Bone In Young Adults Research Articles

Evaluation of curettage, synthetic bone grafting and fixation with implant in benign osteolytic and cystic lesions of long bones in children and young adults

<p class="abstract"><strong>Background:</strong> Curettage is one of the most common treatment options for benign lytic bone tumors and cystic lesions. In children and young adults, the resultant defect is usually filled with synthetic bone graft, which is a natural calcium phosphate hydroxyappatite (HA) in crystalline ceramic form.</p><p class="abstract"><strong>Methods:</strong> Sixteen cases of benign lytic and cystic lesions of bone were managed by simple curettage and grafting using hydroxyappatite blocks. Displaced pathological fractures or impending peritrochanteric fractures were fixed by implant. Commercially available HA was used for this purpose. Mean duration of follow up was 17.5 months (range 12<strong> </strong>–30 months). Mean patient age was 11.2 years (range 6–20 years). Radiological staging of graft incorporation was done as per criteria of Irwin et al.<strong></strong></p><p class="abstract"><strong>Results:</strong> Among 16 cases, 2 patients presented with non-ossifying fibroma and 2 patients with simple bone cyst, 12 cases were aneurysmal bone cyst. 5 patients had pathological fracture. Healing of lesion and graft incorporation is seen in all of the cases. At 6 months of follow up 3 cases were in Irwin stage III, 9 cases were in Irwin stage II and 4 cases were in Irwin stage I. At final follow up 10 cases were in Irwin stage III and rest was in Irwin stage II. No recurrence seen till date.</p><p class="abstract"><strong>Conclusions:</strong> We conclude that meticulous curettage and filling of bone cavity by calcium phosphate hydroxyappatite and fixation with implant in displaced pathological fracture or impending fracture is the procedure of choice of management of benign lytic lesions of bone.</p>

“Can you tell me why you made that choice?”: A qualitative study of the influences on treatment decisions in advance care planning among adolescents and young adults undergoing bone marrow transplant

Background: Adolescent and young adult advance care planning is beneficial in improving communication between patients, surrogates, and clinicians. The influences on treatment decisions among adolescents and young adults are underexplored in the literature. Aim: The aim of this study was to explore and better understand the influences on decision-making for adolescent and young adult bone marrow transplant patients about future medical care. Design: Clinical case studies and qualitative inductive content analysis of treatment decisions made during the Respecting Choices® Next Steps Pediatric Advance Care Planning conversation as a component of the Family-Centered Advance Care Planning Intervention. Settings/participants: A total of 10 adolescent and young adult patients (aged 14–27 years) undergoing bone marrow transplant at an academic Midwest children’s hospital were involved in the study. Results: Influences on participants’ decisions were consideration for family, quality of life, and awareness of self. Desire to avoid suffering and maintain an acceptable quality of life was often in competition with participant’s concern over the perceived negative impact of discontinuing treatment on their families. Conclusion: This study highlights that adolescent and young adult bone marrow transplant patients are capable of meaningful deliberation about future treatment decisions. Influences on decision-making should be incorporated into advance care planning conversations to facilitate communication between patients and their surrogates. Longitudinal research is needed to explore these influences throughout the trajectory of illness.

Prognostic profiling of the immune cell microenvironment in Ewing´s Sarcoma Family of Tumors

ABSTRACTEwing´s Sarcoma Family of Tumors (ESFT) are clinically aggressive bone and soft tissue tumors in children and young adults. Analysis of the immune tumor microenvironment (TME) provides insight into tumor evolution and novel treatment options. So far, the scarcity of immune cells in ESFT has hindered a comprehensive analysis of rare subtypes. We determined the relative fraction of 22 immune cell types using 197 microarray gene expression datasets of primary ESFT tumor samples by using CIBERSORT, a deconvolution algorithm enumerating infiltrating leucocytes in bulk tumor tissue. The most abundant cells were macrophages (mean 43% of total tumor-infiltrating leukocytes, TILs), predominantly immunosuppressive M2 type macrophages, followed by T cells (mean 23% of TILs). Increased neutrophils, albeit at low number, were associated with a poor overall survival (OS) (p = .038) and increased M2 macrophages predicted a shorter event-free survival (EFS) (p = .033). High frequency of T cells and activated NK cells correlated with prolonged OS (p = .044 and p = .007, respectively). A small patient population (9/32) with combined low infiltrating M2 macrophages, low neutrophils, and high total T cells was identified with favorable outcome. This finding was confirmed in a validation cohort of patients with follow up (11/38). When comparing the immune TME with expression of known stemness genes, hypoxia-inducible factor 1 α (HIF1α) correlated with high abundance of macrophages and neutrophils and decreased T cell levels. The immune TME in ESFTs shows a distinct composition including rare immune cell subsets that in part may be due to expression of HIF1α.

Proteomic and N-Terminomic TAILS Analyses of Human Alveolar Bone Proteins: Improved Protein Extraction Methodology and LysargiNase Digestion Strategies Increase Proteome Coverage and Missing Protein Identification.

With 2129 proteins still classified by the Human Proteome Organisation Human Proteome Project (HPP) as "missing" without compelling evidence of protein existence (PE) in humans, we hypothesized that in-depth proteomic characterization of tissues that are technically challenging to access and extract would yield evidence for tissue-specific missing proteins. Paradoxically, although the skeleton is the most massive tissue system in humans, as one of the poorest characterized by proteomics, bone falls under the HPP umbrella term as a "rare tissue". Therefore, we aimed to optimize mineralized tissue protein extraction methodology and workflows for proteomic and data analyses of small quantities of healthy young adult human alveolar bone. Osteoid was solubilized by GuHCl extraction, with hydroxyapatite-bound proteins then released by ethylenediaminetetraacetic acid demineralization. A subsequent GuHCl solubilization extraction was followed by solid-phase digestion of the remaining insoluble cross-linked protein using trypsin and then 6 M urea dissolution incorporating LysC digestion. Bone extracts were digested in parallel using trypsin, LysargiNase, AspN, or GluC prior to liquid chromatography-mass spectrometry analysis. Terminal Amine Isotopic Labeling of Substrates was used to purify semitryptic peptides, identifying natural and proteolytic-cleaved neo N-termini of bone proteins. Our strategy enabled complete solubilization of the organic bone matrix leading to extensive categorization of bone proteins in different bone matrix extracts, and hence matrix compartments, for the first time. Moreover, this led to the high confidence identification of pannexin-3, a "missing protein", found only in the insoluble collagenous matrix and revealed for the first time by trypsin solid-phase digestion. We also found a singleton proteotypic peptide of another missing protein, meiosis inhibitor protein 1. We also identified 17 proteins classified in neXtprot as PE1 based on evidence other than from MS, termed non-MS PE1 proteins, including ≥9-mer proteotypic peptides of four proteins.

Functional outcome of limb salvage surgery in gaint cell tumour around knee with mega-endoprosthetic reconstruction

Introduction: Giant cell tumors (GCTs) represent 3-4% of all primary tumors of bone [1]. These tumour are locally aggressive and predominantly affect the ends of long bones (usually the distal femur and proximal tibia) in young adults. The ideal aim in the management of GCT is to eradicate the tumor without sacrificing the joint. Wide resection should be the treatment of choice, especially for situations such as recurrences, pathological fractures and tumors which are frankly malignant tumorAim: To determine the functional outcome and complications of mega endoprosthesis in treatment of gaint cell tumour around knee joinMaterials and Methods: Retrospective study conducted from 2010 to 2016 with age ranging from 16 to 30 years with follow up period- 48 months. All patient with primary GCTs around knee who had met with inclusion criteria underwent surgery. All patient underwent definitive wide local resection and Mega-endoprosthetic reconstruction, Functional outcome was scored by musculoskeletal tumour society scoring (MSTS). Complications related to surgery such as Infection, Aseptic loosening, Dislocation, Skin necrosis and Fractures were evaluated. The diagnosis was based on histopathological features noted on a core biopsy. Patients with a high-grade GCT were subjected to computed tomography of the chest and bone scan for metastatic evaluation.Results: The average MSTS functional score was 75% (Range- 60% to 100%), 4-year survival rate was 100% in our study. Average range of movements at 4 years was 80 (70-90). Among the 8 patients, 2 had complications related to surgery. One had infection which required intravenous antibiotics treatment but infections did not subsided so patient underwent allograft bone transplant with arthrodesis. One had foot drop secondary to common peroneal palsy, Six months post-surgery, he was able to walk with a single crutch and coped well with his foot drop. Conclusions: Wide resection and endoprosthetic replacement should be considered as a preferred treatment option in treatment of aggressive gaint cell tumour around knee joint. Mega-endoprosthetic reconstruction provides good functional outcome in patients with these kind of tumour and can be considered as treatment of choice if and when the limb can be salvageable.

Smoking Modifies the Genetic Risk for Early-Onset Periodontitis

Periodontitis has low-prevalence, highly severe disease manifestations with an early onset and rapid progression. The diagnosis is based on severe destruction of the alveolar bone in adolescents and young adults. Genetic susceptibility variants and smoking are well-established risk factors, but their interactions in modifying disease susceptibility have not been studied. We aimed to identify genetic risk variants of early-onset periodontitis that unmask their effects on tobacco smoke exposure. To this end, we analyzed 79,780,573 common variants in 741 northwest Europeans diagnosed to have >30% bone loss at >2 teeth before 35 y of age, using imputed genotypes of the OmniExpress BeadChip. Never versus ever smokers were compared in a logistic regression analysis via a case-only approach. To explore the effect of tobacco smoke on the expression of the G×S-associated genes, cultures of primary gingival fibroblasts (n = 9) were exposed to cigarette smoke extract, and transcripts were quantified by reverse transcription polymerase chain reaction. We identified 16 loci for which our analysis suggested an association with G×S increased disease risk (P < 5 × 10−5). Nine loci had previously been reported to be associated with spirometric measures of pulmonary function by an earlier G×S genome-wide association study. Genome-wide significant cis expression quantitative trait loci were reported for G×S-associated single-nucleotide polymorphisms at ST8SIA1 and SOST, indicating a causal role of these genes in tobacco-related etiopathology. Notably, SOST is a negative regulator of bone growth, and ST8SIA1 has a role in tissue remodeling. Cigarette smoke extract significantly altered the expression of 2 associated genes: SSH1 (P = 5 × 10−07), which is required for NF-κB activation and innate immune responses to bacterial invasion, and ST8SIA1 (P = 0.0048). We conclude that the genetic predisposition to early-onset periodontitis is in part triggered by smoking and that tobacco smoke directly affects the expression of genes involved in bone homeostasis, tissue repair, and immune response.

Sex-Specific Muscular Mediation of the Relationship Between Physical Activity and Cortical Bone in Young Adults.

Muscle mass is a commonly cited mediator of the relationship between physical activity (PA) and bone, representing the mechanical forces generated during PA. However, neuromuscular properties (eg, peak force) also account for unique portions of variance in skeletal outcomes. We used serial multiple mediation to explore the intermediary role of muscle mass and force in the relationships between cortical bone and moderate-to-vigorous intensity PA (MVPA). In a cross-sectional sample of young adults (n = 147, 19.7 ± 0.7 years old, 52.4% female) cortical diaphyseal bone was assessed via peripheral quantitative computed tomography at the mid-tibia. Peak isokinetic torque in knee extension was assessed via Biodex dynamometer. Thigh fat-free soft tissue (FFST) mass, assessed via dual-energy X-ray absorptiometry, represented the muscular aspect of tibial mechanical forces. Habitual MVPA was assessed objectively over 7 days using Actigraph GT3X+ accelerometers. Participants exceeded MVPA guidelines (89.14 ± 27.29 min/day), with males performing 44.5% more vigorous-intensity activity relative to females (p < 0.05). Males had greater knee extension torque and thigh FFST mass compared to females (55.3%, and 34.2%, respectively, all p < 0.05). In combined-sex models, controlling for tibia length and age, MVPA was associated with strength strain index (pSSI) through two indirect pathways: (i) thigh FFST mass (b = 1.11 ± 0.37; 95% CI, 0.47 to 1.93), and (i) thigh FFST mass and knee extensor torque in sequence (b = 0.30 ± 0.16; 95% CI, 0.09 to 0.73). However, in sex-specific models MVPA was associated with pSSI indirectly through its relationship with knee extensor torque in males (b = 0.78 ± 0.48; 95% CI, 0.04 to 2.02) and thigh FFST mass in females (b = 1.12 ± 0.50; 95% CI, 0.37 to 2.46). Bootstrapped CIs confirmed these mediation pathways. The relationship between MVPA and cortical structure appears to be mediated by muscle in young adults, with potential sex-differences in the muscular pathway. If confirmed, these findings may highlight novel avenues for the promotion of bone strength in young adults. © 2019 American Society for Bone and Mineral Research.

