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.