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  • 1. Abstracts derausgewählten Beiträge der ReferentenInhaltsverzeichnisThema direkt ansteuern: STRG + Anklicken......................................................................3Ösophagus/Magen/Duodenum..........................................................................................4Leber.................................................................................................................................29Hepatology 2004; Vol. 40, No. 4, Suppl.1: 238A..............................................................38BMJ. 2004 May 1;328(7447):1046. Epub 2004 Mar 30...................................................50Non-absorbable disaccharides for hepatic encephalopathy: systematic review ofrandomised trials.Als-Nielsen B, Gluud LL, Gluud C.Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical InterventionResearch, Copenhagen University Hospital, Department 7102, H:S Rigshospitalet,DK-2100 Copenhagen, Denmark. bodil.a@ctu.rh.dkOBJECTIVE: To assess the effects of non-absorbable disaccharides (lactulose andlactitol) in patients with hepatic encephalopathy. DATA SOURCES: Cochrane Hepato-Biliary Group controlled trials register, Cochrane Library, Medline, and Embase untilMarch 2003; reference lists of relevant articles; authors and pharmaceutical companies.REVIEW METHODS: Randomised trials that compared non-absorbable disaccharideswith placebo, no intervention, or antibiotics for hepatic encephalopathy were included.The primary outcome measures were no improvement of hepatic encephalopathy andall cause mortality. RESULTS: 22 trials were included. Compared with placebo or nointervention, non-absorbable disaccharides seemed to reduce the risk of noimprovement in patients with hepatic encephalopathy (relative risk 0.62, 95% confidenceinterval 0.46 to 0.84, six trials). However, high quality trials found no significant effect(0.92, 0.42 to 2.04, two trials). Compared with placebo or no intervention, non-absorbable disaccharides had no significant effect on mortality (0.41, 0.02 to 8.68, fourtrials). Non-absorbable disaccharides were inferior to antibiotics in reducing the risk ofno improvement (1.24, 1.02 to 1.50, 10 trials) and lowering blood ammoniaconcentration (weighted mean difference 2.35 micromol/l, 0.06 micromol/l to 13.45micromol/l, 10 trials). There was no significant difference in mortality (0.90, 0.48 to 1.67,five trials). CONCLUSIONS: There is insufficient evidence to support or refute the use of
  • 2. non-absorbable disaccharides for hepatic encephalopathy. Antibiotics were superior tonon-absorbable disaccharides in improving hepatic encephalopathy, but it is unclearwhether this difference is clinically important. Non-absorbable disaccharides should notserve as comparator in randomised trials on hepatic encephalopathy............................50Darmerkrankungen/Pankreas..........................................................................................51 Authors: H. Ogata, T. Matsui, M. Nakamura , M. Iida, M. Takazoe, Y. Suzuki, T. Hibi...........................................................................................................................56ST diameter......................................................................................................................702. DDW Abstracts.............................................................................................................75.........................................................................................................................................77Onkologie / Ernährung......................................................................................................78 Thema direkt ansteuern: STRG + Anklicken
  • 3. Ösophagus/Magen/DuodenumReflux W. Voderholzer1. Abstracts von OriginalarbeitenGastroenterology. 2005 Mar;128(3):532-40.Nonresorbable copolymer implantation for gastroesophageal refluxdisease: a randomized sham-controlled multicenter trial.Deviere J, Costamagna G, Neuhaus H, Voderholzer W, Louis H, Tringali A,Marchese M, Fiedler T, Darb-Esfahani P, Schumacher B.Service de Gastro-Enterologie et dHepato-Pancreatologie, Universite Libre deBruxelles, Hopital Erasme, Brussels, Belgium. & AIMS: This aim was to determine whether endoscopic implantation ofa biocompatible nonresorbable copolymer (Enteryx; Boston Scientific Corp, Natick, MA)is a more effective therapy for gastroesophageal reflux disease (GERD) than a shamprocedure. METHODS: In a randomized, single-blind, prospective, multicenter clinicaltrial, 64 patients with GERD were enrolled whose symptoms were well controlled byproton pump inhibitor (PPI) therapy and rapidly recurred after cessation of PPI therapy.Thirty-two patients were assigned to Enteryx implantation and 32 to a sham procedureconsisting of standard upper endoscopy. Patients in both groups with unsatisfactorysymptom relief after 3 months were eligible for re-treatment by Enteryx implantation. Theprimary study end point was > or =50% reduction in PPI use. Secondary end pointsincluded > or =50% improvement in GERD score and the proportion of patients notundergoing re-treatment procedure. Follow-up evaluations were performed at 3 and 6months. RESULTS: The percentage of Enteryx-treated patients achieving a > or =50%reduction in PPI use (81%) was greater than that of the sham group (53%), with a rateratio of 1.52 (confidence interval [CI], 1.06-2.28; P=.023). A higher proportion of theEnteryx (68%) than sham group (41%) ceased PPI use completely (rate ratio, 1.67; CI,1.03-2.80; P=.033). GERD health-related quality of life heartburn score improvement >or =50% was achieved by 67% of the Enteryx group versus 22% of the sham group (rateratio, 3.05; CI, 1.55-6.33; P <.001). More Enteryx-treated (81%) than sham-treated(19%) patients did not undergo re-treatment (rate ratio, 4.33; CI, 2.23-9.29; P <.001).CONCLUSIONS: Enteryx implantation more effectively reduces PPI dependency andalleviates GERD symptoms than a sham procedure.
  • 4. Am J Gastroenterol. 2004 Dec;99(12):2317-23.Characteristics and clinical relevance of proximal esophageal pHmonitoring.Cool M, Poelmans J, Feenstra L, Tack J.Department of Medicine, Division of Gastroenterology, University Hospitals Leuven,Belgium.OBJECTIVE: It is well established that various ENT disorders and symptoms may be amanifestation of gastroesophageal reflux disease (GERD). Measuring proximalesophageal acid exposure might be useful in the evaluation of patients with suspectedreflux-related ENT manifestations, but the limited available data are conflicting. The aimof the present study was to study the determinants of proximal esophageal acidexposure (PR) and to evaluate the clinical usefulness of ambulatory proximal pHmonitoring. METHODS: Twenty healthy controls and 346 patients with suspected refluxdisease underwent typical and atypical GERD symptom assessment, endoscopy,esophageal manometry and ambulatory combined dual esophageal pH, and Bilitecduodeno-gastro-esophageal reflux exposure (DGER) monitoring. The presence ofpathological PR and its relation to symptom pattern and distal esophageal acid exposure(DR) and DGER exposure were analyzed. RESULTS: Fifty-seven patients (16%) hadpathological PR. Demographic characteristics, symptom pattern, and manometricfindings did not differ in patients with normal or pathological PR. Patients withpathological PR had significantly higher DR and DGER. The multivariate analysisidentified only pathological DR as an independent risk factor for the presence ofpathological PR (odds ratio 4.515, 95% CI 2.48-8.23, p < 0.0001). Only 20 patients (6%)had pathological proximal reflux without pathological distal acid reflux. CONCLUSION:The findings of the present article do not support routine proximal esophageal pHmonitoring as a clinical tool: PR does not differentiate patients with typical or atypicalGERD manifestations and depends mainly on DR.
  • 5. 2. DDW AbstractsDDW Abstract T1692-Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A531.Disclosures: Organization - Astra Zeneca, Sweeden, Relationship - Grant / ResearchSupportBaclofen Reduces Weakly Acidic Reflux in Ambulant Patients WithGERDD. Sifrim, J. Tack, J. Arts, P. Caenepeel, X. Zhang, J. Silny, H. Rydholm, J.JanssensWeakly acidic gastroesophageal reflux (pH drop between 7-4) might be associated withpersisting symptoms in patients with GERD “on” PPI, and also with chronic cough inadults or cardio-respiratory events in infants. Treatment with PPI does not affectsignificantly weakly acidic reflux. By reducing TLESRs, baclofen decreases acid reflux inpatients with GERD and bile reflux in patients refractory to PPI. Baclofen can alsoreduce postprandial weakly acidic reflux in patients with GERD studied in stationaryrecumbent position. However, most weakly acidic reflux occurs during daytime in uprightambulant conditions. We aimed to assess the effect of baclofen on total, acid andweakly acidic reflux in ambulant GERD patients. Methods: In a double blind,randomized, placebo controlled, cross-over designed study, 24h ambulatory ph-impedance monitoring, endoscopy and symptoms assessment were performed in 15patients with GERD “off” PPI therapy [5 men, 55 years (27-73)] before and after 4 weeksof treatment with placebo or Baclofen 20 mg (t.i.d). At inclusion, patients had NERD(n=6), esophagitis gradeA (n=7) esophagitis gradeB (n=2). 8 patients had HH. Refluxwas classified as acid (pH drop below 4), weakly acidic (nadir pH between 4 and 7) andweakly alkaline (impedance drops without pH change below 7). Results: Baclofen reducedthe 24h total number of reflux events by 38%, acid reflux by 46% and weakly acidicreflux by 28%. The main effect was observed in upright position and during thepostprandial periods (43%, 44% and 33% reduction, respectively, p< 0.05). Baclofen didnot modify supine reflux. Baclofen reduced, but not significantly, 24h esophageal acidexposure (7.5±1.4 vs. 5.5±0.9) and did not affect the air-liquid composition or theproximal extent of reflux. Esophagitis was healed in 4/9 patients and scores for the mostsevere symptom were improved in 10/15 patients. Conclusion: The total number ofreflux episodes (acid and weakly acidic) can be reduced by baclofen in ambulantpatients with GERD “off” PPI. Outcome studies from adult patients with persistingsymptoms “on” PPI or chronic cough as well as from infants with cardio-respiratoryevents are required to establish the clinical usefulness of pharmachological reduction ofweakly acidic reflux in GERD.* total reflux acid weakly Weakly all refluxp<0.05 acidic alkaline pH>424hs 61±7 - 30±5 - 24±3 - 7±4 - 3±1 31±5 - 22±4 41±6* 18±3* 19±4upright 57±7 - 28±5 - 23±3 - 6±3 - 4±1 29±4 - 19±3* 34±4* 15±2* 16±3*
  • 6. DDW Abstract 630- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A95.Disclosures: NoneDoes Surgical Fundoplication Improve Chronic Laryngeal Symptomsand Signs Unresponsive To Aggressive Medical Therapy? aProspective Cohort Study.J.M. Swoger, C. Millstein, J.E. Richter, D. Hicks, J. Ponsky, M. VaeziObjective: In patients with persistent laryngeal symptoms despite aggressive PPItherapy, gastroesophageal reflux disease (GERD) continues to be implicated.Continued reflux of intermittent or low volume acid or non-acid gastric contents issuggested as the potential cause. Such suggestions implicate surgical fundoplication asthe ultimate therapy for these unresponsive patients. However, there are no prospectivestudies assessing this contention. Methods: 72 patients with suspected GERD relatedlaryngeal symptoms/signs were initially treated with BID PPI’s for 4 months. All hadbaseline manometry, 24-hour pH, Bilitec, and laryngoscopy, with repeat pH monitoringon therapy at 4-months. 4-month symptomatic non-responders (<50% improvement)with continued laryngeal “inflammation” and normalized esophageal acid exposure wereoffered laparoscopic Nissen Fundoplication. Post surgery, all underwent symptomassessment at 1, 3, 6, and 12 months; manometry and 24-hour pH at 3-months;laryngoscopy at 6- and 12months, and BRAVO pH monitoring at 12-months. Primaryoutcome of the study was symptom improvement/resolution at 12-months post-surgery.The outcome was then compared to the cohort who refused surgical fundoplication andcontinued on PPI therapy. Results: 26/72 (36%) patients (study cohort) remainedunresponsive to 4 months of aggressive PPI therapy. 10 patients (38%) agreed toundergo surgical fundoplication (mean age = 51.1, M= 4) and 16 patients (62%) did not(mean age = 50.6, M=4). The most common laryngeal symptoms were sore throat,hoarseness, and cough. Symptom severity (0-5) did not differ between groups (3.5 vs.3.53). pH studies at 3-months and at 12-months were normal in all patients postfundoplication (mean % time pH < 4 = 0.27%, 0.34%; respectively). 1/10 (10%) of thesurgical group reported improvement of their chronic laryngeal symptoms at 1 yearcompared to 1/16 of the control group (6.25%) (p= 1.0). Treatment of causes other thanGERD (allergies or asthma) improved symptoms in 2/10 (20%) of the surgical group,and 10/16 (62%) non-surgical cohort (p= 0.1).Conclusions: 1) Surgical fundoplicationdoes not improve laryngeal symptoms in patients unresponsive to aggressive PPItherapy. 2) In this group, the argument of intermittent, low volume or non-acid reflux asthe cause of persistent laryngeal symptoms needs to be replaced with evaluation andtherapy for other non-GERD causes.
  • 7. Barrett T. Rösch1. OriginalarbeitenGastroenterology. 2004 Jul;127(1):310-30.A critical review of the diagnosis and management of Barrettsesophagus: the AGA Chicago Workshop.Sharma P, McQuaid K, Dent J, Fennerty MB, Sampliner R, Spechler S, Cameron A,Corley D, Falk G, Goldblum J, Hunter J, Jankowski J, Lundell L, Reid B, ShaheenNJ, Sonnenberg A, Wang K, Weinstein W; AGA Chicago Workshop.University of Kansas School of Medicine and VA Medical Center, Kansas City, Missouri64128-2295, USA. psharma@kumc.eduBACKGROUND & AIMS: The diagnosis and management of Barretts esophagus (BE)are controversial. We conducted a critical review of the literature in BE to provideguidance on clinically relevant issues. METHODS: A multidisciplinary group of 18participants evaluated the strength and the grade of evidence for 42 statementspertaining to the diagnosis, screening, surveillance, and treatment of BE. Each memberanonymously voted to accept or reject statements based on the strength of evidenceand his own expert opinion. RESULTS: There was strong consensus on moststatements for acceptance or rejection. Members rejected statements that screening forBE has been shown to improve mortality from adenocarcinoma or to be cost-effective.Contrary to published clinical guidelines, they did not feel that screening should berecommended for adults over age 50, regardless of age or duration of heartburn.Members were divided on whether surveillance prolongs survival, although the majorityagreed that it detects curable neoplasia and can be cost-effective in selected patients.The majority did not feel that acid-reduction therapy reduces the risk of esophagealadenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associatedwith a cancer risk reduction and are of promising (but unproven) value. Participantsrejected the notion that mucosal ablation with acid suppression preventsadenocarcinoma in BE but agreed that this may be an appropriate strategy in asubgroup of patients with high-grade dysplasia. CONCLUSIONS: Based on this reviewof BE, the opinions of workshop members on issues pertaining to screening andsurveillance are at variance with published clinical guidelines.
  • 8. Am J Gastroenterol. 2004 Nov;99(11):2107-14.Identification of Barretts esophagus in relatives by endoscopicscreening.Chak A, Faulx A, Kinnard M, Brock W, Willis J, Wiesner GL, Parrado AR, GoddardKA.Division of Gastroenterology, Department of Medicine, University Hospitals of Cleveland,Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.AIM: Familial aggregation of Barretts esophagus and its associated cancers has beentermed familial Barretts esophagus (FBE). The aim of the study was to determinewhether endoscopic screening would identify Barretts esophagus (BE) in relatives ofprobands with BE or esophageal adenocarcinoma (EAC). METHODS: All living first-degree relatives of patients with long segment BE or EAC presenting to the endoscopysuite of two academic hospitals were sent validated questionnaires inquiring aboutgastroesophageal reflux symptoms and prior endoscopic evaluation. First-degreerelatives of affected probands or affected relatives who reported no prior upperendoscopy were offered screening unsedated esophagoscopy. Relatives with chronicgastroesophageal reflux symptoms were also offered an alternative of conventionalsedated upper endoscopy. The yield of screening endoscopy was measured. Screeningendoscopy findings were then compared between family members of known FBEpatients and those with "isolated" disease. RESULTS: One hundred and ninety-eightrelatives from 69 families, 23 known FBE probands and 46 probands with apparently"isolated" disease, were enrolled. Forty relatives (29 FBE relatives and 11 relatives ofprobands with "isolated" disease) reported prior upper endoscopy. Screening upperendoscopies performed on 62 (25 FBE and 37 "isolated" disease relatives) of theremaining 158 relatives identified Barretts epithelium in 13 (21%). Compared toprobands with apparently "isolated" disease, Barretts epithelium (EAC, BE, or SSBE)was identified significantly more often in siblings and offspring of FBE probands, p</=0.05. Endoscopic screening of relatives of FBE probands identified a multigenerationmultiplex FBE pedigree consistent with an autosomally dominant inherited trait.Endoscopic screening of relatives of probands with reported "isolated" diseased did notidentify any new FBE pedigrees. CONCLUSIONS: Endoscopy identified EAC, long-segment BE, and short-segment BE in a substantial proportion of first-degree relativesof affected members of FBE families. A familial susceptibility to develop Barrettsepithelium appears to be present in a subset of patients with BE and EAC.
  • 9. Gut. 2004 Oct;53(10):1402-7.The Munich Barrett follow up study: suspicion of Barrettsoesophagus based on either endoscopy or histology only--what is theclinical significance?Meining A, Ott R, Becker I, Hahn S, Muhlen J, Werner M, Hofler H, Classen M,Heldwein W, Rosch T.Central Interdisciplinary, Endoscopy Unit, Department of Gastroenterology, CampusVirchow, Charite University Hospitals, Berlin, Germany. Thomas.Roesch@charite.deBACKGROUND: The incidence of distal oesophageal adenocarcinoma is rising, withchronic reflux and Barretts oesophagus being considered risk factors. Reliable detectionof Barretts oesophagus during upper endoscopy is therefore mandatory but requiresboth endoscopy and histology for confirmation. Appropriate management of patientswith endoscopic suspicion but negative on histology, or vice versa, or of patients with noendoscopic suspicion but with a biopsy diagnosis of intestinal metaplasia at the gastro-oesophageal junction, has not yet been studied prospectively. PATIENTS ANDMETHODS: In a prospective multicentre study, 929 patients (51% male, mean age 50years) referred for upper gastrointestinal endoscopy were included; 59% had refluxsymptoms. The endoscopic aspect of the Z line and any suspicion of Barrettsoesophagus were noted, and biopsies were taken in all patients from the Z line (n = 4),gastric cardia (n = 2), and body and antrum (n = 2 each). Biopsies positive forspecialised intestinal metaplasia (SIM) were reviewed by a reference pathologist for afinal Barretts oesophagus diagnosis. All patients with endoscopic and/or histologicalsuspicion of Barretts oesophagus were invited for a follow up endoscopy; the remainingcases (no endoscopic or histological suspicion of Barretts oesophagus) were followedclinically. RESULTS: Of 235 patients positive for Barretts oesophagus on endoscopyand/or histology, 63% agreed to undergo repeat endoscopy (mean follow up period 30.5months). 46% of patients with an endoscopic Barretts oesophagus diagnosis but nohistological confirmation (group A) showed the same distribution, a further 42% did nothave Barretts oesophagus, and 11% had confirmed Barretts oesophagus on bothendoscopy and biopsy on follow up. In the group with a histological Barrettsoesophagus diagnosis but negative on initial endoscopy (group B), follow up showed thesame in 26% whereas 46% had no Barretts oesophagus, and confirmed Barrettsoesophagus (endoscopy plus histology) was diagnosed in 17%. Of the study population,16 patients had Barretts oesophagus on initial endoscopy confirmed by histology whichremained constant in 70% at follow up (group C). Of the remaining patients without aninitial Barretts oesophagus diagnosis on either endoscopy or histology (group D) andonly clinical follow up (mean follow up period 38 months), one confirmed Barrettsoesophagus case was found among 100 patients re-endoscoped outside of the studyprotocol. However, no single case of dysplasia or cancer of the distal oesophagus wasdetected in any patient during the study period. CONCLUSIONS: Even in a specialisedgastroenterology setting, reproducibility of presumptive endoscopic or histologicaldiagnoses of Barretts oesophagus at follow up were poor. Only 10-20% of cases witheither endoscopic or histological suspicion of Barretts oesophagus had establishedBarretts oesophagus after 2.5 years of follow up. The risk of dysplasia in this populationwas very low and hence meticulous follow up may not be required.
  • 10. World J Gastroenterol. 2005 Feb 28;11(8):1182-6.Long-term follow-up after complete ablation of Barretts esophaguswith argon plasma coagulation.Madisch A, Miehlke S, Bayerdorffer E, Wiedemann B, Antos D, Sievert A, Vieth M,Stolte M, Schulz H.Medical Department I, Technical University Hospital, Fetscherstr. 74, D-01307 Dresden,Germany. To report the long-term outcome of patients after complete ablation of non-neoplastic Barretts esophagus (BE) with respect to BE relapse and development ofintraepithelial neoplasia or esophageal adenocarcinoma. METHODS: In 70 patients withhistologically proven non-neoplastic BE, complete BE ablation was achieved by argonplasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mgomeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy.At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BEmucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion.RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving atotal of 280.5 patient years. A mean of 6 biopsies were taken during surveillanceendoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were foundduring endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse wasconfirmed histologically giving a histological relapse rate of 3% per year. In none of thepatients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected.Logistic regression analysis identified endoscopic detection of islands or tongues as theonly positive predictor of BE relapse (P = 0.0004). CONCLUSION: The long-termrelapse rate of non-neoplastic BE following complete ablation with high-power APC islow (3% per year).
  • 11. Endoscopy. 2004 Sep;36(9):782-7.Circumferential endoscopic mucosal resection in Barretts esophaguswith high-grade intraepithelial neoplasia or mucosal cancer.Preliminary results in 21 patients.Giovannini M, Bories E, Pesenti C, Moutardier V, Monges G, Danisi C, Lelong B,Delpero JR.Endoscopic Unit, Institut Paoli-Calmettes, 232 Boulevard St-Marguerite, 13273Marseilles Cedex 9, France.BACKGROUND AND STUDY AIMS: Treatment by endoscopic mucosal resection(EMR) has been established for early lesions in Barretts esophagus. However, theremaining Barretts esophagus epithelium remains at risk of developing further lesions.The aim of this study was to evaluate the efficacy of circumferential endoscopicmucosectomy (circumferential EMR)s in removing not only the index lesion (high-gradeintraepithelial neoplasia (HGIN) or mucosal cancer), but also the remaining Barrettsesophagus epithelium. PATIENTS AND METHODS: A total of 21 patients were includedin the study (11 men, 10 women), who had Barretts esophagus and either HGIN (n =12) or mucosal cancer (n = 9). Of the patients, 17/21 were at high surgical risk and fivehad refused surgery. On the basis of preprocedure endosonography their lesions wereclassified as T1N0 (n = 19) or T0N0 (n = 2). The lesions and the Barretts esophagusepithelium were removed by polypectomy after submucosal injection of 10-15 ml ofsaline; a double-channel endoscope was used in 15/21 cases. Circumferential EMR wasperformed in two sessions, the lesion and the surrounding half of the circumferentialBarretts esophagus mucosa being removed in the first session. In order to prevent theformation of esophageal stenosis, the second half of the Barretts esophagus mucosawas resected 1 month later. RESULTS: Complications occurred in 4/21 patients (19 %),consisting of bleeding which was successfully managed by endoscopic hemostasis in allcases. No strictures were observed during follow-up (mean duration 18 months) andendoscopic resection was considered complete in 18/21 patients (86 %). For threepatients, histological examination showed incomplete removal of tumor: one of theseunderwent surgery; two received chemoradiotherapy, and showed no evidence ofresidual tumor at 18 months and 24 months follow-up, respectively. Two patients inwhom resection was initially classified as complete later presented with local recurrenceand were treated again by EMR. Barretts esophagus mucosa was completely replacedby squamous cell epithelium in 15/20 patients (75 %). CONCLUSIONS: CircumferentialEMR is a noninvasive treatment of Barretts esophagus with HGIN or mucosal cancer,with a low complication rate and good short-term clinical efficacy. Further studies shouldfocus on long-term results and on technical improvements.
  • 12. Gastrointest Endosc. 2003 Jun;57(7):854-9.Circumferential EMR and complete removal of Barretts epithelium: anew approach to management of Barretts esophagus containing high-grade intraepithelial neoplasia and intramucosal carcinoma.Seewald S, Akaraviputh T, Seitz U, Brand B, Groth S, Mendoza G, He X, Thonke F,Stolte M, Schroeder S, Soehendra N.Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf,Germany.BACKGROUND: There is no study of circumferential EMR in patients with Barrettsesophagus containing early stage malignant lesions. This study investigated theeffectiveness and safety of circumferential EMR by using a simple snare techniquewithout cap. METHOD: Patients with Barretts esophagus containing multifocal high-grade intraepithelial neoplasia or intramucosal cancer, and patients with endoscopicallynonidentifiable early stage malignant mucosal changes incidentally detected in randombiopsy specimens were included in the study. A 30 x 50-mm polypectomy snare made ofmonofilament 0.4-mm steel wire was used without any additional device or submucosalinjection. RESULTS: Twelve patients (10 men, 2 women; median age 63.5 years, range43-88 years) underwent circumferential EMR; 5 had multifocal lesions, and 7 had novisible lesions. Segments of Barretts epithelium were circumferential (median length 5cm) and completely removed. The median number of EMR sessions was 2.5. Themedian number of snare resections per EMR session was 5. The medial total area ofmucosa in resected specimens per session was 3.8 cm(2). Two patients developedstrictures that were successfully treated by bougienage. Minor bleeding occurred during4 of 31 EMR sessions. During a median follow-up of 9 months, no recurrence ofBarretts esophagus or malignancy was observed. CONCLUSIONS: CircumferentialEMR with a simple snare technique is feasible, safe, and effective for complete removalof Barretts epithelium with early stage malignant changes.
  • 13. 2. Kongreßabstracts DDWDDW Abstract 644-Gastrointestsinal Endoscopy, 2005 Apr.;61(5):AB103Does Barrett’s Esophagus Develop Over Time in Patients with ChronicGERD?Lauren Gerson ; Julie Stoltey ; Nighat Ullah ; Peyman Sahbaie ; Harpreet ReebaBackground: Barrett’s esophagus (BE), a metaplastic change of the distal esophagealsquamous mucosa to specialized intestinal metaplasia (IM), is present in approximately8-20% of patients with chronic GERD undergoing upper endoscopy (EGD). Decisionanalytic models (Inadomi 2003) have assumed that 0.5% of GERD patients will developnew cases of BE per year. We performed a cohort study to determine the incidence ofBE in patients with chronic GERD and normal index EGD.Methods: We identified patients with GERD or BE between 1998-2004 by primary orsecondary ICD-9 codes of 530.81 and/or 530.2. Patients were eligible for study entry if2 or more EGDs were performed at least 6 months apart. Patients were excluded if theyunderwent < 1 EGD, or 2 EGDs within < 6 months. BE was defined as the presencesalmon-colored mucosa extending from the esophagogastric junction (EGJ) of at least0.5 mm with IM on biopsy. We reviewed all primary endoscopy records and pathologyreports in order to confirm IM and to distinguish SIM-EGJ from BE. In addition, weperformed a retrospective analysis of BE patients who underwent index EGD at eitherinstitution.Results: We screened 5669 patients (10,047 data entries by ICD-9 code). 309 (6%)GERD patients and 125 (2%) BE patients who had at least 2 EGDs were enrolled. Fivepatients with erosive esophagitis on index EGD and BE detected on subsequent examwere excluded. The mean + SEM age of the GERD cohort was 60.6 + 0.85 (range23-91), 30% were female, and 29% veterans. Most (238, 77%) of the patients wereCaucasian, 25 (8%) were African-American, 18 (6%) Hispanic, and 28 (9%) Asian. Themean number of EGDs performed was 3.1 + 0.1 (range 2-15) over a mean number of3.4 + 0.1 (range 0.5-12) years. Based upon a projected annual incidence of 0.5% newBE cases per year, we expected approximately 1.5 incident cases of BE per year, or atotal of 5 new cases over the mean patient follow-up period. None of the patients withGERD and normal index EGD were found to develop BE. In addition, none of the 125patients with BE were found to have normal distal esophageal biopsies on index EGDwithin a mean retrospective time period of 4.3 + 0.2 years.Conclusions: Patients with chronic GERD do not appear to develop Barrett’sesophagus over time if it is not present on the index endoscopy. Our results support theconcept of “once in a lifetime” endoscopic screening for BE, however further prospectivestudies are indicated to confirm our results.
