Reconstruction of the anatomic defect following extra-articular shoulder resection is a challenging problem, particularly in cases when function of the deltoid muscle and rotator cuff are compromised. Standard reconstruction techniques often result in either instability or rigidity. Constrained implants have been used to overcome these problems; however, they have been associated with a high rate of aseptic loosening. Recently, a novel double-constrained implant has been introduced, yielding promising functional results. Nonetheless, this implant exhibited a cosmetic defect related to protrusion of the humeral component that becomes apparent with time as result of surrounding muscle atrophy. An updated improved design of the implant has been developed to counteract this.We report the case of a 15-year-old patient who underwent an extra-articular (Malawer type V) shoulder resection due to osteosarcoma and received an innovated custom-made double-constrained implant. Moreover, we describe a new modification of the Malawer utilitarian approach to the shoulder girdle that enhances tumor visibility and allows safer dissection. The patient recovered well with satisfactory outcomes at 18 months follow-up, highlighting the potential benefits of this implant design and surgical approach.

• MeSH
• Arthroplasty, Replacement, Shoulder * methods   MeSH
• Humans MeSH
• Adolescent MeSH
• Bone Neoplasms * surgery   pathology   MeSH
• Shoulder Prosthesis * MeSH
• Osteosarcoma * surgery   pathology   MeSH
• Proof of Concept Study MeSH
• Prognosis MeSH
• Prosthesis Design * MeSH
• Shoulder Joint * surgery   pathology   MeSH
• Treatment Outcome MeSH
• Plastic Surgery Procedures * methods   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

BACKGROUND: Periprosthetic infections pose a devastating complication in skeletally immature patients treated for an orthopaedic oncological condition. Reconstructive approaches to revision procedures are often limited, and many cases still require amputation. CASE PRESENTATION: In this report, we present our unique experience with the bio-expandable MUTARS® BioXpand prosthesis, utilized during the second stage of a revision surgery in an adolescent female patient. Initially, the patient underwent reconstruction using a conventional endoprosthesis following the resection of a high-grade distal femur osteosarcoma; however, she developed a deep infection six months later. During a two-stage revision procedure, the infection was successfully eradicated at the cost of loss of growth potential at also the site of proximal tibia. The initial 5 cm limb-length discrepancy was restored through the application of bioexpandable endoprosthesis, which allowed for an 8 cm gain in bone stock. At the last follow-up appointment, the patient was fully weight-bearing and demonstrated excellent clinical outcomes, with no evidence of infection or tumor recurrence. CONCLUSION: This successful limb-salvage procedure indicates that bioexpandable endoprosthesis may serve as a viable and effective reconstructive option in revision surgery for skeletally immature individuals.

• MeSH
• Femur * surgery   pathology   MeSH
• Prosthesis-Related Infections * surgery   etiology   MeSH
• Humans MeSH
• Adolescent MeSH
• Femoral Neoplasms * surgery   pathology   MeSH
• Bone Neoplasms * surgery   pathology   MeSH
• Osteosarcoma * surgery   pathology   MeSH
• Prognosis MeSH
• Reoperation MeSH
• Limb Salvage * methods   MeSH
• Plastic Surgery Procedures * methods   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

PURPOSE: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting. EXPERIMENTAL DESIGN: Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphologic features could serve as a potential marker for OS in the neoadjuvant setting. RESULTS: Excellent correlation between the trained network and pathologists was obtained for the quantification of necrosis content (R2 = 0.899; r = 0.949; P < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). The morphology-based supervised approach predicted OS; P = 0.0028, HR = 2.43 (1.10-5.38). The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS [log-2 hazard ratio (lg2 HR); -2.366; -1.164; -1.175; 95% confidence interval, (-2.996 to -0.514)]. Viable/partially viable tumor and fat necrosis were associated with worse OS [lg2 HR; 1.287; 0.822; 0.828; 95% confidence interval, (0.38-1.974)]. CONCLUSIONS: Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphologic biomarkers specific to the necrotic and tumor regions, which could serve as predictors.

• MeSH
• Deep Learning MeSH
• Child MeSH
• Adult MeSH
• Kaplan-Meier Estimate MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Bone Neoplasms * mortality   pathology   MeSH
• Necrosis * MeSH
• Neoadjuvant Therapy * methods   MeSH
• Neural Networks, Computer * MeSH
• Osteosarcoma * mortality   pathology   therapy   MeSH
• Prognosis MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The aim of this study was to develop multifunctional magnetic poly(ε-caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three-step approach. Then, a series of PCL-based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow-derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS-2 osteoblast-like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention.

• MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Escherichia coli drug effects   MeSH
• Bone and Bones MeSH
• Rats MeSH
• Ascorbic Acid * chemistry   pharmacology   MeSH
• Humans MeSH
• Magnetite Nanoparticles chemistry   MeSH
• Cell Line, Tumor MeSH
• Nanocomposites chemistry   MeSH
• Osteoblasts metabolism   cytology   MeSH
• Osteosarcoma pathology   MeSH
• Polyesters * chemistry   MeSH
• Staphylococcus aureus * drug effects   growth & development   MeSH
• Materials Testing MeSH
• Tissue Engineering * MeSH
• Tissue Scaffolds chemistry   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Ifosfamid je protinádorový lék ze skupiny alkylačních cytostatik, jenž zabudováním alkylové skupiny do řetězce DNA naruší replikaci nukleotidových řetězců. Jedná se sice již o historický medikament, jehož vznik se datuje do 70. let minulého století, ale stále se s ním běžně setkáváme v onkologické praxi, např. u nádorů kostí, sarkomů měkkých tkání, ale i recidivujících nonhodgkinských lymfomů či lymfomů CNS. Tato terapie je zatížena řadou nežádoucích účinků, z nichž ke klasickým akutním nežádoucím účinkům patří reverzibilní encefalopatie a hemoragická cystitida. V této kazuistice z německé kliniky bych se rád zaměřil na renální toxicitu ifosfamidu, respektive poškození proximálního tubulu, v jehož důsledku se může rozvinout až tzv. Fanconiho synrom.

Ifosfamide is an anticancer drug from the group of alkylating cytostatics that disrupts the replication of nucleotide chains by incorporating an alkyl group into the DNA chain. Although it is a historical drug dating back to the 1970s, it is still commonly encountered in cancer treatment, e. g. in bone tumours, sarcomas and recurrent non-Hodgkin's lymphomas or CNS lymphomas. This therapy is burdened with a number of adverse effects, of the classic acute side effects include reversible encephalopathy and hemorrhagic cystitis. In this case report, I would like to focus on the renal toxicity of ifosfamide or damage to the proximal tubule, which may result in the development of Fanconi syndrome.

• MeSH
• Acidosis chemically induced   etiology   MeSH
• Adult MeSH
• Etoposide administration & dosage   adverse effects   MeSH
• Sarcoma, Ewing * diagnostic imaging   drug therapy   complications   physiopathology   MeSH
• Fanconi Syndrome * chemically induced   pathology   MeSH
• Ifosfamide administration & dosage   adverse effects   MeSH
• Drug Therapy, Combination methods   MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Recent studies have highlighted the significant role of 5-hydroxymethylcytosine (5hmC) in carcinogenesis. However, the specific role of 5hmC in osteosarcoma (OS) remains largely unexplored. The-re-fore, this study aimed to investigate the function of 5hmC and TET3 in OS. In this study, we found a decreased total level of 5hmC in OS tissues. The expression of the TET3 protein was also decreased in OS. Importantly, the decreased levels of TET3 were associated with a decreased disease-free survival (DFS) rate in patients. To investigate the role of TET3 and 5hmC in OS, we manipulated the levels of TET3 in MG-63 cells. Silencing TET3 in these cells resulted in a twofold increase in proliferation. Additio-nally, the level of 5hmC decreased in these cells. Con-versely, over-expression of TET3 in MG-63 cells led to the expected inhibition of proliferation and invasion, accompanied by an increase in 5hmC levels. In conclusion, both 5hmC and TET3 protein levels were decreased in OS. Additionally, the over-expression of TET3 inhibited the proliferation of MG-63 cells, while the suppression of TET3 had the opposite effect. These findings suggest that decreased levels of 5hmC and TET3 may serve as potential markers for OS.

• MeSH
• 5-Methylcytosine * analogs & derivatives   metabolism   MeSH
• DNA Demethylation * MeSH
• Dioxygenases * metabolism   MeSH
• Epigenesis, Genetic * MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Bone Neoplasms genetics   metabolism   pathology   MeSH
• Osteosarcoma genetics   metabolism   pathology   MeSH
• Cell Proliferation * MeSH
• Proto-Oncogene Proteins metabolism   genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.

• MeSH
• Biological Specimen Banks MeSH
• Sarcoma, Ewing * therapy   pathology   diagnosis   MeSH
• Humans MeSH
• Biomarkers, Tumor MeSH
• Bone Neoplasms * therapy   pathology   MeSH
• Specimen Handling * methods   standards   MeSH
• Osteosarcoma * therapy   pathology   diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• Europe MeSH

The case report discusses diagnostic approach and course of the disease of a 13-year-old female with osteosarcoma of the knee, which has presented as unilateral, escalating night pain in knee. Then briefly summarizes essential parts of patient's history used in the differential diagnosis of musculoskeletal pain in children and adolescents and the use of basic imaging methods when malignant disease is suspected.

Kazuistika pojednává o diagnostice a průběhu onemocnění 13leté dívky s osteosarkomem pravého kolene, který se primárně prezentoval jednostrannými stupňujícími se nočními bolestmi. Následně krátce shrnuje podstatné anamnestické údaje v diferenciální diagnostice muskuloskeletálních bolestí dětí a mladistvých a využití základních zobrazovacích metod při podezření na maligní onemocnění.

• MeSH
• Diagnostic Imaging MeSH
• Humans MeSH
• Neoplasm Metastasis diagnostic imaging   MeSH
• Adolescent MeSH
• Musculoskeletal Pain diagnosis   etiology   MeSH
• Osteosarcoma * diagnosis   pathology   MeSH
• Tomography, Emission-Computed MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

PURPOSE OF THE STUDY: Managing bone tumours is complex, relying on limited evidence, expert opinions, and retrospective reviews. Multidisciplinary approaches and early diagnosis are crucial for better outcomes, especially in young patients with growing skeletons. The aim of this systemic review and meta-analysis is to give a comprehensive review of common malignant tumors affecting long bones in children and adolescents. MATERIAL AND METHODS: A PubMed/Medline search for "primary malignant long bone tumours in children" initially retrieved 1120 papers, which were subsequently narrowed down to 110 articles based on inclusion and exclusion criteria. These articles were reviewed, focusing on clinical presentation, diagnostic workup, treatment options, surgical planning, and variations in presentation, including rare tumours. The two most commonly reported tumours were osteosarcoma and Ewing sarcoma, leading to the division of studies into five groups. The inclusion criteria encompassed malignancies in patients aged 2-25 years, work-up, imaging, surgical treatment, rare tumour case reports, and surgical management principles, resulting in a heterogeneous group of articles. To enhance categorisation, it was clarified that studies with 10 or more cases were considered retrospective reviews. RESULTS: Reviewing of results thus demonstrate that the two likely tumours in children under consideration were osteosarcoma and Ewing sarcoma. Their presentation findings and clinical features were discussed in detail in the review. It is worth noting here that in case of differential diagnosis this should be the first on the list. DISCUSSION AND CONCLUSIONS: Although focus of literature is more on the two most common tumours. However, rare tumours should be considered as they can mimic these common tumors. KEY WORDS: primary, malignant, bone tumors, children, adolescent.

• MeSH
• Child MeSH
• Sarcoma, Ewing * diagnosis   therapy   MeSH
• Humans MeSH
• Adolescent MeSH
• Bone Neoplasms * diagnosis   pathology   MeSH
• Osteosarcoma * diagnosis   therapy   MeSH
• Child, Preschool MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

The last 2 decades have attended a dynamic evolution in the nosology of poorly differentiated sinonasal tract malignancies, with several new molecularly defined entities having been described in addition to delineation of the genetic driver/s of some established older entities. These discoveries, however, mostly concerned epithelial-derived neoplasms (carcinomas). Adamantinoma-like Ewing sarcoma and biphenotypic sinonasal sarcoma are the major representatives of the newly defined mesenchymal categories. The colorectal cancer associated 2 (COLCA2) has been discovered recently as a colorectal cancer risk gene locus, but fusions involving this gene have not been well characterized. We, herein, describe clinicopathologic and molecular features of a novel sinonasal sarcoma characterized by undifferentiated spindle/round cell morphology and defined by recurrent EWSR1::COLCA2 fusions. All patients (n=5) were adults (3 female and 2 male) with a median age of 46 years (range, 23 to 60 y). The tumors originated in different subsites of the sinonasal tract with frequent multisite involvement. Original diagnoses were undifferentiated or unclassified round cell/spindle cell neoplasm/sarcoma (n=4) and neuroendocrine carcinoma (n=1). Surgery with or without adjuvant chemoradiation was the treatment in all cases. At the last follow-up, 1 patient developed multiple local recurrences over 21 years and another developed local recurrence and distant metastasis to bone 27 months after diagnosis. A third patient developed local recurrence 11 months later. Two patients were disease-free at 23, and 24 months. Histology showed nondescript highly cellular neoplasms with an admixture of spindled and round cells disposed into solid sheets and fascicles with brisk mitotic activity. Immunohistochemistry was negative for all lineage-specific markers with only limited focal membranous CD99 (4 of 5 cases) and weak pankeratin (1 of 5 cases) expression. Targeted RNA sequencing revealed an EWSR1::COLCA2 fusion, verified by EWSR1 fluorescence in situ hybridization, in all cases. This series identifies a novel member in the undifferentiated spindle/round cell sarcoma category with strong predilection for the sinonasal tract. None of >10,000 epithelial and mesenchymal neoplasms tested at the authors' centers during the same period showed this fusion, highlighting rarity of tumors carrying this gene fusion. Accordingly, molecular testing of unclassified sinonasal malignancies/sarcomas showing round and spindle cell morphology is recommended to enhance the identification and further characterization of this entity.

• MeSH
• Adult MeSH
• Sarcoma, Ewing * genetics   MeSH
• Oncogene Proteins, Fusion genetics   MeSH
• In Situ Hybridization, Fluorescence MeSH
• Colorectal Neoplasms * MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Biomarkers, Tumor genetics   MeSH
• Neoplasm Proteins genetics   MeSH
• Soft Tissue Neoplasms * MeSH
• Paranasal Sinus Neoplasms * MeSH
• Paranasal Sinuses * pathology   MeSH
• RNA-Binding Protein EWS genetics   MeSH
• Sarcoma * genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH