Validity of the Musculoskeletal Tumor Society Score for lower extremity in patients with bone sarcoma or giant cell tumour of bone undergoing bone resection and reconstruction surgery in hip and knee.

BACKGROUND: The Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE). METHODS: The study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements. RESULTS: Content validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items' response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels. CONCLUSION: The Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

Postoperative challenges addressed through nursing care of patients receiving lower extremity tumor prosthesis.

BACKGROUND: Patients with primary Bone Sarcoma and Giant Cell Tumors in the lower extremities often require major surgery involving tumor prostheses. The postoperative course for this patient group can be complex and influenced by various factors and challenges that demand careful nursing care. This study aims to identify challenges related to the nursing care of individuals with primary bone tumors following surgery for tumor prostheses in the lower extremities. METHODS: A retrospective cohort study of 15 patients treated at Rigshospitalet, Copenhagen, Denmark, between November 5. 2016, and April 1. 2020 was conducted by medical record review, focusing on challenges related to postoperative nursing care. All patients with the surgery code "Bone Excision" were identified within the surgery booking system and screened for eligibility. RESULTS: Patients experienced postoperative challenges such as severe pain, prolonged time to mobilization (mean: 4 days), and defecation (mean: 5 days). The mean length of stay at the Rigshospitalet was 13 days. Furthermore, eleven patients (73%) reported disrupted sleep and nausea. CONCLUSION: Patients undergoing tumor prosthesis surgery in the lower extremities face considerable postoperative challenges that contribute to a prolonged hospital stay. These challenges, including severe pain, delayed mobilization, and gastrointestinal issues, significantly impact recovery. The findings highlight the urgent need for targeted nursing interventions to address these issues effectively. Enhanced pain management protocols, early mobilization strategies, and comprehensive postoperative care plans are essential to improve patient outcomes and reduce the length of hospital stays. Addressing these challenges through dedicated nursing care is crucial for optimizing the recovery process for patients receiving lower extremity tumor prostheses.

Discontinuing the recommendation of hip precautions does not increase the risk of early dislocation after primary total hip arthroplasty using 36-mm heads: a population-based study from the Danish Hip Arthroplasty Register.

BACKGROUND AND PURPOSE: Dislocation is a severe complication following total hip arthroplasty (THA). Hip precautions have been recommended in the initial postoperative period but evidence supporting this practice is limited. We therefore conducted a population-based study to evaluate the association between discontinuing recommending postoperative hip precautions and the risk of early dislocation. METHODS: This is a cohort study with data from the Danish Hip Arthroplasty Register and the Danish National Patient Register. We included patients who underwent primary THA for osteoarthritis in 2004-2019 in public hospitals in the Capital Region of Denmark. The cohort was divided into the hip precautions group, comprising patients operated on between 2004 and 2009, and the no-precautions group operated on between 2014 and 2019. The primary outcome was the difference in the absolute risk of dislocation within 3 months post-surgery. The secondary outcome assessed the same risk within 2 years. We evaluated the difference in absolute risk using absolute risk regression (ARR). RESULTS: The cumulative incidence of dislocation within 3 months was 2.9% (confidence interval [CI] 2.5-3.3) in the hip precautions group and 3.5% (CI 3.1-3.9) in the no-precautions group. The risk of dislocation was higher in the no-precautions group but failed to reach statistical significance in the crude (ARR 1.2, CI 0.9-1.6) and multivariate model (ARR 1.4, CI 0.9-2.2). CONCLUSION: We found a higher but statistically insignificant increase in the risk of early dislocation in the no-precautions group. The lack of significance in the association may be explained by the increased use of 36-mm femoral heads after the guideline revision.

Elevated cobalt levels in metal-on-polyethylene knee megaprostheses: a prospective 1-year cohort study of 56 patients with hip and knee megaprostheses.

BACKGROUND AND PURPOSE: Concerns have emerged regarding elevated levels of cobalt and chromium in patients with metal-on-metal megaprostheses. This prospective study aims to identify systemic cobalt and chromium levels in metal-on-polyethylene knee and hip megaprostheses and their associations with other factors. METHODS: 56 patients underwent knee or hip megaprosthesis surgery at 2 sarcoma centers. Serum cobalt and chromium levels were measured preoperatively and thrice within the first year using inductively coupled plasma mass spectrometry. RESULTS: A statistically significant difference in serum cobalt levels (1.4 ppb; 95% confidence interval [CI] 0.0-3.3) was observed 1 year after knee megaprosthesis surgery compared with preoperative levels. In contrast no difference in chromium levels was observed after 1 year compared with preoperative levels (0.05 ppb; CI 0.0-0.8). An association between younger age, higher eGFR, and increased cobalt levels was observed. No significant correlations were found between ion levels and resection length or the number of modular connections. CONCLUSION: We found elevated serum ion levels in metal-on-polyethylene knee megaprostheses in contrast to metal-on-polyethylene hip megaprostheses. Furthermore, a positive correlation between cobalt and chromium levels, and between cobalt and eGFR was identified, along with a negative correlation between cobalt and age. This study highlights the importance of monitoring systemic cobalt and chromium levels in patients with megaprostheses.