Abstract 2605: Mithramycin enhances the efficacy of etoposide in Ewing sarcoma cells and a mouse xenograft tumor model

Abstract Ewing sarcoma (ES) tumors arise in bone or soft tissue of children, adolescents, and young adults. The fusion protein and transcription factor, EWS-FLI1 is over-expressed in &amp;gt;85% of ES tumors. High throughput screening with approximately 50,000 compounds identified Mithramycin (MIT) as an inhibitor of EWS-FLI1. A previous clinical trial to test the efficacy of MIT was not successful, presumably due to toxicity from the high dose required to inhibit EWS-FLI1. We hypothesize that the efficacy and safety of treatment can be enhanced if MIT is used along with standard chemotherapeutic agents. Accordingly, preclinical experiments were conducted to test combination treatment with chemotherapeutic agents used for the treatment (standard care) of ES. After screening several chemotherapeutic agents used in the standard treatment of ES, Etoposide (VP-16) was tested for further experiments. ES cells, CHLA10 and TC205 were treated in the presence of vehicle (Dimethyl sulfoxide), or optimized doses of MIT, VP-16 or MIT+VP-16. The effect of these treatments on cell growth inhibition was studied at 48-hour post-treatment using a luminescent (CellTiter-Glo®) cell viability assay kit. The effect of these treatments on programmed cell death was measured by evaluating the apoptotic cell population using Flow cytometry with Annexin V Apoptosis Detection Kit and the expression of a protein marker, Cleaved-Poly (ADP-ribose) polymerase (c-PARP), by Western blot analysis. Nude mice were injected subcutaneously with TC205 cells, treated with MIT, ETO or MIT+VP-16 and the tumor growth inhibition was assessed. As expected, all treatments showed a dose and time-dependent effect on ES cell growth inhibition; however, the combination treatment of MIT+VP-16 was significantly (p&amp;lt;0.01) more effective than individual agents. The cell growth inhibition in combination treatment was accompanied by an increase in apoptotic cells and c-PARP expression in both ES cell lines. The combination treatment significantly (p&amp;lt;0.01) decreased the tumor weight and volume when compared to control or the groups treated by either MIT or VP-16. The combination of MIT and VP-16 is effective when compared to individual treatments in the TC205 and CHLA10 cell lines and inhibited tumor growth in a mouse model. Among the two cell lines tested, CHLA10 cell line expresses EWS-FLI1 while mTC205 cell line does not express EWS-FLI1. These results demonstrate that the combination of MIT and VP-16 is inhibiting both cell lines, suggesting a novel mechanism of targeting the ES cells even in the absence of EWS-FLI1 expression. These results demonstrate that MIT in combination with the chemotherapeutic agent VP-16 increases therapeutic efficacy in a preclinical model for ES and demonstrates strong potential for translational application. Citation Format: Anish Ray, Umesh T. Sankpal, Lina Albeer, Abigail Hunter, Holly Lout, Kathryn Dunlap, W. Paul Bowman, Don Eslin, Riyaz M. Basha. Mithramycin enhances the efficacy of etoposide in Ewing sarcoma cells and a mouse xenograft tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2605.

