tendency and over the 24 h thereafter(24 h VAS sum score) significant (p values ranging from 0.04-0.02)less bloating and less pain in group 1 (VAS sum score of 2.7, 1.5; 5.0 and 3.4) compared to group 2 (4.3, 2.1, 11.0 and 6.1). Finally, a higher satisfaction score (p=0.008) could be noted. The overallacceptance of the colonoscopy was excellent. Conclusion: The preliminary data of this study indicate that CO2

insufflation can significantly reduce bloating and pain in routinecolonoscopy. The procedure seems to be safe as no significant differences in CO2 measurements were seen.

18Distal Roux-en-Y Gastric Bypass: Mid-term Results Jean-Marc Heinicke, Pietro Renzulli, Yves Borbely, Phaedra Müller,Daniel Candinas Department of Visceral and Transplantation Surgery, Inselspital, BernUniversity Hospital and University of Bern Background: Classical Roux-en-Y gastric bypass (cRYGB) is a com-bined restrictive and slightly malabsorptive operation. Excess -BMI-loss (EBMIL) in cRYGB is ~60%, but is diminished for super obesepatients (BMI > 50 kg/m2). We therefore designed a modified, mainlymalabsorptive distal RYGB (dRYGB). Methods: We report mid-term results after 77 consecutive dRYGB inwhich malabsorption is inversely related to the length of the commonchannel. The common channel was 100–150 cm long depending onpreoperative BMI, the biliopancreatic limb was 100 cm long, which left >>250 cm for the alimentary channel. To avoid the potentiallydangerous combination of malabsorption with sustained restrictionthe pouch size was increased to ~50ml and a 25 mm circular staplerwas used for the gastro-jejunostomy. Results: 33 open and later on 44 laparoscopic interventions havebeen performed. Median preoperative BMI was 50.2 kg/m2. No severeintraoperative complications have been observed and no anastomoticleakage was noted in the postoperative period. 5 patients neededballoon dilation of an anastomotic stricture. 3 marginal ulcersoccurred at the gastrojejunostomy. The 54 patients with a follow-uptime of over 12 months (median 24 months) showed an overallmedian BMI-reduction of 17 to an actual median BMI of 31.6 kg/m2,corresponding to a EBMIL of 74.5%. Obesity-related comorbid conditions were significantly reduced or cured. Intermittent diarrheaor steatorrhea in 12 patients was easily treated by pancreatic enzymesupplementation. Conclusion: dRYGB is technically more demanding than cRYGB, but shows excellent results in terms of weight-loss and therefore also in reduction of comorbidity especially in super-obese patients.Measuring all three limb lengths allows for a calibration of the malabsorption. The quality of food-intake being important to (super-)obese patients in terms of quality of life, a less restrictive pouchseems more adapted to them. Lifelong multidisciplinary follow-up is mandatory.

19Propofol administration has no significant effect on hepaticvenous pressure gradient measurements Mona Y. Hellstern1, Ludwig T. Heuss2, Markus H. Heim1

1 Abteilung für Gastroenterologie und Hepatologie, UniversitätsspitalBasel, 2 Spital Zollikerberg, Zürich Background: Hepatic venous pressure gradient HVPG) measure-ments provide reliable information about the portal venous pressure.Recently it could be shown that HVPG can provide prognostic information about the risk of variceal bleeding and efficacy of phar-macological treatment of portal hypertension. For many patients, the procedure causes some degree of discomfort and sometimespain. Sedation during the procedure would increase patient comfort.Formore than 6 years propofol has routinely and safely been used in our department for sedation during endoscopies. Propofol can lead to alowering of the arterial blood pressure and therefore maylead to an incorrect result of the HVPG measurement in sedatedpatients. Aim: The aim of the present study was to investigate if sedation ofpatients with propofol has a significant effect on HVPG measure-ments. Methods: HVPG measurements were performed in 11 patients withliver disease before and during propofol sedation.Results: 10 of the 11 patients had portal hypertension. The meanHVPG before sedation was 16.5 mmHg (SEM 1.6) and during seda-tion with propofol 14.4 (SEM 1.4). In 3 of the 10 patients with portalhypertension, HVPG was more than 20% lower during sedation. Inthis small group of patients, the changes of HVPG values did notcorrelate with changes of the mean arterial blood pressure.Conclusion: Propofol sedation is safe and increases patient comfortduring HVPG measurements. However, in some patients, HVPGvalues are significantly lowered by propofol sedation. This has to beconsidered for the interpretation of the individual patient values in the the context of published series difficult.

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20Results of in situ adult-child split liver transplantation in a Swiss program Majno P, Wildhaber B*, Bihl F, Morel Ph, Giostra E, BednarkiewiczM,Berney T, Buhler L, Chardot C* Mentha GVisceral Surgery, Transplantation and Pediatric Surgery*,Geneva University Hospitals, Switzerland Background: To share the results of in situ split liver transplantationin a mixed adult and pediatric program while this procedure is tosome extent controversial in the opinion of adult transplant centers.Patients and methods: Since November 1999, 27 in situ splits for 7 adult and 20 pediatric recipients have been performed in our center.Results: Pediatric patients were between 6 months and 15 yearsold(median 1.6 years), adult recipients were between 33 and 66 yearsold (median 50 years). After a median follow-up of 3.5 years, overallpatient survival was 90% for pediatric patients (one death from massivepulmonary embolism in a patient with Budd-Chiari syndrome and a childwith graft-versus-host associated to recipient’s bone marrow aplasiaaccompanying fulminant hepatic failure) and 86% for adult patients(onelate death from neurodegenerative disease). Complications in children included primary non-function (1), requiring retransplantation,hepatic artery thrombosis (2), and biliary problems (7, 36%), none causing graft loss. In adult patients there were no cases of primary non-function or vascular complications. Biliary complications occurred in two patients andwere solved by surgical revision of the anastomosis.Conclusions: in the current era of organ shortage, in situ SLTappears justified despite the increased work burden inherent to theprocedure, asit generates grafts of superior quality. For adults inparticular, patient and graft survival figures are excellent and shouldencourage promoting of the technique in other centers.

21Alterations of the mitochondrial functions by the HIT proteinHint2 Juliette Martin1, Nadège Bellance2, Giovanni Benard2, Dagmar Hahn3,Olivier Maurhofer1, Rodrigue Rossignol2 and Jean-François Dufour1

1 Institute of Clinical Pharmacology, University of Berne, Switzerland, 2 INSERM, U688 Physiopathologie mitochondriale, Université VictorSegalen-Bordeaux 2, Bordeaux, France, 3 Department of ClinicalChemistry, Inselspital, Berne, Switzerland Background: We identified previously HINT2, a protein expressedpredominantly in the liver and the first human HIT protein to be local-ized in mitochondria. We previously reported that over-expression of HINT2 resulted in enhanced apoptosis after treatment with anti-Fas/actinomycin D and that the expression of HINT2 was down-regu-lated in hepatocellular carcinoma. The aim of this study was to inves-tigate the effects of HINT2 expression on mitochondrial function. Methods: HepG2 cell lines over-or under-expressing HINT2 and theirrespective controls were studied. The activity of the complexes I to IV of the respiratory chain was determined, O2 consumption as wellas ATP levels were measured and the morphology of fluorescentlylabelled mitochondria microscopically assessed. Results: Over-expression of HINT2 resulted in a 30% increase in ATP content, whereas down-regulation of HINT2 resulted in a 20%decrease in ATP content. The activity of the respiratory chain com-plexes in homogenized isolated mitochondria was not differentbetween the cell lines. In condition of ATP synthesis, O2 consumptionwas decreased by 30% in the mitochondria isolated from cellsexpressing less HINT2 than their controls, the same observed withpermeabilized cells. Over-expression of HINT2 did not affect O2 con-sumption but resulted in a denser mitochondrial network. Conclusion: The level of expression of HINT2 affects the mitochon -drial network and its functional capacity. The decrease in O2 con-sumption and ATP content may represent an advantage for tumoralcells having less HINT2.

22Results of living donor liver transplantation in a Swiss program Mentha G, Majno P, Chardot C*, Bihl F, Giostra E, Morard I,Bednarkiewicz M, Wildhaber B*, Berney T, Buhler L, Hadengue A,Morel, P. Visceral Surgery, Transplantation and Pediatric Surgery*, GenevaUniversity Hospitals, Switzerland Background: To share the results of living donor liver transplan -tation(LDLT) in a mixed adult and pediatric program while this proce-dure is tosome extent controversial in the opinion of Swiss HealthSystem decision makers. Patients and methods: Since April 1999, 17 adult-to-adult (A-LDLT)and 8 pediatric (P-LDLT) (left lobe: segments 2-3) have been per-formed in our center. Results: For A-LDLT, the 17 donors were between 20 and 63 yearsold (median 37 years), 11 women and 6 men. All had been dischargedhomeafter 2 weeks, with normal liver function. Major complicationswere abilioma, drained under CT, pneumonia, an occipital patch ofalopecia that had to be excised under local anesthesia, and a biliaryfistula that resolved spontaneously. For P-LDLT, donors were dis-charged after 6-10 days without major complications. The 17 adultrecipients were between 29 and 58 years old (median 53y), there were6 women and 11 men. Median graft to recipient weight ratio was 1%with 2 cases below 0.8%. The middle hepatic vein was harvestedwith the graft and in 3 cases avenoplasty with the hepatic venousbranches to segment 5 and 8 was done. Vascular complicationsoccurred in two patients, both having required interposition grafts(portal and arterial), and biliary complications in 6 patients, (2 leaksand 4 strictures), none leading to graft loss. Three patients died: onepatient at two months from MOF, another at 11 months because oftumor recurrence (sarcomatous hepatocellular carcinoma), and onepatient at 4 years because of HCV recurrence. All P-LDLT recipientsare alive with a functioning graft (follow up 6-44 months). After amedian follow-up of 48 months, (range 1 to 104 months), actuarialpatient and graft survival were 85% at 1 year, 78% at 3 years and72% at 5 years.Conclusions: In the current era of graft shortage LDLT appears justified by the results that are similar to LT from deceased donors.The procedure seems particularly appropriate for patients withoutforeseeable surgical problems, and quality of life deterioration that is underweighted by the current allocation system.

23avb6 integrin is a highly specific marker in the diagnosis ofcholangiocarcinoma Eleonora Patsenker1, Ludwig Wilkens2, Vanessa Banz3, Adrian Keogh3,Deborah Stroka3, Felix Stickel11 Institute of Clinical Pharmacology, University of Bern, Switzerland; 2 Departments of Visceral and Transplantation Surgery, and 3 Pathology, Inselspital Bern, Switzerland Background and Aims: Hepatocellular carcinoma (HCC) and cholan-giocarcinoma (CC) are the most common primary hepatic malignan-cies. Immunohistological differentiation of both tumors is pivotal fortreatment and prognosis. Recently, avb6 integrin was found stronglyupregulated in experimental biliary fibrosis and patients withcholestatic liver disease, but its hepatic expression, diagnostic applicability and role as a therapeutic target in CC is unknown.Methods: 77 HCC and 73 CC paraffin-embedded tissues frompatients who underwent partial hepatectomy were collected andimmunostained for avb6 integrin. avb6 integrin mRNA expressionwas quantified from CC and HCC tissues, and normal liver. Also,gene expression of the b6 chain was quantified by RT-PCR in humancell lines including cholangiocarcinoma cells (TFK-1), hepatocellularcarcinoma cells (HepG2), immortalized cholangiocytes (MMNK-1) andprimary liver cells. Results: Immunohistological staining for the b6 receptor was stronglypositive on proliferating biliary epithelia in 86% of CC specimens,whereas all HCC were negative. b6 mRNA expression was induced in CC tissues and about 100-fold upregulated compared to HCC andnormal liver tissues. In vitro, an extremely high expression of the b6chain was detected in TFK-1 cells (73-fold), while expression inMMNK-1 cells was low, and absent in HepG2 cells. No associationwith tumor grade, tumor location, pattern of tumor, fibrosis and mucinexpression was found. Conclusions: avb6 integrin is dramtically upregulated in CC and canbe considered a highly specific immunohistological marker for differ-ential dianosis of primary liver tumors.

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24mTOR Activation by HCV Core Protein Protects Hepatoma Cells from TGF Beta Induced Apoptosis Valerio Pazienza1, Sophie Clément1, Paolo Pugnale1, StephanieConzelman1, Alessandra Mangia2, Francesco Negro1,3

From the 1 Divisions of Clinical Pathology and of 3 Gastroenterologyand Hepatology, University Hospital School of Medicine of GenevaSwitzerland; 2 Division of Gastroenterology, Ospedale «Casa Sollievodella Sofferenza», S. Giovanni Rotondo, Italy Background and aims: Several HCV proteins have been shown toaffect the interferon signaling and the pathways leading to apoptosisin in vitro expression systems. Such modulatory effects may representa key mechanism to circumvent host innate and adaptive immuneresponses in order to establish persistent infection. In addition, theymay promote HCV associated tumorigenesis, leading to hepatocellularcarcinoma and B cell lymphoma. Methods: We used a human hepatocyte hepatoma cell line transientlyexpressing the HCV core proteins of genotypes 1b ad 3a to investi-gate their effects of on interferon alpha signaling and hepatocyte apop-tosis induced by a variety of stimuli (IFN a, TRAIL, TNF a and TGF- b). Results: HCV core proteins of both genotypes 1b and 3a failed tomodify the gene expression and activation of factors classically acti-vated by IFN a (Mx protein, 2’ 5’ OAS, PKR). However, we found that thetransient expression of the HCV 1b core protein (but not 3a) renderedHuh 7 cells resistant to apoptosis induced by TGF- b (1b vs 1b+TGF - bp= NS, GFP vs GFP+TGF - b p= 0.014). To test whether mTOR activa-tion induced by HCV 1b core was involved in the resistance to apopto-sis, we co incubated transfected cells with TGF -b and rapamycin, whichresulted in a ~100% increase in the number of apoptotic cells (testedby FACS). TGF - b induced nuclear translocation of SMAD3, was signi -ficantly reduced in cells transfected with HCV core protein 1b (52.66 ± 0.08%) as compared to those expressing only the GFP protein ascontrol (83.55 ± 0.05%; p= 0.048). However, when hepatocytesexpressing the HCV core protein 1b were co incubated with TGF - b andrapamycin, the nuclear translocation of SMAD3 increased to levelscomparable to controls (86.57 ± 0.04%; p= NS). In parallel, in Huh 7cells expressing the core protein 1b, the SMAD3 mRNA expressionlevels increased after co incubation with TGF - b and rapamycin (1b vs 1b +TGF - b + rapamycin p= 0.036) whereas the TGF - b alonefailed to increase SMAD3 mRNA levels (1b vs 1b+TGF - b p= 0.25432). Conclusion: The HCV 1b core protein activates mTOR in Huh 7 cells:this results in decreased sensitivity to TGF - b induced apoptosis.

25Liver regeneration is impaired in hepatocyte-specific Pten defi cient mice Anne-Christine Piguet1, Monika Ledermann1, Jean-François Dufour1

1 Institute of Clinical Pharmacology, University of Berne, Switzerland Background: Signaling by growth factors plays an important role inliver regeneration. Pten dephosphorylates the lipid messenger PtdIns -3,4,5-P3 (PIP3) thereby decreasing the activity of phosphoinositide-3 kinase (PI3K), a key enzyme that relays signaling by growth factors.Pten-deficiency leads to unbalanced activation of PI3K, resulting incellular hyperproliferation and oncogenesis. Conditional knockoutmice lacking hepatocellular expression of Pten (AlbCrePtenf/f) sponta-neously develop hepatomegaly and hepatocellular carcinomas. Theaim of our study was to investigate whether liver regeneration wasaffected by the lack of Pten. Methods: 2⁄3 partial hepatectomy (PH) was performed in femaleAlbCrePtenf/f and C57BL/6 mice (10 weeks-old). Animals were sacri-ficed at 48 and 72 hours post PH and the remaining livers weighed.Restoration of liver mass was calculated as: liver weight (g) / totalliver weight at the time of PH (g). Hepatocyte proliferation wasassessed by BrdU immunohistostaining. Data are means±SD. Results: In C57BL/6 mice, liver mass was 36±3% of total liver weightat PH, increased by 13% to 49±5% at 48 hours (n=4) and increasedby 31% to 67±7% (n=7) at 72 hours postoperatively. In AlbCrePtenf/f,the liver mass was 34±2% of total liver weight at PH, increased by20% to 54±2% at 48 hours (n=4) but did not increase further in 72 hours (56±7% of the total liver mass) (n=7). BrdU incorporationconfirmed that liver mass in AlbCrePtenf/f was static between 48 and 72 hours (184±113 positive hepatocytes counts/mm2 vs 199±62,respectively), whereas livers from C57BL/6 mice continued to regen-erate, showing high BrdU incorporation at 48 hours (754±285 positivehepatocytes counts/mm2), and at 72 hours (393±124 positive hepa-

tocytes counts/mm2). The number of positive hepatocytes count was also significantly lower in AlbCrePtenf/f mice. Conclusion: Absence of hepatocellular Pten influences the timecourse of liver regeneration. Hepatocyte-specific Pten-deficient miceregained more of their liver mass 48 hours after partial hepatectomy,but failed to increase further their liver mass at 72 hours. Theseresults suggest a complex role for Pten in liver regeneration.

26The influence of gastric bypass surgery on gastroesophagealreflux and esophageal motility in morbidly obese patients –studies using 24h -Multichannel-Impedance-pH-metry and high resolution manometry D. Pohl1, M. Müller2, M. Weber2, S. Wildi2, P. Janiak1, M. Fried1, R. Tutuian1

1 Division of Gastroenterology and Hepatology, 2 Departement of Visceral Surgery, University Hospital Zurich, Switzerland, Background: The most effective weight-loss treatment for morbidlyobese patients is gastric bypass surgery. The effects of this proce-dure on esophageal function and gastroesophageal reflux are under-investigated. The aim of our study was the evaluation of esophagealperistalsis and gastroesophageal reflux before and after gastricbypass surgery. Methods: Patients evaluated for primary gastric bypass surgeryunderwent pre-, 6-8 weeks and 6-8 months post-operativelyesophageal manometry testing and gastroesophageal reflux moni -toring. Esophageal high resolution manometry (HRM) was performedusing a 32-channel water-perfused system and included 10 water(10ml each) swallows. Following HRM testing, 24-h ambulatory combined impedance-pH monitoring was done. Results: Preoperative data were collected from 48 patients. Tenpatients returned for the 6-8 weeks and 8 patients for the 6 monthsevaluations. Distal esophageal acid exposure, number of refluxepisodes and manometric parameters are summarized in table 1. The percentage of patients with abnormal distal esophageal acidexposure decreased from 22/48 (46%) to 1/10 (10%) at 6 weeks and0/8 (0%) at 6 months (p=0.003).Conclusion: Gastric bypass surgery is an effective anti-reflux proce-dure as it decreases distal esophageal acid and number of acid refluxepisodes. Gastric bypass surgery has no influence on esophagealperistalsis.

Table 1: all data mean ± SEM

pre- 6 weeks 6 months p-valueoperative post-Op post-Op

(% time pH<4) total 4.2 ± 0.7 0.7 ± 0.3 0.3 ± 0.1 0.017

(% time pH<4) upright 5.2 ± 0.8 0.8 ± 0.4 0.2 ± 0.0 0.006

(% time pH<4) 2.7 ± 0.7 0.7 ± 0.6 0.2 ± 0.1 0.217recumbent

# MII-detected 47.7 ± 3.4 60.1 ± 18.8 28.0 ± 6.0 0.098refluxes total

# MII-detected 33.2 ± 2.9 7.4 ± 4.1 3.4 ± 2.1 0.000refluxes acid

# MII-detected 14.4 ± 1.3 52.7 ± 17.9 24.6 ± 5.3 0.000refluxes non-acid

HRM % normal 89.3 ± 3.3 87.2 ± 8.9 96.2 ± 2.9 0.687 contractions

HRM LES resting 25.9 ± 1.8 29.7 ± 3.7 24.9 ± 2.8 0.607pressure (mm Hg)

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27Increased intrabolus pressure: a novel pathophysiologic factor in non obstructive dysphagia? D. Pohl, M. Ribolsi, E. Savarino, M. Fried, R. Tutuian Division of Gastroenterology and Hepatology, University HospitalZurich, Switzerland Background: There are only limited data on the pathophysiologicmechanisms esophageal dysphagia in the absence of structural lesionsor major motility abnormalities. The aim of our study was therefore to compare intrabolus pressure in patients with dysphagia, gastro - esophageal reflux (GERD) symptoms and non-cardiac chest pain. Methods: Patients referred to our laboratory underwent combinedimpedance-manometry testing using 10 saline (5ml each) and 10 bread swallows in recumbent position. Manometric and impe -dance data were recorded at 5, 10, 15 and 20cm above the LES. In each channel intrabolus pressure (IBP) was calculated as averagepressure measured during the time interval elapsed between bolusentry and exit. Results (table 1): In 58 patients (34 females, mean age 47, range 23-81; 18 dysphagia, 17 chest pain and 12 GERD ) intrabolus pres-sure was higher during bread compared to saline swallows (p<0.001).Dysphagia patients had higher IBP during saline (p<0.05) and bread(p<0.05) swallows compared to chest pain and GERD patients.Patients with dysphagia had shorter LES relaxations compared tochest pain patients (p=0.01) during bread swallows.

Conclusion: Increased intrabolus pressure might be a key factor in the pathophysiology of non-obstructive dysphagia. Providing pressure and bolus presence data combined impedance manometry (MII-EM) is an ideal tool for monitoring IBP.

28Hepatitis Delta Virus Inhibits Alpha Interferon Signaling Paolo Pugnale1, Valerio Pazienza1, Kévin Guilloux1 and FrancescoNegro1,2

1 Divisions of Clinical Pathology and of 2 Gastroenterology andHepatology, University Hospital, Geneva, Switzerland Background: Hepatitis delta virus (HDV) can cause severe acute and chronic liver disease in patients infected with hepatitis B virus.Interferon (IFN) alpha is the only treatment reported to provide somebenefit in chronic hepatitis delta. Unfortunately, only a minority ofHDV infected patients respond to IFN therapy. The molecular mecha-nisms underlying resistance to therapy are unclear. IFN induced acti-vation of the Janus kinase signal transducer and activator of transcrip-tion (Jak STAT) signaling cascade is essential for the induction of anantiviral state. Interference of HDV with the Jak STAT pathway couldbe responsible for the observed IFN resistance in patients withchronic hepatitis delta. Methods: We analyzed IFN induced signal transduction through theJak STAT pathway in human hepatoma cells expressing HDV proteins.The expression of IFN stimulated genes was investigated with reversetranscription real time PCR. STAT1 and STAT2 activations were exam-ined by immunofluorescence and Western blots. Results: We observed that the expressions of the interferon stimu-lated genes coding for the antiviral proteins myxovirus resistance A(MxA), dsRNA dependent protein kinase (PKR) and oligoadenylatesynthetase (2’,5’ OAS) were downregulated in HDV infected hepatoma

cells in response to IFN treatment. We provide evidence that HDVinhibits the type I interferon signaling by severely impairing the phos-phorylation of both STAT1 and STAT2 and consequently blocking their translocation from the cytoplasm to the nucleus. Conclusions: IFN alpha induced intracellular signaling is impaired inHDV infected human hepatoma cells. HDV subverts the Jak STATpathway by selectively preventing activation and translocation to thenucleus of STAT1 and STAT2. Interference of HDV with IFN signalingcould represent an important mechanism of viral persistence andtreatment resistance.

29Decreased levels of liver specific microRNA miR-122 in hepatitis C patients with poor response to interferon therapy Magdalena Sarasin-Filipowicz1, Jacek Krol2, Ilona Markiewicz2, Witold Filipowicz2, Markus H. Heim1

1 Department of Biomedicine, University Hospital Basel, 2 FriedrichMiescher Institute for Biomedical Research, Basel Background: Liver-specific microRNA miR-122 is important for effi-cient replication of HCV RNA in Huh7 cells stably expressing anHCVreplicon. This observation raised much interest in a role of miR 122 inHCV infection and as potential therapeutic target. Furthermore, it wasreported recently that levels of miR-122 and several other miRNAsare regulated by interferon (IFN) in Huh7 cells and that miRNAs might-mediate at least some effects of IFN on HCV RNA replication in vitro. Methods: We measured IFNb-mediated regulation of six miRNAs(miR 1, miR-122, miR-196, miR-296, miR-351, and miR-448) in Huh7cells. We then analyzed levels of these miRNAs and of known IFNstimulated genes in livers of IFNa-treated mice and in paired biopsiesof patients with chronic hepatitis C (CHC) undergoing pegIFNa/ribavirin therapy. Measurements were performed by quantitative PCR. Results: Four miRNAs were induced by IFNb in Huh7 cells. The miR 122 level was decreased in response to IFN, but only 20 to 40%rather than 4-fold as previously reported. There was either no signifi-cant expression or no significant regulation of any of these miRNAs inthe livers of IFNa-treated mice. None of these miRNAs were regulatedin human liver after pegIFNa administration. Unexpectedly, miR-122expression levels were significantly lower in pre-treatment biopsies of patients with a primary non-response to treatment (PNR) than inpatientswith a complete early virological response (cEVR).Conclusions: Our analysis of miRNAs revealed only limited IFN in-duced changes, inconsistent with a major role of miRNAs in media -ting anti-viral effects of IFN. Low miR-122 expression levels are nega-tive predictors of response to pegIFNa/ribavirin treatment.

30Stepwise Radical Endoscopic Mucosal Resection forCompleteRemoval of Barrett’s Esophagus with Early Neoplasia Stefan Seewald1, Karl Yu Kim Teng1, Philipp Bertschinger2, Josef Altorfer2, Yan Zhong1, Nib Soehendra1

1 Department of Interdisciplinary Endoscopy, University MedicalCenter Hamburg-Eppendorf, Hamburg, Germany, 2 GastroZentrum,Klinik Hirslanden, Zürich, Switzerland Background: Endoscopic mucosal resection (EMR) of high-gradeintraepithelial neoplasia (HGIN) or intramucosal cancer (IMC) in Barrett’s esophagus (BE) is an effective and safe alternative to surgi-cal treatment. However, after localized EMR metachroneous lesionsmay develop in the residual BE. Stepwise radical endoscopicmucosal resection (SRER) aims at removing the entire BE. This studyaims to evaluate the safety and efficacy of the concept of SRER.Methods: Patients with HGIN/IMC in BE ≤5cm, without submucosalinfiltration were included. EMR was performed using simple snareresection technique or multiband ligation technique(Duette, CookEndoscopy). In patients with Short Segment Barrett`s Esophagus, thewhole Barrett´s epithelium was removed in one session. Otherwise,subsequent resections were performed with intervals of 4 weeks until complete eradication of all visible BE.Results: Fifty seven patients with HGIN/IMC, treated between Jan.2000 and Sept. 2006 were included. Complete eradication ofHGIN/IMC was achieved in 56/57 patients (98%) after a median -number of two EMR sessions (IQR 2-3). Perforation was noted in 1 patient. Complete eradication of BE was achieved in 56/57patients(98%). During a median FU of 18 months (IQR 7-31),

Dysphagia GERD Chestpain p-values(n=18) (n=23) (n=17)

SALINE IBP 10cm 9.4 ± 0.3 7.0 ± 0.2 7.2 ± 0.2 <0.001above LES (mm Hg)

IBP 5cm 10.5 ± 0.3 9.1 ± 0.2 7.76 ± 0.2 <0.001above LES (mm Hg)

LES relaxation 7.9 ± 0.2 8.2 ± 0.1 8.4 ± 0.1 0.089duration (sec)

BREAD IBP 10cm 16.4 ± 0.9 14.0 ± 0.5 12.2 ± 0.6 <0.001above LES (mm Hg)

IBP 5cm 15.7 ± 0.7 14.3 ± 0.6 11.2 ± 0.5 <0.001above LES (mm Hg)

LES relaxation 8.0 ± 0.3 8.2 ± 0.2 9.1 ± 0.3 <0.01duration (sec)

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1 patient(1.7%) had recurrence of HGIN and 4 patients (7%) hadrecurrence of BE detected on FU biopsies and were successfullytreated with repeat EMR. There were no patients with “buried glands”noted. Symptomatic stenoses occurred in 34/57 patients (59.6%)which were effectively treated with bougienage. One patient devel-oped a huge tear with a suspected perforation during bougienage. He was subsequently sent to surgery. Histopathological evaluation of the operative specimen showed no perforation.Conclusion: SRER of BE ≤5cm containing HGIN and/or IMC is an effective treatment modality with a low rate of recurrence. SRER ishowever associated with esophageal stenosis in more than half of thepatients which can be successfully managed by bougienage. None ofthe patients showed dysphagia after completion of treatment.

31First Experiences with Radiofrequency Ablation (BARRX®)in Patients with Barrett’s Esophagus Stefan Seewald1; Philipp Bertschinger2, Josef Altorfer2, Karl Yu KimTeng1, Yan Zhong1; Nib Soehendra1

1 Department of Interdisciplinary Endoscopy, University MedicalCenter Hamburg-Eppendorf, Hamburg, Germany, 2 GastroZentrum,Klinik Hirslanden, Zürich, Switzerland Background: Stepwise circumferential and focal ablation usingradiofrequency ablation [(RFA) BARRX® HALO system] is a relativelynew endoscopic treatment option for Barrett’s esophagus (BE) with-out the known drawbacks of other ablation techniques. In patientswith BE containing high-grade intraepithelial neoplasia (HGIN) orintramucosal cancer (IMC), endoscopic mucosal resection (EMR) isthe first line therapy. However, after localized EMR metachroneous lesions occur frequently in the remaining BE. Treatment of the residualBE by RFA could be a potential treatment option. We report our initialexperiences with RFA in patients with BE ± previous localized EMR ofHGIN/IMC as part of an on going study.Methods: Patients with BE ± previous localized EMR of HGIN/IMC in which treatment was completed was included in the analysis. Allvisible lesions were resected prior to ablation. A balloon-based elec-trode (HALO360) or an endoscope mounted electrode (HALO90) wasused for circumferencial and/or focal ablation of the remaining BE.Eradication of dysplasia, IMC or BE was the main outcome measure. Results: RFA treatment was completed in 7 patients with a medianBE length of 5cm (3-12cm). In 6 patients, localized EMR [median EMRsession: 1 (1-7)] was performed before RFA (Histology of EMR: IMC:4HGIN:2). Biopsy of the remaining BE showed HGIN in 1 patient andBE with no dysplasia in 5 patients. One patient was treated for BEwith no dysplasia. A total of 19 RFA sessions [median: 3 (1-6)] wereperformed (HALO 360: 6 times, HALO 90: 13 times). Alacerationoccurred in 1 patient. None of the patients developed stenosis. Aftera median follow-up of 5 month (range 3-12), 6 of 7 patients showedneither recurrent HGIN/IMC nor recurrent Barrett´s or “buried glands”.One patient had a recurrence of HGIN after 4 month and is presentlyundergoing RFA re-treatment. Conclusion: RFA seems to be a safe and effective method for theablation of Barrett’s metaplasia. Interestingly, neither stenosis norburied glands were observed in a short term follow-up. Scaring afterextensive EMR may lead to severe laceration during RFA. In patientswith long segment Barrett’s esophaguscontaining HGIN/IMC, thecombination of localized EMR and RFA seems to be apotential treat-ment approach. Prospective randomized controlled trials are war-ranted.

32Loss of Notch-1 signaling leads to portal hypertension and dedifferentiation of the adult hepatic sinusoidalmicrovasculature Michael Dill1, Valentin Djonov2, Ruslan Hlushchuk2, Luigi Terracciano3,Silvia Meili-Butz1, Freddy Radtke4, Markus Heim1,5 and David Semela1,5

1 Department of Biomedicine, University Basel, 4031 Basel, 2 Instituteof Anatomy, University Fribourg, 1700 Fribourg, 3 Institute of Pathology,University Hospital Basel, 4031 Basel, 4 Swiss Institute for ExperimentalCancer Research (ISREC), 1066 Epalinges, 5 Division of Gastro -enterology and Hepatology, University Hospital Basel, 4031 Basel Background: Nodular regenerative hyperplasia (NRH) is a liver dis-ease characterized by transformation of the liver parenchyma intosmall nodules with little to no fibrosis. The etiology of NRH is incom-

pletely understood and thought to be induced by vascular injury ofthe hepatic microcirculation. We have previously reported that Notch-1 knockout leads to NRH in mice. The aim of our study is to furtherinvestigate the role of Notch-1 in the pathogenesis of NRH. Methods: Since deletion of Notch-1 is embryonically lethal we used a murine conditional knockout system by crossing MxCre+/-withNotch-1 lox/lox mice. The MxCre system leads to deletion of Notch1in all cell populations of the liver. Knockout (KO) was induced byinjection of poly(I:C) 4 weeks after birth. In a second set of experi-ments a hepatocyte-specificconditional KO was created by crossingNotch-1 lox/lox with AlbCre+/-mice. Mice were sacrificed at differenttime points and liver samples were analyzed macro-and microscopi-cally. Proliferation was quantified histologically after BrdU-staining.Portal vein pressure was measured in anesthetized mice via a pres-sure transducer. Morphology of hepatic vasculature was assessed byelectron microscopy of vascular casts after perfusion with Mercoxpolymer solution. Results: MxCre induced KO mice developed NRH within 14 daysafter deletion of Notch-1. BrdU-staining of liver samples at differenttime points after KO showed on average a 5-fold increase in prolifera-tion of hepatocytes and endothelial cells in MxCre Notch-1 KO mice.Analysis of vascular casts showed profound vascular remodeling ofhepatic sinusoidal architecture with features of intussusceptive angio-genesis. MxCre Notch-1 KO mice developed portal hypertension(4.95 ± 0.55 mmHg (n=10) vs. controls 2.38 ± 0.44 mmHg (n=7),p<0.0041). In contrast, hepatocyte-specific Notch-1 KO mice werephenotypically normal. Conclusions: Loss of Notch-1 signaling leads to dedifferentiation ofthe hepatic microcirculation and portal hypertension in the absence offibrosis. The absence of phenotypic changes in hepatocyte-specificNotch-1 KO mice suggests that the development of NRH is secondaryto vascular changes.

