Andreas Leithner | Medical University of Graz (original) (raw)
Papers by Andreas Leithner
Acta Biomaterialia, 2020
, A lean magnesium-zinc-calcium alloy ZX00 used for bone fracture stabilization in a large growin... more , A lean magnesium-zinc-calcium alloy ZX00 used for bone fracture stabilization in a large growing-animal model,
Cells
Particle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the ... more Particle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the side effects of radiation oncology, especially in pediatric patients. To investigate the influence of PT on growing bone, we exposed an organotypic rat ex vivo femur culture model to PT. After irradiation, histological staining, immunohistochemical staining, and gene expression analysis were conducted following 1 or 14 days of in vitro culture (DIV). Our data indicated a significant loss of proliferating chondrocytes at 1 DIV, which was followed by regeneration attempts through chondrocytic cluster formation at 14 DIV. Accelerated levels of mineralization were observed, which correlated with increased proteoglycan production and secretion into the pericellular matrix. Col2α1 expression, which increased during the cultivation period, was significantly inhibited by PT. Additionally, the decrease in ColX expression over time was more pronounced compared to the non-IR control. The chondrogen...
BMC Musculoskeletal Disorders
Background Despite numerous scientific investigations, the tribological advantages of mobile bear... more Background Despite numerous scientific investigations, the tribological advantages of mobile bearing inserts have not been sustainably confirmed or refuted for modern knee prostheses in clinical studies. The purpose of this study was to compare fixed and mobile bearing inserts in order to draw conclusions regarding clinical benefits. Methods The present prospective single center cohort study of 2 non-randomized stratified groups consisted of 67 patients. All included patients received cemented total knee arthroplasty (Attune®) due to osteoarthritis. 34 patients were treated with a mobile and 33 patients with a fixed insert. The WOMAC score and the Visual Analogue Scale was used for the subjective assessment of success, while the Knee-Society-Score was used considering the Range of Motion for the objective assessment. The subjective and the clinical scores showed improvements for both compared groups postoperatively at 2 years of minimum follow-up. Results The overall postoperative r...
BMC Cancer
Background Although chondrosarcoma is the second most common primary malignant bone tumor, treatm... more Background Although chondrosarcoma is the second most common primary malignant bone tumor, treatment options are limited due to its extensive resistance to a chemo- and radiation therapy. Since shikonin has shown potent anticancer activity in various types of cancer cells, it represents a promising compound for the development of a new therapeutic approach. Methods The dose-relationships of shikonin and its derivatives acetylshikonin and cyclopropylshikonin on two human chondrosarcoma cell lines were measured using the CellTiter-Glo®. The changes in the cell cycle were presented by flow cytometry. Protein phosphorylation and expression apoptotic markers, MAPKs and their downstream targets were analyzed using western blotting and gene expression were evaluated using RT-qPCR. Results Chondrosarcoma cells showed a dose-dependent inhibition of cell viability after treatment with shikonin and its derivatives, with the strongest effect for shikonin and IC50 values of 1.3 ± 0.2 µM. Flow cy...
International Journal of Medical Sciences, 2021
Background: Periprosthetic joint infection (PJI) represents a serious complication following tota... more Background: Periprosthetic joint infection (PJI) represents a serious complication following total knee arthroplasty. In the setting of chronic infections, the two-staged approach has traditionally been the preferred treatment method. The aim of this study was to determine the optimal period of rest between the first and second stage. Furthermore, we analyzed potentially outcome-relevant parameters, such as general and local conditions and the presence of difficult-to-treat or unidentified microorganisms, with regard to their impact on successful treatment of PJI. Patients and Methods: We performed a retrospective analysis of prospectively collected data for all patients treated for PJI at our institution. Seventy-seven patients who had undergone two-stage revision arthroplasty for PJI of the knee were included into the study. Antibiotic-loaded cement spacers were used for all patients. Results: After a median follow-up time of 24.5 months, infection had reoccurred in 14 (18.7%) patients. A prolonged spacer-retention period of more than 83 days was related to a significantly higher proportion of reinfections. Furthermore, significant compromising local conditions of the prosthetic tissue and surrounding skin, as well as repeated spacer-exchanges between first-and second-stage surgery, negatively influenced the outcome. Neither the patients' age nor gender exerted a significant influence on the outcome regarding reinfection rates for patients' age or gender. Conclusions: We observed the best outcome regarding infection control in patients who had undergone second-stage surgery within 12 weeks after first-stage surgery. Nearly 90% of these patients stayed free from infection until the final follow-up. An increased number of performed spacer-exchanges and a bad local extremity grade also had a negative impact on the outcome.
