Forsker Dag. Åben. 28. april 2011 TRINITY Hotel & Conference Centre ABSTRACTS. Syddansk Sundhedsvidenskabeligt Forskningsforum

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1 ABSTRACTS Syddansk Sundhedsvidenskabeligt Forskningsforum Åben Forsker Dag 28. april 2011 TRINITY Hotel & Conference Centre Gl. Færgevej 30, Snoghøj, Fredericia

2 PROGRAM Åben Forsker Dag 28. april 2011 Formiddag kl Workshops med foredrag om forskningsprojekter i Syddanmark LOKALE 1- Infektion og cancer Radiation dose to the heart and survival in NSCLC treated with definitive radiotherapy. Reversal of Methicillin Resistance in Staphylococcus aureus by Thioridazine: a universal phenomenon? Prognostiske faktorer hos patienter med lokal avanceret bugspytkirtelkræft behandlet med kemoradioterapi. HIF-1α and GLUT-1 expressions do not correlate with response and survival after preoperative chemoradiotherapy in rectal cancer. SIRS og sepsis blandt akutte medicinske patienter. The clinical significance of quantitative HER2 determination in breast cancer. Identification and Ranking of Side-effects in Patients Receiving Radiotherapy and Concomitant Weekly Cisplatin. A Multinational Collaborative Survey. Screening med en 8-plex PCR for enteropatogene Escherichia coli direkte på DNA fra fæcesprøver. Pause A new everyday life - Rehabilitation after radiotherapy for prostate cancer. Netværket som med- og modspiller i et kræftbehandlingsforløb. Human macrophage foam cells generate a specific proteolytic fragment of CRP - a novel method for evaluation of macrophage foam cell activity. ER, HER2, and TOP2A expression in primary tumor, axillary nodes, and asynchronous metastases in breast cancer. Antibiotikaforbrug forud for samfundserhvervede urinvejsinfektioner med extended-spectrum β-lactamase (ESBL) Escherichia coli. Er C-reaktivt protein en uafhængig mortalitetsprædiktor hos voksne bakteriæmi-patienter med kendt sepsisgrad? et DORISprojekt. Estimation of immunohistochemical expression of VEGF in ductal carcinomas of the breast. The Prognostic Value of Syndecan-1 in Ovarian Cancer Patients with Long-Term Follow up. LOKALE 2- Knogle, urologi/gynækologi og diabetes Hip Structure Analysis (HAS) in patients with Osteogenesis Imperfecta (OI) compared with age and sex matched healthy controls. The combination of structural parameters and areal bone mineral density improve strength prediction in the proximal femur. An in vitro study with high resolution peripheral quantitative computed tomography. Symptoms and Quality of Life before and after Urogynecological Surgery for Pelvic Organ Prolapse an Analysis of the Danish Urogynecological Database. Global gene expression profiling to identify the mechanisms involved in the protection of pancreatic islets by vitamin D. Studying of in vitro and in vivo mechanisms of enhancing osteoblastic functions and bone formation by a protein kinase inhibitor (KIx): potential novel drug for treatment of bone-loss diseases. Glucocorticoid-induced changes in the geometry of osteoclast resorption cavities are sufficient to alter bone quality: an assessment through a model simulating bone stiffness. Phenotypic characterization of the mononucleated cells appearing during the reversal phase of bone remodelling. Pause Increased frequency of capillaries at remodelling sites in adult human bone. Studies of association between STX5 variants with Type 2 Diabetes and related metabolic traits in Danes. Arrest of the reversal phase is a critical mechanism involved in Glucocorticoid-induced bone loss. Does treatment of multiple myeloma with a combination of bortezomib and dexamethasone result in opposite effects on osteoclasts and osteoclast precursors? Behandling af Visceral smerte udgående fra øvre urinveje efter perkutan nyrestensoperation. Are reversal cells critical players in the bone loss occurring in postmenopausal osteoporosis? Separate developmental programs for HLA-A and B expression during differentiation from embryonic stem cells to lymphocytes, adipocytes and osteocytes. Diabetes mellitus, metaboliske risikofaktorer og autoimmunitet hos kvinder med tidligere gestationel diabetes mellitus (GDM). Mechanisms controlling the direction and termination of osteoclastic resorption. 2

3 PROGRAM Åben Forsker Dag 28. april 2011 LOKALE 3- Akut/organisation og andet Patientforløb ved akut abdomen i akutmodtagelser. Dokumentation og udredning af komplekse posttraumatiske reaktioner hos bosniske flygtninge i danske behandlingscentre. Characterization of regulatory mechanisms influencing the class-specific differential expression of HLA-A, -B and -C. "Risikostratificeret screening for osteoporose i Region Syddanmark" - Et studie med fokus på patientperspektivet. Løbende evaluering af DDKM og kvalitetsudviklingstiltag i kontekst-proces-effekt perspektiv. Astma, livskvalitet og erhvervsaktivitet hvordan hænger det sammen? Sårbarhed og risiko for udviklingen af kroniske smerter: Tilknytning og PTSD undersøgt i forskellige smertepopulationer. Klinisk konsekvens af ekstrakardielle fund ved Hjerte-CT. Pause Patients with hypertension are still not treated to target blood pressure. A cross sectional study comprising 5413 hypertensive patients treated in general practice in Denmark. Har forskellige typer ambulant opfølgning betydning for, hvordan self-efficacy udvikler sig hos patienter med leddegigt? SPACE for Physical Activity - A Child Perspective. Afslutning af behandling på intensivt afsnit - hvordan fungerer det tværfaglige samarbejde? Collagen type VI neo-epitope as biochemical marker of liver fibrosis. Ultralydsskanning af lunger, lungehinder og hjerte hos akut indlagte patienter med respiratoriske symptomer. Prominent polyfarmaci blandt patienter i antikoagulans-behandling. Fælles medicinsk modtageafsnit reducerer indlæggelsestiden. Overførbarhed af tværfaglige evalueringer af telemedicin KOL kufferten som case. Eftermiddag kl Tema: Hvilke effekter ønsker vi os af Sundhedsforskningen i Syddanmark Kl Kl Kl Kl Kl Kl Kl Kl Kl Kl Frokost Velkomst Formandskabet for Ledelsesforum for Medicinsk Sundhedsforskning i Syddanmark/Syddansk Sundhedsvidenskabeligt Forskningsforum: Direktør sundhedsområdet Per Busk, Region Syddanmark Dekan Ole Skøtt, Det Sundhedsvidenskabelige Fakultet, Syddansk Universitet. Universiteterne Rektor og formand for Danske Universiteter Jens Oddershede. Region Syddanmark Regionsrådspolitiker og næstformand i Regionsrådet Poul-Erik Svendsen. Erhvervslivet Specialkonsulent Jakob Bjerg Larsen, Lægemiddel industri foreningen (Lif) Pause Funktions- og specialeplanlægning Direktør Henrik Villadsen, Odense Universitetshospital i Region Syddanmark. Den kliniske forsker Professor Torben Plesner, Institut for Regional Sundhedsforskning, Center Sygehus Lillebælt Translationel forskning Institutleder Uffe Holmskov, Institut for Molekylær Medicin, Det Sundhedsvidenskabelige Fakultet, Syddansk Universitet. Panel og Afslutning Paneldeltagere: Oplægsholdere. Ordstyrer: Dekan Ole Skøtt 3

4 Indholdsfortegnelse Infektion Reversal of Methicillin Resistance in Staphylococcus aureus by Thioridazine: a universal phenomenon?.. 8 SIRS og sepsis blandt akutte medicinske patienter... 9 Screening med en 8-plex PCR for enteropatogene Escherichia coli direkte på DNA fra fæcesprøver...10 Human macrophage foam cells generate a specific proteolytic fragment of CRP - a novel method for evaluation of macrophage foam cell activity...11 Antibiotikaforbrug forud for samfundserhvervede urinvejsinfektioner med extended-spectrum β- lactamase (ESBL) Escherichia coli...12 Er C-reaktivt protein en uafhængig mortalitetsprædiktor hos voksne bakteriæmi-patienter med kendt sepsisgrad? et DORIS-projekt...13 Cancer Radiation dose to the heart and survival in NSCLC treated with definitive radiotherapy Prognostiske faktorer hos patienter med lokal avanceret bugspytkirtelkræft behandlet med kemoradioterapi HIF-1α and GLUT-1 expressions do not correlate with response and survival after preoperative chemoradiotherapy in rectal cancer The clinical significance of quantitative HER2 determination in breast cancer...18 Identification and Ranking of Side-effects in Patients Receiving Radiotherapy and Concomitant Weekly Cisplatin. A Multinational Collaborative Survey...19 A new everyday life - Rehabilitation after radiotherapy for prostate cancer Netværket som med- og modspiller i et kræftbehandlingsforløb...21 ER, HER2, and TOP2A expression in primary tumor, axillary nodes, and asynchronous metastases in breast cancer...22 Estimation of immunohistochemical expression of VEGF in ductal carcinomas of the breast...23 The Prognostic Value of Syndecan-1 in Ovarian Cancer Patients with Long-Term Follow up...24 Knogle Hip Structure Analysis (HAS) in patients with Osteogenesis Imperfecta (OI) compared with age and sex matched healthy controls...26 The combination of structural parameters and areal bone mineral density improve strength prediction in the proximal femur. An in vitro study with high resolution peripheral quantitative computed tomography...27 Studying of in vitro and in vivo mechanisms of enhancing osteoblastic functions and bone formation by a protein kinase inhibitor (KIx): potential novel drug for treatment of bone-loss diseases

5 Glucocorticoid-induced changes in the geometry of osteoclast resorption cavities are sufficient to alter bone quality: an assessment through a model simulating bone stiffness...29 Phenotypic characterization of the mononucleated cells appearing during the reversal phase of bone remodelling...30 Increased frequency of capillaries at remodelling sites in adult human bone...31 Arrest of the reversal phase is a critical mechanism involved in Glucocorticoid-induced bone loss...32 Does treatment of multiple myeloma with a combination of bortezomib and dexamethasone result in opposite effects on osteoclasts and osteoclast precursors?...33 Are reversal cells critical players in the bone loss occurring in postmenopausal osteoporosis?...34 Separate developmental programs for HLA-A and B expression during differentiation from embryonic stem cells to lymphocytes, adipocytes and osteocytes Mechanisms controlling the direction and termination of osteoclastic resorption...36 Diabetes Global gene expression profiling to identify the mechanisms involved in the protection of pancreatic islets by vitamin D...38 Studies of association between STX5 variants with Type 2 Diabetes and related metabolic traits in Danes...39 Diabetes mellitus, metaboliske risikofaktorer og autoimmunitet hos kvinder med tidligere gestationel diabetes mellitus (GDM)...40 Urologi/gynækologi Symptoms and Quality of Life before and after Urogynecological Surgery for Pelvic Organ Prolapse an Analysis of the Danish Urogynecological Database...42 Overvægt, graviditet & kommunikation...43 Behandling af visceral smerte udgående fra øvre urinveje efter perkutan nyrestensoperation Akut/organisation Patientforløb ved akut abdomen i akutmodtagelser...46 Dokumentation og udredning af komplekse posttraumatiske reaktioner hos bosniske flygtninge i danske behandlingscentre...47 "Risikostratificeret screening for osteoporose i Region Syddanmark" - Et studie med fokus på patientperspektivet Løbende evaluering af DDKM og kvalitetsudviklingstiltag i kontekst-proces-effekt perspektiv...50 Sårbarhed og risiko for udviklingen af kroniske smerter: Tilknytning og PTSD undersøgt i forskellige smertepopulationer Patients with hypertension are still not treated to target blood pressure. A cross sectional study comprising 5413 hypertensive patients treated in general practice in Denmark...53 Har forskellige typer ambulant opfølgning betydning for, hvordan self-efficacy udvikler sig hos patienter med leddegigt?

