The management of pathological fractures due to Metastatic Bone Disease (MBD) and Primary Bone Tumours (PBTs) has implications for the Trauma service due to the extra pressures on staff, service delivery and budgets. We undertook an analysis of a cohort of patients presenting with MBD and PBTs. A retrospective chart review of all cases with MBD and PBTs admitted to a 40-bed Trauma Unit between 2005 and 2009 was conducted. The study looked at frequency, primary pathology, and site of pathology/fracture, time from primary diagnosis to referral, subsequent interventions and others. The results identified 34 patients, 21 females (62%) and 13 males (38%) (mean age: 64.6 years) with MBD or PBTs. Metastases secondary to breast cancer (n=13, 38%) and Myeloma (n=5, 15%) were the most common with the majority being found in the femur (n=22, 65%) and the Humerus (n=6, 18%). The mean time from primary tumour diagnosis to fracture referral was 29.6 months with 27 (79%) patients undergoing definitive surgical management within the unit. The conclusions of the study demonstrate that a wide variety of pathology presented to the unit over a 5 year period. Considerable variation was noted in the time from primary tumour diagnosis to presentation with a fracture. This could be due to improvements in treatments of specific cancers or a lack of understanding of what an Orthopaedic surgeon can offer the cancer patient. No definitive increase in pathological fractures was seen. The consensus opinion is that prompt and appropriate management of pathological fractures in cancer patients is cost effective. Management of these injuries, in a Trauma Unit, represents a small, but significant part of the annual work-load. While no significant trend has been seen, with respect to an increased incidence, it is noted that a proportion of these patients were a number of years from their initial diagnosis. With improvements in the survivorship of cancer patients, close scrutiny will be required to determine whether this ultimately translates into an increased fracture burden

Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response.

Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care.

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence.

Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated.

The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells.

Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.

Primary malignant bone tumours are a scarce entity with limited population-based data from developing countries. The aim of the study is to investigate the frequency and anatomical distribution of primary malignant bone tumours in a local South African population.

This will be an epidemiological retrospective study. Data will be used of patients that were diagnosed with primary malignant bone tumours over a period of nine years spanning from 1 January 2014 to 31 December 2022. This data will be received from private and government laboratories. Data to be considered are type of primary malignant bone tumours diagnosed, incidence of primary malignant bone tumours over a period of nine years and the most common anatomical sites of primary malignant bone tumours. The rationale behind our study is to assess the frequency of different primary malignant bone tumours in another geographic area of South Africa and to compare these findings to local and international literature. With a projected increase in diagnosis of primary malignant bone tumours in developing countries it is important to have more available data about primary malignant bone tumours from these areas to have a better understanding of these conditions and to understand the impact of the burden they impose on healthcare systems so that management of these conditions can also be improved. Preliminary results show that 23.83% of primary malignant bone tumours occurred in the age group 0–24 years of age, 49.22% in the 25–59 age group and 26.95% in the 60+ age group. The most common tumour that occurred was chondrosarcoma (49.21%) followed by osteosarcoma (41.80%) then Ewing's sarcoma (4,69%) and lastly chordoma (4.30%). From the 256 samples that met the inclusion criteria the five most common anatomical sites were distal femur (63), proximal tibia (41), proximal humerus (38), pelvis (34) and proximal femur (20).

In the past decades, a huge amount of effort has been devoted to translate evidence based on standard preclinical models of bone tumours to effective tools for clinical applications. Although cancer is a genetic disease, hence the emphasis on -omics approaches, the complexity of cancer tissue, a mix of competing clones of transformed elements that react differently to microenvironmental stimuli, may hardly be reproduced by standard approaches. Cost, biological differences and ethical concerns are increasingly recognized as weaknessess of animal models. To overcome these limitations and provide reliable, reproducible, and affordable tools for predicting the effectiveness of treatments, environmental-controlled 3D cultures and co-cultures (spheroids, organoids) coupled with microfluidics and advanced imaging have recently being considered as effective instrument to increase knowledge on the pathophysiology of bone tumours and define effective therapeutic solutions.

Introduction

“Bioexpandable” prostheses after resection of malignant bone tumors in children to lengthen the bone using the method of callus distraction may offer new perspectives and better long-term results.

En bloc resection for primary bone tumours and isolated metastasis are complex surgeries associated with a high rate of adverse events (AEs). The primary objective of this study was to explore the relationship between frailty/sarcopenia and major perioperative AEs following en bloc resection for primary bone tumours or isolated metastases of the spine. Secondary objectives were to report the prevalence and distribution of frailty and sarcopenia, and determine the relationship between these factors and length of stay (LOS), unplanned reoperation, and 1-year postoperative mortality in this population.

This is a retrospective study of prospectively collected data from a single quaternary care referral center consisting of patients undergoing an elective en bloc resection for a primary bone tumour or an isolated spinal metastasis between January 1st, 2009 and February 28th, 2020. Frailty was calculated with the modified frailty index (mFI) and spine tumour frailty index (STFI). Sarcopenia, determined by the total psoas area (TPA) vertebral body (VB) ratio (TPA/VB), was measured at L3 and L4. Regression analysis produced ORs, IRRs, and HRs that quantified the association between frailty/sarcopenia and major perioperative AEs, LOS, unplanned reoperation and 1-year postoperative mortality.

One hundred twelve patients met the inclusion criteria. Using the mFI, five patients (5%) were frail (mFI ³ 0.21), while the STFI identified 21 patients (19%) as frail (STFI ³ 2). The mean CT ratios were 1.45 (SD 0.05) and 1.81 (SD 0.06) at L3 and L4 respectively. Unadjusted analysis demonstrated that sarcopenia and frailty were not significant predictors of major perioperative AEs, LOS or unplanned reoperation. Sarcopenia defined by the CT L3 TPA/VB and CT L4 TPA/VB ratios significantly predicted 1-year mortality (HR of 0.32 per one unit increase, 95% CI 0.11-0.93, p=0.04 vs. HR of 0.28 per one unit increase, 95% CI 0.11-0.69, p=0.01) following unadjusted analysis. Frailty defined by an STFI score ≥ 2 predicted 1-year postoperative mortality (OR of 2.10, 95% CI 1.02-4.30, p=0.04).

The mFI was not predictive of any clinical outcome in patients undergoing en bloc resection for primary bone tumours or isolated metastases of the spine. Sarcopenia defined by the CT L3 TPA/VB and L4 TPA/VB and frailty assessed with the STFI predicted 1-year postoperative mortality on univariate analysis but not major perioperative AEs, LOS or reoperation. Further investigation with a larger cohort is needed to identify the optimal measure for assessing frailty and sarcopenia in this spine population.

Kyphoplasty is an efficient tool in the treatment of primary tumours (plasmocytoma) and osteolytic metastasis. Especially in plasmocytoma the current chemotherapy has increased life expectancy significantly. Therefore minimal-invasive stabilisation is not only a palliative treatment but really increases quality of life in those cases.

Kyphoplasty offers several special tools and techniques to lower the leakage rate which is especially high with other cementoplasty techniques in the osteolytic spine.

Materials and Methods: Prospective study of all vertebral tumours compared to osteoporotic fractures treated with kyphoplasty in 2004. 6 months follow up with VAS, SF36 and Oswestry score.

Results: In 2004 we performed 67 Kyphoplasties. 12 kyphoplasties were performed in tumour cases (5 plasmocytoma and 7 metastasis). No complications occurred during surgery and during hospital stay. Follow-up included 11 tumours (1 death during F/U) and 46 osteoporotic fractures. 1 patient was treated with combined decompression/kyphoplasty. The pain level (VAS) was significantly reduced in all cases within 2 days (osteoporotic group 2,2 – tumour group 5,4) and reached nearly the same result after 6 weeks which persisted for 6 months (osteoporotic group 1,6, tumour group 2,1). The SF 36/Oswestry Score improved accordingly in both groups. At 6 weeks and 6 months F/U no statistical difference in the scores was seen.

