Session 1: Experimentel and Tumor

Onsdag den 26. oktober
09:00 – 10:30
Lokale: Reykjavik
Chairmen: Thomas Jakobsen / Johnny Keller

1. In vivo drug release behavior and osseointegration of a doxorubicin-loaded tissue-engineered scaffold
Ming Sun, Muwan Chen, Miao Wang, Jakob Hansen, Anette Anette Baatrup, Frederik Dagnaes-Hansen, Jan Rölfing, Jonas Jensen, Helle Lysdahl, Mogens Johannsen, Dang Le, Jørgen Kjems, Cody Bünger
Orthopaedic Research Lab , Aarhus University Hospital; Interdisciplinary Nanoscience Center (iNANO), Aarhus University; Orthopaedic Research Lab , Aarhus University Hospital; Department of Forensic Medicine, Aarhus University; Orthopaedic Research Lab , Aarhus University Hospital; Department of Biomedicine, Aarhus University; Orthopaedic Research Lab , Aarhus University Hospital; Orthopaedic Research Lab , Aarhus University Hospital; Orthopaedic Research Lab , Aarhus University Hospital; Department of Forensic Medicine, Aarhus University; Orthopaedic Research Lab , Aarhus University Hospital; Interdisciplinary Nanoscience Center (iNANO), Aarhus University; Orthopaedic Research Lab , Aarhus University Hospital


Background: Bone tissue-engineered scaffolds with therapeutic effects must meet the basic requirements as to support bone healing at the defect side and to release an effect drug within the therapeutic window.
Purpose / Aim of Study: Here, a rapid prototyped PCL scaffold embedded with chitosan/nanoclay/β-tricalcium phosphate composite (DESCLAYMR) loaded with chemotherapeutic drug doxorubicin (DESCLAYMR _DOX) is proposed as a potential multifunctional medical application for patients who undergo bone tumor resection.
Materials and Methods: In this study, we have set up two animal models: 1) mouse model was used to investigate the in vivo release behavior of DOX from the DESCLAYMR scaffold. Local release behavior in treated area was obtained using an in vivo imaging system (IVIS) and systemic pharmacokinetics were analyzed by UHPLC- MS/MS. 2) Pig model was employed to investigate the bone biocompatibility of the DESCLAYMR scaffold loaded with or without DOX.
Findings / Results: We showed the DESCLAYMR_DOX scaffold released DOX locally in a sustained manner in mice without significantly increasing the plasma DOX concentrations. The evaluation of osseointegration in a porcine study showed increased mineralized bone formation, unmineralized collagen fibers and significantly higher alpha Smooth Muscle Actin (α- SMA) positive areas relative to total investigated area (TA) in defects treated solely with the DESCLAYMR scaffold than in the DESCLAYMR_DOX; and Alkaline phosphatase activity, α-SMA/TA and bone formation were higher in the DESCLAYMR loaded with 100 μg/scaffold DOX (DOX_low) than with 400 μg/scaffold DOX (DOX_high).
Conclusions: Our results suggest that the DESCLAYMR_DOX can be a viable candidate as a multifunctional medical application by delivering the chemotherapeutic agent to target remaining tumor cells and facilitate bone formation.

2. Comparison of sheep adipose and bone marrow stem cells on bone formation identified by anti-human vimentin stain in an ectopic mouse model
Kristian Kjærgaard, Chris H Dreyer, Nicholas Ditzel, Christina M Andreasen, Li Chen, Søren P Sheikh, Søren Overgaard, Ming Ding
Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research,University of Southern Denmark, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research,University of Southern Denmark, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Department of Endocrinology and Metabolism, Molecular Endocrinology Laboratory (KMEB), Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 25.1, DK-5000, Odense C, Denmark; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research,University of Southern Denmark, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Department of Endocrinology and Metabolism, Molecular Endocrinology Laboratory (KMEB), Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 25.1, DK-5000, Odense C, Denmark; Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J. B. Winsløws Vej 21.3, DK-5000 Odense C, Denmark; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research,University of Southern Denmark, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research,University of Southern Denmark, Sdr. Boulevard 29, DK-5000 Odense C, Denmark


Background: Scaffolds for bone tissue engineering (BTE) can be loaded with mesenchymal stem cells (MSC) to improve osteogenesis. MSC can be found in bone marrow, adipose tissue and other tissues. Little is known about osteogenic potential of adipose-derived stem cells (ASC).
Purpose / Aim of Study: This study aims to compare in vivo ostegenic capacity between ASC and bone marrow derived stem cells (BMSC).
Materials and Methods: ASC and BMSC were isolated from five female sheep and seeded on hydroxyapatite granules prior to subcutaneous implantation in 14 immunodeficient mice, four implants in each mouse. The doses of cells of the implants were 0.5×10^6, 1.0×10^6 and 1.5×10^6 ASC and 0.5×10^6 BMSC, respectively. After eight weeks, bone volume vs. total volume was quantified using histomorphometry. Origin of new bone was assessed using human vimentin (HVIM) antibody staining.
Findings / Results: BMSC yielded significantly more bone than any ASC group, and differences between ASC groups were not statistically significant. HVIM antibody stain was successfully used to identify sheep cells in this model.
Conclusions: ASC and BMSC were capable of forming bone. Though ASC were capable of forming new bone as assessed by vimentin staining, in vitro treatment to enhance osteogenic capacity is suggested as further research in ovine bone tissue engineering.

3. Epidemiology in surgical treatment of metastatic bone disease of the appendicular skeleton -Reporting from a consecutive prospective population based cohort.
Michala Skovlund Sørensen, Klaus Hindsø, Anders Troelsen, Stig Dalsgaard, Tobias Fog, Tomasz Zimnicki, Michael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen; Pediatric section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen; Clinical Orthopedic Research Hvidovre, Copenhagen University Hospital Hvidovre, Copenhagen; Department of Orthopedic Surgery, Herlev University Hospital, Herlev; Department of Orthopedic Surgery, Nordsjællands Hospital, Hillerød; Department of Orthopedic Surgery, Bispebjerg and Frederiksberg University Hospital, Copenhagen; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen


Background: Cancer related skeletal events in need of surgical treatment (SEST) is a devastating event for patients suffering from cancer. Epidemiological data and the incidence rate is lacking in current literature.
Purpose / Aim of Study: 1) find the incidence and epidemiological composition of SEST in the appendicular skeleton. 2) see if the general health status of the patient (HOP) influences the referral pattern.
Materials and Methods: A consecutive prospective population-based cohort in the Capital Region of Denmark was systematically screened for metastatic lesions treated surgically in the appendicular skeleton for a two-year period.
Findings / Results: 174 lesions were identified giving an incidence of 48.6 SEST/million inhabitants/year. Twelve patients had more than one SEST during the period of whom nine patients was treated for two lesions in same anesthesia. Ninety-nine surgeries (57%) were treated at a tertiary referral center (TRC). The 5 most common cancers causing the lesions were: Mamma (n=39), lung (n=31), renal cell (n=25), prostate (n=24) and myeloma (n=19). Anatomical location of lesions was: 126 femur (97 hip), 29 humerus (16 proximal), 14 pelvis, and 5 others. Fractured lesions/impending fractures =131/43. Surgical treatment was: no reconstruction (n=10), reconstruction with prosthesis (n=94) and osteosynthesis (n=70). Mean Karnofsky score 7.39 (TRC 7,47, p=0.47). Mean ASA score was 2.60 (TRC 2.45, p=0.02). One-year survival was 44% (95%CI: 36%-53%). Patients being treated at a TRC one-year survival were 52% (95%CI: 41%-63%) and outside 34 % (95%CI: 22%-47%), p<0.05. No biopsy peroperative n=61.
Conclusions: Incidence of SEST was found. Surgical technique, anatomical location of lesion and cancer causing the lesions were identified. HOP did influence the referral pattern indicating a selection of patients to highly specialized surgery.

4. Surveillance for development of local recurrence after primary surgical excision of soft tissue sarcomas and borderline tumours of the extremities and trunk wall
Thea Hovgaard, Tine Nymark, Michael Mørk Petersen
Orthopaedic Department, Rigshospitalet; Orthopaedic Department, Odense University Hospital; Orthopaedic Department, Rigshospitalet


Background: Current routine follow-up policy for soft tissue sarcomas (STS) lacks evidence. Early detection and surgical removal of a local recurrence (LR) is associated with improved survival. In Jan 2010 we introduced a new follow-up program for the first 2 postoperative years where STS were examined 4 times a year; high-grade malignant STS alternating between clinical examination (CE) preceded by focal MRI and chest CT-scan (CT) and a CE with chest X-ray (XR). Low-grade malignant STS alternated between a CE and a CE preceded by focal MRI.
Purpose / Aim of Study: To evaluate the new surveillance program for identification of LR within the first 2 years postoperatively.
Materials and Methods: We retrospectively assessed the medical files of all patients (n=232, mean age 57 (18-88) years, F/M=117/115) with STS (including borderline tumours) of the extremities and trunk wall, who underwent surgery from 2010-2013. We extracted information on how LR were detected during the first 25 months post-surgery. Statistics: Kaplan Meier survival analysis and 2x2 contingency table with chi2-test.
Findings / Results: 25/232 patients experienced LR within the first 25 months post-surgery (25 months-LR free rate 92%). Compared to CE, local imaging (LI) mainly MRI led to a larger amount of suspicions of LR (37/557 versus 8/703, p<0.001). Furthermore the suspicions from LI were more accurate than from CE (17/37 affirmed versus 0/8 affirmed, p<0.015). LI (n=557) finds a larger number of LR than CE (n=703) (17 (3%) versus 0 (0%), p<0.016). 33 patients suspected LR themselves; 8 of them were affirmed.
Conclusions: Bi-annual LI (MRI) the initial first 2 postoperative years after surgical treatment of STS, will detect LR better than CE, and therefore render regular CE between these MRIs unnecessary, but patients´ own suspicion of LR is still important.

5. Investigating time point for stimulation of vascular endothelial growth factor and mesenchymal stem cell on bone formation in severe immunodeficiency mice
Chris Dreyer, Kristian Kjærgaard, Nicholas Ditzel, Jørgensen Niklas , Søren Overgaard, Ming Ding
Department of Orthopaedic Surgery and Traumatology, Odense University Hospital Institute of Clinical Research, University of Southern Denmark; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital Institute of Clinical Research, University of Southern Denmark; Department of Endocrinology, Odense Unversity Hospital; Center for Ageing and Osteoporosis, Glostrup, Rigshospitalet; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital Institute of Clinical Research, University of Southern Denmark; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital Institute of Clinical Research, University of Southern Denmark


Background: To get sufficient bone formation, optimal conditions are needed, and insufficient blood supply may be a limitation. VEGF promotes angiogenesis by increasing endothelial proliferation and migration, vessel permeability, tube formation and survival.
Purpose / Aim of Study: To evaluate time points for stimulation with VEGF of mesenchymal stem cell derived bone formation in severe immunodeficiency (SCID) mice.
Materials and Methods: Twenty-eight SCID mice were divided into 7 groups. All groups received hydroxyapatite (HA) granules coated with 5x10^5 MSCs. One group without VEGF served as the control without. 6 groups had different VEGF stimulation time points through degradable pellets: Day 1-7 post-operatively; day 1- 14; day 1- 21; day 1-42; day 7-14 and day 21-42. Granules+MSCs+VEGF were placed subcutaneously dorsally in 3 pockets of the mice. Each group contained 4 randomly allocated mice. At sacrifice, the implant samples were stained with haematoxylin eosin (HE) for histomorphometric analysis. Human vimentin staining (HVIM) was performed to confirm the origin of sheep stem cell. Serum blood samples were collected for determination of bone-related markers: Osteoprotegerin (OPG), Receptor activator of nuclear factor kappa-B ligand (RANKL), osteocalcin, type 1 procollagen (P1NP), sclerostin and C- terminal telopeptide (CTX).
Findings / Results: The histomorphometric analysis revealed the VEGF stimulation in the day 1-14, and day 1-21 groups showed more bone formation relative to the control group and the day 21-42 group (p<.01). Serum biomarkers of the 6 groups with VEGF stimulation were not significantly different compared to control group. HVIM staining confirmed bone regenerative effect was caused by MSCs from sheep.
Conclusions: The most bone formation was shown when stimulating with VEGF in 1-14 or 1-21 days after surgery.

6. Preoperative plasma YKL-40 levels in bone and soft tissue sarcoma patients
Andrea P. Thorn, Mette L. Harving, Gunnar S. Lausten, Julia S. Johansen, Michael M. Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark; Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark


Background: YKL-40 is a glycoprotein that has showed expression in several types of cells such as cancer cells. Previous studies have shown that elevated plasma concentrations of YKL- 40 in patients with various types of cancer constitute an independent prognostic variable for survival.
Purpose / Aim of Study: The aim of this study was to identify if YKL- 40 in plasma can serve as a marker for prediction of the outcomes in patients with bone and soft tissue sarcomas.
Materials and Methods: Sixty-seven patients (mean age 61 (29-90) years, F/M= 34/33) with bone sarcoma (BS) or soft tissue sarcoma (STS) (BS/STS=15/52) of the extremities, spine or trunk wall treated by surgical excision at the Department of Orthopaedics, Rigshospitalet, during the time-period August 2009 until April 2012 were included in the study. All patients had a blood sample taken at the day of surgery or the day before surgery. The samples were analysed using ELISA in order to determine the amount of YKL-40 in plasma. Patient files were reviewed for various information, patient overall survival was updated January 2016 (minimum follow up of 3.75 years for patients still alive).
Findings / Results: The probability of 5-year survival for all sarcoma patients (n=67) was 64%. Patients with a YKL-40 concentration below the mean (147 μg/L (18-576 μg/L), n=52, 5- year survival 76%) had a better survival (p=0.001) than patients with YKL-40 concentration above the mean (n=15, 5- year survival 15%). YKL-40 concentration for patients that were still alive at the end of follow-up was lower than patients who died during the follow up (p=0.02).There was a tendency to higher YKL-40 concentration in patients that had local recurrence (p=0.09) and higher malignancy grades (p=0.11).
Conclusions: A high YKL-40 plasma concentration measured preoperatively in sarcoma patients are connected to a poor overall survival.

7. The intracortical accumulation of enlarged lacunae is a key contributor to the increased cortical porosity and trabecularization during aging
Christina M. Andreasen, Jean-Marie Delaissé, Bram C.J. van der Erden, Dorie Birkenhäger- Frenkel, Johannes P. T. M. van Leeuwen, Ming Ding, Thomas L. Andersen
Orthopedic Surgery and Traumatology, Orthopedic Research Laboratory, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Denmark; Clinical Cell Biology, Vejle Hospital/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Denmark; Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; Orthopedic Surgery and Traumatology, Orthopedic Research Laboratory, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Denmark; Clinical Cell Biology, Vejle Hospital/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Denmark


Background: In order to improve treatment of the patients we need to enhance our understanding of the intracortical bone remodeling.
Purpose / Aim of Study: To investigate the characteristics of the intracortical pores contributing to the increased cortical porosity and trabecularization during aging.
Materials and Methods: A histomorphometric analysis of the intracortical pores was performed on sections from transiliac bone specimens from 35 women (16-78 years) undergoing forensic examination due to a sudden unexpected death.
Findings / Results: The bone specimens had a statistically significant age-dependent increase in cortical porosity (p<0.05) and mean pore diameter (p<0.05), and a reduction in cortical thickness (p<0.01). The analysis included in total 3969 intracortical pores: 68.3% of these pores were refilled osteons with a quiescent surface, 8.8% were asymmetrically refilled osteons with both a quiescent and eroded surface, 6.5% had only eroded surfaces and no osteoid surfaces, 7.0% had osteoid surfaces, while 5.9% were refilled osteons with extensive erosions widening the previously quiescent pores. In 34.8% of the latter pores, the widening resulted in the merge of two or more previously quiescent pores, forming enlarged irregular shaped lacunae. Although the widened pores and the formed lacunae only account for 5.9% and 2.1% of the pores, they on average contribute to 44.4±22.1% and 30.3±23.3% of the cortical porosity. These two types of pores showed a statistically significant age-dependent increase in their contribution to the cortical porosity (p<0.001) and pore density (p<0.01), while the pores with osteoid surfaces showed an age- dependent decrease (p<0.01).
Conclusions: Collectively, this study supports that the accumulation of widened previously quiescent pores and lacunae contributes to the increased cortical porosity during aging.

8. Implant fixation with BMP-2 and Zolendronate in a peri-implant gap - with and without allograft
Rasmus Cleemann, Mette Sørensen, Jørgen Baas, Joanie Bechtold, Kjeld Søballe
Orthopedic, Orthopedic Research Laboratory & Elective Surgery Centre, Aarhus University Hospital & Silkeborg Regional Hospital - DK; Orthopedic Research Laboratory, Aarhus University Hospital - DK; Orthopedic, Aarhus University Hospital - DK; , University of Minnesota, Minneapolis, MN - USA; Orthopedic, Aarhus University Hospital - DK


Background: BMP-2 stimulates formation of new bone; if Zolendronate can prevent BMP-2 associated bone resorption, this may improve implant fixation.
Purpose / Aim of Study: To quantify effects in a peri-implant gap with or without allograft, with 3 BMP-2 doses locally and with systemic Zolendronate.
Materials and Methods: In 12 male canines, 4 implants were inserted in 2.5 mm allografted gaps in bilateral proximal humerei, and 4 implants were inserted in 0.75 mm non-grafted gaps in bilateral femoral condyles. The implant surface was coated with 240 μg, 60 μg, 15 μg of BMP-2 or control. Zolendronate (0.1 mg/kg) was administered once IV, 10 days post surgery. After 28 days, specimens were evaluated by histomorphometry and mechanical push- out.
Findings / Results: Grafted gap: Compared to any BMP-2 dose, control had the best mechanical fixation, the most bone at implant surface, the most volume of new bone near the implant (from 0-1 mm but not 1-2 mm), and the most retained allograft. With any BMP-2 dose, volume of allograft decreased near the surface (0-1 mm) and dose dependently further away (1-2 mm). Non-grafted gap: 15 μg BMP-2 had the best mechanical fixation, the most bone at implant surface and in the gap compared to control, 60 μg and 240 μg BMP-2.15 μg and control did not differ in volume of new bone in the gap. Outside the original implant gap, volume of new bone correlated to increasing BMP-2 dose.
Conclusions: The different surface fraction and volume of new bone in the grafted and non-grafted gap settings suggest a variable response to the combined anabolic and catabolic stimuli when graft is present. BMP-2 can augument implant fixation, but the therapeutic window seems narrow and addition and timing of Zolendronate administration is essential to harvest a positive effect on initial implant fixationt. Both areas need further experimental investigation.

9. Collagen type IV-induced changes in expression of stress-related proteins in normal and osteoarthritic chondrocytes are mediated by integrins - α2β1 and ανβ3
Casper Bindzus Foldager, Martin Lind, Wei Seong Toh, Helle Lysdahl
Orthopaedic Research Laboratory, Aarhus University Hospital; Sports Trauma Clinic, Aarhus University Hospital; Faculty of Dentistry, National University of Singapore; Orthopaedic Research Laboratory, Aarhus University Hospital


Background: Chondrocytes in healthy cartilage express collagen type IV (COL4) in the pericellular matrix (PCM) and the expression is decreased around osteoarthritic (OA) chondrocytes.
Purpose / Aim of Study: The aim was to investigate the role of COL4 in the expression of stress-related proteins in healthy and OA chondrocytes and to determine the role of COL4-binding integrins (α1β1, α2β1, and ανβ3).
Materials and Methods: Chondrocytes isolated from three healthy patients undergoing anterior cruciate ligament reconstruction and OA chondrocytes were isolated from three patients undergoing knee replacement surgery. Cells in passage one were seeded at 10,000 cells/cm2 in COL4-coated wells or non-coated control wells and cultured for 1, 5, and 14 days. Integrin profiles of α1β1, α2β1, and ανβ3 were performed using flow cytometry. Evaluation of stress-related proteins was performed on day 5, with and without five-hour prior integrin blocking by antibodies, using Proteome Profiler™ Human Cell Stress Array. Data was analyzed using Kruskal-Wallis and Wilcoxon-Mann-Whitney tests.
Findings / Results: Both cell types expressed the evaluated integrins. On days 5 and 14, OA chondrocytes had higher α1β1 expression than normal chondrocytes. COL4 decreased the expression of α2β1 on both cell types on day 5. The expression of stress-related proteins was increased by COL4 in normal chondrocytes, while it was decreased in OA chondrocytes. Integrin blocking with neutralizing antibodies indicated that α2β1, and ανβ3 were comparatively more involved than α1β1 in mediating the stress-response induced by COL4.
Conclusions: Integrin blocking revealed α2β1, and ανβ3 as primary mediators of changes in the expression of stress-related proteins induced by the PCM molecule COL4.

10. Prognostic Factors for Survival of High Grade Osteosarcoma - A 20 Year Single-institution Assessment from Eastern Denmark
Thomas Colding-Rasmussen, Andrea Pohly Thorn, Peter Frederik Horstmann, Michael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark ; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark ; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark ; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark


Background: Overall survival of patients diagnosed with high- grade osteosarcoma (HO) – the most common primary bone cancer – has not improved significantly the last 20 years. Accordingly, treating HO remains a major challenge.
Purpose / Aim of Study: To evaluate prognostic factors for survival in patients diagnosed with HO between 1990 and 2010 at the department of orthopedic tumor surgery, Rigshospitalet, Copenhagen, Denmark (RH).
Materials and Methods: 156 patients received an osteosarcoma diagnosis in the RH Pathologic database from 1990-2010. 101 patients (mean age=29 years, F/M ratio=56/45) were suited for further analysis. 55 patients were excluded due to either low grade classification (n=22), non-confirmed tentative diagnosis (n=11), tumor in axial skeleton (n=18) or metastatic/relapsed tumor (n=4). Statistics: Kaplan Meier survival analysis and Cox regression.
Findings / Results: The probability of 5 – and 10 year survival from time of diagnosis was 51% and 46% respectively. Metastatic disease (multivariate cox: HR=3.5, CI 95%: 1.5-7.8) and tumor-size ≥10 cm (multivariate cox: HR: 2.9, CI 95%: 1.5-5.4) at time of diagnosis, were statistically significant risk factors for decreased overall survival. Among patients treated with curative intent (preoperative chemotherapy and surgery, n=79), the survival rate was higher (multivariate cox: HR=2.8 CI 95%: 1.2-6.5), if the degree of tumor cell necrosis was ≥90%.
Conclusions: Overall survival for patients with HO in East Denmark is consistent with the international average survival for this patient-group. Metastasis and tumor- size ≥10 cm at time of diagnosis are significant prognostic factors for surviving HO, as well as degree of chemotherapeutic induced tumor necrosis among patients treated with curative intent.

11. Comparison of two alternative wound closure methods for tumor arthroplasty of the hip.
Werner Hettwer, Peter Horstmann, Michael Mørk Petersen
Ortopedisk Tumorsektion, Rigshospitalet; Ortopedisk Tumorsektion, Rigshospitalet; Ortopedisk Tumorsektion, Rigshospitalet


Background: Prolonged wound drainage is a common complication after extensive surgery involving the hip, such as tumor resection and endoprosthetic reconstruction.
Purpose / Aim of Study: We wished to determine a possible beneficial effect of an alternative wound closure method compared to routine wound closure with skin staples in this challenging patient population.
Materials and Methods: A retrospective case-control study of a cohort of 70 frequency matched patients with metastatic bone disease or malignant hematologic bone disease, treated at our center between 2012 and 2014 was performed. All patients underwent tumor resection and subsequent endoprosthetic reconstruction of the proximal femur and either occlusive wound closure (OWC), with a combination of intradermal suture, Steristrips and an occlusive skin adhesive (Investigational group, n=35) or routine wound closure with conventional staples (Control group, n=35).
Findings / Results: Patients with OWC were significantly faster to achieve dry wound status and experienced significantly shorter administration of antibiotics and hospital stay accordingly. Compared to the patients in the control group their wounds were already dry after a mean 3.4 days (vs 6.7 days, p<0.0001), they received antibiotics for a mean 4.2 days (vs 6.8 days, p<0.0001) and their mean hospital stay was 6.3 days (vs 8.0 days, p<0.015). Prolonged wound drainage (PWD) for 7 days or more was observed in 34% of patients (n=12) closed with staples, compared to (n=0) of patients with OWC.
Conclusions: Compared to conventional staples, occlusive wound closure (OWC) appears to significantly reduce wound complications, use of antibiotics and hospital stay in patients undergoing tumor hip arthroplasty, which may also contribute to a reduction of the potentially increased risk for periprosthetic joint infection (PJI) in this patient population.