Session 15: Infection and Amputation / Tumor

Tue Smith jørgensen, ylva hellsten, Hans gottlieb , Christopher D. Askew, stig brorson, Birgitte Høier
orthopedic, sport and foot section, Gentofte; Nutrition Exercise and Sports, university of copenhagen; Orthopedic, Herlev; Shcoll of Health and sports sciences, casoactive research group, University of sunshine coast Australia; orthopedic, Zealand university hospital; Nutrition Exercise and Sports, university of copenhagen


Background: In peripheral arterial disease (PAD), alterations in microvascular density and structure are believed to contribute to chronic skeletal muscle ischemia. Impaired formation of vascular endothelial growth factor (VEGF), which is critical for capillary growth, may be a cause of the vascular rarefaction.
Purpose / Aim of Study: To determine the presence and release of VEGF protein in skeletal muscle and isolated muscle myocytes from critically ischemic limbs of patients with PAD.
Materials and Methods: Skeletal muscle biopsies were collected from proximal less ischemic muscle and from distal highly ischemic muscle of 15 patients with critical limb ischemia undergoing transfemoral amputation. Control samples were obtained from five age-matched healthy individuals. Muscle samples were analyzed for VEGF content and other angiogenic, mitochondrial and -vascular proteins. Skeletal muscle cells were also isolated and cultured to determine muscle specific VEGF content and release.
Findings / Results: Compared with age-matched individuals, the VEGF receptor 2 protein level was higher (p=0.042) in PAD patients. No differences were found for the other proteins. In the cell study, muscle cells from the proximal and distal limb regions showed similar amounts of VEGF protein and the capacity for VEGF protein release did not differ.
Conclusions: Our results indicate, that critically ischemic muscle has a similar angiogenic potential as healthy muscle. As VEGF availability and VEGF receptor density are not limited in CLI, therapeutic strategies to improve angiogenesis should focus on other targets.

Mathias Rædkjær, Katja Maretty-Kongstad, Thomas Baad-Hansen, Akmal Safwat , Michael Mørk Petersen, Johnny Keller, Peter Vedsted
Department of Orthopedic Surgery, Aarhus University Hospital; Department of Pathology, Aarhus University Hospital; Department of Orthopedic Surgery, Aarhus University Hospital; Department of Oncology, Aarhus University Hospital; Department of Orthopedic Surgery, Rigshospitalet, University Hospital of Copenhagen; Department of Orthopedic Surgery, Aarhus University Hospital; The Research Unit of General Practice, Aarhus University


Background: Sarcoma is a rare, heterogenic type of cancer that originates from muscle, bones and connective tissue. Less than 1% of newly diagnosed cancer patients have sarcoma. Survival in sarcoma patients depends on a range of tumour related prognostic factors. An association between cancer survival and socioeconomic position is known for other cancers.
Purpose / Aim of Study: The aim of this study was to examine the relations between three socioeconomic factors and the risk of presenting with known prognostic factors (size, grade, stage) and the overall mortality of the different socioeconomic and prognostic factors in 1919 patients treated for sarcoma in Denmark 2000-2013.
Materials and Methods: Patients with sarcoma in extremities or trunk wall aged 30 years or more at diagnosis were identified in the Danish Sarcoma Registry, and linked on an individual level to Danish national registries. We obtained data on educational level, disposable income and cohabitation status. Odds ratios (ORs) were estimated for the association between the socioeconomic factors and grade, stage and tumour size. Survival analyses were performed using Cox proportional hazard models and Kaplan Meier survival curves.
Findings / Results: In adjusted analyses, educational level, income and cohabitation status were not associated with grade, stage or tumour size at the time of diagnosis. Patients with a short education, low income, who lived alone, with comorbidity or a large tumour had a significantly higher mortality.
Conclusions: In this nationwide, multicentre, population-based study we found that soft tissue sarcoma patients living alone had significantly greater risk of presenting with a large tumour at time of diagnosis. Patients with a short education, low income, who lived alone, had a statistically significant higher mortality. Thus, the social differences in mortality seems to be related to treatment aspects rather that the diagnostic process. More attention on socioeconomic factors in the treatment of sarcomas is needed in order to improve survival in patients with lower socioeconomic position.

Thomas Falstie-Jensen, Jeppe Lange, Henrik Daugaard, Anne Katrine Belling Sørensen, Bo Zerahn, Janne Ovesen, Mikkel Vendelbo, Lars Christian Gormsen
Department of Orthopedic Surgery, section for shoulder and elbow surgery, Aarhus University Hospital; Department of Orthopedic Surgery, Regional Hospital Horsens; Department of Orthopedic Surgery, Gentofte Hospital; Department of Orthopedic Surgery, section for shoulder and elbow surgery, Herlev Hospital; Department of Clinical Physiology, Herlev Hospital ; Department of Orthopedic Surgery, section for shoulder and elbow surgery, Aarhus University Hospital; Department of Nuclear Medicine & PET Centre, Aarhus University Hospital; Department of Nuclear Medicine & PET Centre, Aarhus University Hospital


Background: Chronic low-grade periprosthetic joint infection (PJI) of a shoulder replacement can be challenging to diagnose. 18F-FDG PET/CT is suggested as a modality to diagnose lower limb PJI, but no studies on shoulder replacements exist.
Purpose / Aim of Study: The aim of this study was to determine the diagnostic accuracy of 18F-FDG PET/CT in diagnosing chronic PJI of the shoulder.
Materials and Methods: Patients evaluated for a failed shoulder replacement during a 3-year period were prospectively included in the study. All patients underwent pre-operative 18F-FDG PET/CT and were evaluated for signs of infection by three independent reviewers using newly developed shoulder-specific criteria. Interrater-agreement was calculated between the reviewers. If the patient was revised, biopsy specimens were obtained and cultured with bacterial growth in the cultures serving as gold standard of infection.
Findings / Results: A total of 86 patients were included in the study. Nine patients were 18F-FDG PET/CT positive for infection; with only 3 true positive. Using the gold standard, infection was diagnosed after revision-surgery in 22 cases. All infections were chronic and caused by low-virulent microbes. The sensitivity of 18F-FDG PET/CT was 0.14 95%CI(0.03-0.36), specificity 0.91 95%CI(0.81-0.97), positive predictive value was 0.40 95%CI(0.15-0.71) and negative predictive value 0.71 95%CI(0.67-0.75). The interobserver agreement was 0.56 (Fleiss’ kappa) indicating moderate agreement of the visual FDG-PET evaluation using the shoulder-specific criterion.
Conclusions: 18F-FDG PET/CT has poor diagnostic accuracy in diagnosing low-grade PJI of the shoulder. 18F-FDG PET/CT cannot be recommended as a part of the preoperative workup to diagnose low-grade infection of a shoulder replacement.

Michala Skovlund Sørensen, Thomas Colding-Rasmussen, Peter Frederik Horstmann, Klaus Hindsø, Christian Dehlendorff, Julia Johansen, Michael Mørk Petersen
Musculoskeletal tumour section, Department of Orthopaedic Surgery, Rigshospitalet, University of Copenhagen; Musculoskeletal tumour section, Department of Orthopaedic Surgery, Rigshospitalet, University of Copenhagen; Musculoskeletal tumour section, Department of Orthopaedic Surgery, Rigshospitalet, University of Copenhagen; Paediatric section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen; Unit of Statistics and Pharmacoepidemiology, Danish Cancer Society Research Center; Departments of Oncology and Medicine, Herlev and Gentofte Hospital, University of Copenhagen; Musculoskeletal tumour section, Department of Orthopaedic Surgery, Rigshospitalet, University of Copenhagen


Background: YKL-40 is up-regulated in diseases characterized by inflammation, injury, and remodeling. High YKL-40 concentrations in patients with different cancer types are associated with short overall survival (OS). Interleukine-6 (IL-6) plays a role in inflammation and high IL-6 is a prognostic for short OS in different cancer types. The prognostic value for YKL-40 and IL-6 in patients undergoing surgery for metastatic bone disease (MBD) is unknown.
Purpose / Aim of Study: The aims of study were to identify (1) if plasma YKL- 40 is associated with OS in patients undergoing surgery for MBD and (2) if this association was independent of plasma IL-6 levels.
Materials and Methods: A prospective study including patients undergoing surgery for MBD in the extremities at a tertiary referral center. In case of multiple surgeries during the inclusion period (May 2014-November 2018) only blood samples from index surgery were included also excluding revison surgeries. Blood samples were collected preoperatively. YKL-40 and IL-6 concentrations were determined by ELISA. Two-hundred-thirty-two patients (median age 66 years, IQR 58-74; female 51%) were included. Eighty-two percent of the patients had disseminated disease at time of surgery and 70% of the treated lesions were completely fractured. Cox regression analysis was performed to identify if YKL40 and IL-6 was independent prognostic factors for OS. Spearmann’s test was used to adress correlation between YKL-40 and IL-6.
Findings / Results: Plasma IL-6 and YKL-40 were significantly correlated (rho: p<0.001). In univariate analysis, both high plasma IL-6 (> 50 percentile: HR=1.99, 95% CI: 1.47-2.68, p<0.001) and YKL-40 (age- adjusted >50 percentiles: HR=1.59, 95% CI: 1.10-2.32, p=0.014) were associated with short OS. In multivariable analysis, adjusted for known risk factors for survival, high IL-6 was prognostic for short OS (HR=2.21; 95% CI 1.41-3.19, p<0.001) but YKL-40 was not (HR=1.00, 95% CI: 0.64-1-56, p=0.99).
Conclusions: IL-6 and YKL-40 were associated with short OS in patients undergoing surgery for MBD. After adjusting for known clinical risk factors for poor OS only IL-6 remained significantly associated with OS. We therefore advocate for adjusting for IL-6 in prognostic studies of OS in MBD disease

