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
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
This study aims to assess first, whether mutations in the epidermal
growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes
are associated with overall survival (OS) in patients who present
with symptomatic bone metastases from non-small cell lung cancer
(NSCLC) and secondly, whether mutation status should be incorporated into
prognostic models that are used when deciding on the appropriate
palliative treatment for symptomatic bone metastases. We studied 139 patients with NSCLC treated between 2007 and 2014
for symptomatic bone metastases and whose mutation status was known.
The association between mutation status and overall survival was
analysed and the results applied to a recently published prognostic
model to determine whether including the mutation status would improve
its discriminatory power.Aims
Patients and Methods
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
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
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
While primary squamous-cell carcinoma of the hand is common, metastasis of a squamous-cell carcinoma to the hand is very rare. It has been reported to arise from carcinoma of the lung and oesophagus and, rarely, from other tumours. We describe a patient with metastatic squamous-cell carcinoma occurring in the first web space of the hand from primary
We present two cases of metastatic
The management of spinal metastases is palliative and aimed at improving quality of life at an acceptable risk. This population study uses administrative databases and measures survivorship and complication rates after surgery for spinal metastases. The effects of various potential predictor variables were evaluated. We identified 987 patients with a median survival for all types of cancer of 227 days. The one and three-month mortality was 9% and 29%, respectively. Increasing age, male gender and primary
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).
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%).
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
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
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
We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton. We conducted a retrospective study on a population-based cohort of all adult patients treated surgically for bony metastases of the appendicular skeleton between January 2014 and December 2019. We excluded patients in whom the status of bone metastases and resection margin was unknown. Patients were followed until the end of the study or to their death. We had no loss to follow-up. We used Kaplan-Meier analysis (with log-rank test) to evaluate patient survival. We identified 506 operations in 459 patients. A total of 120 operations (in 116 patients) were for solitary metastases and 386 (in 345 patients) for multiple metastases. Of the 120 operations, 70 (in 69 patients) had no/an unknown status of visceral metastases (solitary group) and 50 (in 49 patients) had visceral metastases. In the solitary group, 45 operations (in 44 patients) were R0 (resections for cure or complete remission) and 25 (in 25 patients) were R1/R2 (resections leaving microscopic or macroscopic tumour, respectively). The most common types of cancer in the solitary group were kidney (n = 27), lung (n = 25), and breast (n = 20).Aims
Methods
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
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
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. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve.Aims
Methods
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