Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Aims. Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells. Methods. We investigated the specific role of GNAQ using GNAQ wild-type cell lines (non-small-cell lung cancer cell lines; A549 cell lines), GNAQ knockdown cell lines, and patient-derived cancer cells. We evaluated GNAQ, RANKL, macrophage colony-stimulating factor (M-CSF), nuclear transcription factor-κB (NF-κB), inhibitor of NF-κB (IκB), and protein kinase B (Akt) signalling in the GNAQ wild-type and the GNAQ-knockdown cells. Osteoclastogenesis was also evaluated in both cell lines. Results. In the GNAQ-knockdown cells, RANKL expression was significantly upregulated (p < 0.001). The expression levels of M-CSF were also significantly increased in the GNAQ-knockdown cells compared with control cells (p < 0.001). GNAQ knockdown cells were highly sensitive to tumour necrosis factor alpha (TNF-α) and showed significant activation of the NF-κB pathway. The expression levels of RANKL were markedly increased in GNAQ mutant compared with GNAQ wild-type in patient-derived tumour tissues. Conclusion. The present study reveals that the alterations of GNAQ activate NF-κB pathway in cancers, which increase RANKL and M-CSF expression and induce osteoclastogenesis in cancers. Cite this article:Bone Joint Res. 2020;9(1):29–35

Lung cancer is the most common cancer diagnosed, the leading cause of cancer-related deaths, and bone metastases occurs in 20–40% of lung cancer patients. They often present symptomatically with pain or skeletal related events (SREs), which are independently associated with decreased survival. Bone modifying agents (BMAs) such as Denosumab or bisphosphonates are routinely used, however no specific guidelines exist from the National Comprehensive Cancer Center or the European Society of Medical Oncologists. Perhaps preventing the formation of guidelines is the lack of a high-quality quantitative synthesis of randomized controlled trial (RCT) data to determine the optimal treatment for the patient important outcomes of 1) Overall survival (OS), 2) Time to SRE, 3) SRE incidence, and 4) Pain Resolution. The objective of this study was to perform the first systematic review and network meta-analysis (NMA) to assess the best BMA for treatment of metastatic lung cancer to bone. We conducted our study in accordance to the PRISMA protocol. We performed a librarian assisted search of MEDLINE, PubMed, EMBASE, and Cochrane Library and Chinese databases including CNKI and Wanfang Data. We included studies that are RCTs reporting outcomes specifically for lung cancer patients treated with a bisphosphonate or Denosumab. Screening, data extraction, risk of bias and GRADE were performed in duplicate. The NMA was performed using a Bayesian probability model with R. Results are reported as relative risks, odds ratios or mean differences, and the I2 value is reported for heterogeneity. We assessed all included articles for risk of bias and applied the novel GRADE framework for NMAs to rate the quality of evidence supporting each outcome. We included 132 RCTs comprising 11,161 patients with skeletal metastases from lung cancer. For OS, denosumab was ranked above zoledronic acid (ZA) and estimated to confer an average of 3.7 months (95%CI: −0.5 – 7.6) increased survival compared to untreated patients. For time to SRE, denosumab was ranked first with an average of 9.1 additional SRE-free months (95%CI: 4.0 – 14.0) compared to untreated patients, while ZA conferred an additional 4.8 SRE-free months (2.4 – 7.0). Patients treated with the combination of Ibandronate and systemic therapy were 2.3 times (95%CI: 1.7 – 3.2) more likely to obtain successful pain resolution, compared to untreated. Meta-regression showed no effect of heterogeneity length of follow-up or pain scales on the observed treatment effects. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for SRE incidence, and low for pain resolution. While a generally high risk of bias was observed across studies, whether they were from Western or Chinese databases. The overall GRADE for the evidence underlying our results is High for Pain control and SRE incidence, and Moderate for OS and time to SRE. This study represents the most comprehensive synthesis of the best available evidence guiding pharmacological treatment of bone metastases from lung cancer. Denosumab is ranked above ZA for both overall survival and time to SRE, but both treatments are superior to no treatment. ZA was first among all bisphosphonates assessed for odds of reducing SRE incidence, while the combination of Ibandronate and radionuclide therapy was most effective at significantly reducing pain from metastases. Clinicians and policy makers may use this synthesis of all available RCT data as support for the use of a BMA in MBD for lung cancer

