[Is there a magic bullet for sarcomas? : Personalised treatment for maligant tumours of bone and soft tissue]. / Gibt es eine Magic Bullet für Sarkome? : Personalisierte Therapie von malignen Tumoren des Stütz- und Bewegungsapparates.

BACKGROUND: Personalised tumour therapies aim to selectively target pathways and structures to which a tumour shows an oncogenic addiction. OBJECTIVE AND METHOD: This article aims to provide an overview of relevant genetic alterations in bone and soft-tissue tumours, which might serve as potential therapeutic targets for personalised medicines in the future. Recent approaches towards a personalised treatment of various tumours of bone and soft tissues are reviewed. RESULTS: Molecular diagnosis has become an essential tool for the characterisation of bone and soft-tissue tumours. Currently, no targeted therapies are routinely available for bone sarcomas. Denosumab is merely a symptomatic treatment for giant cell tumours of the bone. Imatinib has become the paradigm of a targeted treatment for subgroups of malignant gastrointestinal stromal tumours (GISTs) and dermatofibrosarcoma protuberans. Antiangiogenic multikinase inhibitors, various other tyrosine kinase inhibitors (TKIs) and monoclonal antibodies are currently being evaluated in several (sub-)types of soft-tissue sarcomas. Sorafenib showed promising results in the treatment of aggressive desmoid-type fibromatosis. Histology-tailored chemotherapies did not yield superior results in a prospective randomised multicentre trial. CONCLUSION: More in-depth knowledge is required for many sarcomas to link their genetic alterations to tumorigenesis in order to develop efficient personalised treatment strategies. Clinical trial designs need to be adapted to evaluate new therapeutic strategies in these ultra-rare tumours and their various sub-types more efficaciously.

[Silver coating on tumour prostheses]. / Silberbeschichtung auf Tumorendoprothesen.

BACKGROUND: Modular endoprostheses, so-called "tumour or megaprostheses" are mainly used for limb salvage surgery after resection of malignant soft tissue or a bone tumour. Sometimes, this type of prosthesis is also used for revision surgeries after failed primary joint arthroplasty. Despite continuously improving techniques and quality management systems, periprosthetic infection is one of the most serious complications. AIM OF THE STUDY: Review of the literature in the PubMed data base with the main focus on silver coatings in joint arthroplasty and their effect on infection rate, outcome and patients' safety. RESULTS: The current literature shows that there is a beneficial role of silver coatings in megaprostheses in terms of revision rates for septic complications, especially following tumour resection with bad soft tissue coverage or in (multimorbid) high-risk patients, compared to uncoated implants. DISCUSSION: Based on the results of previous publications examining blood or serum silver concentrations or silver levels in urine, silver coatings do not appear to have side effects, except for local argyria. Continuous monitoring of silver levels in blood or serum is still recommended, and additional long-term studies will be necessary to verify the effectiveness and safety of silver coatings.

Clinical Results and Serum Metal Ion Concentrations following Ceramic-on-Metal Total Hip Arthroplasty at a Mean Follow-Up of 60 Months.

Background. Increased metal ion levels following total hip arthroplasty (THA) with metal-on-metal bearings are a highly debated topic. Local soft tissue reactions with chronic pain and systemic side effects such as neuropathy are described. The aim of the current study was to determine the serum metal ion concentrations of Cobalt (Co) and Chrome (Cr) after THA with a ceramic-on-metal (CoM) bearing. Patients and Methods. Between 2008 and 2010, 20 patients underwent THA using a CoM bearing. Clinical function was evaluated by standardized scores systems (Harris Hip Score and WOMAC Score) and radiological examination included X-rays. Patient's blood samples were obtained for metal ion analysis and correlation analysis was done between these results and implant position. Results. Overall, 13 patients with 14 CoM devices were available for the current series. The mean age at time of surgery was 61 years (range, 41 to 85). The postoperative follow-up ranged from 49 to 68 months (mean, 58). Metal ion determination showed mean concentrations of 3,1 µg/L (range, 0,3-15,2 µg/L) for Co and 1,6 µg/L (range, 0,1-5,5 µg/L) for Cr, respectively. A correlation between cup anteversion and Co and Cr concentrations was shown. Conclusion. The current series showed increments for Co and Cr following CoM THA. However, these levels are lower compared to metal ion concentrations in patients with metal-on-metal bearings and the international accepted threshold for revision of MoM devices. We recommend routine follow-up including at least one obligatory evaluation of serum metal ion concentrations and an MRI once to exclude local soft tissue reactions.