33The severity of histological lesions is predictive of outcome in 138 patients with alcoholic steatohepatitis Laurent Spahr, Emile Giostra, Antoine Hadengue, Laura Rubbia-BrandtGastroenterology/Hepatology, Clinical Pathology, HUG GenèveBackground: The diagnosis of alcoholic steatohepatitis (ASH) isbased on histology (hepatocellular damage with ballooning/Mallorybodies; steatotic changes; inflammation with predominance of neu-trophils; pericellular fibrosis). Additional features include bile pigmentaccumulation, iron deposits, and some degree of ductular reaction.Whether the intensity of histological damage is of clinical significanceis ill-defined. We studied the prognostic value of individual featureson liver biopsy, as well as other parameters (age, MELD and Maddrey)to predict the 90-day mortality in patients with ASH. Methods: 138 patients (age 55 yrs, cirrhosis > 95%) and biopsy -proven ASH (no associated viral hepatitis or infection at admission)admitted over a 3-year period were studied. Clinical scores werecalculated at time of biopsy (median time of 3 days [0-10] afteradmission). All patients with Maddrey � 32 (= 73 % ) received steroids.A semi-quantitative evaluation of the followings was performed, whileblinded to patients’ outcome: macrovesicular steatosis (>50%: +1);microvesicular steatosis (present: +1); hepatocellular damage (numer-ous Mallory: +1; frequent ballooning: +1); neutrophilic infiltration(severe: +1); iron deposits (moderate/severe: +1); ductular reaction(marked: +1); and bile pigments accumulation (moderate/ severe: +1). Fibrosis was not scored as almost all patients had cirrhosis. The 3-month survival status was based on hospital recordsand phone calls. Results: Survival was 74%. Sixty patients died (median time 26 days[1-88]). At univariate analysis, age > 50 yrs, Maddrey � 32, MELD > 19, bile pigments accumulation (all p<0.001), marked iron deposits(p<0.015), were associated with death. Bilirubin showed a weak butsignificant correlation with bile pigments (Kendall tau = 0.49,p<0.0001). On multivariate analysis (OR [95% CI]), an age > 50 yrs(3.8 [1.35-10.9]; a Maddrey > 32 (5.7 [1.7-19.7]; and bile pigments on biopsy (2.5 [1.2 5.2] were independent predictors of death. Conclusions: A part from the description of features for the diagnosisof ASH, histology identifies bile pigments accumulation with a prog-nostic significance, together with an age > 50 yrs and a Maddrey’sscore > 32.

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34Budesonide as Induction Treatment for active EosinophilicEsophagitis in Adolescents and Adults: A randomized, double-blind, placebo-controlled Study (BEE Trial) Alex Straumann1, Lukas Degen1, Christian Bussmann2, SebastienConus3, Christina Thalmann4, Susanne Portmann1 and Hans-UweSimon3

1. Department of Gastroenterology, University Hospital Basel,Switzerland, 2. Institute for Pathology, Kantonsspital, Luzern,Switzerland, 3. Department of Pharmacology, University of Bern,Switzerland, 4. AstraZeneca Switzerland, Zug, Switzerland Background: Eosinophilic Esophagitis (EE) is a clinico-pathologicaldefined condition characterized by PPI-refractory esophagus-relatedsymptoms in combination with a dense esophageal eosinophilia.Topical corticosteroids have shown to be an efficient therapy in chil-dren with EE and, on an anecdotal base, in adults. The purpose ofthis study is to assess the efficacy of budesonide in adolescents andadults with active EE and to analyze the reversibility of symptoms andsigns in EE. Methods: In this randomized, double-blind trial, 36 adolescent oradult patients (m/f = 31/5; mean age 35.7yrs, range 17-65) with activeEE (>20 eos/hpf and dysphagia) swallowed either nebulized aqueousbudesonide suspension formulation (Pulmicort® Respules 0.25 mg/ml)at a dose of 1 mg (4 ml) twice daily or placebo twice daily for 15 days.Pre-and post-treatment the activity of the disease was assessedclinically, endoscopically, histologically and via biomarkers in theblood and in the tissue. Symptoms were recorded with a diary. Theprimary endpoint was histological reaction, defined as remission (max <5 eos/hpf), response (max 5-20 eos/hpf) or persistent activeinflammation (max >20 eso/hpf). Results: At baseline, both groups were histologically comparable(p=0.52, Wilcoxon test). After the 15-day induction therapy, the remis-sion rates were 61.1% (11/18 patients) in the budesonide group ascompared with 5.7% (1/18 patients) in the placebo group (p=0.0009).The rates of response were 11.1% (2/18 patients) in the budesonidegroup and 5.7% (1/18 patients) in the placebo group. The inflamma-tion was still active in 27.8% (5/18 patients) of the budesonide groupand in 88.9% (16/18 patients) in the placebo group. The treatmentwas well tolerated and no serious adverse events occurred. Thecourse of symptoms reflected fairly well the activity of the inflamma-tion. Among the endoscopical sings, white exudates and red furrowsdisappeared in parallel with the eosinophilic infiltration, whereascorrugated and solitary rings persisted. Conclusions: A 15-day course with the topical corticosteroid bude -sonide is highly effective in inducing a remission in adolescent andadult patients with active EE. Symptoms correspond fairly well withdegree of inflammation. White exudates and red furrows are asso -ciated with active inflammation and are reversible, whereas corru-gated and solitary rings do not respond to anti-inflammatory therapyand likely reflect fibrosis. However, the long-term management of this chronic-inflammatory disease remains further investigation. (ClinicalTrials.gov number NTC00271349)

35Reversibility of esophageal dysmotilities after conversion from gastric band to gastric bypassBorovicka, Jan; van der Weg, Boudewijn;Thurnheer, Martin; Schultes, Bernd; Grübel, Claudia; Kuenzler, Patrizia; Pohl, Daniel; Fried, Michael; Meyenberger, Christa; Tutuian, RaduDivision of Gastroenterology Kantonsspital St.Gallen; Department ofSurgery, Kantonsspital St. Gallen; Division of GastroenterologyUniversity of ZurichBackground: Recent studies report on esophageal motility disordersinduced by gastric banding, on occa-sions severe enough to mimicpseudoachalasia. To date there are insufficient data whether thesechanges are reversible or not. Aim: Evaluate changes in esophageal symptoms, peristalsis, bolustransit and clearance be-fore and 3 months after conversion fromgastric ban-ding to gastric bypass. Methods: Patients scheduled for conversions from gastric banding to gastric bypass were evaluated before and 3 months after con -versions. Clinical assessment included 7-point Likert scale rating of dysphagia, heartburn, regurgitation and chest pain. Esophageal persistalsis and bolus transit were assessed using combined impedance-manometry. Esophageal emptying was assessed using a modified timed barium swallow. Results: Twenty-four patients (20 F, mean age 45, range 28-61 years)completed pre- and post-operative (average 98, range 63 186 days)evaluations. Conversion from gastric banding to bypass improvedesophageal symptoms, esophageal bolus transit (impedance) andclearance (timed barium swallow) while there was only a trend inimproved esophageal peristalsis (manometry). Conclusions: Conversion from gastric band to gastric bypassimproves esophageal symptoms and function. Abnormal motilitycaused by gastric banding may persist in some patients after togastric bypass. However few of these patients are symptomatic andhave abnormal bolus transit.

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P1Significance of serum adiponectin levels in patients with chronic liver disease Maria L. Balmer, Jeannine Joneli, Felix Stickel, Wolfgang Thorman,Jean-François DufourInstitute of Clinical Pharmacology, University of Berne, Berne,Switzerland Background: Adiponectin plays a pivotal role in metabolic liver diseases. It increases fatty acid beta-oxidation, decreases hepatictriglyceride content and hepatic insulin resistance. Recent studiesreported reduced serum levels of adiponectin in patients with non -alcoholic steatohepatitis. The aim of this study was to establish a correlation between adiponectin and metabolic, laboratory and diagnostic findings in patients with liver disease.Methods: Adiponectin serum concentrations were measured byenzyme-linked immunoassays in 208 fasting patients (118 men, 90 women) with chronic liver disease: 31 nonalcoholic fatty liver disease (NAFLD), 53 HCV, 16 HBV, 38 biopsy-proven cirrhosis. Results: Circulating adiponectin levels were significantly increased in patients with cirrhosis compared to those with simple steatosis orother chronic liver diseases (19 ug/ml vs. 5.4 ug/ml vs. 10.3 ug/ml,p=0.00000017). Serum adiponectin concentrations positively corre-lated with serum bile acid levels (p=6.6E-12), serum hyaluronic acid(p=0.00000036), fibroscan values (p=0.00013) and negatively withBMI (p=0.0029). Analysis by gender revealed further sex-relateddifferences in the correlation of adiponectin with BMI, hyaluronic acidand elastography. Conclusion: Adiponectin levels are decreased in patients withNAFLD and do not help to separate patients with NASH from thosewith steatosis. Serum adiponectin levels decrease with BMI inwomen, but not in men. Adiponectin levels correlate positively withelastography and fasting bile acids and were significantly elevated incirrhosis. These results underscore the importance of interpretingfasting serum adiponectin levels after taking into account the genderand stage of liver disease.

P2Geldanamycin and 17-DMAG lead to an increase of basal NDRG1 expression and a loss of phosphorylation inhepatocellularcarcinoma cell lines Vanessa Banz, Michaela Medova, Adrian Keogh, Yitzak Zimmer, Daniel Candinas, Deborah Stroka Background: N-myc downstream regulated gene-1 (NDRG1) is reported to be involved in cellular differentiation, cell-cycle arrest andp53-mediated apoptosis. In several cancers, it is a suggested tumoursuppressor gene and more specifically, an inhibitor of metastases. Inhepatocellular carcinomas (HCC), it is highly over-expressed. Heat-shock protein 90 (HSP90), a molecular chaperone protein, has beenshown to be over-expressed in many different cancers. HSP90inhibitors (HSP90i) such as Geldanamycin (GA) and 17-N Allylamino-17-demethoxygeldanamycin (17-AAG) are currently being tested invitro and phase I clinical trials in various tumours with some promis-ing results so far. In this study, we investigated the in vitro effect ofHSP90i on NDRG1 in primary human hepatocytes (PHH) and (HCC)cell lines. We were particularly interested in post transcriptional alter-ations such as changes in phosphorylation of the NDRG1 protein. Methods: PHH and HCC-cell lines (Hep3B, HUH-7,HepG2) werepretreated with GA and 17-DMAG at 100nm, 500nM and 1000nM for24h. The induction of NDRG1 and the mRNA up-regulation werequantified by Western blotting and real time polymerase chain reac-tion (rtPCR). Results: PHH and HCC-cell lines showed a dose response up-regu-lation of NDRG1 protein when treated with GA and DMAG. IncreasedNDRG1 mRNA levels were detected by rtPCR with up to a 28-foldincrease. Co-IP showed the two proteins to be linked. Furthermorewe demonstrate that inhibition of HSP90 directly targets the kinasesresponsible for the phosphorylation of NDRG1, which results in theloss of its phosphorylated form Further analysis revealed that the lossof phosphorylation is probably due to inhibition of glycogensynthasekinase 3 (GSK3) by HSP90 inhibition.Conclusions: Interestingly, blocking HSP90 leads to an up-regulationof NDRG1 and a loss of phosphorylation. Our data suggest thatNDRG1 and HSP90 are interacting proteins and their interaction is independent of the ATPase activity of HSP90.

P3Is a sustaining rod necessary for diverting loop ileostomy? Vanessa Banz, Lukas Brügger, Christian Egloff, Hans Gelpke, Marco Decurtins, Daniel Candinas Objective: The presence of a loop ileostomy (LI) facilitates clinicalmanagement after leakage following distal colorectal anastomosis.Generally, diverting LI are secured at skin level with a supportingdevice in order to prevent retraction of the ostomy. A supporting rodmay result indifficult stoma bag application and leakage of faeceseven with correct eversion of the limbs. We compared morbidity andtime to self-sufficient stoma-care in patients having a LI with rod tothose without rod.Methods: 60 patients requiring LI (30 with rod, 30 rodless) wereanalyzed for morbidity according to a scoring system ranging from 0 to 4 points for bleeding, necrosis, skin irritation, abscess, stenosis,retraction, fistula, prolapse, parastomal hernia, incomplete diversion,where 0 = no complication and 4 = severe complication. Continuousvariables were expressed as median (95% CI). Inter-group compar-isons used the Mann-Whitney U test, categorical variables the �2 test. Results: There were no differences in age, gender, rate of emergency- operations, number of diabetics and hospital stay length between the two groups. The total morbidity score also was not significantlydifferent (p=0.5), but severe complications (score>5) occurred signi -ficantly more in the rod group (p=0.04). Although not significant,patients having a LI with rod had a tendency towards more stoma-related reoperations. There was no significant difference in time toself-sufficient stoma-care between the groups (p=0.88). However, thenumber of patients reaching total self sufficiency regarding stoma-carewas higher after rodless LI (26 v. 20 regarding changing the stoma-bag respectively 24 v. 17 patients for changing of the stoma plate; p= 0.07 and 0.05 respectively).Conclusions: According to our data, rodless LI seem to fare just aswell as those with a supporting rod, with the rodless group havinglower severe morbidity rates and more patients reaching self-suffi-cient stoma-care. Therefore routine application of a rod for divertingLI seems unnecessary.

P4Langzeit Follow-up nach laparoskopischer Sigmaresektion beiDivertikelkrankheit G. Basilicata, N. Wiedemann, G. MelcherChirurgische Klinik Spital Uster Fragestellung: Analyse des Langzeitverlaufes nach laparoskopischerSigmaresektion bei Divertikelkrankheit mit Analyse der postoperati venLebensqualität anhand des Eypasch-Scores. Patienten und Methoden: Retrospektive Langzeitanalyse einer kon sekutiven Serie von 130 Pat. mit einem Durchschnittsalter von 62 Jahren, die einer elektiven laparoskopischen Sigmaresektionunterzogen wurden. Alle Patienten wurden 3 Monate postoperativklinisch nachkontrolliert und anhand eines detaillierten Fragebogens(erweiterter Eypasch-Score, GLQI) durchschnittlich 43 (10-97) Monatepostoperativ befragt. Die Rücklaufquote der Fragebogen betrug 80%. Resultate: Bei 6,1% der Patienten kam es im oben erwähntenBeobachtungszeitraum zu einer Rezidiv-Divertikulitis. Bei einemdieser Patienten musste eine chirurgische Nachresektion durchge-führt werden. Die Auswertung bezüglich der gastrointestinalen Lebens-qualität anhand des Eypasch-Scores (Normwert > 100) ergab einesignifikante Verbesserung der postoperativen Werte (p < 0.0001). Das Durchschnittsalter der Patienten mit persistierenden Beschwer-den war mit 52.3 Jahren deutlich unter demjenigen des Gesamt -kollektivs. Hingegen zeigte sich auch bei den Patienten mit einemDivertikulitis-Rezidiv eine deutliche Verbesserung des Scores undsomit der Lebensqualität.

Zusammenfassung: Die lap. Sigmaresektion bei Divertikelkrankheitführt in rund 85-90% der Fälle zu guten bis sehr guten Langzeiterge b-nissen. Die Rezidive konnten fast ausschliesslich konservativ thera-piert werden. Trotz allem bleibt ein kleines Patientenkollektiv, dasüber persistierende Beschwerden klagt, ohne dass ein Rezidivnachgewiesen werden konnte. Eine genaue Analyse dieser Patienten-gruppe ist entsprechend erforderlich.

Eypasch-Score praeoperativ 12 Mt 43 (10-97) Mt

> 100 52 % 83 % 83 %

< 100 48 % 17 % 7 %

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P5In Vietnam HBV and HCV prevalence is higher in urban setting than in rural areas José M. Bengoa, Tran Thi My Trinh, Ngo Van Huy, Cécile Potié, Pierre Jean Malè, Emiliano GiostraGFMER Geneva Foundation Medical Education Research Bênh ViênFV, D-7, Ho Chi Minh City, Vietnam, Division de Gastroentérologie et Hépatologie, Hôpitaux Universitaires de Genève Background: Vietnam has a very high prevalence of HBV of 10 to20% in three community based studies. HCV prevalence is reportedat 1% in rural areas and estimated over 5% in Ho Chi Minh City(HCM). In urban areas the higher prevalence of HBV and HCV may be due to increased healthcare related risk factors. Results recordedin a hospital in HCM are reported. Methods: 1) HBV and HCV serology was done during a World Diges-tive Health Day 2007 campaign in patients coming to the hospital 2) two cohorts of HBV and HCV patients were studied from May toAugust 2007.Results: 1) serology in 378 Vietnamese attending a city hospital:mean age 36.9 y, HBsAg+ 105 (27.7%), antiHBc+ 145 (38.3%), anti-HCV+ 27 (7.1%), co-infection HBV/HCV 21 (5.5%), negative serol-ogy122 (32.2%). 2) HBsAg+ cohort (397patients): 57.2% men,HBeAg+ 29% with 93.4% HBV-DNA>104 IU/ml, HBeAg-71% with39.7% HBV DNA>104 IU/ml. 3) HCV cohort (228 cases): 47.4% men,68.2% genotype 1, 12.9% genotype 2, 18.1% genotype 6. Conclusions: In a patient population attending a hospital in HCM the prevalence of HBV was higher than that reported in rural zones.HBeAg was found in 29% and high HBV-DNA in 59.4%. The preva-lence of HCV was 7.1%. Genotype 1 and 6 were the most frequent(86.3%). Preventive measures are being promoted as a huge liverdisease related burden is projected in Vietnam.

P6Health care related risk factors, difficult genotypes and moderate fibrosis underlie the management of hepatitis C in the south of Vietnam Ngo Van Huy, José M. Bengoa, Ho Hoang Thao Quyen, Pierre Jean Malè, Emiliano GiostraGFMER Geneva Foundation Medical Education Research Bênh ViênFV, D-7, Ho Chi Minh City, Vietnam, Service de Gastroentérologie et Hépatologie, Hôpitaux Universitaires de Genève Background: Few reports are published on hepatitis C in Vietnamand none with liver biopsy. We aimed to fully characterize clinicalfactors and liver histology in a setting with high prevalence in order to base clinical management. Methods: a series of 100 consecutive liver biopsies performed inHCV+ patients attending an hospital in Ho Chi Minh City was studied,and epidemiological and biochemical factors are analyzed in order tofind predictors of advanced fibrosis. Results: The group included 50% men, 98% Vietnamese, mean agewas 47.5 years, BMI was <23 in 63%. Risk factors were: previousinvasive medical procedure in 48%, blood transfusion in 25%,acupuncture in 18%, heroin injection in 2%. Only 17% drank more than20 g of alcohol per day. HCV genotypes were: 66% type 1, 7% type 2,1% type 3, and 23% type 6. Metavir scores of fibrosis were F0/F1 in69%, F2/F3/F4 in 31%. Sex, age, BMI, alcohol, viral load, and othersrisk factors were not predictive of advanced fibrosis. APRI score wasthe only independent variable predictive of advanced fibrosis. Conclusions: There is predominance of genotype 1 and high frequencyof genotype 6 in this series of patients. Liver biopsy showed that benignhistological forms were more frequent than severe. Risk factors for infec-tion were related to healthcare and risk factors for progression of fibrosissuch as alcohol and overweight were found only in a minority. This back-ground of moderate fibrosis on histology and difficult to treat genotypesunderlies clinical management of hepatitis C in the south of Vietnam.