Dislocation rate after hip arthroplasty due to metastatic bone disease: a retrospective cohort study evaluating the postoperative dislocation risk across different articulating solutions.

BACKGROUND AND PURPOSE: Joint stability after hip replacement (HR) in patients with metastatic bone disease (MBD) is of special importance. Dislocation is the second leading cause of implant revision in HR, while survival after MBD surgery is poor with an expected 1-year survival of around 40%. As few studies have investigated the dislocation risk across different articulation solutions in MBD, we conducted a retrospective study on primary HR for patients with MBD treated in our department. PATIENTS AND METHODS: The primary outcome is the 1-year cumulative incidence of dislocation. We included patients with MBD who received HR at our department in 2003-2019. We excluded patients with partial pelvic reconstruction, total femoral replacement, and revision surgery. We assessed the incidence of dislocation with competing risk analysis with death and implant removal as competing risks. RESULTS: We included 471 patients. Median follow-up was 6.5 months. The patients received 248 regular total hip arthroplasties (THAs), 117 hemiarthroplasties, 70 constrained liners, and 36 dual mobility liners. Major bone resection (MBR), defined as resection below the lesser trochanter, was performed in 63%. The overall 1-year cumulative incidence of dislocation was 6.2% (95% CI 4.0-8.3). Dislocation stratified by articulating surface was 6.9% (CI 3.7-10) for regular THA, 6.8% (CI 2.3-11) for hemiarthroplasty, 2.9% (CI 0.0-6.8) for constrained liner, and 5.6% (CI 0.0-13) for dual mobility liners. There was no significant difference between patients with and without MBR (p = 0.5). CONCLUSION: The 1-year cumulative incidence of dislocation is 6.2% in patients with MBD. Further studies are needed to determine any real benefits of specific articulations on the risk of postoperative dislocation in patients with MBD.

Plate-assisted bone-segment transport in the femur with 2 internal lengthening nails: a technical note and a case report.

A novel technique to resolve large bone defects, using 2 internal lengthening nails (ILNs), one antegrade and one retro-grade, aligned in a custom-made tube is presented. A 28-year-old, healthy, asymptomatic male presented with a slowly growing mass in the left femur.

Clinically Important Reductions in Physical Function and Quality of Life in Adults with Tumor Prostheses in the Hip and Knee: A Cross-sectional Study.

BACKGROUND: Patients with a bone sarcoma who undergo limb-sparing surgery and reconstruction with a tumor prosthesis in the lower extremity have been shown to have reduced self-reported physical function and quality of life (QoL). To provide patients facing these operations with better expectations of future physical function and to better evaluate and improve upon postoperative interventions, data from objectively measured physical function have been suggested. QUESTIONS/PURPOSES: We sought to explore different aspects of physical function, using the International Classification of Functioning, Disability, and Health (ICF) as a framework, by asking: (1) What are the differences between patients 2 to 12 years after a bone resection and reconstruction surgery of the hip and knee following resection of a bone sarcoma or giant cell tumor of bone and age-matched controls without walking limitations in ICF body functions (ROM, muscle strength, pain), ICF activity and participation (walking, getting up from a chair, daily tasks), and QoL? (2) Within the patient group, do ICF body functions and ICF activity and participation outcome scores correlate with QoL? METHODS: Between 2006 and 2016, we treated 72 patients for bone sarcoma or giant cell tumor of bone resulting in bone resection and reconstruction with a tumor prosthesis of the hip or knee. At the timepoint for inclusion, 47 patients were alive. Of those, 6% (3 of 47) had undergone amputation in the lower limb and were excluded. A further 32% (14 of 44) were excluded because of being younger than 18 years of age, pregnant, having long transportation, palliative care, or declining participation, leaving 68% (30 of 44) for analysis. Thus, 30 patients and 30 controls with a mean age of 51 ± 18 years and 52 ± 17 years, respectively, were included in this cross-sectional study. Included patients had been treated with either a proximal femoral (40% [12 of 30]), distal femoral (47% [14 of 30]), or proximal tibia (13% [4 of 30]) reconstruction. The patients were assessed 2 to 12 years (mean 7 ± 3 years) after the resection-reconstruction. The controls were matched on gender and age (± 4 years) and included if they considered their walking capacity to be normal and had no pain in the lower extremity. Included outcome measures were: passive ROM of hip flexion, extension, and abduction and knee flexion and extension; isometric muscle strength of knee flexion, knee extension and hip abduction using a hand-held dynamometer; pain intensity (numeric rating scale; NRS) and distribution (pain drawing); the 6-minute walk test (6MWT); the 30-second chair-stand test (CST); the Toronto Extremity Salvage Score (TESS), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The TESS and the EORTC QLQ-C30 were normalized to 0 to 100 points. Higher scoring represents better status for TESS and EORTC global health and physical functioning scales. Minimum clinically important difference for muscle strength is 20% to 25%, NRS 2 points, 6MWT 14 to 31 meters, CST 2 repetitions, TESS 12 to 15 points, and EORTC QLQ-C30 5 to 20 points. RESULTS: Compared with controls, the patients had less knee extension and hip abduction strength in both the surgical and nonsurgical limbs and regardless of reconstruction site. Mean knee extension strength in patients versus controls were: surgical limb 0.9 ± 0.5 Nm/kg versus 2.1 ± 0.6 Nm/kg (mean difference -1.3 Nm/kg [95% CI -1.5 to -1.0]; p < 0.001) and nonsurgical limb 1.7 ± 0.6 Nm/kg versus 2.2 ± 0.6 Nm/kg (mean difference -0.5 Nm/kg [95% CI -0.8 to -0.2]; p = 0.003). Mean hip abduction strength in patients versus controls were: surgical limb 1.1 ± 0.4 Nm/kg versus 1.9 ± 0.5 Nm/kg (mean difference -0.7 Nm/kg [95% CI -1.0 to -0.5]; p < 0.001) and nonsurgical limb 1.5 ± 0.4 Nm/kg versus 1.9 ± 0.5 Nm/kg (-0.4 Nm/kg [95% CI -0.6 to -0.2]; p = 0.001). Mean hip flexion ROM in patients with proximal femoral reconstructions was 113° ± 18° compared with controls 130° ± 11° (mean difference -17°; p = 0.006). Mean knee flexion ROM in patients with distal femoral reconstructions was 113° ± 29° compared with patients in the control group 146° ± 9° (mean difference -34°; p = 0.002). Eighty-seven percent (26 of 30) of the patients reported pain, predominantly in the knee, anterior thigh, and gluteal area. The patients showed poorer walking and chair-stand capacity and had lower TESS scores than patients in the control group. Mean 6MWT was 499 ± 100 meters versus 607 ± 68 meters (mean difference -108 meters; p < 0.001), mean CST was 12 ± 5 repetitions versus 18 ± 5 repetitions (mean difference -7 repetitions; p < 0.001), and median (interquartile range) TESS score was 78 (21) points versus 100 (10) points (p < 0.001) in patients and controls, respectively. Higher pain scores correlated to lower physical functioning of the EORTC QLQ-C30 (Rho -0.40 to -0.54; all p values < 0.05). Less muscle strength in knee extension, knee flexion, and hip abduction correlated to lower physical functioning of the EORTC QLQ-C30 (Rho 0.40 to 0.51; all p values < 0.05). CONCLUSION: This patient group demonstrated clinically important muscle weaknesses not only in resected muscles but also in the contralateral limb. Many patients reported pain, and they showed reductions in walking and chair-stand capacity comparable to elderly people. The results are relevant for information before surgery, and assessments of objective physical function are advisable in postoperative monitoring. Prospective studies evaluating the course of physical function and which include assessments of objectively measured physical function are warranted. Studies following this patient group with repetitive measures over about 5 years could provide information about the course of physical function, enable comparisons with population norms, and lead to better-designed, targeted, and timely postoperative interventions. LEVEL OF EVIDENCE: Level III, therapeutic study.

Quantitative measurements of adaptive bone remodeling around the cemented Zimmer® segmental stem after tumor resection arthroplasty using dual-energy x-ray absorptiometry.

BACKGROUND: Limb salvage surgery (LSS) is the preferred method for treatment of patients with sarcomas and to a greater extent also to patients with metastatic bone disease. The aim of the present study was to evaluate the adaptive remodeling of the periprosthetic cortical bone after insertion of a tumor prosthesis with cemented stem. 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 resection due to a tumor, 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) (g/cm2) were done postoperatively and after 3, 6, and 12 months using dual-energy X-ray absorptiometry. BMD was measured in 4 regions of interest around the cemented stem and in one region of interest 1 cm proximal from the ankle joint of the affected limb and measurement of the contralateral ankle was used as reference. Repeated measures ANOVA and students paired t-test was used to evaluate BMD changes over time. RESULTS: At 1-year follow-up, BMD decreased compared to baseline in all four 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 trabecular metal (TM) collar and lowest (8%) adjacent to the tip of the stem. CONCLUSION: After 1 year the decrease in bone mineral density of the ankle on the affected limb was 9% and the contralateral ankle was close to baseline, thus suggesting that the periprosthetic bone mineral density changes during follow-up, mainly are caused by stress shielding and immobilization. TRIAL REGISTRATION: The study was approved by the Scientific Ethical Committee of the Capital Region of Denmark (J. No. H-2-2014-105) and the Danish Data Protection Agency (J. No.: 2012-58-00004 ).

In vitro 4-1BB stimulation promotes expansion of CD8+ tumor-infiltrating lymphocytes from various sarcoma subtypes.

Tumor-specific tumor-infiltrating lymphocytes (TILs) can be in vitro expanded and have the ability to induce complete and durable tumor regression in some patients with melanoma following adoptive cell therapy (ACT). In this preclinical study, we investigated the feasibility of expanding TIL from sarcomas, as well as performing functional in vitro analyses on these. TILs were expanded in vitro by the use of IL2 stimulation with or without the addition of 4-1BB and CD3 antibodies. Phenotypical and functional analyses were mainly performed by flow cytometry. TILs were expanded from 25 of 28 (89%) tumor samples from patients with 9 different sarcoma subtypes. TILs were predominantly αß T-cells of effector memory subtype with CD4+ dominance. In particular, CD8+ TIL highly expressed LAG3 and to a lesser degree PD-1 and BTLA. In total, 10 of 20 TIL cultures demonstrated in vitro recognition of autologous tumor. In some cases, the fraction of tumor-reactive T cells was more than 20%. 4-1BB stimulation augmented expansion kinetics and favored CD8+ occurrence. In conclusion, TIL expansion from sarcoma is feasible and expanded TILs highly express LAG3 and comprise multifunctional tumor-reactive T-cells.

No detectable remodelling in adult human menisci: an analysis based on the C14 bomb pulse.

OBJECTIVES: Bone and other human tissues remodel through life, for example, as a response to increasing load, and this prevents permanent destruction of the tissue. Non-traumatic meniscal rupture is a common musculoskeletal disease, but it is unknown if it is caused by inability of the menisci to remodel. The aim of this study was to determine whether meniscal collagen is remodelling throughout life. METHODS: The life-long turnover of the human meniscal collagens was explored by the 14C bomb pulse method. 14C levels were determined in menisci from 18 patients with osteoarthritis and 7 patients with healthy knees. RESULTS: There was a negligible turnover of the meniscal collagen in adults. This low turnover was observed in menisci from patients with knee osteoarthritis and in healthy menisci. CONCLUSION: This study provides evidence that essentially no remodelling occurs in the adult human meniscal collagen structure and explains the clinical degeneration that is often seen in menisci of middle-aged and elderly persons. It suggests that strengthening of the collagen structure of menisci, as response to physical activity, may occur during childhood, while it is not possible in the adult population.

No-Fault Compensation From the Patient Compensation Association in Denmark After Primary Total Hip Replacement in Danish Hospitals 2005-2017.

BACKGROUND: There is an annually rising number of performed total hip arthroplasty (THA) surgeries in Denmark and this is expected to become even more common. However, there are still risks of adverse events, which become the basis for compensation claims. In Denmark, there are no studies available concerning filed claims after THA. The aims of this study are to determine the incidence of claims related to THAs in Denmark, the reasons to claim, which claims lead to compensation, the amount of compensation, and trends over time. METHODS: In this observational study, we analyzed all closed claims between 2005 and 2017 from the Danish Patient Compensation Association (DPCA). With the intention to contribute to prevention, we have identified the number and outcome of claims. RESULTS: There were 2924 cases (ie, 2.5% of all THAs performed in this period). The approval rate was 54%. The number of claims filed was stagnant over time, except for a spike of metal-on-metal (MoM) prosthesis cases. The total payout was USD 29,591,045, and 87% of this was due to nerve damage (USD 9,106,118), infection (USD 6,046,948), MoM prosthesis (USD 4,624,353), insufficient or incorrect treatment (USD 472,500), and fracture (USD 2,088,110). CONCLUSION: In total, 2.5% of all THAs performed between 2005 and 2017 lead to a claim submission at the DPCA. One of 2 claims were approved. The majority of payouts were due to nerve damage, infection, MoM prosthesis, insufficient or incorrect treatment, and fracture. Although DPCA manages claims for patients, the data can also provide beneficial feedback to arthroplasty surgeons with the aim of improving patient care.