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360

The spine is one of the most common sites of bony metastasis, with 80% of prostate, lung, and breast cancers metastasizing to the vertebrae resulting in significant morbidity. Current treatment modalities are systemic chemotherapy, such as Doxorubicin (Dox), administered after resection to prevent cancer recurrence, and systemic antiresorptive medication, such as Zolendronate (Zol), to prevent tumor-induced bone destruction. The large systemic doses required to elicit an adequate effect in the spine often leads to significant side-effects by both drugs, limiting their prolonged use and effectiveness. Recently published work by our lab has shown that biocompatible 3D-printed porous polymer scaffolds are an effective way of delivering Dox locally over a sustained period while inhibiting tumor growth in vitro. Our lab has also generated promising results regarding antitumor properties of Zol in vitro. We aim to develop 3D-printed scaffolds to deliver a combination of Zol and Dox that can potentially allow for a synergistic antitumor activity while preventing concurrent bone loss locally at the site of a tumor, avoiding long systemic exposure to these drugs and decreasing side effects in the clinical setting. The PORO Lay polymer filaments are 3D-printed into 5mm diameter disks, washed with deionized water and loaded with Dox or Zol in aqueous buffer over 7 days. Dox or Zol-containing supernatant was collected daily and the drug release was analyzed over time in a fluorescence plate reader. The polymer-drug (Dox or Zol) release was tested in vitro on prostate and lung cancer cell lines and on prostate- or lung-induced bone metastases cells. Alternatively, direct drug treatment was also carried out on the same cells in vitro. Following treatment, all cells were subject to proliferation assay (MTT and alamar blue), viability assay (LIVE/DEAD), migration assay (Boyden chamber) and invasion assay (3D gel matrix). 3D-printed scaffolds loaded with both Dox and Zol will also be tested on cells. We have established an effective dose (EC50) for prostate and lung cancer cell lines and bone metastases cells with direct treatment with Zol or Dox. We have titrated the drug loading of scaffolds to allow for a release amount of Dox at the EC50 dose over 7 days. In ongoing experiments, we are testing the release of Zol. We have shown Dox releasing scaffolds inhibit cancer cell growth in a 2D culture over 7 days using the above cellular assays and testing the scaffolds with Zol is currently being analyzed. 3D-printed porous polymers like the PORO Lay series of products offer a novel and versatile opportunity for delivery of drugs in future clinical settings. They can decrease systemic exposure of drugs while at the same time concentrating the drugs effect at the site of tumors and consequently inhibit tumor proliferation. Their ability to be loaded with multiple drugs can allow for achieving multiple goals while taking advantage of synergistic effects of different drugs. The ability to 3D-print these polymers can allow for production of custom implants that offer better structural support for bone growth

Surgical management for acute or impending pathologic fractures in metastatic bone disease (MBD) places patients at high-risk for post-operative venous thromboembolism (VTE). Due to the combination of malignancy, systemic cancer treatment, and surgical treatment, VTE-risk is increased 7-fold in patients with MBD compared to non-cancer patients undergoing the same procedure. The extent and duration of post-operative hypercoagulability in patients with MBD remains unknown and thromboprophylaxis guidelines were developed for non-cancer patients, limiting their applicability to address the elevated VTE-risk in cancer patients. Thrombelastography (TEG) analysis is a point-of-care test that measures clot formation, stabilization, and lysis in whole blood samples. The TEG parameter, maximal amplitude (MA), indicates clot strength and the threshold of ≥65 mm has been used to define hypercoagulability and predict VTE events in non-cancer patients requiring orthopaedic surgery. Therefore, this study aims to quantify the extent and duration of post-operative hypercoagulability in patients with MBD using serial TEG analysis. Consecutive adults (≥18 years) with MBD who required orthopaedic surgery for acute or impending pathologic fractures were enrolled into this single-centre, prospective cohort study. Serial TEG analysis was performed onsite using a TEG®6s haemostasis analyzer (Haemonetics Corporation, Boston, MA) on whole blood samples collected at seven timepoints: pre-operatively; on post-operative day (POD) 1, 3, and 5; and at 2-, 6-, and 12-weeks post-operatively. Hypercoagulability was defined as MA ≥65 mm. Participants received standardized thromboprophylaxis for four weeks and patient-reported compliance with thromboprophylaxis was recorded. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were performed and difference between pre-operative MA values of participants with VTE versus no VTE was evaluated using Student's t-test (p≤0.05). Twenty-one participants (10 female; 47.6%) with a mean age of 70 ± 12 years were enrolled. Nine different primary cancers were identified amongst participants, with breast (23.8%), colorectal (19.0%), and lung cancer (14.3%) most frequently reported. Most participants (57.1%) were hypercoagulable pre-operatively, and nearly half remained hypercoagulable at 6- and 12-weeks post-operatively (47.1 and 46.7%, respectively). VTE occurred in 5 patients (23.8%) and mean MA was 68.1 ± 4.6 mm at the time of diagnosis. Mean pre-operative MA values were significantly higher (p=0.02) in patients who experienced VTE (68.9 ± 3.5 mm) compared to those who did not (62.7 ± 6.5 mm). VTE incidence was highest in the first week post-operatively, during which time four VTE events (80%) occurred. The proportion of patients in a hypercoagulable state increased at three consecutive timepoints, beginning on POD3 (85.0%), increasing on POD5 (87.5%), and peaking at 2-weeks post-operatively (88.9%). Current thromboprophylaxis guidelines do not consider cancer-associated risk factors that contribute to increased VTE incidence and prescription duration may be inadequate to address prolonged post-operative hypercoagulability in patients with MBD. The high rate of VTE events observed and sustained hypercoagulable state indicate that thromboprophylaxis may be prematurely terminated while patients remain at high risk for VTE. Therefore, extending thromboprophylaxis duration beyond 4-weeks post-operatively in patients with MBD warrants further investigation

