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Overview ideogram of CGH data of all chordoma cell lines. Every cell line corresponds to one color. Lines on the left side are losses, and on the right side are gains of chromosomal material. Arrows mark the CDK6 region on 7q and p16 region on 9p.

Detailed CGH karyograms of the chordoma cell lines as shown in the ideogram in Supplementary Figure 1 (according to ISCN: International System for Human Cytogentic Nomenclature).

Results of the single tandem repeats analysis of the cell lines U-CH1, U-CH2, UCH3, UCH6, UCH7, U-CH10, U-CH11 and UCH12. The results of the sex typing marker AMEL and the detected alleles for the markers D3S1358, D1S1656, D2S441, D10S1248, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, FGA, D22S1045 are given.

Expression data of mRNA as shown by box plot graphs for brachyury (A), collagen 2A1 (B) and CD24 (C).

Unsupervised cluster analysis of mRNA expression data of all chordoma cell lines. The T-gene (i.e., brachyury) is overexpressed (red). Cluster Analysis of chordoma cell lines with chondrocyte, liposarcoma and sarcoma expression data from GEO and own data from a cell line with cartilaginous differentiation and from tissue of a vertebral disc.

Effect of Abemaciclib (LY2835219) on the growth of chordoma lines U-CH1, U-CH6, CAL51 (negative control), and MCF7 (positive control). Cells were grown in 96-well-plates were incubated for 3 days at 37{degree sign}C with increasing concentrations of Abemaciclib (3, 6, 10, 30, 60, 100, 300, 600, 1000 nM) in the medium or left untreated for control. The amount of viable cells was determined by using the MTS cell viability test (GraphPad Prism software, Version 6).

Western blot analyses of 8 chordoma cell lines showing expression of brachyury at 47 kDa.

Clinical data of chordoma patients. Every sample was positive for brachyury. Asterisks (*) mark the parental chordomas of the established chordoma cell lines.

Proliferation assay using Alamar Blue assay for U-CH2, 3, 6 and 10. Increasing concentrations of Palbociclib lead to an increase of growth inhibition of chordoma cells.

Inversion microscopy views of the published chordoma cell lines U-CH1, U-CH2, U-CH 3, 6, 7, 10, 11, and 12. The cells showing the typical physaliphorous cytology; bars=100µm.

Supplementary Figure Legend

Immunocytology of U-CH1 control vs inhibited cells with 1000 nM Palbociclib for 3 days. Ki-67 decreases from 20% down to

Data Supplement from Preclinical Characterization of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway

Expression data of mRNA as shown by box plot graphs for brachyury (A), collagen 2A1 (B) and CD24 (C).

List of up and down regulated genes on expression level with a p-value of 10-4 a FC of 10.

FISH results regarding the CDKN2A status in chordoma cell lines and the corresponding parental tumor.

Western blot analysis for cleaved PARP and cleaved caspase 3 of all chordoma cell lines as compared to HEK-293 cells (+/- stimulation with TNFα and Bortezomib for 18h). No corresponding bands are apparent in the cell lines after inhibition with 1000 nM Palbociclib for 3 days. U-CH 1-6 (A) and U-CH 7-12 (A).

AIMS Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. METHODS AND RESULTS Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed. CONCLUSIONS We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone.

Giant cell tumor of bone (GCTB) is a locally aggressive lesion of intermediate malignancy. Malignant transformation of GCTB is a rare event. In 2013, the humanized monoclonal antibody against receptor activator of nuclear factor-κb-Ligand (RANKL) denosumab was approved for treatment of advanced GCTB. Since then, several reports have questioned the role of denosumab during occasional malignant transformation of GCTB. We report on three patients with H3F3A-mutated GCTBs, treated with denosumab. The tissue samples were analysed by histomorphology, immunohistochemistry, and in two instances by next generation panel sequencing of samples before and after treatment. One patient had a mutation of ARID2 in the recurrence of the GCTB under treatment with denosumab. One patient developed a pleomorphic sarcoma and one an osteoblastic osteosarcoma during treatment. Sequencing revealed a persisting H3F3A mutation in the osteosarcoma while the pleomorphic sarcoma lost the H3F3A mutation; however, a FGFR1 mutation, both in the recurrence and in the pleomorphic sarcoma persisted. In addition, the pleomorphic sarcoma showed an AKT2 and a NRAS mutation. These data are inconclusive concerning the role denosumab plays in the event of malignant progression/transformation of GCTB and point to diverging pathways of tumor progression of GCTB associated with this treatment.

