Diagnostic algorithm, prognostic factors and surgical treatment of metastatic cancer diseases of the long bones and spine

Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases.Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses.The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention.The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices.In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 15% of the cases), a promising three to five years of survival may be achieved, especially in cases of metastases from breast and kidney cancer.Spinal metastases require meticulous evaluation because decisions on treatment mostly depend on the tumour type, segmental stability, the patient's symptoms and general state of health.Advanced radiotherapy combined with minimally invasive surgical techniques (minimally invasive stabilisation and separation surgery) provides durable local control with a low complication rate in a number of patients. Cite this article: EFORT Open Rev 2017;2:372-381

Bone turnover markers for early detection of fracture healing disturbances: A review of the scientific literature

Imaging techniques are the standard method for assessment of fracture healing processes. However, these methods are perhaps not entirely reliable for early detection of complications, the most frequent of these being delayed union and non-union. A prompt diagnosis of such disorders could prevent prolonged patient distress and disability. Efforts should be directed towards the development of new technologies for improving accuracy in diagnosing complications following bone fractures. The variation in the levels of bone turnover markers (BTMs) have been assessed with regard to there ability to predict impaired fracture healing at an early stage, nevertheless the conclusions of some studies are not consensual. In this article the authors have revised the potential of BTMs as early predictors of prognosis in adult patients presenting traumatic bone fractures but who did not suffer from osteopenia or postmenopausal osteoporosis. The available information from the different studies performed in this field was systematized in order to highlight the most promising BTMs for the assessment of fracture healing outcome.As técnicas imagiológicas são o método convencional para a avaliação dos processos de cicatrização das fraturas. No entanto, estes métodos não são talvez totalmente confiáveis para a deteção precoce de complicações, as mais frequentes destas sendo o atraso da união e a não-união. Um diagnóstico eficaz destas desordens poderia prevenir a dor e a incapacidade prolongada do paciente. Esforços devem ser dirigidos no sentido do desenvolvimento de novas tecnologias para melhorar a exatidão no diagnóstico de complicações após fraturas ósseas. A variação nos níveis dos marcadores do turnover ósseo (BTMs) têm sido avaliados com vista à sua capacidade para prever o comprometimento da cicatrização das fraturas numa fase inicial, no entanto, as conclusões de alguns estudos não são consensuais. Neste artigo os autores fizeram uma revisão do potencial dos BTMs como fatores de previsibilidade precoce do prognóstico em doentes adultos que apresentavam fraturas ósseas traumáticas mas que não sofriam de osteopenia ou osteoporose pós-menopausa. A informação disponível nos diferentes estudos realizados neste campo foi sistematizada com vista a evidenciar-se os BTMs mais promissores para a avaliação da evolução da cicatrização das fraturas.SFRH/BD/45018/200

Biological and molecular profile of fracture non-union tissue: current insights

Delayed bone healing and non-union occur in approximately 10% of long bone fractures. Despite intense investigations and progress in understanding the processes governing bone healing, the specific pathophysiological characteristics of the local microenvironment leading to non-union remain obscure. The clinical findings and radiographic features remain the two important landmarks of diagnosing non-unions and even when the diagnosis is established there is debate on the ideal timing and mode of intervention. In an attempt to understand better the pathophysiological processes involved in the development of fracture non-union, a number of studies have endeavoured to investigate the biological profile of tissue obtained from the non-union site and analyse any differences or similarities of tissue obtained from different types of non-unions. In the herein study, we present the existing evidence of the biological and molecular profile of fracture non-union tissue

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Defective proliferation and osteogenic potential with altered immunoregulatory phenotype of native bone marrow-multipotential stromal cells in atrophic fracture non-union

Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271highCD45low cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271highCD45low cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing

Der bewaffnete Konflikt innerhalb Angolas zwischen 1992 und 2002

Der Begriff der sogenannten "neuen Kriege" bezieht sich auf eine bestimmte Form bewaffneter Konflikte, welche im Verlauf der 1980er Jahre, aber besonders nach dem Ende der Blockkonfrontation zwischen Ost und West und im Kontext der voranschreitenden Globalisierung sowie dem Zerfall staatlicher Strukturen Eingang in das weltweite Kriegsgeschehen gefunden haben. Diese bewaffneten Konflikte unterscheiden sich aufgrund ihrer ganz spezifischen Charakteristika in mehrfacher Hinsicht deutlich sowohl vom klassischen Staaten- als auch Bürgerkrieg. Somit scheint der von Carl von Clausewitz bereits im 19. Jahrhundert postulierte permanente Formenwandel des Krieges bis heute nichts von seiner Gültigkeit eingebüßt zu haben. Auch im Falle des bewaffneten Konfliktes innerhalb Angolas zwischen 1992 und 2002 ließen sich verschiedene Merkmale der "neuen Kriege" ausmachen. So ebnete etwa der angolanische Staatszerfalls dem vermehrten Auftreten privater beziehungsweise nicht-staatlicher Gewaltakteure den Weg, während MPLA und UNITA historisch entstandene identitätsbezogene Differenzen unter den Menschen dazu nutzten, Anhänger und Unterstützung für ihre jeweiligen Ziele und Zwecke zu mobilisieren. Aber auch noch weitere Charakteristika der "neuen Kriege", wie zum Beispiel die Finanzierungsstrategien der Konfliktakteure, welche sich durch den kontinuierlichen Ressourcenzufluss von außerhalb sowie verschiedene Formen des innergesellschaftlichen Transfers von Vermögen alimentieren, waren im angolanischen Krieg auszumachen. Trotz der Dominanz von Merkmalen der "neuen Kriege" im angolanischen bewaffneten Konflikt, kann eben jener letztendlich aber nicht als solch ein "neuer Krieg" klassifiziert werden, was dafür spricht, diesen eher unter dem Begriff des internationalisierten Bürgerkrieges zu fassen.The concept and idea of so-called "new wars" refer to a specific form of armed conflict, which has not only become influential for all global war events in the course of the 1980s, but especially so after the end of the confrontation between East and West and in the context of advancing globalization and state failure. These armed conflicts are significantly distinguished by their very specific characteristics in multiple regard concerning classical state wars as well as civil wars. Thus the permanent structural change of war, as postulated by Carl of Clausewitz in the 19th century, seems to have lost nothing of his validity to this day. In the case of armed conflict within Angola between 1992 and 2002, various elements of the "new wars" could be identified as well. So it happened that the Angolan state failure paved the way for a higher incidence of private or non-state force protagonists, while the MPLA and the UNITA used the historically constituted identity-related differences among the people to mobilize supporters and support for their respective aims, goals and objectives. But also other characteristics of the "new wars", such as the financing strategies of the actors in the conflict, who were financed by the continuous inflow of resources from outside as well as by various forms of internal social transfers of assets, could be observed in the Angolan war. Despite the fact that the characteristics of the "new wars" dominate in the armed conflict dealt with in this thesis, the Angolan war cannot ultimately be classified as such a "new war". Rather, it ought to be subsumed under the notion of internationalized civil war

Bisegmental posterior stabilisation of thoracolumbar fractures with polyaxial pedicle screws: Does additional balloon kyphoplasty retain vertebral height?

We retrospectively evaluated single-level compression fractures (T12-L3) scheduled for a short-segment POS (posterior-only stabilization) using polyaxial screws. Patients averaged 55.7 years (range, 19-65). Patients received either POS or, concomitantly, BK (balloon kyphoplasty) of the fractured vertebrae as well. Primary endpoint was the radiological outcome at the last radiographic follow-up prior to implant removal. POS together with BK of the fractured vertebrae resulted in a significant improvement of the local kyphosis angle and vertebral body compression rates immediately post-OP. During the further course of FU, a considerable loss of correction was observed post-OP in both groups. (Local KA: pre-OP/ post-OP/ FU: 12.6±4.8/ 3.35±4.8/ 11.6±6.0; anterior vertebral body compression%: pre-OP/post-OP/ FU: 71.94±12.3/ 94.78±19.95/ 78.17±14.74). VAS was significantly improved from 7.2±1.3 pre-OP to 2.7±1.3 (P<0.001) at FU. We found a significant restoration of the vertebral body height by BK. Nevertheless, follow-up revealed a noticeable loss of reduction. Given the fact that BK used together with polyaxial screws did not maintain intra-operative reduction, our data do not support this additional maneuver when used together with bi-segmental polyaxial pedicle screw fixation