Cartilage, synovium and bone, 2018
USA). At least three random fields were evaluated for each type of ST, quantifying the expression... more USA). At least three random fields were evaluated for each type of ST, quantifying the expression of INHBA, TNF-a, MMP12 and CD209 in all segmented CD163 + macrophages. Macrophages density was normalised based on selected tissue area(mm 2). After background subtraction, data were plotted using Graph-Pad software (GraphPad Software, La Jolla, CA, USA). Results: CD163 + sublining (SL) macrophages from UA-RA expressed abundantly the INHBA-encoded activin A, whereas TNFa and MMP12 were variably detected. Regarding the M-CSF-associated marker CD209, 2 populations of CD163 + macrophages were found in the SL of UA-RA, CD163 + CD209 + and the other CD163 + CD209-, with higher than 100 arbitrary units (au) for CD163 + CD209 + and lower than 100 au for CD163 + CD209-. Similarly, INHBA, MMP12 and TNFa expression and 2 populations of CD209 were detected in CD163 + macrophages from UA-PsA. Macrophage density was also found comparable between UA, with 650/mm 2 in UA-RA and 649/mm 2 in UA-PsA. Quantification of the above indicated markers in CD163 +ST macrophages from established RA and PsA revealed similar levels of INHBA, TNFa, MMP12 and CD209 than those from UA-RA and UA-PsA. Conclusions: This study shows for the first time that the polarisation state of ST CD163 + macrophages in UA progressing to RA and PsA is similar to that of established RA and PsA in terms of INHBA, MMP12, TNFa and CD209 expression. Therefore, the inflammatory polarisation state of macrophages is similar in RA and PsA and it is already detected at the earlier steps.
Osteoarthritis and Cartilage, 2016
Journal of Orthopaedic Research, 2014
The development of osteoarthritis (OA) depends on genetic and environmental factors, which influe... more The development of osteoarthritis (OA) depends on genetic and environmental factors, which influence the biology of the chondrocyte via epigenetic regulation. Changes within the epigenome might lead the way to discovery of new pathogenetic pathways. We performed a genome-wide methylation screening to identify potential differences between paired mild and severe osteoarthritic human cartilage. Sixteen female patients suffering from OA underwent total knee joint replacement. Cartilage specimens collected from corresponding macroscopically undamaged and from damaged areas were processed for DNA extraction and histology to evaluate the histological grading of the disease. Paired specimens were analysed for the methylation status of the whole genome using human promoter microarrays (Agilent, Santa Clara, CA). Selected target genes were then validated via methylation-specific qPCR. One thousand two hundred and fourteen genetic targets were identified differentially methylated between mild and severe OA. One thousand and seventy of these targets were found hypermethylated and 144 hypomethylated. The descriptive analysis of these genes by Gene Ontology (GO), KEGG pathway and protein domain analyses points to pathways of development and differentiation. We identified a list of genes which are differently methylated in mild and severe OA cartilage. Within the pathways of growth and development new therapeutic targets might arise by improving our understanding of pathogenetic mechanisms in OA.
The variety of radiographic diagnostics used to diagnose pain localised close to metal implants i... more The variety of radiographic diagnostics used to diagnose pain localised close to metal implants is still limited. Especially magnetic resonance results can not be analysed because of artefacts. In this article we present for the first time a direct correlation between an increase in skin temperature and existent frontal (anterior) knee pain after implantation of artificial knee joints measured with thermography. In a standardised way 26 knees were analysed. Thermographic photos were taken from frontal, inner (medial) and outer (lateral) directions with a computer-assisted infrared thermograph. Temperatures in locations with pain were significantly higher compared to the reference field in inner location (median 0.95 °C, p=0.0043), as well as in outer location (median 0.5 °C, p=0.032). Median temperature difference between pain localization and localizations without pain was 0.7 °C and ranged from 0.1 °C to 1.7 °C. In the receiver operating characteristic (ROC) analysis the sensitivity of this method was 1.0 and specificity was 0.917. The evidence of a significant increase in skin temperature on the painful sites opens up the possibility to localize and assess pain more precisely in patients with joint prosthesis. We consider this novel, rapid, inexpensive and non-invasive technology to posses the potential to become a useful and objective tool for diagnosis of pain and inflammation and to generate digital data that can be stored and analysed in clinical practice.