  • 14. DDW Abstract S1762-Suppl. to Gastroenterol.2, 2005 April; 128(4):A251High-Resolution Endoscopy Is More Important ThanChromoendoscopy or Narrow Band Imaging for Detecting EarlyNeoplasia in Barrett Esophagus: a Prospective Randomized Cross-Over StudyMohammed Kara ; Femke Peters ; Wilda Rosmolen ; Kausilia Krishnadath ; Fieboten Kate ; Albert Bultje ; Paul Fockens ; Jacques BergmanBackground: High resolution endoscopy (HRE) used in combination with indigocarmine chromoendoscopy (ICC) or narrow band imaging (NBI) may improve thedetection of high-grade dysplasia and early cancer (HGD/EC) in Barrett esophagus(BE). We conducted a randomized cross-over study to compare HRE-ICC with HRE-NBIfor detecting HGD/EC in BE. Patients and Methods: We included BE patients whowere referred for work-up of endoscopically inconspicuous HGD/EC (n=17), scheduledfor follow-up after endoscopic treatment for HGD/EC (n=6), or scheduled for regularsurveillance (n=5). All 28 patients underwent two procedures, HRE-ICC and HRE-NBI (6weeks interval), in a randomized sequence. The two procedures were performed by twoexperienced endoscopists who were blinded to the findings of the other examination. Ahigh-resolution zoom endoscope (Q240Z, Olympus) and a prototype NBI-system(Olympus, Tokyo, Japan) were used in all examinations .The BE was first inspected withHRE without using the zoom mode followed by detailed inspection (overview and zoom)with ICC or NBI. Two targeted biopsies were taken from detected lesions followed by 2-cm-interval-4-quadrant biopsies. Pathologists were blinded to the imaging techniqueused. Results: Using the combined histology results of the two procedures, 14 patientswere diagnosed with HGD/EC. Both techniques identified 11 patients (79%) withHGD/EC by targeted biopsies and in all these patients HRE was sufficient to detect atleast one lesion with HGD/EC. ICC and NBI detected additional lesions with HGD/ECoccult to HRE in 2 and 3 patients, respectively, without increasing the number ofpatients diagnosed with HGD/EC. Conclusion: In this group of high-risk BE patients,HRE performed by experienced endoscopists led to the identification of most patientswith HGD/EC. In this setting, ICC and NBI are more suited for targeted detailedinspection and delineation of lesions than for primary detection of HGD/EC. HRE shouldbe considered the imaging technique of choice in patients with BE.Outcome measurement HRE-ICC HRE-NBIPatients diagnosed with HGD/EC 13/14 (93%) 12/14 (86%)Patients with HGD/EC in target biopsies 11/14 (79%) 11/14 (79%)Patients with HGD/EC in lesions detected with HRE 11/14 (79%) 11/14 (79%)onlyPatients diagnosed with HGD/EC from random biopsies 2/14 (14%) 1/14 (7%)only
  • 15. DDW Abstract 1204-Gastrointestinal Endoscopy, 2005 Apr.;61(5):AB142Ablative Therapy of Barretts Esophagus (BE) By Endoscopic ArgonPlasma Coagulation (APC)Heinz Wolfgang Schimming ; Maik Bartikowsky ; Michael Vieth ; Manfred Stolte ;Ahmed Madisch ; Stephan MiehlkeBackround:Barrett’s esophagus is a premalignant condition. Medical or surgicaltreatment of GERD usually fails to induce complete regression of BE. The aim of thisprospective randomised study was to evaluate the effectiveness of endoscopic APC incombination with high-dose omeprazole therapy for the ablation of BE.Methods: Consecutive patients with BE were evaluated. The presence of CELLO wasconfirmed histologically by using alcian-blue and H&E staining; mucosal biopsies wereobtained from each quadrant every 2cm and any abnormal-appearing area. BE wereablated by using an argon beamer device (ERBOTOM ICC200, Germany) as a contact-free thermal coagulation technique (gas flow 2l/min, power setting 90W). Ablation wasperformed longitudinally from the distal toward the proximal epithelial junction of up to3cm in length in a single session of about 12 minutes‘ duration. This procedure wasrepeated every 3 weeks until there was visible complete reepithelialization withsquamous epithelium, confirmed by histology using a standard biopsy protocol. Duringthe entire treatment period acid suppression was obtained and patients wererandomised to receive either 40mg omeprazole (arm A) or tid (arm B). Results: 103 patients agreed to participate in the study. In the 56 patients (37 men, 19women), mean age 58,7 years (range 36 to 75 years), who completed treatment, themean length of BE was 3,7cm (range 1 to 12cm). 3 patients had a low grade dysplasia,all other had CELLO without dysplasia. There were 32 patients with long segment BE,mean length 6cm (range 4 to 12cm) and 24 patients with short segment BE, meanlength 1,9cm (range 1 to 3cm). The mean number of APC sessions was 2,8 (range 1 to10), 2,2 (range 1 to 5) for short segment BE, 3,2 (range 1-10) for long segment BE,respectively 3,1 (arm A) vs. 2,6 sessions (arm B), p<0,05. Complete squamousreepithelialization was obtained in 53 patients (94,6%) but 1 patient (1,8%) who had amacroscopically non visible island of residual BE without dysplasia in histology. 1 patientdeveloped a mild stricture of the lower esophagus (1,8%), that resolved after 2 sessionsof bougie dilation, another patient a perforation of the cardia (1,8%), that wasstraightaway successful operated.There has been no relapse of BE under continuousacid suppression with 40mg omeprazole during a follow-up of 12 months Conclusion: APC in combination with high-dose omeprazole treatment is an effectivetechnique for complete ablation of BE.
  • 16. DDW Abstract 1179- Gastrointestinal Endoscopy, 2005 Apr.;61(5):AB136A Prospective Multicenter Trial on Ablation of Non-NeoplasticBarrett’s Epithelium by Endoscopic Argon Plasma Coagulation inCombination with Esomeprazole (APBANEX)Hendrik Manner ; Andrea May ; Stephan Miehlke ; Walter Kraemer ; GabrieleNiemann ; Bernd Wigginghaus ; Stephan Dertinger ; Wolfgang Schimming ; RalfKiesslich ; Manfred Stolte ; Christian EllBACKGROUND: In contrast to former clinical trials concerning the ablation of non-neoplastic Barrett’s epithelium (BE), Schulz et al. (Gastrointest Endosc, 2000) obtaineda complete squamous regeneration after argon plasma coagulation (APC) in 98,6 % oftreated patients. The aim of this prospective study was to evaluate for the first time theeffectiveness of APC at a high power setting for the ablation of BE in a multicenter trial.METHODS: In 8 study centers, 60 patients (mean age 57, range 27-77; 47 male, 13female) with endoscopic and histologically proven non-neoplastic BE (length of BE 1-8cm) were recruited for treatment by APC in combination with esomeprazole. Afterbaseline documentation by video endoscopy (VE) plus chromoendoscopy with 0,5%methylene blue (MB) and four quadrant biopsies (4QB) including the gastroesophagealtransition zone, BE was treated by repeated APC using a power setting of 90 W; thenumber of APC sessions was restricted depending on the length of BE. During thetreatment period, all patients received esomeprazole 80 mg daily; 2 weeks aftercompletion of treatment the esomeprazole dose was reduced to 20 mg on demand dailyor adapted to the result of 24 h pH monitoring. Endoscopic examinations including VE,chromoendoscopy with MB, and 4QB depending on pretreatment length of BE wereperformed 3 weeks, 6 and 12 months after completion of treatment. The effect ofablation was classified either as complete remission (CR; complete macroscopic andmicroscopic regression of BE), partial remission (macroscopic regression more than50% depending on pretreatment length of BE) or minor response (macroscopicregression of BE less than 50%).RESULTS: 51/60 recruited patients were treated within the study. 3 patients were lostfor follow-up (FU) after complications had occurred. In 37 of 48 patients (77%) CR wasachieved after a mean FU of 14 months (range 12-32). To achieve complete ablation ofBE (mean length 3,6 cm), a mean of 2,6 APC sessions (range 1-5) were used. Transientcomplications (chest pain, fever) were noted in 9/51 patients (17,6%). Majorcomplications (stricture formation, bleeding, perforation) occurred in 5/51 patients(9,8%).CONCLUSIONS: The fact that esophageal cancer incidence rate in non-neoplastic BE islow and the goal of ablation treatment namely complete ablation of BE is not reached inall patients together with the risk for morbidity due to ablation does not justify APC forablation of non-neoplastic BE.
  • 17. DDW Abstract 223- Gastrointestinal Endoscopy, 2005 Apr.;61(5):AB80A Novel Multiband Mucosectomy Device Facilitates CircumferentialEndoscopic Mucosal Resection in Barrett’s Esophagus with EarlyMalignant ChangesStefan Seewald ; Salem Omar ; Stefan Groth ; Uwe Seitz ; Andreas de Weerth ;Yan Zhong ; Frank Thonke ; Soeren Schroeder ; Nib SoehendraBACKGROUND: Various techniques are available for EMR in the upper and lowergastrointestinal tract. For early cancers of the esophagus, “suck and cut” techniqueusing a transparent cap or variceal band ligator is the most commonly practiced method.To facilitate multiple or circumferential EMR (CEMR), a modified multiband varicealligator (MBL) is introduced which allows sequential banding and snare resection withoutthe need to withdraw the endoscope.Method: To enable band delivery with a snare inserted in the therapeutic endoscope, thethreading channel of the cranking device is enlarged from 2 mm to 3.3 mm. The sixshooter MBL (Multiband Mucosectomy Device, CE0123, Cook Ireland Ltd., Limerick,Ireland) was used. Ten consecutive male patients (median age: 62 years, range 43-82)with Barrett’s esophagus (BE) containing high-grade intraepithelial neoplasia (HGIN)and/or intramucosal cancer (IMC) were treated. EMR was performed with purecoagulating current using a mini hexagonal polypectomy snare sized 1.5 x 2.5 cm. Nosubmucosal saline injection was performed prior to resection.Results: In 5 of 10 patients with circumferential BE of 2-9 cm in length (median: 4 cm),complete CEMR was performed in one session using 3-18 (median: 6) bands. Fourpatients with 3-10 cm (median: 4 cm) long-segment BE required 2-5 (median: 3)sessions using a total of 5-42 (median: 12) bands. Another patient having multifocalHGIN and/or IMC in 24 of a total of 49 specimens was finally recommended for surgerybecause of technical difficulties caused by mural thickening after 4 sessions. No seriousprocedure related complications were observed accept for 2 minor bleedings which werecontrolled endoscopically. Seven patients developed strictures after CEMR. All acceptone patient was successfully managed by weekly bougienage after a median of 5(range: 3-11) sessions. Deep wall tears developed in one patient during the fourthbougienage session for which limited distal esophageal resection was performed withuneventful outcome.Conclusion: The novel technique of MBL-EMR is a safe and effective method whichfacilitates and simplifies circumferential removal of BE containing HGIN and/or IMC.However, the method is associated with a very high stricture rate if CEMR is performedin one single session. Complete removal of BE should be achieved by repeated partialEMR. Long-term follow-up is needed to observe for late recurrence and determining theclinical impact.
  • 18. DDW Abstract S1196- Gastrointestinal Endoscopy, 2005 Apr.;61(5):AB140Barrett Esophagus (BE) with High-Grade Dysplasia (HGD) and/or EarlyCancer (EC): Stepwise Radical Endoscopic Resection (SRER) forComplete Removal of the BE Is Safe and EffectiveFemke Peters ; Mohammed Kara ; Wilda Rosmolen ; Fiebo ten Kate ; SheilaKrishnadathBackground and Aim: Endoscopic resection in BE is usually used for removal of focallesions with HGD/EC. Studies have shown that these ER’s are often irradical and up to30% of patients develop metachronous lesions elsewhere in the BE during FU. Our aimwas to prospectively evaluate the safety and efficacy of SRER in patients with HGD/ECin a BE.Patients and methods: After work-up with high-resolution endoscopy (HRE), video-autofluorescence imaging (AFI), narrow-band imaging (NBI) and EUS, and review of allbiopsies by an expert pathologist, pts with HGD/EC in a BE <5 cm, without signs ofsubmucosal infiltration, lymphatic and hematogenous dissemination were included. Ptsfirst underwent a diagnostic ER of the most suspicious lesion to evaluate infiltrationdepth, followed by SRER with intervals of 6 weeks. In all ER’s the cap-technique wasused after submucosal lifting and at each SRER procedure resection of 50% of theoriginal BE was attempted. Follow-up (FU) endoscopies (with lugol-staining and jumbobiopsies) were scheduled every 3 months, with EUS after 6 and 12 months.Results:Between Jan ‘03 and Oct ‘04, 41 consecutive pts (33 m/8 f, mean age 65 (SD8.2), median length BE 4 cm) were included. Thirty-five patients had visibleabnormalities on HRE, AFI and/or NBI. Complete removal of BE was achieved in 26 ptsafter a median of 3 (2-3) SRER procedures. Therapy was discontinued in 2 patients dueto unrelated comorbidity (19eukaemia, pulmonary cancer), 13 are still under treatment.Early complications occurred in 12/87 procedures (14%): 11 bleedings (all treatedendoscopically without a drop in Hb or the need for blood transfusions) and 1asymptomatic perforation treated conservatively. Symptomatic stenosis occurred in 5/26(19%) pts, requiring a median of 3 dilatations. Histopathology of ER-specimensrevealed: HGD in 16 and EC in 14 pts. In all specimens, deeper resection margins werefree. Although revision of pre-treatment biopsies confirmed HGD/EC, 11 pts did not haveHGD/EC in the ER-specimens (4 no dysplasia, 4 indefinite, 3 LGD).During a median FUof 7 months (5-12) none of the patients had signs of residual BE or buried Barrett in anyof the biopsies and no signs of lymph node metastasis on EUS.Conclusions: SRER is a safe and effective treatment for selected pts with HGD/EC in aBE. SRER provides optimal histopathological diagnosis and may reduce the number ofrecurrences, since all the mucosa at risk is effectively removed.
  • 19. DDW Abstract S1152- Gastrointestinal Endoscopy, 2005 Apr.;61(5):AB140Can Piecemeal Mucosectomy Completely Remove BarrettsEsophagus with High Grade Dysplasia or Adenocarcinoma?Pierre Henri Deprez ; Tarik Aouattah ; Hubert Piessevaux ; Jacques Grodos ; ReneFiasse ; Yves Horsmans ; Christine SempouxAim: Prospective evaluation of piecemeal mucosectomy using the cap method (EMR-c)in patients presenting with Barrett’s esophagus and high grade dysplasia of superficialadenocarcinoma and aiming at complete removal of the neoplastic lesion and theintestinal metaplasia. Patients and methods: Inclusion criteria: long or short Barrett’sesophagus with high grade dysplasia or T1m N0 adenocarcinoma staged by radial orlinear Pentax EUS scope (EG-3630-UR or EG-3830-UT) with the Hitachi EUB 6500processor and 20MHz miniprobe. Resection was performed under general anesthesia,starting at the site of the tumour, after submucosal injection of 2-5 ml aliquots of salinefor a total of 10-50 ml, than resecting the remaining Barrett’s mucosa from anal to oraldirection. Circumferential resection was avoided if the height of Barrett’s metaplasiaexceeded 1 cm. Oblique or straight transparent rigid cap was used and resection wascompleted if necessary by APC (0.6 L, 60 W) for residual bridging or short remainingtongs of metaplasia. Patients were discharged one or two days after mucosectomyunder liquid diet and omeprazole 40mg bid was started before treatment and continuedfor 8 weeks minimum. Results: 20 patients (mean age 68y, range 47-85, 3 women/17men) were included with HGD in 15 and mucosal adenocarcinoma in 5. Circonferentiallength of Barrett’s mucosa (C) was 19 mm (5-70) and highest limit (M) 26 mm (5-80). Atotal of 26 EMR-c sessions were performed (1.3; 1-5), removing 95 specimens (4.8; 1-13per patient). Follow-up is now 13.3 months (3-38 months). Successful resection of HGDand adenocarcinoma was observed in all patients. Complete removal of intestinalmetaplasia was observed in 65% of patients (13/20), with 2 patients still presenting lowgrade dysplasia. Remaining Barrett’s mucosa was however limited to sections of < 5mm in 6/7 patients. Complications occurred in 4 patients: 3 minor bleeding episodesduring EMR treated by endoscopic hemostasis (APC or hemoclip) and 1 oesophagealstricture requiring endoscopic dilatation. Conclusions: Although EMR-C piecemealresection is acceptable for treatment of intraepithelial or mucosal adenocarcinomacomplicating Barrett’s esophagus, it is only successful in 2/3 of patients when aiming atcomplete resection of intestinal metaplasia. Improvements in endoscopic techniques ofesophageal mucosectomy and new appropriate devices to improve efficacy and safetyare mandatory to obtain higher success rates.
  • 20. Helicobacter/Dyspepsie P. Malfertheiner G. TreiberDDW Abstract 43-Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-8Development Of Premalignant Gastric Lesions in Area With HighGastric Cancer Incidence: Role Of H. Pylori Genotypes and CytokineGene PolymorphismsWai K Leung ; Martin CW Chan ; Ka-fai To ; Ellen PS Man ; Enders KW Ng ; San-ren Lin ; Joseph JY SungCytokine gene polymorphisms and H. pylori (HP) virulent genotypes have been linked togastric cancer development in western countries. We determined the role of cytokinepolymorphisms of the host and bacterial virulent factors in the development ofpremalignant gastric lesions in region with high gastric cancer incidence.Methods: DNA samples of 302 HP infected individuals who had participated in achemoprevention trial were available for analysis (mean age = 52, male 46%). Thesesubjects were living in Shandong province of China where the gastric cancer incidenceis among the highest. None of these subjects had gastric cancer on baselineendoscopy. Polymorphisms in different loci of inflammatory cytokines IL-1B (-31, -511,IL1RN), IL-8 (-251), IL-10 (-1082, -819, -592), IL-18 (-607, -137) and TNFa (-308G/A)were determined by allelic discriminating TaqMan PCR or variable number of tandemrepeats. Presence of HP virulence factors cagA, vacA (s and m region) and babA2 wasdetermined by PCR. Baseline gastric biopsies were assessed for severity of gastritis andpresence of glandular atrophy (GA) or intestinal metaplasia (IM) according to theupdated Sydney Classification.Results: GA and IM was found in 119 (39.4%) and 123 (40.7%) subjects, respectively.There was near linkage disequilibrium between IL1B -31C and -511T as well asbetween IL10 -819C and -592C in this study population. Carriers of IL1B -511T*/-31C*were associated with a modest increase in prevalence of IM (OR =1.9, 95% CI 1.1-3.5)and GA (OR = 2.0, 1.1-3.5). However, there was no association between presence ofIM/GA and polymorphisms in IL-1RN or other inflammatory cytokines. Although mostsubjects from this region harbored the virulent HP strains (97.5% cagA+, 100% vacA s1,83.5% babA2), carriage of vacA m1 strain was associated with a significantly increase inprevalence of IM (OR=1.7, 1.1-2.8) and GA (OR = 1.7, 1.0-2.7). The presence of bothhost (IL-1B-511T*) and HP (vacA m1) high-risk genotype further increased the risk of IM(OR= 5.7, 2.0-16) and GA (OR = 5.4, 1.9-15.3) when compared to individuals with CCgenotype and vacA m2 strain.Conclusion: The carriage of pro-inflammatory IL-1B polymorphism and HP vacAgenotype was associated with the development of premalignant gastric lesions inregions with high gastric cancer incidence. Determination of these host and bacterialgenotypes may help to identify individuals at high risk of developing gastric cancer.
  • 21. DDW Abstract 108- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-19The Interleukin-8-251 Promoter Polymorphism and Risk Of GastricCancer in Caucasian and Japanese Populations.Emad M El-Omar ; Malcolm G Smith ; Georgina L Hold ; Charles Rabkin ; Wong-Ho Chow ; Joseph F Fraumeni ; N. Ashley G Mowat ; Takafumi Ando ; HidemiGotoBackground: Interleukin 8 is of critical importance in the inflammatory response toHelicobacter pylori. It is a powerful chemotactic factor that induces many of the earlyinflammatory responses to the infection. We have recently shown that a functionalpromoter polymorphism (IL-8–251 A/T) is associated with an increased risk ofdeveloping the pre-malignant changes of hypochlorhydria and gastric atrophy. We havealso demonstrated that carriage of the IL-8–251 A allele is associated with higher IL-8levels and a more pronounced inflammatory response in the gastric mucosaAim: To evaluate the effect of the IL-8–251 (A/T) polymorphism on the risk ofdeveloping gastric carcinoma, using case control studies from two populations ofdiffering ethnic backgrounds.Subjects and Methods: We used a 5’ nuclease assay to genotype the IL-8–251 A/Tpolymorphism in two gastric cancer case control studies: 1) a Caucasian gastric cancercase-control study consisting of 306 gastric cancer cases and 211 controls and 2) aJapanese gastric cancer case-control study consisting of 237 gastric cancer cases and98 controls. Odds ratios and 95% confidence intervals (CI) were calculated and logisticregression was used to adjust for confounding variables.Results: Carriage of the pro-inflammatory IL-8–251 A allele in the Caucasian case-control study was not associated with an increased risk of developing gastric carcinoma(OR = 1.006, 95% CI 0.7 – 1.5). No significant differences were observed when thecases were subdivided into cardia (OR = 0.811, 95% CI 0.5 – 1.3) and non-cardiagastric cancers (OR 1.173, 95% CI 0.8 – 1.8). Similarly in the Japanese populationcarriage of the A allele did not increase the risk of having gastric cancer (OR = 1.166,95% CI 0.7 – 1.9).Conclusion: Although carriage of the IL-8–251 A allele is associated with a morepronounced inflammatory response in the gastric mucosa of H. pylori infected subjectsand an increased risk of developing pre-malignant changes, it does not appear to alterthe risk of developing the eventual outcome of gastric cancer. This applies topopulations of differing ethnicity. We postulate that this polymorphism is important at anearly stage in the inflammatory response to H. pylori and may facilitate the action ofother mediators in the development of gastric cancer.
  • 22. DDW Abstract M1021- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-293Development Of Gastric Cancer From Helicobacter- Related Gastritis--Findings From a Ten Year Follow-Up StudyKimihiko Yanaoka ; Chizu Mukoubayashi ; Hisanobu Deguchi ; Hirohito Magari ;Izumi Inoue ; Mikitaka Iguchi ; Hideyuki Tamai ; Kenji Arii ; Masashi Oka ;Yasuhito ShimizuIn high-risk area like Japan, the main route of stomach carcinogenesis is considered tobegin with gastritis, proceeds to extensive atrophy together with intestinal metaplasia,then to dysplasia, and finally to cancer. However, there is a controversy whether the riskof gastric cancer increases as the progression of atrophyÐintestinal metaplasia resultingfrom the gastritis, or whether the high level of gastritis activity poses a high risk. In orderto clarify this point, we conducted a longitudinal cohort study over a ten-year period.MATERIALS AND METODS: 4,655 healthy asymptomatic male subjects between ages40 and 60 were evaluated in terms of Helicobacter pylori (HP)-related gastritis based onserum pepsinogen (PG) and serum HP antibody titer, with a follow-up study conductedover the ensuing ten years from 1994 to 2003 to track the incidence of gastric cancerand to examine the rate of gastric cancer occurrence accompanying the progression ofatrophic gastritis. Atrophic gastritis was evaluated through endoscopic diagnosis, serumPG チ@testing and H. pylori (hereafter noted as HP) titer measurement, and the subjectswere divided into four groups labeled A through D [A Group: HP (-) PG (-), B Group: HP(+) PG (-), C Group: HP (+) PG (+), D Group: HP (-) PG (+)]. RESULTS ANDDISCUSSION: Gastric cancer developed in 63 cases during the ten-year follow-upperiod, 54 of which were early-stage gastric cancer. There were 23 cases in the groupB, 37 in group C, three in group D, and no occurrences of gastric cancer in group A. Theincidence rate of gastric cancer was null in group A, 0.09 チ“ person-years in group B,0.20 チ“person-years in group C, and 1.25 チ“person-years in group D. Histologically,there were 44 cases of intestinal type gastric cancer and 19 cases of diffuse type gastriccancer, with the background being such that 74% of the former were accompanied byextensive atrophic changes in the gastric mucosa, while 40% of the latter exhibited thisbackground. There was no gastric cancer developed from healthy stomachs, while therisk for the cancer increased in a stepwise fashion as the progression of HP-relatedgastritis. Although these results clearly indicate that the progression of atrophic gastritisis the main route of stomach carcinogenesis in Japan, the fact cannot be overlookedthat in the majority of cases of diffuse type gastric cancer, as well as one fourth ofintestinal type gastric cancer develop from mild cases of HP-related gastritis.
  • 23. DDW Abstract W1571- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-639The Effect Of Second Look Endoscopy in Patients With BleedingPeptic UlcersSeung Yup Lee ; Myung Kwon LEE ; Chang Min Cho ; Won Young Tak ; Young OhKweon ; Sung Kook Kim ; Yong Hwan ChoiBackground: Recurrent bleeding is one of the most important risk factors for mortality inpatients with peptic ulcer bleeding. Second look endoscopy has been suggested in orderto reduce recurrent bleeding. But whether a clinical value of second look endoscopy withretreatment after initial hemostasis is controversial. We assessed whether a scheduledsecond look endoscopy with retreatment reduces the risks of recurrent bleeding,mortality rate in patients with peptic ulcer bleeding.Methods: From February 2003 to June 2004, we have performed a prospective,randomized, controlled study of 143 patients with bleeding gastric or duodenal ulcersadmitted to Kyungpook National University Hospital. Seventy patients in the study groupwere randomized to receive scheduled second look endoscopy in case of Forrest type I,IIa, or IIb ulcers beginning within 24 hours after initial hemostasis. Seventy threepatients in the control group were observed closely. Endoscopic therapy wasstandardised to hypertonic saline epinephrine injection and subsquent hemoclipping.Results: Nineteen of the 143 patients had recurrent bleeding after initial therapeuticendoscopy. The overal rebleeding rate was 13.3 %. Although duration of hospital staywas significantly lower in the study group than control group(5 days versus 7 days,p=0.035), rebleeding rate was similar for both groups(10% versus 16%, p=0.257). Thetwo groups were similar in respect of blood units transfused, mortality within 30 days,volume of hypertonic saline epinephrine injection and number of hemoclips used. Weanalysed the probability of recurrent bleeding within 30 days, the results showed lowprobability of rebleeding tendency in the study group, but the difference was statisticallyinsignificant(p=0.28).Conclusions: According to above results, we can conclude that scheduled second lookendoscopy with retreatment did not reduce the risk of recurrent bleeding in patients withpeptic ulcer bleeding. Therefore a scheduled second look endoscopy does not seem tobe recommended routinely in all patients following initial endoscopic treatment, but alarger group study in high risk patients seems to be needed.
  • 24. DDW Abstract 835 - Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-133Eradication Of H. Pylori for the Prevention Of Recurrent UlcerBleeding in High-Risk Aspirin Users: a 4-Year Prospective CohortStudyFrancis K.L. Chan ; Jessica Y.L. Ching ; B.Y. Suen ; Vincent W.S. Wong ;Lawrence C.T. Hung ; Aric J. Hui ; Justin C.Y. Wu ; W.K. Leung ; James Y.W. Lau ;Y.T. Lee ; Henry L.Y. Chan ; Joseph J.Y. SungBackground We previously reported that among patients with H. pylori (HP) infectionand a history of ulcer bleeding who received low-dose aspirin, eradication of HP wascomparable to omeprazole in preventing recurrent ulcer bleeding in 6 months. Aim Todetermine the long-term incidence of recurrent ulcer bleeding in aspirin users with a hito-y of ulcer bleeding after eradication of HP. Methods We prospectively followed up threecohorts of aspirin users. The first cohort consisted of HP positive aspirin users with a re-ent episode of ulcer bleeding. After ulcer healing and HP eradication, they received aspi-in 80 mg od without anti-ulcer drugs (HP eradicated, prior GI bleed cohort). The secondcohort consisted of aspirin-naive patients who had no previous ulcer bleeding. They re-ceived aspirin 80 mg od for vascular prophylaxis (Average-risk cohort). The third cohortconsisted of HP negative aspirin users with a recent episode of ulcer bleeding. After ul-cer healing, they received enteric-coated aspirin 100 mg od without anti-ulcer drugs (HPnegative, prior GI bleed cohort). Patients who used anti-ulcer drugs, steroid, anticoagu-lants, other anti-platelet agents or non-aspirin NSAIDs during the follow-up period werecensored. The primary endpoint was the cumulative incidence of ulcer bleeding associa-ted with low-dose aspirin. Results There were 250 patients in the HP eradicated prior GIbleed cohort (median follow-up 41.3 months, range 0.5 – 48.0), 548 in the average-riskcohort (median follow-up 48.0 months, range 3.7 – 48.0), and 118 in the HP negativeprior GI bleed cohort (median follow-up 22.0 months, range 0.5 – 48.0). The cumulativeincidence rates of ulcer bleeding in 48 months were 4.5% in the HP eradicated prior GIbleed cohort, 2.0% in the average-risk cohort, and 18.4% in the HP negative prior GIbleed cohort (Figure). Conclusion Among aspirin users with HP infection and a historyof ulcer bleeding, the long-term incidence of recurrent bleeding after HP eradication iscomparable to that of average-risk aspirin users. In contrast, HP negative aspirin userswith a history of ulcer bleeding have a high incidence of recurrent bleeding. l .
  • 25. DDW Abstract 629- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-95Coxibs, NSAIDs, Aspirin, PPIs and the Risks Of Upper GI Bleeding inCommon Clinical PracticeAngel Lanas ; Luis Alberto García-Rodríguez ; María-Teresa Arroyo ; FernandoGomollón ; Eva Zapata ; Luis Bujanda ; Faust Feu ; Enrique Quintero ; ManuelCastro ; Santos Santolaria ; on behalf of investigators of AEGBackground and Aims: The overall safety profile of COX-2 selective inhibitors is underintense debate, since in addition to the potential/actual CV risk, even the benefits ofthese drugs on the GI tract have been questioned. Aim: To determine the risk of pepticulcer upper GI bleeding (UGIB) associated with use of COX-2 selective, non-selectiveNSAIDs, aspirin or combination of these drugs. Methods: Type of Study: case-controlstudy with prospective data collection. Setting: A network of 40 hospitals integratedwithin the Spanish Association of Gastroenterology. Cases were consecutive patientswith endoscopy-proven major UGIB. Controls (2:1) matched by age (5 years range),hospital and month of admission were patients who had been hospitalized with anyprimary diagnosis that was neither an indication nor a known contraindication oftreatment with NSAIDS. A structured questionnaire with pictures of marketed drugs andcareful review of prescriptions were used. Relative Risk (RR) of UGIB by logisticregression analysis is provided. Results: 2,777 cases and 5,532 controls were included;47.9% of cases and 18.6% of controls had used either NSAIDs, coxibs, aspirin orcombinations. The RR of UGIB associated with NA-NSAIDs was 5.0 (95% CI: 4.3-5.9).There was a dose-dependent risk associated with low-dose aspirin use (100 mg/day =2.4;1.9-3.1), which was similar to that observed with clopidogrel (3.1; 2.2-4.4) oranticoagulants (3.0; 2.3-3.8). Coxib use was not associated with UGIB (1.3; 0.8-2.1)(celecoxib:1.0; 0.5-2.2; rofecoxib:1.6; 0.9-3.0), but the combination of coxib+low-doseaspirin was associated with the same RR (9.5; 2.5-36.2) to that observed with NA-NSAID+low-dose aspirin (10.2; 6.2-16.7). Among NA-NSAIDs, diclofenac (2.9; 2.2-3.8)had the lowest RR, but meloxicam was associated with a higher RR (7.9;3.6-17.2). Useof proton pump inhibitors or nitrates were associated with significant risk reduction ofUGIB (range: 40-90%) in NSAID/aspirin users. Unlike NSAID+PPI, the use ofPPI+coxib was associated with prevention of UGIB (RR <1). Conclusion: Coxibtreatment without the concomitant use of low-dose aspirin is not associated with asignificant increase of the risk of UGIB. PPI co-therapy with NSAIDs, aspirin, andspecially coxib reduce ulcer bleeding risk. Antiplatelet non-aspirin therapy is associatedwith the same risk of UGIB to low-dose aspirin.
