Functional outcome after surgery in patients with bone sarcoma around the knee; results from a long-term prospective study

Background and Objectives: In a previous conducted study functional outcome of young patients with bone sarcoma located around the knee was longitudinally evaluated during the first 2 years postoperatively. Functional outcome improved significantly over the first 2 years. The purpose of this descriptive study was to evaluate the functional outcome of these patients at long-term follow-up of 7 years. Methods: Functional outcome was assessed with the TESS, MSTS, Baecke questionnaire, and three functional performance tests: time up and down stairs (TUDS), various walking activities (VWA), and the 6-min walking test (6MWT). Linear Mixed Model has been employed fo

Cathepsin K Is the Principal Protease in Giant Cell Tumor of Bone

Giant cell tumor (GCT) of bone is a neoplasm of bone characterized by a localized osteolytic lesion. The nature of GCT is an enigma and the cell type(s) and protease(s) responsible for the extensive localized clinicoradiological osteolysis remain unresolved. We evaluated protease expression and cellular distribution of the proteolytic machinery responsible for the osteolysis. mRNA profiles showed that cathepsin K, cathepsin L, and matrix metalloproteinase (MMP)-9 were the preferentially expressed collagenases. Moderate expression was found for MMP-13, MMP-14, and cathepsin S. Specific protease activity assays revealed high cathepsin K activity but showed that MMP-9 was primarily present (98%) as inactive proenzyme. Activities of MMP-13 and MMP-14 were low. Immunohistochemistry revealed a clear spatial distribution: cathepsin K, its associated proton pump V-H(+)-ATPase, and MMP-9 were exclusively expressed in osteoclast-like giant cells, whereas cathepsin L expression was confined to mononuclear cells. To explore a possible role of cathepsin L in osteolysis, GCT-derived, cathepsin L-expressing, mononuclear cells were cultured on dentine disks. No evidence of osteolysis by these cells was found. These results implicate cathepsin K as the principal protease in GCT and suggest that osteoclast-like giant cells are responsible for the osteolysis. Inhibition of cathepsin K or its associated proton-pump may provide new therapeutic opportunities for GCT

In Reply

The authors respond to the observations and remarks of Cavanna et al. concerning the clinical guidance paper on giant cell tumor of bone (GCTB) in the era of denosumab and update the paper with respect to the European Medicines Agency’s recent positive opinion recommending denosumab for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or for which surgical resection is likely to result in severe morbidit

Clinical management of spinal metastases—The Dutch national guideline

This article is a summary of the revised Dutch multidisciplinary evidence-based guideline ‘Spinal metastases’ (English translation available at: https://www.oncoline.nl/spinal-metastases) that was published at the end of 2015. This summary provides an easy-to-use overview for physicians to use in their daily practice

No Haploinsufficiency but Loss of Heterozygosity for EXT in Multiple Osteochondromas

Multiple osteochondromas (MO) is an autosomal dominant disorder caused by germline mutations in EXT1 and/or EXT2. In contrast, solitary osteochondroma (SO) is nonhereditary. Products of the EXT gene are involved in heparan sulfate (HS) biosynthesis. In this study, we investigated whether osteochondromas arise via either loss of heterozygosity (2 hits) or haploinsufficiency. An in vitro three-dimensional chondrogenic pellet model was used to compare heterozygous bone marrow–derived mesenchymal stem cells (MSCs EXTwt/−) of MO patients with normal MSCs and the corresponding tumor specimens (presumed EXT−/−). We demonstrated a second hit in EXT in five of eight osteochondromas. HS chain length and structure, in vitro chondrogenesis, and EXT expression levels were identical in both EXTwt/− and normal MSCs. Immunohistochemistry for HS, HS proteoglycans, and HS-dependent signaling pathways (eg, TGF-β/BMP, Wnt, and PTHLH) also showed no differences. The cartilaginous cap of osteochondroma contained a mixture of HS-positive and HS-negative cells. Because a heterozygous EXT mutation does not affect chondrogenesis, EXT, HS, or downstream signaling pathways in MSCs, our results refute the haploinsufficiency theory. We found a second hit in 63% of analyzed osteochondromas, supporting the hypothesis that osteochondromas arise via loss of heterozygosity. The detection of the second hit may depend on the ratio of HS-positive (normal) versus HS-negative (mutated) cells in the cartilaginous cap of the osteochondroma

The Dutch national guideline on metastases and hematological malignancies localized within the spine; a multidisciplinary collaboration towards timely and proactive management

Here, we describe the development of a Dutch national guideline on metastases and hematological malignancies localized within the spine. The aim was to create a comprehensive guideline focusing on proactive management of these diseases, enabling healthcare professionals to weigh patient perspectives, life expectancy, and expected outcomes to make informed treatment recommendations. A national multidisciplinary panel consisting of clinicians, a nurse, a patient advocate, an epidemiologist, and a methodologist drafted the guideline. The important role of patients in the realization of the guideline enabled us to identify and address perceived shortcomings in patient care. The guideline covers not only metastatic epidural spinal cord compression, but also the treatment of uncomplicated metastases and hematological malignancies localized within the spine. The guideline is applicable in daily practice and provides an up-to-date and concise overview of the diagnostic and treatment possibilities for patients suffering from a disease that can have a serious impact on their quality of life. Suggestions for the practical implementation of patient care in hospitals are also provided, including approaches for pursuing proactive management. The crucial role of the patient in decision making is emphasized in this guideline

Measurement of the mass of the Z boson and the energy calibration of LEP

In 1985 the French government created a unique circuit for the dissemination of doctoral theses: References went to a national database “Téléthèses” whereas the documents were distributed to the university libraries in microform. In the era of the electronic document this French network of deposit of and access to doctoral theses is changing. How do you discover and locate a French thesis today, how do you get hold of a paper copy and how do you access the full electronic text? What are the catalogues and databases referencing theses since the disappearance of “Téléthèses”? Where are the archives, and are they open? What is the legal environment that rules the emerging structures and tools? This paper presents national plans on referencing and archiving doctoral theses coordinated by the government as well as some initiatives for creating full text archives. These initiatives come from universities as well as from research institutions and learned societies. “Téléthèses” records have been integrated in a union catalogue of French university libraries SUDOC. University of Lyon-2 and INSA Lyon developed procedures and tools covering the entire production chain from writing to the final access in an archive: “Cyberthèses” and “Cither”. The CNRS Centre for Direct Scientific Communication at Lyon (CCSD) maintains an archive (“TEL”) with about 2000 theses in all disciplines. Another repository for theses in engineering, economics and management called “Pastel” is proposed by the Paris Institute of Technology (ParisTech), a consortium of 10 engineering and commercial schools of the Paris region