6 Afslutning af behandling på intensivt afsnit - hvordan fungerer det tværfaglige samarbejde?...55 Ultralydsskanning af lunger, lungehinder og hjerte hos akut indlagte patienter med respiratoriske symptomer Fælles medicinsk modtageafsnit reducerer indlæggelsestiden...57 Andet Characterization of regulatory mechanisms influencing the class-specific differential expression of HLA-A, -B and -C...59 Astma, livskvalitet og erhvervsaktivitet hvordan hænger det sammen?...60 Klinisk konsekvens af ekstrakardielle fund ved Hjerte-CT...61 SPACE for Physical Activity - A Child Perspective...62 Collagen type VI neo-epitope as biochemical marker of liver fibrosis...63 Prominent polyfarmaci blandt patienter i antikoagulans-behandling...64 Overførbarhed af tværfaglige evalueringer af telemedicin KOL kufferten som case

7 7 Infektion

8 Reversal of Methicillin Resistance in Staphylococcus aureus by Thioridazine: a universal phenomenon? Forfattere Marianne Ø. Poulsen 1,2, Janne K. Klitgaard 1,2, Marianne N. Skov 1, Birgitte H. Kallipolitis 2, Hans Jørn Kolmos 1 1 Institute of Clinical Research, University of Southern Denmark, Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark. 2 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Foredrag Metode Resultater Konklusion Odense, Denmark. mpoulsen@health.sdu.dk, jkklitgaard@health.sdu.dk, marianne.skov@ouh.regionsyddanmark.dk, bhk@bmb.sdu.dk, hans.joern.kolmos@ouh.regionsyddanmark.dk Marianne Ø. Poulsen Thioridazine, a phenothiazine agent, has been shown to reverse oxacillin resistance in methicillin-resistant Staphylococcus aureus (MRSA) in vitro. The molecular mechanism underlying this effect is not fully understood. So far this has been shown with only one clinical MRSA isolate. The aim of this study was to determine if resistance reversal with thioridazine could be reproduced in a broader selection of clinical isolates, and if the molecular mechanism was the same in all isolates. To this end, we tested the effect of thioridazine on major Danish epidemic clones of MRSA and Staphylococcal cassette chromosome mec (SCCmec) types, 3 VISA (Vancomycin-intermediate S. aureus) strains and 3clinical MRSE strains (Methicillin-resistant S. epidermis). Growth of MRSA isolates was examined in liquid media in the presence of the methicillin analogue oxacillin and the non-antibiotic thioridazine alone and in combination. Furthermore, the transcription of meca was analyzed by Primer extension under the same conditions. Levels of the penicillin binding protein, PBP2a, was analysed by Western Blotting. We observed an increased susceptibility of MRSA towards oxacillin in the presence of oxacillin and thioridazine compared to bacteria grown with oxacillin or thioridazine alone in all isolates tested. Transcription of the resistance marker, meca, was reduced with increasing concentrations of thioridazine in the presence of oxacillin compared to bacteria grown with oxacillin or thioridazine alone. However, in a few isolates meca was transcribed constitutively and did not display a reduced transcription of meca with increasing concentrations of thioridazine in the presence of oxacillin. Thioridazine itself did not affect the growth of MRSA or the level of meca mrna. The synergistic effect was less definite in the VISA and the MRSE strains. Results from the present study indicate that the reversal effect of thioridazine on oxacillin resistance is universal for clinical MRSA isolates of various epidemiological origins. This reversal effect was more diverse in the VISA and MRSE strains. Furthermore, the data indicates that the molecular mechanism behind the reversal effect of thioridazine is independent of resistance. 8

9 SIRS og sepsis blandt akutte medicinske patienter Forfattere Foredrag Design Metode Resultater Konklusion Daniel Pilsgaard Henriksen, Læge, Ph.d. stud. Klinisk Institut, Det Sundhedsvidenskabelige Fakultet, SDU; Hanne Madsen Akut Medicinsk Modtageafdeling AMA, OUH; Court Pedersen Infektionsmedicinsk afdeling Q, OUH; Annmarie Lassen Akut Medicinsk Modtageafdeling AMA, OUH Daniel Pilsgaard Henriksen Svær sepsis og septisk shock er livstruende tilstande, men den eksakte hyppighed i Danmark og resten af Europa er ukendt. Forekomst og anvendelighed af symptomer på systemisk inflammatorisk respons (SIRS) i den primære vurdering, hos akutte medicinske patienter, er ligeledes ukendt. et er, at beskrive incidens, risikofaktorer og prognose af SIRS, samfundserhvervet infektion, sepsis, svær sepsis og septisk shock blandt akut indlagte medicinske patienter. Prospektivt kohortestudie af alle patienter, der bliver indlagt i akut medicinsk modtageafdeling samt alle patienter indlagt via skadestue/lægeambulance direkte i medicinsk intensivt regi på OUH i en etårig periode. Alle indlagte patienter får rutinemæssigt registreret vital- værdier ved ankomst (blodtryk, puls respirationsfrekvens, temperatur) samt taget blodprøver inklusiv leukocyttal. På basis af journaloplysninger afgøres det om patienten - i henhold til prædefinerede kriterier - har SIRS, infektion, sepsis, svær sepsis samt septisk shock ved ankomst eller udviklet indenfor det første døgn. Fra 1. september 2010 til 17. marts 2011 er der registreret 4580 patientforløb fordelt på 3674 patienter. Der er indtil videre et vellykket inklusionsforløb hvor tidsplanen overholdes og patientantallet er som forventet. 9

10 Screening med en 8-plex PCR for enteropatogene Escherichia coli direkte på DNA fra fæcesprøver Forfattere Foredrag Design Metode Resultater Konklusion Jens K. Møller, Birte Kolmos, Margrethe Dahl, Lone Pødenphant & Dorthe Ørnskov Klinisk Mikrobiologisk Afdeling, Vejle Sygehus Jens K. Møller Undersøge en in-house 8-plex PCR test (7 specifikke virulens gener og 1 intern kontrol) i en enkelt-rørs reaktion for evnen til at finde fem patotyper af diaré-fremkaldende E. coli i DNA ekstraheret ved tre protokoller: (1) direkte fra fæcesprøve vha. NorDiag Bullet, (2) fra skrab fra konventionel primær dyrkningsplade SSI Enteric Medium (Statens Serum Institut), (3) fra E. coli som repræsenterer forskellige kolonimorfologier rendyrket på chromid CPS plader (biomerieux). Prospektivt studie af 387 tilfældigt udvalgte fæcesprøver indsendt fra patienter med kronisk diaré. DNA blev ekstraheret direkte fra fæcesprøver vha. Bullet stool DNA sample kit og protokol fra NorDiag (Oslo), og fra dyrkningsplader ved kogning og fortynding af skrab eller E. coli kolonier. Primere for virulensgenerne Stx1, Stx2, og eaea for enterohæmorrhagiske E. coli (EHEC), eaea for enteropatogene E. coli (EPEC), STIb og LTI for enterotoksigene E. coli (ETEC), ipah for enteroinvasive E. coli (EIEC) og aggr for entero-aggregative E. coli (EAEC) blev anvendt. Forward primer blev mærket med fluorochrome og PCR produkterne separeret ved multicolour capillary electrophoresis på en ABI PRISM 3130 Genetic Analyzer (Applied Biosystems). Sande positive prøver blev defineret som PCR positive i mindst 2 af de 3 protokoller. I alt 102 (26,4 %) fæcesprøver indeholdt en eller flere af de 7 virulensgener. Sensitiviteten af 8-plex PCR på fæces direkte, skrab fra primær dyrkningsplade, og rendyrkede E. coli kolonier var henholdsvis 97,1 % (99/102), 91,2 % (93/102) og 76,5 % (78/102). Specificiteten var tilsvarende 98,2 % (280/285), 98,6 % (281/285) og 100 % (285/285). Hyppigste fund var eaea genet med 54,6 % (53/97) i PCR-positive skrab, 61,5 % (64/104) i PCR-positive fæcesprøver direkte, 48,7 % (38/78) i PCR-positive E. coli. Næsthyppigst var aggr genet i 45,4 %, 44,2 % og 52,6 % af de tilsvarende PCR-positive prøver. Screening for virulensgener med PCR på DNA ekstraheret direkte fra fæces efterfulgt af dyrkning alene af PCR-positive prøver udgør et effektivt og hurtigt alternativ til den nuværende dyrkningsbaserede påvisning af enteropatogene E. coli. 10

11 Human macrophage foam cells generate a specific proteolytic fragment of CRP - a novel method for evaluation of macrophage foam cell activity Forfattere Helene Skjøt-Arkil 1,2, Diana Leeming 1, Morten Karsdal 1. 1 Nordic Bioscience, Herlev Hovedgade 207, Herlev, Denmark, Southern University of Foredrag Metode Resultater Konklusion Denmark, Falculty of Health Sciences hbe@nordicbioscience.com Helene Skjøt-Arkil Atherosclerotic plaque remodeling may in part be the result of proteolytic degradation of type I collagen by proteases secreted by macrophage-foam cells (MFs). In addition to being a risk marker, there is more evidence indicating that C-reactive protein (CRP) may actively participate in atherogenesis. The aim of the present study was to investigate the role of CRP on the activity of MFs and the derived matrix remodeling. The activity of MFs was evaluated by the newly identified MMP generated degradation fragment of CRP the CRP-25. The remodeling of the matrix was measured by CO1-764, which is a MMP generated fragment of type I collagen. Human CD14 positive monocytes were isolated and differentiated into MFs. Subsequently, MFs were cultured for 10 days on a collagen type I rich matrigel in presence/absence of the MMP inhibitor GM6001, the cysteine inhibitor E64, different doses of TNFa and CRP. Levels of CRP-25 were monitored in the conditioned media using a newly developed ELISA, which only monitor the MMP degraded form of CRP (CRP-25) and not the elongated peptide nor total CRP. CO1-764 was measured by an ELISA specific for MMP degraded type I collagen and not intact type I collagen. Exposing MFs to CRP caused a dose-dependent release of CRP-25 during the 10 days incubation; e.g. 100ng/mL CRP elevated the levels with 280%. MFs cultured on a collagen type I rich matrix generated 183% more CO1-764 when exposed to TNFa compared to no treatment. This level was abrogated by addition of the MMP inhibitor GM6001. Treatment by 100ng/mL CRP increased the release of CO1-764 by 330%. This is to our knowledge the first study describing a CRP activated fragment generated by macrophage foam cells. This may allow for investigation of the direct macrophage inflammation driven pathophysiological processes. In addition, we clearly demonstrate that CRP induces MMP generated matrix degradation through modulation of macrophage activity directly. 11

12 Antibiotikaforbrug forud for samfundserhvervede urinvejsinfektioner med extended-spectrum β-lactamase (ESBL) Escherichia coli Forfattere Foredrag Design Metode Variable Resultater Kim Oren Gradel, Forskningsenheden for Klinisk Epidemiologi, Klinisk Institut, Syddansk Universitet, Kompetencecenter Syd for Landsdækkende Kliniske Databaser, OUH, Hans Jørn Kolmos, Klinisk Mikrobiologisk Afdeling, OUH Kim Oren Gradel Incidensen af samfundserhvervede urinvejsinfektioner med ESBL E. coli er stigende, men der er meget sparsom viden om mulige årsager til dette. Vi ønsker at undersøge om der er en sammenhæng mellem antibiotikaforbrug og samfundserhvervede urinvejsinfektioner med ESBL E. coli. Alle incidente urinvejsinfektioner med ESBL eller fuldt antibiotikafølsomme E. coli, indsendt fra praktiserende læger i Fyns Amt, Kontroller er tilfældigt udtrukket fra baggrundsbefolkningen. Eksponering er receptindløste antibiotika i året forud for urinvejsinfektionen. Der justeres for alder, køn, komorbiditet, indlæggelser og urinvejsmisdannelser. Antal patienter muliggør desuden stratificerede analyser. Case-kontrol design, hvor ESBL E. coli og fuldt følsomme E. coli sammenlignes med kontroller i to separate logistiske regressionsanalyser. Odds ratios fra hver af disse analyser sammenlignes for at vurdere om antibiotikaindløsninger er associeret med udvikling af ESBL. Fra Lægemiddelregisteret fås oplysninger om receptindløste antibiotika. I analyserne indgår om antibiotika er indløst i året forud for urinvejsinfektionen (ja/nej) samt antal indløste recepter. Fra Landspatientregisteret udtrækkes data om komorbiditet, indlæggelser i året forud for urinvejsinfektionen samt urinvejsmisdannelser. Kontroller udtrækkes tilfældigt fra CPR-registeret. Analyserne er ikke påbegyndt. Vi estimerer der vil være 350 ESBL E. coli og fuldt følsomme E. coli. Hertil udtrækkes kontroller. 12

13 Er C-reaktivt protein en uafhængig mortalitetsprædiktor hos voksne bakteriæmi-patienter med kendt sepsisgrad? et DORIS-projekt Forfattere Kim Oren Gradel, Forskningsenheden for Klinisk Epidemiologi, Klinisk Institut, Syddansk Universitet, Kompetencecenter Syd for Landsdækkende Kliniske Databaser, OUH; Court Pedersen, Infektionsmedicinsk Afdeling Q, OUH; Thøger Gorm Jensen, Klinisk Mikrobiologisk Afdeling, OUH; Pernille Just Vinholt, Afdeling for Klinisk Biokemi og Farmakologi, OUH; Hans Jørn Kolmos, Klinisk Mikrobiologisk Afdeling, OUH; Annmarie Touborg Lassen, Akut Modtage Afdeling, OUH Foredrag Kim Oren Gradel Vi ønsker at evaluere om niveauet af C-reaktivt protein (CRP) ved indlæggelse er en uafhængig prognostisk prædiktor for korttids-dødelighed hos voksne patienter med incident samfundserhvervet bakteriæmi for hvilke sepsisgraden kendes. Design Under Danish Observational Registry of Infectious Syndromes (DORIS) er for perioden indsamlet data for alle incidente samfundserhvervede bakteriæmier med de hyppigst forekommende bakteriearter hos patienter >15 år fra Fyn. Metode Prognostisk kohorte-studie med 30-dages dødelighed som outcome. I Model 1 indgår alder, køn, komorbiditet, speciale ved indlæggelse og bakterietyper i Cox s regressionsanalyse. Model 2 er Model 1 med inklusion af sepsisgrad (ikke sepsis [ref.], mulig sepsis, sepsis, svær sepsis eller septisk shock, organsvigt uden SIRS). Model 3 er Model 1 med inklusion af CRP-værdien på dagen for første bakteriepositive bloddyrkning. Model 4 er Model 1 med inklusion af sepsisgrad og CRP. Modellerne sammenlignes v.hj.a. ændringer i de enkelte mortalitets-rate-ratioer (MRR) med 95 % konfidensintervaller (KI). I Model 4 evalueres om CRP er en uafhængig mortalitetsprædiktor ved samtidig justering for sepsisgrad. Variable Kliniske data (temperatur, puls, respiration, blodtryk, tegn til svigt fra: CNS, lunger, nyrer, lever, koagulation, kredsløb) og speciale stammer fra OUH-journaler og laboratoriedata, mens komorbiditetsoplysninger er fra Landspatientregisteret. CRP-data kommer fra NetLabsystemet, Afdeling for Klinisk Biokemi og Farmakologi, mens mikrobiologiske data er fra MADS-systemet, Klinisk Mikrobiologisk Afdeling. Vital status er fra CPR-registeret. Alder og køn er udledt af cpr-nummeret. Resultater Blandt 1999 patienter døde 416 (20,8 %) indenfor 30 dage. I Model 1 var stigende alder og komorbiditet, gram-positive bakterier og indlæggelse på onkologisk eller intensiv afdeling positivt associeret med 30-dages dødelighed. Disse MRR ændredes ikke i Model 2-4. I Model 2 var MRR (95 % KI) for sepsis-patienter 0,58 (0,31-1,06) og for patienter med svær sepsis eller septisk shock 2,21 (1,32-3,72). I Model 3 øgedes 30-dages dødeligheden lineært med 1,7 % for hver 10 mg/l stigning i CRP-værdien. Eneste ændring i Model 4 var øget 30-dages dødeligheden på 1,2 % for hver 10 mg/l CRP-stigning. Konklusion For voksne patienter med samfundserhvervet bakteriæmi var CRP en uafhængig prædiktor for 30-dages dødeligheden, selv efter justering for sepsisgrad. 13

14 14 Cancer

15 Radiation dose to the heart and survival in NSCLC treated with definitive radiotherapy. Forfattere Tine Schytte 1,3, Olfred Hansen, Thomine Stolberg-Rohr 2 and Carsten Brink 2. Department of Oncology 1 and Radiophysic Laboratory 2 Odense University Hospital, Institute of Clinical Research, SDU, Denmark tine.kjestrup.schytte@ouh.regionsyddanmark.dk Foredrag Tine Schytte Lung and oesophageal toxicity has been regarded as main toxicity in definitive radiotherapy (RT) of non-small cell lung cancer (NSCLC), whereas cardiac toxicity has not been offered much concern. This is probably due to the poor prognosis for patients with unresectable NSCLC. In this study we report dosimetric and volumetric of the heart as mean heart dose (MHD) to NSCLC patients (pts) treated with definitive RT in our centre. Metode All RT was applied as 3D-RT in 2 Gy/F without elective nodal irradiation. The planned RT-dose was Gy. All patients were followed to death. Median follow-up was 79 months with 14 month as a minimum. In each patient the heart was delineated in following volumes: Left ventricle, both ventricles and the whole heart. Mean dose was calculated for each volume in the treatment plan. Resultater From , 387 pts with NSCLC (stage I-IIIB and recurrent disease) were treated with definitive RT. Median survival was 18.3 month and overall survival for 1, 2 and 5 year was 67%, 39% and 14%, respectively. High mean dose ( upper quartile) to both ventricles 16.9 Gy was associated to a poorer prognosis (13.7 vs month p=0.47). High mean dose to left ventricle ( 13.8 Gy), or whole heart ( 24.7 Gy) was not associated to poorer prognosis. In a Cox-regression analysis of survival, age >65year, induction chemotherapy high mean dose to left + right ventricles were not a statistically significant factors whereas poor PS and high lung V20, large GTV and gender were. Konklusion When high MHD to left and right ventricle is not a significant factor in Cox-regression analysis, we can not conclude that high MHD to left and right ventricle is relevant for overall survival in this patient group. This might have been different if the amount of long-time survivor was significant longer as in patients with breast cancer. 15

16 Prognostiske faktorer hos patienter med lokal avanceret bugspytkirtelkræft behandlet med kemoradioterapi. Forfattere Jon Kroll Bjerregaard, Onkologisk afd. R, OUH. Michael Bau Mortensen, Kirurgisk afd., OUH. Helle Anita Jensen Onkologisk afd.r, OUH. Morten Nielsen, Onkologisk afdeling R, OUH. Per Pfeiffer, Onkologisk afdeling R, OUH Foredrag Jon Kroll Bjerregaard Den optimale behandling af patienter med lokalavanceret bugspytkirtelkræft er ikke kendt. De fleste patienter har ingen udsigt til at blive raske og en dårlig prognose med en forventet overlevelse på 9 måneder. Studier har dog vist at undergrupper af disse patienter kan have gavn af intensiv behandling med blandt andet kemoradioterapi, og kan derved forlænge livet og eventuelt få en helbredende operation. Vi har lavet en prognostisk model til at forudsige disse undergrupper. Design Retrospektiv analyse af 178 patienter behandlet med kemoradioterapi i perioden Metode Enkelt og multivariabel Cox og logistisk regression, med henblik på overlevelse samt sandsynlighed for resektion. Variable Diverse kliniske variabler. Resultater For overlevelse var tumor størrelse, forbehandling med gemcitabin samt efterfølgende resektion forbundet med signifikant overlevelse. Patienter med stadium III sygdom og lav blodprocent havde en meget lille sandsynlighed for efterfølgende resektion Konklusion Undergrupper af patienter med lokalavanceret bugspytkirtelkræft har øget gavn af intensiv behandling. Patienter der har modtaget kemoterapi forud for kemoradioterapi har forlænget overlevelse. Den prognostiske model giver mulighed for rationel udvikling af nye forsøg og behandlings strategier, til at optimere behandlingen til denne gruppe patienter. 16

