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Background Malignant tumors occurring around both the spinal column and posterior chest wall are uncommon. Surgical resection of chest wall tumors adjacent to the spinal column is still challenging due to the surrounding anatomical structures. The purpose of the present study was to evaluate the long-term outcomes of surgical management in malignant tumors involving the spinal column and posterior chest wall. Methods Between 1999 and 2007, 10 consecutive patients underwent en bloc resection combined with the posterior chest wall in the treatment of malignant tumors around the spinal column. There were 6 males and 4 females with a mean age at the surgery of 40.9 years old (range, 14–62 years old). The mean postoperative follow-up period was 159.7 months (range, 84–245 months). The clinical history, physical examination, laboratory data, radiological findings, and operative findings for each patient were retrospectively reviewed. Results All surgeries were performed via a combined anterior and posterior approach. The mean numbers of partially resected vertebrae and ribs were 3.1 and 4.1, respectively. Lower or upper lobectomy was performed in four patients, and the diaphragm was partially resected in two patients. The surgical margin was wide in seven patients and marginal in two patients. Although five patients had postoperative respiratory problem, all patients improved immediately without life-threatening complications. There were no patients with respiratory insufficiency after surgery. One patient with osteosarcoma died of lung metastases 99 months after surgery. At the final follow-up, only one patient had local recurrence, five had been continuously disease-free, and three were alive with no evidence of disease. Conclusions En bloc resection and reconstruction in selected patients with malignant tumors involving both the spinal column and posterior chest wall demonstrated good long-term results for local control and the respiratory function.

The final stage of spine neoplasm diagnostics is histological examination. In order to obtain the tissue from neoplasm punction biopsy is used.Objective: to assess the efficacy of punctional biopsy with further pathohistological examination in patients with neoplasm in thoracic and lumbar spine.Methods: we analyzed 259 case histories of patients with pathological spine changes.Results: punction biopsy was made in 238 patients (89 %). In 30 (11 %) patients it was no effective because of the large amount of obtained material, in 27 (10 %) pathohistological diagnosis was not established. Pepeated biopsy was made in these cases. As a result at primary and secondary biopsies the diagnosis was confirmed in 95.5 %.Conclusions: punctional biopsy with pathohystological examination is integral part of diagnostic process at spine neoplasm. It allows to obtain enough material for studying (inspite of the dense of tissues) to decrease the risks of contamination of surrounded tissues. Such minimalinvasive method gives possibility to use it in patients with comorbidities. Most of primary spine cancer is represented by myeloma and malignant lymphoma. Episodic were cases of hondrosarcoma, osteosarcoma and fibrosarcoma, when the lesion was spread on one or two vertebrae. Most frequent non malignant lesions were haemangioma and eosino­philic granuloma. Metastatic disease were revealed in 74 (28 %) of patients and often appeared in cases of low grade cancer and adenocarcinoma., Заключительным этапом диагностики опухолевых заболеваний позвоночника является гистологическое исследование. Для получения ткани из очага поражения используют пункционную биопсию.Цель: оценить эффективность пункционной биопсии (с последующим патогистологическим исследованием) у пациентов с новообразованиями в грудном и поясничном отделах позвоночника.Методы: проанализировано 259 историй болезни пациентов с патологическими изменениями в позвоночнике.Результаты: пункционная биопсия выполнена всем больным. При этом у 30 (11 %) человек она оказалась неэффективной из-за небольшого количества полученного материала, а у 27 (10 %) не установлен патогистологический диагноз. Этим 57 (21 %) пациентам проведена повторная биопсия очага поражения. В результате первичной и вторичной биопсии у 95,5 % обследованных патоморфологически диагноз подтвержден.Выводы: пункционная биопсия с последующим патогистологическим исследованием является неотъемлемым этапом диагностического процесса при новообразованиях позвоночника. Она позволяет получить достаточное количество материала (независимо от плотности ткани) для изучения и уменьшить риск контаминации окружающих тканей. Малоинвазивность метода дает возможность использовать его у пациентов с тяжелыми сопутствующими соматическими патологиями. Большинство злокачествен­ных первичных поражений позвоночника представлены плазмоклеточной миеломой (миеломной болезнью) и злокачественной лимфомой; одиночными были случаи хондросаркомы, остеосаркомы и фибросаркомы, когда очаг поражения распространялся на один или два позвонка. Наиболее часто обнаружены такие доброкачественные поражения позвоночника, как гемангиома и эозинофильная гранулема. Метастатические изменения в позвоночнике выявлены у 74 (28 %) пациентов и чаще всего развивались в случае низкодифференцированного рака и аденокарциномы., Заключним етапом діагностики пухлинних захворювань хребта є гістологічне дослідження. Для отримання тканини з вогнища ураження використовують пункційну біопсію.Мета: оцінити ефективність пункційної біопсії (з подальшим патогістологічним дослідженням) у пацієнтів із новоутвореннями в грудному та поперековому відділах хребта.Методи: проаналізовано 259 історій хвороби пацієнтів із патологічними змінами в хребті.Результати: пункційну біопсію виконано всім хворим. При цьому в 30 (11 %) осіб вона виявилася неефективною через невелику кількість отриманого матеріалу, а у 27 (10 %) не встановлено патогістологічний діагноз. Цим 57 (21 %) пацієнтам проведено повторну біопсію вогнища ураження. У результаті первинної та вторинної біопсії у 95,5 % обстежених патоморфологічно діагноз підтверджений.Висновки: пункційна біопсія з наступним патогістологічним дослідженням є невід’ємним етапом діагностичного процесу в разі новоутворень хребта. Вона дозволяє отримати достатню кількість матеріалу (незалежно від щільності тканини) для вивчення та зменшити ризик контамінації прилеглих тканин. Малоінвазивність методу дає можливість використовувати його в пацієнтів із важкими супутніми соматичними патологіями. Більшість злоякісних первинних уражень хребта представлені плазмоклітинною мієломою (мієломною хворобою) і злоякісною лімфомою; поодинокими були випадки хондросаркоми, остеосаркоми та фібросаркоми, коли вогнище ураження поширювалося на один або два хребця. Найчастіше визначали такі доброякісні ураження хребта, як гемангіома й еозинофільна гранульома. Метастатичні зміни в хребті виявлено в 74 (28 %) пацієнтів і найчастіше розвивалися в разі низькодиференційованого раку й аденокарциноми.

Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo. In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved., Graphical abstract Image 1, Highlights • The PDA-ALN-DOX presented high bone targeting property, photothermal conversion efficiency, drug loading capacity, and multimodal imaging modalities. • CPT is a more efficient and convenient therapy for bone tumors.

This paper reports four cases of osteosarcoma of the jaw, a rare malignant bone tumor in the oral and maxillofacial region. Two patients were males and two were females. The age at the first visit ranged 55–69 years (average age, 63.8 years). Three and one patients had a tumor in the mandible and the maxilla, respectively. One mandibular patient had a history of radiotherapy for laryngeal cancer. Radiologically, two cases were of the osteolytic type, and two were of the osteosclerotic type. Two cases of the osteolytic type were diagnosed as malignant tumors, while the other two cases of the osteosclerotic type were as benign lesions (e.g., epulis osteoplastica and osteomyelitis). Pathologically, three and one cases were classified as conventional (osteoblastic type) and secondary (radiation-induced) osteosarcomas, respectively. All patients underwent surgical tumor resection without any adjunctive treatments. Consequently, one patient had no recurrence for 14 years after surgical treatment and the other three had local recurrence and/or distant metastasis, resulting in unfavorable outcomes despite further treatments. Osteosarcoma should be included as a differential diagnosis for bone-forming lesions of the jaw. Furthermore, complete surgical resection combined with adjuvant therapies would be necessary to improve the treatment outcome of jaw osteosarcomas.

Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial–mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.

Extraskeletal osteosarcoma is a very rare type of sarcoma that is considered as one of the subtypes of osteosarcoma. This sarcoma type is very rare in the head and neck area. There is no reported case in the parapharyngeal area. Our case is the first in the literature since it is located in the parapharyngeal area. We present the 69- year-old male patient with extra-skeletal osteosarcoma arising from the parapharyngeal area, with current literature.

Osteosarcoma is the most common primary malignancy of the jaws and is treated by radical surgical resection. Early detection is crucial since removing the lesion with clean margins contributes most to outcome. We present three cases of osteosarcoma occurring in the interradicular region of the mandible, two of which were thought to represent non-malignant processes upon initial presentation. All three demonstrated early but significant clinical and radiographic features indicative of the malignant disease process. Radiographically, all of these cases had in common unilateral periodontal ligament (PDL) space widening, displacement of teeth, and growth of the crestal bone. Clinically, all three cases presented with a painless intraoral swelling. Case 1: A 20 year old African American male presented with a swelling and loose teeth of 1.5 months duration. Histopathological diagnosis of osteoblastic osteosarcoma, high grade was made. Case 2: A 75 year old Caucasian male presented with a 2 × 2 cm expansile lesion of two months duration. Histopathological diagnosis of chondroblastic osteosarcoma was made. Case 3: A 63 year old Caucasian female presented with a 5-6 mm lesion for at least 1 month duration. Histopathological diagnosis of chondroblastic osteosarcoma was made. All three cases were treated with wide surgical resection.

Background There is a paucity of veterinary literature on the safety or outcome of zoledronic acid (ZA) use in dogs for either bone pain or hypercalcemia. Hypothesis/Objectives The primary aim was to report the adverse events in dogs receiving intravenous administration of ZA. Animals Ninety‐five dogs with ZA use. Methods A retrospective cohort study was performed; all dogs that received at least 1 dose of ZA and had a serum biochemistry profile performed before and after treatment were reviewed. Diagnosis, indication for treatment, adverse events and survival times were recorded. Results Ninety‐five dogs met the inclusion criteria. Thirty‐one (33%) received multiple intravenous infusions of ZA (range, 2‐7), making a total of 166 administrations in all dogs. The dose range was 0.13 to 0.32 mg/kg, given at intervals of 4 to 6 weeks. Thirteen adverse events were recorded in 10 dogs: azotemia (n = 8), vomiting (n = 2), pancreatitis (n = 1), cutaneous ulceration (n = 1), and diarrhea (n = 1). Zoledronic acid could not be confirmed as the cause of azotemia in any case. The change in serum creatinine concentration from dose to dose was not related to the total dose received (P = .46). Five dogs (5%) changed Veterinary Comparative Oncology Group Common Terminology Criteria (VCOG‐CTAE) renal/genitourinary grade after administration of ZA; their total dose 0.4 mg/kg (range, 0.26‐0.66) was not significantly different to the group which did not change VCOG‐CTAE renal/genitourinary grade 0.35 mg/kg (range, 0.2‐1.50; P = .93). Conclusions and Clinical Importance Multiple doses of ZA were well tolerated in dogs within this study. A small number of dogs developed progressive azotemia which was not associated with cumulative dose.

OBJECTIVE To describe signalment, clinical signs, serologic test results, treatment, and outcome of dogs with Coccidioides osteomyelitis (COM) and to compare those findings with findings for dogs with osteosarcoma (OSA). ANIMALS 14 dogs with COM and 16 dogs with OSA. PROCEDURES Data were retrospectively gathered from electronic medical records. RESULTS Dogs with COM were younger and weighed less than dogs with OSA. Six dogs with COM had appendicular lesions, 5 had axial lesions, and 3 had both appendicular and axial lesions; 9 had monostotic disease, and 5 had polyostotic disease. Axial lesions and nonadjacent polyostotic disease were more common in dogs with COM than in dogs with OSA, but radiographic appearance was not different between the 2 groups. Median IgG titer at diagnosis of COM was 1:48 and was significantly decreased after 6 and 12 months of treatment. Percentage of dogs with COM that had clinical signs was significantly decreased after 1, 3, 6, and 12 months of treatment. One year after initiation of treatment, 9 of 9 dogs were still receiving fluconazole and 8 of 9 dogs had positive results for serum IgG titer testing. CLINICAL RELEVANCE Dogs with COM typically had a rapid improvement in clinical signs after initiating treatment with fluconazole but required long-term antifungal treatment. Dogs with COM differed from dogs with OSA, but radiographic features had a great degree of overlap between groups, confounding the ability to make a diagnosis on the basis of diagnostic imaging alone.

Background: Paediatric tumours are often characterised by the presence of recurrent DNA copy number alterations (CNAs). These DNA copy number profiles, obtained from a tissue biopsy, can aid in the correct prognostic classification and therapeutic stratification of several paediatric cancer entities (e.g. MYCN amplification in neuroblastoma) and are part of the routine diagnostic practice. Liquid biopsies (LQBs) offer a potentially safer alternative for such invasive tumour tissue biopsies and can provide deeper insight into tumour heterogeneity. Procedure: The robustness and reliability of LQB CNA analyses was evaluated. We performed retrospective CNA profiling using shallow whole-genome sequencing (sWGS) on paired plasma circulating cell-free DNA (cfDNA) and tissue DNA samples from routinely collected samples from paediatric patients (n = 128) representing different tumour entities, including osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, Wilms tumour, brain tumours and neuroblastoma. Results: Overall, we observed a good concordance between CNAs in tissue DNA and cfDNA. The main cause of CNA discordance was found to be low cfDNA sample quality (i.e. the ratio of cfDNA (700 bp)). Furthermore, CNAs were observed that were present in cfDNA and not in tissue DNA, or vice-versa. In neuroblastoma samples, no false-positives or false-negatives were identified for the detection of the prognostic marker MYCN amplification. Conclusion: In future prospective studies, CNA analysis on LQBs that are of sufficient quality can serve as a complementary assay for CNA analysis on tissue biopsies, as either cfDNA or tissue DNA can contain CNAs that cannot be identified in the other biomaterial.

Primary osteosarcomas involving the base of the skull in middle-aged patients are rare. We describe the case of a 59-year-old Asian woman presenting with lethargy, epistaxis, left maxillary and mandibular pain, and headache. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large left greater sphenoid wing tumour with extensive local infiltration and intracranial extension. The tumour was diagnosed as osteosarcoma based on histological examination. In this report, we discuss the clinical presentations, radiological features, and imaging differential diagnoses of this case.

Yucheng Fu, Guoyu He, Zhuochao Liu, Jun Wang, Zhusheng Zhang, Qiyuan Bao, Junxiang Wen, Zhijian Jin, Weibin Zhang Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaCorrespondence: Weibin ZhangDepartment of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of ChinaTel +86-21-64370045, Ext 666983Fax +86-21-54660217Email zhangweibin10368@163.comBackground: Inflammatory response took part in the progression of tumor and was regarded as the hallmark of cancer. However, the prognostic relationship between osteosarcoma and inflammatory response-associated genes (IRGs) was unclear. This research aimed to explore the correlations between osteosarcoma prognosis and IRG signature.Methods: The inflammatory response-associated differentially expressed messenger RNAs (DEmRNAs) were screened out through Gene Expression Omnibus (GEO) and Molecular Signature Database (MSigDB) databases. Univariate and multivariate cox regression analyses were utilized to construct the IRG signature. The prognostic value of signature was investigated through Kaplan–Meier (KM) survival curve and nomogram. DEmRNAs among high and low inflammatory response-associated risks were identified and functional enrichment analyses were conducted. ESTIMATE, CIBERSORT and single-sample gene set enrichment analyses (ssGSEA) were implied to reveal the alterations in immune infiltration. All the above results were validated in Target database. The expression of IRGs was also validated in different cell lines by quantitative real-time PCR (qRT-PCR) and osteosarcoma patient samples by immunohistochemistry.Results: The IRG signature that consisted of two genes (MYC, CLEC5A) was established. In training and validation datasets, patients with lower risk scores survived longer and the IRG signature was confirmed as the independent prognostic factor in osteosarcoma. The nomogram was constructed and the calibration curves demonstrated the reliability of this model. Functional analysis of risk score-associated DEmRNAs indicated that immune-related pathways and functions were significantly enriched. ssGSEA revealed that 14 immune cells and 11 immune functions were significantly dysregulated. The qRT-PCR results indicated IRGs were significantly differently expressed in osteosarcoma and osteoblast cell lines. The immunohistochemistry analyses of patients’ samples revealed the same result.Conclusion: The novel osteosarcoma inflammatory response-associated prognostic signature was established and validated in this study. This model could serve as the biomarker and therapeutic target for osteosarcoma in the future.Keywords: osteosarcoma, inflammatory response, metastasis, prognosis, immune

Background The prognosis of high-risk osteosarcoma, defined by the presence of chemo-resistance, metastatic disease at diagnosis, and relapse, remains poor. The efficacy of high-dose chemotherapy (HDC) and autologous stem-cell transplantation (ASCT) for high-risk osteosarcoma is still unclear. Methods We retrospectively reviewed pediatric patients with high-risk osteosarcoma who underwent HDC and ASCT at our institution between 2002 and 2018 and performed a review of the literature regarding the efficacy of HDC and ASCT for high-risk osteosarcoma. Results Six patients with high-risk osteosarcoma underwent high-dose melphalan (180 mg/m2)-based chemotherapy followed by ASCT. Two patients received HDC consisting of ifosfamide and melphalan. Three patients received HDC consisting of etoposide, carboplatin, and melphalan. One patient underwent tandem HDC consisting of thiotepa and etoposide followed by melphalan, thiotepa, and etoposide. Non-hematological toxicities presented mainly as mucositis and diarrhea. Two patients developed grade 3 mucositis. No life-threatening toxicities were observed in any of the six patients. One patient with disease progression before HDC died of multiple metastases, while five patients, with no evidence of disease in the peri-transplant periods, were alive at the time of publication; there was no disease recurrence at a median follow-up period of 144 months (range, 24–215 months). Our review of the literature supports the use of HDC with a higher dose of melphalan (180–280 mg/m2) for high-risk osteosarcoma. Conclusions Melphalan-based HDC and ASCT can be a promising treatment for high-risk osteosarcoma. Additionally, surgical removal of macroscopic residual lesions may be essential in peri-transplant periods.

A. Kawai43, K. Kopeckova44, D. A. Krakorova45, A. Le Cesne46, F. Le Grange1, E. Legius47, A. Leithner48, A. Lopez Pousa49, J. Martin-Broto36, O. Merimsky50, C. Messiou51, A. B. Miah52, O. Mir53, M. Montemurro54, B. Morland55, C. Morosi56, E. Palmerini57, M. A. Pantaleo58, R. Piana59, S. Piperno-Neumann60, P. Reichardt61, P. Rutkowski62, A. A. Safwat63, C. Sangalli64, M. Sbaraglia19, S. Scheipl48, P. Schoffski65, S. Sleijfer66, D. Strauss67, K. Sundby Hall13, A. Trama68, M. Unk69, M. A. J. van de Sande70, W. T. A. van der Graaf66,71, W. J. van Houdt72, T. Frebourg73x, R. Ladenstein41z, P. G. Casali2,74z &

Diagnosis of osteosarcoma can be challenging because of its diverse histological patterns and the lack of diagnostic biomarkers for most examples. This review summarizes the key pathologic findings of osteosarcoma subtypes (high-grade central, parosteal, low-grade central, periosteal, high-grade surface, and secondary) with an emphasis on describing and illustrating histological heterogeneity to help general pathologists. Differential diagnoses are listed for each entity, and histological subtype and distinguishing features, including molecular genetic findings (eg, MDM2, IDH, H3F3A, FOS, and USP6), are discussed. The review also covers recently established and emerging concepts and controversies regarding osteosarcoma.

Background/aim Recurrent osteosarcoma is recalcitrant with poor response rates to first-line chemotherapy due to heterogeneity and metastatic potential. This disease requires novel drug discovery and precision treatment. Materials and methods The osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model mimics the clinical disease and has identified effective clinically-approved drugs and experimental agents, especially drug combinations, that hold much clinical promise. Results Effective treatment for drug-resistant osteosarcoma includes regorafenib, as monotherapy, and temozolomide-irinotecan, trabectedin-irinotecan, sorafenib-everolimus, sorafenib-palbociclib, and olaratumab-doxorubicin-cisplatinum, as combinations. Conclusion The PDOX model can be used to improve the outcome of osteosarcoma patients, including individualized, precision therapy.

Objective This retrospective study of patients with osteosarcoma investigated the following biomarkers of inflammation and nutritional status: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index (PNI), and systemic immune-inflammation index (SII). The efficacies of these indicators to predict overall survival (OS) of young and elderly patients were compared. Methods The data of 125 patients with osteosarcoma, comprising the young (≤20 years) and elderly (60-80 years), were reviewed. Receiver operating characteristic (ROC) curves were calculated to determine the optimal cut-off value and area under the ROC curve of each potential biomarker. Kaplan-Meier curves and a Cox proportional hazards model were used to perform survival analyses. Results The cut-off values for low and high PNI ( ≤48.5, >48.5) and low and high SII (≤607.3, >607.3) were determined. Osteosarcoma patients in low PNI group or high SII group exhibited poorer OS relative to those in high PNI or low SII groups. The univariate and multivariate analyses indicated that preoperative PNI and SII were independent prognostic factors for OS in both the young and elderly subjects. Conclusion Preoperative PNI and SII can be viable biomarkers of prognosis for both young and elderly patients with osteosarcoma. Awareness of these valuable indexes will enable clinicians to evaluate the inflammatory and nutritional status of these patients and establish a framework for individualized therapy.

Background. Osteosarcoma is the most prevalent bone cancer that affects young adults and adolescents. It is the most frequent malignancy of the bone. In spite of the fact that complete surgical resection and chemotherapy have increased the overall survival of osteosarcoma patients considerably, the prognosis remains dismal in patients with recurring and/or metastasized osteosarcoma. Thus, finding predictive biomarkers representing osteosarcoma's biological variability may result in more effective treatment for osteosarcoma patients. Methods. In this research, RNA data and clinical information were obtained from TARGET database. The risk score was calculated using a technique that incorporated both univariate and multivariate Cox regression. A variety of statistical methods were employed to assess the risk score's accuracy. These included ROC curves, nomograms, and Kaplan-Meier curves. Following that, bioinformatics studies were carried out in order to investigate the possible biological processes that influence the prognosis of osteosarcoma patients. GSEA was used to investigate the variations in pathway enrichment among the different groups of genes. To examine the disparities in the immune microenvironment, the analytical methods CIBERSORT and ssGSEA were employed. Results. We discovered three differentially expressed lncRNAs (RPARP-AS1, AC009159.3, and AC124312.3) that are linked to osteosarcoma prognosis. Kaplan-Meier analysis showed the presence of a signature of high-risk lncRNAs linked with a poor prognosis for osteosarcoma. Furthermore, the AUC of the lncRNAs signature was 0.773, indicating that they are useful in predicting osteosarcoma prognosis in certain cases. In predicting osteosarcoma prognosis, our risk assessment approach outperformed conventional clinicopathological characteristics. In the high-risk group of people, GSEA showed the presence of tumor-related pathways as well as immune-related pathways. Furthermore, TARGET revealed that immune-related functions such as checkpoint, T-cell coinhibition, and costimulation were significantly different between the high-risk and low-risk groups. LAIR1, LAG3, CD44, and CD22, as well as other immune checkpoints, were shown to be expressed differentially across the two risk groups. Conclusion. This study established that pyroptosis-derived lncRNAs had a significant predictive value for osteosarcoma patients' survival, indicating that they may be a viable target for future therapy.

Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro. circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment., Graphical abstract

Han Zhang,1,2 Guanhong Chen,2 Xiajie Lyu,3 Chun Rong,4 Yingzhen Wang,1 Ying Xu,2 Chengyu Lyu1 1Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, People’s Republic of China; 2Department of Orthopaedics, Shanxian Central Hospital, Heze City, Shandong Province, People’s Republic of China; 3Weifang Medical University, Weifang, Shandong, People’s Republic of China; 4Department of Operation Room, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, People’s Republic of ChinaCorrespondence: Chengyu Lyu Email 18266390138@163.comPurpose: Long non-coding RNAs (lncRNAs) have diverse roles in modulating gene expression on both transcriptional and translational levels, but their involvement in osteosarcoma (OS) metastasis remains unknown.Patients and Methods: Transcriptional and clinical data were downloaded from TARGET datasets. A total of seven lncRNAs screened by univariate cox regression, lasso regression, and multivariate cox regression analysis were used to establish the OS metastasis model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model.Results: The established model showed exceptional predictive performance (1 year: AUC = 0.92, 95% Cl = 0.83– 0.99; 3 years: AUC = 0.87, 95% Cl = 0.79– 0.96; 5 years: AUC = 0.86, 95% Cl = 0.76– 0.96). Patients in the high group had a poor survival outcome than those in the low group (p < 0.0001). GSEA analysis revealed that “NOTCH_SIGNALING” and “WNT_BETA_CATENIN_SIGNALING” were significantly enriched and that resting dendritic cells were associated with AL512422.1, AL357507.1, and AC006033.2 (p < 0.05).Conclusion: Based on seven prognosis-related lncRNAs, we constructed a novel model with high reliability and accuracy for predicting metastasis in OS patients.Keywords: lncRNAs, osteosarcoma, tumor metastasis, prognosis

Osteosarcoma occurs mostly in adolescence, this being the primary bone tumor (malignant) formed by the production of immature bone. Immature bone cell's production occurs from the premature bone cells. The commonly used treatments form is lesions removal. Chemotherapy is also used to treat metastasis of the osteoid cells (cancerous). Sometimes the micro metastasis can't be diagnosed in time to can be cured with neoadjuvant chemotherapy. Pulmonary metastatic disease is the most common complication of the osteosarcoma (musculoskeletal cancer). I have presented a case of osteosarcoma of right proximal tibia in an18year old boy who come to the hospital for swelling and pain which were increasing during walking. Before that he hadn't any complaints in his knees. Magnetic resonance imaging was done by which the diagnosis was confirmed. After that, tumor resection was performed and post-operative chemotherapy was administered. The case report states that the adolescents age group should be properly monitored because they have the highest risk of suspicion by premature bone growth of osteoid.

Background Doxorubicin (Dox) is one of the most effective chemotherapy agents used to treat adolescent and young adult sarcoma patients. Unfortunately, Dox causes cardiotoxicities that compromise long‐term survival. We investigated whether exercise prevented cardiotoxicity and increased survival following myocardial infarction. Methods Juvenile mice received Dox, Dox + exercise (Exer), Dox then exercise or were exercised during and after Dox. Mice were evaluated by echocardiography and histology immediately after therapy and 12 weeks later. Mice subjected to permanent ligation of the left anterior descending artery 90 days after therapy were assessed for survival at 45 and 100 days. Results Mice treated with Dox, but not Dox + Exer, had decreased ejection fraction (EF) and fractional shortening (FS) immediately after Dox therapy, which continued to deteriorate over 12 weeks with the development of diastolic failure and fibrosis. Acute Dox‐induced cardiotoxicity was documented by induction of autophagy and abnormal mitochondria and vascular architecture with decreased pericytes. These abnormalities persisted 12 weeks after therapy. These acute and late changes were not seen in the Dox + Exer group. Initiating exercise after Dox therapy promoted recovery of EF and FS with no functional or histologic evidence of Dox‐induced damage 12 weeks after therapy. Survival rates at 100 days after MI were 67% for control mice, 22% for mice that received Dox alone, and 56% for mice that received Dox + Exer. Conclusions Exercise inhibited both early and late Dox‐induced cardiotoxicity and increased recovery from an ischemic event. Exercise interventions have the potential to decrease Dox‐induced cardiac morbidity., This study indicates that exercise prevents Doxorubicin‐induced vascular damage, maintaining cardiac blood flow. Exercise initiated during or after Doxorubicin therapy inhibited the acute and late cardiotoxicities and increased recovery from an ischemic event.

Background:. Computed tomography (CT) and magnetic resonance imaging (MRI) data can be fused to identify the tumor boundaries. This enables surgeons to set close but tumor-free surgical margins and excise the tumor more precisely. This study aimed to report our experience in performing computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction to treat bone sarcoma in the diaphysis and metaphysis of the femur and tibia. Methods:. Between September 2008 and December 2015, 24 patients with bone sarcomas underwent surgical resection and joint-sparing reconstruction under image-guided computer navigation. The cohort comprised 16 males and eight females with a median age of 19.5 years (range: 12–48 years). The tumor location was the femoral diaphysis in three patients, distal femur in 19, and proximal tibia in two. The tumors were osteosarcoma (n = 15), chondrosarcoma (n = 3), Ewing sarcoma (n = 3), and other sarcomas (n = 3). We created a pre-operative plan for each patient using navigation system software and performed navigation-aided resection before reconstructing the defect with a custom-made prosthesis with extracortical plate fixation. Results:. Pathological examination verified that all resected specimens had appropriate surgical margins. The median distance from the tumor resection margin to the joint was 30 mm (range: 13–80 mm). The median follow-up duration was 62.5 months (range: 24–134 months). Of the 24 patients, 21 remain disease free, one is alive with disease, and two died of the disease. One patient developed local recurrence. Complications requiring additional surgical procedures occurred in six patients, including one with wound hematoma, one with delayed wound healing, one with superficial infection, one with deep infection, and two with mechanical failure of the prosthesis. The mean Musculoskeletal Tumor Society score at the final follow-up was 91% (range: 80%–100%). The 5- and 10-year implant survival rates were 91.3% and 79.9%, respectively. Conclusions:. Computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction with extracortical plate fixation is a reliable surgical treatment option for bone sarcoma in the diaphysis and metaphysis of the femur and tibia.

To evaluate the efficacy and toxicity of dose-escalated image guided-intensity modulated radiation therapy (IG-IMRT) in osteosarcoma (OGS), chondrosarcoma (CS) and chordoma (CH) of head and neck (HN) and pelvis.In this prospective non-randomized study, 65 patients of HN or pelvic OGS (24), CS (7) and CH (34) mandating definitive or post-operative radiotherapy from May 2013 to December 2018 were included. Radiotherapy doses in definitive setting were 72.0 Gy for CH and 70.2 Gy for OGS and CS; while in post-operative setting it was 66.6 Gy and 64.8 Gy respectively (at 1.8 Gy per fraction).Planned doses of radiotherapy could be completed in 61 (93.8%) patients; with grade III or higher acute and late toxicities of 3% and 0% respectively. With a median follow-up of 52 (range 6-92) months, the five-year actuarial local control (LC) rates were 66% in OGS, 38.1% in CS and 75.9% in CH; while cause-specific survival (CSS) rates were 54.7%, 64.3% and 92.2% respectively. There was no statistically significant difference in outcomes for patients receiving definitive and post-operative radiotherapy. Locally controlled disease at first follow-up after radiotherapy was associated with improved CSS and OS in CS (p = 0.014) and CH (p 0.001). Radiotherapy resulted in significant and sustained improvement in Musculoskeletal tumour society (MSTS) score and reduction in pain score. Salvage re-irradiation was feasible in local progression after radiotherapy, with good outcomes and tolerability.Dose-escalated IG-IMRT results in good LCfunctional improvement with minimal toxicity in OGS, CS and CH.

The rib is an unusual location for osteosarcoma and is reported in only 2% of all cases. The major histological variants of osteosarcoma are osteoblastic, chondroblastic, and fibroblastic, with a few rare variants including one epithelioid type. This report describes a 44-year-old male with an osteolytic mass in the right seventh rib. Histological examination revealed osteosarcoma with unique features of epithelioid appearance and rosette structures. To the best of our knowledge, this is the first reported case of a rosette-forming osteosarcoma of the rib that showed epithelioid morphology. Despite successful surgery, the patient’s prognosis was poor because this malignancy had an unusual location within the axial skeleton and was a rare histological variant.

Primary malignant bone tumors are uncommon and their accurate classification requires careful correlation of clinical, radiological, and pathologic findings. It is a heterogeneous group of tumors with a wide spectrum of morphology and their biological potential can be of low- or high-grade, depending on their risk for developing metastases. Over the past several decades, the classification of bone sarcomas has remained largely constant. However, some of the tumors have been reclassified and several new entities have emerged. In this review, we will focus on pleomorphic fibrosarcoma/UPS and dedifferentiated bone tumors, discuss their key diagnostic features, differential diagnosis, and their relation to prognosis.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Osteosarcomas are highly aggressive tumors that historically have had a dismal prognosis. However, the survival rate has improved significantly with the addition of adjuvant and neoadjuvant chemotherapy. Here, we present a case report of a 13-year-old male with a history of a left humeral osteosarcoma whose course was complicated by recurrent sarcoma-related pneumothoraces. Despite recurrent pneumothoraces being a relatively uncommon complication of osteosarcoma, they present a great challenge to providing treatment that optimizes outcomes and quality of life for patients.

While survival rates for patients with relapsed/refractory osteosarcoma are low, kinase inhibitors have shown efficacy in its treatment. The multikinase inhibitor lenvatinib, plus ifosfamide and etoposide, showed antitumor activity in a Phase II study in patients with relapsed/refractory osteosarcoma. This Phase II randomized controlled trial (OLIE) will assess whether the combination of lenvatinib + ifosfamide + etoposide is superior to ifosfamide + etoposide alone in children, adolescents and young adults with relapsed/refractory osteosarcoma. The primary end point is progression-free survival; secondary and exploratory end points include, but are not limited to, overall survival, objective response rate, safety and tolerability, pharmacokinetic characterization of lenvatinib in the combination treatment, quality of life and quantification of baseline unresectable lesions that are converted to resectable.Lay abstract Traditional treatment for osteosarcoma (bone cancer) includes drugs that cause cell damage, such as ifosfamide and etoposide. The study in this article looked at adding lenvatinib, a drug that works to block development of blood vessels, to traditional chemotherapy to see whether it worked better. ‘OLIE’ is a Phase II clinical study comparing lenvatinib + chemotherapy (ifosfamide + etoposide) to the chemotherapy alone (ifosfamide + etoposide). An earlier study indicated that this drug combination may be successful. The study includes children, adolescents and young adults with osteosarcoma that has come back after, or did not respond to, previous treatment. OLIE will look at the antitumor activity and the side effects of this drug combination. The OLIE study is currently enrolling patients worldwide.

Background Osteosarcoma is a common primary malignant bone tumor susceptible to distant metastasis. The clinical outcome for patients remains poor due to the resistance to chemotherapy and lacking effective therapeutic targets. Recepteur d'origine nantais (RON), a transmembrane protein of the c-MET proto-oncogene family, has been reported to contribute to the malignant progression and bone metastasis in several tumors. The present study aimed to explore the prognostic significance of RON in primary high-grade osteosarcoma. Methods Immunohistochemistry (IHC) and western blotting (WB) were used to investigate the protein expression of RON in 80 surgically resected specimens (50 high-grade osteosarcoma specimens and 30 non-neoplastic bone tissues) and 6 cell lines. The χ2 test or independent-sample Student's t-test was used to assess the significance of RON difference between osteosarcoma and non-neoplastic bone tissues. The χ2 test and Fisher's exact test were used to analyze the association of RON with the clinicopathological features of osteosarcoma patients. Kaplan–Meier method and Cox proportional hazards model were used to assess the significance of RON for the survival of osteosarcoma patients. Results The results of IHC and WB observed significant overexpression of RON in osteosarcoma specimens (P Conclusions The present study demonstrated that high expression of RON held independent value for unfavorable survival in primary high-grade osteosarcoma. Its potential role as a therapeutic target for osteosarcoma treatment deserves further research.

Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. It is an aggressive tumor with a tendency to spread to the lung, which is the most common site of metastasis. Patients with advanced OS with metastases have poor prognoses despite the application of chemotherapy, thus highlighting the need for novel therapeutic targets. The tumor microenvironment (TME) of OS is confirmed to be essential for and supportive of tumor growth and dissemination. The immune component of the OS microenvironment is mainly composed of tumor-associated macrophages (TAMs). In OS, TAMs promote tumor growth and angiogenesis and upregulate the cancer stem cell-like phenotype. However, TAMs inhibit the metastasis of OS. Therefore, much attention has been paid to investigating the mechanism of TAMs in OS development and the progression of immunotherapy for OS. In this article, we aim to summarize the roles of TAMs in OS and the major findings on the application of TAMs in OS treatment.

Background: Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy. Methods: The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed. Results: The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed. Conclusion: Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.

Stereotactic body radiation therapy (SBRT) is an established limb-sparing treatment for dogs with appendicular osteosarcoma (OSA) and pathologic fractures are a common sequela. The objectives of this retrospective, observational, and descriptive study were to develop and evaluate objective CT criteria for predicting pathologic fractures and assess impacts on survival time. Included dogs had confirmed or suspected appendicular OSA, available CT scans, available outcome data, and were treated with SBRT. For each study, the number of quartiles affected by lysis on the most severely affected transverse slice, longest measurable length of contiguous full cortical lysis, presence of subchondral bone lysis, and ratio of the length of the affected bone to normal bone were recorded. A scoring system was developed for assigning grades (summed score 1-4 = grade 1, 5-7 = grade 2, and 8 or greater = grade 3.) A total of 127 CT datasets were sampled (123 patients). The median summed score was 7. The grade was correlated with pathologic fracture development (23% of grade 1, 35% of grade 2, and 57% of grade 3 resulting in fracture, P = 0.028). Subchondral bone lysis was correlated with fracture (odds ratio, 2.2, P = 0.02). Percent affected bone ≥40% was associated with decreased survival (P = 0.002). Dogs with

Background. Osteosarcoma is a common and highly metastatic malignant tumor, and m5C RNA methylation regulates various biological processes. The purpose of this study was to explore the prognostic role of m5C in osteosarcoma using machine learning. Methods. Osteosarcoma gene data and the corresponding clinical information were downloaded from the GEO database. Machine learning methods were used to screen m5C-related genes and construct m5C scores. In addition, the clusterProfiler package was used to predict the m5C-related functional pathways. xCell and CIBERSORT were used to calculate the immune microenvironment cells. GSVA was applied to analyze different categories of m5C genes, and the correlation between the GSVA and m5C scores was evaluated. Results. Twenty m5C genes were identified, and 54 related genes were screened. The m5C score was constructed based on the PCA score. With an increase in the m5C score, the expression of m5C genes and their related genes changed. Functional analysis indicated that the focal adhesion, cell-substrate adherens junction, cell adhesion molecule binding, and E2F targets might change with the m5C score. The naive B cells and CD4+ memory T cell also changed with the m5C score. The results of the correlation analysis showed that the m5C score was significantly correlated with the reader and eraser genes. Conclusion. The m5C score might be a prognostic index for osteosarcoma.

Osteosarcoma is a major form of malignant bone tumor that typically occurs in young adults and children. The combination of aggressive surgical strategies and chemotherapy has led to improvements in survival time, although individuals with recurrent or metastatic conditions still have an extremely poor prognosis. This disappointing situation strongly indicates that testing novel, targeted therapeutic agents is imperative to prevent the progression of osteosarcoma and enhance patient survival time. Curcumin, a naturally occurring phenolic compound found in Curcuma longa, has been shown to have a wide variety of anti-tumor, anti-oxidant, and anti-inflammatory activities in many types of cancers including osteosarcoma. Curcumin is a highly pleiotropic molecule that can modulate intracellular signaling pathways to regulate cell proliferation, inflammation, and apoptosis. These signaling pathways include RANK/RANKL, Notch, Wnt/β-catenin, apoptosis, autophagy, JAK/STAT, and HIF-1 pathways. Additionally, curcumin can regulate the expression of various types of microRNAs that are involved in osteosarcoma. Therefore, curcumin may be a potential candidate for the prevention and treatment of osteosarcoma. This comprehensive review not only covers the use of curcumin in the treatment of osteosarcoma and its anti-cancer molecular mechanisms but also reveals the novel delivery strategies and combination therapies with the aim to improve the therapeutic effect of curcumin.

Background: Most children with recurrent metastatic solid tumors have high mortality rates. Recent studies have shown that proteasome inhibition leads to effective tumor killing in cells that have acquired treatment resistance and metastatic properties. Objective: The purpose of this study was to test the potential of Carfilzomib (CFZ), a proteasome inhibitor, in refractory pediatric solid tumors which is currently unknown. Methods: A panel of pediatric solid tumor cell lines, including neuroblastoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma and atypical teratoid rhabdoid tumor (ATRT), was used to evaluate the cytotoxic and proteasomal inhibitory effects of CFZ. A drug scheduling experiment was performed to determine the optimal dose and time to obtain effective cell killing. Combination studies of CFZ with chemotherapeutic drugs of different classes were performed to determine the extent of synergy. Results: CFZ showed effective cytotoxicity against all cell lines tested (mean IC50 = 7nM, range = 1-20nM) and activity in a fluorophore-tagged cell-based proteasome assay. Drug scheduling experiments showed that the minimum exposure of 4-8 hours/day is needed for effective cumulative killing. CFZ, when combined with chemotherapeutic drugs of different classes, synergistically enhanced the extent of cell death. Conclusions: CFZ showed cytotoxic activity against all the solid pediatric cancer cell lines tested. This study provides initial in vitro data on the potential of CFZ to treat pediatric solid tumors and supports further investigations into the components of drug scheduling, biological correlates and drug combinations for future early phase clinical trials in children.

Purpose : To investigate the clinical effects and complications that may arise as a result of ipsilateral clavicle turnover during tumorous bone defect repair of the proximal humerus, and to explore the feasibility of performing combined free fibula transplantation and internal fixation in reducing complications Methods: We treated 13 patients with clavicle turnover or free fibular transplantation from September 1998 to February 2020. There were 7 males and 6 females with the average age of 26.2 years (7–50 years). The histological diagnoses were osteosarcoma in 6 patients (Enneking IIB), giant cell tumors in 3 patients (Campanacci III) and one patient each with Ewing’s sarcoma (Enneking IIB), chondrosarcoma (Canceration of multiple osteochondromatosis), fibrosarcoma and metastatic cancer of bone (Bone metastasis of lung cancer). Pathological fractures were found in 7 of the 13 patients. Results : The operation was successfully performed for all 13 patients. We followed 12 patients for 18 to 274 months (average 92.7 months). For 6 patients treated with simple clavicle turnover using a short plate, the average healing time was 7 months (4–12 months). Among them, there were 3 cases of clavicle fracture and 3 cases of overturned bone healed well. For the 7 patients treated with clavicle turnover and free fibula using a long plate, the healing time was 6.7 months. However, one patient died of tumor metastasis 19 months after operation, without reversal of clavicle fracture and other complications. Conclusion : Clavicle turnover is a feasible method for the treatment of tumorous bone defect of the proximal humerus. Flipping clavicle fracture is the most common complication. The application of total clavicle fixation and free fibular transplantation strengthens the flipping clavicle and reduces the risk of clavicle fracture.

Objective: To study the expression of Transforming Growth Factor beta-1 (TGF-β1) and Tumor protein 53 (Tp53) in osteoblastoma and osteosarcoma and the role of TGF-β paradox in the progression of these tumors. Materials and Methods: Twenty-two paraffin blocks were collected and classified into 7 blocks with classical osteoblastoma and 15 blocks with osteosarcoma. From each block, slide preparation for H&E and immunohistochemical staining by two markers: anti TGF-β1 antibody and anti Tp53 antibody were applied. Then we estimated the expression of each marker by ImageJ (version 1.41) and area fractions were measured. Results: Both classical osteoblastoma and osteosarcoma showed positive expression of TGF-β1. The expression of Tp53 was positive in osteosarcoma, but it was negative in osteoblastoma. Our statistical analysis revealed that the expression of TGF-β1 in osteosarcoma was stronger than in osteoblastoma but with no statistically significant difference. There was a significant moderate negative correlation between expression of the two markers in osteosarcoma. Conclusion: The mutual signaling is the main pillar in the progression of osteosarcoma and osteoblastoma. Interaction pathways between Tp53 and TGF-β1 may have a role in TGF-β paradox. Understanding this interaction may help in improving of the management and prognosis of osteosarcoma.

Guangxian Zhong,1,&ast; Yunqing Wang,1,&ast; Hongxiang Wei,1 Meifang Chen,2 Huangfeng Lin,1 Zhen Huang,1 Jinlong Huang,3 Shenglin Wang,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 2The Health Management Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China&ast;These authors contributed equally to this work.Correspondence: Jianhua Lin; Shenglin Wang Tel/Fax +86 591 87981029Email jianhual@126.com; Shenglinwang0216@163.comPurpose: The aim of this research was to investigate the clinical significance of the expression of flap structure-specific endonuclease 1 (FEN1) in primary osteosarcoma.Methods: The expression of FEN1 was detected by immunohistochemistry analysis. The association of the expression of FEN1 in osteosarcoma with clinicopathological parameters was analyzed by using χ2 test or Fisher’s exact test. Survival analyses were performed by Kaplan–Meier method and Cox proportional hazards regression model.Results: Of the 40 osteosarcoma patients, 19 (47.5%) patients presented with FEN1 high expression, while in the non-neoplastic bone specimens, the FEN1 high expression was observed in 10% (3/30), the positive expression rate in osteosarcoma patients was significantly higher than that of non-neoplastic bone specimens (P< 0.01). Univariate analysis indicated that the progression-free survival (PFS) and overall survival (OS) were correlated with the expression level of FEN1 (PFS, P < 0.001; OS, P = 0.002), Enneking staging (PFS, P = 0.026; OS, P = 0.044) and chemotherapy response (PFS, P = 0.019; OS, P = 0.031). Multivariate analysis demonstrated that FEN1 expression was an independent prognostic factor for the PFS (HR = 4.73, P = 0.002) and OS (HR = 4.01, P = 0.038) of osteosarcoma patients.Conclusion: This study showed that FEN1 was overexpressed in osteosarcoma patients and positively associated with poor prognosis of osteosarcoma patients. Further studies should focus on the relative mechanisms and the targeted FEN1 therapies for osteosarcoma.Keywords: osteosarcoma, flap endonuclease 1, immunohistochemistry, prognosis

There is increasing preference for limb salvage techniques in the management of pediatric musculo- skeletal tumors. This study was aimed at evaluating femoral growth following proximal tibia resection (PTR) and placement of an extendible endoprosthesis with sliding stem. This was a retrospective study. The demographic and clinical data were collected. All the patients with malignant tumors were fully staged and commenced on appropriate chemotherapy. An expected discrepancy of > 3cm was considered sub- stantial enough to warrant extendible prosthesis. Twelve patients who had follow up full length scanogram of the lower limbs were included for the evaluation of femoral growth. The last available scanograms were used for growth comparison of the femur. The age at resection for all twelve patients ranged from 4-13 years. The commonest histological diagnosis was Osteosarcoma. In the twelve patients assessed for the growth of femur, the mean femoral length was 96% [89%-102%] of the unaffected femur. Distal femoral physeal growth continued after im- plantation of a sliding extendible prosthesis after resection of proximal tibia tumors.

Background/aim Auranofin (AUR), a thioredoxin reductase (TXNRD) inhibitor, shows anticancer activity against several cancers. This study investigated the effects of AUR on the local progression and pulmonary metastasis of osteosarcoma (OS). Materials and methods Publicly available expression cohorts were analysed to study the relationship between TXNRD-2 expression and the survival of patients with OS. The murine OS cell line LM8 was stimulated with AUR. Cell viability, apoptosis-related protein levels, caspase activity, and wound healing were analysed. Tumor progression and pulmonary metastasis were investigated in C3H mice implanted with LM8 cells. Results High-level expression of TXNRD-2 represented a negative prognostic factor for metastasis and overall survival in patients with OS. AUR induced apoptosis of OS cells via the oxidative stress-MAPK-Caspase 3 pathway, and suppressed the migration of OS cells. AUR inhibited the pulmonary metastasis of OS, but not local progression. Conclusion AUR represents a potential therapeutic drug for suppressing pulmonary metastasis of OS.

Background/aim Primary osteosarcoma of the breast is an exceedingly-rare malignant tumor that shares histological characteristics with osteosarcoma of the bone. Since effective therapies have not yet been established, standard therapy for osteosarcoma of the bone was examined in the present study for efficacy against primary osteosarcoma of the breast in a patient-derived orthotopic xenograft (PDOX) nude-mouse model. Materials and methods The PDOX mouse models were established by surgical implantation of the primary osteosarcoma of the breast specimen into the mammary gland of nude mice. Mice with tumors were randomized into four groups, each n=4: control group; cisplatinum (CDDP)-treatment group; doxorubicin (DOX)-treatment group; and CDDP/DOX-combination-treatment group. Mice were treated for twenty-one days, three weeks after implantation. Tumor size and body weight were measured during three weeks of treatment. Results Significant tumor growth inhibition was observed, compared to the control, in the CDDP-treatment group, the DOX-treatment group, and the combination-treatment-group. Only the combination treatment regressed the tumor. Conclusion CDDP and DOX which are standard first-line therapies for osteosarcoma, may be clinically effective against primary osteosarcoma of the breast, and in particular, their combination.

BACKGROUND Although pathology in the maxillary and mandibular bones is rare in young patients, the differential diagnosis is broad. The World Health Organization (WHO) updated its classification of maxillofacial bone pathology in 2017. Using these updated guidelines, a systematic review of common maxillofacial bone lesions in the pediatric population was performed. METHODS A PubMed search was conducted capturing English language articles from inception to July 2020. Thirty-one articles were identified that described the frequency of maxillofacial bone pathology. Data were extracted and organized using the WHO 2017 classification of odontogenic and maxillofacial bone tumors. Prevalence data were analyzed among diagnostic categories and geographical regions. The SAS version 9.4 was used to complete statistical analyses. RESULTS The articles included patients from birth to a maximum age of 14 to 19 years. The most common odontogenic cysts included radicular cyst (42.7%) and dentigerous cyst (39.0%) followed by odontogenic keratocyst (15.0%). Among odontogenic bone tumors, odontoma (49.3%) was most common followed by ameloblastoma (29.1%). The most common nonodontogenic bone tumor was fibrous dysplasia (42.4%), and the most common malignant bone tumor was osteosarcoma (75.0%). Significant variations were found by geographic region, with dentigerous cyst more common than radicular cyst, and ameloblastoma more common than odontoma in African and Asian countries (P

Osteosarcoma is the most common primary bone cancer in children and young adults. Recent experimental evidence has indicated that Runx2/OPN axis play important roles in the metastasis of osteosarcoma cells. The present study aimed to explore their relationship and prognostic significance in surgically resected osteosarcoma. The expression of runt‐related transcription factor2(Runx2) and osteopontin (OPN) in clinical specimens from 105 osteosarcoma patients were detected by immunohistochemistry. The correlations between Runx2, OPN, and clinicopathologic data were analyzed by Chi-square (χ2) tests. The prognostic values were determined by univariate and multivariate survival analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics curves. The results showed there is a significant positive correlation between Runx2 and OPN expression at protein levels (P = 0.015). Runx2 and OPN were both independent predictors for overall survival and metastasis-free survival. When Runx2 and OPN were taken into consideration together, the predictive range was extended and the sensitivity was improved, and more significant and better biomarkers for osteosarcoma metastasis and survival. These results suggest that a combined Runx2/OPN expression could be a valuable independent predictor of tumor metastasis and survival in osteosarcoma patients.

Timely diagnosis of Ewing's sarcoma is an actual problem of our time, since this tumor is characterized by fairly rapid growth and aggressive course. According to literature data, it ranks 2-nd among all bone tumors, second only to osteosarcoma, and is 8.64%. This review article discusses the possibilities of radiation research methods in the early diagnosis of this tumor on the example a clinical observation of the extra-skeletal form of Ewing's sarcoma.

Limb salvage is the benchmark for pediatric extremity bone sarcomas. However, reconstructive strategies must account for any anticipated remaining growth potential and the resultant limb inequality. Expandable endoprostheses offer the theoretical advantage of immediate weight-bearing, predictable function, and reliable maintenance of leg-length equality. The evolution of the lengthening mechanism now permits noninvasive lengthening, opposed to the multiple open procedures of the past. These design improvements have contributed to their growing popularity. Experience has indicated that these noninvasive implants more reliably achieve leg-length equality, have longer failure-free survival, and decreased complications, although some have noted gearbox and lengthening failures. Currently, no standardize technique exists for managing patients with noninvasive expandable implants from the time of reconstruction to final lengthening at skeletal maturity. This blueprint aims to provide a detailed surgical technique, lengthening schedule, and recommendations for the mitigation and management of complications to achieve successful limb salvage with noninvasive expandable endoprostheses.

Gnathic Osteosarcoma (GOS) is a subtype of osteosarcoma (OS) that primarily affects the maxilla and mandible. An accurate diagnosis, usually facilitated by Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Biopsy, is required to define the stage of the disease and plan adequate treatment. Early diagnosis and complete tumor resection are mandatory to improve the prognosis of GOS. We present a case of GOS in a 17-years-old female based on clinical-radio-pathological correlation.