Session 9: Tumor and Infection

19. November
09:30 - 10:30
Lokale: 102-103
Chairmen: Michael Bendtsen & Michala Skovlund

66. The effect of sole gentamicin loaded bio-composite treatment following limited or extensive debridement of osteomyelitis lesions in a porcine model
Sophie Amalie Blirup-Plum, Thomas Bjarnsholt, Henrik Elvang Jensen, Kasper N Kragh, Bent Aalbæk, Hans Gottlieb, Mats Bue, Louise Kruse Jensen
Department of Veterinary and Animal Sciences, University of Copenhagen; Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen; Department of Clinical Microbiology, Copenhagen University Hospital; Department of Orthopedic Surgery, Herlev Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital

Background: CERAMENTTM|G is an absorbable gentamicin loaded bio-composite, trusted by several clinical studies as an on-site vehicle of antibiotics for the treatment of chronic osteomyelitis.
Aim: We aimed to assess the sole effect of CERAMENTTM|G, i.e. without additional systemic antibiotic therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.
Materials and Methods: Osteomyelitis was induced in nine pigs by inoculation of 104 CFU of Staphylococcus aureus into a drill hole in the left tibia. After one week, the pigs were allocated into three groups. Group A (n=3) received no treatment during the study period (19 days). Group B (n=3) and C (n=3) received limited or extensive debridement 7 days post inoculation, respectively, followed by injection of CERAMENTTM|G into the bone voids. The pigs were euthanized 10 (Group C) and 12 (Group B) days after the intervention.
Results: All animals demonstrated confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENTTM|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the peak post-mortem gentamicin concentrations in CERAMENTTM|G and surrounding bone tissue samples were 16.6 µg/mL and 6.2 µg/mL, respectively.
Interpretation / Conclusion: CERAMENTTM|G may not be used as a standalone alternative to extensive debridement or be used without the addition of systemic antibiotics.

67. A scheduled operation day might reduce early surgical failures within 30 days after major dysvascular lower limb amputation A single-center 2-year prospective cohort study of 163 patients compared with a historical control group of 165 patients
Martha Ella T L M Ignatiussen, Poul Pedersen , Morten Grove Thomsen, Gitte Holm, Morten Tange Kristensen
Department of Orthopaedic Surgery, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; Department of Orthopaedic Surgery, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; Department of Orthopaedic Surgery, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; Department of Orthopaedic Surgery, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; PMR-C, Departments of Physiotherapy & Orthopaedic Surgery, Copenhagen University Hospital – Amager and Hvidovre & Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

Background: Patients who undergo a major dysvascular lower limb amputation (LLA) often have a poor outcome. Even though advancements in perioperative risk stratification and care have improved, the short-term mortality and complications remains high.
Aim: The aim of this study is to investigate whether a scheduled operation day can reduce early surgical failure in patients undergoing a major LLA.
Materials and Methods: A total of 328 consecutive patients undergoing major LLA at a university hospital from January 2016 through December 2019 were enrolled. Early failure was defined as re-amputation or revision within 30 days of the primary amputation. In January 2018, a new regime was introduced entailing two scheduled operation days (Tuesday and Friday). No other changes were made in the standard care and regime. Follow up (until death or 30-days post-amputation) and data analysis comparing the two cohorts (year 2016-2017, n=165 vs. 2018-2019, n=163) was done for continuous and categorical data, as appropriate.
Results: The overall median (25-75% quartiles) age of patients was 74 (66-83) years, 61 % were men, 91% had an ASA grade =3, and was primarily amputated due to atherosclerosis and diabetes mellitus (92 %). The index amputee levels were 36% below knee, 60 % trans femoral, and 4% major bilateral with no significant difference between the two cohorts, and correspondingly for other patient characteristics. In the study cohort 59% of amputations were done on the scheduled Tuesday or Friday versus 36% in the control group (p<0.001). Correspondingly, more patients (72.4% vs 57.6%, p=0.005) were amputated during daytime, while no significant increase was seen for senior surgeons present during amputations (53% vs. 47%, p=0.174). The cause of early failure was primarily related to infection or necrosis, and the 30-day failure rate was reduced to 11.0% (n=18) in the study cohort compared to 16.4% (n=27) in the control group (p=0.2). The failure rate in the study cohort was 8.3% for amputation on the scheduled Tuesday or Friday versus 14.9% when done on other days (p=0.186).
Interpretation / Conclusion: Scheduled operation days for patients who undergo a major LLA might reduce the early failure rates.

68. Development and comparison of one-year survival models in patients with primary bone sarcomas.External validation of a Bayesian belief ne
Christina Holm, Clare F. Grazal, Mathias Raedkjaer, Thomas Baad-Hansen, Rajpal Nandra, Robert Grimer, Jonathan Agner Forsberg, Michael Moerk Petersen, Michala Skovlund Sørensen,
The Musculoskeletal Tumor Section, The Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark; Orthopaedics, USU-Walter Reed Department of Surgery, Bethesda, MD, USA;Department of Orthopaedic Surgery, Tumor Section, Aarhus University Hospital, Aarhus, Denmark; The Royal Orthopaedic Hospital, Birmingham, UK

Background: Bone sarcomas often presents late with advanced stage at diagnosis, resulting in varying short-term survival. In 2016 Nandra et al. generated a Bayesian belief network model (BBN) for 1-year survival of patients with bone sarcomas.
Aim: The purpose of present study is to: 1) External validate the prior 1-year BBN prediction model for survival of patients with bone sarcomas, 2) To develop a Gradient Boosting machine (GBM) model using Nandra et al.’s cohort and evaluate if the GBM model outperform the BBN model suggested by Nandra et al. when externally validated on an independent Danish population cohort.
Materials and Methods: The training cohort comprised 3493 patients newly diagnosed with bone sarcoma from the institutional prospectively maintained database at The Royal Orthopaedic Hospital, Birmingham UK. The validation cohort comprised 771 patients with newly diagnosed bone sarcoma included from The Danish Sarcoma Registry between January 1st, 2000 and June 22sd, 2016. Predictive performance of models was evaluated by area under receiver operator characteristic curve (AUC ROC) analysis, Brier score and decision curve analysis (DCA).
Results: External validation of the BBN 1-year prediction model demonstrated AUC ROC of 68% (95%CI, 62%-73%). AUC ROC of the GBM model demonstrated 75% (95%CI: 70%-80%), overall model performance by Brier score was 0.09 (95%CI: 0.077-0.11) and DCA demonstrated a positive net- benefit for threshold probabilities above 0.5. External validation of the developed GBM model demonstrated AUC ROC of 63% (95%CI: 57%-68%) and the Brier score was 0.14 (95%CI: 0.12-0.16).
Interpretation / Conclusion: External validation of the 1-year Bayesian belief network survival model yielded poor outcome and is hence not recommendable for clinical usage. The developed Gradient Boosting Machine 1-year survival model did not outperform the prior Bayesian belief network model, and modernization is pending.

69. Quantitative measurements of adaptive bone remodeling around the Cemented Zimmer® Segmental stem after tumor resection arthroplasty using dual-energy X-ray absorptiometry.
Christina Holm, Peter Horstmann, Michala Skovlund Sørensen, Karen Dyreborg, Michael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark

Background: Limb salvage surgery is currently offered to more than 90% of patients with bone or soft tissue sarcomas and to a greater extent also to patients with metastatic bone disease.
Aim: The aim of the present study was to evaluate the adaptive remodeling of the periprosthetic cortical bone after insertion of a tumor prosthesis with a cemented stem.
Materials and Methods: A prospective study of 21 patients (F/M=12/9), mean age 55 years (range 15-81) with metastatic bone disease (n=9), sarcomas (n=8) or aggressive benign tumors (n=4) who underwent bone tumor resection and reconstruction with a tumor prosthesis (Zimmer® Segmental 130 mm straight fluted cemented stem with trabecular metal (TM) collars) in the proximal femur (n=10), distal femur (n=9) or proximal tibia (n=2) . Measurements of bone mineral density (BMD) were done postoperatively and after 3, 6, and 12 months of the periprosthetic bone and in both ankles by using dual-energy X-ray absorptiometry. BMD (/g/cm2) was measured in 4 regions of interest around the cemented stem and in one region of interest 1 cm proximal from the ankle joint. Repeated measures ANOVA and students paired t-test was used to evaluate BMD changes over time.
Results: At 1-year follow-up, BMD compared to the postoperative value was seen in all 4 regions of interest with a statistically significant bone loss of 8- 15%. The bone loss was most pronounced (14- 15%) in the 2 regions of interest closest to the TM collar and lowest (8%) adjacent to the tip of the stem. We found the largest reduction in BMD around proximal femoral stems (11%-18%). After 1 year the decrease in BMD of the ankle on the affected extremity was 9% and the ankle on the contralateral extremity was close to baseline.
Interpretation / Conclusion: The periprosthetic BMD around the cemented 130 mm Segmental stem decreased significantly during the first postoperative year and is considered caused by a combination of stress shielding and immobilization.

70. Clinically relevant reductions in physical function in patients undergoing resection and reconstruction surgery with tumour prostheses due to bone sarcoma
Linda Fernandes, Christina Holm, Allan Villadsen, Michala Skovlund Sørensen, Mette Kreutzfeldt Zebis, Michael Mørk Petersen
Department of Midwifery, Physiotherapy, Occupational Therapy and Psychomotor Therapy, University College Copenhagen, Copenhagen, Denmark; Musculoskeletal Tumor Section, Department of Orthopedic Surgery, University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Background: Physical function and quality of life (QoL) are patient-important outcomes but are sparsely reported for patients that due to bone sarcoma undergo resection and reconstruction of bone in lower limb.
Aim: The aim of this study was therefor to describe physical function and QoL for this patient group.
Materials and Methods: Thirty patients operated between 2006 and 2016 (proximal femur [n=12], distal femur [n=14], proximal tibia [n=4]) were compared to 30 matched controls in a cross-sectional design. Differences between groups were tested for: isometric muscle strength in hip abduction, knee extension and knee flexion, six-minute walk test (6MWT) and 30s sit-to-stand test (STS). In the patient group, measures of physical function were correlated to the EORTC QLQ-C30 Global Health (GH) and Physical functioning (PF) subscales. Paired samples t-test was used for analyses of between group differences and Spearman’s rank test for correlations within the patient group. The significance level was set to p<0.05.
Results: The patients were assessed 2-12 years after surgery. Mean age was 51 years and mean BMI 26. Between group differences were found for hip abduction and knee extension strength, both for patients’ surgical and contralateral leg. Differences were also seen for the 6MWT (499 vs. 607 m, p<0.001) and the STS (12 vs. 18, p<0.001). Lower scorings of GH correlated to muscle weaknesses in hip abduction (rho 0.43, p=0.019) and lower scorings of PF correlated to muscle weaknesses in hip abduction (rho 0.51, p=0.006) and knee extension (rho 0.40, p=0.034).
Interpretation / Conclusion: Compared to controls, patients with bone sarcoma receiving resection-reconstruction surgery with a tumour prosthesis showed muscle strength deficits in both surgical and contralateral leg and less walk and sit-to-stand capacity. Compared to reference values, patients’ walk and sit-to-stand capacity were at levels of 80- year-old men and women. Muscle weaknesses were associated to lower QoL scorings, indicating that muscle strength influence the perception of QoL. These results reflect physical function at long term and to provide patients facing this surgery with a tangible image of future function, it should be included in preoperative patient information.

71. Challenges in the orthopedic nursing of tumor patients receiving a tumor prosthesis in the lower extremities
Marina Golemac, Müjgan Yilmaz, Michael Mørk Petersen
Department of Orthopedic Surgery, University Hospital of Copenhagen Rigshospitalet Inge Lehmanns Vej 6 2100 Copenhagen, Denmark

Background: Bone sarcomas are often localized in the lower extremities, and frequently the surgical treatment is major surgery using tumor prostheses. Giant cell tumors are not categorized as malignant tumors, but they are locally aggressive and therefore sometimes treated surgically with tumor prostheses.
Aim: This study aims to evaluate challenges in the nursing aftercare of orthopedic tumor patients receiving a tumor prosthesis in the lower extremities.
Materials and Methods: In a retrospective cohort study, we included 15 patients (F/M=11/4, mean age 42 years (range: 18-72)) treated at Rigshospitalet between 05.11.16 - 01.4.20 with a tumor prosthesis in the lower extremities (proximal femur (n=4), distal femur (n=5), proximal tibia (n=4), femoral shaft or total femur (n=2)) due to Ewing sarcoma (n=3), osteosarcoma (n=5), chondrosarcoma (n=4), giant cell tumor (n=2) or myksofibrosarcoma (n=1). We performed a medical record review with focus on challenges related to nursing aftercare. One patient had an amputation the day after primary surgery due to arterial thrombosis thus leaving 14 patients for the study.
Results: The mean duration of hospital stay was 13 days (range: 5-32). Six patients had neoadjuvant chemotherapy prior to surgery. Nine patients needed a blood transfusion during surgery and/or postoperatively (SagM n=68, fresh frozen plasma n=26, thrombocytes n=9, human albumin n=3). Four patients had extra supervision from an anesthesiologist due to severe pain, 7 patients needed medication more than 5 times a day besides planned medication. Twelve patients had nausea and treated with medication. All patients were treated with cefuroxime 1.5g x 3 postoperatively (mean: 8 days, range: 4-22), 3 patients (no. 6, 12, 15) were treated with other antibiotics after termination of cefuroxime, 3 patients (no. 2, 10, 12) had leakage from the surgery wound after 5, 6 and 8 days. The mean days until the first attempt to mobilization to the bed edge were 3 days (range: 2-4).
Interpretation / Conclusion: Orthopedic nurses can help minimize the challenging aspects during hospital stay identified in this study. Further studies are needed to identify which aspects are important for the patients, this could be done in a prospective qualitative setup.

72. Ewing´s sarcoma of the calcaneus treated by limb sparing surgery with calcanectomy and reconstruction with a composite of an allograft and a vascularized osteocutaneous fibula graft
Michael Mørk Petersen, Lisa Toft Jensen, Christian Bonde, Werner Herbert Hettwer
Department of Orthopedics (Musculoskeletal Tumor Section) and Department of Plastic Surgery Rigshospitalet, University of Copenhagen, Denmark.

Background: Primary malignant bone tumors of the calcaneus are very seldom, and due to poor possibilities to do surgery with wide margins in this region and limited options for reconstruction after calcanectomy many orthopedic oncologists use amputation as the preferred surgical treatment in such cases.
Aim: We present two cases of Ewing´s sarcoma of the calcaneus treated with calcanectomy and reconstruction with a composite of an allograft and a vascularized osteocutaneous fibula graft.
Materials and Methods: The medical cases of 2 girls suffering from Ewing´s sarcoma of the calcaneus that were almost 6 years old (case 1) and 16 years old (case 2) at the time of surgical treatment with calcanectomy in respectively August 2012 and October 2013 are presented. Both patients were without metastatic disease and received pre- and post-operative chemotherapy.
Results: In both cases removal of the calcaneus was performed using a combined medial and lateral incision. In case 1 a femoral head allograft was fitted to replace the removed calcaneus, and in case 2 a calcaneus allograft was used. In both cases, with the aim of obtaining arthrodesis, the allograft was fixed to the talus and cuboid bone with screws. A distally pedicled osteocutaneous flap was use for reconstruction of soft tissue, and a 5-6 cm piece of vascularized fibula bone was fitted into the allograft and fixed using staples Arthrodesis between talus and the graft healed and full weight-bearing was allowed in both cases 8-9 months postoperatively. At follow-up 6½ and 4½ years after surgery both patients were without local recurrence or metastases, and they were both pain-free and able to walk using normal footwear without any walking-aids.
Interpretation / Conclusion: Biological reconstruction is possible after removal of the calcaneus because of primary malignant bone tumors and long-term good functional results can be achieved.