  • 26. DDW Abstract 347- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-50Early Administration Of High-Dose Intravenous Omeprazole Prior ToEndoscopy in Patients With Upper Gastrointestinal Bleeding; a DoubleBlind Placebo Controlled Randomized TrialJames YW Lau ; Wai Keung Leung ; Justin Cy Wu ; Francis KL Chan ; VincentWong ; Lawrence CT Hung ; Ka Yin Cheung ; MY Yung ; Vivian Wy Lee ; Philip WYChiu ; Enders KW Ng ; Kenneth KC Lee ; Joseph JY SungBackground: We previously showed that adjunctive use of high dose omeprazoleinfusion after endoscopic hemostasis prevented rebleeding and improved outcomes inpatients with bleeding peptic ulcers. We hypothesize that early administration of highdose omeprazole before endoscopy hastens stigmata resolution and thereby reducesthe need for endoscopic therapy. Methods: Consecutive patients admitted with overtsigns of upper gastrointestinal bleeding were volume resuscitated. They were thenrandomized to receive omeprazole (80mg intravenous bolus followed by 8mg/hr) or itsplacebo prior to scheduled endoscopy. At endoscopy, actively bleeding ulcers or ulcerswith non-bleeding visible vessels or clots were treated by epinephrine injection andheater probe thermo-coagulation. Omeprazole infusion was then continued for 72 hoursafter endoscopic hemostasis. Results: Between March and November 2004, 369patients were randomized (omeprazole 179, placebo 190). Of them, 220 weredocumented to have bleeding ulcers (omeprazole 110, placebo 112) Analysis was byintention-to-treat. The need for endoscopic treatment was significant reduced in thosewho received omeprazole (19/110 vs. 40/112, OR, 95%CI; 2.7, 1.4-4.9, P=.002).Table 1. Secondary outcomes in Omeprazole Placebo Ppatients with bleeding peptic ulcers N=110 N=112Endoscopic stigmata of bleeding 20 41 .003 Spurter 1 3 Oozing 2 15 Non-bleeding visible vessel 13 14 Clots 4 9 Flat pigment and clean base 90 71Surgery 1 4 .15Mean VAS (10cm scale) for difficulty in 4.2, 2.2 5.1, 3.1 .30therapy, SDMean transfusion in units, SD 1.9, 2.2 2.2, 3.1 .43Mean hospital stay in days, SD 3.7, 3.8 4.7, 5.9 .12Recurrent bleeding in 30-day 5 5 .9930-day mortality from all causes 1 1 .99Conclusion: Pre-emptive high dose omeprazole infusion prior to scheduled endoscopyhastens resolution of bleeding stigmata in ulcers and reduces need for therapy.
  • 27. DDW Abstract 863- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A138-139Comparing Rates Of Dyspepsia With Coxibs Versus NSAID+ppi: aSystematic Review and Meta-Analysis Of Clinical Trial DataBrennan M. R. Spiegel ; Mary Farid ; Gareth S. Dulai ; Ian M. Gralnek ; FasihaKanwalBackground: Although it is well established that both Coxibs and the NSAID+PPIcombination reduce ulcer complications by 50% vs NSAID therapy alone, the impact ofthese therapies on dyspeptic symptoms is unclear. Because dyspeptic symptoms are farmore prevalent than ulcer complications in NSAID users, economic models indicate thatdyspepsia rates are the major determinant of cost-effectiveness in treating arthritis. Wetherefore performed a meta-analysis to compare rates of dyspeptic symptoms for twocommonly used therapies in high-risk patients with arthritis: 1) Coxib alone, and 2)NSAID+PPI combination.Methods: We performed a structured search of MEDLINE and published abstracts toidentify English-language randomized trials from 1990-2004 comparing either a Coxib vsNSAID or NSAID+PPI combination vs NSAID alone in chronic arthritis. Two reviewersindependently selected studies that report incident dyspeptic symptoms, defined a priorias “epigastric pain,” “dyspepsia,” and “nausea.” The reviewers independently abstracteddata and assigned a quality score for each study. We performed meta-analysis with afixed effects model to compare the relative risk reduction (RRR) and Absolute RiskReduction (ARR) of dyspeptic symptoms for Coxib vs NSAID and NSAID+PPI vsNSAID, and performed an Egger’s test to assess for publication bias.Results: We identified 840 titles, of which 37 were selected for final review (kappa>0.9for agreement). Meta-analysis of 32 studies (N=60,163 patients) comparing dyspepticsymptoms between Coxibs and NSAIDs revealed a 12% RRR for Coxibs (RR=0.88;95% CI=0.85-0.90) with an ARR of 3.7%. Meta-analysis of 5 studies comparingdyspeptic symptom between the NSAID+PPI combination and NSAIDs alone revealed a66% RRR for NSAID+PPI (RR=0.34; CI=0.22-0.54) with an ARR of 9%. There was noevidence of heterogeneity (p>0.05) or publication bias (p>0.05) in either analysis.Compared to the NSAID strategy, the number needed to treat in order to prevent adyspeptic symptom was 27 for Coxibs and 11 for NSAID+PPI.Conclusions: The NSAID+PPI strategy affords a greater risk reduction for dyspepsiathan Coxibs alone when compared to the common baseline of NSAIDs alone. Becausethere are limited head-to-head data comparing Coxibs vs NSAID+PPI, these meta-analytic data provide the best indirect evidence that the NSAID+PPI strategy may besuperior to Coxibs in minimizing incident dyspeptic symptoms during the treatment ofchronic arthritis.
  • 28. LeberVirushepatitis T. Berg1. OriginalarbeitenHepatology. 2004 Oct;40(4):883-91.Clinical outcome of HBeAg-negative chronic hepatitis B in relation tovirological response to lamivudine.Di Marco V, Marzano A, Lampertico P, Andreone P, Santantonio T, Almasio PL,Rizzetto M, Craxi A; Italian Association for the Study of the Liver (AISF)Lamivudine Study Group, Italy.Cattedra e U.O.C. di Gastroenterologia, Clinica Medica, Universita di Palermo, Palermo,Italy. vito.dimarco@tin.itThe effect of lamivudine treatment on the outcome of patients with hepatitis B e antigen(HBeAg)-negative chronic hepatitis is unclear. In a retrospective multicenter study, wehave analyzed the virological events observed during lamivudine therapy in patients withHBeAg-negative chronic hepatitis and evaluated the correlation between virologicalresponse and clinical outcomes. Among 656 patients (mean age 49.1 years) included inthe database, 54% had chronic hepatitis, 30% had Child-Turcotte-Pugh (CTP) Acirrhosis, and 16% had CTP B/C cirrhosis. On therapy (median 22 months, range 1-66),a virological response was obtained in 616 patients (93.9%). The rate of maintainedvirological response was 39% after 4 years. During follow-up, 47 (7.2%) patientsunderwent liver transplantation, liver disease worsened in 31 (4.7%), hepatocellularcarcinoma (HCC) developed in 31 (4.7%), and 24 patients (3.6%) died of liver-relatedcauses. Patients who had cirrhosis and who maintained virological response were lesslikely than those with viral breakthrough to develop HCC (P <.001) and diseaseworsening (P <.001). Survival was better in CTP A patients with cirrhosis andmaintained virological response (P =.01 by rank test). Multivariate analysis revealed thatpresence of cirrhosis and viral breakthrough were independently related to mortality anddevelopment of HCC. In conclusion, lamivudine is highly effective in reducing viral loadin HBeAg-negative patients. After 4 years of therapy, 39% of patients maintain avirological and biochemical response. Loss of virological response may lead to clinicaldeterioration in patients with cirrhosis.
  • 29. Hepatology. 2004 Dec;40(6):1421-5.Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection.van Bommel F, Wunsche T, Mauss S, Reinke P, Bergk A, Schurmann D,Wiedenmann B, Berg T.Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charite,Universitatsmedizin Berlin, Campus Virchow, Berlin, Germany.Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudine-resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender ofadefovir that is used in the treatment of HIV infected patients, has recently been shownto also be effective in patients with lamivudine-resistant HBV infection. We thereforecompared the two substances in a study of 53 patients defined by high HBV DNA (>6log10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-fivepatients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks.Early viral kinetics were compared on matched subgroups of 5 patients each.Individually, all tenofovir-treated patients showed a strong and early suppression of HBVDNA within a few weeks whether they were coinfected with HIV or were withoutcomorbidity. In contrast, considerable individual variations in HBV DNA decline wereobserved in the adefovir group. Thus at week 48, only 44% of these patients had HBVDNA levels below 10(5) copies/mL in contrast to 100% of the tenofovir-treated patients(P = .001). No severe side effects were noticed in either group. No evidence ofphenotypic viral resistance could be demonstrated in the tenofovir-treated patients in thelong term (up to 130 weeks). In conclusion, tenofovir may become an effectivealternative for the treatment of patients with lamivudine-resistant HBV infection.
  • 30. 2. Kongreßabstracts EASL und AASLDHepatology, Vol.40, No.4, Suppl., 1, 2004; Nr. 20Peginterferon Alfa-24 (40KD) (PEGASYS®) monotherapy and incombination with lamivudine is more effective than lamivudinemonotherapy in HBeAG-positive chronic hepatitis B: Results from alarge, multinational studyGeorge Lau, Queen Mary Hospital, Hong Kong, Hong Kong Special AdministrativeRegion of China; Teerha Piratvisuth, Songklanakarin Hospital, Songkla, Thailand;Kang Xian Luo, Nangfang Hospital, Guangzhou, China; Patrick Marcellin, HôpitalBeaujon, Clichy, France; Satawat Thongasawat, Chiang Mai University, ChiangMai, Thailand; Graham Cooksley, Royal Brisbane Hospital, Herston, Australia;Eward Gane, Middlemore Hospital, Otahuhu, New Zealand; Michael Fried,University of North Carolina, Chapel Hill, NC; Wan Cheng Chow, SingaporeGeneral Hospital, Singapore, Singapore; Sseung Woon Paik, Samsung MedicalCentre, Seoul, Republic of Korea; Wen Yu Chang, Kaohsiung Medical UniversityHospital, Kaohsiung, Taiwan Republic of China; Thomas Berg, Charité HumboldtUniversität zu Berlin, Berlin, Germany; Robert Flisiak, University of Bialystok,Bialystok, Poland; Friederike Zahm, Roche, Basel, Switzerland; Nigel Pluck,Roche, Welwyn, United KingdomBackground: Recent data show that peginterferon alfa-2a (40KD) (Pegasys®) givessignificantly higher post-therapy response rates than lamivudine in HBeAg-negativechronic hepatitis B (CHB). Combining peginterferon alfa-2a and lamivudine did notomprove response rates over peginterferon alfa-2a alone [Marcellin et al, J Hepatol2004]. In this study, the efficacy and safety of peginterferon alfa-2a with and withoutlamivudine vs lamivudine alone has been evaluated in HBeAg-positive CHB.Methods: Randomized, partially double-blind multinational study. Patients with HBeAg-positive CHB (n=814) received (1:1:1): 1) Peginterferon alfa-2a (40KD) (PEGASYS®) 180 µg once weekly (qw) + placebo once daily (qd) 2) Peginterferon alfa-2a (40KD) (PEGASYS®) 180 µg qw + lamivudine 100 mg qd 3) Lamivudine 100 mg qd.Patients were treated for 48 weeks and assessed after 24 weeks of treatment-freefollow-up.Results: Baseline characteristics were comparable in all treatment groups. The overallpatients population was predominantly Asian (85-87%). After 24 weeks follow-up (week72), the proportion of patients achieving predefined co-primary endpoints (HBeAgseroconversion or HBF DNA <100,000 copies/ml), and secondary endpoints (HBeAgloss and ALT normalization), was significantly higher with peginterferon alfa-2amonotherapy or combination therapy than with lamivudine monotherapy.HBsAg seroconversion at week 72 was reported in 16 patients receiving peginterferonalfa-2a (± lamivudine) compared with none receiving lamivudine monotherapy.
  • 31. Withdrawals from treatment for safety reasons were low across all groups (<=3%). Themajority of adverse events were mild in nature and incidense of serious adverse eventswas low in all treatment groups (2-6%). Adverse events were comparable betweenpeginterfereon alfa-2a monotherapy and the combination therapy.Conclusions: Significantly higher post-therapy response rates were achieved withpeginteferon alfa-2a (40KD) (PEGASYS®) monotherapy or combination therapy thanwith lamivudine monotherapy in patients with HBeAg-positive CHB. Combiningpeginterferon alfa-2a and lamivudine did not improve response rates over peginterferonalfa-2a alone. No unexpected adverse events were reported for peginterferon alfa-2aand the addition of lamivudine did not significantly alter the peginterferon alfa-2a safetyprofile. PEGASYS® + placebo PEGASYS® + lami- lamivudine (n=271) vudine (n=271) (n=27)Co-primary endpointsHBeAg seroconversion 32% (P<0.001)* 27% (P=0.023)* 19 %HBV DNA < 100,000Copies/ml 32% (P=0.012)* 34% (P=0.003)* 22 %Secondary endpointsHBeAg loss 34% (P<0.001)* 28% (P=0.043)* 21 %ALT normalization 41% (P=0.002)* 39% (P=0.006)* 28 %* compared with lamivudine therapy
  • 32. J. of Hepatology, Suppl. 2 Vol. 42, General Session 2: Hepatits BPEGINTERFERON α-2a (40 kDa) (PEGASYS®) VERSUSPEGINTERFERON α-2a PLUS LAMIVUDINE VERSUS LAMIVUDINE INHBeAg-POSITIVE CHRONIC HBV: EFFECT OF PREVIOUSTREATMENT AND DRUG EXPOSURE ON SUSTAINED RESPONSEG.K.K. Lau1. T. Piratvisuth2, K-X. Luo3, P. Marcellin4, S. Thongsawat5, E. Gane6,M.W. Fried7, G. Cooksley8, P. Button9, Y-F. Liaw10.1 Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong,China; 2Department of Medicine, Songklanakarin Hospital, Sonkgla, Thailand;3 Department of Infectious Diseases, Nangfang Hospital, Guangzhou, China; 4Serviced’Hépatologie, INSERM Unité 481 and Centre de Recherches Claude Bernard sur lesHépatites Virales, Hôpital Beaujon, Clichy, France; 5Department of Internal Medicine,Chiang Mai University, Chiang Mai, Thailand; 6Gastroenterology Department,Middlemore Hospital, Otahuhu, New Zealand; 7University of North Carolina LiverProgram, University of North Carolina, Chapel Hill, NC, USA; 8Clinical ResearchDepartment, Royal Brisbane Hospital, Brisbane, Australia; 9Roche, Dee Why, Australia;10 Chang Gung Memorial Hospital, Linkou, TaiwanBackground: In chronic hepatitis C, previous treatment and extent of drug exposureseem to have an impact on response rates. In patients with chronic hepatits B (CHB) theeffects of previous anti-HBV treatment and exposure to study drug on responses topegylated interferon are less well investigated.Objectives: To investigate the effect of previous treatment and drug exposure onefficacy and safety in a randomised, partially double-blind, multinational study.Methods: HBeAg-positive patients (n=814) received (1:1:1) either peginterforn α-2a(180 µg once weekly) + placebo, peginterferon α-2a + lamivudine (100 mg once-daily) orlamivudine. Patients were treated for 48 weeks and assessed 24 weeks after the end oftreatment (week 72). Treatment with any anti-HBV drug 6 months before study entrywas not permitted. Analysis of drug exposure was performed only in the peginterferonα-2a monotherapy arm.HBeAg seroconversion rates at week 72 by previous treatment PEGASYS + PEGASYS + Lamivudine Placebo lamivudine (n=272) (n=271) (n=271)All patients (ITT) 32% 27% 19% P<0.001* p=0.023*Pts without previous 66/214 (31%) 59/221 (27%) 42/208 (20%)Anti-HBV therapy** p=0.018* p=0.115*Pts with previous exposure 13/30 (43%) 11/32 (34%) 4/32 (13%)to conventional IFN p=0.047* p=0.038*
  • 33. Pts with previous exposure 10/31 (32%) 6/24 (25%) 7/42 (17%)To Lamivudine P=0.065* P=0.253**vs. lamivudine** Includes lamivudine and conventional or pegylated interferonResults: The effects of previous treatment with either interferon and/or lamivudine onHBeAg seroconversion rates are shown in the table. Regardless of whether patientswere pre-treated or not, HBeAg seroconversion rates at week 72 were higher withpeginterferon α-2a and combination therapy than with lamivudine. The rate ofadherence to peginterferon α-2a was high, with 78% of patients receiving ≥90% of thetotal drug dosage (≥776µg). HBeAg seroconversion rates were 28% in those receiving<90% of the total drug dosage and 33% in those receiving ≥of the total drug dosage.Conclusions: Peginterferon α-2a (40 kDa) (PEGASYS®) provided higher rates ofHBeAg seroconversion than lamivudine, irrespective of whether the patients had or hadnot received previous anti-HBV therapy. Previous treatment with interferon or lamivudinedid not substantially affect HBeAg seroconversion rates with peginterferon α-2a in thisstudy. Adherence to peginterferon α-2a in this study was excellent.
  • 34. J. of Hepatology, Suppl .2 Vol.42, 2005 General Session 2: Hepatits B, Abstract 35ELEVATED SERUM LEVEL OF HEPATITIS B VIRUS DNA IS ANINDEPENDENT RISK FACTOR FOR HEPATOCELLULAR CARCINOMA:A LONG-TERM FOLLOW-UP STUDY IN TAIWANC.J. Chen1, H.I. Yang1, J.Su2, C.L. Jen1, E. Kuo3, S.L. You1, U.H. Iloeje2.1 2 National Taiwan University, Taipei, Taiwan; Bristol-Myers SquibbPharmaceutical Research Institute, Wallingford, USA; 3Bristol-Myers Squibb,Taipei, TaiwanIntroduction: Reduction in circulating HBV DNA level is a marker of efficacy for anti-viral treatment of chronic hepatitis B. However, there has never been a long-term follow-up study to examine the dose-response relation between serum HBV DNA level andhepatocellular carcinoma (HCC). This study was carried out to elucidate independentand interactive effects of serum HBV DNA on the development of HCC adjusting forHBeAg status and serum ALT level.Methods: A cohort of 3,851 subjects seropositive for HBV surface antigen (HbsAG) wasrecruited from seven townships in Taiwan between 1991 and 1992. Serum samplesobtained at enrolment and follow-up examination were tested for HbsAg, HbeAg, HBVDNA by PCR, and serum ALT. The diagnosis of HCC was ascertained through datalinkage with computerized profiles of the National Cancer Registry and DeathCertification System in Taiwan. Multivariable adjusted relative risks (RRadj) werederived using Cox proportional hazard models.Results: During 43,993 person-years of follow-up, 176 patients were newly diagnosedwith HCC. After adjustment for gender, age, habits of cigarette smoking, and alcoholconsumption, antibodies against hepatitis C virus, and HBeAg status, the risk ofdeveloping HCC was strongly associated with HBV DNA level in a dose-responserelationship (P<0.001). The RRadj was 6.6 (95%CI: 3.8-11.6) for those who had analevated HBV DNA level (>105 copies/ml). In people with ALT<1xULN, HBV DNA≥105copies/ml had a higher risk of HCC compared to those with undetectable HBV DNA,RRadj 10.2 (95%CI:5.7-18.4). In people with high DNA at baseline, the HCC risk washigher with persistent elevation, compared to those clearing DNA on repeat samplingRRadj 6.4 (95%CI:4.4-9.5).Conclusion: Persistently elevated serum level of HBV DNA is a strong risk predictor ofHCC independent of HBeAg status, chronic HCV infection, and elevated serum ALTlevel. Reduction in HBV DNA level overtime was associated with a decreased HCC risk.
  • 35. Hepatology, Vol. 40, No. 4, Suppl. 1, 2004; Nr. 1136Entecavir is superior to lamivudine at reducing HBV DNA in patientswith chronic hepatitis B regardless of baseline alanineaminotransferase levels.M Rosmawati, University Malaya Medical Center, Kuala Lumpur, Malaysia; ESchiff, University of Miami, Miami, FL; RE Parana, Federal University of Bahia,Salvador, Brazil; W Sievert, MMC Clayton, Victoria, Australia; J Zhu, A Cross, DDehertogh, D Apelian, Bristol-Myers Squibb Pharmaceutical Research Insitute,Wallingford, CT; the BEHoLD Study GroupBackground: Entecavir (ETV) is a potent and selective inhibitor of hepatitis B virus(HBV) polymerase. Chronic hepatitis B patients with low serum alanineaminotransferase (ALT) levels typically show reduced or absent responses to interferonand lamivudine (LVD). Data from a Phase II dose-ranging trial in nucleoside-naïvepatients suggested that this is not the case for ETV. This analysis assesses theinfluence of baseline ALT levels on the clinical efficacy of ETV 0,5 mg QD compared toLVD 100 mg QD in a Phase III trial in 709 nucleoside-naïve patients with chronichepatitis B (ETV-022).Methods: Patients were HBeAg (+) with baseline HBV DNA ≥ 3 MEq/ml by bDNAassay and ALT ≥ 1,3 x ULN. Efficacy endpoints included proportions of patients withHBV DNA < 0,7 MEq/ml by bDNA, proportions with HBV DNA < 400 copies/mL by PCR,and HBV DNA reduction by PCR. Efficacy results for both treatment groups wereanalysed within subgroups with baseline ALT < 2,6 x ULN or ≥ 2.6 x ULN.Results: Baseline disease characteristics were comparable in the ETV and LVD groups.Mean baseline viral loads were ETV: 9.61 log10 c/mL; LVD: 9.69 log10 c/mL. The baselineALT < 2.6 x ULN and ≥ 2.6 x ULN subgroups comprised 186 and 168 ETV patients,respectively, and 190 and 164 LVD patients, respectively. Virologic efficacy results atweek 48 by treatment and baseline ALT subgroup are shown in the table. ETV washighly effective at reducing HBV DNA regardless of baseline ALT level, and wassuperior to LVD by all virologic assessments. In contrast, among LVD-treated patients,HBV DNA reduction and the proportion of patients with undetectable HBV DNA levels bybDNA or PCR assays was attenuated in the lower baseline ALT subgroup.Conclusions: These data confirm Phase II observations showing that in patients withchronic hepatitis B, entecavir 0.5 mg is highly effective and is superior to LVD atreducing HBV DNA regardless of baseline ALT levels. Baseline ALT ETV LVD p-value*Log reduction < 2.6 x ULN - 6,79 - 4.85 < 0.0001from baseline in ≥ 2.6 x ULN - 7.18 - 6,15 < 0.0001HBV DNA by PCR% of patients with:HBV DNA < 0.7MEq/mL < 2.6 x ULN 90 % 58 % < 0.0001by DNA ≥ 2.6 x ULN 92 % 74 % < 0.0001HBV DNA < 400 < 2.6 x ULN 59 % 28 % < 0.0001copies/mL by PCR ≥ 2.6 x ULN 81 % 49 % < 0.0001
  • 36. J. of Hepatology No.2 Vol.42, 2005 General Session 2: Hepatits B, Abstract 36INCIDENCE AND PREDICTORS OF EMERGENCE OF ADEFOVIRRESISTANT HBV DURING FOUR YEARS OF ADEFOVIR DIPIVOXIL(ADV) THERAPY FOR PATIENTS WITH CHRONIC HEPATITIS B (CHB)S. Locarnini1, X. Qi2, S. Arterburn2, A. Snow2, C.L.Brosgart2, G. Currie2, M.Wulfsohn2, M.D. Miller2, S.Xiong2. 1VIDRL Melburne, Australia; 2Gilead ScienceInc., Foster City, CA, USABackground: Lamivudine-resistant (LAM-R) HBV emerged in 70% of CHB patients by 4years of LAM therapy. Higher baseline HBV DNA, higher body mass index (BMI), andmale were predictors for developing LAM-R (Lai_JID_2003;36:687).Aims: To determine the incidence of ADV resistance (ADV-R) mutations after 192weeks of ADV therapy and the predictors for ADV-R.Methods: This analysis included 629, 293, 221, and 67 patients who received ADVthrough 48, 96, 144, and 192 weeks, respectively, from 5 studies. At baseline, patientshad wild-type or LAM-R HBV. The majority of patients received ADV monotherapy. Mostpatients with LAM-R HBV received 3 years of ADV+LAM. ADV-R mutations wereidentified by sequencing HBV RT. The culmulative probability (CP) of ADV-R wascalculating using the Life Table method. Logistic regression was used to identifypredictors of ADV-R.Results: 22 patients developed ADV-R mutations (N236T and/or A181V) by 4 years.The incidence per period was 0% (o/629) for 8-48 weeks, 2% (6/293) for 49-96 weeks,5% (11/217) for 97-144 weeks, and 8% (5/62) for 145-192 weeks. The CP fordeveloping ADV-R by week 192 was 15% for all patients (18% for patients in ADVmonotherapy trials). No ADV-R mutations were identified in patients on LAM+ADV. TheN236T mutation was observed 4 times more frequently than A181V. Dual mutationsA181V(/T)+N236T were observed in 4 (18%) patients. Development of ADV-R mutationswas associated with serum HBV DNA rebound (≥1 log) in most patients. Logisticregressions analyses of baseline HBV DNA, ALT, race, age, gender, BMI, liverhistology, prior HBV therapy, and week 48 HBV DNA identified only higher serum HBVDNA at week 48 (median 4.2 log with ADV-R vs. 3 log without ADV-R) as a predictor ofADV-R.Conclusions: The cumulative probability of developing adefovir resistance wa 18% b192 weeks of ADV therapy in CHB patients. LAM+ADV combination therapy appears tolower the chance of developing ADV-R. Higher HBV DNA at week 48 during ADVtherapy predicted emergence of ADV resistance. The chance of developing reistancewas over 4-fold lower with ADV monotherapy compared to that reported for LAMmonotherapy by 4 years.
  • 37. Hepatology 2004; Vol. 40, No. 4, Suppl.1: 238AReduction of the relative relapse rate by prolongation of the durationof a therapy with Peginterferon alfa-2a plus Ribavirin in patients withgenotype 1 infection up to 72 weeksBerg T, v.Wagner M, Hinrichsen H, Heintges T, Buggisch P, Goeser T, Rasenack J,Pape G, Schmidt W, Kallinowski B, Klinker H, Spengler U, Alshuth U, Zeuzem S.Background: The reasons for the relatively high virological relapse rates after antiviralcombination therapy in patients with HCV genotype 1 are unknown. A prolongation ofthe duration of the therapy could represent a strategy for reducing relapse rates in thisdifficult-to-treat patient group.Patients and methods: In a German multicentre study 456 patients with histologicallyproven chronic HCV type 1-infection were treated with 180 µg peginterferon alfa-2a perweek plus 800 mg ribavirin per day for either 48 weeks (n=231) or 72 weeks (n=225).The intention to-treat analysis didnt show a significant difference in the sustainedvirological response rate between the two treatment groups. In this study we examinedthe influence of the duration of therapy on the relative relapse rate in relation to viralkinetics.Results: Overall the relative relapse rate (related to the number of patients withnegative HCV RNA at the end of therapy) was 23% (72/314). In patients treated for 48or 72 weeks, the relapse rates were 27% (44/165) and 19% (28/149) (p=0.09),respectively. A significant reduction in the relative relapse rate was evident with theprolonged duration of therapy (72 weeks) in patients with a late virological response.46% and 81% of patients with HCV RNA >1000 IU/ml after week 4 or 12, who weretreated for 48 weeks, suffered a relapse, while the corresponding relapse rates after 72weeks of treatment were 34% and 44%, respectively (p = 0.03; OR 2.1 95% CI: 1.04-4.1and OR 5.4 95% CI: 1.14-25.6). No significant difference was evident for sustainedvirological response and relapse rates in patients who were HCV RNA negative (< 1000IU/ml) at week 4 or 12.Conclusion: In patients with a late virological response (HCV RNA positive atweek 12 and negative at week 24) a significant reduction of the relapse rate maybe achieved by prolonging the duration of therapy up to 72 weeks.
  • 38. Hepatology, Vol. 40, No. 4, Suppl. 1, 2004; Nr. 169Reduction of the relative relapse rate by prolongation of the durationof a therapy with peginterferon alfa-2a plus ribavirin in patients withgenotype 1 infection up to 72 weeksThomas Berg, Charité, Campus Virchow-Klinikum, Berlin, Germany; Michael vonWagner, Universitätskliniken des Saarlandes, Homburg/Saar, Germany; HolgerHinrichsen, Christian Albrechts-Universität Kiel, Kiel, Germany; Tobias Heintges,Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany; Peter Buggisch,Universitätsklinik Eppendorf, Hamburg, Germany; Tobias Goeser, Universität zuKöln, Köln, Germany; Jens Rasenack, Medizinische Universitätsklinik Freiburg,Germany; Gerd R Pape, Klinikum Grosshadern, Ludwig-Maximilians Universität,München, Germany; Wolfgang E Schmidt, Medizinische Universitätsklinik, St.Josephhospital, Bochum, Germany; Birgit Kallinowski, Universitätsklinik,Heidelberg, Germany; Hartwig Klinker, Klinikum der Universität Würzburg,Würzburg, Germany; Ulrich Spengler, Medizinische Einrichtung der Rh. Fr.Wilhelm Universität, Bonn, Germany; Ulrich Alshuth, Hoffmann-La Roche,Grenzach, Germany; Stefan Zeuzen, Universitätskliniken des Saarlandes,Homburg/Saar, Germany; For the German Study Group PEGASYS + COPEGUS inHCV Genotype 1Background: The reasons for the relatively high virological relapse rates after antiviralcombination therapy in patients with HCV genotype 1 are unknown. A prolongation ofthe duration of the therapy coluld represent a strategy for reducing relapse rates in thisdifficult-to-treat patient group.Patients and Methods: In a German multicentre study 456 patients with histologicallyproven chronic HCV type 1-infection were treated with 180 µg peginterferon alfa-2a perweek plus 800 mg ribavirin per day for either 48 weeks (n=231) or 72 weeks (n=225).The intention to-treat analysis didn’t show a significant difference in the sustainedvirological response rate between the two treatment groups. In this study we examinedthe influence of the duration of therapy on the relative relapse rate in relation to viralkinetics.Results: Overall the relative relapse rate (related to the number of patients withnegative HCV RNA at the end of therapy), was 23% (72/314). In patients treated for 48or 72 weeks, the relapse rates were 27% (44/165) and 19% (28/149) (p=0,09),respectively. A. significant reduction in the relative relapse rate was evident with theprolonged duration of therapy (72 weeks) in patients with a late virological response.46% and 81% of patients with HCV RNA >1000 IU/ml after week 4 or 12, who weretreated for 48 weeks, suffered a relapse, while the corresponding relapse rates after 72weeks of treatment were 34% and 44%, respectively (p=0,03; OR 2.1 95% CI: 1.04-4.1and OR 5.4 95% CI: 1.14-25.6). No significant difference was evident for sustainedvirological response and relapse rates in patients who were HCV RNA negative (< 1000IU/ml) at week 4 or 12.
  • 39. Conclusion: In patients with a late virological response (HCV RNA positive at week 12and negative at week 24) a significant reduction of the relapse rate may be achieved byprolonging the duration of therapy up to 72 weeks.Hepatology, Vol. 40, No. 4. Suppl. 1, 2004; LB 02Randomized multicenter study comparing 16 VS. 24 weeks ofcombination therapy with peginterferon alfa-2a plus ribavirin inpatients chronically infected with HCV genotype 2 or 3.Michael von Wagner, Universitätsklinikum des Saarlandes, Homburg/Saar,Germany; Miriam Huber, Johann Wolfgang Goethe Universität, Frankfurt/Main,Germany; Thomas Berg, Charité, Campus Virchow-Klinikum, Berlin, Germany;Holger Hinrichsen, Christian-Albrecht-Universität, Kiel, Germany; Jens Rasenack,Medizinische Universitätsklinik, Freiburg, Germany; Tobias Heintges, Heinrich-Heine-Universität, Düsseldorf, Germany; Alexandra Bergk, Charité, CampusVirchow-Klinikum, Berlin, Germany; Christine Bernsmeier, Christian-Albrecht-Universität, Kiel, Germany; Stafan Zeuzem, Universitätsklinikum des Saarlandes,Homburg/Saar, GermanyBackground: Extending treatment duration with peginterfeeron alfa plus ribavirin form24 to 48 weeks did not improve sustained virologic response rates in patients infectedwith HCV genotype 2 or 3 (Ann Intern Med 2004; 140:346-355, J Hepatol 2004;40:993-999). Whether shorter treatment durations are possible for these patients withoutcompromising sustained virologic response rates is unknown. Aim: To comparevirologic response rates in patients with chronic HCV-2 or –3 infection treated for 16 vs.24 weeks. Methods: Previously untreated patients (mean age 39 ± 10 yrs.) chronicallyinfected with HCV genotype 2 (n=39) or 3 (n=114) were treated with 180 µgpeginterferon alfa-2a once weekly in combination with ribavirin (800-1200 mg/day). HCVRNA was assessed after 4 weeks by quantitative RT-PCR assay (Cobas AmplicorMonitor). Patients with HCV RNA below the limit of detection of the assay (600 IU/mL)were randomised for a total treatment duration of 16 weeks (group A) or 24 weeks(group B). All patients with detectable HCV RNA levels at week 4 (group C) were treatedfor 24 weeks. End-of-treatment and sustained virologic response after a 24-week follow-up period were assessed by qualitative RT-PRC (Cobas Amplicor HCV, sensitivity 50 IU/mL). Results: Only 14/153 patients (9%) were allocated to group C. In contrast, 139/153patients infected with HCV genotype 2 or 3 achieved HCV RNA levels below 600 IU/mLat week 4 of treatment and were randomised to groups A and B. Intent-to-treat virologicresponse rates are given in the Table: On-treatment dorp-out rates in groups A, B, Cwere 5.6%, 13.2%, 14.3%, respectively. Adverse events and laboratory abnormalitieswere similar to previous trials using peginterferon alfa-2a and ribavirin combinationtherapy. Conclusion: At week 4 of treatment with peginterferon alfa-2a plus ribavirin anearly virologic response was observed in mor than 90% of patients chronically infectedwith HCV genotype 2 or 3. Combination therapy for 16 or 24 weeks achieved similarsustained virologic response rates in these early virologic response rate in patientswithout an early virologic response at week 4 (group C) implies that a treatment durationlonger than 24 weeks may be necessary in this small subset of patients.TableVirologic All Group A Group B Group Cresponse
  • 40. End of treatment 135/153 (88.2%) 67/71 (94.4%) 58/68 (85.3%) 10/14 (71.0%)End of follow-up 111/153 (72.5%) 57/71 (78.9%) 51/68 (75.0%) 4/14 (28.6%)NASH / ASH / Autoimmun M. PirlichHepatology. 2004 May;39(5):1390-7.A double-blind randomized controlled trial of infliximab associatedwith prednisolone in acute alcoholic hepatitis.Naveau S, Chollet-Martin S, Dharancy S, Mathurin P, Jouet P, Piquet MA, DavionT, Oberti F, Broet P, Emilie D; Foie-Alcool group of the Association Francaisepour lEtude du Foie.Services dHepato-Gastroenterologie, Hopital Antoine Beclere, Clamart, AssistancePublique-Hopitaux de Paris, France. sylvie.naveau@abc.ap-hop-paris.frTumor necrosis factor-alpha (TNF-alpha) may contribute to the progression of acutealcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of anassociation of infliximab and prednisolone at reducing the 2-month mortality rate amongpatients with severe AAH. Patients with severe AAH (Maddrey score >/=32) wererandomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) inweeks 0, 2, and 4; or group B receiving a placebo at the same times. All patientsreceived prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacitieswere monitored over 28 days. After randomization of 36 patients, seven patients fromgroup A and three from group B died within 2 months. The probability of being dead at 2months was higher (not significant [NS]) in group A (39% +/- 11%) than in group B (18%+/- 9%). The study was stopped by the follow-up committee and the sponsor (AssistancePublique-Hopitaux de Paris). The frequency of severe infections within 2 months washigher in group A than in group B (P <.002). This difference was potentially related to asignificantly lower ex vivo stimulation capacity of neutrophils. There were no differencesbetween the two groups in terms of Maddrey scores at any time point. In conclusion,three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmfulin patients with severe AAH because of the high prevalence of severe infections.
  • 41. Hepatology. 2004 Mar;39(3):770-8Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis:results of a randomized trial.Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P,Lymp JF, Burgart L, Colin P.Division of Gastroenterology and Hepatology, Mayo Clinic-W19A, 200 1st Street SW,Rochester, MN 55905, USA. lindor.keith@mayo.eduNo effective medical therapy is available for all patients with nonalcoholic steatohepatitis(NASH). Ursodeoxycholic acid (UDCA) has been suggested to be of benefit based onopen label clinical studies. We randomized 166 patients with liver biopsy-proven NASHto receive between 13 and 15 mg/kg/d of UDCA or placebo for 2 years. End pointsincluded changes in liver test results and liver histology at 2 years of therapy. Thetreatment groups were comparable at entry with regard to age, gender, risk factors forNASH, serum liver biochemistries, and baseline liver histology. A total of 126 patientscompleted 2 years of therapy. Pre- and posttreatment liver biopsies were available in107 patients for review at the end of the study. UDCA was well tolerated and bodyweight was stable during the study duration. Serum liver biochemistries were stable orimproved in both the UDCA and placebo-treated groups. Changes in the degree ofsteatosis, necroinflammation, or fibrosis that occurred with therapy were not significantlydifferent between the UDCA and placebo groups. In conclusion, 2 years of therapy withUDCA at a dose of 13 to 15 mg/kg/d, although safe and well tolerated, is not better thanplacebo for patients with NASH.
  • 42. Hepatology. 2004 Jan;39(1):188-96.A pilot study of pioglitazone treatment for nonalcoholicsteatohepatitis.Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, GhanyM, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH.Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes andDigestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which thereis no known effective therapy. A proportion of patients with NASH progress to advancedfibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolicsyndrome in which insulin resistance plays a central role. This prospective studyevaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteennondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mgdaily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liverbiopsies were performed before and at the end of treatment. By 48 weeks, serumalanine aminotransferase values fell to normal in 72% of patients. Hepatic fat contentand size as determined by magnetic resonance imaging decreased, and glucose andfree fatty acid sensitivity to insulin were uniformly improved. Histological features ofsteatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis weresignificantly improved from baseline (all P < 0.05). Using strict criteria, histologicalimprovement occurred in two-thirds of patients. Pioglitazone was well tolerated; the mainside effects were weight gain (averaging 4%) and an increase in total body adiposity. Inconclusion, these results indicate that treatment with an insulin-sensitizing agent canlead to improvement in biochemical and histological features of NASH and support therole of insulin resistance in the pathogenesis of this disease. The long-term safety andbenefits of pioglitazone require further study.
  • 43. Portale Hypertension M. PeckGastroenterology. 2004 Oct;127(4):1123-30Recombinant factor VIIa for upper gastrointestinal bleeding in patientswith cirrhosis: a randomized, double-blind trial.Bosch J, Thabut D, Bendtsen F, DAmico G, Albillos A, Gonzalez Abraldes J,Fabricius S, Erhardtsen E, de Franchis R; European Study Group on rFVIIa in UGIHaemorrhage.Hospital Clinic, Liver Unit, Barcelona, Spain. jbosch@medicina.ub.esBACKGROUND & AIMS: Upper gastrointestinal bleeding (UGIB) is a severe andfrequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) hasbeen shown to correct the prolonged prothrombin time in patients with cirrhosis andUGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients withvariceal and nonvariceal UGIB. METHODS: A total of 245 cirrhotic patients (Child-Pugh< 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal =29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment.The primary end point was a composite including: (1) failure to control UGIB within 24hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or(3) death within 5 days. RESULTS: Baseline characteristics were similar between rFVIIaand placebo groups. rFVIIa showed no advantage over standard treatment in the wholetrial population. Exploratory analyses, however, showed that rFVIIa significantlydecreased the number of failures on the composite end point (P = 0.03) and the 24-hourbleeding control end point (P = 0.01) in the subgroup of Child-Pugh B and C varicealbleeders. There were no significant differences between rFVIIa and placebo groups inmortality (5- or 42-day) or incidence of adverse events including thromboembolic events.CONCLUSIONS: Although no overall effect of rFVIIa was observed, exploratoryanalyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIasignificantly decreased the proportion of patients who failed to control variceal bleeding.Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.
  • 44. Gastroenterology. 2004 Feb;126(2):469-75Improved clinical outcome using polytetrafluoroethylene-coatedstents for TIPS: results of a randomized study.Bureau C, Garcia-Pagan JC, Otal P, Pomier-Layrargues G, Chabbert V, Cortez C,Perreault P, Peron JM, Abraldes JG, Bouchard L, Bilbao JI, Bosch J, Rousseau H,Vinel JP.Service dHepato-Gastro-Enterologie, Federation Digestive, Centre HospitalierUniversitaire Purpan et U531 Institut National de la Sante et de la Recherche Medicale,Toulouse, France. bureau.c@chu-toulouse.frBACKGROUND & AIMS: A 50% dysfunction rate at 1 year is one of the main drawbacksof the transjugular intrahepatic portosystemic shunt procedure. Preliminary experimentaland clinical studies suggest that the use of stents covered with polytetrafluoroethylenecould tremendously decrease this risk. METHODS: Eighty patients with cirrhosis anduncontrolled bleeding (n = 23), recurrent bleeding (n = 25), or refractory ascites (n = 32)were randomized to be treated by transjugular intrahepatic portosystemic shunts witheither a polytetrafluoroethylene-covered stent (group 1; 39 patients) or a usualuncovered prosthesis (group 2; 41 patients). Follow-up Doppler ultrasound wasscheduled at day 7, at 1 month, and then every 3 months for 2 years. Angiography andportosystemic pressure gradient measurements were performed 6, 12, and 24 monthsafter the transjugular intrahepatic portosystemic shunt procedure and wheneverdysfunction was suspected. Dysfunction was defined as a >50% reduction of the lumenof the shunt at angiography or a portosystemic pressure gradient >12 mm Hg.RESULTS: After a median follow-up of 300 days, 5 patients (13%) in group 1 and 18(44%) in group 2 experienced shunt dysfunction (P < 0.001). Clinical relapse occurred in3 patients (8%) in group 1 and 12 (29%) in group 2 (P < 0.05). Actuarial rates ofencephalopathy were 21% in group 1 and 41% in group 2 at 1 year (not significant).Estimated probabilities of survival were 71% and 60% at 1 year and 65% and 41% at 2years in groups 1 and 2, respectively (not significant). CONCLUSIONS: The use ofpolytetrafluoroethylene-covered prostheses improves transjugular intrahepaticportosystemic shunt patency and decreases the number of clinical relapses andreinterventions without increasing the risk of encephalopathy.
  • 45. Hepatology. 2004 Oct;40(4):793-801.Influence of portal hypertension and its early decompression by TIPSplacement on the outcome of variceal bleeding.Monescillo A, Martinez-Lagares F, Ruiz-del-Arbol L, Sierra A, Guevara C, JimenezE, Marrero JM, Buceta E, Sanchez J, Castellot A, Penate M, Cruz A, Pena E.Digestive Disease Department, Hospital Universitario Insular de Gran Canaria, CanaryIslands, Spain. monescillo@eresmas.comIncreased portal pressure during variceal bleeding may have an influence on thetreatment failure rate, as well as on short- and long-term survival. However, theusefulness of hepatic hemodynamic measurement during the acute episode has notbeen prospectively validated, and no information exists about the outcome ofhemodynamically defined high-risk patients treated with early portal decompression.Hepatic venous pressure gradient (HVPG) measurement was made within the first 24hours after admission of 116 consecutive patients with cirrhosis with acute varicealbleeding treated with a single session of sclerotherapy injection during urgentendoscopy. Sixty-four patients had an HVPG less than 20 mm Hg (low-risk [LR] group),and 52 patients had an HVPG greater than or equal to 20 mm Hg (high-risk [HR] group).HR patients were randomly allocated into those receiving transjugular intrahepaticportosystemic shunt (TIPS; HR-TIPS group, n = 26) within the first 24 hours afteradmission and those not receiving TIPS (HR-non-TIPS group). The HR-non-TIPS grouphad more treatment failures (50% vs. 12%, P =.0001), transfusional requirements (3.7+/- 2.7 vs. 2.2 +/- 2.3, P =.002), need for intensive care (16% vs. 3%, P <.05), and worseactuarial probability of survival than the LR group. Early TIPS placement reducedtreatment failure (12%, P =.003), in-hospital and 1-year mortality (11% and 31%,respectively; P <.05). In conclusion, increased portal pressure estimated by early HVPGmeasurement is a main determinant of treatment failure and survival in varicealbleeding, and early TIPS placement reduces treatment failure and mortality in high riskpatients defined by hemodynamic criteria.
  • 46. Hepatology. 2005 Mar;41(3):572-8.Variceal ligation plus nadolol compared with ligation for prophylaxisof variceal rebleeding: a multicenter la Pena J, Brullet E, Sanchez-Hernandez E, Rivero M, Vergara M, Martin-Lorente JL, Garcia Suarez C.Hospital Universitario Marques de Valdecilla, Santander, Spain. jpena@humv.esbeta-Blockers and endoscopic variceal ligation (EVL) have proven to be valuablemethods in the prevention of variceal rebleeding. The aim of this study was to comparethe efficacy of EVL combined with nadolol versus EVL alone as secondary prophylaxisfor variceal bleeding. Patients admitted for acute variceal bleeding were treated duringemergency endoscopy with EVL or sclerotherapy and received somatostatin for 5 days.At that point, patients were randomized to receive EVL plus nadolol or EVL alone. EVLsessions were repeated every 10 to 12 days until the varices were eradicated. Eightypatients with cirrhosis (alcoholic origin in 66%) were included (Child-Turcotte-Pugh A,15%; B, 56%; C, 29%). The median follow-up period was 16 months (range, 1-24months). The variceal bleeding recurrence rate was 14% in the EVL plus nadolol groupand 38% in the EVL group (P = .006). Mortality was similar in both groups: five patients(11.6%) died in the combined therapy group and four patients (10.8%) died in the EVLgroup. There were no significant differences in the number of EVL sessions to eradicatevarices: 3.2 +/- 1.3 in the combined therapy group versus 3.5 +/- 1.3 in the EVL alonegroup. The actuarial probability of variceal recurrence at 1 year was lower in the EVLplus nadolol group (54%) than in the EVL group (77%; P = .06). Adverse effectsresulting from nadolol were observed in 11% of the patients. In conclusion, nadolol plusEVL reduces the incidence of variceal rebleeding compared with EVL alone. Acombined treatment could lower the probability of variceal recurrence after eradication.
  • 47. Gastroenterology. 2004 Aug;127(2):476-84.A placebo-controlled clinical trial of nadolol in the prophylaxis ofgrowth of small esophageal varices in cirrhosis.Merkel C, Marin R, Angeli P, Zanella P, Felder M, Bernardinello E, Cavallarin G,Bolognesi M, Donada C, Bellini B, Torboli P, Gatta A; Gruppo Triveneto perlIpertensione Portale.Department of Clinical and Experimental Medicine, University of Padua, Padova, Italy.carlo.merkel@unipd.itBACKGROUND & AIMS: Beta-blockers are extensively used to prevent varicealbleeding in patients with large esophageal varices. It is not established if beta-blockersdelay the growth of small varices. METHODS: A total of 161 patients with cirrhosis andsmall esophageal varices (F1 according to the classification of Beppu et al.) withoutprevious bleeding were enrolled. A total of 83 patients were randomized to nadolol (doseadjusted to decrease resting heart rate by 25%; mean dose given, 62 +/- 25 mg/day)and 78 to placebo. The principal end point was occurrence of large esophageal varices(F2 or F3 according to the classification of Beppu et al.). Endoscopic examination wasperformed after 12, 24, 36, 48, and 60 months of follow-up. Mean follow-up was 36months. RESULTS: The 2 groups were well matched for demographic and clinicalcharacteristics. During the study period, 9 patients randomized to nadolol and 29randomized to placebo had growth of esophageal varices. At the end of follow-up, thecumulative risk was 20% versus 51% (P < 0.001) (absolute risk difference, 31%; 95%confidence interval, 17%-45%). When possible confounding factors were taken intoaccount, treatment was a significant factor predicting growth of varices (odds ratio, 4.0;95% confidence interval, 1.95-8.4). The cumulative probability of variceal bleeding wasalso lower in patients randomized to nadolol (P = 0.02). Survival was not different (P =0.33). Adverse effects resulting in withdrawal of drug occurred in 9 in the nadolol groupand one in the placebo group (P = 0.01). CONCLUSIONS: This study suggests thatbeta-blocker prophylaxis of variceal bleeding in patients with compensated cirrhosisshould be started when small esophageal varices are present.
  • 48. Hepatology. 2005 Mar;41(3):588-94.+#Pantoprazole reduces the size of postbanding ulcers after varicealband ligation: a randomized, controlled trial.Shaheen NJ, Stuart E, Schmitz SM, Mitchell KL, Fried MW, Zacks S, Russo MW,Galanko J, Shrestha R.Division of Gastroenterology and Hepatology, University of North Carolina School ofMedicine, Chapel Hill, NC, USA.Elective esophageal variceal ligation (EVL) is performed to decrease the risk of varicealhemorrhage. Side effects of EVL include hemorrhage, chest pain, dysphagia, andodynophagia. Because gastric acid may exacerbate postbanding ulcers and delayhealing, proton pump inhibition may decrease side effects associated with EVL. The aimof this study was to assess the efficacy of pantoprazole, a proton pump inhibitor, as anadjunct to elective EVL. We performed a double-blinded, randomized, placebo-controlled trial of pantoprazole after elective EVL. Subjects in the pantoprazole armreceived 40 mg pantoprazole intravenously after EVL followed by 40 mg oralpantoprazole for 9 days. Control subjects received intravenous and oral placebo.Subjects underwent upper endoscopy 10 to 14 days after banding. Primary outcomesincluded the size and number of ulcers and the subjects reports of dysphagia, chestpain, and heartburn. Forty-four subjects were randomized: 42 completed the protocol. Atfollow-up endoscopy, the mean number of ulcers was similar in the two groups.However, the ulcers in the pantoprazole group were on average half as large as in theplacebo group (37 mm(2) vs. 82 mm(2), P < .01). Chest pain, dysphagia, and heartburnscores were not significantly different. Four subjects, all in the placebo group, hadadverse outcomes, including 3 who bled from postbanding ulcers and 1 with sepsis. Inconclusion, subjects receiving pantoprazole after elective EVL had significantly smallerpostbanding ulcers on follow-up endoscopy than subjects receiving placebo. However,the total ulcer number and patient symptoms were not different between the groups.
  • 49. BMJ. 2004 May 1;328(7447):1046. Epub 2004 Mar 30.Non-absorbable disaccharides for hepatic encephalopathy:systematic review of randomised trials.Als-Nielsen B, Gluud LL, Gluud C.Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical InterventionResearch, Copenhagen University Hospital, Department 7102, H:S Rigshospitalet,DK-2100 Copenhagen, Denmark. bodil.a@ctu.rh.dkOBJECTIVE: To assess the effects of non-absorbable disaccharides (lactulose andlactitol) in patients with hepatic encephalopathy. DATA SOURCES: Cochrane Hepato-Biliary Group controlled trials register, Cochrane Library, Medline, and Embase untilMarch 2003; reference lists of relevant articles; authors and pharmaceutical companies.REVIEW METHODS: Randomised trials that compared non-absorbable disaccharideswith placebo, no intervention, or antibiotics for hepatic encephalopathy were included.The primary outcome measures were no improvement of hepatic encephalopathy andall cause mortality. RESULTS: 22 trials were included. Compared with placebo or nointervention, non-absorbable disaccharides seemed to reduce the risk of noimprovement in patients with hepatic encephalopathy (relative risk 0.62, 95% confidenceinterval 0.46 to 0.84, six trials). However, high quality trials found no significant effect(0.92, 0.42 to 2.04, two trials). Compared with placebo or no intervention, non-absorbable disaccharides had no significant effect on mortality (0.41, 0.02 to 8.68, fourtrials). Non-absorbable disaccharides were inferior to antibiotics in reducing the risk ofno improvement (1.24, 1.02 to 1.50, 10 trials) and lowering blood ammoniaconcentration (weighted mean difference 2.35 micromol/l, 0.06 micromol/l to 13.45micromol/l, 10 trials). There was no significant difference in mortality (0.90, 0.48 to 1.67,five trials). CONCLUSIONS: There is insufficient evidence to support or refute the use ofnon-absorbable disaccharides for hepatic encephalopathy. Antibiotics were superior tonon-absorbable disaccharides in improving hepatic encephalopathy, but it is unclearwhether this difference is clinically important. Non-absorbable disaccharides should notserve as comparator in randomised trials on hepatic encephalopathy.
  • 50. Darmerkrankungen/PankreasCED: Neue Substanzen A. Dignaß1. OriginalarbeitenGastroenterology (im Druck, Juni-Ausgabe)Infliximab as rescue therapy in severe to moderately severe ulcerativecolitis. A randomised placebo controlled study.Gunnar Järnerot, Erik Hertervig, Inga-Lill Friis-Liby, Lars Blomquist, Per Karlén,Christer Grännö, Mogens Vilien, Magnus Ström, Åke Danielsson,. Hans Verbaan,Per M Hellström, Anders Magnuson and Bengt Curman.Background & Aims: In spite of treatment with corticosteroids, severe - moderatelysevere attacks of ulcerative colitis have a high colectomy rate. We intended to findanother rescue therapy than cyclosporine A, which imposes a high risk of side-effectsand cyclosporine related mortality.Methods: This was a randomised double-blind trial of infliximab or placebo in severe -moderately severe ulcerative colitis not responding to conventional treatment. Patientswere randomised to infliximab/placebo either on Day 4 after initiation of corticosteroidtreatment if they fulfilled the index criteria for fulminant ulcerative colitis on Day 3 or onDay 6-8 if they on Day 5-7 fulfilled index criteria for a severe -moderately severe acuteattack of ulcerative colitis. Results were analysed according to the intention - to - treatprinciple. The primary end point was colectomy or death 3 months after randomisation.Secondary end points were clinical and endoscopic remission at that time in patients notoperated.Results: 45 patients were included (24 infliximab, 21 placebo). No patient died. Sevenpatients in the infliximab and 14 in the placebo group had a colectomy (p=0.017. OR 4.9(95%CI 1.4-17) within 3 months after randomisation. No serious side-effects occurred.Three patients in the placebo group required surgery for septic complications.Conclusions: Infliximab in a dose of 4-5 mg/kg is an effective and safe rescue therapy inpatients suffering from an acute severe or moderately severe attack of ulcerative colitisnot responding to conventional treatment.
  • 51. Gastroenterology. 2005 Mar;128(3):552-63.Autologous hematopoietic stem cell transplantation in patients withrefractory Crohns disease.Oyama Y, Craig RM, Traynor AE, Quigley K, Statkute L, Halverson A, Brush M,Verda L, Kowalska B, Krosnjar N, Kletzel M, Whitington PF, Burt RK.Division of Immunotherapy, Department of Medicine, Northwestern University MedicalCenter, Chicago, Illinois 60611, USA. y-oyama@northwestern.eduBACKGROUND & AIMS: Crohns disease (CD) is an immunologically mediatedinflammatory disease of the gastrointestinal tract. Due to a high morbidity and/or anincrease in mortality in refractory cases, a new treatment approach is needed. In theory,maximum immune ablation by autologous hematopoietic stem cell transplantation(HSCT) can induce a remission. METHODS: We conducted a phase 1 HSCT study in 12patients with refractory CD. Candidates were younger than 60 years of age with aCrohns Disease Activity Index (CDAI) of 250-400 despite conventional therapiesincluding infliximab. Peripheral blood stem cells were mobilized with cyclophosphamideand granulocyte colony-stimulating factor and CD34 + enriched. The immune ablative(conditioning) regimen consisted of 200 mg/kg cyclophosphamide and 90 mg/kg equineantithymocyte globulin. RESULTS: The procedure was well tolerated with anticipatedcytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea,and vomiting. The median days for neutrophil and platelet engraftment were 9.5 (range,8-11) and 9 (range, 9-18), respectively. The initial median CDAI was 291 (range,250-358). Symptoms and CDAI improved before hospital discharge, whereasradiographic and colonoscopy findings improved gradually over months to yearsfollowing HSCT. Eleven of 12 patients entered a sustained remission defined by a CDAI< or =150. After a median follow-up of 18.5 months (range, 7-37 months), only onepatient has developed a recurrence of active CD, which occurred 15 months after HSCT.CONCLUSIONS: Autologous HSCT may be performed safely and has a markedsalutary effect on CD activity. A randomized study will be needed to confirm the efficacyof this therapy.
  • 52. Gastroenterology. 2005 Apr;128(4):825-32Trichuris suis therapy for active ulcerative colitis: a randomizedcontrolled trial.Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV.James A. Clifton Center for Digestive Diseases, Department of Internal Medicine,University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. robert-summers@uiowa.eduBACKGROUND & AIMS: Ulcerative colitis is most common in Western industrializedcountries. Inflammatory bowel disease is uncommon in developing countries wherehelminths are frequent. People with helminths have an altered immunological responseto antigens. In animal models, helminths prevent or improve colitis by the induction ofregulatory T cells and modulatory cytokines. This study determined the efficacy andsafety of the helminth Trichuris suis in therapy of ulcerative colitis. METHODS: This wasa randomized, double blind, placebo-controlled trial conducted at the University of Iowaand select private practices. Trichuris suis ova were obtained from the US Departmentof Agriculture. The trial included 54 patients with active colitis, defined by an UlcerativeColitis Disease Activity Index of > or =4. Patients were recruited from physicianparticipants and were randomly assigned to receive placebo or ova treatment. Patientsreceived 2500 Trichuris suis ova or placebo orally at 2-week intervals for 12 weeks.RESULTS: The primary efficacy variable was improvement of the Disease Activity Indexto > or =4. After 12 weeks of therapy, improvement according to the intent-to-treatprinciple occurred in 13 of 30 patients (43.3%) with ova treatment compared with 4 of 24patients (16.7%) given placebo (P = .04). Improvement was also found with the SimpleIndex that was significant by week 6. The difference in the proportion of patients whoachieved an Ulcerative Colitis Disease Activity Index of 0-1 was not significant.Treatment induced no side effects. CONCLUSIONS: Ova therapy seems safe andeffective in patients with active colitis.
  • 53. 2. DDW AbstractsDDW Abstract 689- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-105Disclosures: Organization - Centocor, Inc., Relationship - EmployeeA Randomized Placebo-Controlled Trial Of Infliximab Therapy forActive Ulcerative Colitis: Act I TrialP. Rutgeerts, B.G. Feagan, Dr., A. Olson, Dr., J. Johanns, Dr., S. Travers, Dr., D.Present, Dr., B.E. Sands, Dr., W. Sandborn, Dr. , A. OlsonBackground: There is a need for an effective therapy for active ulcerative colitis (UC).Two randomized, placebo-controlled trials (ACT 1 and ACT 2) were designed toevaluate the safety and efficacy of infliximab (IFX) for active UC. Results from ACT 1,which evaluated patients treated with corticosteriods and/or 6-MP/AZA, are presented.Methods: Patients (n=364) with active UC despite use of corticosteroids/AZA/6-MP, withendoscopic evidence of moderate or severe UC (endoscopy score>=2) and a total Mayoscore of 6-12 inclusive, were randomized to receive placebo, IFX 5 mg/kg or 10 mg/kg atwks 0, 2, and 6 then every 8 wks through wk 46. The primary endpoint was induction ofclinical response, defined as a decrease in the Mayo score of >=30% and >=3 points,accompanied by a decrease in rectal bleeding score of >=1 or a rectal bleeding score of0 or 1 at wk 8. Secondary endpoints included clinical remission, defined as a Mayoscore <=2, with no individual subscores >1, and mucosal healing defined as anendoscopy subscore of 0 or 1.Results: Significantly higher proportions of patients receiving IFX 5 mg/kg (69.4%) and10 mg/kg (61.5%) were in clinical response at wk 8 vs. placebo-treated patients (37.2%,p<0.001). At wk 30, 52.1% and 50.8% of IFX 5 and 10 mg/kg treated patients,respectively, achieved clinical response vs. 29.8% of placebo-treated patients (p<0.001and p=0.002). At wk 8, 38.8% and 32.0% of IFX 5 and 10 mg/kg treated patients,respectively, were in clinical remission vs. 14.9% of placebo-treated patients (p<0.001and p=0.002). These differences in remission rates persisted at wk 30 (33.9%, 5 mg/kg;36.9%, 10 mg/kg vs. 15.7%, placebo; p=0.001 and p<0.001). Mucosal healing wasachieved at wk 8 in 62% and 59% of patients receiving IFX 5 and 10 mg/kg, respectivelyvs. 33.9% of placebo-treated patients (p<0.001). This difference in mucosal healing wasmaintained at wk 30 (50.4%, 5 mg/kg; 49.2%, 10 mg/kg vs. 24.8%, placebo; p<0.001 forboth). The proportion of patients who were able to discontinue corticosteroids while inclinical remission at wk 30 was greater in the combined IFX treatment group than in theplacebo group (21.7% vs. 10.1%; p=0.039). IFX was generally well tolerated with asafety profile similar to that previously reported.Conclusion: IFX is effective in treating active UC by reducing signs and symptoms,inducing remission, attaining mucosal healing, and facilitating corticosteroid withdrawalwhile maintaining remission.
  • 54. DDW Abstract 688- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-104Disclosures: Organization - Schering-Plough, Centocor, Inc., Relationship - Grant /Research SupportInfliximab Induction and Maintenance Therapy for UlcerativeColitis: the Act 2 TrialW.J. Sandborn, D. Rachmilewitz, Dr., S.B. Hanauer, Dr., G.R. Lichtenstein, Dr.,W.J. de Villiers, Dr., A. Olson, Dr., J. Johanns, Dr. , S. Travers, Dr. , J. Colombel,Dr.Background: The efficacy of infliximab (IFX) for the treatment of ulcerative colitis (UC)was previously unknown. Two Phase 3 trials, ACT I and ACT 2, evaluated the safetyand efficacy of IFX for treatment of active UC. Results from ACT 2 are presented.Methods: 364 patients with UC, refractory to at least one standard therapy including 5-ASA, corticosteroids, or immunosuppressants, were randomized to receive IFX 5 mg/kg,IFX 10 mg/kg, or placebo at wks 0, 2, 6, 14 and 22. The primary endpoint was inductionof clinical response, defined as a decrease in the Mayo score of >=30% and >=3 points,accompanied by a decrease in the rectal bleeding score of >=1 or a rectal bleedingscore of 0 or 1 at wk 8. Clinical remission, a secondary endpoint, was defined as a Mayoscore <=2, with no individual subscores >1, and mucosal healing was defined as anendoscopy subscore of 0 or 1.Results: 64.5% of patients receiving IFX 5 mg/kg and 69.2% receiving 10 mg/kg were inclinical response at wk 8 vs 29.3% who received placebo (p<0.001 for both). At wk 30,47.1% of patients receiving IFX 5 mg/kg and 60% receiving 10 mg/kg were in clinicalresponse vs 26% of patients receiving placebo (p<0.001 for both). Clinical remissionwas achieved at wk 8 in 33.9% and 27.5% of IFX 5 and 10 mg/kg patients, respectively,compared to 5.7% of placebo-treated patients (p<0.001 for both). Differences inremission rates persisted at wk 30 (25.6%, 5 mg/kg; 35.8%, 10 mg/kg; 10.6%, placebo;p=0.003 and p<0.001). Mucosal healing was achieved at wk 8 in 60.3% and 61.7% ofpatients receiving IFX 5 mg/kg and 10 mg/kg, respectively, compared to 30.9% ofplacebo-treated patients (p<0.001 for both). Mucosal healing at wk 30 was achieved in46.3% and 56.7% of patients receiving IFX 5 and 10 mg/kg, respectively, vs 30.1% ofplacebo-treated patients (p=0.009 and p<0.001). The proportion of patients who wereable to discontinue corticosteroids while in clinical remission at wk 30 was significantlygreater in both IFX groups compared with the placebo group (18.3%, 5 mg/kg; 27.3%,10 mg/kg; 3.3%, placebo; p<0.001 and p=0.010, respectively). IFX was generally welltolerated with a safety profile similar to that previously reported.Conclusion: In patients with moderate-to-severe UC, IFX induces and maintains clinicalresponse, clinical remission and mucosal healing, and permits the tapering ofcorticosteroids while maintaining remission.
  • 55. DDW Abstract 489 - Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-74Disclosures: NoneRemission-Induction and Steroid-Sparing Efficacy By OralTacrolimus (FK506) Therapy Against Refractory UlcerativeColitisAuthors: H. Ogata, T. Matsui, M. Nakamura , M. Iida, M. Takazoe, Y. Suzuki, T. HibiBACKGROUND: The effectiveness of immunosuppressive therapy with oral tacrolimus(FK506) for patients with refractory ulcerative colitis (UC) is not known except for pilotstudies. AIMS: We conducted a randomized, placebo-controlled, double-blind study todetermine the effective trough level, the efficacy and safety of oral tacrolimus therapyfollowed by an open-labeled trial subsequently performed to moderate/severe, refractoryactive UC. SUBJECTS and METHODS: Sixty patients with refractory UC were enrolledand randomized into either a placebo (PLC), low or high trough groups (LTG and HTGrespectively) for a two-week treatment period. Patients in LTG and HTG were dose-adjusted with the levels of 5-10 ng/mL and 10-15 ng/mL respectively. Patients wereevaluated with the response rate of Disease Activity Index (DAI) Score. The open-labeled trial was subsequently performed, and all patients were dose-adjusted with thelevels of 5-15ng/mL. The DAI was re-evaluated and the doses of prednisolone werealso calculated at 10 weeks after open-labeled trial started. RESULTS: Trough levelswere well-controlled within their respective target levels under double-blind conditions.At 2 weeks after study entry, the response rates were 13/19 (68.4%) in HTG, 8/21(38.1%) in LTG and 2/20 (10%) in PLC. Thus the HTG showed a significantimprovement compared with PLC (P<0.001). All evaluation parameters (stool frequency,rectal bleeding, endoscopic findings and physicians global impression) weresignificantly improved in HTG compared with those in PLC or respective pre-values. Theincidence of side effects, which consisted of minor side effects such as shaking offingers and decreases in serum magnesium, in HTG was significantly higher than that inPLC. In the open-labeled trial, the response rate in former LTG and PLC wassignificantly improved (50.0% and 57.9%, respectively) including “CompleteResponders”. Furthermore the mean doses of prednisolone were significantly decreased(7.8mg/day) compared with those in the study entry (19.7mg/day). CONCLUSION:Blood trough levels of tacrolimus by oral administration could be well-controlled, the highpotency and rapid onset of oral tacrolimus therapy were demonstrated, and the steroid-tapering effect was also observed. Those results suggest that the oral administration oftacrolimus represents a safe and effective treatment option for patients withmoderate/severe refractory active UC.
  • 56. DDW Abstract S1349- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-198Disclosures: NoneTacrolimus (FK506) Rescue Therapy Is Safe and Effective in PatientsWith Severe and Refractory Inflammatory Bowel Disease – a LongTerm Follow-UpD. Baumgart, M.D., J.P. Pintoffl, A. Sturm, B. Wiedenmann, A.U. DignassBACKGROUND: Tacrolimus, a macrolide immunosuppressant inhibiting T cellactivation, is currently approved for the prophylaxis of organ rejection in patientsreceiving allogeneic liver or kidney transplants. We have recently reported its low doseoral use in refractory inflammatory bowel disease (IBD). Here we report the outcome ofa long term follow-up of 48 patients.METHODS: In this retrospective, observational single center study the charts of 48 (22female, 26 male) adult (mean age: 41±13.1 SD years) IBD patients with steroid-dependent (n=16) or steroid-refractory (n=32) inflammatory bowel disease (Crohn’sdisease, n=10; ulcerative colitis, n=36; pouchitis, n=2) were reviewed. Tacrolimus (0.1mg/kg body weight per day) was administered orally in 46 patients and initiallyintravenously in 2 patients (0.01 mg/kg body weight per day), aiming for serum troughlevels of 4–8 ng/mL. 37 of 48 (77.1%) patients were receiving concomitant azathioprine.No PCP prophylaxis was administered. The mean treatment duration was 24±4.7 SDmonths (range, 0.6–161 months). Patients were followed-up for a mean of 37±4.3 SDmonths (range, 2–161 months). Response was evaluated using a modified clinicalactivity index (M-CAI). Colectomy free survival was calculated using the Kaplan-Meierand Cox regression models.RESULTS: 44 patients (91.6%) experienced a clinical and laboratory response and 27(56.2%) went into remission. Mean M-CAI values dropped from 13.5 at initiation to 2.7 at42 months follow-up. Eight ulcerative colitis patients (16.7%) underwent colectomybetween 2 and 41.3 months after tacrolimus initiation. Mean overall colectomy freesurvival was 119.9±12.3 SE months (limited to 166.3 months). Cumulative colectomyfree survival was estimated at 0.6976±0.093 SE (see also chart). Steroids were reducedor discontinued in 36 of 40 patients (90%) taking steroids. Side-effects included atemporary rise of creatinine (n=4, 8.3%), tremor or paresthesias (n=4, 8.3%),hyperkalemia (n=1, 2.08%), hypertension (n=1, 2.08%) and an opportunistic infection(n=2, 4.17%).CONCLUSION: Oral low dose tacrolimus is safe and effective in refractory inflammatorybowel disease. Large randomized, controlled trials are warranted to further evaluate itsrole in the management of IBD.
  • 57. DDW Abstract W1048- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-583Disclosures: NoneLong-Term Outcome Of Treatment With Tacrolimus Therapy inPatients With Inflammatory Bowel Disease.H. Nakase, H. Tamaki, S. Inoue, M. Matsuura, N. Uza, S. Ueno, A. Nishio, T. ChibaBackground: Tacrolimus has been shown to be effective in the treatment ofinflammatory bowel disease (IBD). However, it remains unclear whether long termadministration of tacrolimus to patients with IBD is effective and safe. Aim: To evaluatethe efficacy and safety of long term administration of tacrolimus in patients withulcerative colitis (UC) and Crohn’s disease (CD). Patients and Methods: Fourteenactive CD patients ( 2 ileum, 10 ileum and colon, 2 colon ) who were refractory toconventional therapy (antibiotics, azathioprine, and infliximab) and 12 UC patients whowere unable to taper off steroids, were enrolled in a prospective, uncontrolled, open-label study. Initially, tacrolimus was administered orally to aim for serum trough level of10~15ng/ml. After patients achieved their clinical remission, tacrolimus was tapered tothe serum trough level 5~10ng/ml. In CD patients, clinical improvement (decrease inCDAI of>/=70), and clinical remission (CDAI</=150) were assessed after treatment. InUC patients, UCAI was assessed as well. The treatment duration in CD and UC was 12months and 11 months, respectively. Results: In CD patients, mean CDAI at study entrywas 320; and mean dose of prednisolone (PSL) was 18mg. After 6wk of treatment, 12patients (86%) achieved clinical improvement off steroid and 7 patients (50%) went intoremission. After 16wk of treatment, 11 patients (78.5%) were still in clinical improvementand 8 patients (57%) went into remission. Overall, after 1 year, 10 patients (71%) wentinto remission and 4 patients had relapse, who were treated by the combination oftacrolimus and infliximab, thereafter. In UC patients, mean UCAI at study entry was9.5±1.0; mean dose of PSL was 28mg. After starting tacrolimus, all patients coulddiscontinue taking steroid. The mean UCAI was 3.2±0.6, 2.1±0.8, and 3.4±1.5 after2wks, 12wks, and 24wks, respectively. Seven patients (58.3%) were still in remissionafter 11months of treatment. Four of 5 patients (41.7%) who had relapsed, receivedcolectomy. The remaining one got clinical remission with leukocytapheresis therapy.Among UC and CD patients, two patients (7.6%) experienced the increase of serumcreatinine level, but this side effect was managed with dose reduction. Conclusion:Long term use of tacrolimus is effective and safe for refractory IBD patients by carefullycontrolling its trough level. Randamized studies are required to compare tacrolimus with6-MP in terms of efficacy and safety.
  • 58. DDW Abstract 493- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-75Disclosures: Organization - Protein Design Laboratories, Relationship - Grant /Research SupportA Phase I-Ii Study: Multiple Dose Levels Of Visilizumab Are WellTolerated and Produce Rapid and Sustained Improvement inUlcerative Colitis Patients Refractory To Treatment With Iv Steroids(ivsr-Uc).S.R. Targan, MD, B.A. Salzberg, MD, L. Mayer, MD, D. Hommes, MD, S. Hanauer,MD, U. Mahadevan, MD, W. Reinisch, MD, S.E. Plevy, MD, A.U. Dignass, MD, G.Van Assche, MD, A. Buchman, MD, G. Mechkov, MD, Z. Krastev, MD, J.N. LowderPurpose: An earlier Phase I study of visilizumab, a humanized anti-CD3 antibody, inIVSR-UC patients, showed tolerability and clinical activity of 10 or 15µg/kg dosesadministered on the first 2 consecutive days. The current open-label study was designedto evaluate the safety and determine the optimal clinical dose of visilizumab in a largernumber of IVSR-UC patients. Methods: Patients with undetectable whole blood copiesof EBV (EBVc/mL) were randomized to 5, 7.5, 10 or 12.5 µg/kg doses of visilizumab.Patients with detectable EBVc/mL (< 5000 copies/mL) were dose escalated through thedose levels. Efficacy was assessed with a Modified Truelove-Witts’ Severity Index(MTWSI); response defined as an index of < 10. Results: To date, a total of 53 (34 EBV-and 19 EBV+) patients have been enrolled. The mean baseline MTWSI was EBV-,12.6,and EBV+, 12.9. The majority of treatment-related AEs (in decreasing order offrequency) included general disorders, GI, nervous system, respiratory, musculoskeletal/connective tissue, skin, and psychiatric disorders. Mild to moderate cytokine releasesyndrome, unrelated to dose, occurred in the majority of patients. The 15 serious AEswere neither dose-dependent nor considered related to study medication. The incidenceof serious infectious disorders was < 1%. No lymphoproliferative, malignant or life-threatening AEs were reported. Anti-visilizumab antibodies, the majority of which wereneutralizing antibodies, occurred in 32% of patients. Decreases in MTWSI generallyoccurred by Day 8 and were maintained in many patients up to Day 90. At Day 30 therewas no apparent dose-effect in mean difference from baseline in MTWSI. Percent of IVSR-UC Patients with MTWSI < 10 (n=number of patients) Tx Day 8 15 22 30 EBV-/+ - + - + - + - + % 61.8 68.4 58.8 63.2 61.8 63.2 67.6 63.2There was no apparent increase in the incidence of infection in EBV+ patients ordifference in clinical response. Complete results from Days 60 and 90 will be madeavailable. Conclusion: All visilizumab doses studied were well tolerated and produced arapid and sustained improvement in a majority of IVSR-UC patients.
  • 59. Genetik und Immunologie R. DuchmannBlood. 2004 Aug 1;104(3):895-903. Epub 2004 Apr 15.Large-scale in vitro expansion of polyclonal human CD4(+)CD25highregulatory T cells.Hoffmann P, Eder R, Kunz-Schughart LA, Andreesen R, Edinger M.Department of Hematology and Oncology, University Hospital Regensburg,Regensburg, Germany.CD4(+)CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance,and their adoptive transfer gives protection from autoimmune diseases and pathogenicalloresponses after solid organ or bone marrow transplantation in murine modelsystems. In vitro, human CD4(+)CD25+ Treg cells display phenotypic and functionalcharacteristics similar to those of murine CD4(+)CD25+ Treg cells: namely,hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- Tcells. Thus far, the detailed characterization and potential clinical application of humanCD4(+)CD25+ Treg cells have been hampered by their paucity in peripheral blood andthe lack of appropriate expansion protocols. Here we describe the up to 40 000-foldexpansion of highly purified human CD4(+)CD25high T cells in vitro through the use ofartificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in thepresence of high-dose interleukin 2 (IL-2). Expanded CD4(+)CD25high T cells werepolyclonal, maintained their phenotype, exceeded the suppressive activity of freshlyisolated CD4(+)CD25high T cells, and maintained expression of the lymph node homingreceptors L-selectin (CD62L) and CCR7. The ability to rapidly expand humanCD4(+)CD25high Treg cells on a large scale will not only facilitate their furtherexploration but also accelerate their potential clinical application in T cell-mediateddiseases and transplantation medicine.
  • 60. Nat Genet. 2004 May;36(5):471-5. Epub 2004 Apr 11Functional variants of OCTN cation transporter genes are associatedwith Crohn disease.Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, Newman B, VanOene M, Cescon D, Greenberg G, Griffiths AM, St George-Hyslop PH, SiminovitchKA.Department of Medicine, University of Toronto, and Department of Immunology, MountSinai Hospital Samuel Lunenfeld Research Institute, Ontario, Canada.Crohn disease is a chronic, inflammatory disease of the gastrointestinal tract. A locus ofapproximately 250 kb at 5q31 (IBD5) was previously associated with susceptibility toCrohn disease, as indicated by increased prevalence of a risk haplotype of 11 single-nucleotide polymorphisms among individuals with Crohn disease, but the pathogeniclesion in the region has not yet been identified. We report here that two variants in theorganic cation transporter cluster at 5q31 (a missense substitution in SLC22A4 and aG-->C transversion in the SLC22A5 promoter) form a haplotype associated withsusceptibility to Crohn disease. These variants alter transcription and transporterfunctions of the organic cation transporters and interact with variants in another geneassociated with Crohn disease, CARD15, to increase risk of Crohn disease. Theseresults suggest that SLC22A4, SLC22A5 and CARD15 act in a common pathogenicpathway to cause Crohn disease.
  • 61. Gastroenterology. 2005 Feb;128(2):260-9.A risk haplotype in the Solute Carrier Family 22A4/22A5 gene clusterinfluences phenotypic expression of Crohns disease.Newman B, Gu X, Wintle R, Cescon D, Yazdanpanah M, Liu X, Peltekova V, VanOene M, Amos CI, Siminovitch KA.Department of Medicine, University of Toronto, Toronto, Ontario, Canada.BACKGROUND AND AIMS: Previously, we identified 2 functionally relevantpolymorphisms in the SLC22A4 / 22A5 genes at the IBD5 locus that alter gene/proteinfunction and comprise a 2-allele haplotype ( SLC22A -TC) associated with increased riskfor Crohns disease (CD). Here we examine the contribution of this susceptibilityhaplotype alone and in combination with CARD15 variants to CD subphenotypes and tosusceptibility to ulcerative colitis (UC). METHODS: Phenotype-genotype associationswere evaluated in a Canadian cohort including 507 patients with CD, 216 patients withUC, and 352 ethnically matched controls genotyped for SLC22A4 C1672T, SLC22A5G-207C, and the major CD-associated CARD15 variants. RESULTS: The SLC22A -TChaplotype was strongly associated ( P < .0001) with CD in the non-Jewish subgroup ofthis cohort, and the combination of SLC22A -TC homozygosity and one or more of thecommon CARD15 disease susceptibility alleles engendered a 7.5-fold increase in riskfor CD ( P = 9 x 10 -8 ) and a 4.5-fold increase in risk for ileal disease ( P = .001). Therisk haplotype showed only a suggestive association with CD in the Jewish subgroupand no association with UC in the cohort or in subgroups stratified by CARD15genotypes. CONCLUSIONS: The SLC22A -TC haplotype acts together with CARD15disease susceptibility alleles to increase risk for CD and ileal disease among CDpatients but does not contribute to risk for UC in this Canadian cohort. The associationof the SLC22A -TC haplotype and CARD15 alleles with ileal disease suggests that thesevariants have biologically intertwined effects in the pathogenesis of CD
  • 62. Gastroenterology. 2005 May;128(5):1219-28.Recombinant Probiotics for Treatment and Prevention ofEnterotoxigenic Escherichia coli Diarrhea.Paton AW, Jennings MP, Morona R, Wang H, Focareta A, Roddam LF, Paton JC.Background & Aims: We have developed a therapeutic strategy for gastrointestinalinfections that is based on molecular mimicry of host receptors for bacterial toxins on thesurface of harmless gut bacteria. The aim of this study was to apply this to thedevelopment of a recombinant probiotic for treatment and prevention of diarrhealdisease caused by enterotoxigenic Escherichia coli strains that produce heat-labileenterotoxin. Methods: This was achieved by expressing glycosyltransferase genes fromNeisseria meningitidis or Campylobacter jejuni in a harmless Escherichia coli strain(CWG308), resulting in the production of a chimeric lipopolysaccharide capable ofbinding heat-labile enterotoxin with high avidity. Results: The strongest heat-labileenterotoxin binding was achieved with a construct (CWG308:pLNT) that expresses amimic of lacto- N -neotetraose, which neutralized >/=93.8% of the heat-labile enterotoxinactivity in culture lysates of diverse enterotoxigenic Escherichia coli strains of bothhuman and porcine origin. When tested with purified heat-labile enterotoxin, it wascapable of adsorbing approximately 5% of its own weight of toxin. Weaker toxinneutralization was achieved with a construct that mimicked the ganglioside GM2.Preabsorption with, or coadministration of, CWG308:pLNT also resulted in significant invivo protection from heat-labile enterotoxin-induced fluid secretion in rabbit ligated ilealloops. Conclusions: Toxin-binding probiotics such as those described here haveconsiderable potential for prophylaxis and treatment of enterotoxigenic Escherichia coli -induced travelers diarrhea.
  • 63. Nat Immunol. 2004 Aug;5(8):800-8. Epub 2004 Jun 27NOD2 is a negative regulator of Toll-like receptor 2-mediated T helpertype 1 responses.Watanabe T, Kitani A, Murray PJ, Strober W.Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergyand Infectious Diseases, National Institutes of Health, Building 10 Room 11N238, 10Center Drive, Bethesda, Maryland 20892, USA.The mechanism by which mutations in CARD15, which encodes nucleotide-bindingoligomerization domain 2 (NOD2), cause Crohn disease is poorly understood. Becausesignaling via mutated NOD2 proteins leads to defective activation of the transcriptionfactor NF-kappa B, one proposal is that mutations cause deficient NF-kappa B-dependent T helper type 1 (T(H)1) responses and increased susceptibility to infection.However, this idea is inconsistent with the increased T(H)1 responses characteristic ofCrohn disease. Here we used Card15(-/-) mice to show that intact NOD2 signalinginhibited Toll-like receptor 2-driven activation of NF-kappa B, particularly of the NF-kappa B subunit c-Rel. Moreover, NOD2 deficiency or the presence of a Crohn disease-like Card15 mutation increased Toll-like receptor 2-mediated activation of NF-kappa B-c-Rel, and T(H)1 responses were enhanced. Thus, CARD15 mutations may lead todisease by causing excessive T(H)1 responses.
  • 64. Pankreatitis / ERCP-Themen S. Faiss1. OriginalarbeitenGastrointest Endosc. 2005 Mar;61(3):407-15.High-dose allopurinol for prevention of post-ERCP pancreatitis: aprospective randomized double-blind controlled trial.Katsinelos P, Kountouras J, Chatzis J, Christodoulou K, Paroutoglou G, MimidisK, Beltsis A, Zavos C.Department of Endoscopy and Motility Unit, Central Hospital, Thessaloniki, Greece.BACKGROUND: Pancreatitis is the most common major complication of diagnostic andtherapeutic ERCP. Allopurinol, a xanthine oxidase inhibitor that blocks generation ofoxygen-derived free radicals, potentially may prevent post-ERCP pancreatitis. This studyassessed the efficacy of high-dose oral allopurinol for prevention of post-ERCPpancreatitis. METHODS: A prospective, double-blind, placebo-controlled trial wasconducted in 250 patients undergoing ERCP. Patients were randomized to receiveallopurinol (600 mg) or placebo orally at 15 and 3 hours before the procedure. Patientswere clinically evaluated, and serum amylase levels were determined before ERCP andat 6 and 24 hours thereafter. Standardized criteria were used to diagnose and to gradethe severity of post-ERCP pancreatitis. RESULTS: A total of 243 patients were includedin the analysis. The two groups were similar with regard to age; gender; underlyingdisease; indication for treatment; ERCP findings; and type of treatment, except for biliarysphincterotomy. Only 43 patients in the allopurinol group underwent biliarysphincterotomy vs. 87 in the placebo group ( p < 0.001). The frequency of acutepancreatitis was significantly lower in the allopurinol vs. the placebo group in the finalmultinomial regression analysis: allopurinol group, 4/125 (3.2%), with all 4 cases gradedas mild, vs. placebo group, 21/118 (17.8%), of which 8/118 (6.8%) were graded as mild,11/118 (9.3%) as moderate, and 2/118 (1.6%) as severe with fatal outcome ( p < 0.001).The protective effect of allopurinol was also apparent in the diagnostic ERCP and thebiliary sphincterotomy subgroups when the frequency of post-ERCP pancreatitis wasanalyzed after stratification by procedure. The mean duration of hospitalization forpancreatitis was significantly shorter in the allopurinol compared with the placebo group(2.5 vs. 5.67 days; p < 0.001). CONCLUSIONS: Pretreatment with high-dose, orallyadministered allopurinol decreases the frequency of post-ERCP pancreatitis. Despitethe promising results of this prospective, randomized trial, further studies are needed toverify these observations before allopurinol can be recommended for routine clinicaluse.
  • 65. 2. DDW-AbstractsDDW Abstract 557-Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB100Does Prophylactic Allopurinol Administration Reduce the Risk andSeverity of Post-ERCP Pancreatitis: Randomized ProspectiveMulticenter StudyStuart Sherman ; Patrick Mosler ; Jeffrey Marks ; James L Watkins ; Joseph EGeenen ; Priya Jamidar ; Evan L Fogel ; Laura Lazzell-Pannell ; Mhamed Temkit ;Paul Tarnasky ; James Frakes ; Arif Aziz ; Pramod Malik ; Nicholas Nickl ; AdamSlivka ; John Goff ; Glen A. LehmanBACKGROUND: Pancreatitis is the most common major complication of ERCPoccurring in up to 30% of high-risk patients. Efforts have been made to identifypharmacological agents capable of reducing its incidence and severity. Numerous drugshave been evaluated during the last 30 years, but only a few have shown any potentialefficacy, including somatostatin, gabexate mesilate, glyceryl trinitrate and diclofenac.The aim of this randomized, prospective, double-blind, multicenter trial was to determinewhether prophylactic allopurinol, an inhibitior of oxygen-derived free radical production,would reduce the frequency and severity of post-ERCP pancreatitis.METHODS: 701 patients were randomized to receive either allopurinol or placebo 4hours and 1 hour prior to ERCP. A database was prospectively collected by a definedprotocol on patients undergoing ERCP. Standardized criteria were used to diagnose andgrade the severity of post-procedure pancreatitis (GI Endosc 1991; 37:383).RESULTS: The groups were similar with regard to patient demographics and patientand procedure risk factors for pancreatitis. The overall incidence of pancreatitis was12.55%. It occurred in 46 of 355 patients in the allopurinol group (12.96%), and in 42 of346 patients in the control group (12.14%; p=0.52). The pancreatitis was graded mild in7.89%, moderate in 4.51% and severe in 0.56% of the allopurinol group and mild in6.94%, moderate in 4.62% and severe in 0.58% of the control group. There was nosignificant difference between the groups in the frequency or severity of pancreatitis.The study had at least a 90% power of detecting a true difference of 7% in post-ERCP-pancreatitis incidence between placebo (12%) and allopurinol treatment (5%).CONCLUSION: Prophylactic oral allopurinol did not reduce the frequency or severity ofpost-ERCP pancreatitis. These results are in agreement with other smaller clinicalstudies, which did not show any benefit of allopurinol. Therefore, allopurinol cannot berecommended for post-ERCP pancreatitis prevention. Future studies evaluating theefficacy of low cost, safe, easy to administer agents aimed at prevention of post-ERCPpancreatitis are warranted. This study was supported by an ADHF/ASGE EndoscopicResearch and Outcomes and Effectiveness Award.
  • 66. DDW-Abstract T1217- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB195Allopurinol to Prevent Post-ERCP Pancreatitis: Blind Interim Analysisof a Randomized Placebo-Controlled TrialJoseph Romagnuolo ; Gurpal Sandha ; Caroline Kruger ; Gary May ; Marty Cole ;Syd Bass ; Eoin Lalor ; Vince Bain ; John McKaigney ; Richard FedorakBackground: Although ERCP is extremely useful in the management of biliopancreaticdisease, it is associated with a risk of post-ERCP pancreatitis (PEP). Animal studiessuggest that allopurinol (xanthine oxidase inhibitor with high oral bioavailability and long-lasting active metabolites) may reduce PEP via decreased oxygen radicals. Arandomized pilot was promising.Aim: To determine if allopurinol decreases the rate of PEP.Methods: Patients referred for ERCP at 2 tertiary centers were randomized toallopurinol 300 mg or identical placebo orally 60 min (+/-20) prior to ERCP.Randomization used computer-generated random numbers and blocking by center andby high-risk (manometry, pancreatic therapy) ERCP. Demographics, indications andother potential confounders were recorded. The primary outcome (PEP) wasdefined/graded according to a modified (incl. those seeking medical attention but notadmitted (“ultra-mild”)) Cotton consensus definition. Patients were contacted at 48 hand 30 days. Secondary outcomes included severe PEP, length of stay, days lost fromusual activities, and mortality. PEP rates in each group were compared with Chi-square.Planned interim analysis was performed at 18 mos, blinded by treatment allocation(group A vs. B). Stochastic curtailment analysis (SCA) was performed to assess yield offurther recruitment.Results: The interim analysis included 220 patients (112 A, 108 B); mean age 55 yrs(SD 18). The mean procedure time was 50 min (SD 35); 59% had biliarysphincterotomy; 40% had a pancreatic injection; 20% had stones removed; 19%received a biliary stent; 5.9% a pancreatic stent. The PEP rates were 9.3% (A) and 8.9%(B) (p=0.9; dif=0.4% [95%CI: -7.3% to 7.9%]. For the non-high risk subgroup (n=198),the rates were 5.2% and 7.9% (NS). There was no difference in severe PEP overall (1vs 2 patients; p=0.6), nor in any subgroups. The 2 SCAs, assuming subsequentrecruitment at either 1) the same PEP rates as the sample size calculation (7%, 3.5%),or 2) the anticipated relative risk, but the observed baseline PEP rate, both indicatedthat a statistically significant result could still be achieved with target enrolment (p=0.04,p=0.004, respectively). External monitoring committee felt the study should proceed.Conclusion: The interim (blind) analysis shows no reason for early trial termination.The 95%CI for the PEP rate difference remains wide, and to date, allopurinol does notappear to significantly affect PEP rates.
  • 67. DDW Abstract T1198- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB190The Incidence of Pancreatitis After ERCP/Manometry Has Fallen withthe Increasing Use of Temporary Pancreatic Stents Experience of 2861Patients Over 10 YearsPeter Cotton ; Patrick D Mauldin ; Joseph Romagnuolo ; Robert H HawesThere is increasing evidence that temporary pancreatic stenting reduces the incidenceof post-ERCP pancreatitis (PEP) in patients at increased risk, such as those undergoingsphincter manometry. We have analysed the use of pancreatic stents and thepancreatitis rates for patients having manometry in our unit. Data were derived from theGITrac database, into which all procedures and their outcomes have been enteredprospectively. Pancreatitis (and severity levels) was defined by established consensuscriteria.Over a period of 10 years, 2861 patients underwent biliary and/or pancreaticmanometry. Most underwent both, as well as sphincteromy based on the results. Theoverall rate of PEP in 1481 patients without stents was 8.1%, which was significantlyhigher (p=0.002) than the incidence (5.3%; 95% CI: 4.2–6.6%) in 1380 patients withstents. The odds ratio for PEP with stents was 0.63 (95% CI: 0.5-0.9). There was atrend to more episodes of moderate and severe pancreatitis in patients without stents(2.0%), compared to 1.3% in those with stents (p=NS). The progressive increase in theproportion of patients receiving stents correlated (Pearson coefficient -0.840) with aprogressive decrease in the rate of pancreatitis (figure). The data were comparable inthe 1790 patients who had not undergone prior endoscopic treatments. There were only6 episodes (3.7%) of PEP in 162 cases undergoing manometry during the first 6 monthsof 2004.Conclusion. These data confirm that sphincter manometry can be performed with a lowrisk of pancreatitis, using temporary pancreatic stents.
  • 68. DDW Abstract T1219- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB195Reduction of the Risk of Post-ERCP Acute Pancreatitis byProphylactic Pancreatic StentCarmelo Sciume ; Girolamo Geraci ; Franco Pisello ; Tiziana Facella ; GiuseppeModicaBackground: It is well known the high incidence variability of post-ERCP acutepancreatitis (1-40%), which may depend not only for the different definition of post-ERCP acute pancreatitis but also for different patients and procedures related factorsacting synergistically. Impaired drainage of pancreatic juice after ERCP is the mostrelevant cause of post- ERCP acute pancreatitis. To evaluate the potential reduction ofthe incidence of ERCP-related acute pancreatitis, we used a prophylatic Wirsungstenting in high risk patients (SOD, difficult cannulation, reiterate Wirsung cannulation).Materials and methods: 97 patients (14.1% of all 686 ERCP performed at the Service ofDigestive Endoscopy, Section of General and Thoracic Surgery, Policlinico, University ofPalermo) observed between 2000 and 2003, were randomized into Group A (56patients) treated with “free-hand” pre-cut papillotomy and Group B (41 patients) with pre-cut papillotomy after pancreatic stent The results were prospectically analyzed. Stentswere selected according to morphological Wirsung parameters. Stents were removedafter 7-10 days.Results: In our study, the difference between incidence of post-ERCP acute pancreatitisin the Group A (17.8%) was found dramatically different with respect to Group B (2.5%),(p < 0.05).Conclusions: in our experience, the use of a temporary and prophylactic pancreatic stentsignificantly decreases the incidence of post-ERCP acute pancreatitis in high riskpatients, as well as failed biliary and reiterate Wirsung cannulations and aftersphincterotomy in SOD.
  • 69. DDW Abstract T1222- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB196A Prospective Comparative Stent Study for Prophylaxis of Post ERCPPancreatitis: Comparison of 5 Fr Straight Stent vs 3 FR Pigtail StentMiriam Thomas ; Marc F. Catalano ; Joseph E. GeenenPancreatitis is the most frequent ERCP complication and pancreatic stenting is aneffective method to prevent this complication particularly, in high risk pts. AIM: 1. Tocompare frequency of post ERCP pancreatitis in high-risk pts after placement of either amodified 5Fr straight ST versus a 3Fr pigtail ST. 2. To compare ST efficacy and safetyand determine the rate of spontaneous outward migration of these ST. METHODS: 38pts undergoing ERCP with high risk factors for developing post ERCP pancreatitis(SOD-12, ARP-13, abd pain-13 pts) were enrolled in this randomized, prospective,blinded study over a period of 1-yr with placement of 3Fr pigtail (15 pts) or 5Fr modified(no internal flap) (23 pts) straight ST. Pts had baseline amylase level drawn prior to aswell as 6 & 24 hrs after procedure. Post ERCP pancreatitis was determined clinically &with enzyme levels >3ULN. Abd radiograph was obtained at 24-hrs & 7 days post ERCPto determine ST position. Pain scores from a scale of 1 to 10 were assessed pre ERCPat 6hrs, 24-hrs and 1 wk post ERCP. Phone contact was made at 24-hrs & 1 wk after theprocedure to assess the clinical condition of the pt. 7 pts underwent repeat ERCP afterST placement & pancreatograms were compared. RESULTS: Post ERCP pancreatitisrate with 3F & 5F ST were 33.3% (5/15) and 17.4% (4/23 pts) respectively (p= 0.26).Mild post ERCP pancreatitis with 3F & 5F ST was 60% (3/5) & 75% (3/4) while that ofmoderate pancreatitis was 40% (2/5) & 25% (1/4 pts) (p= 1.0) respectively.Spontaneous ST dislodgement at 24-hrs occurred in 7/13 pts with 3 Fr ST (53.8%)compared to 12/23 pts (52.2%) with 5Fr ST (p= 0.92). There was no significantdifference between the rate of pancreatitis and ST dislodgment at 24-hrs. No pt requiredrepeat procedures for ST removal as all spontaneously passed within a wk. Among ptswho underwent repeat ERCP none had duct changes or complications attributable to STplacement. CONCLUSIONS: Post ERCP pancreatitis rate seemed to be lower withmodified straight 5Fr ST. However, there was no significance when compared with thepigtail 3Fr ST. None of these patients needed repeat endoscopy for ST removal norwere there any ST induced duct changes in those who had repeat pancreatogram. Pancreatitis rate Mild panc Mod panc Spont dislodge at 24 hrs ST diameter 3 Fr 5/15 (33.3%) 3/5 (60%) 2/5 (40%) 7/13 (53.8%) 5 Fr 4/23 (17.4%) 3/4 (75%) 1/4 (25%) 12/23 (52.2%)
  • 70. DDW-Abstract 554- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB99Endoscopic Versus Surgical Drainage of the Pancreatic Duct inChronic Pancreatitis: A Prospective Randomised TrialDjuna L. Cahen ; Dirk J. Gouma ; Yung Nio ; Myriam Delhaye ; Erik A.J. Rauws ;Marja A. Boermeester ; Olivier R. Busch ; Jaap Stoker ; Johan S. Laméris ; MarcelG.W. Dijkgraaf ; Kees Huibregtse ; Jacques Devière ; Marco J. BrunoObjectives: Increased pancreatic pressure due to ductal outflow obstruction isconsidered to be one of the mechanisms of intractable pain in patients with chronicpancreatitis (CP). In symptomatic patients with a dilated pancreatic duct (PD), ductaldecompression is therefore advocated. The aim of this prospective randomised trial wasto provide a direct comparison between endoscopic and surgical drainage of the PD.Methods: All symptomatic CP patients presented at the Academic Medical Hospital witha dominant obstruction of the PD (due to strictures and/or stones), without aninflammatory mass (size pancreatic head < 4 cm), were eligible for this study. Patientswere randomised between endoscopic drainage by temporary stent insertion (precededby extracorporeal shock wave lithotripsy (ESWL) in Brussels if indicated) and surgicaldrainage by pancreaticojejunostomy. Follow-up data were obtained during 2 years byscheduled visits to the outpatient clinic. Primary endpoint was the average Izbicki painscore, measured during the 2 years of follow-up. Secondary endpoints were clinicalsuccess rate (> 50 % decrease in pain score), morbidity, mortality and intervention rate.Results: In October 2004 the study was discontinued after an interim analysis revealeda highly significant difference with respect to the primary endpoint. From January 2000,39 patients have been included. In 87 % intraductal stones were present with a meandiameter of 10 mm. 19 patients were treated endoscopically with a median stentduration of 27 weeks (16 of which underwent ESWL) and 20 were operated upon.During a median follow up for both groups of 24 months (range 6-24), the averageIzbicki pain score was significantly less after surgical drainage (51 versus 25, p=0.001).Moreover, pain response after surgery was immediate (within 6 weeks) and consistentduring the follow-up period. Furthermore, clinical success rates were 33 and 75 % forendoscopic and surgical drainage, respectively. One patient taking high dose NSAID’sdied 4 days after ESWL from a perforated duodenal ulcer. Complication rates weresimilar for both groups but endoscopically treated patients underwent more therapeuticinterventions (5 versus 1, p<0.001).Conclusions: In this series of patients with advanced CP, surgical drainage of the PDwas more effective than endoscopic treatment (ESWL and temporary stenting).Moreover, surgery resulted in more rapid pain relief and required significantly lessinterventions.
  • 71. IBS H. Mönnikes1. OriginalarbeitenGastroenterology. 2004 Jun;126(7):1657-64.Molecular defects in mucosal serotonin content and decreasedserotonin reuptake transporter in ulcerative colitis and irritable bowelsyndrome.Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, CrowellMD, Sharkey KA, Gershon MD, Mawe GM, Moses PL.Department of Anatomy and Neurobiology, University of Vermont College of Medicine,Burlington, VT 05405, USA.BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory,vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerativecolitis (UC) and irritable bowel syndrome (IBS) are both associated with clinicalsymptoms that include alterations in the normal patterns of motility, secretion, andsensation. Our aim was to test whether enteric 5-HT signaling is defective in thesedisorders. METHODS: Rectal biopsy specimens were obtained from healthy controlsand patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Keyelements of 5-HT signaling, including measures of 5-HT content, release, and reuptake,were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1messenger RNA, serotonin transporter messenger RNA, and serotonin transporterimmunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. Theenterochromaffin cell population was decreased in severe UC samples but wasunchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal andmechanical stimulation conditions, no changes were detected in any of the groupsrelative to controls. CONCLUSIONS: These data show that UC and IBS are associatedwith similar molecular changes in serotonergic signaling mechanisms. While UC and IBShave distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findingsrepresent the first demonstration of significant molecular alterations specific to the gut inpatients with IBS and support the assertion that disordered gastrointestinal function inIBS involves changes intrinsic to the bowel.
  • 72. Gastroenterology 2005 Mar;128(3):541-51.Lactobacillus and bifidobacterium in irritable bowel syndrome:symptom responses and relationship to cytokine profiles.OMahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, OSullivan GC, Kiely B,Collins JK, Shanahan F, Quigley EM.Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.BACKGROUND & AIMS: The aim of this study was to compare the response ofsymptoms and cytokine ratios in irritable bowel syndrome (IBS) with ingestion ofprobiotic preparations containing a lactobacillus or bifidobacterium strain. METHODS:Seventy-seven subjects with IBS were randomized to receive either Lactobacillussalivarius UCC4331 or Bifidobacterium infantis 35624, each in a dose of 1 x 10 10 livebacterial cells in a malted milk drink, or the malted milk drink alone as placebo for 8weeks. The cardinal symptoms of IBS were recorded on a daily basis and assessedeach week. Quality of life assessment, stool microbiologic studies, and blood samplingfor estimation of peripheral blood mononuclear cell release of the cytokines interleukin(IL)-10 and IL-12 were performed at the beginning and at the end of the treatmentphase. RESULTS: For all symptoms, with the exception of bowel movement frequencyand consistency, those randomized to B infantis 35624 experienced a greater reductionin symptom scores; composite and individual scores for abdominal pain/discomfort,bloating/distention, and bowel movement difficulty were significantly lower than forplacebo for those randomized to B infantis 35624 for most weeks of the treatmentphase. At baseline, patients with IBS demonstrated an abnormal IL-10/IL-12 ratio,indicative of a proinflammatory, Th-1 state. This ratio was normalized by B infantis35624 feeding alone. CONCLUSIONS: B infantis 35624 alleviates symptoms in IBS; thissymptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine, suggesting an immune-modulating role forthis organism, in this disorder.
  • 73. Gut. 2005 May;54(5):601-7.Amitriptyline reduces rectal pain related activation of the anteriorcingulate cortex in patients with irritable bowel syndrome.Morgan V, Pickens D, Gautam S, Kessler R, Mertz H.Department of Radiology and Radiological Scienes, Vanderbilt University, Nashville, TN37205, USA.BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is a disorder of intestinalhypersensitivity and altered motility, exacerbated by stress. Functional magneticresonance imaging (fMRI) during painful rectal distension in IBS has demonstratedgreater activation of the anterior cingulate cortex (ACC), an area relevant to pain andemotions. Tricyclic antidepressants are effective for IBS. The aim of this study was todetermine if low dose amitriptyline reduces ACC activation during painful rectaldistension in IBS to confer clinical benefits. Secondary aims were to identify other brainregions altered by amitriptyline, and to determine if reductions in cerebral activation aregreater during mental stress. METHODS: Nineteen women with painful IBS wererandomised to amitriptyline 50 mg or placebo for one month and then crossed over tothe alternate treatment after washout. Cerebral activation during rectal distension wascompared between placebo and amitriptyline groups by fMRI. Distensions wereperformed alternately during auditory stress and relaxing music. RESULTS: Rectal paininduced significant activation of the perigenual ACC, right insula, and right prefrontalcortex. Amitriptyline was associated with reduced pain related cerebral activations in theperigenual ACC and the left posterior parietal cortex, but only during stress.CONCLUSIONS: The tricyclic antidepressant amitriptyline reduces brain activationduring pain in the perigenual (limbic) anterior cingulated cortex and parietal associationcortex. These reductions are only seen during stress. Amitriptyline is likely to work in thecentral nervous system rather than peripherally to blunt pain and other symptomsexacerbated by stress in IBS.
  • 74. 2. DDW AbstractsDDW Abstract M1206- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-330Disclosures: NoneSymptomatic Overlap Between Irritable Bowel Syndrome andMicroscopic ColitisD. Limsui, D. Pardi, E. Loftus, Jr., P. Kammer, W. Tremaine, M. Camilleri, W.SandbornPurpose: Microscopic colitis is diagnosed by histologic criteria and irritable bowelsyndrome (IBS) is diagnosed by symptom-based criteria. There has been noinvestigation into the overlap in diagnoses of microscopic colitis and IBS. Our aim wasto assess the prevalence of clinical criteria for IBS in a population-based cohort ofpatients with microscopic colitis.Methods: The Rochester Epidemiology Project, a unique medical records linkagesystem providing data on all health care for the defined population of Olmsted County,MN was used to identify all county residents with a diagnosis of microscopic colitisbetween 1/1/85-12/31/01, as previously reported (Pardi, et al. Gastroenterology2004:A124). The medical records of these individuals were reviewed to ascertainsymptoms consistent with Rome, Rome II, and Manning criteria for IBS.Results: 131 cases of microscopic colitis were identified. Median age was 68 (24-95);71% were women. 73 (56%) and 69 (53%) met Rome II and Rome criteria for IBS,respectively. 54 (41%) had three or more Manning criteria. Patients meeting the criteriafor IBS were younger and more likely to be female. 43 (33%) were initially diagnosedwith IBS and later had a change in diagnosis to microscopic colitis. 88 (67%) hadbiopsy proven microscopic colitis during their initial evaluation, prior to consideration of adiagnosis of IBS. If the criteria for duration of symptoms were excluded, 92 (70%) wouldhave met both Rome II and Rome criteria for IBS.Conclusions: In this population-based cohort, approximately half of those withhistologically confirmed microscopic colitis met clinical criteria for the diagnosis of IBS.Women and younger patients more often met clinical criteria for the diagnosis of IBS.The clinical symptom-based criteria for IBS are not specific enough to rule out thediagnosis of microscopic colitis. Therefore, patients with suspected diarrhea-predominate irritable bowel syndrome should undergo random biopsies of the colon toinvestigate for possible microscopic colitis.
  • 75. DDW Abstract 788- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-124Disclosures: NoneThe Impact Of Somatization on the Use Of Gastrointestinal HealthcareResources in Irritable Bowel SyndromeB. Spiegel, F. Kanwal, B. Naliboff, E. MayerBackground: Although it is well documented that patients with irritable bowel syndrome(IBS) consume a disproportionate amount of health care resources compared tomatched controls, the reasons for this disparity are unclear. One possibility is thatresource utilization is partly driven by the presence of comorbid somatization – aprocess marked by multiple unexplained somatic complaints that is highly prevalent inIBS. We sought to determine whether higher levels of somatization are associated withhigher levels of gastrointestinal (GI) resource utilization in IBS.Methods: 1410 patients >18 years with IBS were evaluated at a university-basedreferral center. Subjects completed a symptom questionnaire, the SCL-90 psychometricchecklist, and the SF-36 Health Survey. We measured two outcomes: (1) one-yearaggregated direct GI health care costs (including physician visits and pre-specified tests,procedures, and surgeries) and, (2) one-year cumulative number of gastroenterologyphysician visits. Our primary regressor was somatization as measured by thesomatization subscale of the SCL-90. We first developed a list of hypothesis-drivenpredictors of resource utilization within a conceptual framework, and then performedmultivariate regression analyses to measure the adjusted influence of somatization onGI resource utilization.Results: There was no difference in the adjusted probability of expending versus notexpending any GI health care costs in the previous year in patients with high (+1standard deviation) versus low (-1 standard deviation) somatization (RR=1.02; 95%CI=1.02, 1.03). Similarly, there was no difference in one-year GI physician visitsbetween patients with high versus low somatization (group difference=0.35 visits, 0.33,0.38). However, in the subset of patients expending at least $1.00 in GI costs in theprevious year (47.7% of cohort), there was a significantly higher cost of care for subjectswith high versus low somatization (group difference=$2053 per year; $1963, $2178).Conclusions: IBS patients with high levels of somatization are not more likely to seekGI care compared to patients with low levels of somatization. However, once they areevaluated for care, patients with high somatization expend significantly more GI healthcare costs. This suggests that somatization is positively associated with health carecosts in IBS, and that the association may be driven more by physicians than patients.
  • 76. DDW Abstract T1160- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-469Disclosures: NoneBenefits Associated With Supplementation With An EncapsulatedProbiotic Preparation in Subjects With Irritable Bowel SyndromeP.J. Whorwell, L. Altringer, J. Morel, Y. Bond, L. OMahony, B. Kiely, F. Shanahan,E. QuigleyBackground. We have previously demonstrated benefits in irritable bowel syndrome(IBS) with a milk-based probiotic preparation of a novel probiotic strain, Bifidobacteriuminfantis 35624. Aim. To evaluate benefits in IBS with an encapsulated preparation of thesame probiotic strain.Methods. After a 2 week run-in phase, 291 female subjects with Rome II-positive IBSwere randomized to placebo (n=73), or one of three doses of B. infantis 35624: 106(n=74), 108 (n=74), or 1010 (n=70) CFU/capsule, given once daily for 4 weeks. IBSsymptoms were monitored daily, by telephone, using an interactive voice responsesystem (IVRS) and scored according to a 6-point Likert scale; stool frequency and form(using the Bristol Stool Scale) were also monitored daily. The primary efficacy variablewas the abdominal pain score; secondary efficacy variables included other IBSsymptoms, a composite symptom score, subject’s global assessment (SGA) of IBSsymptom relief and quality of life. In all IBS symptom efficacy analyses, “centers” and“subjects within centers” were treated as random factors. All results were adjusted bybaseline so dosage comparisons (placebo vs. 106 vs. 108 vs. 1010 ) were based onLeast-square Means.Results. For the primary efficacy variable, abdominal pain/discomfort (-0.58±0.10 vs.-0.41±0.10 vs. -0.89±0.10 vs. -0.46±0.10) as well as for all secondary variables ofcomposite score (-1.16±0.26 vs. -1.11±0.26 vs. -2.13±0.26 vs. -1.07±0.26),bloating/distension (-0.41±0.10 vs. -0.37±0.10 vs. -0.71±0.10 vs. -0.39±0.10),incomplete evacuation (-0.22±0.10 vs. -0.26±0.10 vs. -0.52±0.10 vs. -0.21±0.10),passage of gas (-0.26±0.09 vs. -0.21±0.09 vs. -0.51±0.09 vs. -0.27±0.09) and SGA forsymptom relief (-0.20±0.26 vs. -0.20±0.25 vs. 0.74±0.27 vs. -0.74±0.28), bifidobacteriumin a dose of 108 was significantly superior (P-value < 0.05) to placebo and all otherbifidobacterium doses. The efficacy variable SGA for symptom relief was analyzed usinga logistic model so its associated results are given on the logit scale. The correspondingsuccess rates are 45% vs. 45% vs. 68% vs. 32%. No significant adverse events wererecorded.Conclusion. B. infantis 35624, in a dose of 108 bacteria/day is effective in relieving allof the cardinal symptoms of irritable bowel syndrome. This study confirms benefitsobserved in previous studies, at a lower daily dose of probiotic in a capsule form, whiledemonstrating the complexity of achieving stable probiotic formulations.
  • 77. Onkologie / ErnährungKoloskopie / Screening P. Bauerfeind M. Fried1. OriginalarbeitenGastroenterology. 2004 Aug;127(2):452-6.Colonoscopic miss rates for right-sided colon cancer: a population-based analysis.Bressler B, Paszat LF, Vinden C, Li C, He J, Rabeneck L.Department of Medicine, University of Toronto, Ontario, Canada.BACKGROUND & AIMS: Colonoscopy contains an inherent miss rate for colorectalcancer. Although miss rates from academic centers or units known for their endoscopicexpertise have been previously reported, the colorectal cancer miss rate of colonoscopyperformed in usual clinical practice is unknown. We conducted a population-based studyto estimate the proportion of right-sided colon cancers missed during colonoscopy inOntario. METHODS: All persons > or =20 years old with a new diagnosis of right-sidedcolon cancer admitted to the hospital for surgical resection in Ontario from April 1, 1997,to March 31, 2001, were identified. Patients who had a colonoscopy within 3 years oftheir diagnosis were divided into 2 groups: detected cancers (those who had acolonoscopy up to 6 months before the diagnosis) and missed cancers (those who hada colonoscopy between 6 and 36 months before the diagnosis). Data were obtainedfrom the Canadian Institute for Health Information Discharge Abstract Database, theOntario Health Insurance Plan database, and the Registered Persons Database.RESULTS: Between April 1, 1997, and March 31, 2001, we identified 4920 persons witha new diagnosis of right-sided colon cancer, of whom 2654 (53.9%) had had at least 1colonoscopy within 3 years of their admission for surgical resection. Most (96.0%) hadhad their most recent colonoscopy up to 6 months before admission (detected cancers).However, 105 patients (4.0%) had their most recent colonoscopy between 6 and 36months before admission to the hospital (missed cancers). CONCLUSIONS: Amongpersons undergoing resection for right-sided colon cancer, the miss rate of colonoscopyfor detecting cancer in usual clinical practice was 4.0%.
  • 78. Dig Dis Sci. 2005 Jan;50(1):47-51.Relationship of colonoscopy completion rates and endoscopistfeatures.Harewood GC.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota55905, USA. harewood.gavin@mayo.eduThe success rate for reaching the cecum has been widely discussed as an indicator oftechnical expertise for colonoscopy. However, few studies have addressed the impact ofendoscopist-specific parameters on cecal intubation rates. The aim of this study was tocharacterize the relationship between endoscopist-specific parameters (age, gender,experience level, annual procedure volume, insertion and withdrawal times) and cecalintubation rates for colonoscopy. Procedural data from all colonoscopies performed bygastroenterologists at the outpatient endoscopy unit of Rochester Methodist Hospital,Minnesota, between January and December 2003 were reviewed. Procedural data of 45endoscopists who performed 17,100 colonoscopies over the study period wereanalyzed. The average cecal intubation rate was 93.9% (SD, 2.9%). Higher experiencelevel (>9 years [median]) was significantly predictive of a cecal intubation rate >94% (OR= 3.43; 95% CI, 1.03-12.29; P = 0.04). Although higher procedure volume was notpredictive of higher colonoscopy completion rates overall, when analysis was confinedto the junior faculty members (<5 years experience), completion rates for thoseendoscopists doing >200 per year (92.5%) was significantly higher than for those doing<200 per year (88.5%; P = 0.04). Our observations suggest that cecal intubation ratesincrease with increasing endoscopist experience. Moreover, among junior endoscopists,an annual volume of at least 200 procedures appears to be required to maintainadequate competence. Future prospective studies should provide data to supportconsensus guidelines recommending minimum annual procedure numbers required formaintenance of endoscopic competence among trained endoscopists.
  • 79. New Engl J Med. 2005 May 19;352(20):2061-8.Colonoscopic screening of average-risk women for colorectalneoplasia.Schoenfeld P, Cash B, Flood A, Dobhan R, Eastone J, Coyle W, Kikendall JW, KimHM, Weiss DG, Emory T, Schatzkin A, Lieberman D; CONCeRN StudyInvestigators.Division of Gastroenterology, University of Michigan School of Medicine and VeteransAffairs Center for Excellence in Health Services Research, Ann Arbor 48105, USA.pschoenf@umich.eduBACKGROUND: Veterans Affairs (VA) Cooperative Study 380 showed that someadvanced colorectal neoplasias (i.e., adenomas at least 1 cm in diameter, villousadenomas, adenomas with high-grade dysplasia, or cancer) in men would be missedwith the use of flexible sigmoidoscopy but detected by colonoscopy. In a tandem study,we examined the yield of screening colonoscopy in women. METHODS: To determinethe prevalence and location of advanced neoplasia, we offered colonoscopy toconsecutive asymptomatic women referred for colon-cancer screening. The diagnosticyield of flexible sigmoidoscopy was calculated by estimating the proportion of patientswith advanced neoplasia whose lesions would have been identified if they hadundergone flexible sigmoidoscopy alone. Lesions were considered detectable by flexiblesigmoidoscopy if they were in the distal colon or if they were in the proximal colon inpatients who had concurrent small adenomas in the distal colon, a finding that wouldhave led to colonoscopy. The results were compared with the results from VACooperative Study 380 for age-matched men and women with negative fecal occult-blood tests and no family history of colon cancer. RESULTS: Colonoscopy wascomplete in 1463 women, 230 of whom (15.7 percent) had a family history of coloncancer. Colonoscopy revealed advanced neoplasia in 72 women (4.9 percent). If flexiblesigmoidoscopy alone had been performed, advanced neoplasia would have beendetected in 1.7 percent of these women (25 of 1463) and missed in 3.2 percent (47 of1463). Only 35.2 percent of women with advanced neoplasia would have had theirlesions identified if they had undergone flexible sigmoidoscopy alone, as compared with66.3 percent of matched men from VA Cooperative Study 380 (P<0.001).CONCLUSIONS: Colonoscopy may be the preferred method of screening for colorectalcancer in women. Copyright 2005 Massachusetts Medical Society.
  • 80. Ann Intern Med. 2003 Dec 16;139(12):959-65.Using risk for advanced proximal colonic neoplasia to tailorendoscopic screening for colorectal cancer.Imperiale TF, Wagner DR, Lin CY, Larkin GN, Rogge JD, Ransohoff DF.Indiana University School of Medicine, Indiana University, Roudebush Veterans AffairsMedical Center, Indianapolis, Indiana, USA.BACKGROUND: Colonoscopic screening for colorectal cancer has been suggestedbecause sigmoidoscopy misses nearly half of persons with advanced proximalneoplasia. OBJECTIVE: To create a clinical index to stratify risk for advanced proximalneoplasia and to identify a subgroup with very low risk in which screeningsigmoidoscopy alone might suffice. DESIGN: Cross-sectional study. SETTING: Acompany-based program of screening colonoscopy for colorectal cancer. PATIENTS:Consecutive persons 50 years of age or older undergoing first-time screeningcolonoscopy between September 1995 and June 2001. MEASUREMENTS: A clinicalindex with 3 variables was created from information on the first 1994 persons. Pointswere assigned to categories of age, sex, and distal findings. Risk for advanced proximalneoplasia (defined as an adenoma 1 cm or larger or one with villous histology, severedysplasia, or cancer) was measured for each score. The index was tested on the next1031 persons from the same screening program. RESULTS: Of 1994 persons, 67(3.4%) had advanced proximal neoplasia. A low-risk subgroup comprising 37% of thecohort had scores of 0 or 1 and a risk of 0.68% (95% CI, 0.22% to 1.57%). Among thevalidation group of 1031 persons, risk for advanced proximal neoplasia in the low-risksubgroup (comprising 47% of the cohort) was 0.4% (upper confidence limit of 1.49%).Application of this index detected 92% of persons with advanced proximal neoplasmsand, if applied following screening sigmoidoscopy, could reduce the need forcolonoscopy by 40%. The marginal benefit of colonoscopy among low-risk persons wassmall: To detect 7 additional persons with advanced proximal neoplasia, 1217 additionalcolonoscopies would be required. CONCLUSIONS: This clinical index stratifies the riskfor advanced proximal neoplasia and identifies a subgroup at very low risk. If it isvalidated in other cohorts or groups, the index could be used to tailor endoscopicscreening for colorectal cancer.
  • 81. N Engl J Med. 2004 Dec 23;351(26):2704-14.Fecal DNA versus fecal occult blood for colorectal-cancer screeningin an average-risk population.Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME; ColorectalCancer Study Group.Department of Medicine, Indiana University, and the Regenstrief Institute, Indianapolis,IN 46202, USA.BACKGROUND: Although fecal occult-blood testing is the only available noninvasivescreening method that reduces the risk of death from colorectal cancer, it has limitedsensitivity. We compared an approach that identifies abnormal DNA in stool sampleswith the Hemoccult II fecal occult-blood test in average-risk, asymptomatic persons 50years of age or older. METHODS: Eligible subjects submitted one stool specimen forDNA analysis, underwent standard Hemoccult II testing, and then underwentcolonoscopy. Of 5486 subjects enrolled, 4404 completed all aspects of the study. Asubgroup of 2507 subjects was analyzed, including all those with a diagnosis of invasiveadenocarcinoma or advanced adenoma plus randomly chosen subjects with no polypsor minor polyps. The fecal DNA panel consisted of 21 mutations. RESULTS: The fecalDNA panel detected 16 of 31 invasive cancers, whereas Hemoccult II identified 4 of 31(51.6 percent vs. 12.9 percent, P=0.003). The DNA panel detected 29 of 71 invasivecancers plus adenomas with high-grade dysplasia, whereas Hemoccult II identified 10 of71 (40.8 percent vs. 14.1 percent, P<0.001). Among 418 subjects with advancedneoplasia (defined as a tubular adenoma at least 1 cm in diameter, a polyp with a villoushistologic appearance, a polyp with high-grade dysplasia, or cancer), the DNA panelwas positive in 76 (18.2 percent), whereas Hemoccult II was positive in 45 (10.8percent). Specificity in subjects with negative findings on colonoscopy was 94.4 percentfor the fecal DNA panel and 95.2 percent for Hemoccult II. CONCLUSIONS: Althoughthe majority of neoplastic lesions identified by colonoscopy were not detected by eithernoninvasive test, the multitarget analysis of fecal DNA detected a greater proportion ofimportant colorectal neoplasia than did Hemoccult II without compromising specificity.Copyright 2004 Massachusetts Medical Society.
  • 82. Gastroenterology. 2004 May;126(5):1270-9Fecal DNA testing compared with conventional colorectal cancerscreening methods: a decision analysis.Song K, Fendrick AM, Ladabaum U.Department of Medicine, Division of Gastroenterology, University of California-SanFrancisco, 513 Parnassus Avenue, San Francisco, CA 94143-0538, USA.BACKGROUND & AIMS: Fecal DNA testing is an emerging tool to detect colorectalcancer (CRC). Our aims were to estimate the clinical and economic consequences offecal DNA testing vs. conventional CRC screening. METHODS: Using a Markov model,we estimated CRC incidence, CRC mortality, and discounted cost/life-year gained forscreening by fecal DNA testing (F-DNA), fecal occult blood testing (FOBT) and/orsigmoidoscopy, or colonoscopy (COLO) in persons at average CRC risk from age 50 to80 years. RESULTS: Compared with no screening, F-DNA at a screening interval of 5years decreased CRC incidence by 35% and CRC mortality by 54% and gained 4560life-years per 100,000 persons at USD $47,700/life-year gained in the base case.However, F-DNA gained fewer life-years and was more costly than conventionalscreening. The average number of colonoscopies per person was 3.8 with COLO and0.8 with F-DNA. In most 1-way sensitivity analyses and Monte Carlo simulationiterations, F-DNA remained reasonably cost-effective compared with no screening, butCOLO and FOBT dominated F-DNA. Assuming fecal DNA testing sensitivities of 65% forCRC and 40% for large polyp, and 95% specificity, a screening interval of 2 years and atest cost of USD $195 would be required to make F-DNA comparable with COLO.CONCLUSIONS: Fecal DNA testing every 5 years appears effective and cost-effectivecompared with no screening, but inferior to other strategies such as FOBT and COLO.Fecal DNA testing could decrease the national CRC burden if it could improveadherence with screening, particularly where the capacity to perform screeningcolonoscopy is limited.
  • 83. Gastroenterology. 2004 Nov;127(5):1300-11.Computed tomographic colonography without cathartic preparationfor the detection of colorectal polyps.Iannaccone R, Laghi A, Catalano C, Mangiapane F, Lamazza A, Schillaci A,Sinibaldi G, Murakami T, Sammartino P, Hori M, Piacentini F, Nofroni I, Stipa V,Passariello R.Department of Radiological Sciences, University of Rome, Rome, Italy.r_iannaccone@yahoo.itBACKGROUND AND AIMS: We prospectively compared the performance of low-dosemultidetector computed tomographic colonography (CTC) without cathartic preparationwith that of colonoscopy for the detection of colorectal polyps. METHODS: A total of 203patients underwent low-dose CTC without cathartic preparation followed bycolonoscopy. Before CTC, fecal tagging was achieved by adding diatrizoate meglumineand diatrizoate sodium to regular meals. No subtraction of tagged feces was performed.Colonoscopy was performed 3-7 days after CTC. Three readers interpreted the CTCexaminations separately and independently using a primary 2-dimensional approachusing multiplanar reconstructions and 3-dimensional images for further characterization.Colonoscopy with segmental unblinding was used as reference standard. The sensitivityof CTC was calculated both on a per-polyp and a per-patient basis. For the latter,specificity, positive predictive values, and negative predictive values were alsocalculated. RESULTS: CTC had an average sensitivity of 95.5% (95% confidenceinterval [CI], 92.1%-99%) for the identification of colorectal polyps > or =8 mm. Withregard to per-patient analysis, CTC yielded an average sensitivity of 89.9% (95% CI,86%-93.7%), an average specificity of 92.2% (95% CI, 89.5%-94.9%), an averagepositive predictive value of 88% (95% CI, 83.3%-91.5%), and an average negativepredictive value of 93.5% (95% CI, 90.9%-96%). Interobserver agreement was high on aper-polyp basis (kappa statistic range, .61-.74) and high to excellent on a per-patientbasis (kappa statistic range, .79-.91). CONCLUSIONS: Low-dose multidetector CTCwithout cathartic preparation compares favorably with colonoscopy for the detection ofcolorectal polyps.
  • 84. 2. DDW-AbstractsDDW-Abstract M1264- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB148Use of Colonoscopy in Medicare Beneficiaries Increased SubstantiallyBetween 1999 and 2002 While the Use of Other Colorectal CancerDiagnostic Tests DeclinedStacey J. Ackerman ; Kathryn P. Anastassopoulos ; Michael J. Lacey ; Stacey L.Amorosi ; Tyler G. Knight ; David A. LiebermanPurpose: To examine trends in the use of colonoscopy, flexible sigmoidoscopy, double-contrast barium enema, and fecal occult blood test (FOBT) in Medicare beneficiariesfrom 1999 to 2002.Background: In January 1998, Medicare began paying for colorectal cancer screeningin average risk persons over age 50 using annual FOBT and/or flexible sigmoidoscopyevery five years, or double-contrast barium enema every five to ten years. Screeningcolonoscopy for high risk persons once every ten years also was paid for. Payment wasexpanded to include average risk persons in July 2001.Methods:The Medicare 5% Carrier Standard Analytic File (SAF) for 1999 to 2002 wasused to identify patient records with claims for colonoscopy, flexible sigmoidoscopy,double-contrast barium enema, and FOBT. The Carrier SAF is a representative 5%sample of final action claims for physician/supplier Part B services for all settings ofcare. The 5% Denominator SAF was used to obtain patient demographic information.Standard sampling methodology was used to extrapolate total volumes.Results:From 1999 to 2002, the number of Medicare beneficiaries increased by 4%.Beneficiaries in the study sample averaged 72 years of age, were 61% female, and 90%Caucasian. The number of procedures performed to evaluate colon health increased by2% (from 7.77 to 7.92 million), and the number of colonoscopies increased by 52%(from 2.14 to 3.25 million). Conversely, there was a 59% decrease in sigmoidoscopy(810,000 to 334,000), 41% decrease in barium enema (522,000 to 306,000), and 6%decrease in FOBT (4.30 to 4.03 million). The percent of procedures with a primarydiagnosis of polyp detection (ICD-9 211.3) remained constant for both colonoscopy(32% in 1999 and 33% in 2002) and sigmoidoscopy (7% in both 1999 and 2002).Conclusions:From 1999 to 2002, the number of procedures performed to evaluatecolon health in Medicare beneficiaries remained steady, but the mix of procedures usedchanged. Colonoscopy use increased substantially while there was a marked decline insigmoidoscopy and barium enema. Of note, the percent of colonoscopies with polypdetection remained unchanged despite a large increase in colonoscopy use. This maybe explained by changes in screening patterns, patient mix, and increased publicawareness. This study showed a dramatic shift in use of colon procedures over fouryears. Future study should monitor trends in colonoscopy use and patient outcomes,and the impact on system capacity.
  • 85. DDW-Abstract Sp751- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB107Predictors of Missed Colorectal Cancer During Colonoscopy: APopulation-Based AnalysisBrian Bressler ; Lawrence Paszat ; Deanna Rothwell ; Zhongliang Chen ; ChrisVinden ; Linda RabeneckBackground: In previous work we have shown that the miss rate for colorectal cancer(CRC) at colonoscopy (COL) is 2-6% depending on the site of CRC. However predictorsof a missed CRC at COL are unknown.Aim: To identify predictors of missed CRC at COL.Methods: Using electronic data from the Canadian Institute for Health Information (CIHI)and the Ontario Health Insurance Program (OHIP), we identified all individuals ³ 20years old, with a new diagnosis (dx) of right-sided CRC, transverse CRC, andrectal/sigmoid CRC, in the province of Ontario from 1/4/1997 to 31/3/2002. Weexcluded those who did not have a COL within 3 years prior to their dx. We dividedeach group into 2 categories. The detected cancers category consisted of individualswho had a COL within 6 months prior to dx. The missed cancers category consisted ofthose who had a COL within 6-36 months prior to dx. We combined the 3 groups andused a logistic regression model to examine patient (age, sex, history of previousabdominal/pelvic surgery, history of diverticulosis, site of CRC), procedure (performancedate, polypectomy procedure), physician (specialty, experience), and setting (hospital,office-based) characteristics that might predict missed CRC. We defined a physician’sexperience based on the number of COLs s/he performed in the year preceding themost recent COL prior to the dx of CRC.Results: We identified 25,877 patients with a new dx of right, transverse, orrectal/sigmoid CRC and excluded 13,038 who did not have a COL within 3 years of theirCRC dx. The remaining 12,839 patients comprised our study cohort, of whom 3,060had right-sided CRC, 945 had transverse CRC, and 8,834 had rectal or sigmoid CRC.The proportions of missed cancers were: 190 patients (6.2%) with right-sided CRC, 41patients (4.3%) with transverse CRC, and 182 patients (2.1%) with rectal/sigmoid CRC.In multivariate analysis, patients who were older, female, had a history of previousabdominal/pelvic surgery, history of diverticulosis, those with right-sided or transverseCRC, those in whom an internist or family physician performed the COL, those in whomthe physician was less experienced, and those who had an office-based COL were allindependent predictors of a missed CRCConclusion: In addition to patient characteristics, having a COL performed in an officesetting, or by a less experienced endoscopist, or by an internist or family physician wereindependent predictors of missed CRC at COL.
  • 86. DDW-Abstract 242- Gastrointestinal Endoscopy, 2005 Apr.;61(5): AB81Cecal Intubation Rates and Endoscopist Features: Implications forMaintaining Endoscopic CompetenceGavin Harewood ; Beverly OttIntroduction: Cecal intubation has been proposed as a benchmark for measuringtechnical competence for colonoscopy. However, few studies have assessed the impactof endoscopist-specific parameters on cecal intubation rates. This study aimed tocharacterize the relationship between endoscopist-specific parameters (experiencelevel, annual procedure volume) and cecal intubation rates for colonoscopy. Methods:Procedural data from all routine colonoscopies performed by staff gastroenterologists atour outpatient endoscopy unit between January and December, 2003 were reviewed.Results: Procedural data of 45 staff endoscopists who performed 17,100 colonoscopieswere analyzed. Mean cecal intubation rate was 93.9% (SD, 2.9). Higher experiencelevel (> 9 years [median]) was predictive of cecal intubation rate >94%, OR = 3.43 (95%C.I., 1.03 – 12.29), p = 0.04. Higher procedure volumes were not associated with highercolonoscopy completion rates. However, when analysis was confined to junior facultymembers with <5 years experience (18 endoscopists), completion rates for thoseendoscopists doing >200 per year (92.5%) was significantly higher than for those doing<200 per year (88.5%), p = 0.04 (figure).Conclusions: Cecal intubation rates appear to increase with increasing endoscopistexperience. Among junior staff endoscopists, an annual volume of at least 200procedures appears necessary to maintain competence. Future studies should providefurther data to support evidence-based guidelines recommending minimum annualprocedure numbers required for maintaining endoscopic competence.
  • 87. DDW-Abstract 424- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-63Stool DNA Screening for Colorectal Cancer: Prospective MulticenterComparison With HemoccultDavid A Ahlquist ; Daniel J Sargent ; Theodore R Levin ; Douglas K Rex ; DennisAhnen ; Kandice L Knigge ; M. Peter Lance ; Charles L Loprinzi ; Lawrence JBurgart ; James E Allison ; Michael J Lawson ; Shauna L Hillman ; Mary E DevensStool DNA testing can detect colorectal neoplasms, but performance data onrepresentative populations are needed. Aim: To compare the accuracy of PreGenPlus(PGP), a multi-target DNA-based stool assay, with that of Hemoccult (HO) for detectionof screen-relevant neoplasia (cancer (CRC), high grade dysplasia (HGD), adenoma >1cm) in an average-risk population. Methods: The first 2502 evaluable subjects from ablinded multicenter NCI study (UO1 CA 89389) are analyzed. Subjects are age 50-80,have had no structural colon exam within 10 yrs, and have < one 10 relative with CRC.Results are reported due to a change in the commercial PGP made prior to completionof the planned 4434 enrollment. Subjects collect 3 whole stools and smear HO cardswith same-day shipment to a central processing facility. Stools received > 48 hours afterdefecation are disqualified. PGP is performed on a single stool/subject at ExactSciences and HO on 3 stools/subject at Mayo Clinic. PGP is considered positive if anyof 23 targeted markers is detected; HO is positive if either window on any of 3 cardsreacts. After stool collection, a verified complete colonoscopy is required for evaluabilityand serves as the gold standard. All colorectal lesions are re-examined by a singlepathologist. Tissue from all available CRC/HGD are tested by PGP. Results: Medianage was 59 and 46% were men. Of 146 subjects with screen-relevant neoplasia (SRN),PGP detected 30 (20%) and HO 17 (12%), p=0.03. Of 23 subjects with CRC/HGD, PGPdetected 8 (35%) and HO 9 (39%), p=0.76. Specificities were 96% for PGP and 98% forHO, p<0.0001. SRN detection by long DNA, a component marker on PGP panel, fellfrom 11% to 1.8% to 0% on stools received <24, 24-35, and >35 hours after defecation,respectively, p=0.04. Other PGP markers were stable. Among 17 CRC/HGD tissuestested, 11 expressed > 1 genetic alteration by PGP assay (65% tissue sensitivity) andcorresponding stools were PGP positive in 5 (45%). Median size of CRC/HGD was24mm in PGP positives and 12mm in PGP negatives, p=0.03. Conclusions: In thescreening setting: PGP detects more SRN than HO but at lower specificity. Both testsmiss the majority of SRN. PGP insensitivity is affected by instability of long DNA in stool,non-expression of panel markers in SRN tissue, and incomplete marker recovery fromstool. Enrollment continues to allow assessment of a next generation assay with moreinformative markers and better DNA capture.
  • 88. Onkologie GI-Trakt H. Scherübl1. OriginalarbeitenN Engl J Med. 2004 Jul 22;351(4):337-45.Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D,Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E.Royal Marsden Hospital, London, United Kingdom. The epidermal growth factor receptor (EGFR), which participates insignaling pathways that are deregulated in cancer cells, commonly appears oncolorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks theEGFR. We compared the efficacy of cetuximab in combination with irinotecan with thatof cetuximab alone in metastatic colorectal cancer that was refractory to treatment withirinotecan. METHODS: We randomly assigned 329 patients whose disease hadprogressed during or within three months after treatment with an irinotecan-basedregimen to receive either cetuximab and irinotecan (at the same dose and schedule asin a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In casesof disease progression, the addition of irinotecan to cetuximab monotherapy waspermitted. The patients were evaluated radiologically for tumor response and were alsoevaluated for the time to tumor progression, survival, and side effects of treatment.RESULTS: The rate of response in the combination-therapy group was significantlyhigher than that in the monotherapy group (22.9 percent [95 percent confidence interval,17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1percent], P=0.007). The median time to progression was significantly greater in thecombination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). Themedian survival time was 8.6 months in the combination-therapy group and 6.9 monthsin the monotherapy group (P=0.48). Toxic effects were more frequent in thecombination-therapy group, but their severity and incidence were similar to those thatwould be expected with irinotecan alone. CONCLUSIONS: Cetuximab has clinicallysignificant activity when given alone or in combination with irinotecan in patients withirinotecan-refractory colorectal cancer. Copyright 2004 Massachusetts Medical Society
  • 89. J Clin Oncol. 2005 Apr 1;23(10):2310-7.Chemoradiation with and without surgery in patients with locallyadvanced squamous cell carcinoma of the esophagus.Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, Klump B, BudachW, Teichmann R, Schmitt M, Schmitt G, Franke C, Wilke H.Department of Medical Oncology and Hematology, Kliniken Essen-Mitte, Henricistr 92,D-45136 Essen, Germany. m.stahl@kliniken-essen-mitte.dePURPOSE: Combined chemoradiotherapy with and without surgery are widely acceptedalternatives for the curative treatment of patients with locally advanced esophagealcancer. The value of adding surgery to chemotherapy and radiotherapy is unknown.PATIENTS AND METHODS: Patients with locally advanced squamous cell carcinoma(SCC) of the esophagus were randomly allocated to either induction chemotherapyfollowed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the sameinduction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery(arm B). Primary outcome was overall survival time. RESULTS: The median observationtime was 6 years. The analysis of 172 eligible, randomized patients (86 patients perarm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in thesurgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) thanin the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI,28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003).Treatment-related mortality was significantly increased in the surgery group than in thechemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regressionanalysis revealed clinical tumor response to induction chemotherapy to be the singleindependent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001). CONCLUSION: Adding surgery to chemoradiotherapy improves local tumorcontrol but does not increase survival of patients with locally advanced esophagealSCC. Tumor response to induction chemotherapy identifies a favorable prognostic groupwithin these high-risk patients, regardless of the treatment group.
  • 90. N Engl J Med. 2005 May 26;352(21):2184-92.Statins and the risk of colorectal cancer.Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M,Greenson JK, Rennert G.Department of Epidemiology, University of Michigan, Ann Arbor 48109-0638, USA.BACKGROUND: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme Areductase and effective lipid-lowering agents. Statins inhibit the growth of colon-cancercell lines, and secondary analyses of some, but not all, clinical trials suggest that theyreduce the risk of colorectal cancer. METHODS: The Molecular Epidemiology ofColorectal Cancer study is a population-based case-control study of patients whoreceived a diagnosis of colorectal cancer in northern Israel between 1998 and 2004 andcontrols matched according to age, sex, clinic, and ethnic group. We used a structuredinterview to determine the use of statins in the two groups and verified self-reportedstatin use by examining prescription records in a subgroup of patients for whomprescription records were available. RESULTS: In analyses including 1953 patients withcolorectal cancer and 2015 controls, the use of statins for at least five years (vs. thenonuse of statins) was associated with a significantly reduced relative risk of colorectalcancer (odds ratio, 0.50; 95 percent confidence interval, 0.40 to 0.63). This associationremained significant after adjustment for the use or nonuse of aspirin or othernonsteroidal antiinflammatory drugs; the presence or absence of physical activity,hypercholesterolemia, and a family history of colorectal cancer; ethnic group; and levelof vegetable consumption (odds ratio, 0.53; 95 percent confidence interval, 0.38 to0.74). The use of fibric-acid derivatives was not associated with a significantly reducedrisk of colorectal cancer (odds ratio, 1.08; 95 percent confidence interval, 0.59 to 2.01).Self-reported statin use was confirmed for 276 of the 286 participants (96.5 percent)who reported using statins and whose records were available. CONCLUSIONS: The useof statins was associated with a 47 percent relative reduction in the risk of colorectalcancer after adjustment for other known risk factors. Because the absolute risk reductionis likely low, further investigation of the overall benefits of statins in preventing colorectalcancer is warranted. Copyright 2005 Massachusetts Medical Society.
  • 91. 2. KongreßabstractsDDW-Abstract 622- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-93Statins Reduce the Incidence Of Esophageal Cancer:a Study Of Half aMillion Us Veterans.Vikas Khurana ; Ramu Chalasani ; Gloria Caldito ; Charlton FortBACKGROUND: Statins are commonly used cholesterol-lowering agents that are notedto suppress tumor growth in several animal models, however clinical data for achemoprotective role of statins in esophageal cancer is lacking.DESIGN: The VISN 16 database, which contains clinical and demographic informationabout all veterans (>1.4 million patients) cared for in the South Central VA Health CareNetwork, was queried from Oct 1998 to June 2004. Retrospective case control designwas used. Statistical analysis was performed using SAS software version 9.0 (Chicago,IL). Multiple logistic regression analysis was used with calculation of odds ratios and95% confidence intervals. The data was adjusted for age, smoking, alcohol use anddiabetes.RESULTS: A total of 484,226 patients were studied. The mean age was 61.2(SD+/-15.1) years and 91.7% were men, 164,645 (34%) were using statins. Esophagealcancer (ICD code of 150) was seen in 659 (0.14%). Statin users were less likely todevelop esophageal cancer (Odds ratio 0.44: 95% CI 0.36-0.53). The data wascontrolled for age, smoking (p=0.1), alcohol use (p=0.67) and diabetes (p=0.52). Age(OR 1.03, 95% CI 1.02 -1.04, p <0.0001) and reflux (OR 2.42, 95% CI 2.05-2.85, p<0.0001) were significant covariates.DISCUSSION: An internal consistency of the database is reflected by an increased riskassociated with documented risk factors. Our data should be evaluated with caution,given the limitations of the population, the database and the fact that this is a casecontrol study. Patients were placed in the statins users group if they were using statinsprior to the diagnosis of esophageal cancer but the dose, duration and type of statinused was not factored into the analysis. Some factors known to increase the risk ofesophageal cancer like Barrett’s esophagus was not incorporated into the study.CONCLUSION: Statins are associated with a 56% reduced incidence of esophagealcancer after controlling for age, gender, smoking, alcohol use and diabetes.
  • 92. DDW Abstract 605- Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-89-90Multi-Center Prospective Randomized Trial Comparing StandardEsophagectomy Against Definitive Chemo-Irradiation for Treatment OfSquamous Esophageal Cancer: Early Results From the ChineseUniversity Research Group for Esophageal Cancer (cure)Philip Wai Yan Chiu ; Angus Chi Wai Chan ; Enders Kwok Wai Ng ; Sing Fai Leung; Danny WH Lee ; JF Griffith ; Simon Kin Hung Wong ; Anthony Chi Ngan Li ;Wing Tai Siu ; Michael Ka Wah Li ; Peter Kwok Hung Kwong ; Hing Tat Leong ;Alex Auyeung ; Candice Lam ; Sydney Sheung Chee ChungIntroductionSquamous cell carcinoma of the esophagus is well known to have a poor prognosis.From our preliminary study, combining chemotherapy with concomitant irradiation couldachieve a significant tumor reduction and even complete regression. We conducted aprospective randomized trial to compare the efficacy and survival achieved by primarychemoirradiation to that by esophagectomy for patients with advanced squamous cellcarcinoma of the esophagus. Methods: From July 2000 to 2004, 80 patients withpotentially operable squamous cell carcinoma of mid or lower thoracic esophagus wererandomized. Two or three-staged esophagectomy with 2-field dissection wereperformed. Patients treated with chemo-irradiation received continuous 5-fluorouracilinfusion (200mg/m2/day) from day 1 to 42 and cis-platin (60mg/m2) on day 1 and 22.The tumor and regional lymphatics were concomitantly irradiated with a total of 60 Gy.Tumor response was assessed by endoscopy, EUS and CT scan. Salvageesophagectomy was performed for incomplete response or recurrence. The quality oflife was assessed by EORTC OES-18 before, 6 weeks and 3 months after therapy.Results: 44 patients received standard esophagectomy, while 36 were treated withprimary chemoirradiation. Median followup was 19 months. The operative mortality was7.1%. The rate of postoperative complication was 38.1%. There was no difference in theearly cumulative survival between the two groups (Log rank test p = 0.48). There were ahigher proportion of patients complain of indigestion in the esophagectomy group (p =0.001). Otherwise there is no different between the groups in other aspects of EORTCOES-18 before and 3 months after treatment. Esophagectomy Chemoirradiation p-valueNo. of patients randomized 44 36 -No. of patients analyzable 42 33 -Median age 62 (47-76) 62 (42-74) 0.91Pre-treatment stagingT2 : T3 9 : 33 12 : 21 0.2N1 22 (52.4%) 12 (36.4%) 0.13Salvage esophagectomy - 5 (16.7%) -Recurrence 14 (32.6%) 14 (42.4%) 0.87Cumulative survival at 24 months 62.8% 63.6% 0.48ConclusionsFrom the early results of our prospective randomized trial, we found that both standardesophagectomy and definitive chemoirradiation achieved comparable intermediate-termsurvival.
  • 93. ASCO meeting 2005, Abstract 4001Perioperative chemotherapy in operable gastric and loweroesophageal cancer: final results of a randomised, controlled trial (theMAGIC trial, ISRCTN 93793971).D. Cunningham, W. H. Allum, S. P. Stenning, S. Weeden, for the NCRI Upper GICancer Clinical Studies GroupBackground: Epirubicin, Cisplatin and infused 5-FU (ECF) shows significant benefit inadvanced oesophagogastric cancer, particularly locally advanced disease. This trial wasdesigned to determine whether this effect translates into a survival advantage inoperable disease. Methods: Patients with operable adenocarcinoma of the stomach,oesophagogastric junction or lower oesophagus were randomised to perioperativechemotherapy (CSC arm) or surgery alone (S arm). In the CSC arm, chemotherapycomprised three pre-operative and three post-operative cycles, 3 weeks apart, of E50mg/m2 IV bolus, C 60mg/m2 infusion and 5-FU 200mg/m2/day continuous infusion. Thetrial was powered (2α=5%, 1-β=90%) to detect a 15% increase in 5-year survival (~250events required), with pre-planned analysis with another European trial of the samedesign, collectively giving ~90% power to detect a 10% increase in survival. The lattertrial closed early, therefore to increase power to detect a 10% increase from MAGICalone, the final analysis was deferred until sufficient events had occurred to give at least70% power (~320 deaths) to detect a hazard ratio (HR) of 0.75, equivalent to anabsolute difference in survival of approximately 10% at 2 and 5 years. Results:Between 1994 and 2002, 503 patients (250 CSC, 253 S) were randomised; 74% gastric,11% oesophago-gastric junction and 15% lower oesophagus. Initial analysis (ASCO2003) demonstrated statistically significant differences in favour of CSC with respect tocurative resection rate, resected tumour diameter and, for gastric and junctionalpatients, T stage. As of 12/2004, with median follow-up >3 years and 90% of patientsfollowed to death or >2 years, 319 deaths have occurred, (149 CSC, 170 S). Thesurvival HR is 0.75, 95% CI (0.60, 0.93), p=0.009; 5 year survival rates for CSC and Sare 36% (30%, 43%) and 23% (17%, 29%) respectively. Progression-free survival wasalso significantly prolonged; HR 0.66 (0.53, 0.81), p=0.0001. Conclusions:Perioperative chemotherapy significantly improves resectability, progression-free andoverall survival in operable gastric and lower oesophageal cancer
  • 94. ASCO Meeting Abstract LBA3500A phase III trial comparing FULV to FULV + oxaliplatin in stage II or IIIcarcinoma of the colon: Results of NSABP Protocol C-07N. Wolmark, H. S. Wieand, J. P. Kuebler, L. Colangelo, R. E. Smith Background: The primary aim of this two-arm randomized prospective study was to determine whether FULV + oxaliplatin (FLOX) would prolong 3-year disease-free survival (DFS) compared to FULV. Methods: Between February 2000 and November 2002, 2,407 patients with follow-up (1207 and 1200 in the respective arms) with stage II (28.6%) or III carcinoma of the colon were randomized to receive either FULV (5-FU, 500 mg/m2 iv bolus weekly x 6; LV, 500 mg/m2 iv weekly x 6, each 8 week cycle x 3) or FLOX (same FULV regimen with oxaliplatin 85 mg/m2 iv administered on weeks 1, 3, and 5 of each 8 week cycle x 3). The primary end point was DFS. Events were defined as first recurrence, second primary cancer, or death. Results: The median follow-up for patients who were still alive was 34 months. The hazard rate (FLOX vs. FULV) was 0.79 with 95% CI (0.67, 0.93), a 21% risk reduction in favor of FLOX. (See table below.) Grade 3 NCI-Sanofi neurosensory toxicity was noted in 8% of patients on FLOX and 1% of those receiving FULV. Hospitalization for diarrhea or dehydration associated with bowel wall thickening occurred in 56 patients on FLOX and 34 patients on FULV. There were 14 and 15 deaths while patients were on treatment for FULV and FLOX, respectively. Conclusion: The addition of oxaliplatin to weekly FULV significantly improved 3-year DFS in patients with Stage II and III colon cancer. Supported by Public Health Service grants U10-CA-12027 and U10-CA-69651 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. N. Wolmark and J. P. Kuebler have served on advisory boards and have received honoraria from Sanofi-Synthelabo, Inc. N Events 3yr % DFSFULV 1207 332 71.6FLOX 1200 272 76.5 P = 0.004
  • 95. Onkologie hepatobiliär und Pankreas G. Schachschal1. OriginalarbeitenHepatology. 2005 Apr;41(4):707-16.Prognosis of hepatocellular carcinoma: comparison of 7 stagingsystems in an American cohort.Marrero JA, Fontana RJ, Barrat A, Askari F, Conjeevaram HS, Su GL, Lok AS.Division of Gastroenterology, Department of Internal Medicine, University of Michigan,Ann Arbor, MI 48109-0362, USA. jmarrero@umich.eduCurrently there is no consensus as to which staging system is best in predicting thesurvival of patients with hepatocellular carcinoma (HCC). The aims of this study were toidentify independent predictors of survival and to compare 7 available prognostic stagingsystems in patients with HCC. A total of 239 consecutive patients with cirrhosis andHCC seen between January 1, 2000, and December 31, 2003, were included.Demographic, laboratory, and tumor characteristics and performance status weredetermined at diagnosis and before therapy. Predictors of survival were identified usingthe Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C,56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did notreceive any cancer treatment. At the time of censorship, 153 (63%) patients had died.The 1- and 3-year survival of the entire cohort was 58% and 29%, respectively. Theindependent predictors of survival were performance status (P < .0001), MELD scoregreater than 10 (P = .001), portal vein thrombosis (P = .0001), and tumor diametergreater than 4 cm (P = .001). Treatment of HCC was related to overall survival. TheBarcelona Clinic Liver Cancer (BCLC) staging system had the best independentpredictive power for survival when compared with the other 6 prognostic systems. Inconclusion, performance status, tumor extent, liver function, and treatment wereindependent predictors of survival mostly in patients with cirrhosis and HCC. The BCLCstaging system includes aspects of all of these elements and provided the bestprognostic stratification for our cohort of patients with HCC.
  • 96. Gastroenterology (im Druck, Juni-Ausgabe)A Randomized Controlled Trial of Radiofrequency Ablation withEthanol Injection for Small Hepatocellular Carcinoma : Rf Ablation vs.Ethanol Injection for HCCS. SHIINA, T. TERATANI, S. OBI, S. SATO, S. TATEISHI, T. FUJISHIMA, T.ISHIKAWA, Y. KOIKE, H. YOSHIDA, T. KAWABE, and M. OMATADepartment of Gastroenterology, University of Tokyo, Tokyo, JapanBackground & Aims: Percutaneous radiofrequency ablation is a recently introducedtreatment for hepatocellular carcinoma, while ethanol injection is now a standardtherapy. We compared their long-term outcomes.Methods: Two hundreds and thirty-two patients with hepatocellular carcinoma who hadthree or fewer lesions, each 3 cm or less in diameter, and liver function of Child-Pughclass A or B were entered onto a randomized controlled trial. The primary endpoint wassurvival, and the secondary endpoints were overall recurrence and local tumorprogression.Results: One hundred and eighteen patients were assigned to radiofrequency ablationand 114 to ethanol injection. The number of treatment sessions was smaller (2.1 timesvs 6.4 times, p < 0.0001) and the length of hospitalization was shorter (10.8 days vs26.1 days, p < 0.0001) in radiofrequency ablation than in ethanol injection. Four-yearsurvival rate was 74% (95% CI 65 – 84%) in radiofrequency ablation and 57% (95% CI45 – 71%) in ethanol injection. Radiofrequency ablation had a 46% smaller risk of death(adjusted relative risk 0.54 [95% CI 0.33 - 0.89], p = 0.02), a 43% smaller risk of overallrecurrence (adjusted relative risk 0.57 [95% CI 0.41 - 0.80], p = 0.0009) and an 88%smaller isk of local tumor progression (relative risk 0.12 [95% CI 0.03 - 0.55], p = 0.006)than ethanol injection. The incidence of adverse events was not different between thetwo therapies.Conclusions: Judging from higher survival but similar adverse events, radiofrequencyablation is superior to ethanol injection in the treatment of small hepatocellularcarcinoma.
  • 97. Z Gastroenterol. 2005 May;43(5):439-43.Is 18F-FDG-PET Suitable for Therapy Monitoring after PalliativePhotodynamic Therapy of Non-Resectable HilarCholangiocarcinoma?]Muller D, Wiedmann M, Kluge R, Berr F, Mossner J, Sabri O, Caca K.Klinik und Poliklinik fur Nuklearmedizin, Universitat Leipzig.BACKGROUND: If existing biliary drainage is insufficient, photodynamic therapy (PDT,laser treatment after application of a photosensitizer) is an already established adjunctto palliative therapy for progressing hilar cholangiocarcinoma (Klatskin tumours), since itprolongs survival and improves quality of life. Experimental studies of other tumourentities showed that (18)F-FDG-PET ( (18)F-fluorodeosxyglucose-positron emissiontomography) may play a role in monitoring tumour response to PDT. Furthermore,previous studies have revealed a high accuracy of this method for the detection of hilarcholangiocarcinoma. Therefore, the aim of the present study was to investigate thefeasibility of (18)F-FDG-PET as a follow-up screening method in patients with hilarcholangiocarcinoma who underwent PDT. PATIENTS AND METHODS: 10 patientswere examined by (18)F-FDG-PET before and 4 - 6 weeks after PDT. The followingparameters were evaluated: maximum and mean SUV in the tumour, the ratio ofmaximum SUV in the tumour and mean SUV in the liver, the vital tumour volume, as wellas bilirubin and CA 19 - 9 levels. RESULTS: All tumours were detected by (18)F-FDG-PET. Within a period of 4 - 6 weeks after PDT the cholestasis parameter bilirubindecreased significantly. However, SUV-associated parameters did not show a significantchange after treatment while the estimated vital tumour volume even increased.DISCUSSION: PDT does not effect a relevant reduction of tumour mass in non-resectable hilar cholangiocarcinoma. However, PDT leads to a significant reduction ofcholestasis. If (18)F-FDG-PET is suitable for monitoring the effect of new palliativetherapeutic approaches, like brachytherapy, the use of modern chemotherapeuticals,COX-2 and receptor-tyrosine kinase inhibitors, perhaps also in combination with PDT,has to be further investigated.
  • 98. Endoscopy. 2005 May;37(5):425-33.Prospective study of the effectiveness of percutaneous transhepaticphotodynamic therapy for advanced bile duct cancer and the role ofintraductal ultrasonography in response assessment.Shim CS, Cheon YK, Cha SW, Bhandari S, Moon JH, Cho YD, Kim YS, Lee LS, LeeMS, Kim BS.Institute for Digestive Research and Digestive Disease Center, Soon Chun HyangUniversity College of Medicine, Seoul, Korea. AND STUDY AIMS: We evaluated the therapeutic effects ofpercutaneous transhepatic photodynamic therapy (PDT) in patients with advanced bileduct cancer. The utility of intraductal ultrasonography (IDUS) for the assessment ofresponses and for regular follow up after PDT was also examined. METHODS:Percutaneous transhepatic biliary drainage (PTBD) was initiated before PDT. Followingdilation and maturation of the PTBD tract, percutaneous PDT was performed.Intraluminal photoactivation was carried out using percutaneous cholangioscopy 2 daysafter intravenous application of a hematoporphyrin derivative. All patients wereadditionally provided with percutaneous bile duct drainage catheters after PDT. IDUSwas conducted monthly to measure the thickness of the tumor mass before and afterPDT. RESULTS: 24 patients with advanced cholangiocarcinomas (Bismuth IIIa, n = 4;IIIb, n = 10; IV, n = 10) were treated with PDT. At 3 months after PDT, the meanthickness of the tumor mass had decreased from 8.7 +/- 3.7 mm to 5.8 +/- 2.0 mm (P <0.01). At 4 months after PDT, the thickness of the mass had increased to 7.0 +/- 3.7mm. Quality of life indices improved dramatically and remained stable 1 month afterPDT; the Karnofsky index increased from 39.1 +/- 11.36 to 58.2 +/- 22.72 points (P =0.003). The 30-day mortality rate was 0 %, and the median survival time was 558 +/-178.8 days (current range 62 - 810 days). CONCLUSIONS: PDT using percutaneouscholangioscopy is safe and effective for advanced hilar cholangiocarcinoma, and seemsto prolong survival. IDUS is useful for evaluating changes in the thickness of the tumormass after PDT.
  • 99. 2. DDW-AbstractsDDW Abstract 245Disclosures: NoneMELD Score Predicts Mortality in Cirrhotic Patients UndergoingHepatic Resection for Hepatocellular CarcinomaS.H. Teh, S.S. Cha, J.D. Christein, J.H. Donohue, M.L. Kendrick, F.G. Que, M.B.Farnell, W.R. Kim, P.S. Kamath, D.M. NagorneyBACKGROUND: Hepatic resection for hepatocellular carcinoma (HCC) in patientswith cirrhosis is generally recommended for those who are Child-Pugh Class A. TheModel for End-Stage Liver Disease (MELD) has been shown to accurately predictsurvival in patients with cirrhosis. Whether MELD can be used to select patients withcirrhosis for hepatic resection is unknown. AIMS: To determine the risk factors formortality in cirrhotic patients undergoing hepatic resection. METHODS: Aretrospective chart review of all patients with HCC and cirrhosis who underwentsurgical resection between January 1993 and December 2003 was undertaken todetermine risk for mortality. RESULTS: There were 82 patients, 62 male, 20 female(mean age 62.1 years); 45 patients had a MELD score ≥ 9 (range 9-15). Child-Pughscore ranged between 5-9 points. The mean size of the tumor was 5.2 cm. Fifty-nine patients had minor (≤ 3 segments) hepatic resection (MELD ≤ 8, n= 29; MELD ≥9, n= 30 ), and 23 patients had major (≥ 4 segments) hepatic resections (MELD ≤ 8,n= 8 ; MELD ≥ 9, n= 15 ). Hospital mortality and 30-day mortality were 12% and 16%respectively, predominantly due to liver failure. Multivariate analysis demonstratedthat factors significantly associated with increasing mortality were: MELD score ≥ 9(p< 0.0001); presence of symptoms (p=0.0001); tumor larger than 5 cm (p=0.01), andhigh grade (p=0.03), but not Child-Pugh class (p=0.6), vascular invasion or multilobardisease. Overall, MELD score ≤ 8 was associated with 0% 30-day mortality ascompared with 29% for those with MELD score of ≥ 9 (p=0.002) (Table). For MELD≥ 9, 30-day mortality (p=0.6) and long-term survival was similar between minor andmajor hepatic resection. CONCLUSION: MELD is a strong predictor of bothperioperative mortality and long-term survival in cirrhotic patients undergoing hepaticresection. In patients with cirrhosis, hepatic resection (minor or major) for HCC isrecommended if the MELD score is ≤ 8. In patients with MELD score ≥ 9, othertreatment modalities should be considered.Table 1: Overall Survival by MELD ScoreSurvival MELD ≤ 8 MELD ≥ 9 P value(%) (n=37) (n=45)30 days 100 71 0.0021 year 89 48 0.0023 years 63 365 years 51 24
  • 100. DDW Abstract M1667-Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-761-2Disclosures: NoneRadiofrequency Ablation for Hepatocellular Carcinoma: Long-TermResultsS. Shiina, T. Teratani, R. Tateishi, T. Fujishima, Y. Kondo, N. Yamashiki, N.Mine, R. Masuzaki, M. Yanase, T. Ishikawa, S. Obi, H. Yoshida, T. Kawabe, M.OmataBackground: Radiofrequency ablation (RFA) has been reported to be efficacious forhepatocellular carcinoma (HCC). However, there have not been many reports on itslong-term results. The aim of this study was to evaluate survival and recurrence afterRFA for HCC.Subjects and Methods Indications of RFA were as follows; 1) unresectable lesionsor refusal of surgery, 2) no extrahepatic metastasis or vascular invasion, 3) absenceof refractory ascites, 4) PT > 50 % and Plt > 50,000, 4) T. Bil < 3.0 mg/dl, 5)obtainment of informed consent. We put no restrictions on lesion location. Thesubjects of this study were 434 consecutive patients with HCC who received RFA asthe initial treatment between 1999 and 2004. There were 283 males and 151females. The age was 66.3 + 8.5 (mean + S.D.) years. Lesion number was 1.9 + 1.5(1-12). Maximum lesion size was 2.8 + 1.3 (0.9-9.7) cm. Liver function was in Child-Pugh A in 296 cases, in B in 134, and in C in 4. We performed RFA percutaneouslywith a cooled-tip electrode. As a general rule, we ablated not only the tumor but alsosome amount of the surrounding tissue. One to three days after RFA, CT wasperformed to determine the efficacy. If there were any possible undestroyedportions, RFA was repeated until the entire tumor necrosis. All patients had CT andUS every 4 months to find any recurrence. We examined 20 factors (age, sex, tumorsize, tumor number, AFP, AFP-L3 & DCP before RFA, AFP, AFP-L3 & DCP afterRFA, histological grade of tumor differentiation, Alb, T. Bil, ALT, PT, Plt, Child-Pughliver dysfunction, presence of cirrhosis, HBs-Ag, HCV-Ab) to predict survival andrecurrence.Results Survival rates after RFA were 95% at 1-year, 88% at 2-years, 78% at 3-years, 68% at 4-years, and 56% at 5-years. Alb, T. Bil and tumor size weresignificant predictive factors for survival. Overall recurrence after RFA was 19% at 1-year, 43% at 2-years, 60% at 3-years, 66% at 4-years, and 76% at 5-years. Tumorsize, tumor number and AFP were significant predictive factors for overall recurrence.Local recurrence after RFA was 1.1% at 1-year, 2.2% at 2-, 3-, 4-, and 5-years.Complications were encountered in 16 cases. However, there was no mortalityrelated to RFA.Conclusion RFA achieved considerably good survival. RFA may be a valuabletherapy for HCC. 101
  • 101. Ernährung J. Ockenga1. OriginalarbeitenJAMA. 2005 Jan 5;293(1):43-53.Comparison of the Atkins, Ornish, Weight Watchers, and Zone dietsfor weight loss and heart disease risk reduction: a randomized trial.Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ.Division of Endocrinology, Diabetes, and Metabolism, Atherosclerosis ResearchLaboratory, Tufts-New England Medical Center, Boston, Mass 02111, USA.mdansinger@tufts-nemc.orgCONTEXT: The scarcity of data addressing the health effects of popular diets is animportant public health concern, especially since patients and physicians areinterested in using popular diets as individualized eating strategies for diseaseprevention. OBJECTIVE: To assess adherence rates and the effectiveness of 4popular diets (Atkins, Zone, Weight Watchers, and Ornish) for weight loss andcardiac risk factor reduction. DESIGN, SETTING, AND PARTICIPANTS: A single-center randomized trial at an academic medical center in Boston, Mass, ofoverweight or obese (body mass index: mean, 35; range, 27-42) adults aged 22 to 72years with known hypertension, dyslipidemia, or fasting hyperglycemia. Participantswere enrolled starting July 18, 2000, and randomized to 4 popular diet groups untilJanuary 24, 2002. INTERVENTION: A total of 160 participants were randomlyassigned to either Atkins (carbohydrate restriction, n=40), Zone (macronutrientbalance, n=40), Weight Watchers (calorie restriction, n=40), or Ornish (fat restriction,n=40) diet groups. After 2 months of maximum effort, participants selected their ownlevels of dietary adherence. MAIN OUTCOME MEASURES: One-year changes inbaseline weight and cardiac risk factors, and self-selected dietary adherence ratesper self-report. RESULTS: Assuming no change from baseline for participants whodiscontinued the study, mean (SD) weight loss at 1 year was 2.1 (4.8) kg for Atkins(21 [53%] of 40 participants completed, P = .009), 3.2 (6.0) kg for Zone (26 [65%] of40 completed, P = .002), 3.0 (4.9) kg for Weight Watchers (26 [65%] of 40completed, P < .001), and 3.3 (7.3) kg for Ornish (20 [50%] of 40 completed, P = .007). Greater effects were observed in study completers. Each diet significantlyreduced the low-density lipoprotein/high-density lipoprotein (HDL) cholesterol ratio byapproximately 10% (all P<.05), with no significant effects on blood pressure orglucose at 1 year. Amount of weight loss was associated with self-reported dietaryadherence level (r = 0.60; P<.001) but not with diet type (r = 0.07; P = .40). For eachdiet, decreasing levels of total/HDL cholesterol, C-reactive protein, and insulin weresignificantly associated with weight loss (mean r = 0.36, 0.37, and 0.39, respectively)with no significant difference between diets (P = .48, P = .57, P = .31, respectively).CONCLUSIONS: Each popular diet modestly reduced body weight and severalcardiac risk factors at 1 year. Overall dietary adherence rates were low, althoughincreased adherence was associated with greater weight loss and cardiac risk factorreductions for each diet group. 102
  • 102. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004183.Antioxidant supplements for preventing gastrointestinal cancers.Bjelakovic G, Nikolova D, Simonetti RG, Gluud C.Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for ClinicalIntervention Research, Dept. 7102, H:S Rigshospitalet, Copenhagen UniversityHospital, Blegdamsvej 9, DK 2100 Copenhagen, Denmark. g.bjelakovic@ctu.rh.dkBACKGROUND: Oxidative stress may cause gastrointestinal cancers. The evidenceon whether antioxidant supplements are effective in preventing gastrointestinalcancers is contradictory. OBJECTIVES: To assess the beneficial and harmful effectsof antioxidant supplements in preventing gastrointestinal cancers. SEARCHSTRATEGY: We identified trials through the trials registers of the four CochraneReview Groups on gastrointestinal diseases, The Cochrane Central Register ofControlled Trials on The Cochrane Library (Issue 1, 2003), MEDLINE, EMBASE,LILACS, and SCI-EXPANDED from inception to February 2003, and The ChineseBiomedical Database (March 2003). We scanned reference lists and contactedpharmaceutical companies. SELECTION CRITERIA: Randomised trials comparingantioxidant supplements to placebo/no intervention examining the incidence ofgastrointestinal cancers. DATA COLLECTION AND ANALYSIS: Two reviewersindependently selected trials for inclusion and extracted data. The outcomemeasures were incidence of gastrointestinal cancers, overall mortality, and adverseevents. Outcomes were reported as relative risks (RR) with 95% confidence interval(CI) based on fixed and random effects meta-analyses. MAIN RESULTS: Weidentified 14 randomised trials (170,525 participants), assessing beta-carotene (9trials), vitamin A (4 trials), vitamin C (4 trials), vitamin E (5 trials), and selenium (6trials). Trial quality was generally high. Heterogeneity was low to moderate. Neitherthe fixed effect (RR 0.96, 95% CI 0.88 to 1.04) nor random effects meta-analyses(RR 0.90, 95% CI 0.77 to 1.05) showed significant effects of supplementation withantioxidants on the incidences of gastrointestinal cancers. Among the seven high-quality trials reporting on mortality (131,727 participants), the fixed effect (RR 1.06,95% CI 1.02 to 1.10) unlike the random effects meta-analysis (RR 1.06, 95% CI 0.98to 1.15) showed that antioxidant supplements significantly increased mortality. Twolow-quality trials (32,302 participants) found no significant effect of antioxidantsupplementation on mortality. The difference between the mortality estimates in high-and low-quality trials was significant by test of interaction (z = 2.10, P = 0.04). Beta-carotene and vitamin A (RR 1.29, 95% CI 1.14 to 1.45) and beta-carotene andvitamin E (RR 1.10, 95% CI 1.01 to 1.20) significantly increased mortality, while beta-carotene alone only tended to do so (RR 1.05, 95% CI 0.99 to 1.11). Increasedyellowing of the skin and belching were non-serious adverse effects of beta-carotene.In four trials (three with unclear/inadequate methodology), selenium showedsignificant beneficial effect on gastrointestinal cancer incidences. REVIEWERSCONCLUSIONS: We could not find evidence that antioxidant supplements preventgastrointestinal cancers. On the contrary, they seem to increase overall mortality.The potential cancer preventive effect of selenium should be studied in adequatelyconducted randomised trials. 103
  • 103. Lancet. 2005 Feb 26;365(9461):764-72.Effect of timing and method of enteral tube feeding for dysphagicstroke patients (FOOD): a multicentre randomised controlled trial.Dennis MS, Lewis SC, Warlow C; FOOD Trial Collaboration.Department of Clinical Neurosciences, Western General Hospital, Edinburgh EH42XU, UK. Undernutrition is common in patients admitted with stroke. Weaimed to establish whether the timing and route of enteral tube feeding after strokeaffected patients outcomes at 6 months. METHODS: The FOOD trials consist ofthree pragmatic multicentre randomised controlled trials, two of which includeddysphagic stroke patients. In one trial, patients enrolled within 7 days of admissionwere randomly allocated to early enteral tube feeding or no tube feeding for morethan 7 days (early versus avoid). In the other, patients were allocated percutaneousendoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome wasdeath or poor outcome at 6 months. Analysis was by intention to treat. FINDINGS:Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitalsin 15 countries into the early versus avoid trial. Early tube feeding was associatedwith an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) anda reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versusnasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries.PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5,p=0.05). INTERPRETATION: Early tube feeding might reduce case fatality, but at theexpense of increasing the proportion surviving with poor outcome. Our data do notsupport a policy of early initiation of PEG feeding in dysphagic stroke patients. 104
  • 104. Am J Gastroenterol. 2005 Feb;100(2):432-9A randomized study of early nasogastric versus nasojejunal feeding insevere acute pancreatitis.Eatock FC, Chong P, Menezes N, Murray L, McKay CJ, Carter CR, Imrie CW.Lister Department of Surgery and Department of Nutrition and Dietetics, GlasgowRoyal Infirmary, Alexandra Parade, Glasgow G31 2ER, Scotland.BACKGROUND: After 50 yr in which nasoenteric feeding was consideredcontraindicated in acute pancreatitis (AP), several clinical studies have shown thatearly nasojejunal (NJ) feeding can be achieved in most patients. A pilot study of earlynasogastric (NG) feeding in patients with objectively graded severe AP proved thatthis approach was also feasible. A randomized study comparing NG versus NJfeeding has been performed. METHODS: A total of 50 consecutive patients withobjectively graded severe AP were randomized to receive either NG or NJ feedingvia a fine bore feeding tube. The end points were markers of the acute phaseresponse APACHE II scores and C-reactive protein (CRP) measurements, and painpatterns by visual analogue score (VAS) and analgesic requirements. Complicationswere monitored and comparisons made of both total hospital and intensive-carestays. RESULTS: A total of 27 patients were randomized to NG feeding and 23 toNJ. One of those in the NJ group had a false diagnosis, thereby reducing the numberto 22. Demographics were similar between the groups and no significant differenceswere found between the groups in APACHE II score, CRP measurement, VAS, oranalgesic requirement. Clinical differences between the two groups were notsignificant. Overall mortality was 24.5% with five deaths in the NG group and sevenin the NJ group. CONCLUSIONS: The simpler, cheaper, and more easily used NGfeeding is as good as NJ feeding in patients with objectively graded severe AP. Thisappears to be a useful and practical therapeutic approach to enteral feeding in theearly management of patients with severe AP.Editorial hierzu:Am J Gastroenterol. 2005 Feb;100(2):440-1.What route to feed patients with severe acute pancreatitis: vein,jejunum, or stomach?Raimondo M, Scolapio JS. 105
  • 105. Eur J Gastroenterol Hepatol. 2004 Nov;16(12):1375-80.Combining steroids with enteral nutrition: a better therapeuticstrategy for severe alcoholic hepatitis? Results of a pilot study.Alvarez MA, Cabre E, Lorenzo-Zuniga V, Montoliu S, Planas R, Gassull MA.Department of Gastroenterology, University Hospital Germans Trias i Pujol,Badalona, Catalonia, Spain.BACKGROUND: Results of a previous randomized controlled trial comparing theoutcome of patients with severe alcoholic hepatitis treated with total enteral nutrition(TEN) or corticosteroids suggest that these treatments act through differentmechanisms and may be complementary. We report a pilot study of combinedtreatment with TEN and a shorter course of steroids in patients with severe alcoholichepatitis. METHODS: Thirteen patients with severe alcoholic hepatitis were treatedwith systemic steroids and TEN. Steroid therapy started with 40 mg oral prednisolonedaily, and was progressively tapered as soon as both serum bilirubin andprothrombin time decreased below 50% of their baseline values. TEN (2000 kcal, or8374 kJ, daily) was administered throughout the hospital stay. Patients were followedfor at least 12 months or until death. RESULTS: Tapering of prednisolone dose couldbe started after a mean (SD) of 15.4 (3.8) days, whereas TEN was maintained for 22(3.8) days. TEN was tolerated in 10 of the 13 patients. The major adverse eventattributable to therapy was hyperglycemia requiring insulin therapy, which occurred in12 of 13 patients. Only two patients (15%) died during the treatment period. Anotherpatient died within the first 2 months of follow-up. In no case was the death due toinfectious complications, despite two-thirds of patients developing infections duringthe treatment period. Infections during follow-up occurred only in three patients.CONCLUSION: This pilot study suggests that TEN associated with a short course ofsteroids could be a good therapeutic strategy for severe alcoholic hepatitis. Thispossibility deserves investigation in a randomized controlled trial.Paper zum vorigen:Hepatology. 2000 Jul;32(1):36-42.Short- and long-term outcome of severe alcohol-induced hepatitistreated with steroids or enteral nutrition: a multicenter randomizedtrial.Cabr inverted question marke E, Rodr inverted question markiguez-Iglesias P,Caballer inverted question markia J, Quer JC, S inverted question markanchez-Lombrana JL, Par inverted question markes A, Papo M, Planas R, Gassull MA.Steroids are recommended in severe alcohol-induced hepatitis, but some datasuggest that artificial nutrition could also be effective. We conducted a randomizedtrial comparing the short- and long-term effects of total enteral nutrition or steroids inthese patients. A total of 71 patients (80% cirrhotic) were randomized to receive 40mg/d prednisolone (n = 36) or enteral tube feeding (2,000 kcal/d) for 28 days (n =35), and were followed for 1 year or until death. Side effects of treatment occurred in5 patients on steroids and 10 on enteral nutrition (not significant). Eight enterally fed 106
  • 106. patients were prematurely withdrawn from the trial. Mortality during treatment wassimilar in both groups (9 of 36 vs. 11 of 35, intention-to-treat) but occurred earlier withenteral feeding (median 7 vs. 23 days; P =.025). Mortality during follow-up washigher with steroids (10 of 27 vs. 2 of 24 intention-to-treat; P =. 04). Seven steroidpatients died within the first 1.5 months of follow-up. In contrast to total enteralnutrition (TEN), infections accounted for 9 of 10 follow-up deaths in the steroid group.In conclusion, enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis, although death occurs earlier withenteral nutrition. However, steroid therapy is associated with a higher mortality rate inthe immediate weeks after treatment, mainly because of infections. A possiblesynergistic effect of both treatments should be investigated. 107
  • 107. 2. DDW AbstractsDDW Abstract 54-Suppl. to Gastroenterol.2, 2005 Apr.;128(4):A-778Disclosures: NoneEnteral Nutrition Improves Functional Parameters in Liver CirrhosisK. Norman, H. Kirchner, U. Friedrich, H. Lochs, J. Ockenga, M. PirlichIntroduction: Malnutrition is a frequent problem in liver cirrhosis, occurring in up to60% of all patients. It has devastating consequences affecting morbidity andmortality. Both physical and metabolic functions are severely compromised.Aim: We investigated whether short term enteral nutrition is useful in improvingphysical and metabolic parameters in patients with advanced liver cirrhosis.Methods: We randomized 25 patients with decompensated liver cirrhosis (Child Pughscore B or C) to receive either high protein enteral nutrition (35 kcal/kg bodyweightand 1.5 g protein/kg bodyweight) via nasogastric tube (n=13) or standard hospitaldiet for 2 weeks (n=12). Patients with malignant or terminal disease were notincluded. The patients were assessed before and after nutritional intervention.Nutritional status on admission was characterized by the Subjective GlobalAssessment. Liver function was determined by prothrombin time, bilirubin andalbumin. Muscle function was assessed by hand grip strength dynamometry. Bodycomposition was measured by bioelectrical impedance analysis.Results: 20 (77 %) patients were classified as malnourished and 23 (92%) had handgrip strength values below 85 % of gender and age related norm. Intervention andcontrol patients did not differ regarding age, nutritional status, muscle function, andseverity of disease.Enteral nutrition significantly improved muscle function in the intervention group (from25.2 +/- 10.9 kg to 29.9 +/- 9.2 kg, p=0.035), whereas it did not change significantly inthe control group (from 27.1 +/- 12.1 kg to 30.5 +/- 12.5 kg, n.s.). Simultaneously,prothrombin time increased significantly in the intervention group (from 52.4 +/- 17.8% to 61.2 +/- 21.8 %, p<0.05) but no significant improvement occurred in controls(from 53.1 +/- 14.3 % to 58.0 +/- 15.2%, n.s.). Bilirubin, albumin and bodycomposition did not change significantly during the study period, although there wasa slight increase in body cell mass in the intervention group, which however did notreach statistical significance.Conclusion: The majority of our patients with advanced liver cirrhosis were classifiedmalnourished according to the SGA (77%). Short term enteral nutrition initiated onadmission to hospital however succeeded in improving both muscle function andprothrombin time. Intensive nutritional therapy should therefore be part of thetherapeutic concept in these patients. 108