Results: Subsequent second metastasis formation occurred at the tip of the nail compounded by pathological fracture. Salvage surgery was achieved in one case with a total femoral replacement and in the other by bi-columnar plating of the humerus with cement augmentation.
Neck of femur fractures are a common trauma presentation and patients with a history of malignancy are sent for long leg femur views (LLF), to exclude a distal lesion which would alter the management plan (Intra-medullary nail/Long stem Hemiarthroplasty). The aim of this is to identify incidence of malignancy on LLF views, the length of time in between each xray (XR) and to identify demographics. Data was retrospectively collected from 01/01/2021 to 31/01/2021 from a single centre. All patients admitted to the Queen Elizabeth University Hospital had their electronic records (Bluespier, PACS, Clinical Portal) accessed. These confirmed if patients had a past medical history of malignancy, if they had LLF view and the time differences between diagnostic pelvis XR and LLF XR. A total of 784 patients were identified in the specified time period. Of these, 138 were identified with a malignancy and there were 85 LLF views completed. LLF views diagnosed 1 patient with known prostate cancer that had a new distal femoral metastasis (Incidence = 1.28 cases per 1000). This patient underwent further imaging (MRI Femur) and received a long stem hip hemiarthroplasty. The average length of wait between the images was 9 hours 27 minutes. LLF views can alter management of patients with malignancy and are therefore useful to perform. There can be a long delay between each image. Therefore we recommend imaging tumour with common bony metastasis (Renal, Thyroid, Breast, Prostrate, Lung) and other remaining tumours with known secondary metastasis. Imaging primary low risk (eg basal cell carcinoma) can lead to long delays in a frail patient cohort and consideration should be given to rationalise appropriate use of resources.
Evaluate the complications and outcomes of off-hours spinal metastasis surgery. Retrospective analysis of a prospective collected data. Preoperative, operative and post-operative data were collected as well as the complications and Frankel score at all time checkpoints. Off-hours surgery was defined as surgery starting between 17:00 and 8:00 the following day or surgery during the weekend. p < 0 .05 was defined as statistical significance threshold. 376 patients were included with an incidence of off-hours surgery of 32%. There was an increase of neurologic complication in the off hours group. This was associated with a higher ASA score and older population group. Oddly, there was decreased operative time with off-hours surgery with no difference in bleeding and number of fusion levels. Nonetheless, there was a higher percentage of neurologic improvement with off hours surgery compared to in-hours surgery. Finally, there were no effect on patients' survival in this patient population. To our knowledge, this is the first report of the effect of off-hours surgery on complications and outcomes of spinal metastasis. Greater neurological compromise and higher age and ASA scores were associated with higher incidence of off-hours surgery. It is associated with decreased surgical time with higher percentage of neurological improvement. Finally, there is no effect of surgical timing on survival rates.
Mirels’ score predicts the likelihood of sustaining pathological fractures using pain, lesion site, size and morphology. The aim is to investigate its reproducibility, reliability and accuracy in upper limb bony metastases and validate its use in pathological fracture prediction. A retrospective cohort study of patients with upper limb metastases, referred to an Orthopaedic Trauma Centre (2013–18). Mirels’ was calculated in 32 patients; plain radiographs at presentation scored by 6 raters. Radiological aspects were scored twice by each rater, 2-weeks apart. Inter- and intra-observer reliability were calculated (Fleiss’ kappa test). Bland-Altman plots compared variances of individual score components &total Mirels’ score. Mirels’ score of ≥9 did not accurately predict lesions that would fracture (11% 5/46 vs 65.2% Mirels’ score ≤8, p<0.0001). Sensitivity was 14.3% &specificity was 72.7%. When Mirels’ cut-off was lowered to ≥7, patients were more likely to fracture (48% 22/46 versus 28% 13/46, p=0.045). Sensitivity rose to 62.9%, specificity fell to 54.6%. Kappa values for interobserver variability were 0.358 (fair, 0.288–0.429) for lesion size, 0.107 (poor, 0.02–0.193) for radiological appearance and 0.274 (fair, 0.229–0.318) for total Mirels’ score. Values for intraobserver variability were 0.716 (good, 95% CI 0.432–0.999) for lesion size, 0.427 (moderate, 95% CI 0.195–0.768) for radiological appearance and 0.580 (moderate, 0.395–0.765) for total Mirels’ score. We showed moderate to substantial agreement between &within raters using Mirels’ score on upper limb radiographs. Mirels’ has poor sensitivity &specificity predicting upper limb fractures - we recommend the cut-off score for prophylactic surgery should be lower than for lower limb lesions.
Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease pathophysiology and novel advanced therapies is one of the major challenges that will predict more effectively and efficiently the clinical response. Preclinical traditional models have been largely used as they can provide standardization and simplicity, moreover, further advancements have been made with 3D cultures, by spheroids and artificial matrices, patient derived xenografts and microfluidics. Despite these models recapitulate numerous aspects of tumour complexity, they do not completely mimic the clinical native microenvironment. Thus, to fulfil this need, in our study we developed a new, advanced and alternative model of human breast cancer bone metastasis as potential biologic assay for cancer research. The study involved breast cancer bone metastasis samples obtained from three female patients undergoing wide spinal decompression and stabilization through a posterior approach. Samples were cultured in a TubeSpin Bioreactor on a rolling apparatus under hypoxic conditions at time 0 and for up to 40 days and evaluated for viability by the Alamar Blue test, gene expression profile, histology and immunohistochemistry. Results showed the maintenance and preservation, at time 0 and after 40 days of culture, of the tissue viability, biological activity, as well as molecular markers, i.e. several key genes involved in the complex interactions between the tumour cells and bone able to drive cancer progression, cancer aggressiveness and metastasis to bone. A good tis sue morphological and microarchitectural preservation with the presence of lacunar osteolysis, fragmented trabeculae locally surrounded by osteoclast cells and malignant cells and an intense infiltration by tumour cells in bone marrow compartment in all examined samples. Histomorphometrical data on the levels of bone resorption and bone apposition parameters remained constant between T0 and T40 for all analysed patients. Additionally, immunohistochemistry showed homogeneous expression and location of CDH1, CDH2, KRT8, KRT18, Ki67, CASP3, ESR1, CD8 and CD68 between T0 and T40, thus further confirming the invasive behaviour of breast cancer cells and indicating the maintaining of the metastatic microenvironment. The novel tissue culture, set-up in this study, has significant advantages in comparison to the pre-existent 3D models: the tumour environment is the same of the clinical scenario, including all cell types as well as the native extracellular matrix; it can be quickly set-up employing only small samples of breast cancer bone metastasis tissue in a simple, ethically correct and cost-effective manner; it bypasses and/or decreases the necessity to use more complex preclinical model, thus reducing the ethical burden following the guiding principles aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes; it can allow the study of the interactions within the breast cancer bone metastasis tissue over a relatively long period of up to 40 days, preserving the tumour morphology and architecture and allowing also the evaluation of different biological factors, parameters and activities. Therefore, the study provides for the first time the feasibility and rationale for the use of a human-derived advanced alternative model for cancer research and testing of drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses.
Lymph node metastasis are a rare occurrence in soft tissue sarcomas of the extremity, arising in less than 5% of patients. Few studies have evaluated the prognosis and survival of patients with a lymph node metastasis. Early reports compared lymph node involvement to lung metastasis, while others suggested a slightly better outcome. The purpose of this study was to evaluate the impact of lymph node metastasis on patient survival and to investigate the histologic and clinical features associated with lymph node involvement. A retrospective review was done of the prospectively collected soft tissue sarcoma database at our institution. Two thousand forty-five patients had surgery for soft tissue sarcoma of an extremity between January 1986 and August 2017. Included patients either presented with a synchronous lymph node metastasis or were diagnosed with a lymph node metastasis after their initial treatment. Demographic, treatment, and outcome data for patients with lymph node involvement were obtained from the clinical and radiographic records. Lymph node metastases were identified as palpable adenopathy by physical examination and were further characterized on cross-sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) scans. All cases were confirmed by pathologic examination of biopsy specimens. A pathologist with expertise in sarcoma determined the histologic type and graded tumors as 1, 2, or 3. One hundred eighteen patients with a mean age of 55.7 (SD=18.9) were included in our study. Seventy-two (61.3%) out of 119 patients were male. Thirty six patients (57.1%) had lymph node involvement at diagnosis. The mean follow-up from the date of the first surgery was 56.3 months. The most common histological diagnoses were Malignant fibrous histiocytoma (35) and liposarcoma (12). Ninety eight patients (89%) underwent surgical treatment of the lymph node metastasis while 21 (17.6%) were treated with chemotherapy and/or radiation therapy. The mean survival was 52.6 months (range 1–307). Our results suggest that patients with a lymph node metastasis have a better prognosis than previously described. Their overall survival is superior to patients diagnosed with lung metastasis. A signifant proportion of patients may expect long term survival after surgical excision of lymph node metastasis. Furthermore, our study also indicates that different histological subtypes such as liposarcoma or malignant peripheral nerve sheath tumor (MPNST) may also be responsible for lymph node metastasis. Additional studies to further improve the treatment of soft tissue sarcoma nodal metastasis are warranted.
Spinal metastases are seen in 10–30% of cancer patients. Twenty percent of these metastases occur in the lumbo-sacral spine. Lumbo-sacral spine has different mechanical properties and encloses the cauda equina. Few studies took interest in this spinal segment. The objective of this study is to evaluate prognostic factors of lumbo-sacral spinal metastasis treated in our center. We retrospectively reviewed 376 patients who were operated in our center from 2010 to 2018. Eighty-nine patients presented lumbo-sacral metastases and thus were included. Data collected included age, smoking, tumor histology, American spinal injury association (ASIA) score, modified Tokuhashi score, modified Bauer score, ambulation status and adjuvant treatment. The mean population age was 60.9 years old (35–85). The tumor histology was predominantly lung (19 patients, 21.3%), breast (13 patients, 14.6%), kidney (11 patients, 12.4%) and prostate (9 patients 10.1%). Twenty-two patients (24.7%) were unable to walk preoperatively. Seventy-nine patients (88.8%) underwent a posterior open approach with corpectomy in 65 patients (73%). Eighteen patients regained ambulation post-operatively (81.8%). The mean survival was 24.03 months (CI95% 17,38–30,67, Range 0–90) and the median of survival was 9 months (CI95% 4.38–13.62). Better preoperative ASIA score had a significant favorable effect (p=0.03) on survival. Patients who regained their ability to walk had better survival (25.1 months (CI95% 18.2–32) VS 0.5 months (CI95% 0–1.1). Postoperative radiotherapy had a benefic effect on survival (p=0.019): Survival Increased from 10.5 months (CI95% 2.4–18.7) to 27.6 months (CI95% 19.5–35.8). The modified Tokuhashi and the modified Bauer scores underestimated the survival of the patients with lumbosacral metastases. Lumbosacral spinal metastases has better survival than expected by Tokuhashi and Bauer score. Surgical procedure have an important impact on survival and the ability to walk.
Osteosarcoma (OS) is the most prevalent bone tumor in children and young adults. Most tumors arise from the metaphysis of the long bones and easily metastasize to the lungs. Current therapeutic strategies of osteosarcoma are routinely surgical resection and chemotherapy, which are limited to the patients suffering from metastatic recurrence. Therefore, to investigate molecular mechanisms that contribute to osteosarcoma progression is very important and may shed light on targeted therapeutic approach to improve the survival of patients with this disease. Several miRNAs have been found expressed differentially in osteosarcoma (OS), In this study, we found that miR-144 significantly suppresses osteosarcoma cell proliferation, migration andinvasion ability in vitro, and inhibited tumor growth and metastasisin vivo. The function and molecular mechanism of miR-144 in Osteosarcoma was further investigated. Tissue samples from fifty-one osteosarcoma patients were obtained from Shanghai Ninth People's Hospital. The in vitro function of miR-144 in Osteosarcoma was investigated by cell viability assay, wound healing assay, invasion assay, the molecular mechanism was identified by Biotin-coupled miRNA capture, Dual-luciferase reporter assays, etc. the in vivo function of miR-144 in osteosarcoma was confirmed by osteosarcoma animal model and miR-144−/− zebrafish model. Mechanically, we demonstrated that Ras homolog family member A (RhoA) and its pivotal downstream effector Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) were both identified as direct targets of miR-144. Moreover, the negative co-relation between downregulated miR-144 and upregulated ROCK1/RhoA was verified both in the osteosarcoma cell lines and clinical patients' specimens. Functionally, RhoA with or without ROCK1 co-overexpression resulted a rescue phenotype on the miR-144 inhibited cell growth, migration and invasion abilities, while individual overexpression of ROCK1 had no statistical significance compared with control in miR-144 transfected SAOS2 and U2-OS cells. This study demonstrates that miR-144 inhibited tumor growth and metastasis in osteosarcoma via dual-suppressing of RhoA and ROCK1, which could be a new therapeutic approach for the treatment ofosteosarcoma.
The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of pathological fractures in patients with bone metastases from advanced cancers by evaluating all available randomized controlled trials (RCTs) on this subject. A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing zoledronic acid with denosumab in prevention of pathological fractures in bone metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were pathological fractures. Four RCTs (7320 patients) were included. Denosumab was superior to ZA in reducing the likelihood of pathological fractures, when all tumour types were combined (OR 0.86, 95% CI [0.74, 0.99], Denosumab significantly reduces the likelihood of pathological fractures in comparison to ZA in patients with bone metastases. When pathological fractures were grouped by tumour origin (endodermal or mesodermal), there was no significant difference between denosumab and ZA. Further long-term studies are needed to confirm the effectiveness of these treatment regimens.
We present the long-term surgical outcomes, complications, implant survival and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins. A cohort of 50 consecutive patients who underwent the modified Harrington procedure along with cemented THA for peri-acetabular metastasis or haematological malignancy between 1990 and April 2018 were studied. The median follow-up time for all patients was 14 years (interquartile range, 9 – 16 years).Aim
Patients and Methods
Incoming of a spine metastasis remains a major bad prognosis factor in cancer evolution. Consensus over the years is now well accepted in most of European teams dealing with spinal metastasis. Two major opportunities exist in the treatment of spine metastasis: Conservative treatment with an association of radio and or chemotherapy and or hormonotherapy. Efficiency of such treatments is well documented and must not be considered as a patient abandon. Surgical treatment is based on two major options. The first one is palliative with the aim of decompression and stabilization. Aim is to cure pain and neurological involvement. The second one is curative with total or partial vertebrectomy in the aim to cure the cancer. In all cases decision must be made considering age- general condition histo – pathology – neurological status Considering surgical indications through out this symposium we would like to address three controversial points. The first topic to be addressed will be: “Total vertebrectomy: when?” presented successively Doctor MARTIN BENLLOCH and Professor BORIANI. The goal of this presentation is to determine the indications of total vertebrectomy more than the surgical technique. These indications appearing essential within the framework of the metastatic patients, while insisting not only on the natural history, but also on the tumoral extension which determines the feasibility of the vertebrectomy. Professor POINTILLART and Professor BORIANI will then discuss about the strategy to adopt when confronted with multi-metastatic patients “Multi-metastatic patients: what strategy?”. This topic will focus primarily on the problem of multi level spinal metastatic lesions: the strategies to be adopted with respect to the patients presenting other metastatic lesions, as well as on a functional forecast (fragility of the long bone), or on the other hand, on metastasis without immediate functional incidence. We also would like to discuss the treatment of the primitive tumour, i.e. if it is the metastasis which is revealing cancer, is it necessary to first treat the primitive tumour, than proceed to the treatment of the metastatic lesions? The third topic of this session will be “When Not to Operate on Metastatic Patients?”, presented by Professor POINTILLART. The goal of this discussion is to be able to give a progress report on the surgical indications within the framework of a spinal metastatic patient. In a certain number of cases surgery is questionable with the discovery of lesions, because of their extended character, or the extreme malignity of the primitive tumour. In other situations, too many lesions will make surgery disputable. Last case scenario is a recurring tumor, because of its extension, its development, even its neurological complications, will make surgery challenging. All these points in our opinion should be openly discussed. Each session will be followed by a 10 minute discussion
Neurological deficits resulting from spinal cord compression occur infrequently. When presented with neurological compromise, the most common management was radiotherapy, with surgery only being offered to patients who developed neurological deficit or pathological fracture resulting in unresolved severe pain post radiotherapy. Nasopharyngeal carcinoma has been reported to have a higher incidence of distant metastases to the spine. This study was conducted to evaluate the incidence, presentation and management of neurological involvement related to spinal metastasis from nasopharyngeal carcinoma.Summary
Introduction
Surgical treatment of spinal metastasis belongs to the standards of oncology. The risk of spinal cord compression represents an operative indication. Intraoperative bleeding may vary, depending on the extent of the surgical technique. Some primary tumors, such as the renal cell carcinoma, present a major risk for hemorrhage and preoperative embolisation is mandatory. The purpose of this study is to evaluate the possible benefit of embolisation in different types of primary tumors. The charts of 93 patients (42 women, 51 men, mean age 60.5 years) who were operated for spinal metastasis, 30 cases with multiple levels, were reviewed. Surgical procedures were classified as: (1) thoracolumbar laminectomy and instrumentation, (2) thoracolumbar corpectomy or vertebrectomy, (3) cervical corpectomy. A preoperative microsphere embolisation was performed in 35 patients. The following parameters, describing blood loss, were evaluated: hemoglobin variation from beginning to end of surgery, blood volume in suction during the intervention, number transfused packed red blood cells units until day 5 after surgery. A Poisson model was used for statistical evaluation.Introduction
Material and Methods
Myxoid liposarcoma (MLS) is an unusual type of soft tissue sarcoma as it tends to metastasize frequently to sites other than the lungs. This study was aimed to investigate the natural history of patients with MLS to try and identify prognostic factors which could help predict outcome and aid earlier detection of metastases. Data was prospectively collected from patient notes and analysed retrospectively. Prognostic factors and metastatic pattern were examined using Kaplan-Meier curves. There were 124 patients with MLS, aged between 28 and 93, the median size of the tumours was 12cm and the most common site was the thigh. Following treatment with excision and radiotherapy the 5yr survival was 65%. Survival was related to younger age (p=0.010) and proximal site (p=0.003) and was also related to the % round cell component of the tumour but was not related to either size or depth of the tumour. Site and margins of excision were significant prognostic factors for local recurrence of disease. 32% of patients developed metastases, of whom 18 cases (46.2%) developed pulmonary metastases and 21 (53.8%) developed extra pulmonary metastases. The sites of these varied hugely and was not significantly related to the site or size of the primary tumour. There was no difference in time to develop metastases or in overall survival between the two groups. Median survival following metastases was 24 months. Although MLS has an unusual pattern of metastases the site of metastases does not predict a better or worse outcome. Intensive follow up for extraskeletal metastases is probably not justified until they become symptomatic.
Loss of muscle mass (sarcopenia) and function in ageing are associated with reduced functional ability, quality of life and reduced life expectancy. In cancer patients, age related muscle loss may be exacerbated by cachexia and poor nutritional intake. Individuals with widespread disseminated disease are most prone to increasing functional decline, increased morbidity and accelerated death. However subjective assessments of physical performance have been shown to be poor indicators of life expectancy in these patients. To develop an objective measure to aid calculation of life expectancy in cancer by investigating the association between objectively measured lean muscle mass and longevity, in 41 patients with known spinal metastases from all cause primaries.Background
Aims
Lymph node metastasis in soft tissue sarcoma is considered to be a rare event (1.6–8.2%), From 1986 to 2001 1066 patients with extremity soft tissue sarcoma were treated surgically (+/− adjuvant therapy) at our institution. Thirty-nine patients (3.6%) were identified with lymph node metastasis, most common histological subtypes were: Epitheliod sarcoma (3/15), rhabdomyosarcoma (4/21), clear cell sarcoma (2/18), and angiosarcoma (2/18). Comparing expected five- year survivorship, we found that surprisingly in this study, extremity soft tissue sarcoma patients initially presenting with lymph node metastases had survival comparable to patients with high grade soft tissue sarcoma and no metastases. To determine the outcome in patients with soft tissue sarcoma (STS) of the limbs that presented with lymph node metastasis (LNM) at diagnosis or developed them after it, comparing to all STS of limbs population that was treated at our center. LNM in soft tissue sarcoma is considered to be a rare event (1.6–8.2%) with a devastating effect on the outcome,our study represent one of the largest reported cohorts, and suggest that agressive approach to LNM might contribute to survivorship. Thirty-nine patients (3.6%) were identified with LNM along their course of disease Thirteen patients presented with both lymphatic and systemic disease while twenty-six had isolated LNM at time of diagnosis. The mean follow-up from diagnosis of the primary tumor was 46.3 months (range zero to one hundred and forty-eight), and from diagnosis of lymph node involvement was 29.9 months (range zero to one hundred and twenty). Expected five year survival in patients initially presenting with LNM was comparable to patients with high grade soft tissue sarcoma and no metastases. From Jan’ 1986 to Dec’ 2001 1066 patients with extremity STS were treated at our institution. Fifteen patients presented with LNM at time of first diagnosis, and twenty-four subsequently developed LNM after it. Linear regression analysis and Kaplan-meier curves were used to compare expected survivorship in all patients with STS of limbs. Comparing expected five- year survivorship, we found that Surprisingly in this study, extremity STS patients initially presenting with LNM had survival comparable to patients with high grade soft tissue sarcoma and no metastases.
Score and McNab Score were used. CT scans after procedure were performed to detect cement extrusion. The follow up examinations 12 weeks after Kyphoplasty were performed by an independent blinded observer.
Photodynamic therapy (PDT) uses the strong cytotoxicity of singlet oxygen and hyperthermia produced by irradiating excitation light on a photosensitizer. The phototoxic effects of indocyanine green (ICG) and near-infrared light (NIR) have been studied in different types of cancer cells. Plasma proteins bind strongly to ICG, followed by rapid clearance by the liver, resulting in no tumor-selective accumulation after systemic administration. Kimura et al. have proposed using a novel nanoparticle labeled with ICG (ICG-lactosome) that has tumor selective accumulation owing to enhanced permeability and retention (EPR) effect. In this study, we investigated the efficacy of PDT using ICG-lactosome and NIR for a bone metastatic mouse model of breast cancer. Cells from the human breast cancer cell line, MDA-MB-231 were injected into the right tibia of 26 anesthetized BALB/C nu/nu mice at a concentration. The mice were then randomly divided into three groups: the PDT group (n = 9), the laser (laser irradiation only) group (n = 9), and the control group (n = 8). PDT was performed thrice (7, 21, 35 days after cell inoculation) following ICG-lactosome administration via the tail vein 24 hours before irradiation. The mice were percutaneously irradiated with an 810-nm medical diode laser for 10 min. In the laser group, mice were irradiated following saline administration 24 hours before irradiation. Radiographic analysis was performed for 49 days after cell inoculation. The area of osteolytic lesion was quantified. The right hind legs of 3 mice were amputated 24 hours after the third treatment. Histological analysis was performed using hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining of sagittal sections. The data was analyzed using Tukey-Kramer post-hoc test. P-value of <0.05 was considered significant. X-ray on day 49 of the three groups are considered. The area of osteolytic lesion in the PDT group (7.9 ± 1.2 mm2: mean ± SD) was significantly smaller than that of the control (11.4 ± 1.4 mm2) and laser (11.9 ± 1.2 mm2) groups. In histological findings, we observed many TUNEL-positive cells in the metastatic tissue 24 hours after PDT. In the control and laser groups, TUNEL-positive cells were occasionally observed. We have previously reported the effect of ICG-lactosome-enhanced PDT on the cytotoxicity of human breast cancer cells