Aims. Bone is a common site of metastatic disease. Skeletal complications include disabling pain and pathological fractures. Palliative surgery for incurable metastatic bone lesions aims to preserve quality of life and function by providing pain relief and stable mobility with fixation or replacement. Current literature has few treatment studies. We present a 5 year longitudinal cohort study of surgery for metastatic bone disease at our large teaching hospital reviewing our complication and mortality rates. Methods. Patients that underwent palliative surgery for metastatic bone lesions were identified from operative records. Demographics, clinical details and outcomes were recorded. Kaplan-Meier analysis was used to calculate survivorship. Results. 43 patients were treated for 44 bone metastases (34 IM Nails, 9 prosthetic replacements, 1 plate). The median age at primary diagnosis was 66 (33–92). Lung cancer was the most common primary. 56% presented with complete fractures and 44% with impending fractures (median Mirel score of 10). Pertrochanteric bone lesions were the most common (74%). Two out of 43 patients died within one day of surgery. 30 day mortality was 12% and 45% at 1 year. In those surviving the 30 day perioperative period, we report a complication rate of 14%. One patient had a dislocated prosthesis. Two patients had delayed or non union and two patients had failure of metalwork. No patient required re operation. Conclusion. Our series observed a 5% fixation failure rate and significant perioperative mortality. Whilst surgery may offer benefit in the non moribund patient with pathological fracture the decision to offer prophylactic surgery is more difficult in light of the high perioperative mortality seen in our study. Indeed, the patients in our study who died within 24 hours of surgery had prophylactic fixations. We conclude that surgical intervention must be carefully considered with realistic expectations of outcomes

Study purpose: Cancer patients presenting with symptomatic spinal metastases is an increasing problem. It is widely accepted that surgery plays an important role in the management of these patients and recent studies1 conclude that surgical treatment should be more frequently offered. However, who should be offered surgery remains controversial, largely because of a lack of information about outcome. Our study is a prospective analysis of survival and functional outcome in patients with metastatic spinal disease treated primarily by surgical decompression and stabilisation when indicated. Methods: Sixty two patients with radiologically suspected metastatic spinal disease, managed by one consultant neurosurgeon, were enrolled into a prospective cohort study. Patients presented with pain and or myelopathy. Survival, continence, walking, analogue pain scores and short form 36 (SF-36) scores were analysed. Results: Median age was 62 years (22–79 years, 35 female, 27 male) with the commonest primary tumours being breast (26%), lymphoma (13%) and prostate (10%). Lung cancer was poorly represented (1 patient). Survival rates were 56% at 1 year, 49% at 2 years and 28% at 3 years. Of 16 patients not walking pre-op, 8 gained the ability to walk, while 5 out of 7 incontinent patients gained continence following surgery. Conclusion: Our data indicate that long term survival and favourable functional outcomes can be achieved following surgery in patients with metastatic spinal disease. We strongly advocate that patients presenting with metastatic spinal disease be considered for primary surgical treatment but would highlight the importance of appropriate patient selection