Giant cell tumour of bone (GCTB) comprises the eponymous osteoclastic multinucleated giant cells eliciting bone lysis, an H3F3A-mutated neoplastic mononucleated fibroblast-like cell population, and H3F3A wild-type mononucleated stromal cells. In this study, we characterised four new cell lines from GCTB. Furthermore, we compared the genome-wide DNA methylation profile of 13 such tumours and three further cell lines with giant cell-rich lesions comprising three H3F3B-mutated chondroblastomas, three USP6-rearranged aneurysmal bone cysts, three non-ossifying fibromas, two hyperparathyroidism-associated brown tumours as well as mesenchymal stem cells, osteoblasts, and osteoclasts. In an unsupervised analysis, we delineated GCTB and chondroblastomas from the other analysed tumour entities. Using comparative methylation analysis, we demonstrated that the methylation pattern of the cell lines approximately equals that of H3F3A-mutated stromal cells in tissue. These patterns more resemble that of osteoblasts than that of mesenchymal stem cells, which argues for the osteoblast as the cell of origin of giant cell tumours of bone. Using enrichment analysis, we detected distinct hypermethylated clusters containing histone and collagen genes as well as target genes of the tumour suppressor p53. We found that the promotor regions of CDKN1A, CDKN2A, and IGFBP3 are methylated more strongly in GCTB than in the other giant cell-containing lesions, mesenchymal stem cells, osteoblasts, and osteoclasts (p 0.001). This hypermethylation correlates with the lower gene expression at the mRNA level for these three genes in the cell lines, the lack of p16 and p21 in these cell lines, and the lower expression of p16 and p21 in GCTB. Overall, our analysis reveals characteristic DNA methylation patterns of giant cell tumours of bone and chondroblastomas and shows that cell lines of giant cell tumours of bone are a valid model for further analysis of H3F3A-mutated tumour cells. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor that is composed of mononuclear stroma cells, scattered macrophages, and multinucleated osteoclast-like giant cells which cause pathologic osteolysis. The stroma cells represent the neoplastic population of the tumor and are characterized by the H3F3A mutation G34W. This point mutation is regarded as the driver mutation of GCTB. We have established three new stable H3F3A mutated GCTB cell lines: U-GCT1, U-GCT2, and U-GCT3M. MK-1775 is a Wee1-kinase inhibitor which has been used for blocking of sarcoma growth. In the cell lines we detected Wee1, Cdk1, Cyclin B1, H3K36me3, and Rrm2 as members of the Wee1 pathway. We analyzed the effect of MK-1775 and gemcitabine, alone and in combination, on the growth of the cell lines. The cell lines showed a significant reduction in cell proliferation when treated with MK-1775 or gemcitabine. The combination of both agents led to a further significant reduction in cell proliferation compared to the single agents. Immunohistochemical analysis of 13 GCTB samples revealed that Wee1 and downstream-relevant members are present in GCTB tissue samples. Overall, our work offers valuable new tools for GCTB studies and presents a description of novel biomarkers and molecular targeting strategies.

Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G0/G1-phase arrest with decreased S/G2fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare thesein vitrofindings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (n=99patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients.

Es wird uber einen metachronen multifokalen Riesenzelltumor des Knochens (RZTK) berichtet. Der Patient bekam im Alter von 47 Jahren die Erstdiagnose eines RZTK im linken Oberarmknochen. Im Laufe seiner Krankengeschichte wurde ein weiterer RZTK im Kopf des vierten linken Mittelhandknochens und ein dortiges Lokalrezidiv nachgewiesen. Alle Tumorlokalisationen besasen die fur RZTK charakteristische H3F3A-Mutation G34W, die mittels Sanger-Sequenzierung und einem mutationsspezifischen Antikorper detektiert wurde. Der Fall stellt die Erstbeschreibung eines multifokalen H3F3A-mutierten RZTK dar.

ZusammenfassungIm klinischen Alltag wurden Verletzungen der unteren Halswirbelsäule lange Zeit analog zu den Brust- und Lendenwirbelsäulenverletzungen gemäß der AO-Klassifikation beschrieben. Im Rahmen dieser Übersicht wird nun die neue AOSpine-Klassifikation für Verletzungen der subaxialen Halswirbelsäule vorgestellt.

Chordomas are rare tumours of the bone arising along the spine from clivus to sacrum. We compared three chordoma cell lines of the clivus region including the newly established clivus chordoma cell line, U-CH14, with nine chordoma cell lines originating from sacral primaries by morphology, on genomic and expression levels and with patient samples from our chordoma tissue bank. Clinically, chordomas of the clivus were generally smaller in size at presentation and patients with sacral chordomas had more metastases and more often recurrent disease. All chordoma cell lines had a typical physaliphorous morphology and expressed brachyury, S100-protein and cytokeratin. By expression analyses we detected differentially expressed genes in the clivus derived cell lines as compared to the sacral cell lines. Among these were HOXA7, HOXA9, and HOXA10 known to be important for the development of the anterior-posterior body axis. These results were confirmed by qPCR. Immunohistologically, clivus chordomas had no or very low levels of HOXA10 protein while sacral chordomas showed a strong nuclear positivity in all samples analysed. This differential expression of HOX genes in chordomas of the clivus and sacrum suggests an oncofetal mechanism in gene regulation linked to the anatomic site.

To establish a chordoma tissue cohort (n = 43) and to correlate localization, size, metastasis, residual disease (R-status), recurrences, histological subtype, matrix content, and Ki-67 proliferation index with patients’ overall survival (OS). We used routine histopathology supplemented by immunohistochemistry. In our patient cohort (median age 69 years, range 17 to 84 years) the median OS was 8.25 years. 24 chordomas were localized in the sacrum, 6 in lumbar vertebrae, 7 in thoracic and cervical vertebrae, 5 were limited to the clivus, and one was localized in the nasal septum. Ten patients had metastases, with pulmonary, nodal, and hepatic involvement. 23 patients had recurrent disease. 23 chordomas were classified as ‘not otherwise specified’ (NOS). Besides NOS, we found the following differentiation patterns: renal cell cancer like in six cases, chondroid in four cases, hepatoid differentiation in three cases, and anaplastic morphology in six cases. Ki-67 index of ≥10 %, presence of metastasis, and the low content of extracellular matrix were statistically linked to poor OS (p

Chordomas are tumors that arise at vertebral bodies and the base of the skull. Although rare in incidence, they are deadly owing to slow growth and a lack of effective therapeutic options. In this study, we addressed the need for chordoma cell systems that can be used to identify therapeutic targets and empower testing of candidate pharmacologic drugs. Eight human chordoma cell lines that we established exhibited cytology, genomics, mRNA, and protein profiles that were characteristic of primary chordomas. Candidate responder profiles were identified through an immunohistochemical analysis of a chordoma tissue bank of 43 patients. Genomic, mRNA, and protein expression analyses confirmed that the new cell systems were highly representative of chordoma tissues. Notably, all cells exhibited a loss of CDKN2A and p16, resulting in universal activation of the CDK4/6 and Rb pathways. Therefore, we investigated the CDK4/6 pathway and responses to the CDK4/6–specific inhibitor palbociclib. In the newly validated system, palbociclib treatment efficiently inhibited tumor cell growth in vitro and a drug responder versus nonresponder molecular signature was defined on the basis of immunohistochemical expression of CDK4/6/pRb (S780). Overall, our work offers a valuable new tool for chordoma studies including the development of novel biomarkers and molecular targeting strategies. Cancer Res; 75(18); 3823–31. ©2015 AACR.

To explore the diagnostic value of MRI-based 3D texture analysis to identify texture features that can be used for discrimination of low-grade chondrosarcoma from enchondroma. Eleven patients with low-grade chondrosarcoma and 11 patients with enchondroma were retrospectively evaluated. Texture analysis was performed using mint Lesion: Kurtosis, entropy, skewness, mean of positive pixels (MPP) and uniformity of positive pixel distribution (UPP) were obtained in four MRI sequences and correlated with histopathology. The Mann-Whitney U-test and receiver operating characteristic (ROC) analysis were performed to identify most discriminative texture features. Sensitivity, specificity, accuracy and optimal cut-off values were calculated. Significant differences were found in four of 20 texture parameters with regard to the different MRI sequences (p

Aims Giant cell tumour of the bone (GCTB) is a neoplasm predominantly of long bones characterized by the H3F3A mutation G34W. Conventional diagnosis is challenged by the tumour's giant cell-rich morphology, which overlaps with other giant cell-containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell-containing lesions. Methods and results We used the antibody for analysis of 22 H3F3A-mutated GCTB, including two patients with recurrences; for comparison we analysed a cohort of 36 H3F3A wild-type giant cell-rich lesions of the bone and soft tissue, containing one brown tumour, six aneurysmal bone cysts (ABC), six chondroblastomas, five non-ossifying-fibromas, two fibrous dysplasias, nine tenosynovial giant cell tumours, one giant cell-rich sarcoma and six osteosarcomas. Furthermore, among the 22 mutated cases, we included one GCTB with two recurrences and lung metastases; the patient was treated with the anti-receptor activator of nuclear factor κB (RANK) ligand denosumab. We show that all 22 H3F3A-mutated GCTB display strong nuclear H3.3 G34W staining in the neoplastic component, while the osteoclastic giant cells are negative. 36 H3F3A wild-type lesions are negative. The GCTB treated with denosumab revealed a reduction in the H3.3 G34W-positive tumour cells and a decrease in osteoclastic giant cells accompanied by matrix and osteoid formation. Conclusions We conclude that positive H3.3 G34W staining is a specific and sensitive method for detection of H3F3A-mutated GCTB. Denosumab treatment leads to a pathomorphosis of the lesion characterized by matrix and osteoid producing H3.3 G34W-negative stromal cells.

Purpose Malignant soft tissue tumours appear infrequently in comparison to benign lesions. Clinical misdiagnosis leads to inadequate or delayed therapy in many cases of soft tissue sarcoma. The present study explores the question if ultrasonography as a widely-used diagnostic tool allows for a discrimination of benign and malignant soft tissue tumours. Materials and methods In a prospective study over a period of 8 years 224 histologically ascertained solid soft tissue tumours, thereof 120 sarcomas and 27 aggressive benign lesions were investigated by B-mode and colour Doppler sonography. The echotexture was analysed computer-based using the parameters echogenicity, homogeneity and vascularisation in all lesions. Results Different tumour groups showed typical patterns of echotexture, which enabled a classification using 6 categories, distinguishing homogenous hyperechoic, heavily inhomogeneous and homogenous hypoechoic lesions, each group linked to an elevated or low vascularisation. Implementation of the proposed classification revealed a sensitivity in the detection of soft tissue sarcomas and aggressive benign lesions of 94.4 % with a specificity of 79.7 % and an accuracy of 89.7 %. Conclusion Ultrasonography allows for a determination of the diagnostic and therapeutic procedure in soft tissue tumours. Due to the fact that soft tissue sarcomas present hypervascularised almost exclusively, predominantly homogenous hypoechoic, rarely homogenous hyperechoic, and aggressive benign tumours present homogenous hypoechoic predominantly, such patterns require a biopsy prior to further surgical therapy. However, in homogenous hyperechoic lesions displaying a low blood flow either a primary resection or a conservative treatment with follow-up examinations can be discussed depending on clinical findings and history of the patient. Although the group of heavily inhomogeneous tumours within our collective consisted of benign lesions exclusively, biopsy should be recommended in theses cases in order to exclude a soft tissue sarcoma.

The purpose of this study was to evaluate prospectively, whether integrated 2-deoxy-2-[(18)F]fluoro-D: -glucose positron emission tomography-computed tomography (FDG-PET-CT) is more accurate for determination musculoskeletal tumors compared with separate interpretation of CT and FDG-PET, because most of the current clinical data come from patients studied with PET.Eighty patients with newly diagnosed musculoskeletal tumors underwent FDG-PET-CT. CT, FDG-PET, and FDG-PET-CT were interpreted separately to determine the performance of each imaging modality.Assuming that equivocal lesions are benign, performance of diagnostic tests was as follows: sensitivity, specificity and accuracy for CT alone was 81, 84, 83%, for PET 71, 82, 76, and for PET-CT 80, 83 and 86%. Assuming that equivocal lesions are malignant, sensitivity, specificity, and accuracy for CT was 61, 100, 70%, for PET 69, 100, 79, and for PET-CT 69, 100 and 79%.Combined FDG-PET-CT reliably differentiates soft tissue and bone tumors from benign lesions. The value of the information provided by FDG-PET-CT for planning surgical procedures must be evaluated in further studies.

Das Skelettsystem stellt nach Leber und Lunge den dritthaufigsten Manifestationsort von Metastasen dar. 30± 50 % aller Patienten, die an einem Malignom erkranken, entwickeln ossare Metastasen. Viele dieser Metastasen zeigen keine Symptome, konnen jedoch im Sektionsgut nachgewiesen werden. Knochenmetastasen treten am haufigsten in der Wirbelsaule auf (bis zu 60± 80%). Weitere Pradilek− tionsstellen sind Becken, Femur, Rippen und Humerus. Die Inzidenz von Knochenmetastasen ist abhangig vom Primartumor. Sie treten gehauft beim Mamma− karzinom (50 ± 85 %), beim Prostatakarzinom (60 ± 80%), beim Nierenzellkarzinom (20 ± 50%), beim Schildrusen− karzinom (20± 60 %) sowie beim Bronchialkarzinom (20± 60 %) auf.

Stem loosening and stress-shielding are problems encountered in cemented hip arthroplasty. Could proximal stem fixation by partial cementing solve the problem? More physiological transmission of forces with only proximal cement fixation seems to be possible with this recent development (Z-stem, Option 3000, Mathys Orthopaedics, Bettlach, Switzerland). In a prospective clinical trial, this new implant was used for total hip arthroplasty in human patients. One hundred and thirty-three (133) total hip replacements in 123 patients were performed between April 1996 and January 2003. All of them were followed up regularly; 53 were analysed with the EBRA-FCA method (Einzel Bild Röntgen Analyse--femoral component analysis), whereas the rest were analysed using conventional follow-up X-rays. Eighty-six (86) patients with 95 hips could be examined in August 2004 to obtain mid-term results. At this stage, the mean follow-up time was 61 months (5.08 years), with a maximum of 100 months (8.33 years). Up to October 2004, nine cases needed a revision. The clinical data collected reported an average Harris Hip Score of 89.3 (good). The EBRA-FCA analysis reported a mean subsidence of less than 1.5 mm after the first two years, under the EBRA threshold of predicted loosening. At the latest follow-up (at an average of 61 months), there was an average stable subsidence of 2.4 mm in general. Eight (8) patients presented with subsidence of more than 5 mm. The results of the new implant seem to be encouraging. Finally, comparing our results to other fixation concepts will require longer follow-up periods.

Proximal stem fixation by partial cementing is a new concept in hip arthroplasty. We conducted a prospective clinical and radiological analysis to evaluate the preliminary outcome of this new technique with the Option 3000® stem (Mathys Orthopaedics, Bettlach, Switzerland). One hundred and thirty-three hip replacements in 123 patients have been performed between 1996 and 2003: All of them were followed up regularly both clinically and radiological and 53 were analysed with the EBRA-FCA method. Eighty-six patients with 95 hips could be seen in August 2004. At this point of time, the mean follow-up time was 61 months (5.08 years) with a maximum of 100 months (8.33 years) The clinical data reported an average Harris Hip Score of 85.5. Nine stems had to be exchanged over the period of study. The EBRA-FCA analysis reported a mean subsidence less than 1.5 mm after 2 years, then an average stable subsidence of 2.4 mm. So the results are similar to the early results obtained with other fixation concepts and the long-term results appear promising.

Endoscopic minimally invasive techniques have become an established method of fracture stabilisation in the spine. In view of this fact, anterior stabilisation strategies must be reconsidered, as monosegmental A 3.1 compression fractures are increasingly being stabilised endoscopically from the anterior aspect using minimally invasive techniques. This study investigated the biomechanical necessity of anterior two-point or four-point stabilisation in the instrumentation of mono- and bisegmental fractures. In three biomechanical in vitro studies, burst fracture stabilisation was simulated, and anterior short fixation devices were tested under load with pure moments up to 3.75 Nm to evaluate the biomechanical stabilising characteristics of different kinds of instrumentations in flexion/extension, lateral bending, and axial rotation. Only anterior four-point stabilisation resulted in sufficient primary stability both in mono- and bisegmental instrumentation and therefore represents the standard procedure in open as well as in minimally invasive spinal surgery.

Die Differenzierung zwischen degenerativen Krankheitsbildern der Halswirbelsaule (HWS) und unfallbedingten Beschwerden erfordert unfallanalytische Betrachtungen. Probandenversuche ergeben Daten im Niedrigenergiebereich, unfallanalytische Untersuchungen zu strukturellen Verletzungen der HWS fehlen. Im Zeitraum vom 01.01.2000 bis 30.04.2002 wurden 15 Patienten mit strukturellen Schaden der HWS nach einem Pkw-Unfall in der Unfallchirurgischen Klinik der Universitat Ulm behandelt. In 11 Fallen konnte eine unfallanalytische Begutachtung durch die DEKRA (Ulm) angefertigt werden. Strukturelle Verletzungen der HWS konnen bei seitlicher Krafteinleitung auch im Geschwindigkeitsbereich δv=10 km/h auftreten. Verletzungen der Ligg. alaria entstehen bei Frontalkollisionen mit erheblichen Differenzgeschwindigkeiten. Unfallanalytische Daten struktureller Verletzungen der HWS mussen in Kausalitatsbetrachtungen der Distorsion der HWS Berucksichtigung finden.

We investigated the osseointegration of solvent-preserved, xenogenous cancellous bone blocks in the treatment of unstable fractures of the thoracolumbar junction. In 22 patients, the anterior repair procedure was performed by thoracoscopy or minimally invasive retroperitoneal surgery. Twenty-two patients had undergone monosegmental anterior fusion and were surveyed prospectively. Solvent-preserved, bovine cancellous bone blocks were used in 11 patients; iliac crest bone graft was used in the others. Follow-up after 12 months included CT scans, which revealed successful osseointegration in eight out of 11 patients who had received autogenous iliac crest bone grafts, while three patients showed a partial integration. There were no graft fragmentations. In patients who had received solvent-preserved, xenogenous cancellous bone blocks, complete osseointegration was achieved at the graft–bone interface in only two out of 11 cases, after 1 year. Partial integration was found in three patients. In view of these results, autogenous iliac crest bone grafts are still the unrivalled standard for defect repair in spinal surgery.

Whether injuries to the alar ligaments could be responsible for complaints of patients having whiplash injury in the upper cervical spine is still controversially discussed. It is known that these ligaments protect the upper cervical spine against excessive lateral bending and axial rotation movements. The objective of the present in vitro study was therefore to examine whether the alar ligaments or any other structures of the cervical spine are damaged in side collisions. In a specially designed acceleration apparatus, six human osteoligamentous cervical spine specimens were subjected to incremental 90 degrees side collisions from the right (1 g, 2 g, 3 g, etc.) until structural failure occurred. A damped pivot table accounted for the passive movements of the trunk during collision, and a dummy head (4.5 kg) ensured almost physiological loading of the specimens. For quantification of functional injuries, the three-dimensional flexibility of the specimens was tested in a spine tester before and after each acceleration. In all six specimens, structural failure always occurred in the lower cervical spine and always affected the facet joint capsules and the intervertebral discs. In four specimens, this damage occurred during the 2 g collision, while in the other two it occurred during the 3 g and 4 g collision, respectively. The flexibility mainly increased in the lower cervical spine (especially in lateral bending to both sides) and, to a minor extent, in axial rotation. In vitro low-speed side collisions caused functional and structural injury to discoligamentous structures of the lower cervical spine, but did not damage the alar ligaments. Since the effects of muscle forces were not taken into account, the present in vitro study reflects a worst-case scenario. Injury thresholds should therefore not be transferred to reality.

A new instrumentation system for ventral stabilization of the spine that can be used for an endoscopic and minimally invasive approach was developed. We describe the implantation technique and report on the first clinical results. This prospective study covers the first 45 patients to undergo this new technique since it was introduced in 1999. In all patients the operation was successfully performed in a completely minimally invasive procedure. Mono- and bisegmental stabilization was performed mainly at the thoracolumbar junction after initial posterior instrumentation in most cases. Lesions varied from fresh/old fractures to metastases (T5–L3). Pre- and postoperative follow-up included clinical examination and radiological visualization via X-ray and computed tomographic scan. Our experience with this minimally invasive procedure demonstrated the feasibility of the method.

Objective. Current recommendations for spinal implant testing do not consider the determination of axial compression forces of the overbridging implant on the strut graft. No direct data exist on the influence of load transfer through the strut graft and of the kind of instrumentation, especially in thoracolumbar corpectomy models. Design. Therefore in this biomechanical in vitro study a method for measurement of the axial compression force acting across the strut graft in different thoracolumbar instrumentations was developed. Methods. In this in vitro study, a corpectomy model was simulated and anterior, posterior and combined short fixation devices currently available were tested under pure moments to evaluate their biomechanical stabilizing characteristics. Range of motion, neutral zone and the axial compressive force acting on the strut graft were measured continuously in the three primary directions. Results. Without loads, the combined stabilization and followed by anterior instrumentation created a higher axial compression force than the dorsal instrumentation on the strut graft. Especially during maximal extension there was no axial compression of the dorsal instrumentation on the strut graft, which resulted in an increase of the range of motion. Conclusion. The feasibility of the new method was demonstrated in this study. For the purpose of standardization and comparison it should be considered in spinal implant testing.

With the second amendment to the Ordinance on Occupational Diseases (BeKV) of 18 December 1992, discogenic diseases of the spine are included in the disease register of occupational diseases for the first time. If occupations that impose stress on the spine have been practised for many years, the possibility exists of recognizing degenerative diseases as an occupational disease. In assessment practice, the radiological data on the spine exposed to stress is compared with that of regions which are remote from the stress (cervical/thoracic spine). This pattern of the distribution of degenerative disease is then used as the basis for determining a causal relationship between the occupation causing the stress and disease of the axial skeleton. The pattern of degeneration of the cervical spine was investigated in two groups, one with ( n =153) and one without ( n =333) occupations that impose stress on the lumbar spine. A cumulative score of degenerative changes was elaborated and presented as a new classification. No differences were found between the groups with regard to either the frequency of occurrence, segmental distribution or severity of disease. In both groups, degenerative changes correlated with age. The prevailing assessment practice is discussed on the basis of these data.

Object. The authors conducted a study to investigate the biomechanical in vitro influence of a new anchorage system for fixation of anterior stabilization devices and the possibility of using additional cement after screw insertion to compensate for poor bone quality. The incidence of osteoporosis-related fractures has increased nearly twofold in the last decade. Because of problems associated with anterior screw fixation such as loosening, mechanical failure, and the weakness of osteoporotic bone, current surgical treatments of vertebral body (VB) fractures are problematic. This is due to poor fixation strength of anterior screws in the adjacent segments. The aim of this study was to determine whether a new cemented and uncemented VB screw provides improved primary stability following placement of anterior instrumentation in cases of fracture. Methods. The primary stability-related parameters of a new uncemented/cemented screw were compared with those of conventional monocortical screw fixation in a burst fracture model in which strut graft and anterior overbridging instrumentation were used. The use of the new uncemented screw improved the range of motion (ROM) of the stabilized spine in flexion—extension by approximately 22%, in rotation by 20%, and in lateral bending by 15%. Additional cementation improved the ROM by approximately 41% in flexion—extension, 32% in rotation, and 30% in lateral bending compared with conventional monocortical screw fixation. Conclusions. The new cannulated screw improves fixation strength and primary stability parameters. It is useful in the initial treatment of fractures in cases of poor bone quality and as a rescue device if previously inserted screws do not remain securely in place.

Some 30% of unstable vertebral fractures of the thoracic and lumbar spine involve a destruction of the ventral column and thus of the supporting structures of the spine. This requires extensive surgical reconstruction procedures, which are carried out using minimally invasive techniques. The disadvantages of the minimally invasive methods are the high cost, the technical equipment and the expenditure of time required in the initial phase for the performance of the surgical procedure. With the structural reform of the health care system in the year 2000, the private-sector regulatory bodies were called upon to introduce a flat-rate compensation system for hospital services according to section 17b of the Hospital Law (KHG). The previous financing system which involved per-diem operating cost rates has thus been abolished. Calculations of individual entities are now required. Considering the case values to date, a contribution margin deficit of EUR 4628.45 has been calculated for our patients with fractures of the thoracic and lumbar spine without neurological defunctionalization symptoms. An economically efficient medical care is thus no longer possible. Consequently, an adjustment of the German relative weights must urgently be demanded in order to guarantee a high-quality medical care of patients.

Der Einfluss von zusatzlichen Verletzungen dorsaler Wirbelsaulenstrukturen im Rahmen einer Fraktur auf die Stabilitat ventraler Stabilisierungen ist weitgehend unbekannt. Die Zementierung der ventralen Schrauben ist eine Moglichkeit die Stabilitat von ventralen Systemen besonders bei schlechter Knochenqualitat zu erhohen. Mit Hilfe eines neu entwickelten Schraubdubels lasst sich bei schlechter Haltefestigkeit eine genau definierte Menge Knochenzement uber Langsschlitze durch den hohlen Schraubdubel applizieren.

Die Etablierung minimal-invasiver Techniken in der Frakturbehandlung der Wirbelsaule wurde durch das Fehlen geeigneter Implatate und Instrumente erschwert. Mit der Entwicklung des MACS-TL-Systems® ist nun ein an die endoskopische Technik angepasstes System konzipiert worden, welches eine komplett endoskopische Stabilisation von Th5 bis L1, ggf. mit endoskopischem Zwerchfellsplitting von L1 bis L2 und von L2 bis L4 retroperitoneal mono- und mehrsegmental ermoglicht.

Study Design. Conditioned media (CM) of cartilaginous endplates (CEPs) of intervertebral discs were analyzed in a bioassay with regard to their influence on matrix turnover and inflammatory factors on nucleus pulposus (NP) cells of the same patient. CEP tissue underwent further histological and ultrastructural analysis. Objective. To identify possible interactions between the CEP and the disc via molecular factors that may influence disc matrix degradation and to determine degenerative changes of CEP tissue. Summary of Background Data. Impaired endplate perme-ability due to degeneration and calcification is considered to be a key contributor to disc degeneration. An upregulation of metalloproteinases and inflammatory cytokines has been observed in degenerated intervertebral discs. Possibly, the CEP contributes to the regulation of disc matrix degradation via molecular interactions with the disc tissue. Methods. CEP and NP cells from the same patients (n = 6) were investigated in a bioassay with regard to their influence on matrix turnover and inflammatory factors. We determined gene expression of NP cells in alginate beads that were exposed to CM of CEP punches (CEP-CM) from the same patients. The CEP-CMs were analyzed by protein array for inflammatory cytokines. Further CEP samples underwent histological (n = 15) and ultrastructural analysis (n = 8) to determine alterations of cell and matrix structure. Results. NP cells exposed to their donor-corresponding CEP-CM significantly upregulated interleukins (IL-6, IL-8) and matrix metalloproteinase (MMP-3, MMP-13) expression, and significantly decreased aggrecan and collagen type 2 expression. Proinflammatory cytokines were identified in the CEP-CM. The occurrence of apoptotic cells and degraded matrix fragments varied strongly between donors. Conclusion. Our results indicate interactions between the CEP and the NP tissue via molecular factors that upregulate matrix degrading enzymes and inflammatory cytokines and thereby influence the pathophysiology of disc degeneration. Ongoing investigations will further identify the regulative role of potential molecular factors that are responsible for these degenerative alterations. Conclusion. Level of Evidence: N/A