Conclusion: Kyphoplasty is a safe treatment method for osteolytic vertebral tumours with vertebral collapse. Clinically the results don’t differ from conventional cases. In cases with canal compromise, a combination with open techniques is possible. Special kyphoplasty techniques allow a reconstruction of the lytic wall and minimise leakage and cement dislocation. Significant improvement of life quality can be achieved offering the spine surgeon a valuable tool in the treatment of spinal metastasis.

Introduction

Bone tumours rarely involve the joint surface as cartilage is thought to be a good barrier to tumour spread. When the tumour does cross the surface the surgeon is faced with the dilemma of whether to amputate the limb, resect it without reconstruction or reconstruct with an implant. This paper aims to investigate the oncological and functional outcomes of patients undergoing an extra-articular resection and reconstruction with an endoprosthesis.

1. Alkaline and acid phosphatase, non-specific esterase and beta-glucuronidase have been estimated and demonstrated histochemically in a series of bone tumours and allied lesions, of which ten were osteogenic sarcomata, ten were giant-cell lesions, eleven were fibroblastic lesions and seven were tumours of cartilage.

2. Osteogenic sarcoma was found to be characterised by high levels of alkaline phosphatase, with rich staining for this enzyme in the tumour cells. Similar high levels of alkaline phosphatase were found in other bone-forming lesions, such as fibrous dysplasia, a giant-cell sarcoma with osteogenic matrix, and fracture callus.

3. Giant-cell lesions were characterised by high levels of acid phosphatase, and intense staining for this enzyme in the osteoclasts. These cells were also found to be rich in non-specific esterase (as shown by the alpha-naphthyl acetate method) and in beta-glucuronidase, but almost or entirely lacking in alkaline phosphatase. High levels of alkaline phosphatase were not found in giant-cell lesions except in relation to osteogenic matrix.

4. Fibroblastic tumours were characterised by moderate levels of all four enzymes, with little or no staining for phosphatases in the tumour cells; non-specific esterase was generally present in a proportion of the cells.

5. In certain lesions intermediate stages in the differentiation of fibroblasts to osteoblasts were found, notably in fibrous dysplasia, in which the biochemical change preceded the histological. In such lesions high total levels of alkaline phosphatase were found.

6. Cartilaginous tumours were characterised by low levels of all four enzymes, and little histochemical staining except in hypertrophied cells in areas of ossification.

7. It was found in general that the enzyme distributions in these neoplasms and other lesions reflected the findings in comparable reactive and growing normal tissues.

1. Serial arteriograms show not only the anatomical distribution of blood vessels but also the functional state and activity of the peripheral circulation. The technique is of value in the diagnosis of tumours of soft tissues and bone, and particularly in the differential diagnosis of bone tumours from chronic osteomyelitis. It may be used to assess the response of malignant bone tumours to treatment by irradiation.

2. In malignant bone tumours, serial arteriograms show irregular formation of new vessels of uniform diameter, "blood pools," and increased rapidity of flow from the arterial to the venous systems.

3. In osteoclastomas there is new vessel formation and an appearance of "blood pools," but less rapid filling of the veins. In simple tumours there is no new formation of vessels. The tumour itself is often relatively avascular.

4. In osteomyelitis there is no new formation of vessels but only dilatation of existing vessels. The vessels retain their orderly and regular arrangement of successive branches of gradually decreasing diameter.

Introduction

Bone tumours of the foot are rare, representing 3–6% of all bone tumours. Of these 15–25% are thought to be malignant. Obtaining clear surgical margins remains an important factor in improving outcome from tumours. However, the anatomical complexity of the foot can lead to an inadequate resection, particularly if the operating surgeon is attempting to preserve function. The aim of this paper is to identify the clinical course of patients suffering from malignant bone tumours of the foot.