17 HIF-1α and GLUT-1 expressions do not correlate with response and survival after preoperative chemoradiotherapy in rectal cancer. Forfattere Foredrag Design Metode Variable Resultater Konklusion Birgitte Mayland Havelund 1, Flemming Brandt Sørensen 2, Jan Lindebjerg 2, Karen-Lise Garm Spindler 1, Anders Jakobsen 1. 1 Department of Oncology, Vejle Hospital, 2 Department of Clinical Pathology, Vejle Hospital, birgitte.mayland.havelund@slb.regionsyddanmark.dk Birgitte Mayland Havelund The aim of the present study was to investigate the Hypoxia-Inducible Factor 1α (HIF-1α) and Glucose Transporter-1 (GLUT-1) expressions in pre-treatment biopsies from rectal tumors as predictors of chemoradiotherapy response as well as the possible prognostic role of the two markers. Translational study in a retrospective material. The immunohistologic expressions of HIF-1α and GLUT-1 were investigated in pretreatment biopsies from 86 patients with rectal cancer receiving long course preoperative chemoradiotherapy. The immunohistologic stainings were scored by assessing semiquantitatively the percentage of stained cells (P) and staining intensity (I). An immunoreactive score (IRS) was calculated by adding the percentage of cells to the intensity (I+P). The response to the chemoradiotherapy was assessed by the Mandard Tumor Regression Grade system (TRG). The expression of HIF-1α and GLUT-1 in relation to TRG and overall survival The intra- and interobserver reproducibility of the immunohistologic expression of HIF-1α and GLUT-1 was acceptable with kappa values > 0.6. We found no association between HIF-1α or GLUT-1 and clinicopathological variables. HIF-1α and GLUT-1 expression had no predictive impact regarding response to chemoradiotherapy measured by TRG and was not associated with overall survival. The present study did not suggest any predictive or prognostic value of HIF-1α or GLUT-1 expression in pre-treatment biopsies from patients with rectal cancer treated with preoperative chemoradiotherapy. 17

18 The clinical significance of quantitative HER2 determination in breast cancer Forfattere Troels Bechmann 1,2 ; Erik Hugger Jakobsen 2 ; Jonna Skov Madsen 1,3 ; Anne Marie Bak Jylling 4 ; Karina Dahl Steffensen 1,5 ; Anders Jakobsen 1,2 1 Institute of Regional Health Services Research, University of Southern Denmark, 2 Department of Oncology, Vejle Hospital, 3 Department of Biochemistry, Vejle Hospital, 4 Department of Pathology, Vejle hospital, 5 Department of Medicine, Vejle Hospital Troels.Bechmann@slb.regionsyddanmark.dk, Erik.Jakobsen@ slb.regionsydanmark.dk, Jonna.Skov.Madsen@slb.regionsydanmark.dk, Anne.Marie.Bak.Jylling@slb.regionsyddanmark.dk, Karina.Dahl.Steffensen@slb.regionsydanmark.dk, Anders.Jakobsen@slb.regionsydanmark.dk Foredrag Troels Bechman Metode Konklusion The purpose of this PhD project is to elucidate the clinical significance of quantitative human epidermal growth factor receptor-2 (HER2) determination in breast cancer by examining the prognostic significance of quantitative tissue HER2 determination, the correlation between serum HER2 and HER2 status in primary tumor/metastasis, and the prevalence of occult cerebral metastases in patients with elevated serum HER2. HER2 is overexpressed in 20-30% of tumors and is associated with an aggressive tumor and a poor prognosis. Today, the patients are selected for HER2 targeted therapy based on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). A new quantitative enzyme-linked immunosorbent assay (ELISA) technique implies greater sensitivity, but this requires evaluation in the clinical setting. The extracellular domain of HER2 can be measured in serum and several studies show an association between changes in serum HER2 and response to chemotherapy in metastatic breast cancer. Other studies have shown a discrepancy between HER2 status in the primary tumor and metastasis, and it is still discussed if this is associated with serum HER2. In a retrospective study of 405 patients we investigate the clinical outcome in a group of HER2 positive patients defined by IHC/FISH and treated with adjuvant trastuzumab compared to a group defined as HER2 positive by ELISA but not treated with adjuvant trastuzumab. We are monitoring more than 900 patients with serum HER2. In the case of metastatic disease, a biopsy will be obtained and HER2 status in primary tumor/metastasis will be compared using both IHC/FISH and ELISA. In the same group of patients, we will perform brain MRI in the case of elevated serum HER2 > 15 ng/ml during their follow-up to elucidate the prevalence of occult cerebral metastases. The clinical significance of quantitative HER2 determination in breast cancer is still under evaluation. We expect this study to help us define a new group of patients that may benefit from adjuvant trastuzumab. Furthermore, we expect that serum HER2 can be used to guide clinicians when obtaining a biopsy from metastatic disease is not possible and finally, to define a group with increased risk of occult cerebral metastases. 18

19 Identification and Ranking of Side-effects in Patients Receiving Radiotherapy and Concomitant Weekly Cisplatin. A Multinational Collaborative Survey Forfattere Ruhlmann CH 1,2, Iversen TZ 3, Okera M 4, Muhic A 5, Hjelmtvedt A 6, Feyer P 7, Christensen TB 3, Keefe D 4, Specht L 5, Herrstedt J 1,2 1 Department of Oncology, Odense University Hospital, Odense, Denmark, 2 Institute of Foredrag Metode Resultater Konklusion Clinical research, University of Southern Denmark, 3 Department of Oncology, Herlev Hospital, Herlev, Denmark, 4 Department of Oncology, Royal Adelaide Hospital, Adelaide, Australia, 5 The Finsen Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, 6 Department for Gynaecologic Oncology, The Norwegian Radium Hospital, Oslo, Norway, 7 Vivantes Clinic Neukölln, Radiooncology, Berlin, Germany christina.ruhlmann@ouh.regionsyddanmark.dk Christina H. Ruhlmann. A large proportion of patients suffer from various side-effects, which are aggravated by the addition of concomitant chemotherapy (CT). The purpose of this study was to prospectively assess the frequency and severity of side-effects induced by radiotherapy (RT) and concomitant weekly cisplatin. This multinational survey included patients with a diagnosis of cervical cancer, vulval cancer, or head and neck cancer, who were RT and CT-naïve and scheduled to receive at least 15 fractions of RT and 3 doses of weekly cisplatin. Patients completed a questionnaire prior to anti-cancer treatment and again after the third dose of cisplatin. The questionnaire consisted of 54 items, focusing on physical and non-physical items. Patients were asked to rank the five most severe symptoms. Frequency of symptoms before treatment compared to frequency during treatment was analysed using the McNemar s chi squared test. As of May 1 st data from 136 patients was available. Twelve pre-treatment symptoms were experienced by more than 50% of patients, whereas the number expanded to 30 during treatment. Furthermore a significant increase (p-value 0.05) in symptom frequency was observed for 35 of 37 physical symptoms and for 7 of 17 non-physical symptoms. Patients ranking of symptoms demonstrated that nine of the ten most feared symptoms were nonphysical prior to treatment, whereas during treatment physical symptoms represented eight of the ten most feared symptoms. The five most severe symptoms after 15 fractions of RT and 3 courses of cisplatin were: problems with sense of taste, concerns about long-term side-effects, problems with saliva, trouble swallowing, and nausea. Detailed disease orientated results will be presented. Combined chemo-radiation induces an unexpected high number of physical and non-physical side-effects. Future trials focusing on the prevention of side-effects in these patients are highly warranted. 19

20 A new everyday life - Rehabilitation after radiotherapy for prostate cancer. Forfattere Karin Dieperink 1,3 Lis Wagner 2,3 Steinbjørn Hansen 1,3 Olfred Hansen 1,3 Foredrag 1 Department of oncology, Odense University Hospital, 2 Research unit of nursing, 3 Institute of Clinical Research, University of Southern Denmark Karin.dieperink@ouh.regionsyddanmark.dk Karin Dieperink Prostate cancer (PCa) is one of the cancer diseases, where treatment may have late adverse effects and may cause reduced quality of life. The incidence of PCa in Danish men increased 34 percent from 2005 to The increase is caused by a change in the age composition of the population, and to earlier diagnosis. PCa is now the most frequent cancer of men in Denmark. When the disease has not metastasized, it is possible to cure the patient with radiotherapy alone or in combination with anti hormones. Late adverse effects related to the treatment may influence the quality of life of the patients. These are: impotence, incontinence, problem with the bowels, anxiety and depression. This project will, as a part of a Ph.d. study, test and evaluate a rehabilitation programme intended to empower the mens health and give them resources to face a new everyday life. Design Prospective randomised controlled study: Examines whether or not a focused interdisciplinary intervention may influence on the patients general and specific quality of life after curative radiotherapy for prostate cancer. The intervention contains nursing consultations with information about late adverse effects and counselling in toilet habits, smoking cessation, weight control and psychological problems after treatment. Furthermore physiotherapy with physical and pelvic floor examinations and an individualized hometraining programme. Metode 160 patients are included. 80 patients in the intervention group and 80 patients in the control group. Resultater Primary endpoint: Quality of life questionnaires EPIC urinary irriative score. Secondary endpoints: EPIC bowel, sexual and hormonel score, SF12, MiniMac and strength of the pelvic floor at baseline, 1 month and 6 month. The inclusion was initiated at 1. February To date, a total of 105 patients are included. Konklusion We hope this project will give new knowledge of how to rehabilitate men cured from PCa with radiotherapy. We hope this project will give new knowledge of how to rehabilitate men cured from PCa with radiotherapy. 20

21 Netværket som med- og modspiller i et kræftbehandlingsforløb Forfattere Foredrag Design Metode Resultater Konklusion Lene Seibæk. Enheden for Sygeplejeforskning, Klinisk Institut; Lone Kjeld Petersen. Århus Universitetshospital, Skejby; Jan Blaakær. Århus Universitetshospital, Skejby; Lise Hounsgaard. Enheden for Sygeplejeforskning, Klinisk Institut lseibaek@health.sdu.dk, lonpeers@rm.dk, jab@dadlnet.dk, lhounsgaard@health.sdu.dk Lene Seibæk Siden 2008 er alle danskere garanteret udredning og behandling i de såkaldte kræftpakker. Imidlertid er det ikke belyst hvordan kvinder, der opereres på mistanke om ovariecancer, oplever tiden omkring operationen, samt hvad de foretager sig på egen hånd. Kvalitative forskningsinterview. Deltagere inkluderes strategisk og interviewes to gange: på sengeafdelingen aftenen før operationen og i hjemmet 8 uger efter operationen. Inden for en fænomenologisk hermeneutisk ramme udledes temaer som fortolkes kritisk. Derved udvikles viden om kvindernes levede erfaringer i den peri-operative periode. 10 kvinder medvirkede i 19 interview. Et hovedfund omhandler kvindernes egne refleksioner over deres netværk. Resultaterne tyder på, at kvinderne har et stort behov for i en ikke-dømmende kontekst at kunne udtrykke sig frit om deres netværk. I et kræftbehandlingsforløb er der brug for professionel opmærksomhed også på netværkets behov. Det må dog medtænkes, at netværket i kvindens eget perspektiv på en og samme tid kan repræsentere en vigtig ressource og en stor belastning. 21

22 ER, HER2, and TOP2A expression in primary tumor, axillary nodes, and asynchronous metastases in breast cancer Forfattere Jeanette Dupont Jensen 1,2 ; Ann Knoop 1,2 ; Marianne Ewertz 1,2, Anne-Vibeke Laenkholm 3 1 Department of Oncology, Odense University Hospital, Odense, Denmark; 2 Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; 3 Department of Pathology, University Hospital of Copenhagen, Copenhagen, Denmark. jeanette.dupont.jensen@ouh.regionsyddanmark.dk, ann.knoop@ ouh.regionsyddanmark.dk, marianne.ewertz@ouh.regionsyddanmark.dk, annevibeke.laenkholm@rh.regionh.dk Foredrag Jeanette Dupont Jensen At recurrence of breast cancer, the therapeutic target is the metastases. However, it is current practice to base the choice of systemic treatment on the biomarker profile of the primary tumor. In the present study, confirmatory biopsies were obtained from suspected metastatic lesions and compared with the primary tumors with respect to ER, HER2, and TOP2A. Metode In the prospective tissue-collection study, eighty-one patients had biopsy from a suspected relapse. Additional archived paired material was included, leaving a total of 119 patients with paired primary tumor and asyncronous metastases available for analysis. ER, HER2, and TOP2A expression were determined by immunohistochemistry, Chromogenic In Situ Hybridization, and Fluorescence In Situ Hybridization. Resultater These are preliminary results. Of the 81 patients with a biopsy from a suspected relapse, sixty-five (80 %) were diagnosed with recurrent breast carcinoma, three (4 %) were diagnosed with other malignancies, six (7 %) had benign conditions, and in 7 (9 %) patients the biopsy was non-representative. Discordance in ER, HER2, and TOP2A status between primary tumor and corresponding asynchronous metastasis was 12 % (14/118), 9 % (10/114), and 23 % (17/75) respectively. Patients with loss of ER expression had a late recurrence (p=0.04). There were no significant associations with biomarker discordance and prior adjuvant therapy, or location of biopsy. Konklusion Expression of ER, HER2, and TOP2A displayed discordance with a sufficient frequency to emphasize the role of confirmatory biopsies from metastatic lesions in future management of recurrent breast cancer. 22

23 Estimation of immunohistochemical expression of VEGF in ductal carcinomas of the breast Forfattere Else Maae 1,3 MD, Martin Nielsen 2, Karina Dahl Steffensen 1,3 MD, PhD, Erik Hugger Jakobsen 1 MD, Anders Jakobsen 1,3 MD, DMSc, Flemming Brandt Sørensen 2,3 MD, DMSc 1 Department of Oncology and 2 Pathology, Vejle Hospital, Denmark. 3 Institute of Regional Health Services Research, University of Southern Denmark, Odense, Foredrag Design Metode Variable Resultater Konklusion Denmark Else.Maae@slb.regionsyddanmark.dk, Martin.Nielsen@leica-microsystems.com, Karina.Dahl.Steffensen@slb.regionsyddanmark.dk, Erik.Hugger.Jakobsen@slb.regionsyddanmark.dk, Anders.Jakobsen@slb.regionsyddanmark.dk, Flemming.Brandt.Soerensen@slb.regionsyddanmark.dk Else Maae Vascular endothelial growth factor A (VEGF-A) is a very important growth factor in angiogenesis and holds the potential as both a predictive marker for anti-angiogenic cancer treatment and as a prognostic variable. Consequently, reliable estimation of VEGF expression is crucial. The aim of the present study was to investigate the reproducibility of manual and automated immunohistochemical (IHC) scoring of VEGF with a perspective of clinical application. Methodological study of reproducibility We immunostained whole tumor sections for VEGF-A, -B, and VEGF receptor 1 (VEGFR-1) of invasive ductal carcinomas of the breast. We scored the tumors manually with staining intensity as the only parameter and by a combination of staining intensity and the fraction of tumor cells staining. We also introduced an automated method for analyzing VEGF expression (AI score) using the same tumor sections. Analysis of 100% of the tumor area was performed and the results were compared to the reduced analysis of 25% of the tumor area. These analyses were performed at 5x and 10x magnification and each analysis was repeated in a second run with a new delineation of the tumor area VEGF-A, VEGF-B, VEGFR-1 We found that the AI scores were correlated to the manual scoring of VEGF intensity, but reproducibility of manual IHC scores was rather poor. The AI scores were reproducible and the restricted analysis of 25% of the tumor area at 5x magnifications was the most efficient considering time consumption and data load. We describe a method to gain reproducible measurements of VEGF-A, VEGF-B, and VEGFR-1 when analyzing whole tumor sections of invasive ductal breast carcinomas. We suggest further studies to focus on validation and the clinical impact of this method. 23

24 The Prognostic Value of Syndecan-1 in Ovarian Cancer Patients with Long-Term Follow up Forfattere Christine Vestergaard Madsen 1,3 MD, Karina Dahl Steffensen 1,3 MD, PhD, Marianne Waldstrøm 2 MD, & Anders Jakobsen 1,3 MD, DMSc. Departments of 1 Oncology, 2 Pathology and 3 Institute of Regional Health Services Research, University of Southern Denmark. Christine.Vestergaard.Madsen@slb.regionsyddanmark.dk Foredrag Christine Vestergaard Madsen Syndecan-1 plays a role in the cell regulation through cell-extracellular matrix adhesion, cellcell adhesion, migration and morphogenesis. It functions as a co- receptor for several growth factors, modulating the affinity of the growth-factor receptor interactions. Fibroblast growth factor 2 (FGF2) is the best validated example of a heparin-binding growth factor, but also hepatocyt-growth factor (HGF), vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor (EGF), and a variant of platelet derived growth factor (PDGF) have been suggested as examples of growth factors where syndecan-1 can interact with the ligand/receptor activation.. Syndecan-1 has been investigated as a prognostic factor for several malignant cancer types, but its role still seems unclear. The aim of the present study was to investigate the possible role of Syndecan-1as a prognostic factor in ovarian cancer. Metode The expression of syndecan-1 was examined in ovarian cancer specimens from 164 patients who were enrolled in a Danish protocol after primary surgery in the period from Immunohistochemistry and Tissue Microarrays (TMA) were used for the detection of Syndecan-1in both tumor epithelial and stromal cells. Resultater The median duration of follow up for those still alive was 18 years. Positive tumor epithelial syndecan-1 staining was found in 18 % of the patients whereas positive stromal Syndecan-1 immunoreactivity was seen in 50% of the patients. Positive expression of Syndecan-1in epithelial cells was observed less frequently in serous adenocarcinoma, whereas positive stromal expression was found more frequently in poorly differentiated tumors. High epithelial Syndecan-1 expression was associated with unfavorable overall survival in univariate analysis (p = 0.018) which, however, was not confirmed in multivariate analysis, although there was a tendency (p = 0.116) and a hazard ratio of 1.52 Konklusion Syndecan-1 is present in a subset of ovarian carcinomas and may be an indicator of survival, but further investigations are required. 24