Introduction: Total hip replacement in one of the most commonly performed operation in orthopaedics in the UK with similar numbers being operated in other parts of the world (2). The main reasons for this magnitude are marked improvement in function and the quality of life. The hip prosthesis has evolved significantly over half a century and better prostheses are available today. These newer implants are required to have a survival of 90% for a minimum of 10 years. The improved survival of the implant tends to have effect on the quality of life as well as the life expectancy. There has been a continuous attempt to quantify this increased life expectancy and survival following total hip arthroplasty. Materials and Methods: We compared the mortality figures of 3947 patients who had hip resurfacing arthroplasty with the national mortality figures of the UK. The cause of death was determined by telephone call to the next of kin and from the national death register. Results: The average standardized mortality ratio of hip resurfacing patients compared to national figures over the nine year period was 0.524(99 percent C.I. 0.39 to 0.69). Individual SMR for each year is shown in Table. The number of observed deaths were 86 as compared to the expected deaths number 164. Out of the total 86 deaths over a nine year period, 36 deaths were due to cancer, 25 due to cardiovascular causes, eight due to respiratory conditions, four following accidents and 13 due to other causes such as suicide, old age. In the cancer group 7 patients died of lung cancer and 8 died of blood cell neoplasms. National figures for year 2007 were not yet compiled so SIR for cancer was not calculated. Conclusion: The results of this study are comparable to other follow up studies on mortality following total hip replacement. This indicates that increased activity following hip resurfacing may help the patients maintain better fitness. The incidence of cancer needs to be interpreted with caution and can only be ascertained by a prospective study

Corrosion and wear of total hip (THA) and knee (TKA) prostheses extricate metallic particles and soluble metallic compounds. The oncogenic risk of these products should be known. Material and methods: Three Nordic cohorts of total hip (THA) and total knee arthroplasty (TKA) patients operated on for primary osteoarthrosis during 1967–1995 were combined for meta-analysis. The number of THA patients was 49,000 and TKA patients 24,000 totaling 497,000 person years. The mean follow-up time was 6.8 years. Standardized incidence ratios (SIRs) with 95% conþdence intervals (95% CI) were calculated for the observed and expected number of cancers. The expected numbers were based on national incidence rates. Results: The allover SIRs as well as the site-speciþc cancer incidences were similar for the THA and TKA patients. The observed number of all site cancers was 7639 and 8202 expected (SIR 0.93, 95% CI 0.91–0.95). The SIR for lung cancer (0.69, 0.64–0.75) was reduced. The incidence was also low for cancers of the stomach (SIR 0.76, 0.67–0.84), colon (SIR 0.86, 0.79–0.93) and rectum (SIR 0.89, 0.80–0.98). Slightly elevated SIRs were seen among TKA patients in cancer of the endometrium and prostate and among both THA and TKA patients in skin melanoma. Conclusions: Total cancer risk was signiþcantly reduced among THA and TKA patients due to decrease of respiratory and gastrointestinal cancers. The present results do not suggest any oncogenic risk of the components of hip and knee prostheses and their degradation products

Background: It is common practice nowadays to treat patients with metastatic epidural spinal cord compression (MESCC) surgically. Extend and type of surgery should be in proper relation to the expected survival time of the patient. It is still difficult to predict patient’s survival time and several scoring systems are evaluated in literature. Purpose: To evaluate potential prognostic factors for survival after surgery of metastatic spinal cord compression. Material and Methods: In this retrospective study we included all patients who underwent surgery for MESCC in two hospitals in the Netherlands between 2001 and 2007 (n = 56). Medical records were studied for the origin of the primary tumor, the sex, the location of MESCC, the presence of other bone or visceral metastases, the Karnofsky score and the ASA score. Survival data were obtained by computing the time difference between the date of surgery and death. Patients were divided in three groups for the localization of the primary tumor; fast (n=21), moderate (n=19) and slow (n=13) growing tumors. The group of fast growing tumors contains lung cancer, moderate contains renal cancer and slow growing contains breast cancer. Furthermore, groups were made for the location of MESCC and groups were made for the Karnofsky score. Survival times were compared with log-rank tests or cox regression. Results: The overall median survival after surgery was 7,8 months, with a minimal follow-up time of nineteen months. The difference in survival time between the groups of primary tumors was highly significant (p < 0,001). Patients with fast growing tumors had a much shorter survival time (median 3,5 months) than patients with slow growing tumors (median 60 months), and moderate growing tumors (median 15 months). Patients with visceral metastases had a significant shorter survival time, compared to patients without visceral metastases (p = 0,01). The presence of other bone metastases however, was of no influence, as was the location of MESCC. Patients with a baseline Karnofsky score of 80% or higher had a significant longer survival time than patients with a score of 70% or lower (p=0,022). Sex and ASA score are not significantly associated with survival time. Conclusion: The type of the primary tumor seems to be strongly associated with survival time. Besides the type of the primary tumor, the presence of visceral metastases and Karnofksy score are predictors for the survival time after surgery as well. Reliable prediction of survival is mandatory, in that way adjustable surgical treatment can be established