The management of primary malignant bone tumors with metastatic disease at presentation remains a challenge. While surgical resection has been shown to improve overall survival among patients with non-metastatic malignant bone tumors, current evidence regarding the utility of surgery in improving overall survival in metastatic patients remains limited.

The 2004–2016 National Cancer Database (NCDB) was queried using International Classification of Diseases 3rd Edition (ICD-O-3) topographical codes to identify patients with primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8 and C40.9) and/or pelvis (C41.4). Patients with malignant bone tumors of the axial skeleton (head/skull, trunk and spinal column) were excluded, as these cases are not routinely encountered and/or managed by orthopaedic oncologists. Histological codes were used to categorize the tumors into the following groups - osteosarcomas, chondrosarcomas, and Ewing sarcomas. Patients who were classified as stage I, II or III, based on American Joint Commission of Cancer (AJCC) guidelines, were excluded. Only patients with metastatic disease at presentation were included in the final study sample. The study sample was divided into two distinct groups – those who underwent surgical resection of the primary tumors vs. those who did not receive any surgery of the primary tumor. Kaplan-Meier survival analysis was used to report unadjusted 5-year overall survival rates between patients who underwent surgical resection of the primary tumor, compared to those who did not. Multi-variate Cox regression analyses were used to assess whether undergoing surgical resection of the primary tumor was associated with improved overall survival, after controlling for differences in baseline demographics, tumor characteristics (grade, location, histological type and tumor size), and treatment patterns (underwent metastatectomy of distal and/or regional sites, positive vs. negative surgical margins, use of radiation therapy and/or chemotherapy). Additional sensitivity analyses, stratified by histologic type for osteosarcomas, chondrosarcomas and Ewing sarcomas, were used to assess prognostic factors for overall survival.

A total of 2,288 primary malignant bone tumors (1,121 osteosarcomas, 345 chondrosarcomas, and 822 Ewing sarcomas) with metastatic disease at presentation were included – out of which 1,066 (46.0%) underwent a surgical resection of the primary site. Overall 5-year survival rates, on unadjusted Kaplan-Meier log-rank analysis, were significantly better for individuals who underwent surgical resection vs. those who did not receive any surgery (31.7% vs. 17.3%; p<0.001). After controlling for differences in baseline demographics, tumor characteristics and treatment patterns, undergoing surgical resection of primary site was associated with a reduced overall mortality (HR 0.42 [95% CI 0.36–0.49]; p<0.001). Undergoing metastectomy (HR 0.92 [95% CI 0.81–1.05]; p=0.235) was not associated with a significant improvement in overall survival. On stratified analysis, radiation therapy was associated with improved overall survival for Ewing Sarcoma (HR 0.71 [95% CI 0.57–0.88]; p=0.002), but not for osteosarcoma (HR 1.14 [95% CI 0.91–1.43]; p=0.643) or chondrosarcoma (HR 1.08 [95 % CI 0.78–1.50]; p=0.643). Chemotherapy was associated with improved overall survival for osteosarcoma (HR 0.50 [95% CI 0.39–0.64]; p<0.001) and chondrosarcoma (HR 0.62 [95% CI 0.45–0.85]; p=0.003), but not Ewing sarcoma (HR 0.79 [95% CI 0.46–1.35]; p=0.385).

Surgical resection of the primary site significantly improves overall survival for primary malignant bone tumors with metastatic disease at presentation. Physicians should strongly consider surgical resection of the primary tumor, with adjunct systemic and/or radiation therapy (dependent on tumor histology), in patients presenting with metastatic disease at presentation.

Primary bone tumours in the elderly population are relatively rare.

We reviewed the Leeds regional bone tumour registry between 1990–1999 and found them to constitute only 43 of the 341 (12%) bone tumour cases.

Malignant tumours (65%) were more common than benign tumours with primary tumours accounting 92 % and metastatic tumours only 8 % of all the malignancies. Females were more affected than males (55% versus 45 %).

Chondrosarcoma was the most frequent tumour, constituting 24% of primary malignant tumours and 18 % of all bone tumours.

Chondroma was the most common benign tumour accounting for 50% of all benign tumours, and 11% of all tumours.

Survival rate was relatively poor in elderly population with primary malignant tumours.

The majority of malignant tumours were in the lower limb (femur 25%, tibia 14 %).The upper limb accounted for 14% and the axial skeleton 5%.

Bone tumour registries provide a valuable source of cumulative information about both common and uncommon tumours. Such information could not easily be gathered by personal experience. It is also a very good source of information for research education and service.

Aim

We present the greatest study of patients with proximal fibula resection. Moreover we describe a new classification system for tumour resection of the proximal fibula independent of the tumour dignity.

We evaluated the diagnostic accuracy of fine-needle aspiration biopsy in a prospective study of 300 patients with previously undiagnosed bone lesions. Patients with suspected local recurrence of a primary bone tumour or a metastatic lesion of a previously diagnosed malignancy were excluded. Fine-needle aspiration biopsy was performed under radiological control as an outpatient procedure.

The series was grouped into three major categories: 1) benign bone lesions including infections; 2) primary malignant bone tumours; and 3) metastases including lymphomas and myelomas. We compared the cytological diagnosis with the final diagnosis as assessed by histological examination and/or the clinical and radiological features.

Material considered conclusive for cytological diagnosis was obtained from 251 of the 300 patients. Of the 49 failures, there were 24 aspirates with insufficient cellular yield and 25 in which a diagnosis could not be made although the cytological material was adequate in quantity. Most of the inconclusive aspirates (36/49) were obtained from benign bone lesions.

The diagnosis was correct in 239 (95%) of the 251 cases providing adequate cytological material. There were eight (3%) falsely benign diagnoses, one (0.3%) falsely malignant, and three cases in which we were unable to differentiate between sarcoma and a metastasis. Chondrosarcoma (2/12) gave the greatest diagnostic difficulty and Ewing’s sarcoma the least (0/9). There were no decisive errors of treatment. All falsely benign or malignant diagnoses were questioned, and led to open biopsy since they did not correlate with the clinical and radiological features.

Our study suggests that fine-needle aspiration biopsy is a valid option for the diagnosis of bone tumours. It is a simple outpatient procedure which gives sufficient cytological material for the correct diagnosis in 80% of cases. As with histological analysis of material from open biopsy, the cytological assessment must agree with the clinical and radiological findings.

Introduction: Bone transport, or distraction osteogenesis, is a recognised technique to reconstruct extensive bony defects resulting from excision of bony tumours. Ilizarov demonstrated bone formation under tension allowing the movement of a free segment of living bone to fill intercalary defects. This study assesses the use of bone transport in the management of patients with resectable long bone tumours.

Methods: We retrospectively reviewed patients who underwent bone transport in two institutions, performed by a single surgeon. A total of 14 patients were included in the study. There were 11 males and 3 females. Histological results demonstrated osteosarcoma (n=7), Ewing’s sarcoma (n=6), and parosteal chondrosarcoma (n=1). The site of the tumour was the femur and tibia in 8 and 6 cases respectively.

Results: Bone transport was fully completed in 9 patients. Of the 5 patients remaining, 3 are currently in cast, 1 is currently undergoing tibial lengthening, and 1 patient died from local recurrence and distant spread of disease. The average length of bone resected in the tibia was 11 cm (range 8–15 cm), while in the femur the average was higher at 16.5 cm (range 12–27 cm). All patients underwent autologous bone grafting of their docking site from either the anterior or posterior iliac crest on the ipsilateral side. The average time in frame was 24.8 months. One patient undergoing tibial bone transport fell and sustained an ipsilateral supracondylar femoral fracture which was successfully treated with an external ring fixator.

Discussion: Bone transport is a recognised method of reconstructing extensive bony defects and is beneficial for patients with a good prognosis. It is a specialised technique and requires a multidisciplinary approach. Other techniques can be less time consuming however distraction osteogenesis avoids the complications associated with prosthetic or allograft replacements.