Low Recurrence Rate and Risk of Distant Metastases following Marginal Surgery of Intramuscular Lipoma and Atypical Lipomatous Tumors of the Extremities and Trunk Wall.

OBJECTIVE: The purpose of the present study was to determine the local recurrence rate, risk of dedifferentiation, and distant metastasis after surgical excision of intramuscular lipomas (IML) and atypical lipomatous tumors (ALT). SUBJECTS AND METHODS: We retrospectively assessed all IML and ALT surgically removed from the extremities or trunk wall in our clinic between 1997 and 2006. Data from 141 patients with IML and 35 patients with ALT were extracted from the National Pathology Registry and patient files. RESULTS: IML and ALT recurred in 10 and 6 tumors, respectively. No metastases were observed in either group. The 5- and 10-year local recurrence-free survival rates were 97.1% (94.3-99.9) and 94.8% (CI: 91.1-98.6) for IML and 84.6% (CI: 72.1-97.1) and 81.1% (CI: 67.6-94.8) for ALT, respectively. ALT were found to dedifferentiate in 2/35 cases. CONCLUSION: Both IML and ALT showed a low recurrence rate when removed surgically from the extremities or trunk wall with intended marginal resection. No distant metastases were observed in any of the groups. It, therefore, seems safe to treat these tumors with marginal resection.

Bone remodeling of the proximal tibia after uncemented total knee arthroplasty: secondary endpoints analyzed from a randomized trial comparing monoblock and modular tibia trays-2 year follow-up of 53 cases.

Background and purpose - Bone remodeling as a response to bone trauma, postoperative immobilization, and device-related bone reactions can lead to loss of bone stock and increase the risk of periprosthetic fracture and aseptic loosening. This study investigates the adaptive bone remodeling of the proximal tibia after uncemented total knee arthroplasty (TKA). Patients and methods - We performed a 2-year follow up of 53 patients (mean age 62 (38-70) years, 27 of whom were men, who received an uncemented TKA in a randomized controlled trial with bone mineral density (BMD) as secondary endpoint. Patients were randomized to 2 groups of either monoblock (A) or modular (B) polyethylene design. The TKAs were performed using the uncemented Zimmer Nexgen trabecular metal. Measurements of BMD were done postoperatively and after 3, 6, 12, and 24 months. BMD was measured in 3 regions of interest (ROI). Results and interpretation - In group A statistically significant changes in BMD were seen after 24 months in both the medial and lateral ROI. BMD decreased medially by 15% (p = 0.004) and laterally by 13% (p = 0.01). In group B the BMD changes were limited and after 24 months returned to the preoperative values. The differences in BMD change between groups were statistically significant in both the medial (p = 0.03) and lateral (p = 0.02) ROI. In the distal ROI we found no significant change in BMD in either group. A significantly different bone remodeling pattern of the proximal tibia was seen in the 2 groups with a higher degree of bone loss in the knees that received the monoblock polyethylene design, indicating that the flexible monoblock implant design, previously shown to improve fixation, does not decrease the bone loss of the proximal tibia.

Patient survival following joint replacement due to metastatic bone disease - comparison of overall patient and prostheses survival between cohorts treated in two different time-periods.