Purpose: We analysed retrospectively 32 cases of posterior cervicothoracic fixation for spinal tumours. We evaluated spinal stability, spinal alignment, and associated complications. Material and methods: Thirty-two patients underwent surgery: 27 men and five women, mean age 52 years, age range 17–72 years. We implanted 96 articular screws in C4 to C6, 54 screws in C7 and 180 pedicular screws in T1 to T8. Nineteen patients had primary lung cancer with spinal invasion, eleven had spinal metastases, one had a chondrosarcoma and one had a myeloma. For the first group of 19 patients, en bloc resection of the tumour with the vertebra was performed: four total vertebrectomies, 15 partial vertebrectomies. In a second group of 15 patients, palliative posterior fixation was performed with laminectomy decompression. Results: Follow-up ranged from three to 54 months with a mean of 15 months. Mean survival after total or partial vertebrectomy was 16 months (range 3 – 54 months). Survival after palliative decompression was eleven months with a range from five to 19 months. There were no changes in the sagittal alignment in 30 patients: two patients developed mechanical complications late after surgery requiring revision. We did not have any case of screw, plate or rod fracture. There were no neurological complications related to screw insertion either at the thoracic level (180 screws) or the cervical level (96 screws in C4C5C6 and 54 screws in C7). A control scan was available for 21 patients and revealed a malposition of the implanted screws for 2.5% of the screws with no clinical impact. Discussion: Posterior screw fixation is a good method to stabilise the cervicothoracic spine during tumour surgery. Articular cervical screws and transpedicular thoracic screws provide effective stability postoperatively. In addition, this type of instrumentation does not interfere should subsequent laminectomy or wider resection be necessary

Introduction: Despite advances in radiotherapy and chemotherapy, metastatic disease of the spine remains a challenging situation for spinal surgeons. An individual therapy should be chosen to provide the maximum palliative effect (reduction of pain, restoration of stability and function) with a minimum of operative morbidity and mortality. Predicting prognosis is the key factor in selecting the proper treatment. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Patients and Methods: Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Results: Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). Conclusion: The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account

Aims

Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments.

Introduction and Objectives: Half of primary tumors tend to disseminate to bones, and metastasis to bone is the third most common localisation for disseminated disease, after the lungs and liver. It is also the most common form of neoplasia in the skeleton. Treatment of bone metastasis is essentially palliative, and in select cases improves patient survival. We present results from the last 15 years in our centre. Materials and Methods: Between the years 1988–2003, our surgical oncology unit has treated 451 patients with bone metastasis. Of these, 49% were male, and 51% were female. Average age was 64 years (19–98). The most common causes were metastatic breast cancer (34%), unknown tumours (17%), multiple myeloma (9%), prostate cancer (9%), lung cancer (7%), bladder cancer (6%), and others (18%). Tumours localised to the following locations: femur (31%), spine (27%), multiple locations (13%), pelvis (11.5%), humerus (9%), and other locations (8.5%). In 69% of cases the first symptom was pain, in 28% pathologic fracture, and in the remaining 3% medullary compression. Of the 125 pathologic fractures, 71% were on the femur, 18% on the humerus, and the remaining 11% in other locations. Results: In 60% of cases (271 patients) conservative treatment was used, and in the remaining 40% (180 patients) surgical treatment was used. Of the 180 surgeries, 50.5% were for pathologic fractures, and 49.5% were prophylactic surgeries. Of the 125 pathologic fractures, 91 (73%) received surgical treatment, and the other 34 (27%) were treated conservatively. Intramedullary nailing was the most commonly used form of osteosynthesis (47%). Total resolution of pain was achieved in 86.5% of cases, and partial resolution in 13.5%. Mean time in bed from prophylactic surgery was 3 days. Mean time for recovery of function was 7 days for the arms and 11 days for the legs. Discussion and Conclusions: The fundamental goal is to offer short-term individualized treatment to control pain and avoid bedrest and hospitalization of these patients. Prophylactic surgery does not increase life expectancy of these patients. However, it does alleviate pain, avoids bedrest, and improves functionality. It should be kept in mind that the least aggressive surgical technique possible should be used

