Andreas Leithner

Revision surgery after total joint arthroplasty: a complication-based analysis using worldwide arthroplasty registers.

The authors performed a complication-based analysis of total knee (TKA), total hip (THA), and total ankle arthroplasty (TAA) using worldwide arthroplasty registers. We extracted data with respect to reason for revision surgery and pooled causes. The most common causes for revisions in THA were aseptic loosening (55.2%), dislocation (11.8 %), septic loosening (7.5%), periprosthetic fractures (6%), and others. The most common causes in TKA were aseptic loosening (29.8%), septic loosening (14.8%), pain (9.5%), wear (8.2%), and others. The most common causes in TAA were aseptic loosening (38%), technical errors (15%), pain (12%), septic loosening (9.8%), and others. Revisions in TKA and THA differ with respect to type of complication. However, in case of TAA, higher rates of technically related complications are reported.

Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study

A variety of analyses, including fluorescence in situ hybridization (FISH), quantitative PCR (qPCR) and array CGH (aCGH), have been performed on a series of chordomas from 181 patients. Twelve of 181 (7%) tumours displayed amplification of the T locus and an additional two cases showed focal amplification; 70/181 (39%) tumours were polysomic for chromosome 6, and 8/181 (4.5%) primary tumours showed a minor allelic gain of T as assessed by FISH. No germline alteration of the T locus was identified in non‐neoplastic tissue from 40 patients. Copy number gain of T was seen in a similar percentage of sacrococcygeal, mobile spine and base of skull tumours. Knockdown of T in the cell line, U‐CH1, which showed polysomy of chromosome 6 involving 6q27, resulted in a marked decrease in cell proliferation and morphological features consistent with a senescence‐like phenotype. The U‐CH1 cell line was validated as representing chordoma by the generation of xenografts, which showed typical chordoma morphology and immunohistochemistry in the NOD/SCID/interleukin 2 receptor [IL2r]

Increasing incidence rates of soft tissue sarcomas? A population-based epidemiologic study and literature review

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Immunohistochemical analysis of desmoid tumours.

mouse model. In conclusion, chromosomal aberrations resulting in gain of the T locus are common in sporadic chordomas and expression of this gene is critical for proliferation of chordoma cells in vitro. Copyright

Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems.

BACKGROUND Increasing incidence rates of soft tissue sarcomas (STS) have been reported. In the present study, the authors have analyzed the incidence of STS in Austria in a population-based study for the period 1984-2004. PATIENTS AND METHODS Age-adjusted incidence rates, gender and age predilection and geographic differences were analyzed, comprising data from the Austrian National Cancer Registry. RESULTS A total of 5333 cases were registered; male-to-female ratio was 0.8. The most common histotypes were sarcoma not otherwise specified (36%), leiomyosarcoma (24%), liposarcoma (12%), malignant fibrous histiocytoma (9%) and fibrosarcoma (5%). Age-adjusted incidence rate was 2.4 per 100,000 per year. Analysis of annual incidence rates and 3-year periods showed no increase (annual increasing gradient = -0.0025). CONCLUSIONS This study has analyzed the most recent data from a European population in comparison with seven international studies. An increase, as postulated elsewhere, could not be confirmed. The incidence rate of STS in Austria ranges in the lower half of the international incidence rates (1.8-5.0 per 100,000 per year). Different inclusion criteria (Kaposis sarcoma and dermatofibrosarcoma) and classifications in the various studies explain the increase of incidence in some studies rather than true increase of STS due to new or accumulated risk factors.

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

Background/Aims: Although the standard treatment for desmoid tumours is complete surgical resection with wide margins, the optimal adjuvant treatment for recurrent or inoperable disease is unclear, often being based on sporadic immunohistochemical reports with a low number of cases. Therefore, a large immunohistochemical study was performed, to provide a theoretical basis for adjuvant treatment regimens. Methods: One hundred and sixteen tissue samples from 80 patients (49 female, 31 male; mean age, 34 years; range, 0–83) with desmoid tumours (46 extra-abdominal, 21 abdominal, 13 intra-abdominal) were tested for oestrogen receptors α and β, progesterone and androgen receptors, and somatostatin, in addition to HER2, cathepsin D, Ki-67, and c-KIT by immunohistochemistry. Results: All samples were negative for oestrogen receptor α, HER2, and the progesterone receptor. Positive staining for the androgen receptor was found in six extra-abdominal cases. Staining for oestrogen receptor β was positive in four extra-abdominal, two abdominal, and one intra-abdominal case. Staining for somatostatin was positive in six extra-abdominal, two abdominal, and one intra-abdominal case, and staining for cathepsin D was positive in all cases. Positive staining for Ki-67 was found in 14 extra-abdominal, three abdominal, and three intra-abdominal cases. C-KIT was detectable in one abdominal case only. Conclusions: The data from this immunohistochemical study show that the published effects of antioestrogens and imatinib mesylate in the treatment of aggressive fibromatoses may not be attributable to oestrogen receptor α or c-KIT expression.

Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients.

Study Design. Retrospective study. Objective. This study analyzed the predictive value of the scoring systems of Bauer, Bauer modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos as well as the parameters included in these systems. Summary of Background Data. Metastases of the spinal column are a common manifestation of advanced cancer. Severe pain, pathologic fracture, and neurologic deficit due to spinal metastases need adequate treatment. Besides oncologic aspects and quality of life, treatment decisions should also include the survival prognosis. Methods. Two hundred fifty-four patients with confirmed spinal metastases were investigated retrospectively (treatment 1998–2006; 62 underwent surgery and 192 had conservative treatment only). Factors related to survival, such as primary tumor, general condition (Karnofsky Performance Status Scale), neurologic deficit, number of spinal and extraspinal bone metastases, visceral metastases, and pathologic fracture, were analyzed. The survival period was calculated from date of diagnosis of the spinal metastases to date of death or last follow-up (minimum follow-up: 12 months). For statistical analysis, univariate and stepwise multivariate Cox regression analyses were performed. Results. Median overall survival for all patients was 10.6 months. The following factors showed significant influence on survival in multivariate analysis: primary tumor (P < 0.0001), status of visceral metastases (P < 0.0001), and systemic therapy (P < 0.0001). Using the recommended group assignment for each system, only Bauer and Bauer modified showed significant results for the distinction between good, moderate, and poor prognosis. The other systems failed to distinguish significantly between good and moderate prognosis. The hazard ratio of the absolute score of all analyzed systems was, however, statistically significant, with a better score leading to lower risk of death. Conclusion. According to this analysis, the Bauer and the Bauer modified scores are the most reliable systems for predicting survival. Since the Bauer modified score furthermore consists of only four positive prognostic factors, we emphasize its impact and simplicity.

The role of epidermal growth factor receptor in chordoma pathogenesis: a potential therapeutic target.

Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n = 170) and a validation set (n = 170). Besides well‐established clinico‐pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan–Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well‐established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrells concordance index (c‐index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR = 0.41, 95% CI = 0.18–0.97, p = 0.043; HR = 0.39, 95% CI = 0.16–0.91, p = 0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR = 0.33, 95% CI = 0.12–0.90, p = 0.03) and for DFS (HR = 0.36, 95% CI = 0.16–0.79, p = 0.01). The estimated c‐index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre‐operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment.

Incidence, predictive factors, and prognosis of chondrosarcoma in patients with Ollier disease and Maffucci syndrome: an international multicenter study of 161 patients.

Background:Recent data indicate that tumour microenvironment, which is influenced by inflammatory cells, has a crucial role in cancer progression and clinical outcome of patients. In the present study, we investigated the prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection.Methods:In all, 260 STS patients were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS.Results:In univariate analysis, elevated N/L ratio was significantly associated with decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30–4.14; P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI, 1.05–3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9 months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months. Regarding OS, elevated N/L ratio was also significantly associated with decreased survival in univariate analysis (HR, 2.90; 95%CI, 1.82–4.61; P=0.001) and remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14–3.12; P=0.014).Conclusion:In conclusion, our findings suggest that an elevated preoperative N/L ratio predicts poor clinical outcome in STS patients and may serve as a cost-effective and broadly available independent prognostic biomarker.

Wikipedia and osteosarcoma: a trustworthy patients' information?

Chordoma, the molecular hallmark of which is T (brachyury), is a rare malignant bone tumour with a high risk of local recurrence and a tumour from which metastatic disease is a common late event. Currently, there is no effective drug therapy for treating chordomas, although there is evidence that some patients respond to the empirical use of epidermal growth factor receptor (EGFR) antagonists. The aim of this study was to determine the role of EGFR in the pathogenesis of chordoma. Paraffin‐embedded material from 173 chordomas from 160 patients [sacro‐coccygeal (n = 94), skull‐based (n = 50), and mobile spine (n = 16)] was analysed by immunohistochemistry and revealed total EGFR expression in 69% of cases analysed. Of 147 informative chordomas analysed by FISH, 38% revealed high‐level EGFR polysomy, 4% high‐level polysomy with focal amplification, 18% low‐level polysomy, and 39% disomy. Phospho‐receptor tyrosine kinase array membranes showed EGFR activation in the chordoma cell line U‐CH1 and all of the three chordomas analysed. Direct sequencing of EGFR (exons 18–21), KRAS, NRAS, HRAS (exons 2, 3), and BRAF (exons 11, 15) using DNA from 62 chordomas failed to reveal mutations. PTEN expression was absent by immunohistochemistry in 19 of 147 (13%) analysed chordomas, only one of which revealed high‐level polysomy of EGFR. The EGFR inhibitor tyrphostin (AG 1478) markedly inhibited proliferation of the chordoma cell line U‐CH1 in vitro and diminished EGFR phosphorylation in a dose‐dependant manner, a finding supported by inhibition of phosphorylated Erk1/2. p‐Akt was suppressed to a much lesser degree in these experiments. There was no reduction of T as assessed by western blotting. These data implicate aberrant EGFR signalling in the pathogenesis of chordoma. This study provides a strategy for patient stratification for treatment with EGFR antagonists. Copyright