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. firstname.lastname@example.orgOBJECTIVE: 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
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
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. email@example.comBACKGROUND & 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.
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.
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*
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.
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. firstname.lastname@example.orgBACKGROUND & 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.
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.
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.
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. email@example.comAIM: 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).
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 .
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.
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.
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.
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. firstname.lastname@example.orgThe 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.
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.
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.
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
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*
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.
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.
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
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.
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.
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.