Introduction: The skeleton is the most common location for metastases, with life-time prevalences of 15% and 70% during autopsies. The Vienna Bone and Soft Tissue Tumor Registry has been established in 1965 and is collecting data on primary and secondary malignancies of the musculoskeletal apparatus ever since. The objective of this study was to review the epidemiology and survival of patients undergoing spinal stabilization, including an analysis of trends over time. Methods: Data on patients operated on between 1980 and 2007 were available from the Tumor registry. Information on location of metastases, number of metastases within and outside the spine, primary tumor, as well as complications and recurrences after treatment were extracted. Survival after surgery was assessed using the Kaplan-Meier method, adjusting for patient age by Lexis expansion. Furthermore, the dataset was expanded on calendar time to test changes in epidemiology and survival during the observed 28 years. The effect of the abovementioned variables on survival was assessed in a Cox regression model using patient age and calendar time as time frame. Results: Data on 254 patients could be ed. The most common primary diagnoses were hypernephroma (26.4%), breast cancer (19.75), and lung cancer (12.2%), mostly metastasizing to thoracic and lumbosacral spine (40% both). 104 patients (47.9%) had multiple spinal and 41 (16.1%) other osseous non-spinal metastases. 14.6% had complications in the immediate postoperative follow-up, 4.3% suffered from recurrences postoperatively. Average survival after surgery was 0.9 years (95%CI 0.7 to 1.0) with an average patient age of 60.4 years (95%CI 58.8 to 62.0). In the regression model location of metastases (p=0.008), primary malignancy (p< 0.001), and recurrences (p=0.008) were associated with decreases in survival. There was no association between survival time and the decade during which patients were treated (p=0.157). However, there were significantly less complications in patients treated in later decades, demonstrating the patient’s benefit of being referred to a specialized centre (p=0.015). Discussion: For our study, we are able to draw from experience of 28 years with stabilization due to spinal metastases. Analyzing the data from 254 patients we observed that spinal metastases stem from a similar pattern of primary malignancies. The average survival in our cohort was less than a year, with a very narrow confidence interval. While survival was not associated with later periods of follow-up, number of complications was, supporting the recommendation to refer cancer patients to specialized centers with appropriate experience. The external validity of our findings, however, is confined by the source of our patients, which comprises mostly central and eastern European patients, and few cases referred from more remote areas

Purpose: En bloc resection can be proposed for lung cancer involving the apex with invasion of the ribs or the transverse process using a transcervical anterior approach. Cancers invading the intervertebral foramen cannot be resected via this approach despite the classical indication for surgical resection. We report results of a novel surgical technique allowing cancerological resection of these tumours. Material and methods: Fifteen patients with the same grade of cancer were operated using the same surgical technique. The first operative time included: superior lobectomy via anterior cervicothoracic access (without removal of the lobe), dissection of the subclavian vessels and the brachial plexus, section of the ribs and the T1 root, spinal exposure from C6 to T5, hemi-disectomy C7-T1 and discectomy at the level below the invaded foramen, medial vertebral groove, closure. The second operative time included: posterior access, extended instrumentation of the spine, hemi-laminectomy C7 extended as needed, section of the roots (depending on the level of the resection) within the canal, oblique posterior vertebral osteotomy along the medial border of the pedicle terminating in the anterior groove. Finally en bloc ablation via the posterior access of the surgical piece including the lung, the ribs and the hemi-vertebrae. Results: Three- and four-level hemivertebrectomy was performed in eleven and three patients respectively. One patient had two hemivertebrectomies associated with one vertebrectomy. There were six resections (with repair) of the subclavian vessels for tumour invasion. Peroperative mortality was zero. Mean blood loss was 3000 ml. There were no neurological complications. There were eight postoperative complications: pneumonia five patients, cerebrospinal fluid fistula one patient, skin dehiscence one patient, haemorrhage one patient requiring reoperation. All patients were given postoperative radiotherapy. Three- and five-year survival was 36% and 27% respectively. Among the nine deaths, three had local relapse and six had general relapse. Discussion: This techniques enables resection of tumours considered to be inextirpable using other techniques. Survival was the same as for tumours of the apex without invasion of the foramen and better than without surgery. This major surgery requires a well-trained multidisciplinary team (thoracic and vascular surgeons, spinal surgeon, anaesthesiologists, intensive care specialists). Contraindications for this type of surgery are invasion of the spinal canal, the brachial plexus and the vertebral body as well as the presence of a spinal artery entering the foramen to be resected

Aims

Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture.

Aims

Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

Aims

To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism.