Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management.

http://lib.ajaums.ac.ir/booklist/1-s2.0-s1058274614001098-main.pdf

Implant survival after total elbow arthroplasty: a retrospective study of 324 procedures performed from 1980 to 2008.

Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and modern imaging technology (CT, MRI, PET). Sometimes only extensive histopathological investigations on bone specimens from biopsy can suggest the primary malignancy. At other times, a bone lesion can have such a highly undifferentiated histological appearance that a precise pathological classification on routine hematoxylin–eosin-stained section is not possible. The authors reviewed the relevant literature in an attempt to investigate the epidemiology of the histological primaries finally identified in patients with bone metastases from occult cancer, and a strategy of management and treatment of bone metastases from occult carcinomas is suggested. Lung, liver, pancreas and gastrointestinal tract are common sites for primary occult tumors. Adenocarcinoma is the main histological type, accounting for 70 % of all cases, while undifferentiated cancer accounts for 20 %. Over the past 30 years, lung cancer is the main causative occult primary for bone metastases and has a poor prognosis with an average survival of 4–8 months. Most relevant literature focuses on the need for standardized diagnostic workup, as surgery for bone lesions should be aggressive only when they are solitary and/or the occult primaries have a good prognosis; in these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Thus, orthopedic surgery has a mainly palliative role in preventing or stabilizing pathological fractures, relieving pain and facilitating the care of the patient in an attempt to provide the most appropriate therapy for the primary tumor as soon as possible. 5

/pdf/bone-metastases-of-unknown-origin-epidemiology-and-1zwbmtw9zq.pdf

Bone metastases of unknown origin: epidemiology and principles of management

Bone metastases of the long bones often lead to pain and pathological fractures. Local treatment consists of radiotherapy or surgery. Treatment strategies are strongly based on the risk of the fracture and expected survival.Diagnostic work-up consists of CT and biopsy for diagnosis of the primary tumour, bone scan or PET-CT for dissemination status, patient history and blood test for evaluation of general health, and biplanar radiograph or CT for evaluation of the involved bone.A bone lesion with an axial cortical involvement of >30 mm has a high risk of fracturing and should be stabilised surgically.Expected survival should be based on primary tumour type, performance score, and presence of visceral and cerebral metastases.Radiotherapy is the primary treatment for symptomatic lesions without risk of fracturing. The role of post-operative radiotherapy remains unclear.Main surgical treatment options consist of plate fixation, intramedullary nails and (endo) prosthesis. The choice of modality depends on the localisation, extent of involved bone, and expected survival. Adjuvant cement should be considered in large lesions for better stabilisation. Cite this article: Willeumier JJ, van der Linden YM, van de Sande MAJ, Dijkstra PDS. Treatment of pathological fractures of the long bones. EFORT Open Rev 2016;1:136-145. DOI: 10.1302/2058-5241.1.000008.

Treatment of pathological fractures of the long bones.

Clinical and radiologic outcomes of pyrocarbon radial head prosthesis: midterm results

Bone metastases represent an important complication of malignant tumours. Despite improvement in surgical techniques and advances in systemic therapies, management of patients with bone metastatic disease remains a powerful cornerstone for the radiation oncologist. The primary goal of radiation therapy is to provide pain relief, preserving patient's quality of life.

/pdf/the-role-of-radiation-therapy-in-bone-metastases-management-g3ssjl8pr6.pdf

The role of radiation therapy in bone metastases management.

Pathologic fractures of the femur because of bone metastases seriously affect the quality of life of cancer patients. Different surgical options are indicated to achieve a durable and solid fixation, depending on several clinical, prognostic and mechanical factors. Locked intramedullary nailing is currently used to treat pathologic femoral fractures in patients with multiple metastases when the trochanteric region or shaft is mainly involved. This study evaluates intramedullary nailing for treatment of patients with pathologic femoral fractures, focussing on complications, clinical and functional outcomes and survival rates. The series included 80 pathologic fractures treated with a titanium alloy Proximal Nail (Standard or Antirotation) or Lateral Anterograde Femoral Nail (PFN, PFNA or LAFN, Synthes) inserted in a locked static mode. Acrylic cement was used to fill the bone cavity after nail insertion in eight patients; percutaneous cementoplasty was simultaneously performed in 11 cases of severe ipsilateral acetabular osteolysis. Postoperative outcomes focussed on pain relief, postoperative mobility and quality of life and they were analysed retrospectively using QOL-ACD and ECOG. Eleven patients (13.75%) suffered from non-fatal DVT post-surgery, with no pulmonary embolism. Six patients (7.5%) developed superficial wound infections and two patients (2.5%) developed pnaeumonia. There was no loss of reduction, breakage, screw pull out, or hardware or implant failure that required component substitution or revision. Lung histotype and the contemporary presence of cerebral and visceral metastases appeared to be predisposing factors in reducing survival time. All patients attained satisfactory pain relief, early deambulation and a marked clinical improvement during the first 6-10 postoperative months, with gradual worsening thereafter from deterioration of their general condition due to cancer progression. The patients' survival rate was 40% at 1 year, 25% at 2 years and 15% at 3 years. Results confirm that multiple factors related to patients and primary cancer may affect survival rate after femoral fracture. Intramedullary nailing should be indicated for pathologic fractures at femoral diaphysis and metaphysis when cancer is in an advanced stage. This procedure offers good and durable stability, and enables pain relief, early postoperative mobilisation and weight-bearing, thus improving the quality of life of cancer patients.

Intramedullary nailing for treatment of pathologic femoral fractures due to metastases

The outcome of prosthetic elbow surgery is continually evolving. We thoroughly reviewed the literature on this issue to analyse the indications, outcomes and complications of the numerous types of implants currently in use. Radial head replacement is recommended in comminuted fractures of the radial head and in post-traumatic conditions. Medium- and long-term results prove to be satisfactory in the majority of cases, with no evidence to indicate that some prostheses (monopolar vs. bipolar; cemented vs. press-fit) are more effective than others; nonetheless, the bipolar-cemented implant was found to be associated with a lower revision rate than other prostheses. Unicompartmental arthroplasty has recently been used for the treatment of osteoarthritis and rheumatoid arthritis when the lateral compartment is prevalently involved; the results reported to date have been encouraging, although further studies are warranted to confirm the validity of these implants. Total elbow arthroplasty is performed in a range of conditions, including distal humerus fractures in the elderly and elbow arthritis. In the former condition, linked elbow replacement yields excellent results with few complications and a low revision rate. In elbow arthritis, total elbow arthroplasty is indicated when patients suffer from disabling pain, stiffness and/or instability that prevent them from performing daily activities. Unlinked elbow arthroplasty, which is used above all in rheumatoid arthritis, also yields satisfactory results, although the risk of instability persists. The use of linked elbow arthroplasty, which yields similar results but lower revision rates, has consequently increased. Lastly, the results yielded by linked elbow prosthesis in post-traumatic conditions are good, although not quite as good as those obtained in rheumatoid arthritis. Early mechanical failure may occur in younger and more active patients after elbow arthroplasty. However, the careful selection of patients who are prepared to accept functional limitations imposed by elbow implants will enable indications for elbow arthroplasty to be extended to young subjects, particularly when no other therapeutic options are available.

Radial head, radiocapitellar and total elbow arthroplasties: A review of recent literature

Background Terrible triad injury (TTI), one of the main patterns of complex elbow instability, is difficult to treat and yields conflicting surgical results. We analyzed prospectively a series of patient affected by TTI and treated according to the current diagnostic and surgical protocols to investigate whether their application allow to obtain more predictable outcomes. Material and methods We analyzed 26 patients with a mean age of 52 years. Preoperative X-rays and CT were performed; all patients were operated by the same elbow surgeon and underwent the same surgical and rehabilitation treatment. Final functional outcome was assessed by the Mayo Elbow Performance Score (MEPS), Quick-Disability of the Arm Shoulder and Hand-score (Q-DASH) and the modified-American Shoulder and Elbow Surgeons score (m-Ases). A radiographic evaluation was also performed. Results Mean follow-up was 31 months. At final evaluation, mean flexion, extension, supination and pronation were 137°, 10°, 77° and 79°, respectively; mean MEPS, m-ASES and Q-DASH scores were respectively 96, 91 and 8 points. Complications observed after first surgery were: elbow stiffness in 5 cases, mild posterolateral instability in 3 cases, chronic subluxation in 1 case. Radiographic evaluation showed secondary arthritis in 9 cases, symptomatic HO in 3 cases and late hardware displacement in 2 cases. Six out of 26 patient underwent reoperation with final satisfactory results. Conclusion The current diagnostic and therapeutic protocols allow obtaining satisfactory clinical outcomes in majority of cases but a high number of major and minor unpredictable complications persist yet. In this series, low compliance, obesity, and extensive soft elbow tissue damage caused by high-energy trauma represented negative prognostic factors unrelated to surgery. On the other hand, the strict application of current algorithms by an expert elbow surgeon appears to improve clinical results by reducing the influence of other avoidable negative prognostic factors well known in current literature, such as the incomplete recognition of injuries, delayed treatment, inadequate treatment of bony and ligamentous injuries, prolonged immobilization and, last but not least, the surgeon's inexperience. Level of evidence Level IV, Case series, Treatment study.

Terrible triad of the elbow: is it still a troublesome injury?

Curettage is one of the most common method for surgical treatment of bone metastasis. Local adjuvant improve most commonly used for improving the effect of curettage in local cancer surgery may exerted their effects either chemically either physically; in Orthopedic Oncology the most common are phenol, liquid nitrogen, laser, and cement. This article reviewed the main characteristics of the most common chemical and physical agents used in bone oncology, emphasizing the toxic effects of some of them, especially phenol and liquid nitrogen.

Andrea Piccioli

Papers

The role of radiation therapy in bone metastases management.

Intramedullary nailing for treatment of pathologic femoral fractures due to metastases

Radial head, radiocapitellar and total elbow arthroplasties: A review of recent literature

Terrible triad of the elbow: is it still a troublesome injury?

Local adjuvants in surgical management of bone metastases.