Christina Holm, Michala Sørensen, Müjgan Yilmaz, Michael Mørk Petersen
Orthopedic surgery , Rigshospitalet; Orthopedic surgery, Bispebjerg Hospital; Orthopedic surgery, Rigshospitalet; Orthopedic surgery, Rigshospitalet


Background: Previous multicenter studies reports variable outcome and failure rates after mega-prosthetic reconstructions for tumors in the lower extremities.
Purpose / Aim of Study: Purpose of study was to evaluate if 1) use of second-generation mega-prosthesis for reconstruction after resection of primary malignancies result in lower incidence of implant failure and revision and also limb amputation compared to first generation prostheses, and 2) if the overall patient survival in a population based cohort of sarcoma patients has changed over time.
Materials and Methods: A retrospective study of 72 consecutive patients (F/M=30/42), mean age 44 (range 7-84) years with bone or soft tissue sarcomas (n=67) or aggressive benign bone tumors (n=5) having surgery between 2006 and 2016 with bone resection and reconstruction with mega-prostheses.Causes of failure were classified according to Henderson classification. Kaplan-Meier survival analysis was used for evaluation of overall patient survival. Fine and Gray competing risk analysis was used for assessing cumulative incidence of implant failure and limb amputation. Functional outcome was evaluated with the MSTS score
Findings / Results: Forty-seven patients were alive at follow-up.Twenty- eight patients (39%) underwent revision for all causes. Overall 10-year patient survival was 61% (95%CI 48-74%) with no difference over time (p=0.9).Ten-year incidence of implant revision and implant failure was 25% (CI: 14%-36%) and 18% (CI: 9%-28%) respectively. No difference between first and second-generation prostheses was found (p=0.9 and p=0.2 respectively).Ten-year incidence of limb amputation was 11% (95%CI: 3%-18%).No difference between first and second-generation prostheses (p=0.9).The overall predominant failure mode causing revision was non-mechanical (51%). Mean MSTS score was 20 (67%) (range 0-30)
Conclusions: Our results with second-generation mega- prostheses, justifies the use of limb salvage surgery regardless of patient diagnose and staging. We found no difference in implant failure or limb survival compared to our previously published findings (Holm et al. Int Orthop 2018;42:1175-81). For future evaluations of tumor prostheses we advocate using competing risk analyzes in order to achieve valid estimates.

Ines Willerslev Jørgensen, Dorte Dall-Hansen, Hanne Popp, Carsten Jensen
Orthopaedic Surgery and Traumatology, Kolding Hospital; Orthopaedic Surgery and Traumatology, Kolding Hospital; Orthopaedic Surgery and Traumatology, Kolding Hospital; Orthopaedic Surgery and Traumatology, Kolding Hospital


Background: The need to perform amputations has existed since ancient times, but the indication for surgery has changed drastically since World War II. E.g. amputations, due to trauma, have been reduced, while amputations, due to vascular disease and diabetes, have become more frequent. However, there is little knowledge on this group of patients and their in-hospital treatment and physical challenges.
Purpose / Aim of Study: To describe the group of non-traumatic patients undergoing above-knee- amputation (AKA), below-knee- amputation (BKA) and re-amputation (REA). Describe current in-hospital treatment, mortality and readmissions.
Materials and Methods: A retrospective cohort study, the medical records of 142 patients undergoing non-traumatic lower extremity amputation, at Kolding Hospital, Denmark, from March 2015 to December 2016, were included and data from their medical records were extracted using a standardized questionnaire.
Findings / Results: The mean age was 72 (12) years and 64% of the patients were men. Of the 142 patients, 90% had vascular disease and 50% had diabetes. 70% of the patients were ASA 3. 72% was admitted from the outpatient clinic or the vascular surgery department. 35% had medical audits during their hospitalization. 46% was mobilized to chair within 24hours and 83% during hospitalization. Infection was the most common complication (45%). AKA-patients had higher mortality at 30-days (18%) and 1-year (38%) while 8% and 15% for BKA-patients . 31% of AKA-patients were categorized ASA 4 compared with BKA (11%) and REA (21%). There was no difference in 30 days and 1-year readmission rate (13% and 35 %).
Conclusions: Lower extremity amputees deal with severe comorbidities and are in high risk of complications, readmissions and death. The current treatment focus on a multidisciplinary approach, however, does not include doctors of internal medicine. We discuss if the indication for amputation should be viewed as either a life-saving or palliative treatment. The patient’s risks and non-surgical alternatives should be considered. We also point out the need for a scoring system for mobilization that focuses on essential activities.

Karl Viktor Strange Guldagger, Hans Gottlieb, Magnus Petur Bjarnason Obinah
Department of Orthopaedic Surgery, Herlev; Department of Orthopaedic Surgery, Herlev; Department of Plastic and reconstructive surgery, Herlev


Background: Osteomyelitis(OM) are challenging to treat, especially in patients with diabetes mellitus(DM)
Purpose / Aim of Study: We report outcome after one-stage surgery with antibiotic loaded biocomposite(ALB) for management of OM in patients with DM
Materials and Methods: We report a consecutive series of 45 patients with OM and DM, treated at one institution, operated by a few surgeons, managed by a multidisciplinary team, using a one-stage revision protocol. The treatment protocol includes surgical debridement, tissue sampling, dead- space management using an ALB, direct closure when possible and 6 weeks of postoperative empirical antibiotic therapy, adjusted based on culturing. This series includes all patients with OM and DM operated at our institution according to this protocol, from March 2016 – September 2018
Findings / Results: A total of 45 patients were followed-up (FU) by chart review with a minimum FU of 6 months, mean FU was 13.7 months. Mean age was 68,8 years (45 to 92). A total of 34 (76%) patients were males and eleven (24%) females. Twelve patients (27%) were ASA class 2, 30 (67%) ASA class 3, 3 (7%) ASA class 4. Thirty-nine patients (87%) had cardiac issues ranging from essential hypertension to heart failure. Three patients had renal insufficiency and two were in dialysis. Four patients (8%) died within 3 months of surgery. The suspected cause of OM in our series, was soft tissue infection in 37 cases (82%) and surgical management of a closed fracture in 5 cases (11%), while the remaining three cases were suspected to be caused by hematogenous spread, insertion of a prosthesis or previous osteomyelitis in the local area. Following the primary procedure, during our follow-up period, 29 patients (64%) had not required further surgical revision, 9 patients (20%) had subsequent soft- tissue or bone revision and 10 patients (22%) had been amputated. Of the 10 amputations performed, 6 were due to exposed bone or infection in the overlying soft-tissue. Of note, the number of comorbidities was higher in the group of amputated patients compared to non-amputated, 9 patients (90%) were ASA class 3 and 1 was class 2 (10%)
Conclusions: An acceptable outcome was obtained considering the highly comorbid population with a high 3-month mortality of 8%

Anne Kathrine Lorentzen, Janne Horn, Hans Gottlieb, Magnús Petúr Bjarnason Obinah
Plastic Surgery, Herlev Hospital; Plastic Surgery, Herlev Hospital; Orthopedic Surgery, Herlev Hospital; Plastic Surgery, Herlev Hospital


Background: Treatment of chronic osteomyelitis (OM) comprises surgical excision of infected bone and soft tissue, dead space management, and subsequent soft tissue closure. When soft tissue revision results in defects too large for direct closure, assistance from plastic surgeons is needed.
Purpose / Aim of Study: To report outcomes for patients with OM treated by plastic and orthopedic surgeons in a single-stage operation with an antibiotic loaded biocomposite (ALB) and soft tissue closure with a local or free flap.
Materials and Methods: We report data on 11 patients with OM treated at our institution from 02/17 to 05/19. The treatment protocol included surgical debridement, dead-space management using ALB, and soft tissue closure with a local or free flap. The single- stage revision protocol was inspired by a recently published study.
Findings / Results: Mean age at surgery was 62 yrs (33-79), mean BMI was 28 (23-39). Three were females. Five patients suffered from cardiovascular disease, 2 were diabetics, and 7 had other comorbidities. Two were active smokers, and 3 had a history of smoking. Tibia was affected in 5 patients, while ulna, humerus, fibula and calcaneus were affected in the remaining patients. In 5 patients, OM followed surgical management of a closed fracture, 3 followed in open fractures, 1 arose after an overlying soft-tissue infection, 1 followed elective arthrodesis, and 1 was due to previous OM in the affected bone. Local flaps were used in 5 patients, including 1 reverse lateral arm flap, 1 soleus flap, 1 gastrocnemius flap, 1 latissimus dorsi flap, and 1 plantaris flap. Free flaps were used in 6 patients, 4 gracilis muscle flaps and 2 antero-lateral thigh flaps. Patients were followed up by chart review after a mean of 9 months (0-24). Two patients required a soft-tissue revision after 1 and 12 months, and two required bone revision and additional ALB after 7 and 10 months, respectively. No patients required amputation, and no mortalities were reported.
Conclusions: Single-stage treatment of OM using ALB performed by plastic- and orthopedic surgeons led to zero amputations in a highly morbid patient population, where amputation would otherwise have been unavoidable.