P7BCRP deficiency in human colorectal adenomas and in the Apc Min mice promotes accumulation of the coloncarcinogen PhIP and may represent an acquired susceptibilityfactor for colon carcinoma Christoph G. Dietrich1,2, Ann-Kathrin Vehr2, Ina V. Martin2, TimoRath2,3, Elke Roeb3, Andreas Geier2,4

1 Klinikum Aschaffenburg, Med. Klinik II, 2 UniversitätsklinikumAachen, Med. Klinik III, 3 Universitätsklinikum Giessen, Med. Klinik II,all in Germany, 4 Universitätsspital Zürich, DIM, Gastroenterologie &Hepatologie Background: Several molecular changes in colorectal adenomasprovide the basis of the adenoma-carcinoma sequence. We investi-gated the expression of transporters for xenobiotics, which confercellular toxicological resistance, in humans and in Apc Min mice andconducted functional studies estimating the importance of theexpression changes. Methods: 30 adenomas from 25 patients and 8 adenomas from 4 Apc Min mice were analysed regarding the expression of BreastCancer Resistance Protein (BCRP/Bcrp) using Western Blotting andquantitative RT-PCR. In a functional study, Apc Min mice receivedradioactively labelled PhIP, a heterocyclic amine and food colon car-cinogen, by oral gavage, later analyzing adenomatous tissue regard-ing PhIP accumulation. Results: BCRP was significantly downregulated in human colorectaladenomas (35 ± 30 % compared to adjacent healthy tissue). This wasin line with data from Apc Min mice adenomas, where downregulationwas significant as well (58 ± 34 %). In parallel, quantitative RT-PCRshowed mRNA downregulation in human adenomas (17 ± 31 %). 48 hafter oral gavage of PhIP, we could demonstrate a higher carcinogenconcentration in adenomas of Apc Min mice (181 ± 113 % whencompared to normal tissue). Other xenobiotics transporters(MRP2/Mrp2 and MDR1/Mdr1) were unchanged. Conclusion: Significant transcriptional downregulation of BCRP/Bcrpleads to higher carcinogen concentrations in colorectal adenomas. Thismight promote the adenoma-carcinoma sequence by higher genotoxiceffects. The results indicate a possible role of transporter deficiencies insusceptibility for colon carcinoma. Further studies regarding the impacton DNA adduct formation of PhIP in adenomas are ongoing.

P8A biphasic response with enhanced transcription and subcellularshuttling of Y-box protein 1 to inflammatory signals regulateshepatic Mrp2 gene expression Ina V. Martin1, Peter R. Mertens2, Björn Frye2, Sonja Strauch1, ThomasRauen2, and Andreas Geier1,3

1,2 Universitätsklinikum Aachen, Med. Klinik III&II, Germany, 3 Universitätsspital Zürich, DIM, Gastroenterologie & Hepatologie Background: Expression of hepatobiliary transporters is decreasedduring endotoxemia. Reduction of Mrp2 is mediated by IL-1ß-depen-dent signals but the underlying mechanism is still unclear. YB-1 is apredominantly cytoplasmic protein which translocates to the nucleusin response to various insults. Consequently, we characterized themechanisms of YB-1 activation and its potential role as a regulator ofhepatic acute phase genes. Methods: Liver sections from LPS-injected rats (20h) were stainedwith YB-1-specific antibodies. RT- PCR quantification was performedfor Mrp2, MMP-2 and YB-1. YB-1 protein was quantified from IL-1ß-or TNF -stimulated FAO cells and the localization of a CFP-YB-1-YFPfusion protein was visualized by confocal microscopy. ChIP assaysand EMSA were performed analyzing YB-1 DNA-binding. Results: In endotoxemic livers Mrp2 mRNA was down-regulated to20%, while YB-1 mRNA expression increased 2,5-fold. Immunohisto-chemical staining showed a marked up-regulation and predominantnuclear localization of YB-1 protein. In FAO cells IL-1ß caused anincrease in cytoplasmic YB-1 protein up to 16 hours. As a rapid effectwithin 90 min, IL-1ß-stimulation resulted in a 6-fold up-regulation ofendogenous YB-1 in the nuclear compartment concomitantly with anincrease in nuclear fluorescence in CFP-YB-1-YFP-transfected cells.In addition to DNA binding studies in endotoxemic rat livers, ChIPassays revealed an IL-1ß-induced increase in YB-1 binding to theMrp2-promoter in FAO cells.Conclusions: YB-1 is activated during the hepatic acute phaseresponse by time-dependent cellular changes: a IL-1ß-mediatedrapid nuclear shuttling within 90 minutes and a transcriptional induc-tion thereafter. This biphasic response now explains the IL-1ß medi-ated suppression of Mrp2 in endotoxemic rats.

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P9Beware of Colophos® in the elderly! Gerber L.a, Meyer-Heim T.b, Heuss L.T.a, Bleisch J.A.bSpital Zollikerberg, CH-8125 Zollikerberg; a Medizinische Klinik, b Nephrologische Abteilung Background: Phosphate-containing purgatives for bowel cleansingbefore colonoscopy are popular. The potentially hazardous sideeffects are still underestimated. Case study: A 73-year-old woman was referred to our nephrologicalambulatory due to an acute and progressive worsening of a previ-ously mildly impaired kidney function of unknown origin. There wasno history of hypertension or diabetes. A pre- or postrenal kidneyfailure could be excluded. Extensive serum and urine analysis didn’treveal any cause. The kidney biopsy finally showed a distinct phos-phate nephropathy. We identified Colophos®, a phosphate-containingpurgative as the causing agent, which the patient had received forbowel cleansing before a colonoscopy one day before the detectionof the acute kidney failure. During the following months the kidneyfunction initially declined further (Peak Serumkreatinin 264 mmol/l) andthen improved (Serumkreatinin 124 mmol/l one year later). Discussion: Phosphate nephropathy is a rare but underestimatedcause of an acute renal failure. Most cases are associated with theingestion of phosphate-containing purgatives. Persons at risk arewomen, elderly persons, patients with impaired kidney function,hypertension, and dehydration. The consequence is sometimes anirreversible tubulo interstitial injury that can lead to end-stage renaldisease in a minority of the cases. Therefore gastroenterologistsshould be cautious to prescribe phosphate-containing purgatives inthis risk group and should favour safer alternatives.

P10Treatment of HCV in HCV mono-infected and in HIV-HCV co-infected patients: an open-labeled comparison study Jean-Jacques Gonvers, Markus Heim, Mathias Cavassini, Beat Müllhaupt, Daniel Genné, Enos Bernasconi, Giuseppe Pantaleo, Carl Oneta and the Swiss HIV-HCV study group. Background and aims: The treatment of chronic HCV infection hasbecome a priority in HIV+ patients given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluatethe antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HCVmono-infected patients and in HIV-HCV co-infected patients, and toexamine whether 6 months of therapy would suffice in HIV patientswith favourable genotypes 2 and 3. Secondary endpoints were to evaluate predictors of response and frequency of side-effects. Methods: Patients with genotypes 1,4,5 were treated for 48 weekswith Pegasys®180 mg per week plus Copegus® 1,000-1,200 mg dailyat a body weight-related dose and patients with genotypes 2,3 for 24 weeks with Pegasys®180 mg per week plus Copegus® 800 mg daily. Results: 132 patients were included in the study: 85 HCV mono-infected (38 with genotypes 1,4,5; 47 with genotypes 2,3), and 47HIV-HCV co-infected patients (23 with genotypes 1,4,5; 24 with geno-types 2,3). In an intention to treat analysis sustained virologicalresponse (SVR) for genotypes 1,4,5 was observed in 58% of HCVmono-infected and in 13% of HIV-HCV co-infected patients(p=0.001). For genotypes 2,3 SVR was observed in 70% of HCVmono-infected and in 67% of HIV-HCV co-infected patients(p=0.973). Absence of a 2-log drop in HCV-RNA or an undetectableviral load after 12 weeks was a potent negative predictor of treatmentresponse in all patients. Undetectable HCV-RNA at week 4 had a highpositive predictive value of SVR. The Study was not terminated in 22patients (36%) with genotypes 1,4, 5 and in 12 patients (17%) withgenotypes 2,3. Conclusion: Genotypes 2,3 predict the likelihood of SVR in mono-andin co-infected patients. In co infected patients with genotypes 2,3 a 6-months treatment has the same efficacy as in mono-infected patients.To increase SVR it is crucial to avoid withdrawals/treatment-stops.

P11Value of spatiotemporal representation of manometric data Claudia Grübel1,2, Richard Hiscock3, Geoff Hebbard1

1 Dept. of Gastroenterology, The Royal Melbourne Hospital, Australia,2 Dept. of Gastroenterology, Kantonsspital St.Gallen, Schweiz, 3 Dept. of Obstetrics and Gynaecology, Mercy Hospital, Heidelberg,Australia Introduction: High-resolution manometry with spatiotemporal repre-sentation of pressure data is a technique that has developed over thepast 10-15 years. We compared spatiotemporal and traditional line plotrepresentation of manometry data in a group of medical students interms of the ability of the user to come to a rapid and accurate diagno-sis, and evaluated user preferences for the two forms of data display. Methods: Following standardised paper-based and electronic tutori-als, sixty medical students classified 30 typical examples of a rangeof motility disorders in both line plot (10 sensors, including a ‘virtualsleeve’) and spatiotemporal plot format (derived from 16 sensors).Swallows were presented electronically in random order. The accu-racy and speed of the assessment were compared between the twoforms of data presentation, as well as a subjective rating of prefer-ence. Results are presented as mean ± SEM. Results: Classifications based on data presented in spatiotemporalformat were more often correct (89 % ± 1.2% vs. 86% ± 1.3%, p =.002) and correct diagnoses were provided more promptly (25 ± 2.9 svs. 31 ± 3.2 s, p < .001), than in line plot format. 68 % of the studypopulation preferred the spatiotemporal presentation. Conclusions: The analysis of manometry data by manometry naïveindividuals is faster and more accurate when data is presented inspatiotemporal than in line plot format. In addition, users preferredthe spatiotemporal plots. Spatiotemporal presentation of manometricdata is likely to be more easily understood by patients and the ‘non-expert’ physician community.

P12Anastomose colo-anale: Comparaison entre les anastomoseshautes et basses. Résultats péri-opératoires et qualité de vie. Marc-Olivier Guenin, Béatrice Kern, Ida Montali, Markus von FlüeAllgemeinchirurgische Abteilung, St. Claraspital, 4058 Bâle, Suisse Buts: Nous voulions évaluer, à l’aide de formulaires standardisés,pour les reconstructions colo-anales basse avec résection intersphinctériennes, les résultats péri-opératoires et la qualité de vie post opératoire. Patients et méthode: Entre 2003 et 2005, 69 patients ont subis dansnotre clinique une résection antérieure basse avec anastomose colo-anale et stomie de protection. La fermeture de cette stomie à étéeffectuée entre trois et six mois plus tard. Chez 13 patients il s’agis-sait d’une anastomose très basse. On a relevé prospectivement lamorbidité péri-opératoire. Le contrôle à long terme a été effectué àl’aide des formulaires standardisés selon Eypasch (Gastro-IntestinalQuality of LIve score) et Wexner. Résultats: Le groupe de patients comportait 32 femmes et 37 hommes.Chez 13 patients, une résections très basse avec anastomosemanuelle intra anale a été effectuée; chez 56 patients, une résectionantérieure basse avec anastomose colo -anale mécanique a été effec-tuée. La durée opératoire était de 330 min pour les reconstructionsintra anales et de 261 min pour les anastomoses mécaniques. Enpost opératoire, 3 patients ont présenté une infection urinaire. Uneinfection de cathéter central a aussi été relevée. Aucune complicationchirurgicale n’a été relevée La durée d’hospitalisation était de 17 jours.La létalité a été nulle. Tous les patients encore en vie à l’heureactuelle ont reçu le formulaire de contrôle standardisé avec un tauxde retour de 65%. La durée moyenne entre l’opération et la réponseau formulaire était de 1,98 ans. Le score d’Eypasch était de 101 pourles anastomoses manuelles respectivement de 112 pour les anasto-moses mechaniques, différence statistiquement non significative. Le score d’incontinence de Wexner était de 7 pour l’anastomose méca -nique et de 8 pour l’anastomose après résection intersphinc térienne. Conclusion: Les anastomoses colo-anales basses, y compris lors derésections intersphincterienne, sont une technique sûre. Les résultatspéri-opératoires des deux techniques sont (hormis le temps opéra-toire) comparables. Lors du contrôle à long terme: − Les patients ayant subi une anastomose très basse présentent des

résultats inférieurs pour ce qui est de la qualité de vie et de la conti-nence.

Les anastomoses très basses sont faisable techniquement mais lespatients devraient êtres informé des problèmes de continence et dela réduction de la qualité de vie qui en découle.

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P13Acute Liver Failure Upon Insertion of Transjugular Intrahepatic Portosystemic Shunt in a Patient with GlycogenosisType IIIb and Immediate Resolution after Shunt Reduction Ramin Ipaktchi1, Karin Ludwig2, Christian Seiler1, Daniel Candinas1,Felix Stickel31 Departments of Visceral and Transplantation Surgery, 2 Radiology,Inselspital Bern, 3 Clinical Pharmacology, University of Bern,Switzerland Background: Transjugular intrahepatic portosystemic stent shunt(TIPSS) is successful in the management of recurrent variceal bleed-ing in patients with liver cirrhosis. Complications comprise hepaticencephalopathy, stent occlusion, and liver hypoperfusion. Case Report: A 51-year-old female patient with liver cirrhosis due toglycogenosis type IIIb was listed for liver transplantation with CHILDA and MELD 12 score because of recurrent variceal bleeding and asingle episode of grade IV encephalopathy. During the elective TIPSSshunt insertion the portovenous pressure gradient was 22 mm Hg andliver parameters were near normal (ASAT 49U/L, INR 1.1, MELD 8).48hr later hyperacute liver failure developed (ASAT 4802U/L, INR 2.9,encephalopathy grade III, MELD 31) requiring mechanical ventilationand hemofiltration. Toxic, vascular, and infectious causes were ruledout. Portosystemic shunt volume was found at 1,600 ml/min with noevidence for hepatic hypoperfusion. Emergency TIPSS revision andreduction of stent diameter from 10 to 7mm was performed. Hepaticangiography revealed normal liver perfusion. Within 24hr, liver andkidney failure, and encephalopathy resolved. The patient successfullyunderwent liver transplantation 11 days thereafter. Conclusion: Patients with glycogenosis type IIIb may be more sus-ceptible to hepatic hypoperfusion and acute hepatic dysfunction dueto TIPSS-related portosystemic shunting. In such cases, immediatereduction of TIPSS diameter should be considered.

P14Swiss IBD Cohort Study (SIBDCS): Results from physician enrollment questionnaires Juillerat, Pascal1; Pittet, Valérie2; Froehlich, Florian1,3; Mottet, Christian1;Felley, Christian1; Burnand, Bernard2; Vader, John-Paul2; Michetti, Pierre1

and the Swiss IBD Cohort Study group1 Division of Gastroenterology and Hepatology and 2 Institute of Socialand Preventive Medicine, University Hospital of Lausanne (CHUV).

Background: Six university hospital centers (Basle, Bern, Geneva, Lausanne,St. Gallen and Zurich) started recruitment of IBD patients in Nov. 06, in definedareas in collaboration with gastroenterologists in hospitals and private prac-tice. This Swiss endeavor was supported financially by a national fund, on the basis of results of a pilot study initiated in 2004. Prelim-inary data after 15 months (Nov. 06 –Apr. 08) are presented here. Methods: Adult IBD patients were identified according to strict diagnosticcriteria. After screening, epidemiological and clinical data were collectedin a questionnaire completed by the medical investigators, and sent to adata center (DC). Results: 1039 patients were included and 961 physician questionnairesfilled, corresponding to 567 Crohn’s disease (CD), 363 ulcerative colitis (UC)and 29 indeterminate colitis (IC) patients. Females were slightly more numer-ous than males in the CD patients, with the opposite being observed for UC.Age at diagnosis was 30 (+/-14) for CD and 34 (+/ 13) for UC. In CD patientsdisease location at enrollment was ileal 18%, ileo-colonic 44% and coloniconly 24%. 6% had concomitant upper GI involvement. 190 (34%) hadfistulas and 180 (32%) stenosis. In UC patients, 45% had pancolitis, 37%left colitis and 13% proctitis.

Conclusions: The charact eristics of the Swiss IBD Cohort Study patientsare concordant with the previous Swiss pilot study in 2004 and showedsignificant use of thiopurines and increasing anti-TNF use. There is adefinite need for prospective data in order to evaluate disease courseusing these therapies, as well as their appropriateness(http://www.epact.ch).

P15p53 as a Predictor of Response to NeoadjuvantRadiochemotherapy for Rectal Cancer? B. Kern1, N. Devaux1, U. Wagner2, M. von Flüe1

1 Chirurgische Klinik, St. Claraspital, Basel, 2 Histopathologie ViollierAG, Basel Objective: Predictors for pathologic complete response after neo -adjuvant radiochemotherapy for locally advanced rectal cancer arecurrently unknown. The tumor suppressor gene p53 has beenproposed to play a role in tumor response to RCT. The aim of thisstudy was to examine the correlation between p53 expression beforeand tumor response after neodjuvant RCT. Methods: The study included 51 patients with rectal cancer stage T3or T4 and neoadjuvant RCT. Immunhistochemistry was done for p53before RCT. Tumor regression was graded according to Dworak(D0-D4). A semiquantitative grading system and the immune reactivescore were considered in the staining system. Results: p53 expression on tumor biopsies was positive in 40/51cases (78%) and negative in 11/51 cases (22%). Correlation of p53and tumor response to RCT: Conclusion: Immunhistochemical expression of p53 on rectal cancer

cells before RCT does not correlate with tumor regression grade. It isnot helpful to identify patients with good response to the neoadjuvanttreatment.

P16Analysis of Clinical Outcome after NeoadjuvantRadiochemotherapy for Locally Advanced Rectal Cancer B. Kern1, N. Devaux1, M. Thumshirn2, S. Beck3, M. von Flüe1

1 Chirurgische Klinik, St. Claraspital, Basel, 2 Medizinische Klinik, St. Claraspital, Basel, 3 Radiologische Klinik, St. Claraspital, Basel Objective: Neoadjuvant radiochemotherapy (RCT) is currently thegold standard for patients with locally advanced adenocarcinoma of the middle and lower third of the rectum. Methods: The clinical data of a prospective study on 79 patientswere analysed with special interests on downstaging, perioperativmorbidity and short-term follow-up. Results: Median follow-up was 16 months (1-33), mean age was 65 years(20-86). Mean tumor distance from anal verge was 6 cm (1-13). AfterRCT 51% were downstaged with MRI and 45% with endorectal ultra-sound. Rectal amputation was performed in 25%, 75% had a sphincterpreserving operative procedure. Major complications were seen in5.8%, including 2 anastomotic leaks. On histopathologic analysis 21%of specimens were ypT0 ypN0 with tumor regression grade 4. One localrecurrence and 3 distal metastasis occurred 7 to 24 months after RCT. Conclusion: Neoadjuvant RCT is effective with good downstagingand complete pathologic response in 21%. Surgery after RCT is welltolerated and can be performed with very low morbidity.

P17Magenentleerungsstörungen nach pyloruserhaltenderPankreatoduodenektomie nach Longmire-Traverso (PPPD) Rebecca Kraus, Noémie Devaux, Beatrice Kern, Marc-Olivier Gue nin,Markus von FlüeChirurgische Klinik, St. Claraspital, Basel Einleitung: Magenentleerungsstörungen nach Pankreatoduodenek- to mie treten häufig auf. Studien haben gezeigt, dass dieses Problembei der pyloruserhaltenden Resektion vermehrt auftritt als nach klassi scher Whipple-Operation.Methode: In einem Zeitraum von 48 Monaten wurden prospektiv 39 Patienten mit PPPD erfasst und bezüglich Magenentleerung analy siert. Ergebnisse: 39 Patienten (23 Frauen, 16 Männer) mit einem mittlerenAlter von 72 Jahre (39-83) wurden erfasst. 32 Patienten hatten einAdenokarzinom des Pankreas, des Duodenums oder des Gallen -gangs, 7 Patienten eine andere Histologie. Die durchschnittliche Ver-weildau er der intraoperativ eingelegten Magensonde lag bei 8 Tagen

Most frequent Treatments at inclusion

567 CD 363 UC

Mesalazine 114 20% 221 61%

Antibiotics 27 5% 5 1%

Thiopurines 282 50% 128 35%

Anti-TNFs 127 22% 27 7%

Methotrexate 59 10% 11 3%

Steroids 141 25% 118 33%

D 0 n (%) D 1 n (%) D 2 n (%) D 3 n (%) D 4 n (%) Total n (%)

p53+ 1(2) 10(19) 16(31) 6(12) 7(14) 40(78)

p53– 0(0) 2(4) 5(10) 0(0) 4(8) 11(22)

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(2-24). Bei allen Patienten wurde am 7. postoperativen Tag eineMagendarm passage (MDP) durchgeführt. Diese war bei 28 Patienten(72%) un auffällig, bei 9 Patienten (23%) durchgängig, aber leichtverzögert. Zwei Patienten zeigten eine Insuffizienz, wovon ein Patientreoperiert werden musste. Bei 3 Patienten (7.6%) kam es im Verlauf zu einer Magenentleerungsstörung bei normaler MDP. Alle konnten konserva tiv mittels Nahrungskarenz und Prokinetika behandelt werden.Kein Patient benötigte eine sekundäre Einlage einer Magensonde. Schlussfolgerung: Durch eine standardisierte Operationstechnikkann die Magenentleerungsstörung nach pylorus-erhaltender Duodeno pankreatektomie nach Longmire-Traverso tief gehaltenwerden, in un serem Patientenkollektiv unter 10%.

P18Incidence and treatment of incisional hernia after liver transplantation Anita Kurmann, Guido Beldi, Christian Seiler, Daniel Candinas Department of Visceral and Transplant Surgery, Inselspital UniversitätBern, Switzerland Background: The incidence of incisional hernia is a common compli-cation in abdominal surgery. However little data is available regardingincidence and treatment strategies in patients post orthotopic livertransplantation (OLT). Our study was performed to evaluate the out-come after open with laparoscopic incisional hernia repair in thesepatients. A prospective cohort of patients with OLT allows us todescribe the incidence of incisional hernia. Methods: Our study based on 225 patients who had undergone 233 liver transplantation between 1993-2007. The outcome of 31 patients who underwent open hernia repair were compared with those of 13 patients who underwent laparoscopic hernia repairafter OLT. Student’s T-test and Fisher’s exact test were used as statistical tests. Results: The incidence of incisional hernia after OLT in our studygroup was 25.8% (58/225), occurring after a mean of 29 months.Among these patients 44 underwent incisional hernia repair (31patient received open and 13 patients laparoscopic surgery). Thedemographic parameters like age, BMI and MELD score were similarin both groups. Different techniques/mesh were used in the opengroup whereas in the laparoscopic group a single type of mesh wasused. The operative time in the laparoscopic group was significantlylonger (p<0.001) compared to open surgery. No statistical differencewas found for the median length of hospital stay (7 days in the laparo-scopic group vs. 8 days in the open group, p=0.37), postoperativecomplication (16% vs. 7%, p=0.65) and recurrence rate (29% vs.15%, p=0.46). Conclusion: The incidence of incisional hernia post OLT is high.Laparoscopic incisional hernia repair in patients post OLT is safe andassociated with a trend towards a lower rate of complications andrecurrence rate.

P19Predictive factors for morbidity and mortality in patientsundergoing laparoscopic paraesophageal hernia repair Hannes J. Larusson MD1, Urs Zingg MD1, Dieter Hahnloser MD2,Karen Delport MD1, Burkhardt Seifert PhD3, Daniel Oertli MD1, FACS1

1 Department of Surgery, University Hospital Basel, 2 Department of Visceral and Transplantation Surgery, University Hospital, Zurich, 3 Biostatistics Unit, ISPM, University of Zurich, H. Larusson and U. Zingg equally contributed as first authorsBackground: Patients undergoing laparoscopic paraoesophagealhernia (PEH) repair risk substantial morbidity. The aim of this studywas to analyse predictive factors for postoperative morbidity andmortality. Methods: 354 laparoscopic PEH repairs were analyzed from thedatabase of the Swiss Association for Laparoscopic and Thoraco-scopic Surgery (SALTS). Age (<70 and ≥70 years) and risk (low: Amer-ican Society of Anesthesiology (ASA) scores 1 + 2); high ASA 3 + 4)groups were defined and multivariate logistic regression was con-ducted. Results: In patients ≥70 years postoperative morbidity (24.4% versus10.1%) and mortality (2.4% versus 0%) was significantly higher com-pared to patients <70. In patients with gastropexy, this significantdifference was again present (38.8% versus 10.5%) whereas inpatients with fundoplication no difference between age groups

occurred (11.9% versus 10.1%). Mortality did not differ. High riskpatients had a significantly higher morbidity (26.0% versus 11.2%)but not mortality (2.1% versus 0.4%). The multivariate logistic regres-sion identified the following variables as influencing postoperativemorbidity: Age ≥70 years (OR 1.99); ASA 3 + 4 (OR 2.29); type ofoperation (gastropexy) (OR 2.36). Conclusion: Age, ASA score and type of operation influence postop-erative morbidity and mortality significantly. Morbidity is substantial inelderly patients and those with comorbidity, questioning the paradigmfor surgery in all patients. If surgery is considered, repair with fundo-plication should be preferred, independent of patient’s age.

P20Das Darmkrebs Screening mittels Kolonoskopie vermindertMortalität und Auftreten späterer Kolonkarzinome massiv Christine N. Manser*, Urs A. Marbet**, Jakob Brunner*** *Stadtspital Triemli, **Kantonsspital Uri, ***Kantonsspital Glarus.Hintergrund: Die Evidenz für die Effizienz des Screenings (S) mittelsKolonoskopie (K) ist v.a. indirekt. Die Inzidenz kolorektaler Karzinome(CRC) nach Polypektomie wurde einzig mit epidemiologischenKohorten verglichen. Prospektive auf der Durchschnittsbevölkerungbasierende Daten fehlen. Methodik: In Glarus/Uri wurde 2000/01 während eines Jahres allenbeschwerdefreien Leuten > 50 Jahren ohne Risiken und ohne Kwährend der letzten 5 Jahre ein Darmkrebsscreening angeboten.1918 Leute (8.5% der Bevölkerung>50Jahre) hatten K, 26.6% davonmit Polypektomien. Bei 11 wurde dabei ein CRC gefunden. In Urihatten über 12% beim S und zusätzlich 13% in den letzten fünfJahren eine K. Es wurden dann bis inkl 2007 die CRC bei Leuten mitScreening (mS) und ohne Screening (oS) prospektiv erfasst.Tumorstadien, Lokalisation, Risikofaktoren und Berufe (+ in Uri dasGesundheitsverhalten) wurden verglichen. Resultate: Während der Screeningperiode traten mS diskret mehrCRC auf. Die kumulative Inzidenz war nach 1 Jahr mS und oS aus-geglichen. Danach traten 217 CRC oS (62% Männer, 58% im Sigma)und 1 mS auf. 19,4% der CRC oS waren T1-2NoMo, 72% jener mS.Über 25% oS starben, einer mS (Infarkt). Landwirte liessen sich sel-tener screenen. Rauchende und Arbeiter hatten gehäuft CRC, Kader-leute seltener. 1° Verwandte mit CRC waren häufiger mS, der BMI warvergleichbar. Screeningpatienten lebten tendentiell diskret gesund-heitsbewusster. In Uri mit 25% Leuten mit K zeigt sich ein Trend zurAbnahme der Ca. Schlussfolgerung: Das S mittels K reduziert Inzidenz und CRC bezogene Mortalität massiv. Das Stadium der CRC oS ist meist fortgeschritten. Beinahe die Hälfte der CRC treten proximal desSigma auf. Die Screeningpopulation entspricht der Durchschnitts- bevölkerung und hat ein durchschnittliches CRC Risikoprofil.

P21Fulminant Liver Failure due to Sulfasalazine-Induced DRESSSyndrome: Fatal Recurrence after Liver Transplantation Maria Mennicke1, Felix Stickel2, Ludwig Wilkens3, Daniel Inderbitzin1,Werner J. Pichler4, Daniel Candinas 1 Department of Transplant and Visceral Surgery, 2 Department of Clinical Pharmacology, 3 Department of Pathology, 4 Department of Immunology, Inselspital Bern Background: DRESS syndrome (Drug Rash with Eosinophilia andSystemic Symptoms) is a rare drug hypersensitivity reaction with amortality of up to 10% precipitated by anticonvulsants, antibioticsand other drugs. Clinically, fever, eruptive skin rash, hypereosinophiliaand organ involvement like hepatitis, myocarditis or interstitial nephri-tis may evolve. Case Report: A 60-year-old man with polyarthritis had been treatedwith prednisone and sulfasalazine for 6 weeks. After hospitalizationwith fever, antibiotic treatment with Vancocin was started. He subse-quently developed a generalised scaled exanthema and faceoedema, hypereosinophilia 0.78G/l and elevated liver enzymes. Aftera rapid increase of the latter to ASAT 18.473U/l and ALAT 6.745U/l, aliverbiopsy was performed which showed hepatic necrosis andeosinophilic infiltration, compatible with DRESS syndrome. Thepatient deteriorated to fulminant liver failure and underwent superurgent liver transplantation. After recovering well initially, the patientdeveloped generalized exanthema and elevated liver enzymes. Liverbiopsy showed an acute graft rejection together with abundant

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eosinophilic infiltrates. The patient was treated with high-dosemethylprednisolon. After 24 hours, the patient presented with cardiacarrest and died despite immediate resuscitation. Post-mortem exami-nation revealed a total necrosis of the liver transplant and histologyconfirmed recurrent DRESS syndrome. Conclusion: DRESS syndrome with consecutive liver failure mayrecur following liver transplantation and can be fatal despite imme -diate immunosuppressive therapy.

P22Low systemic mannose-binding lectin (MBL) production associ ates with complicated Crohn’s disease, and experimental MBL deficiency leads to more severe pathogen-amplified DSS-colitis Stefan Müller, Thomas Schaffer, Alain M. Schoepfer, Beatrice Flogerzi,Beatrice Seibold-Schmid, Frank SeiboldDepartment of Clinical Research, Division of Gastroenterology, Uni versity of Bern, Switzerland Background: Mannose-binding lectin (MBL) represents a first line ofdefense mechanism against yeasts and certain bacteria. Even thoughwe have observed an association of MBL-deficiency with anti-Sac-charomyces cerevisiae antibodies (ASCA) in Crohn’s disease (CD), therole of MBL in the pathogenesis of CD is unclear. A possi ble correla-tion with distinct disease phenotypes as well as conse quences ofMBL-deficiency in experimental colitis have not been ad dressed sofar. Methods: Serum concentrations of functional MBL were measured byELISA in 164 CD patients, 32 patients with ulcera tive colitis (UC) and 51 healthy controls (hc). CD patients were grouped according to theMontreal classification. MBL was classifiedas deficient (<100 ng/ml), low (100-500 ng/mL) and normal-to-high(>500 ng/mL). MBL was further quantified in samples collected dur ing endoscopy and from fullthickness small bowel specimens. DSS administration was used toinduce experimental colitis. Wild type and MBL-deficient mice wereimmunized with yeast to assess experimen tal ASCA generation. Results: Low MBL levels were positively asso ciated with complicatedCD (P<0.001), while negatively associated with pure inflammatorydisease (P<0.0001). MBL protein as well asmRNA was rarely detectedand only at very low levels in intestinalspecimens. Experimental ASCAhad a prolonged half-life in MBL deficient compared to wild type mice.Furthermore, MBL-deficient mice showed more severe DSS colitisespecially when simultaneously challenged with an adhesive and inva-sive strain of E. coli, originally isolated from the ileum of a CD patient. Conclusions: Serum MBL, but not locally produced MBL in the intes-tine, plays a role in CD phe notype. Sustained ASCA titers in MBL-deficient mice, together with the increased susceptibility to pathogen-amplified DSS colitis suggest, that prolonged persistence of invasivegut pathogens in the absence of MBL may play a role in intestinalinflammation.

P23Intestinal malrotation – A rare cause of bowel obstruction in adults. Markus Naef, Beat Muggli, Wolfgang G. Mouton, Hans E. WagnerDepartment of Surgery, Spital STS AG Thun, CH-3600 Thun Objective: Anomalies of intestinal rotation are very rare and maycause symptoms related to intestinal obstruction, peptic ulcerationand malabsorption. 75% of patients develop intestinal obstruction in infancy. Methods: We present the case of a 83 years old patient with a malro-tation grade II as a rare cause of bowel obstruction and discuss theimplications for diagnosis and therapy. Results: A 83 years old patient was admitted due to crampy abdomi-nal pain in the upper abdomen with nausea and vomiting. Past med-ical history revealed neither previous abdominal operations nor anysigns of bowel obstruction. Clinical examination showed a slighttenderness in the upper abdomen. Laboratory showed a C-reactiveproteine of 42 mg/l. Abdominal X-ray revealed signs of bowelobstruction. CT scan showed upper small bowel obstruction probablydue to adhesions and no signs of a tumor. At laparotomy, intestinalherniation of the small bowel due to intestinal malrotation grade IIwas found with the duodeno-jejunal junction lying on the right sideand the cecum in the upper right quadrant. After reposition of thesmall bowel the defect was closed with a running suture. A Ladd

procedure was not performed, because neither adhesions from thececum to the abdominal wall nor an obstruction of the duodenumexisted. Furthermore, the appendix was removed. The postoperativecourse was uneventful. Conclusions: The midgut of a 10-week-old fetus normally returnsfrom the umbilicus to the abdominal cavity and undergoes counter-clockwise rotation about the superior mesenteric artery axis. Anom-alies of intestinal rotation and fixation include nonrotation, incompleterotation (malrotation grade I), reversed rotation (malrotation grade II)and anomalous fixation of the mesentery and often are associatedwith other anomalies such as duodenal stenosis, gastroschisis,omphalocele and situs inversus. When not operated in infancy adultpatients with intestinal malrotation may present with acute or chronicobstructive symptoms. A Ladd procedure is recommended for incom-plete rotation with obstruction of the duodenum by abnormal peri-toneal bands. The appendix should be removed. Prompt recognitionand surgical treatment usually lead to a successful outcome of thisrare condition with excellent long-term results.

P24Apolipoprotein E Regulates Hepatic Lipid Accumulation andGene Expression in Diet-Induced Steatohepatitis Philipp C. Nett*†‡, Elvira Haas*, Indranil Bhattacharya*, TimDörflinger*, Huy R. Ha‡, Sidney G. Shaw‡, Luigi Tornillo§, DanielCandinas†, Jean-François Dufour‡, Matthias Barton** Department of Internal Medicine, Internal Medicine I, MedicalPoliclinic, University Hospital Zürich, Switzerland; † Department ofVisceral and Transplant Surgery, University Hospital Bern, Switzerland;‡ Cardiovascular Therapy Research Laboratory, Clinical ResearchCenter, University Hospital of Zurich, Switzerland; ‡ Department of Clinical Experimental Research, University of Berne, Switzerland; § Institute of Pathology, University Hospital Basel, SwitzerlandBackground: Recently, it has been shown that apolipoprotein (apo)Ehas the ability to induce cholesterol efflux from macrophage foamcells and its transport of extrahepatic cholesterol to the liver forexcretion out of the body. In order to determine the role of apoE in the development of NASH, we investigated its relationship to themorphologic and molecular changes in an experimental model ofdiet-induced steatohepatitis. Methods: Liver morphology, lipid content as well as gene expressionpatterns were assessed in C57BL/6 wild-type and apoE-deficient(apoE–/–) mice fed with a western-type high fat diet. Results: Plasma levels of triglyceride, total cholesterol, VLDL- andLDL cholesterol increased in both wild type and apoE–/– mice in thehigh fat diet group (both p<0.05). Steatohepatitis was induced after30 weeks of treatment in apoE–/– mice, which was correlated with anincreased hepatic content of triglyceride and cholesterol ester(p<0.05), but not free cholesterol (n.s.). Interestingly, hepatic contentof triglyceride was decreased by almost 5-fold in apoE–/– mice in thenormal diet group (p<0.05), which was in line with a diminishedexpression pattern of genes regulating hepatic lipid metabolism. Conclusion: Our data indicate that the vascular protective role ofapoE might also contribute to a distinct mechanism affecting plasmalipid levels to protect the liver from lipid accumulation during thedevelopment of NASH.

P25Leptin-receptor deficiency protects from alcoholic and non-alcoholic liver fibrosis via lack of Cytochrome P450 2E1 induction in ratsEleonora Patsenker, Vreni Schneider, Monika Ledermann, Hans Saegesser, Felix StickelDepartment of Clinical Pharmacology, University of Bern Background: Alcohol consumption may accelerate fibrosis develop-ment in coexisting non-alcoholic fatty liver disease. Apart from syner-gisms of fat- and alcohol-related pathophysiology, combined effectsof both diseases on leptin-mediated fibrogenesis and cytochromeP450 2E1 (CYP2E1) induction are implicated. Our aim was to investi-gate the effect of chronic alcohol administration on liver fibrogenesisin obese, insulin-resistant rats. Methods: Obese Zucker rats and their lean littermates (4 groups,n=10 each) were pair-fed a Lieber-De Carli alcoholic or control liquiddiet for 12 weeks. Standard serum liver laboratory values were meas-ured. Liver histology was assessed by Hematoxillin/Eosin, and fibro-

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sis and steatosis quantified by Sirius Red and Oil Red O morphome-try, respectively. Liver hydroxyproline (HYP) was assayed, and Fibro-sis-related gene and protein expression was measured by TaqManPCR and Western blotting. Microsomal enzymes CYP2E1 andCYP4A2 were assayed at transcription and protein level. Results: Obese rats had higher liver enzyme, bilirubin and lipid levels,and more steatosis than lean animals but no aggravating impact ofchronic alcohol intake was visible. Histologies and HYP showedsimilar extent of fibrosis in all groups. Fibrosis-related genes includingprocollagen a1(I), aSMA, and TGFb1 showed similar expressionregardless body weight and alcohol intake. CYP2E1 protein wasinduced by 35% in both groups of obese rats, while mRNA levelswere upregulated 3.5-fold in alcoholic lean rats. CYP4A2 was lower in obese rats, but upregulated 2-fold in those fed alcohol. Conclusions: Chronic alcohol feeding in Zucker rats exerts no effecton liver fibrosis formation, possibly due to insuffient leptin/leptinreceptor-mediated CYP2E1 induction.

P26A new method for Colorectal Cancer Screening: Capsule Endoscopy compared to Conventional Colonoscopy Julia B. Pilz1*, Susanne Portmann2*, Shajan Peter3, ChristophBeglinger2, Lukas Degen2

1 Department of Internal Medicine, Kantonsspital Winterthur,Switzerland, 2 Department of Gastroenterology and Hepatology,University Hospital Basel, Switzerland, 3 Department Gastro-enterology and Hepatology, University of Alabama Birmingham, AL Background: Colorectal cancer (CRC) can be prevented by colono-scopic removal of all identified adenomatous polyps during screening(1), and colonoscopy is the gold standard to date. Patient acceptanceremains the main limiting factor to broad spread of screening and inSwitzerland, CRC screening is not regularly promoted by the health-care system (2). Colon capsule endoscopy (CCE) might be a novelmethod for large populations. Methods: Patients referred for screening means or lower gastro -intestinal signs and symptoms were included in this single center pilotstudy. They underwent preparation and then ingested the capsule(PillCam Colon). Standard colonoscopy was performed the nextmorning. Significance was defined as polyps >5 mm in size.Colonoscopy and CCE was performed by independent physicianswith blinding of results until completion of both examinations. Results: A total of 59 patients were included at the University Hospital Basel (males 35, females 24; median age 59), the resultswere evaluable in 56 patients. The capsule endoscopy was completein 36 subjects, and reached the colon in 21 patients but remained in the stomach in 1 case and in the small bowel in 2 cases. Of the 56 patients, 15 had significant findings; 10/27 (37%) of the relevantpolyps were detected by CCE, compared to 24/27 (88,9%) oncolonoscopy. False positive findings on CCE for overall polyps wererecorded in 11/41 (26,8%) cases, and in 3/15 (20%) cases with signi -ficant polyps. Overall sensitivity was 79%, specificity was 54%, positive predictive value was 63% and negative predictive value was71%. Adjusted to significance of findings sensitivity was 33%, speci-ficity was 93%, positive predictive value was 57% and negative pre-dictive value was 93%. No adverse events were recorded. Conclusion: Capsule endoscopy is a new alternative on the horizonfor colorectal cancer screening, as suggested in previous pilot studies(3,4). The high negative predictive value supports its further role as ascreening tool, however CCE was not able to detect all polyps foundduring colonoscopy. Whether CCE will be a valuable tool warrantscontrolled randomized testing.

(1) Winawer SJ, Zauber AG, Ho MT et al. Prevent 1993;329:1977-81 (2) Schoepfer A. Swiss Med Wkly 2005;135(45-46):679-83 (3) Schoofs N et al. Endoscopy 2006;38:971-77 (4) Eliakim R et al. Endoscopy 2006;38:963-70

J.B.P. and S.P. contributed equally to this study

P27The Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS): founding and first observations Valérie Pittet1, Pascal Juillerat2, Christian Mottet2, Christian Felley2,Florian Froehlich2, Pierluigi Ballabeni1, Bernard Burnand1, PierreMichetti2, John-Paul Vader1 and the Swiss IBD cohort study group 1 Health Care Evaluation Unit, Institute for Social and PreventiveMedicine, Lausanne, 2 Division of Gastroenterology and Hepatology,Lausanne University Hospital, CHUV Background: After a pilot population-based cohort, established inthe Canton de Vaud between July 03 and Dec. 04, the project wasexpanded in 2006 to become national-wide. Besides studying riskfactors associated with the disease, major aims of the study relate toappropriateness of therapy, health resource consumption and influ-ence of new biological therapies and psychosocial aspects linkedwith exacerbation of the disease. A Biobank has been set up in orderto study coupling effects of genetics on clinical observations. Methods: 6 major IBD centers at Swiss university-based tertiaryhospitals recruit patients as well as physicians outside the centers. All adult or pediatric IBD patients, with permanent residence status or being treated regularly in Switzerland are eligible for enrolment, on condition that a radiological-, endoscopic- or surgery-confirmeddiagnosis had been established at least 4 months prior to inclusion orafter at least one recurrence of the symptoms. Patients are followedup once a year. Data are collected through physician and patientcontact using questionnaires. Results: 81 physicians are participating since 1st Nov. 06 to patientrecruitment, 75% from the 6 major centers, 11% from regional hospi-tals and 14% are private practitioners. 1039 patients were enrolled,60% suffering from Crohn’s disease and 38% from ulcerative colitis.In 29 cases, the diagnosis was an indeterminate colitis. The propor-tion of females is 50.4%. Mean age of the cohort is 43 yrs (+/- 15),ranging from 16 to 89 years. 74% of the patients have alreadyresponded to the first questionnaire and 15% are on hold (time tosending <= 3 mths). Conclusion: The newly-established Swiss IBD cohort study waslaunched 15 months ago and offers a real challenge in acquiring dataabout epidemiology of IBD in Europe, as well as evaluating patienthealth care and costs linked to these diseases.

P28Assessing dysphagia during esophageal manometry: how well do liquid and solid swallows reproduce patients’ symptoms?

D. Pohl, P. Janiak, E. Savarino, M. Fried, R. TutuianDivision of Gastroenterology and Hepatology, Department of InternalMedicine, University Hospital Zurich, Switzerland

Background: Esophageal motility abnormalities are often reported in patients with dysphagia undergoing esophageal manometry. Explain-ing patients symptoms based on esophageal manometry findings ischallenging. Correlations between esophageal symptoms and manome-try findings are underreported. Our aim was to evaluate correlationbetween esophageal symptoms and high resolution manometry find-ings. Methods: Patients presenting for esophageal manometry were asked toreport severity and frequency of dysphagia during the last 2 weeks priorto testing (dysphagia score). Esophageal high resolution mano metry(HRM) was performed using a 32-channel water-perfused system andincluded 10 water (10 ml each) and 10 solid (bread) swallows. Duringesophageal manometry patients were asked after each swallow if theyexperienced dysphagia or not. Results: Data from 81 manometries performed in 74 patients (43 F, 31 M, mean age 46.3; range 18-87 years) totalling 801 liquid and782 solid swallows were included in the analysis. The per-swallow analy-sis for liquid swallows found manometric simultaneous and ineffectivecontractions more likely to be associated with symptoms (12/49; 24.5%and 21/125; 16.8% respectively) compared to manometric normal con-tractions (24/627; 3.8%). Similar results were noticed during solid swal-lows. The per-patient analysis found signi ficant (p<0.01) but moderate-poor correlations between dysphagia score and % swallows perceivedduring testing (r=0.399 liquid and r=0.409 solid swallows) and betweendysphagia score and % manometric normal contractions during liquidswallows (r=-0.357). Corre lation between % swallows perceived duringtesting and % manometric normal swallows was significant (p<0.01) butpoor (liquid swallows r=-0.368, solid swallows -0.268). Conclusion: While manometric characteristics of esophageal contrac- tions play a role in the perception of individual swallows, the proportionof manometric abnormal contractions is not solely responsible for theintensity of dysphagic symptoms.

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P29Prophylactic drainage after laparoscopic appendectomy in complicated appendicitis. A case matched study Background: Little evidence is currently available about the utility ordanger of prophylactic drainage in open digestive surgery, especiallyin complicated appendectomy. Due to the absence of data inlaparoscopy, we investigated the impact of prophylactic drainage inlaparoscopic appendectomy for complicated appendicitis. Material and methods: 130 consecutive patients operated betweenNovember 2003 and December 2006 with laparoscopic appendec-tomy for complicated appendicitis (perforation or phlegmon) andprophylactic intraperitoneal drainage were matched one by one to130 patients operated with the same conditions but without drainagebetween January 2005 and June 2007,controlling for age, gender,ASA score and Body Mass Index. Primary end-point was surgicallocal complications and secondary were operative duration, transitrecovery time and length of hospital stay. Power calculation with apower of 90% and 20% Beta error gave 105 patients in each group.Uncomplicated appendicitis were excluded from the present study. Results: Patients without drain had significantly less overall compli-cations (7.7% vs. 18.5%, p=0.01). Similarly for the secondary end-points, the omission of drainage was of significant benefit in: opera-tive duration (59.4 min vs.76.4 min, p<0.0001), transit recovery time(2.5 days vs. 3.5 days, p=0.0068) and length of stay (4.2 days vs. 7.3 days, p<0.0001). Conclusion: Prophylactic drainage after laparoscopy in complicatedappendicitis has no benefit and does even increase postoperativecomplications, operation duration and hospital stay. A prospectiverandomized study would have been a better demonstration thatdrainages are useless and even harmful in complicated appendicitis,but due to a change in policy in our department a case matchedretrospective study was preferred. The present study had a sufficientstatistical power and is therefore the best available evidence up tonow. We conclude that prophylactic drainage in complicated appen-dectomy is not to be recommended and may be omitted safely.

P30Ficolin-2 and Ficolin-3 in Crohn’s disease Thomas Schaffer, Alain Schoepfer, Stefan Mueller, Frank SeiboldDept. of Clin. Research, Div. of Gastroenterlolgy, UniversityHospitalBern, Switzerland Background: Ficolins are complement activating soluble pattern rec ognition molecules, the epitope is N-acetyl-glucosamine which isfound in the cell wall of bacteria and yeasts. Ficolin-2 (expressed by liver) and ficolin-3 (expressed by liver/lung) are found in se rum/plasma. The role of ficolins in Crohn’s Disease (CD) is largely unknown. Aim: Evaluation of association between ficolin serum lev els, andserum reactivity to mannans (ASCA) and distinct CD pheno types. Methods: Serum concentrations of ficolin-2, ficolin-3 and ASCA,were measured in 182 CD patients, 67 patients with ulcerative colitis(UC) and 67 healthy controls (HC). CD patients were classified intothe following phenotypes: non-stricturing, non-penetrating (B1), stricturing (B2), and penetrating (B3). Results: Serum levels of fi colin-2 were significantly higher in CD(1683±878ng/mL) and UC (1480±843) compared to HC (1170±765)(P<0.0001 and P=0.028). Serum levels of ficolin-3 in CD patients(22659±10606) were not dif ferent from HC (24265±9690), UC patientshad lower ficolin-3 levels (21288±7582) compared to HC (P=0.037).Serological profiles: Posi tivity for ASCA in CD (in percent): 63; in UC: 4;in HC: 4. ASCA titers were distributed into low, intermediate and highpositive (extinc tion). CD patients with intermediate/high ASCA titers hadsignifi cantly lower ficolin-2 levels (P=0.044) compared to ASCA lowposi tive and ASCA negative CD patients. CD patients with intermedi-ate/high ASCA titers had significantly lower ficolin-3 levels (P=0.0093)compared to ASCA negative CD patients. We found no significant asso-ciation between ficolin-2 and ficolin-3 levels and dis tinct CD phenotypes. Conclusions: CD patients have significantly higher ficolin-2 levels com-pared to HC, possibly reflecting ficolin-2, but not ficolin-3, upregulationduring inflammatory conditions. Asso ciation of high ASCA titers with lowficolin-2 and ficolin-3 levels may indicate reduced clearance of GlcNAc-carrying antigens such as yeast mannans. Ficolin-2 and ficolin-3 con-centrations do not correlate with a distinct CD phenotype.

P31Incidence Rates of Gastric and Esophageal Carcinoma in Central Switzerland Within the Last 26 Years: SignificantChanges for Noncardia Gastric and Esophageal Squamous Cell Carcinoma, But Not for Cardia Type I-III Adenocarcinoma Adrian Schmassmann1, Diana Schmassmann-Suhijar1, Marie-GabrielleOldendorf2, Jan-Olaf Gebbers2

Medizinische Klinik (1) und Pathologisches Institut (2), LuzernerKantonsspital, SurseeBackground: A strong increase of adenocarcinoma incidence ratesof cardia type I-III adenocarcinoma has been reported in several otherWestern countries. The goal of this study was to examine esophagealand gastric carcinoma incidence patterns among the Central Swiss -population within the last 26 years (population size: 720 000 in 2007).Methods: We calculated age-adjusted and gender specific incidencerates for noncardia gastric adenocarcinoma, cardia type I-IIIadenocarcinoma, and esophageal squamous cell carcinoma.Results: The incidence of noncardia gastric adenocarcinoma -decreased within 26 years in males and females by 3.3-fold and 1.8-fold, respectively. Cardia type I-III adenocarcinoma showed no clear trends in incidence rates in all age groups of both genders.Esophageal squamous cell carcinoma showed 1.7-fold decrease in males without relevant changes in females.

Conclusions: As in other Western countries, the incidence of non cardia gastric cancer strongly decreased within the last 26 yearsin Central Switzerland. In contrast to other Western countries, cardia -type I-III adenocarcinoma did not significantly change in males andfemales in all age groups in Central Switzerland.

P32Management of Gastro-Intestinal Stroma Tumors: Surgery,Imatinib and beyond Schmid A., Schnider A., Metzger U.Chirurgische Klinik, Stadtspital Triemli, 8063 Zürich Introduction: Due to advances in molecular diagnostics, Gastro-Intestinal Stroma Tumors (GIST) are increasingly recognized in clinicalpractice. Furthermore, advances in molecular target therapy havedramatically improved treatment options for these patients. Targettherapy has lead to a remarkable change in the surgical manage-ment of GIST. We present our single centre experience over the past 10 years in management of these tumors in an interdisciplinaryapproach and present the current standard of care. Patients and Methods: From 1997 to March 2008 we followedpatients with GIST. 57 patients were operated on for primary or recur-ring GIST. 6 patients were lost to follow up. Mean age was 63 years(28 85), 55% were of male gender. Primary tumor site was most frequently in the stomach (26 cases), followed by the small intestine(19 cases), the colon (6 cases), the peritoneum (4 cases) and theoesophagus (2 cases). Mean tumor size was 6.1 cm (range 2–20 cm).In 11 patients there were multiple tumor locations. 48 patients wereoperated on in curative intent, while in 9 patients, resections weremade for palliation of tumor related symptoms. In 8 patients, secondaryresections for recurring disease were performed. Results: Overall survival of these patients was assessed according to the risk score for GIST described by Fletcher, using tumor size andmitotic activity as predictor for recurrence. Overall survival was:

Fletcher Score 2-year Survival 5-year Survival

Low risk 86% (N=14) 75% (N=10)

Intermediate risk 76% (N=16) 56% (N=11)

High risk 45% (N=13) 29% (N=7)

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Out of these patients, 13 patients received treatment with Imatinib.During the administration of Imatinib, 2 secondary resistances wereobserved. One of these patients was transferred to Sinitinib, while theother abandoned treatment completely. Discussion: Surgical resection with clear margins (R0) remains thestandard of care for primary resectable GIST. Neoadjuvant treatmentwith Imatinib is recommended in patients with primarily irresectibleGIST, to minimize the extent of surgery or to avoid mutilating resec-tions. Multiviszeral resections without neoadjuvant treatment cannotbe considered standard of care. Ongoing studies are investigating the benefit of Imatinib in an adjuvant setting. So far, there was noimprovement in overall survival for patients receiving treatment. For patients with metastatic disease, Imatinib improves prognosisand amends a subgroup to secondary surgery.

P33Longterm follow-up after multimodality treatment for locally advanced distal rectal cancer Schnider A., Lombriser N., Honegger HP., Metzger U. Chirurgische Klinik, Klinik für Radioonkologie und Nuklearmedizin,Institut für Medizinische Onkologie, Stadtspital Triemli Zürich Longterm neoadjuvant chemoradiation of locally advanced low rectalcancer patients has become a strategy to further improve the out-come of patients. This report analyses the longterm follow up ofpatients concerning complications, response rate, local recurrence,disease free-survival (DFS) and overall survival (OS). Method: 149 neoadjuvant treated rectal cancer patients undergoingsurgery at our institution from 9/95 to 12/07 were prospectivelyanalysed. The median distance of the tumour to the dentate line was4,5cm. Either 5-Flurouracil or Capecitabine/Oxaliplatin concurrentwith radiation (25x1,8Gy) was given. Surgery was performed within 4-8weeks after completion of neoadjuvant treatment. Results: 117 (79%) patients got sphincter saving procedures. Histo-logical complete response (CR) was 13,5% (20 patients). 76 (51%)showed a partial response (PR), 32 (21,5%) were stable and 21 (14%)had progressive disease. In hospital-mortality was zero. 89 (60%)patients had no complications. Clinical leakage rate was 16%(19/117). Presacral abscesses were observed in 20% (30/149). Reoperations were necessary in 19% (28/149). Median follow-up was 58 months. 7 patients got APR during follow-up because ofrecurrence (2), faecal incontinence (5) or perforated diverticulitis (1).Therefore, longterm sphincter saving rate after 24 months is 73%(109/149). Patients with pathological CR (20) are all without any recur-rent disease. Local /regional recurrence is 9% (14/149), dedected 1 to 39 months after primary surgery. Overall 5-year-survival is 70%.OS and DFS analysis will be discussed. Conclusion: Our results indicate a benefit of neoadjuvant treatmentconcerning CR and sphincter saving procedures. Pathological CR is a prognostic factor for a excellent longterm disease-free and overallsurvival. Severity of complications after longterm neoadjuvantradiochemotherapy in low rectal cancer should alert surgeons andoncologists. Further investigations should be done on more precisepretreatment and preoperative staging to prevent overtreatment.Selected patients with assumed CR may profit of a simple transanallocal excision to avoid major surgical complications.

P34Phenotypic Associations of Crohn’s Disease with Antibodies to Flagellins A4-Fla2 and Fla-X, ASCA, pANCA, and NOD2 mutations in a Swiss cohort Alain Schoepfer1, Thomas Schaffer2, Stefan Mueller2, BeatriceFlogerzi2, Erik Vassella2, Beatrice Seibold-Schmid2, Frank Seibold1

1 Department of Gastroenterology, Inselspital/Bern University hospital,2 Department of Clinical Research, University of Bern Background: Distinct Crohn’s disease phenotypes correlate withantibody reactivity to microbial antigens. We examined the associa-tion between antibodies to two new flagellins (A4-Fla2, Fla-X), oligo-mannan (ASCA), pANCA, NOD2 mutations, and clinical phenotypes(according Vienna criteria) in CD patients. Methods: The above antibodies as well as NOD2 mutations (R702W,G908R, and L1007fsinsC) were determined in 252 CD patients, 53 with ulcerative colitis (UC) and 43 healthy controls (HC) and correlated with clinical data.

Results: CD patients characteristics: 36% stricturing, 27% fistulizing,37% inflammatory. Serological profiles: Positivity for A4-Fla2/Fla-X/ASCA/pANCA (in percent) in CD: 59/57/62/12; in UC: 6/6/4/51; in HC: 4/4/5/0. Antibodies to A4-Fla2, Fla-X, and ASCA were signi -ficantly associated with stricturing (P=0.006, P=0.023, P<0.0001), and fistulizing (P=0.029, P=0.01, P=0.015) phenotype, small bowel disease (P=0.002, P<0.0001, P<0.0001) and small bowel surgery(P=0.03, P=0.01, P<0.0001). P-ANCA associated significantly withinflammatory phenotype (P<0.0001). NOD2 mutant alleles correlatedwith small bowel disease (P=0.025). Multiple antibody responsestoward microbial antigens were associated with stricturing (P<0.0001)and fistulizing disease (P=0.002), and small bowel surgery (P=0.002). Conclusions: ASCA and anti-flagellin antibodies are strongly asso -ciated with complicated CD phentoypes. CD patients with serumreactivity toward an increasing number of microbes have the greatestfrequency of strictures, perforations, and small bowel surgery. ASCA,anti-flagellin-antibodies and pANCA can help the clinician in riskassessment of CD patients.

P35Dilation in Eosinophilic Esophagitis: Safety, effectiveness and impact on mucosal inflammation Alain Schoepfer1, Nirmala Gonsalves2, Alex Straumann3, Ikuo Hirano2

1 Dpt of Gastroenterology Inselspital/Bern University Hospital, 2 Dpt of Gastroenterology Northwestern University of Chicago, 3 Dpt of Gastroenterology Kantonsspital Olten Background: Topical corticosteroids are effective in Eosinophilicesophagitis (EE), but relapses occur early after cessation of therapy.In contrast, esophageal dilation often leads to long-lasting symptomimprovement. Aim: To evaluate the effect of dilation on the underlyinginflammation and to assess the efficacy and safety of the procedure. Methods: Retrospective analysis of the Swiss and Chicago EE Data-base. Inclusion: EE patients undergoing 1.) Baseline EGD withesophageal biopsies; 2.) Subsequent dilation for dysphagia; and 3.) Follow-up EGD with repeated biopsies. Any therapy with anti-eosinophilic medication had to be discontinued at least 12 weeksprior to dilation and until after the post-dilational EGD. Dysphagia was graded using a validated score (0-4). Eosinophilic peak infiltrationwas graded semiquantitatively (0-3). Results: We identified 46 patients (38m/8f), mean age at symptomonset 28±15years, mean duration of symptoms prior to dilation was13±10years. Mean duration between completed dilation therapy andre-appearance of symptoms was 24±23months. Mean dysphagiascore before dilation was 1.9±0.4 compared with 1.05±0.6 after dila-tion (P<0.0001). A mean of 2.3±2.7 dilation endoscopies were per-formed until dilation therapy was considered effective. No majorcomplications (esophageal perforation or major bleeding) occurred.The grade of eosinophilic peak infiltration before dilation was 2.1±0.8compared to 2±0.4 in the follow-up EGD (P=0.76). Conclusions: 1) In EE, esophageal dilation can be safely performedand is effective in providing long-lasting symptom relief and a signi -ficant reduction of the dysphagia score. 2) Underlying eosinophilicinflammation is not influenced by the dilation. 3) Esophageal remodel-ing likely contributes to the swallowing disturbances in EE.

P36Eosinophilic Esophagitis: Analysis of Food Impaction andPerforation in 251 Adult Patients Alain Schoepfer1, Christian Bussmann2, Markus Zuber3, SimoneVannini1, Hans-Uwe Simon4, Alex Straumann5

1 Dpt of Gastro enterology Inselspital/Bern, University hospital, 2 Dpt of Pathology Kantonsspital Luzern, 3 Dpt of SurgeryKantonsspital Olten, 4 Dpt of Pharmacology University of Bern, 5 Dpt of Gastroenterology Kantonsspital Olten Background: Eosinophilic esophagitis (EE) can lead to esophagealnarrowings. Several case reports indicate that food impaction, proce-dure-induced perforation and spontaneous rupture are EE-inheritedcomplications. There is no information so far if bolus removal byflexible or rigid endoscopy carries comparable risks of esophagealinjury. Aim: to determine in a cohort of EE patients the risk of foodimpaction and of spontaneously occurring and procedure-inducedsevere esophageal injuries. Methods: Retrospective analysis of the Swiss Esophageal EsophagitisDatabase (SEED) which contains 251 consecutively enrolled EE patients.

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Results: During an 18-year period, 87 of the 251 EE-patients (34.7%)experienced a total of 134 long-lasting food impactions requiringendoscopic food removal. Food impaction occurred exclusively inuntreated patients. The impacted bolus was removed 124 times by flexible (= 92.5%) and 10 times (7.5%) by rigid endoscopy. The rate of transmural perforation was significantly higher (p<0.0001) in rigid 2/10 (= 20%) compared with flexible 0/124 (= 0%) procedures. Furthermore, one (= 0.4%) spontaneous esophageal rupture (Boerhaave Syndrome) was observed.Conclusions: Long-lasting food impaction is a frequently observedcomplication in patients with untreated EE. Bolus removal by rigidendoscopy harbors a high risk of transmural esophagus perforationand should be avoided. Whether food impaction and esophageal wallremodeling can be prevented with consequent anti-inflammatorymedication is still undetermined. All Boerhaave syndrome casesshould be evaluated for underlying eosinophilic esophagitis.

P37Low Mannan Binding Lectin serum levels are associated with complicated Crohn’s Disease phenotypes and reactivity to oligomannan (ASCA) Alain Schoepfer, Beatrice Seibold-Schmid, Beatrice Flogerzi, Stefan Mueller, Thomas Schaffer, Frank Seibold and the Swiss IBDcohort study groupDepartment of Gastroenterology and Clinical Research, University of Bern/Inselspital, Switzerland Background: Mannan-binding lectin (MBL) acts as a recognitionmolecule directed against oligomannan which is part of the cell wallof yeasts and different bacteria. We have previously shown an asso -ciation between MBL deficiency and ASCA positivity. Aim: to evaluateif MBL deficiency is associated with complicated CD phenotypes inthe Swiss IBD cohort. Methods: Serum concentrations of MBL and ASCA were measured(ELISA) in 427 CD patients, 70 with ulcerative colitis (UC) and 76 healthycontrols (HC). CD patients were classified according Vienna criteriainto inflammatory (43%), stricturing (26%), and penetrating (31%)phenotype. MBL was classified as low (<500ng/mL), and normal(500-4000ng/mL).Results: Mean MBL in CD patients (1697±1421ng/mL) was not differentfrom UC patients and HC. However, MBL was found significantlylower in CD patients with stenosis and/or fistulae (1539±1426ng/mL)compared to inflammatory phenotypes (1909±1392, P=0.0077). CDpatients with stenosis or fistula more frequently had low MBL com-pared to UC-like CD patients (P=0.011). ASCA-positivity: 56% in CD,3% in UC patients and 1% of HC. CD patients with stenosis andfistulae were more frequently ASCA-positive compared to inflamma-tory CD patients (P<0.0001). Mean MBL was lower in ASCA+ CDpatients (1575±1465) compared to ASCA-negative CD patients(1853± 1353, P=0.044).Conclusions: Low MBL serum levels are significantly associated withcomplicated CD (stenosis and/or fistula) but negatively associatedwith inflammatory CD phenotype. Furthermore, CD patients with low MBL are significantly more frequently ASCA-positive, possiblyreflecting delayed clearance of oligomannan containing microorgan-isms by the innate immune system in case of MBL deficiency.

P38Hepatitis C infections in Opioid-dependent Patients (HepCOP1): A representative survey on the state of care in the canton of ZurichKatja Schulthess1, Kristyna Valkova1, Dimitri Hauri2, Lucas M.Bachmann2, Johann Steurer2, André Seidenberg1

1 Institute Hausarztmedizin University of Zürich, 2 Horten CentreUniversity of Zürich Background: Evidence and various guidelines (e.g. National Instituteof Health, 2002) recommend antiviral treatment for opioid-dependentpatients with chronic Hepatitis C (CHC). The objective of our studywas to assess how many of the opioid-dependent patients in thecanton of Zurich (ZH) were appropriately tested and treated for CHC. Methods: The survey included a representative sample of all patientson opioid maintenance treatment (OMT) in ZH. We developed a ques-tionnaire to collect information from patient’s charts (demographicdata, laboratory tests, antiviral treatment).

Results: 63 physicians or institutions (18% of OMT providers in ZH)participated in this study. They care for 1575 patients, which repre-sents 43 % of all patients on OMT in ZH. 279 randomly selectedpatient’s charts were analyzed. In 197 (70.6%) cases HCV antibodieswere tested; among them 113 (57.4%) were positive and 84 (42.6%)were negative. In 82 (29.4%) charts no HCV antibody testing wasfound and in 67 (24.0%) not even liver enzymes were determined. 88 of the 113 HCV infected patients were positive for HCV-RNA-PCR,none were negative; in 25 cases no PCR-results were found. Geno-type 1 or 4 were identified in 29 (33%) cases, genotype 2 or 3 in 12(13.6%) respectively; in 47 patient charts (53.4%) we did not find anygenotype results. 15 patients received a treatment with interferon andribavirine. 67 (24.0%) patients received less than minimal diagnosticseven according to earlier guidelines. Also among HCV antibody posi-tive patients, we found 72 (25.8%) patients who are not informed onchronicity of the infection (25) or about genotype (47). Conclusions: In every second patient on OMT in ZH, the necessarytests were not performed to determine whether antiviral treatmentshould be offered. Measures to improve adequate testing for HCV arenecessary.

P39Clinical efficacy of infliximab and its effect on ability to workin a Bern IBD cohort Frank Seibold, Alain Schöpfer, Gunther KaindlKlinik für Gastro enterologie, Universitätsspital Insel, Bern Background: Anti-TNF-Alpha-antibodies such as infliximab (IFX)(Remicade®) are used as second and third-line therapy in activeCrohn’s disease (CD) and ulcerative colitis (UC). The aim of this studywas to investigate the clinical efficacy and economical consequencesof an IFX therapy. Methods: The IBD data bank of Bern was screened for patientstreated with IFX in 2006. Data about disease activity (CRP, CDAI,weight increase), doctors opinion about response to treatment andability to work before and under IFX treatment were extracted. Results: 52 patients with IBD were treated with IFX in 2006 (CD=38,UC=8, 6 with indeterminate colitis (IC)). The indication for IFX was asteroid dependent or refractory course of disease in 32%, fistulae in40%, intolerance or ineffectiveness of immune suppressive treatmentin 28% of patients. A total of 186 infusions of IFX were given. Allpatients but 4 were on a IFX maintenance therapy. IFX was stoppedin 13 patients due to a stable remission. 65% of patients respondedwell to IFX according to the opinion of the treating physician. Animprovement was described in 31 %, and 2 patients did not respondto IFX. The average CRP was 23.3mg/L before IFX and 7.1mg/Lunder IFX treatment (p<0.0001). The mean CDAI decreased 60 pointsin CD patients (p<0.0001). The average weight increased after IFX:2.3kg in CD, 2.1kg in UC, 4.5kg in IC. 21 CD patients were sufferingfrom fistulae, 12 (57%) had a complete closure of fistulae. A partialresponse to IFX was seen in 6, no response in 3 CD patients withfistulae. Only 2.6% of CD patients had a 100% ability to work beforebut 48.5% of patients after IFX treatment UC: 25% before, 87% afterIFX (p<0.0001). The overall costs for all 52 patients were SFr.1.365.908 in 2006, the expenses for IFX was SFr. 691.200. Conclusions: In the Bern IBD cohort we observed a good clinicalresponse to IFX regarding disease activity and fistulae closure. Theability to work was significantly increased what may balance therelatively high treatment costs.

P40Simultaneous Interdisciplinary Approach to FGID – Results of a Pilot Study Sendensky Alexander*, Egloff Nik+, Beer Christine+, von KänelRoland+, Gschossmann Juergen Michael* Background: Since July 2007, we run an university outpatient clinic witha simultaneous interdisciplinary approach to functional gastro intestinaldisorders (FGID). This study intended to analyze characteristics ofpatients admitted to our interdisciplinary outpatient clinic for functionalabdominal disorders (IBSP) from July 2007 until January 2008.Methods: Patients have been referred to the ISBP on a nationwidescale by tertiary care outpatient clinics, general practitioners or spon-taneous self-admission. All patients were simultaneously seen by agastroenterologist and a psychosomatic physician. Patients were

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categorized based on the diagnosis of the referring physician, reasonfor referral and prior examinations. ROME III criteria, ROME-FGIDquestionnaires, validated symptom questionnaires for vegetativedisorders and standardized procedures for the exclusion of somaticdisorders were applied. Results: 20 patients were seen. In 8/13 patients (61%) admitted onthe assumption of FGID, diagnosis had to be changed from FGID tofunctional disorders with abdominal symptoms (FDAS): Depression(n=5), PTSD (n=2), and anxiety disorder (n=1). 5 patients (39 %) werediagnosed with Irritable Bowel Syndrome (IBS) according to ROME IIIcriteria. Of 9 patients externally diagnosed for IBS, only 4 met theROME III criteria. Conclusion: Patients are most often sent to the IBSP without ade-quate examination and classification. Due to the simultaneous inter-disciplinary setting of the IBSP patients with FDAS can be sorted outearlier. Even GI associated specialities tend to neglect proper use ofROME III criteria._* Division for Visceral Surgery and Medicine, DMLL, University Hospital

Inselspital Bern, Switzerland+ Division for Psychosomatic Diseases, University Clinic for Internal

Medicine, University Hospital Inselspital Bern, Switzerland

P41Diagnostic performance of liver fibrosis in hepatitis C usingtransient elastography: the Geneva experience Laurent Spahr, Mahnaz Alaei, Emile Giostra, Florian Bihl, DavidBertolini, Isabelle Morard, Mariam Seirafi, Laura Rubbia-Brandt,Antoine HadengueGastroenterology, Clinical Pathology, HUG Background: Transient elastography (Fibroscan, FS) is a non-invasivemethod to evaluate fibrosis in liver diseases. FS has been validated in hepatitis C, although cut-off values for significant fibrosis may varyamong studies. FS values are considered valid provided that meas-urements are made according to the recommended standards(interquartile range IQR < 30%, success rate > 60%). The aim of thestudy was to investigate the diagnostic performance of FS in theevaluation of liver fibrosis in patients with chronic hepatitis C in ourcentre. Patients and Methods: From October 2006 to March 2008, allpatients with chronic hepatitis C who completed a diagnostic work-up in our hospital, using a FS (with values accepted as valid) and aliver biopsy (performed within < 6 months of FS measurement) wereincluded. The METAVIR liver fibrosis stage was determined on theliver biopsy by a single histopathologist (LRB) blinded to the patient’sFS values. Efficiency of FS and optimal cut-off values for significantfibrosis stage assessment were determined by a receiver operatingcharacteristics (ROC) curve analysis. Results: The study population consisted in 98 patients (mean age 43 yrs, M/F: 60/38). FS values ranged from 5 to 45 kPa, with a meanIQR of 8%. The distribution of fibrosis stages (F0/1/2/3/4) amongpatients was as follows (in %): 24.5/27.6/8.2/10.2/29.6. The medianFS values according to METAVIR stage 0/1/2/3/4 fibrosis were4.65/6.2/8.35/9.8/14.5 kPa, respectively. FS values were well corre-lated with fibrosis stages (Spearman rank correlation r = 0.675,p<0.0001). The areas under ROC curves were 0.86 for F0-1 versusF2-3-4, and 0.87 for F0-1-2 versus F3-4. Conclusions: in our local experience, the use of FS for the detectionof significant fibrosis in patients with chronic hepatitis C appearsreliable and compares favourably with published data (Ziol, Hepa -tology 2005; Castera Gastroenterology 2005).

P42Severe hepatotoxicity after ingestion of Herbalife®

nutritional supplements contaminated with Bacillus subtilisFelix Stickel1, Sara Droz2, Eleonora Patsenker1, Katja Bögli-Stuber2,Beat Aebi3, Ludwig Wilkens4, Stephen L. Leib2

1 Department of Clinical Pharmacology, 2 Institute for InfectiousDiseases, 3 Institute of Legal Medicine, and 4 Department ofPathology, University of Bern Background: Recently, severe hepatotoxicity after the ingestion ofHerbalife® preparations was reported, but hepatotoxic mechanismsremained unclear. Patients and Methods: Two patients presented with cholestatic andsevere cytolytic hepatitis. In a male patient, subacute liver failure

developed with coagulopathy, whereas a female patient developedsevere pruritus. Viral, metabolic, autoimmune, neoplastic, toxic andvascular liver diseases were ruled out. Both patients reported long-term intake of Herbalife® products. Patients were tested forimmunoallergic sensitization and Herbalife® products screened forcontamination with drugs, pesticides, heavy metals, and softeners.For microbiological analysis, Herbalife® samples were processed bystandard and molecular procedures. Results: Histology showed cholestatic and mixed hepatitis withcirrhosis in the male patient, and biliary fibrosis with ductopenia in thefemale patient. Toxic contamination was ruled out, and hypersensi -tivity testing towards ingested preparations was negative. Two sam-ples of Herbalife® products from each patient showed growth of gram- positive rods after 48h of culture. Bacteria were identified as Bacillussubtilis by sequencing the 16S rRNA gene and analysis of cellularfatty acids. Bacterial culture supernatants caused dose-dependentincrease of LDH leakage and caspase-3 cleavage. Causality waslabelled “probable” in both patients who recovered after dechallenge. Conclusion: Two novel incidents of severe hepatic injury subsequentto intake of Herbalife® products contaminated with Bacillus subtilisemphasize its potential hazards.

P43Infliximab, a monoclonal Antibody to TNF-a, for severeEosinophilic Esophagitis in Adults: A prospective, translational Pilot-Study Alex Straumann1, Christian Bussmann2, Sebastien Conus3 and Hans-Uwe Simon3

1 Department of Gastroenterology, University of Basel, Basel,Switzerland, 2 Institute for Pathology, Kantonsspital Luzern, Luzern,Switzerland, 3 Department of Pharmacology, University of Bern, Bern,Switzerland Background: Eosinophilic esophagitis (EE) is a clinico-pathologicaldefined condition characterized by PPI-refractory esophagus-relatedsymptoms in combination with a dense esophageal eosinophilia. The pro-inflammatory cytokine TNF-a is up regulated and highlyexpressed in the squamous epithelium of patients with active EE.TNF-a is therefore a promising therapeutic target. Infliximab, achimeric monoclonal IgG1 antibody, is a potent inhibitor of the solu-ble and the membrane-bound form of TNF-a. The purpose of thisstudy was to evaluate the efficacy and the tolerability of infliximab in adults with severe EE unresponsive to conventional therapy. Methods: Three male adult patients (mean age 38 yr) with active EE (>20 eos/hpf and dysphagia), unresponsive to, or dependent oncorticosteroids, received after a 4 week run-in period, infliximab, 5 mg/kg bodyweight, by intravenous infusion at week 4 and 6. Pre-and post-treatment disease activity was assessed clinically,endosco pically, histologically, and via biomarkers in the blood (ECP, TNF-a) and tissue (ECP, tryptase, CD3, TNF-a expression,eotaxin-3). Symptoms were recorded with a diary. Results: All three patients had at baseline highly active EE with adense eosinophilic infiltration of the esophagus (peak values 269, 311 and 79 eos/hpf) and with severe dysphagia. Treatment with nfliximab did neither reduce significantly eosinophilic tissue infiltration(mean value pre-treatment 101 eos/hpf, post-treatment 121 eos/hpf)nor symptoms (symptom-score pre-treatment 8.6, post-treatment7.8). A mild decrease of the TNF-a expression in the tissue wasobserved in two patients. Infliximab was well tolerated and no rele-vant adverse events occurred. Conclusions: The overall-analysis of this first translational study ana-lyzing the efficacy of a TNF-a blockade in adult patients with activeEE, unresponsive to conventional treatment or dependent on corticos-teroids, shows that infliximab in a standard induction dosage-scheduleis not able to induce a resolution of the eosinophilic tissue infiltrationand to reduce markedly the resulting symptoms. In contrast to thegeneral evaluation, the per-patient analysis reveals three differentpatterns of responsiveness: One patient achieved a marked responsewith a 30 percent reduction of his baseline eosinophil load resulting ina mild decrease of his symptoms; one patient experienced histologi-cally a pronounced flare-up with an increase of his baseline eosinophilload of more than 150% leading to a mild increase of his symptoms;and the third patient was almost refractory and did not show anyrelevant changings. The value of this study is limited by its design asan open-label, non-randomized pilot trial with a small patient number.Further studies, working with alternative infliximab application modesand dosages are therefore needed to develop therapeutic options forthe minority of patients with severe, refractory EE.

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P44Hepatitis C infections in Opioid-dependent Patients (HepCOP2): What determines the state of care in the canton of Zurich? Kristyna Valkova1, Katja Schulthess1, Dimitri Hauri2, Lucas M.Bachmann2, Johann Steurer2, André Seidenberg1

1 Institute Hausarztmedizin University of ZH, 2 Horten ZentrumUniversity of ZH. Background: A representative survey in patients on opioid mainte-nance treatment (OMT) in the canton of Zurich (ZH) revealed thatrequired tests to determine whether antiviral treatment should beoffered were not done regularly. Treatment against chronic hepatitis C(CHC) was highly rare. The objective of this study was to identifypatients’, physicians’ and institutional characteristics associated withan appropriate diagnostic work-up of these patients. Methods: The survey included a representative sample of all patientson OMT in ZH. We developed a questionnaire to collect informationfrom patients’ charts (demographic data, laboratory tests, antiviraltreatment) and used a validated questionnaire to gather informationon physicians’ attitudes. Multiple regression analysis was applied. A bootstrap-stepwise selection method was used in order to identifythe most important factors influencing adequate diagnostic work-up. Results: 63 physicians or institutions (18% of OMT providers in ZH)participated in this study. They care for 1575 patients, which repre-sents 43 % of all patients on OMT in ZH. 279 patient’s charts wereanalyzed. 67 patients had an inadequate diagnostic work-up. Physi-cians without own laboratory facilities (OR=4.17, p<0.01), referringtheir clients for primary somatic care (OR=2.19, p=0.01), and physi-cians with an abstinence oriented attitude (OR=1.42, p<0.01) or refusing illicit heroin consumers (OR=1.55, p<0.01) were more likely to work-up patients inadequately. Patient characteristics (job, hous-ing, alcohol consumption) had only a small impact on adequate testing. Conclusions: For adequate diagnostic work-up attitudes of physi-cians and office infrastructure are of higher importance than individualcharacteristics of the patients. Measures to improve adequate testingfor HCV and the rate of CHC treatment are necessary.

P45Air Suctioning During Colon Biopsy Acquisition ReducesBacterial Contamination Stephan R. Vavricka1, Radu Tutuian1, Alexander Imhof2, Stephan Wildi1,Christoph Gubler1, Heiko Fruehauf1, Christian Ruef2, Michael Fried1

1 Division of Gastroenterology and Hepatology, University Hospital of Zurich, 2 Division of Infectious Diseases, University Hospital of Zurich Background and Aim: Contamination of endoscopy suites withbacteria during procedures is of concern. It has been advocated thatsuctioning while removing biopsy forceps could help to reduce hazardous bioaerosols. The aim of the present study was to evaluatethe efficacy of air suctioning during removal of biopsy forceps. Methods: During colonoscopy endoscopists were asked to remove thebiopsy forceps with and without suction after having touched the sig-moid mucosa. Fifty liters of air were collected continuously for 30 sec-onds at 30 cm distance from the colonoscope suction channel. Air-borne bacteria were collected by an impactor air-sampler (MAS-100).Standard 90 mm Petri dishes with CNA blood agar were used to culturegram positive cocci. Room measurements prior to the first endoscopyand after the last endoscopy of the day were used as controls. Results: Measurements were performed during 50 consecutivecolonoscopies. At the beginning and at the end of the endoscopyprogram the bioaerosol burden were 4.2 ± 1.8 cfu/m3 and 15.6 ± 2.5cfu/m3 respectively. Applying suction during removal of the biopsyforceps reduced the bioaresol burden from 29.4 ± 4.6 cfu/m3 to 15.1 ± 2.7 cfu/m3 (p<0.001). The analysis of the colonies on the CNAblood agar identified predominantly enterococci. Conclusion: The present study indicates that the bioaerosol burdenduring handling of biopsy specimens is not neglectable and can bereduced by the simple habit of applying suctioning when removingbiopsy forceps. This practice might be an important infection-controlmeasure during gastrointestinal endoscopies.

P46Colonoscopic withdrawal times in a Swiss tertiary center Stephan R. Vavricka, Michael Manz, Christoph Beglinger, LukasDegenDivision of Gastroenterology, University Hospital Basel Background and Aim: Current literature and expert opinion sug gest6 minutes as the minimum adequate mean withdrawal time forscreening colonoscopy. A recent major study concluded that colono-scopists find more polyps when the examinations take longer. Theaim of the present ongoing study was to record the colonoscopicwithdrawal times in endoscopists, who did not know, that they werebeing monitored. Secondary endpoints were whether gastroenterolo-gists change their withdrawal time habit when they are aware thatthey are being watched and whether they can estimate subjectivelytheir withdrawal times. Methods: In the first part of the study, seven experienced gastro en-terologists performed 350 colonoscopies during a nine-month period.Colon retraction times were measured without the gastro enterolo-gist’s knowledge. In the second part of this study, with drawal timeswere measured with the knowledge of the perform ing gastroenterolo-gist and subjective withdrawal times were re corded. Results: There were large differences among gastroenterologists incolonic withdrawal times from the cecum to the anus. Without theknowledge of the gastroenterologist, the mean withdrawal time with-out intervention was 4.6 ± 1.6 min (range 1-13 min) and with interven-tion 7.0 ± 3.9 min (range 4-25 min). In endoscopists being aware ofmonitoring their withdrawal time without interven tion rose to 7.9 ± 2.6 min and with intervention to 9.9 ± 4.2 min (p<0.05). The subjectivetime feeling was mostly lower than the effective time (without inter-vention 6.2 ± 1.7 min). Conclusions: In this large tertiary referral hospital-based study, weobserved that an announced and monitored measurement of colonicwithdrawal time leads to an increase of the time spent on retractionfrom cecum to anus. Whether this leads to a higher de tection rate ofadenomas needs to be studied in future studies.

P47

Anemia in inflammatory bowel disease. Differences betweenprivate practice and University Hospital: a prospective study Manuela Vögtlin1, Alex Straumann2, Jürg Vögtlin3, Gerhard Rogler4,Andreas Buser5, Michael Manz1, Christoph Beglinger1, Stephan R.Vavricka1

1 Division of Gastroenterology, University Hospital Basel and Zurich, 2 Gastroenterology, Private Practice, Olten and 3 Liestal, 4 Division of Gastroenterology, University Hospital, 5 Blood transfusion center,Swiss Red Cross, Basel Background and Aim: Anemia is a common complication of inflam-matory bowel disease (IBD) in both Crohn’s disease (CD) and ulcera-tive colitis (UC). Studies on anemia in patients with IBD are usuallyconducted in tertiary referral centers. Unfortunately, data from privateclinical practice is missing. The aim of the present ongoing study wasto investigate the occurrence and severity of anemia in IBD patientsfrom two University Hospitals (Zurich and Basel), in patients from two private practices (Olten and Liestal) and to compare those resultsto healthy blood donor candidates. Methods: Data (such as age, gender, hemoglobine level, diseaseseverity) was acquired prospectively from patients included in theSwiss IBD Cohort Study. The control population consisted of healthyfirst-time blood donor candidates at the blood transfusion center,Swiss Red Cross, Basel between 2004 to 2008. Results: 124 patients from University Hospitals (66 CD and 58 UC)and 43 patients from private practices (29 CD and 14 UC) wereincluded and compared to a control population (6074 blood donorcandidates). In women, hemoglobin levels from University Hospitalswere significantly lower (131 g/L in CD, 126 g/L in UC) than in privatepractice and control group (136 g/L in CD, 141 g/L in UC, 139 g/Lcontrol group; p< 0.01). Similar in men, hemoglobin concentrationsfrom University Hospitals were lower (139 g/L in CD, 137 g/L in UC)than in private practice and control group (148 g/L in CD, 152 g/L inUC, 154 g/L in control group; p<0.05). Less severe IBD-activity andmore UC-proctitis manifestations were reported in the private prac-tice patients. Conclusions: Frequency of anemia in IBD patients is overestimatedin the literature due to the center bias of studies mainly performed attertiary referral centers.

02-23 Abstracts Sup 41.qxp 3.9.2008 7:42 Uhr Seite 23

Schweiz Med Forum 2008;8(Suppl. 41) 24 SAUTOREN

Balmer ML 12 SBanz V 12 SBasilicata G 12 SBellecave P 2 SBengoa JM 13 SBernasconi E 2 SBernsmeier C 2 SBihl F 3 SBorovicka J 3 S, 11 SBruggmann P 4 SBusch M 4 S

Clément S 5 S

Dietrich CG 13 SDill M 10 SDufour JF 5 S

Gerber L 14 SGervaz P 5 S

Geyer M 6 SGonvers J-J 14 SGrübel C 14 SGuenin M-O 14 S

Heinicke J-M 6 SHellstern MY 6 S

Ipaktchi R 15 S

Juillerat P 15 S

Kern B 15 SKraus R 15 SKurmann A 16 S

Larusson MD HJ 16 S

Majno P 7 SManser CN 16 S

Martin IV 13 SMartin J 7 SMennicke M 16 SMentha G 7 SMüller S 17 S

Naef M 17 SNett PC 17 S

Patsenker E 7 S, 17 SPazienza V 8 SPiguet A-C 8 SPilz J B 18 SPittet V 18 SPohl D 9 S, 18 SPugnale P 9 S

Sarasin-Filipowicz M 9 SSchaffer T 19 SSchmassmann A 19 S

Schmid A 19 SSchnider A 20 SSchoepfer A 20 S, 21 SSchulthess K 21 SSeewald S 9 S, 10 SSeibold F 21 SSendensky A 21 SSpahr L 10 S, 22 SStickel F 22 SStraumann A 11 S, 22 S

Valkova K 23 SVan Huy Ngo 13 SVavricka SR 23 SVogt N 3 SVögtlin M 23 S

24 Autoren.qxp 3.9.2008 7:43 Uhr Seite 24