Scientific Reports
The aims of this study were to (1) assess reliability of leg length discrepancy (LLD) measurement... more The aims of this study were to (1) assess reliability of leg length discrepancy (LLD) measurements at different anatomical landmarks, (2) longitudinally investigate LLD in patients within the first year following total hip arthroplasty (THA) and to (3) correlate changes in LLD with functional outcome. Ninety-nine patients with short stem THA (53.3% males, mean age: 61.0 ± 8.1 years) were prospectively included. Upright pelvic anteroposterior (a.p.) radiographs taken at 6 timepoints (preoperatively, discharge, 6, 12, 24, 52 weeks postoperatively) were used to assess LLD at 5 anatomical landmarks (iliac crest, upper sacroiliac joint, lower sacroiliac joint, tear drop figure, greater trochanter). WOMAC and Harris Hip Score (HHS) were obtained preoperatively and at 6 and 52 weeks. LLD measures significantly increased in the initial phase following THA, from discharge to 6 weeks postoperatively and remained constant thereafter. Documentation of LLDs is dependent on measurement site: LLDs...
BMC Cancer
Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft ti... more Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate. Questions/purpose This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. Methods This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF. Results Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3–85) were inclu...
Wiener klinische Wochenschrift, 2021
SummarySoft tissue sarcomas (STS) represent a small group of adult solid malignancies, with risk ... more SummarySoft tissue sarcomas (STS) represent a small group of adult solid malignancies, with risk factors such as environmental factors, genetic predisposition, and prior radiotherapy. In STS patients with a novel swelling, differential diagnoses include recurrence, second primary cancer, metastasis from unknown primary cancer, and radiation-associated STS, the latter usually occurring approximately 10 years after radiotherapy. We present the case of a 64-year-old male patient with pleomorphic rhabdomyosarcoma, who underwent resection and radiotherapy. The patient presented again 5 years later with painful swelling in the area of the prior sarcoma, raising suspicion of recurrence. Resection was performed and a diagnosis of pleomorphic sarcoma (not otherwise specified [NOS]) was made. The patient was treated with radiotherapy and remained sarcoma-free for the following 7 years. A molecular analysis of both neoplasms, using RNA next-generation sequencing, did not detect any specific fu...
Orthopaedic Surgery, 2020
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Scientific Reports, 2020
Angiosarcoma of bone (B-AS) is a rare malignant tumor of vascular origin. The aim of this retrosp... more Angiosarcoma of bone (B-AS) is a rare malignant tumor of vascular origin. The aim of this retrospective study is to report on treatments and prognosis. Data were collected from the EMSOS website. 80 patients in 9 centers included: 51 male/29 female; median age 54 years (range 17 to 92); 56% with localized disease, 44% metastatic. Primary tumor surgery: 76% (30% amputation, 26% intralesional margins); radiotherapy (RT): 41%; chemotherapy (CT): 47% (56% in metastatic, 41% in localized cases). With a median follow-up of 31 months (range 40 to 309), 5-year overall survival (OS) was 27% (95%CI 16–30): 41% (95%CI 25–56) for localized patients, and 8% (95%CI 0–20) for metastatic (p = 0.002). In metastatic patients, 1 year OS was significantly influenced by chemotherapy response: 67% (95CI% 29–100) for those who responded or had stable disease (n = 7), and 18% (95CI% 0–41) for patients with progressive disease (n = 11), p 0.002. The surgical complete remission (SCR) status was pivotal in lo...
ESMO Open, 2021
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clin... more Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
Modern Pathology, 2020
Fusions involving NTRK1, NTRK2, and NTRK3 are oncogenic drivers occurring in a spectrum of mesenc... more Fusions involving NTRK1, NTRK2, and NTRK3 are oncogenic drivers occurring in a spectrum of mesenchymal neoplasms ranging from benign to highly malignant tumors. To gain further insights into the staining profile with the pan-TRK assay, we analyzed a large number of soft tissue sarcomas and correlated our findings with molecular testing. Additionally, we expand the spectrum of NTRK-fusion tumors by reporting a mesenchymal lesion in the lung as well as a mesenchymal skin lesion in the spectrum of benign fibrous histiocytoma with NTRK—fusion. We retrospectively reviewed soft tissue sarcomas diagnosed at the Diagnostic and Research Institute of Pathology, Medical University of Graz, between 1999 and 2019, and cases from the consultation files of one of the authors (BLA). In total, 494 cases were analyzed immunohistochemically with pan-TRK antibody (clone EPR17341, RTU, Roche/Ventana) and positive cases (defined as any cytoplasmic/nuclear staining in more than 1% of tumor cells) underwen...