BACKGROUND: Improvements in medical treatment for cancer have increased survival of cancer patients. We hypothesize that improvement in cancer treatment is reflected in increased survival after surgical intervention for metastatic bone disease (MBD) and that subsequent revision surgery does not pose a risk for survival. METHODS: We identified a retrospective consecutive cohort who received bone resection and reconstruction (BRR) with implants (including total joint replacements (with or without wide resection) or bone reconstruction with an intercalary spacer or revisions procedures for failed implants with BBR technique) due to MBD from 2003 to 2008 (early cohort) and 2009 to 2013 (late cohort) at a tertiary referral center. We registered epidemiological data, type of implant (primary or a revision implant), patient survival (Kaplan-Meier), implant survival (competing risk analysis) and complications to surgery. RESULTS: Three hundred and eleven procedures were performed in 291 patients (289 primary BRR (270 patients, early cohort n = 130 late cohort n = 140) and 22 revision BRR (21 patients)). Overall survival was 44% (95% confidence intervals (95% CI): 39-50) and 32% (95% CI: 27-38) after 1 and 2 years. No difference in survival between the early and late cohort was found (p = .458), or between primary and revision BRR (p = .465). Time from diagnosis of cancer to surgery was shorter in the early cohort (p < .001). The cumulative incidence of failure of implant was 2% (95% CI: 0-3%) at 1 year and 3% (95% CI: 1-6%) at 2 years. One year cumulative implant failure for revision implants was 5% (95% CI: 0-13%) at 1 and 2 years. The risk of failure was not statistical significant between primary and revision implant (p = .293) in competing risk analysis. DISCUSSION: We were not able to identify an increased survival after surgery for MBD over time, however, we found an increased interval from diagnosis to surgery for MBD. This study suggests that revision surgery for MBD does not pose a risk for survival.

Survival and prognostic factors at time of diagnosis in high-grade appendicular osteosarcoma: a 21 year single institution evaluation from east Denmark.

BACKGROUND: Survival of patients with high-grade osteosarcoma (HOS), the most common primary bone cancer, has not improved significantly the last 30 years and the disease remains a major challenge. The purpose of this study is to evaluate survival in relation to prognostic factors at time of diagnosis among patients diagnosed with primary appendicular HOS in East Denmark between 1990 and 2010. MATERIAL AND METHODS: 101 patients (median age = 20 years, female/male ratio = 56/45) diagnosed with primary appendicular high-grade osteosarcoma between 1990 and 2010 were included in this study. Initially, 156 patients diagnosed with osteosarcoma between 1990 and 2010 were identified through the population based Regional Database of Pathology, which covers a population of approximately 2.7 million (east Denmark). 55 patients were excluded due to (A) tumor was low grade (n = 22), (B) located in axial skeleton (n = 18), (C) incorrect diagnosis (n = 11) or (D) biopsy represented a tumor relapse from a former primary osteosarcoma (n = 4). Overall survival was evaluated using the Kaplan-Meier survival analysis and log-rank test. Prognostic factors were analyzed using uni- and multivariate cox-regression method with variables scored equally in the model. p Values <.05 were considered statistically significant. RESULTS: The probability of 5- and 10-year survival was 51% (95% CI: 41-61) and 46% (95% CI: 36-56), respectively. Metastatic stage at diagnosis and tumor size ≥10 cm measured radiologically at the largest diameter were independent prognostic factors for decreased survival with significant increased hazard-risks of 3.5 (95% CI: 1.9-6.5) and 1.97 (95% CI: 1.1-3.6), respectively. DISCUSSION: In this single institution evaluation of primary appendicular HOS we found 5-and 10-year survival rates consistent with international standards for this patient group. Distant metastases and tumor size ≥10 cm at the time of diagnosis were independent prognostic factors for decreased survival in our cohort. These results underline the importance of awareness and early referral from the primary sector.

Natural Course of Local Bone Mineralization After Treatment of Benign or Borderline Bone Tumors and Cysts With a Composite Ceramic Bone Graft Substitute.

After surgical bone tumor removal, filling of the bone defect is frequently performed using a bone graft or bone graft substitute. During follow-up, precise quantification of changes in bone mineral density, within the treated bone defect, is very difficult using conventional X-ray examinations. The objectives of this study were to characterize the pattern of resorption/biodegradation of a composite calcium sulfate/hydroxyapatite bone graft substitute and to quantify the bone defect healing with repeated dual-energy X-ray absorptiometry (DXA) measurements. Seventeen patients treated for 18 benign bone lesions, with subsequent defect filling using 2 variants of a composite ceramic bone graft substitute (CERAMENT™|BONE VOID FILLER or CERMAMENT™|G, BONESUPPORT AB, Lund, Sweden), were scanned postoperatively and after 2, 6, 12, 26, and 52 wk using DXA. After an initial increase in bone mineral density after implantation of the bone graft substitute, bone mineral density decreased in the bone defect region throughout the 52 wk: rapidly in the first 12 wk and slower in the remaining weeks. Despite this continuous decrease, bone mineral density remained, on average, 25% higher in the operated extremity, compared with the nonoperated extremity, after 52 wk. The observed pattern of reduction in bone mineral density is consistent with the anticipated resorption of calcium sulfate within the bone graft substitute during the first 12 wk after surgery. We believe the DXA technique provides a precise method for quantification of bone graft resorption, but for evaluation of new bone formation, 3-dimensional imaging is needed.

External Validation and Optimization of the SPRING Model for Prediction of Survival After Surgical Treatment of Bone Metastases of the Extremities.

BACKGROUND: Survival predictions before surgery for metastatic bone disease in the extremities (based on statistical models and data of previous patients) are important for choosing an implant that will function for the remainder of the patient's life. The 2008-SPRING model, presented in 2016, enables the clinician to predict expected survival before surgery for metastatic bone disease in the extremities. However, to maximize the model's accuracy, it is necessary to maintain and update the patient database to refit the prediction models achieving more accurate calibration. QUESTIONS/PURPOSES: The purposes of this study were (1) to refit the 2008-SPRING model for prediction of survival before surgery for metastatic bone disease in the extremities with a more modern cohort; and (2) to evaluate the performance of the refitted SPRING model in a population-based cohort of patients having surgery for metastatic bone disease in the extremities. METHODS: We produced the 2013-SPRING model by adding to the 2008-SPRING model (n = 130) a cohort of patients from a consecutive institutional database of patients who underwent surgery for bone metastases in the extremities with bone resection and reconstruction between 2009 and 2013 at a highly specialized surgical center in Denmark (n = 140). Currently the model is only available as the nomogram fully available in the current article, which is sufficient to use in daily clinical work, but we are working on making the tool available online. As such, the 2013-SPRING model was produced using a consecutive cohort of patients (n = 270) treated during an 11-year period (2003-2013) called the training cohort, all treated with bone resection and reconstruction. We externally validated the 2008-SPRING and the 2013-SPRING models in a prospective cohort (n = 164) of patients who underwent surgery for metastatic bone disease in the extremities from May 2014 to May 2016, called the validation cohort. The validation cohort was identified from a cross-section of the Danish population who were treated for metastatic lesions (using endoprostheses and internal fixation) in the extremities at five secondary surgical centers and one highly specialized surgical center. This cross-section is representative of the Danish population and no patients were treated outside the included centers as a result of public healthcare settings. The indications for surgery for training and the validation cohort were pathologic fracture, impending fracture, or intractable pain despite radiation. Exact date of death was known for all patients as a result of the Danish Civil Registration System and no loss to followup existed. In the training cohort, 150 patients (out of 270 [56%]) and in the validation cohort 97 patients (out of 164 [59%]) died of disease within 1 year postoperatively. The 2013 model did not differ from the 2008 model and included hemoglobin, complete fracture/impending fracture, visceral and multiple bone metastases, Karnofsky Performance Status, and the American Society of Anesthesiologists score and primary cancer. The models were evaluated by area under the receiver operating characteristic curve (AUC ROC) and Brier score (the lower the better). RESULTS: The 2013-SPRING model was successfully refitted with a cohort using more patients than the 2008-SPRING model. Comparison of performance in external validation between the 2008 and 2013-SPRING models showed the AUC ROC was increased by 3% (95% confidence interval [CI], 0%-5%; p = 0.027) and 2% (95% CI, 0%-4%; p = 0.013) at 3-month and 6-month survival predictions, respectively, but not at 12 months at 1% (95% CI, 0%-3%; p = 0.112). Brier score was improved by -0.018 (95% CI, -0.032 to -0.004; p = 0.011) for 3-month, -0.028 (95% CI, -0.043 to -0.0123; p < 0.001) for 6-month, and -0.014 (95% CI, -0.025 to -0.002; p = 0.017) for 12-month survival prediction. CONCLUSIONS: We improved the SPRING model's ability to predict survival after surgery for metastatic bone disease in the extremities. As such, the refitted 2013-SPRING model gives the surgeon a tool to assist in the decision-making of a surgical implant that will serve the patient for the remainder of their life. The 2013-SPRING model may provide increased quality of life for patients with bone metastasis because potential implant failures can be minimized by precise survival prediction preoperatively and the model is freely available and ready to use from the current article. LEVEL OF EVIDENCE: Level I, diagnostic study.

Implant and limb survival after resection of primary bone tumors of the lower extremities and reconstruction with mega-prostheses fifty patients followed for a mean of forteen years.

PURPOSE: Previous studies reported variable outcome and failure rates after mega-prosthetic reconstructions in the lower extremities. The purpose of this study was to make a long-term single-center evaluation of patients treated with limb-sparing surgery and reconstruction with mega-prostheses in the lower extremities. METHODS: We identified 50 patients (osteosarcoma (n = 30), chondrosarcoma (n = 9), osteoclastoma (n = 6), Ewing sarcoma (n = 4), angiosarcoma (n = 1)), who underwent limb-sparing reconstruction of the lower extremities (proximal femur (n = 9), distal femur (n = 29), proximal tibia (n = 9), and the entire femur (n = 3)) between 1985 and 2005. Surviving patients not lost to follow-up were evaluated using the MSTS score. Causes of failure were classified according to the Henderson classification. Kaplan-Meier survival analysis was used for evaluation of patient, prosthesis, and limb survival. RESULTS: Twenty-eight patients were alive at follow-up. Fifty-four percent had revision surgery (n = 27). The ten year patient survival was 60% (95%CI 46-74%); the ten year implant survival was 24% (95%CI 9-41%), and the ten year limb survival rate was 83% (95%CI 65-96%). Type 1 failure occurred in 9%, type 2 in 16%, type 3 in 28%, type 4 in 18%, and type 5 in 3%. Mean MSTS score was 21 (range, 6-30), representing a median score of 71%. CONCLUSIONS: Our long-term results with mega-prostheses justify the use of limb-salvage surgery and prosthetic reconstruction. Our results are fully comparable with other findings, with regard to limb and prosthesis survival, but also with regard to functional outcome.

Prognostic value of biochemical variables for survival after surgery for metastatic bone disease of the extremities.

BACKGROUND AND OBJECTIVE: Prediction of survival in patients having surgery for metastatic bone disease in the extremities (MBDex) has been of interest in more than two decades. Hitherto no consensus on the value of biochemical variables has been achieved. Our purpose was (1) to investigate if standard biochemical variables have independent prognostic value for survival after surgery for MBDex and (2) to identify optimal prognostic cut off values for survival of biochemical variables. METHODS: In a consecutive cohort of 270 patients having surgery for MBDex, we measured preoperative biochemical variables: hemoglobin, alkaline phosphatase, C-reactive protein and absolute, neutrophil and lymphocyte count. ROC curve analyses were performed to identify optimal cut off levels. Independent prognostic factors for variables were addressed with multiple Cox regression analyses. RESULTS: Optimal cut off levels were identified as: hemoglobin 7.45 mmol/L, absolute lymphocyte count 8.5 × 109 /L, neutrophil 5.68 × 109 /L, lymphocyte 1.37 × 109 /L, C-reactive protein 22.5 mg/L, and alkaline phosphatase 129 U/L. Regression analyses found alkaline phosphatase (HR 2.49) and neutrophil count (HR 2.49) to be independent prognostic factors. CONCLUSIONS: We found neutrophil count and alkaline phosphatase to be independent prognostic variables in predicting survival in patients after surgery for MBDex.

Follow-up after initial surgical treatment of soft tissue sarcomas in the extremities and trunk wall.

BACKGROUND/OBJECTIVES: Evaluation of our surveillance program for soft tissue sarcomas (STS) and borderline tumors (BT) for identification of local recurrence and lung metastases the first 2 years postoperatively. METHODS: We retrospectively assessed the medical files of all patients (n = 232) with STS and BT of the extremities and trunk wall who underwent surgery from 2010 to 2013. Two-hundred-and-thirty-two patients were included in the local recurrence study and 116 patients in the lung metastasis study. We extracted information on how local recurrence and lung metastases were detected. Kaplan-Meier survival analysis and 2 × 2-contingency table with Chi-square test were used. Local recurrence and lung metastases were analyzed separately. RESULTS: Twenty-five of 232 patients experienced local recurrence and 19 of 116 patients experienced lung metastases. Compared to clinical examination, local imaging led to a larger amount of local recurrence suspicions (37/560 vs. 8/706). Suspicions occurring on local imaging were more accurate than on clinical examination (17/37 vs. 0/8 affirmed). Local imaging identified a larger amount of local recurrence than clinical examination (17/560 vs. 0/706). Thirty-three patients suspected local recurrence themselves, 8 were affirmed. Compared to x-ray, computerized tomography (CT) led to a larger amount of lung metastasis suspicions (22/284 vs. 6/276). Suspicions occurring on CT seemed more accurate than on x-ray (15/22 vs. 2/6 affirmed). CT found a larger amount of lung metastases than x-ray (15/284 vs. 2/276). Three patients suspected lung metastases themselves, 1 was affirmed. CONCLUSION: Bi-annual local imaging and CT the first 2 years after surgery of STS detect local recurrence and lung metastases better than clinical examination and x-ray. Clinical examination and x-ray between these examinations is unnecessary. Patients' own suspicion of local recurrence and lung metastases is still important.