Langerhans cell sarcoma: a case report and review of the literature.

We present the case of a 62-year-old male patient with a three-month history of pain in the left shoulder. Magnetic resonance imaging of the left scapula showed an osteo-destructive lesion. H and E stained sections revealed a Langerhans cell sarcoma, and immunohistochemistry was performed additionally; CD68, CD163, CD14, fascin, HLA-DR, lysozyme, S100 CD1a and langerin showed a positive reaction, while CD20, CD30, CD34, CD31, pan-cytokeratin, AE/1AE3, SMA, desmin, EMA, ERG, INI-1, CD21, CD4, PLAP, MPO and CD117c were negative. We suggested palliative treatment with chemotherapy and radiation. The patient refused any treatment and died 2 weeks later.

Argyria following the use of silver-coated megaprostheses: no association between the development of local argyria and elevated silver levels.

The aims of this study were to evaluate the incidence of local argyria in patients with silver-coated megaprostheses and to identify a possible association between argyria and elevated levels of silver both locally and in the blood. Between 2004 and 2011, 32 megaprostheses with silver coatings were implanted in 20 female and 12 male patients following revision arthroplasty for infection or resection of a malignant tumour, and the levels of silver locally in drains and seromas and in the blood were determined. The mean age of the patients was 46 years (10 to 81); one patient died in the immediate post-operative period and was excluded. Seven patients (23%) developed local argyria after a median of 25.7 months (interquartile range 2 to 44.5). Patients with and without local argyria had comparable levels of silver in the blood and aspiration fluids. The length of the implant did not influence the development of local argyria. Patients with clinical evidence of local argyria had no neurological symptoms and no evidence of renal or hepatic failure. Thus, we conclude that the short-term surveillance of blood silver levels in these patients is not required.

[Bone metastases treatment strategies]. / Behandlungsstrategien bei Skelettmetastasen.

The primary goals of multimodal, interdisciplinary treatment of bone metastases are to achieve mobility, pain relief, and improve quality of life. In cooperation with radiotherapists and oncologists, an individual therapy plan has to be designed. As bone metastases are a sign of a systemic spread of the disease, cure is not possible in nearly all cases. A singular bone metastasis of a renal cell carcinoma may be regarded as an exemption, where wide resection might cure the patient. The extent of the operation should be based on the 3S principle "save, short & simple". The prognosis of survival should influence the treatment regime. If it is unclear whether a bone metastasis or a primary bone tumor is present, a biopsy is required.

Metal ion levels in large-diameter total hip and resurfacing hip arthroplasty--preliminary results of a prospective five year study after two years of follow-up.

BACKGROUND: Metal-on-metal hip resurfacing is an alternative to metal-on-metal total hip arthroplasty, especially for young and physically active patients. However, wear which might be detected by increased serum ion levels is a matter of concern. METHODS: The aims of this preliminary study were to determine the raise of metal ion levels at 2-years follow-up in a prospective setting and to evaluate differences between patients with either resurfacing or total hip arthroplasty. Furthermore we investigated if the inclination of the acetabular component and the arc of cover would influence these findings. Therefore, 36 patients were followed prospectively. RESULTS: The results showed increments for Co and Cr in both implant groups. Patients treated with large-diameter total hip arthroplasty showed fourfold and threefold, respectively, higher levels for Co and Cr compared to the resurfacing group (Co: p < 0,001 and Cr: p = 0,005). Nevertheless, we observed no significant correlation between serum ion levels, inclination and arc of cover. DISCUSSION: In order to clarify the biologic effects of ion dissemination and to identify risks concerning long-term toxicity of metals, the exposure should be monitored carefully. Therefore, long-term studies have to be done to determine adverse effects of Co and Cr following metal-on-metal hip replacement.