European Journal of Cancer, 2020
No studies extensively compared the young adults (YA, 18e39 years), middle-aged (40e69 years), an... more No studies extensively compared the young adults (YA, 18e39 years), middle-aged (40e69 years), and elderly (70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-aged and elderly population in patients with primary high-grade eSTS treated with curative intent. Methods: In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression.
Journal of Bone and Joint Surgery, 2020
Background: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are r... more Background: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. Methods: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. Results: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years ...
World Journal of Clinical Oncology, 2020
Author contributions: All authors contributed to the present manuscript by performing literature ... more Author contributions: All authors contributed to the present manuscript by performing literature review, summarizing data, compiling tables, and writing as well as reviewing the manuscript.
Journal of Surgical Oncology, 2020
Background and ObjectivesAbdominal metastases (AM) from soft tissue sarcoma (STS) are rare and pr... more Background and ObjectivesAbdominal metastases (AM) from soft tissue sarcoma (STS) are rare and prognosis is poor. The aims of the study were to (a) identify risk factors for the development of AM and to (b) investigate the outcome of AM‐patients.MethodsSeven‐hundred‐sixty‐nine STS‐patients with localised disease at diagnosis treated at three tumour centres (2000‐2016) were retrospectively included (409 males; mean age, 55.6 years [range, 8‐96 years]; median follow‐up, 4.1 years [interquartile‐range, 2.5‐6.6 years]).ResultsTwo‐hundred‐two patients (26.3%) developed secondary metastases, and 24 of them AM (3.1%). Ten patients developed first AM (FAM) after a mean of 2.4 years and 14 patients late AM (LAM, after being diagnosed with metastases to other sites) after a mean of 2.0 years. Patients with liposarcoma had a significantly higher risk of developing AM (P = .007), irrespective of grading. There was no difference in post‐metastasis‐survival (PMS) between patients with AM at any t...
Acta Biomaterialia, 2020
, A lean magnesium-zinc-calcium alloy ZX00 used for bone fracture stabilization in a large growin... more , A lean magnesium-zinc-calcium alloy ZX00 used for bone fracture stabilization in a large growing-animal model,
Cells
Particle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the ... more Particle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the side effects of radiation oncology, especially in pediatric patients. To investigate the influence of PT on growing bone, we exposed an organotypic rat ex vivo femur culture model to PT. After irradiation, histological staining, immunohistochemical staining, and gene expression analysis were conducted following 1 or 14 days of in vitro culture (DIV). Our data indicated a significant loss of proliferating chondrocytes at 1 DIV, which was followed by regeneration attempts through chondrocytic cluster formation at 14 DIV. Accelerated levels of mineralization were observed, which correlated with increased proteoglycan production and secretion into the pericellular matrix. Col2α1 expression, which increased during the cultivation period, was significantly inhibited by PT. Additionally, the decrease in ColX expression over time was more pronounced compared to the non-IR control. The chondrogen...
BMC Musculoskeletal Disorders
Background Despite numerous scientific investigations, the tribological advantages of mobile bear... more Background Despite numerous scientific investigations, the tribological advantages of mobile bearing inserts have not been sustainably confirmed or refuted for modern knee prostheses in clinical studies. The purpose of this study was to compare fixed and mobile bearing inserts in order to draw conclusions regarding clinical benefits. Methods The present prospective single center cohort study of 2 non-randomized stratified groups consisted of 67 patients. All included patients received cemented total knee arthroplasty (Attune®) due to osteoarthritis. 34 patients were treated with a mobile and 33 patients with a fixed insert. The WOMAC score and the Visual Analogue Scale was used for the subjective assessment of success, while the Knee-Society-Score was used considering the Range of Motion for the objective assessment. The subjective and the clinical scores showed improvements for both compared groups postoperatively at 2 years of minimum follow-up. Results The overall postoperative r...
