Session 10: Tumor

Fredag den 23. oktober
09:00 – 10:00
Lokale: Reykjavik
Chairmen: Johnny Keller / Claus Lindkær Jensen

109. Use of pneumatic tourniquet does not reduce the total postoperative blood loss after transtibial amputation. A prospective case-control study of 76 non-traumatic transtibial amputations.
Christian Wied, Morten Tange Kristensen, Peter Toft Tengberg, Gitte Holm, Nicolai Bang Foss, Anders Troelsen
Dept. of Orthopaedic Surgery , Copenhagen University Hospital Hvidovre, Denmark; Physical Medicine and Rehabilitation Research-Copenhagen (PMR-C), Department of Physiotherapy, Copenhagen University Hospital, Hvidovre, Denmark; Department of Anaesthesia, Copenhagen University Hospital Hvidovre, Denmark

Background: Tourniquet reduces the intraoperative blood loss when applied during transtibial amputations (TTA). However, side effects such as damage to vessels and soft tissues as well as hyperperfusion remains unilluminated. Further, the total postoperative blood loss and risk of reoperation needs evaluation to better balance the potential benefits and risks of tourniquet.
Purpose / Aim of Study: The primary aim was to determine the total calculated blood loss within the first four days after TTA's, conducted with and without tourniquet. Secondly, to investigate the association between the use of tourniquets and re-amputations.
Materials and Methods: Primary TTA’s operated in 2013-14 at our institution were eligible for inclusion (n=86). We excluded 8 because of bilateral amputations and 2 because of traumas. The study group consisted of 76 TTA’s performed due to diabetes related complications or severe arteriosclerosis (38 with tourniquet / 38 without tourniquet). The decision to use tourniquet relied on the surgeons. The total blood loss (intraoperative until postoperative day 4) was calculated based on the hemoglobin level using a transfusion trigger of 6mmol/l and the estimated blood volume.
Findings / Results: The demographic data showed no difference between the two groups. The total calculated blood loss on day four after surgery was 930 ml ± 763 in the tourniquet group vs. 947 ml ± 717 in the non- tourniquet group (p=0.98 in a multivariate analysis). Correspondingly, no significant differences were found in transfusion requirements after four days or in the re-operation rates at one and three months follow-up.
Conclusions: Performing a TTA with the use of tourniquet does not reduce the total calculated blood loss or transfusion requirements when evaluated on postoperative day 4. The use of tourniquet does not seem to influence the re-amputation rates.

110. Is there a correlation between Skin Perfusion Pressure and healing after amputation below the knee?
Kate Smidt, Niels Krarup, Jan Abrahamsen, Thomas Jakobsen
Ortopædkirurgisk afdeling, Regionshospital Viborg; Klinisk Fysiologisk afdeling, Regionshospital Viborg

Background: When performing below knee amputation, the vascular status of the limb is of paramount significance for wound healing. Skin Perfusion Pressure (SPP) is one way to measure healing potential. A SPP of 40 mm Hg or above is believed to indicate a good or a very good probability for healing after amputation.
Purpose / Aim of Study: To examine the correlation between SPP and wound healing after below knee amputation.
Materials and Methods: One hundred and six consecutive patients underwent 113 below knee amputations from January 2009 to December 2013 at the Regional Hospital Viborg. The primary outcomes were any need for further wound management, amputation at a higher level or even death within the first 90 days. These informations were obtained from the medical records of the patients. SPP measured by photocell technique was performed less than two days prior to surgery.
Findings / Results: Seventy of 113 below knee amputations (62%) had a SPP performed prior to surgery. Of these seventy amputations twenty had a SPP of 40 mmHg or less. Five (25%) of the amputations with a SPP values of 40 mmHg or less had to be reamputated at a higher level. Four (20%) with a SPP values of 40 mmHg or less needed further wound management. Three of the patients with a SPP values of 40 mmHg or less died within 90 days. Thus 50 amputations (71%) had a SPP above 40 mm Hg. Of these 50 amputations three (6%) needed reamputation at a higher level, one of these patients died afterwards. Seven (7/50=14%) needed further wound management, off which two patients died. In total twenty one of the patients died within 90 days.
Conclusions: Several factors influence the outcome after below knee amputation. The group of patients is very fragile, and in order for a better understanding of the outcome, there is a need for a prospective study.

111. Can inflammatory markers be included into models predicting survival after treatment for metastatic lesions in the extremities?
Michala S. Sørensen, Jonathan A. Forsberg, Klaus Hindsø, Michael M. Petersen
1Mukculoskeletal Section, Department of Orthopedics, Rigshospitalet, University hospital of Copenhagen; Regenerative Medicine, Naval Medical Research Center, Silver Spring, Maryland, USA; Children’s orthopaedics, Department of Orthopedics, Rigshospitalet, University hospital of Copenhagen,

Background: Prediction of survival is considered valuable for surgeons treating metastatic bone disease in the extremities. Different models have been developed however none including inflammatory markers.
Purpose / Aim of Study: We aimed to 1) develop a model that can estimate the likelihood of survival at 3, 6 and 12 months after surgery, based on variables that are easily accessible from patient records including inflammatory markers. 2) Investigate its accuracy using the receiver operator characteristic (ROC) analysis and decision curve analysis (DCA).
Materials and Methods: A consecutive cohort of 130 patients having joint replacement surgery due to metastatic lesions at Rigshospitalet during the period 2003-2008 was included. Demographics, clinical and biochemical variables preoperatively was included into the model (age, gender, primary cancer group, ASA, hemoglobin, C-reactive protein, fracture vs. impending fracture, visceral metastasis, multiple bone metastasis). Primary cancer group was grouped as proposed by Katagiri (1,2). A Bayesian belief network (BBN) for survival status at 3, 6 and 12 months were developed and internally validated and area under the ROC curves calculated. Net benefit of the model was evaluated with DCA.
Findings / Results: BBN for survival status at 3, 6 and 12 months was developed and internal validation showed AUC of ROC curves of 0.77 (CI: 0.66;0.87), 0.83 (CI: 0.74;0.91) and 0.87 (CI: 0.81;0.94) respectively. DCA showed a clinical net benefit using these models compared to expecting all patients to outlive the period.
Conclusions: We successfully developed a BBN for predicting survival status at 3, 6 and 12 months based on various parameters including C-reactive protein. Though these results are encouraging, each of these models should be externally validated prior to being used clinically.

112. Implant and patient survival following limb-sparing surgery with reconstruction using the Global Modular Replacement System (GMRS) due to primary or secondary bone cancer. A retrospective study of 52 patients
Müjgan Yilmaz, Michala S. Sørensen, Michael M. Petersen
Musculoskeletal Tumor Section, Department of Orthopedics, University hospital of Copenhagen, Rigshospitalet, Denmark

Background: Today limb-sparing tumor resection is possible in 90% of patients suffering from bone sarcomas (BS) and the preferred method of reconstruction is the use of mega-prostheses. The same surgical technique is occasionally also used in the treatment of patients suffering from metastatic bone disease (MBD).
Purpose / Aim of Study: To investigate implant and patient survival following limb-sparing surgery using the GMRS mega-prosthesis in BS or MBD patients.
Materials and Methods: A consecutive cohort of 52 patients (mean age 47 (11-78) years, F/M=21/31) treated with limb-sparing surgery due to BS (n=37) or MBD (n=15) of the lower extremities (resection type: distal femur (n= 27), proximal tibia (n=5), proximal femur (n=17), total femur (n=3)) at our orthopedic oncology tertiary referral center from 2005 to 2013. Patients were followed until death or end of study (13.06.2015). Statistical analysis used was Kaplan-Meier analysis
Findings / Results: All-cause one-year and 5 year mortality was 90.4 % and 63.0% for the complete cohort (94.6% vs 72.5% for sarcoma and 80.0% vs 40.0% for metastatic bone disease). 18 patients experienced reoperation of all causes (mean time to first surgery 694 days (range 4-3003 days). 4 patients had removal of bone anchored prosthesis components (median 925 days range 322-1855), resulting in a 5-year estimated risk of revision of 93.5%. 3 patients had amputation due to local recurrence (5 year limb survival rate of 93.6%).
Conclusions: The use of the GMRS prosthesis for reconstruction after limb-sparing bone tumor resection of the lower extremities has an acceptable risk of revision of the bone anchored parts of the implants and the risk of amputation was low. The results should be interpreted with caution due to competing risk of short life survival of especially the MBD patients in this cohort.

113. In-vivo gentamicin concentrations in plasma and drain fluid after bone defect reconstruction using a gentamicin-eluting bone graft substitute
Peter Frederik Horstmann, Werner Hettwer, Zhijun Song, Michael Mørk Petersen
Muskuloskeletal Tumor Section, Rigshospitalet, Copenhagen University Hospital; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital

Background: Reconstruction of bone defects after bone tumor resection is associated with an increased risk of infection. A gentamicin-eluting bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this indication.
Purpose / Aim of Study: To document early in-vivo concentrations of gentamicin in plasma and drain fluid after bone defect reconstruction using a gentamicin- eluting bone graft substitute.
Materials and Methods: We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37-79) years) who underwent bone defect reconstruction with a gentamicin- eluting bone graft substitute (CERAMENT™|G – BONESUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic bone disease (n=3), giant cell tumor (n=2), aseptic prosthetic loosening (n=1) and chondroid tumor (n=1). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed and analyzed using an antibody technique.
Findings / Results: A mean of 14 (10-20) mL gentamicin- eluting bone graft substitute was used. Mean drain fluid concentrations of gentamicin were 1200 (723-2100) mg/L immediately postoperative (0-2 hours), 1054 (300-1999) mg/L on day 1 (17-23 hours) and 509 (38-1000) mg/L on day 2 (39-45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08-1.42) mg/L immediately postoperative, 0.95 (0.25- 2.06) mg/L on day 1 and 0.56 (0.20- 0.88) mg/L on day 2.
Conclusions: Local implantation of a gentamicin- eluting bone graft substitute for bone defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations.

114. Risk Factors for Local Recurrence after Intralesional Curettage for Giant Cell Tumors of Bone
Peter Frederik Horstmann, Peter Holmberg Jørgensen, Mathias Rædkjær, Bjarne Hauge Hansen, Michala Skovlund Sørensen, Werner Hettwer, Tine Nymark, Michael Mørk Petersen
Muskuloskeletal Tumor Section, Copenhagen University Hospital; Department of Orthopedic Surgery, Sarcoma Center, University Hospital of Aarhus; Department of Orthopedic Surgery, Odense University Hospital

Background: Intralesional treatment of giant cell tumors of bone (GCT) increases local recurrence rates compared with wide resection. Adjuvant treatment with PMMA has been proposed to reduce local recurrence rates. However, some surgeons believe that other factors are equally important.
Purpose / Aim of Study: To determine which patient demographics, tumor characteristics, or surgical/clinical parameters are risk factors for local recurrence after intralesional treatment of GCT.
Materials and Methods: Retrospective data from a national cohort of all patients with GCT of the appendicular skeleton (n=74, M/F: 37/37, median age 29 (12-68 years), treated intralesionally between 1998 and 2013, was analyzed for association of risk factors with local recurrence using univariate, multivariate Cox regression and Kaplan-Meier survival analysis.
Findings / Results: The cumulative 4-year recurrence rate was 37%. The only significant independent risk factors associated with local recurrence rate were “preoperative diagnosis confirmed by biopsy” (HR=0.30, CI:0.10-0.90) and “treatment at an oncology center” (HR=0.29 CI:0.08- 0.99). There was no independent association between local recurrence rate and other parameters such as age, gender, tumor location and Campanacci grade, pathological fracture or the use of PMMA.
Conclusions: Our results suggest that confirmation of histological diagnosis before definitive surgery and referral to an orthopedic oncology center are important to avoid local recurrence of GCT. We recommend that surgery for GCT’s is performed at a dedicated orthopedic oncology center, where biopsy typically is a part of the diagnostic routine. It seems that local adjuvant therapy with PMMA in itself is not a guarantee for a lower recurrence rate.

115. Migration pattern of the osseointegrated implant system for transfemoral fixation evaluated with radiostereometry
Rehne Lessmann Hansen , Peter Holmberg Jørgensen, Klaus Kjær Petersen, Kjeld Søballe, Maiken Stilling
Ortopædkirurgisk forskningsenhed, Aarhus Universitetshospital; Tumorsektoren, Aarhus Universitetshospital; Ortopædkirurgisk afd, Aarhus Universitetshospital

Background: The osseointegrated(OI) implant system is a treatment for transfemoral amputees with a short residual femur and/or problems using socket prostheses
Purpose / Aim of Study: To study fixation stability(migration) of the OI- implant up to 24 months follow-up with model- based radiostereometry (mbRSA)
Materials and Methods: 18 consecutive patients(12 males) mean age 49.5(range 32-66) were operated through a two stage procedure(S1,S2). At S1, a titanium implant(fixture) was inserted into the distal part of femur. At S2, 6 months later, a rod(abutment) was inserted into the fixture, exiting through the skin. Weight bearing on the implant was not allowed between S1 and S2(unloading phase) and started after S2 (loading phase). Stereoradiographs were obtained postoperatively every 6 months. X, Y, and Z translations and Total Translations (TT =√(X2+Y2+Z2)) were evaluated using CAD- models. Precision (double examinations) was evaluated as standard deviation (SD)x1.96
Findings / Results: During unloading the mean TT(SD) was 1.07(0.87) mm with Y-translation -0.16(0.34) mm. During the loading phase TT at 6, 12, 18, and 24 months was 0.55(0.40) mm, 0.64(0.57) mm, 0.53(0.39) mm, and 0.87(0.94) mm There was no continuous migration(TT) p>0.68 and no continuous subsidence after S2 p>0.09. Precision along the orthogonal axes were X:0.62mm, Y:0.14mm and Z:0.63mm. At 2 years, 8 OI-implants migrated above the precision limit on the Y-axis, 1 due to trauma, 4 had infections, 2 had no clinical explanation, and 1 with leg pain during loading
Conclusions: MbRSA is feasible for measurements of fixation. Precision is less than with hip stems due to more difficult fitting of the model geometry. Overall, the OI-implant system was found to be stable after S2 on group level, but 8 patients had measureable Y-axis migrations and most had clinical conditions coherent with implant migration

116. Reconstruction of metastatic bone defects with a bisphosphonate eluting bone graft substitute
Werner Hettwer, Peter Horstmann, Michael Mørk Petersen
Orthopaedic Department, Rigshospitalet

Background: Bisphosphonates inhibit the osteoclast mediated bone destruction associated with secondary malignant bone tumors. They also induce apoptosis of tumor cells and could therefore potentially contribute to prevention of local recurrence as well as restoration of bone.
Purpose / Aim of Study: To report an early clinical experience with use of local delivery of zoledronic acid in the reconstruction of metastatic bone defects.
Materials and Methods: Six patients (5f, 1m, mean age 64 (range 37-81) who had undergone reconstruction of metastatic bone defects with implantation of a gentamycin eluting sulphate-apatite bone graft substitute (Cerament™|G, BONESUPPORT, Lund, Sweden) which we additionally loaded with zoledronic acid, were prospectively followed for a mean of 12 months (range 6-17). In all 5 female patients, the indication for treatment was a partially contained bone defect associated with incipient or actual pathologic fracture of the acetabulum (n=3) or proximal humerus (n=2) secondary to metastatic breast cancer. The only male patient had wide resection of a solitary lung cancer metastasis from the proximal femur.
Findings / Results: Sequential imaging (X-ray/CT) demonstrated progressive consolidation of the inserted graft material without any evidence of persistent osteolysis or local recurrence. Rapid and homogeneous remodeling typically started in well- contained areas with cancellous bone contact. Substantial bone formation was also observed in uncontained areas where graft material had been applied to the surface of metallic implants or surrounding cortical bone in some cases.
Conclusions: This small and inhomogenous case series demonstrates that successful restoration of metastatic bone defects with a bisphosphonate eluting bone graft substitute is possible in selected cases.