BMC Cancer
Background Although chondrosarcoma is the second most common primary malignant bone tumor, treatm... more Background Although chondrosarcoma is the second most common primary malignant bone tumor, treatment options are limited due to its extensive resistance to a chemo- and radiation therapy. Since shikonin has shown potent anticancer activity in various types of cancer cells, it represents a promising compound for the development of a new therapeutic approach. Methods The dose-relationships of shikonin and its derivatives acetylshikonin and cyclopropylshikonin on two human chondrosarcoma cell lines were measured using the CellTiter-Glo®. The changes in the cell cycle were presented by flow cytometry. Protein phosphorylation and expression apoptotic markers, MAPKs and their downstream targets were analyzed using western blotting and gene expression were evaluated using RT-qPCR. Results Chondrosarcoma cells showed a dose-dependent inhibition of cell viability after treatment with shikonin and its derivatives, with the strongest effect for shikonin and IC50 values of 1.3 ± 0.2 µM. Flow cy...
International Journal of Medical Sciences, 2021
Background: Periprosthetic joint infection (PJI) represents a serious complication following tota... more Background: Periprosthetic joint infection (PJI) represents a serious complication following total knee arthroplasty. In the setting of chronic infections, the two-staged approach has traditionally been the preferred treatment method. The aim of this study was to determine the optimal period of rest between the first and second stage. Furthermore, we analyzed potentially outcome-relevant parameters, such as general and local conditions and the presence of difficult-to-treat or unidentified microorganisms, with regard to their impact on successful treatment of PJI. Patients and Methods: We performed a retrospective analysis of prospectively collected data for all patients treated for PJI at our institution. Seventy-seven patients who had undergone two-stage revision arthroplasty for PJI of the knee were included into the study. Antibiotic-loaded cement spacers were used for all patients. Results: After a median follow-up time of 24.5 months, infection had reoccurred in 14 (18.7%) patients. A prolonged spacer-retention period of more than 83 days was related to a significantly higher proportion of reinfections. Furthermore, significant compromising local conditions of the prosthetic tissue and surrounding skin, as well as repeated spacer-exchanges between first-and second-stage surgery, negatively influenced the outcome. Neither the patients' age nor gender exerted a significant influence on the outcome regarding reinfection rates for patients' age or gender. Conclusions: We observed the best outcome regarding infection control in patients who had undergone second-stage surgery within 12 weeks after first-stage surgery. Nearly 90% of these patients stayed free from infection until the final follow-up. An increased number of performed spacer-exchanges and a bad local extremity grade also had a negative impact on the outcome.
Cartilage, synovium and bone, 2018
USA). At least three random fields were evaluated for each type of ST, quantifying the expression... more USA). At least three random fields were evaluated for each type of ST, quantifying the expression of INHBA, TNF-a, MMP12 and CD209 in all segmented CD163 + macrophages. Macrophages density was normalised based on selected tissue area(mm 2). After background subtraction, data were plotted using Graph-Pad software (GraphPad Software, La Jolla, CA, USA). Results: CD163 + sublining (SL) macrophages from UA-RA expressed abundantly the INHBA-encoded activin A, whereas TNFa and MMP12 were variably detected. Regarding the M-CSF-associated marker CD209, 2 populations of CD163 + macrophages were found in the SL of UA-RA, CD163 + CD209 + and the other CD163 + CD209-, with higher than 100 arbitrary units (au) for CD163 + CD209 + and lower than 100 au for CD163 + CD209-. Similarly, INHBA, MMP12 and TNFa expression and 2 populations of CD209 were detected in CD163 + macrophages from UA-PsA. Macrophage density was also found comparable between UA, with 650/mm 2 in UA-RA and 649/mm 2 in UA-PsA. Quantification of the above indicated markers in CD163 +ST macrophages from established RA and PsA revealed similar levels of INHBA, TNFa, MMP12 and CD209 than those from UA-RA and UA-PsA. Conclusions: This study shows for the first time that the polarisation state of ST CD163 + macrophages in UA progressing to RA and PsA is similar to that of established RA and PsA in terms of INHBA, MMP12, TNFa and CD209 expression. Therefore, the inflammatory polarisation state of macrophages is similar in RA and PsA and it is already detected at the earlier steps.
Osteoarthritis and Cartilage, 2016
Journal of Orthopaedic Research, 2014
The development of osteoarthritis (OA) depends on genetic and environmental factors, which influe... more The development of osteoarthritis (OA) depends on genetic and environmental factors, which influence the biology of the chondrocyte via epigenetic regulation. Changes within the epigenome might lead the way to discovery of new pathogenetic pathways. We performed a genome-wide methylation screening to identify potential differences between paired mild and severe osteoarthritic human cartilage. Sixteen female patients suffering from OA underwent total knee joint replacement. Cartilage specimens collected from corresponding macroscopically undamaged and from damaged areas were processed for DNA extraction and histology to evaluate the histological grading of the disease. Paired specimens were analysed for the methylation status of the whole genome using human promoter microarrays (Agilent, Santa Clara, CA). Selected target genes were then validated via methylation-specific qPCR. One thousand two hundred and fourteen genetic targets were identified differentially methylated between mild and severe OA. One thousand and seventy of these targets were found hypermethylated and 144 hypomethylated. The descriptive analysis of these genes by Gene Ontology (GO), KEGG pathway and protein domain analyses points to pathways of development and differentiation. We identified a list of genes which are differently methylated in mild and severe OA cartilage. Within the pathways of growth and development new therapeutic targets might arise by improving our understanding of pathogenetic mechanisms in OA.
The variety of radiographic diagnostics used to diagnose pain localised close to metal implants i... more The variety of radiographic diagnostics used to diagnose pain localised close to metal implants is still limited. Especially magnetic resonance results can not be analysed because of artefacts. In this article we present for the first time a direct correlation between an increase in skin temperature and existent frontal (anterior) knee pain after implantation of artificial knee joints measured with thermography. In a standardised way 26 knees were analysed. Thermographic photos were taken from frontal, inner (medial) and outer (lateral) directions with a computer-assisted infrared thermograph. Temperatures in locations with pain were significantly higher compared to the reference field in inner location (median 0.95 °C, p=0.0043), as well as in outer location (median 0.5 °C, p=0.032). Median temperature difference between pain localization and localizations without pain was 0.7 °C and ranged from 0.1 °C to 1.7 °C. In the receiver operating characteristic (ROC) analysis the sensitivity of this method was 1.0 and specificity was 0.917. The evidence of a significant increase in skin temperature on the painful sites opens up the possibility to localize and assess pain more precisely in patients with joint prosthesis. We consider this novel, rapid, inexpensive and non-invasive technology to posses the potential to become a useful and objective tool for diagnosis of pain and inflammation and to generate digital data that can be stored and analysed in clinical practice.
Scientific Reports
The aims of this study were to (1) assess reliability of leg length discrepancy (LLD) measurement... more The aims of this study were to (1) assess reliability of leg length discrepancy (LLD) measurements at different anatomical landmarks, (2) longitudinally investigate LLD in patients within the first year following total hip arthroplasty (THA) and to (3) correlate changes in LLD with functional outcome. Ninety-nine patients with short stem THA (53.3% males, mean age: 61.0 ± 8.1 years) were prospectively included. Upright pelvic anteroposterior (a.p.) radiographs taken at 6 timepoints (preoperatively, discharge, 6, 12, 24, 52 weeks postoperatively) were used to assess LLD at 5 anatomical landmarks (iliac crest, upper sacroiliac joint, lower sacroiliac joint, tear drop figure, greater trochanter). WOMAC and Harris Hip Score (HHS) were obtained preoperatively and at 6 and 52 weeks. LLD measures significantly increased in the initial phase following THA, from discharge to 6 weeks postoperatively and remained constant thereafter. Documentation of LLDs is dependent on measurement site: LLDs...
BMC Cancer
Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft ti... more Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate. Questions/purpose This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. Methods This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF. Results Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3–85) were inclu...
Wiener klinische Wochenschrift, 2021
SummarySoft tissue sarcomas (STS) represent a small group of adult solid malignancies, with risk ... more SummarySoft tissue sarcomas (STS) represent a small group of adult solid malignancies, with risk factors such as environmental factors, genetic predisposition, and prior radiotherapy. In STS patients with a novel swelling, differential diagnoses include recurrence, second primary cancer, metastasis from unknown primary cancer, and radiation-associated STS, the latter usually occurring approximately 10 years after radiotherapy. We present the case of a 64-year-old male patient with pleomorphic rhabdomyosarcoma, who underwent resection and radiotherapy. The patient presented again 5 years later with painful swelling in the area of the prior sarcoma, raising suspicion of recurrence. Resection was performed and a diagnosis of pleomorphic sarcoma (not otherwise specified [NOS]) was made. The patient was treated with radiotherapy and remained sarcoma-free for the following 7 years. A molecular analysis of both neoplasms, using RNA next-generation sequencing, did not detect any specific fu...
Orthopaedic Surgery, 2020
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Scientific Reports, 2020
Angiosarcoma of bone (B-AS) is a rare malignant tumor of vascular origin. The aim of this retrosp... more Angiosarcoma of bone (B-AS) is a rare malignant tumor of vascular origin. The aim of this retrospective study is to report on treatments and prognosis. Data were collected from the EMSOS website. 80 patients in 9 centers included: 51 male/29 female; median age 54 years (range 17 to 92); 56% with localized disease, 44% metastatic. Primary tumor surgery: 76% (30% amputation, 26% intralesional margins); radiotherapy (RT): 41%; chemotherapy (CT): 47% (56% in metastatic, 41% in localized cases). With a median follow-up of 31 months (range 40 to 309), 5-year overall survival (OS) was 27% (95%CI 16–30): 41% (95%CI 25–56) for localized patients, and 8% (95%CI 0–20) for metastatic (p = 0.002). In metastatic patients, 1 year OS was significantly influenced by chemotherapy response: 67% (95CI% 29–100) for those who responded or had stable disease (n = 7), and 18% (95CI% 0–41) for patients with progressive disease (n = 11), p 0.002. The surgical complete remission (SCR) status was pivotal in lo...
ESMO Open, 2021
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clin... more Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
Modern Pathology, 2020
Fusions involving NTRK1, NTRK2, and NTRK3 are oncogenic drivers occurring in a spectrum of mesenc... more Fusions involving NTRK1, NTRK2, and NTRK3 are oncogenic drivers occurring in a spectrum of mesenchymal neoplasms ranging from benign to highly malignant tumors. To gain further insights into the staining profile with the pan-TRK assay, we analyzed a large number of soft tissue sarcomas and correlated our findings with molecular testing. Additionally, we expand the spectrum of NTRK-fusion tumors by reporting a mesenchymal lesion in the lung as well as a mesenchymal skin lesion in the spectrum of benign fibrous histiocytoma with NTRK—fusion. We retrospectively reviewed soft tissue sarcomas diagnosed at the Diagnostic and Research Institute of Pathology, Medical University of Graz, between 1999 and 2019, and cases from the consultation files of one of the authors (BLA). In total, 494 cases were analyzed immunohistochemically with pan-TRK antibody (clone EPR17341, RTU, Roche/Ventana) and positive cases (defined as any cytoplasmic/nuclear staining in more than 1% of tumor cells) underwen...
European Journal of Cancer, 2020
No studies extensively compared the young adults (YA, 18e39 years), middle-aged (40e69 years), an... more No studies extensively compared the young adults (YA, 18e39 years), middle-aged (40e69 years), and elderly (70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-aged and elderly population in patients with primary high-grade eSTS treated with curative intent. Methods: In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression.
Journal of Bone and Joint Surgery, 2020
Background: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are r... more Background: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. Methods: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. Results: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years ...
World Journal of Clinical Oncology, 2020
Author contributions: All authors contributed to the present manuscript by performing literature ... more Author contributions: All authors contributed to the present manuscript by performing literature review, summarizing data, compiling tables, and writing as well as reviewing the manuscript.
Journal of Surgical Oncology, 2020
Background and ObjectivesAbdominal metastases (AM) from soft tissue sarcoma (STS) are rare and pr... more Background and ObjectivesAbdominal metastases (AM) from soft tissue sarcoma (STS) are rare and prognosis is poor. The aims of the study were to (a) identify risk factors for the development of AM and to (b) investigate the outcome of AM‐patients.MethodsSeven‐hundred‐sixty‐nine STS‐patients with localised disease at diagnosis treated at three tumour centres (2000‐2016) were retrospectively included (409 males; mean age, 55.6 years [range, 8‐96 years]; median follow‐up, 4.1 years [interquartile‐range, 2.5‐6.6 years]).ResultsTwo‐hundred‐two patients (26.3%) developed secondary metastases, and 24 of them AM (3.1%). Ten patients developed first AM (FAM) after a mean of 2.4 years and 14 patients late AM (LAM, after being diagnosed with metastases to other sites) after a mean of 2.0 years. Patients with liposarcoma had a significantly higher risk of developing AM (P = .007), irrespective of grading. There was no difference in post‐metastasis‐survival (PMS) between patients with AM at any t...