Abstract CT109: A Phase I dose escalation and expansion study of seclidemstat (SP-2577) a first-in class reversible LSD1 inhibitor for patients with relapsed or refractory Ewing sarcoma

Abstract Introduction: Ewing sarcoma is an aggressive pediatric and young adult bone tumor dependent almost exclusively on the EWS/ETS fusion protein family for transcriptional activity. EWS/FLI is the most common fusion resulting in the repression of vital tumor suppressor genes by the activity of lysine-specific histone demethylase 1 (LSD1). Seclidemstat (SP-2577) is a first in class, orally bioavailable, small molecule with reversible and noncompetitive selective inhibition of LSD1 at low nanomolar concentrations (IC50: 25-50 nM). Seclidemstat has demonstrated disruption of global transcriptional function of EWS/ETS fusions and impairs multiple EWS/ETS-associated oncogenic phenotypes in xenograft models of Ewing sarcoma. This Phase I study aims primarily to assess the safety and tolerability of seclidemstat and to secondarily characterize the pharmacokinetics (PK), food effects, and preliminary anti-tumor activity via RECIST 1.1. Exploratory objectives include using circulating tumor cells, cell-free DNA, and hemoglobin F as pharmacodynamic markers of response. Methods: This multi-center phase I study (NCT03600649) is open-label and non-randomized and utilizes an accelerated dose escalation phase followed by a conventional 3+3 design to determine the maximum tolerated dose (MTD). Initially, one subject per dose cohort will be recruited in the accelerated dose escalation phase until the first instance of grade 2 or greater drug related toxicity or dose limiting toxicity (DLT). Further cohorts will be recruited in cohorts of three subjects in the 3+3 dose escalation phase. Once a declared suitable dose and schedule for further investigation has been identified, 14 additional patients will be enrolled in the dose expansion part of the study for a total of 20 patients treated at the MTD. The starting dose of seclidemstat is 75 mg PO BID with seven dose levels planned by modified Fibonacci schema. Food effects on PK are planned on day 1 and 2 of cycles 1 and 2. Patients at least 12 years of age will be included with histologically confirmed relapsed or refractory Ewing sarcoma with adequate performance status and organ function. Archival tumor tissue is required during screening. Tumor biopsies and measurable disease are required in dose expansion only. This trial is currently open for requirement at five locations in the United States. Dose level 2 (150 mg PO BID) began enrollment in November 2018 with no drug related grade 2 or greater adverse events or DLTs observed in dose level 1. Citation Format: Damon Reed, Steven G. DuBois, Richard Gorlick, Leo Mascarenhas, Douglas Harrison, Jonathan Metts, Stephen L. Lessnick, Brian D. Crompton, David M. Loeb, Rose Hernandez, Jeff Larson, David D. Stenehjem. A Phase I dose escalation and expansion study of seclidemstat (SP-2577) a first-in class reversible LSD1 inhibitor for patients with relapsed or refractory Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT109.

Racial differences in bone histomorphometry in children and young adults treated with dialysis.

Healthy African-Americans are known to have greater bone mineral density and decreased risk of fracture when compared to Caucasians. In fact, comparisons of bone histomorphometry in healthy South African children and adults reveal greater cortical thickness in Black subjects as compared to White. How these differences are reflected in the bone of American children and young adults on dialysis is unknown. Using tetracycline-labeled, iliac crest bone biopsies obtained in prior research protocols in pediatric and young adult dialysis patients, we compared trabecular and cortical parameters between non-Hispanic African-American subjects and non-Hispanic Caucasian subjects matched by age and gender. A linear regression model controlled for trabecular turnover and mineralization was used to further investigate the association of race with cortical thickness. The matched cohort consisted of 52 subjects-26 African-American and 26 Caucasian. Turnover, mineralization and volume parameters in trabecular bone did not show significant differences between racial groups. Characterizing subjects by renal osteodystrophy type did not show a statistically significant difference although Caucasian patients had double the prevalence of mineralization defects. Consistent with this was a trend toward better mineralization parameters in African-Americans including shorter osteoid maturation time and lower osteoid volume. A sub-cohort of patients with cortical measures demonstrated greater median (IQR) cortical thickness in African-Americans (541 μm [354, 694]) than in Caucasians (371 μm [336, 446], p = 0.08). In a linear regression model controlling for trabecular turnover and mineralization, African-American subjects had 36.2% (95% CI 0.28 to 85.1%, p = 0.048) greater cortical thickness as compared to White subjects. There was no significant difference in cortical porosity. Although likely limited by sample size, our findings suggest that, similar to findings in populations of normal children, African-American race in pediatric and young adults on dialysis is associated with greater cortical thickness. Additionally, there was a trend toward greater mineralization defects in Caucasian children. Both findings require further exploration with larger patient samples in order to thoroughly explore these racial differences and the implications on CKD-MBD treatment.

Dental and craniofacial alterations in long-term survivors of childhood head and neck rhabdomyosarcoma

Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma that affects children. Treatment involves chemoradiotherapy. This study aimed at evaluating the long-term alterations to teeth and cranial bones in children, teenagers, and young adults after oncologic treatment. We conducted a cross-sectional study of patients undergoing treatment for head and neck RMS between 1988 and 2011. We evaluated demographic, clinical, and treatment data and performed panoramic radiography, cephalometry, and photography. We evaluated 27 long-term survivors, most of whom had been treated between ages 0 to 5 years (51.9%). The total radiation dose applied was 50.4 Gy, and the chemotherapy combination included vincristine, actinomycin D, and cyclophosphamide in 51.9% of the cases. We observed 603 dental alterations, among which 377 (62.7%) occurred in patients ages 0 to 5 years, and root shortening was the most frequent alteration observed (24.2%). With regard to facial bones, 74% of the patients had some level of facial asymmetry, 70.4% had reduced facial depth, 48.4% had mandibles of short size, and 77.8% had reduced facial height. Children submitted to RMS treatment involving chemotherapy and radiotherapy displayed significant dental and craniofacial alterations, especially when treatment occurred between ages 0 and 5 years.

Molecular mechanisms underlying the inhibitory effects of bovine lactoferrin on osteosarcoma

Osteosarcoma (OS) is one the most common primary malignancies of the bone in children and young adults with high metastasis. The use of non-toxic naturally derived compounds is one of present strategies in OS therapy to reduce secondary effects and chemo-resistance. Lactoferrin (LF), a transferrin protein derived from milk, currently appears to be an anticancer agent. However, its suppressive effects on OS have not been fully investigated. Therefore, we aimed to examine the molecular mechanism underlying the inhibitory effects of bovine LF (bLF) on OS. OS cell lines (NOS1, U2OS, MG63, and 143B) and an osteoblastic (ST2) were treated with bLF. Effects of bLF on OS-cell proliferation and migration were examined by proliferation and wound-healing assays. Expression levels of low-density-lipoprotein-receptor-related protein 1 (LRP1) and cytokines including interleukin-1 beta (IL-1β), IL-6, and receptor-activator of nuclear factor kappa-Β ligand (RANKL) were measured using western blotting. Osteoclast formation was examined by co-culture of 143B, ST2, and bone marrow cells. We found that bLF down-regulated IL-1β, IL-6, and RANKL expression and suppressed phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 in 143B cells; bLF also drastically suppressed 143B-activated RANKL production in ST2 cells. This may have contributed to the reduction in the number of differentiated osteoclasts. Taken together, these data reveal that bLF down-regulates NF-κB to attenuate proliferation, migration, and bone resorption in OS and the OS-microenvironment. This study provides new findings and the precise underlying mechanisms of the inhibitory effects of bLF on OS. bLF can be a possible therapeutic agent for OS patients.

Inter-rater Variability in the Interpretation of Pre and Post Contrast MRI for Pre-Surgical Evaluation of Osteosarcoma in Long Bones in Pediatric Patients and Young Adults

Background and ObjectivesThe value of gadolinium enhanced magnetic resonance imaging (MRI) sequences for extremity osteosarcoma resection planning is unverified. We evaluate the performance of intravenous gadolinium enhanced MRI for identification of neurovascular bundle involvement (NBI) and intraarticular extension (IAE) in patients with osteosarcoma. MethodsTwo pediatric radiologists independently analyzed MRI examinations of patients with pathology proven extremity osteosarcoma for NBI and IAE. Initial evaluation utilized only non-contrast MRI images (PRE) and, after 2 weeks, subsequent evaluation included both the pre and post contrast images (POST). Cohen’s Kappa and McNemar’s test were calculated to assess agreement between PRE and POST image interpretations of NBI and IAE. Results56 patients with 90 preoperative MRI examinations were analyzed. PRE and POST interpretations were rarely discordant; 4/90 cases for NBI (Kappa 0.91) and 2/90 cases for IAE (Kappa 0.95). McNemar’s test did not show a difference between PRE and POST imaging (NBI p=0.62; IAE p=0.48). ConclusionNo significant difference between PRE and POST image interpretation was found. A high level of agreement between PRE and POST image interpretation suggests that pre-contrast MRI may be sufficient for pre-surgical planning for pediatric patients with long bone osteosarcoma.

Documentation of Late-Effects Risks and Screening Recommendations for Adolescent and Young Adult Central Nervous System, Soft Tissue, or Bone Tumor Survivors Treated with Radiotherapy in British Columbia, Canada.

To assess the documentation of late-effects (LE) risks and screening recommendations in medical records of adolescent and young adult central nervous system (CNS), soft tissue, and bone tumor survivors. The medical records of all patients diagnosed with a CNS neoplasm, an arteriovenous malformation, a soft tissue, and bone tumor, at ages 15-39 years, treated between 1985 and 2010 with radiation therapy in the province of British Columbia, Canada, surviving >5 years, alive, and discharged to the community were assessed. The documentation of LE risks and screening recommendations were analyzed descriptively. In the medical records of 132 CNS tumor survivors and 94 soft tissue or bone tumor survivors, 15% and 13% included no documentation of LE risks, 21% and 22% included only nonspecific documentation, and 64% and 65% minimal documentation, respectively. Documentation of at least one specific LE risk increased significantly among CNS tumor patient charts (from 29% in 1980-1989, to 67% in 1990-1999, to 88% in 2000-2010, χ2 [2, N = 132] = 32.257, p < 0.000) and soft tissue or bone tumor patient charts (from 47% [1980-1989] to 56% [1990-1999] to 78% [2000-2010], χ2 [2, N = 94] = 6.702, p = 0.035). There was no documentation of a screening recommendation in 75% of CNS tumor patient charts and 91% of soft tissue and bone tumor charts. The documentation of LE risks and screening recommendations has been limited, highlighting the need to improve written communication with primary care providers.

LncRNA LINC00628 overexpression inhibits the growth and invasion through regulating PI3K/Akt signaling pathway in osteosarcoma.

Osteosarcoma (OS) is the most common primary malignancy, mainly arising from the metaphysic of the long bones of adolescents and young adults. Although osteosarcoma has been studied widely, the underlying molecular mechanism remains unclear. Increasing evidence shows that abnormal long non-coding RNAs (LncRNAs) expression is involved in tumorigenesis. The aim of this study was to identify the detailed role of LncRNA LINC00628 in osteosarcoma. The relative mRNA expression level of LINC00628 in adjacent tissues, osteosarcoma tissues with or without metastasis and osteosarcoma cell lines were detected by qRT-PCR. Overall survival curves for two groups defined by high and low expression level of LINC00628 in osteosarcoma patients. The cell proliferation, invasion and migration in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were detected. The cell cycle distribution and apoptosis rate in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were measured using the Flow cytometry analysis. The relative protein expression level of p-PI3K, p-Akt, P53 and Bcl-2 in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were detected by Western blot. LINC00628 expression was significantly decreased in osteosarcoma tissues compared with adjacent tissues. Meanwhile, osteosarcoma tissues with metastasis were significantly associated with a low expression level of LINC00628 and the low expression level of LINC00628 has a lower overall survival rate. LINC00628 expression was increased in osteosarcoma cell lines after transfection with lncRNA-LINC00628 and the cell proliferation, invasion and migration in osteosarcoma cells after transfection with lncRNA-LINC00628 were significantly inhibited. Moreover, the cell cycle was arrested in G0/G1 phase and the apoptosis rate was increased in osteosarcoma cells after transfection with lncRNA-LINC00628. Mechanistically, the relative protein expression level of p-PI3K, p-Akt and Bcl-2 were significantly increased and the relative expression of P53 was significantly decreased in osteosarcoma cells after transfection with lncRNA-LINC00628. LINC00628 expression was decreased in osteosarcoma. The overexpression of LINC00628 inhibited the proliferation, invasion and migration and promoted cell apoptosis in osteosarcoma cells through the inactivation of PI3K/Akt signaling pathway. This lncRNA may be involved in the development and progression of osteosarcoma.

Primary Intraosseous Carcinoma, Not Otherwise Specified, of the Gnathic Bones: Report of Two Cases

Primary intraosseous carcinoma, NOS (PIOC) is a rare central jaw carcinoma, not classified as any other type of carcinoma, with a suggested odontogenic origin. Here, we present 2 additional cases of PIOC. A 39-year-old man presented with an irregular asymptomatic swelling in the anterior upper vestibule and palate and palpable fixed lymph nodes. Periapical radiography analysis revealed an ill-defined unilocular radiolucency in the periradicular region of endodontically treated maxillary incisors with irregular root resorption. The second case involved a 35-year-old man presenting with an asymptomatic, unilocular, ill-defined radiolucency superimposed on the mandibular molars roots, with loss of lamina dura. Microscopically, both the cases showed small islands of neoplastic epithelial proliferation with cellular atypia and keratinization, confirming the final diagnosis of PIOC. Patients were referred to an oncology service. Clinicians should consider PIOC when evaluating an ill-defined radiolucency in tooth-bearing areas of gnathic bones of young adults.

Contribution of High School Sport Participation to Young Adult Bone Strength

Nearly 8 million American adolescents participate in sports. Participation declines in young adulthood. This study assessed longitudinal effects of high school sport participation and muscle power on young adult bone strength. Two hundred twenty-eight young adults from the Iowa Bone Development Study completed an interscholastic sport participation questionnaire. Current physical activity (PA) behaviors were assessed via questionnaire. Dual x-ray absorptiometry assessed hip areal bone mineral density and was used with hip structure analysis to estimate femoral neck section modulus and hip cross-sectional area. Peripheral quantitative computed tomography provided strength-strain index and bone strength index at 38% and 4% midshaft tibial sites, respectively. Vertical jump estimated muscle power at 17 yr. Sex-specific multiple linear regression predicted young adult bone outcomes based on sport participation groups. Mediation analysis analyzed the effects of muscle power on relationships between sport participation and bone strength. At follow-up, males participating in any interscholastic sport had greater bone strength than males who did not participate in sport. The explained variability in bone outcomes was 2% to 16%. Females who participated in sports requiring muscle power had greater bone strength than females who did not participate in sports or females who participated in nonpower sports (explained variability was 4%-10%). Muscle power mediated 24.7% to 41% of the effect of sport participation on bone outcomes in males and 19.4% to 30% in females. Former male interscholastic sport participants and female interscholastic power sport participants have stronger bones than peers even when adjusting for current PA. Muscle power did not fully explain differences in all bone outcomes, suggesting that sport participation has additional bone health benefits.

Multicentric giant cell tumour of the mandible: a clinical rarity

AbstractGiant cell tumours of bone (GCT) are benign, locally aggressive tumours affecting the epiphyseal regions of long bones in young adults. These non‐odontogenic tumours rarely present in the oral cavity, either peripherally in soft tissues (gingiva) or centrally (in bone). GCT account for &lt;7% of all benign jaw lesions and may present as aggressive or non‐aggressive clinical forms. Histologically, these lesions are usually composed of mononuclear stromal cells and characteristic multinucleated giant cells that exhibit osteoclastic activity. Multicentricity of GCT of bone is an extreme rarity accounting for &lt;1% of these tumours. The biological behaviour and the clinical presentation (e.g. localisation, age, and gender distribution) of multicentric GCT are different from solitary lesions. As other primary bone lesions may also have a polyostotic presentation, the precise diagnosis relies on correlation of clinical and radiographic findings with confirmation of the diagnosis by histopathologic examination. We encountered one such interesting case in a 12‐year‐old boy, who presented with pedunculated fibrous growth arising from the gingiva in the left mandibular posterior region along with extensive osteolytic lesions of ramus of mandible bilaterally. The workup and management of the case is hereby presented along with relevant review of literature.

The top 100 most-cited articles on osteosarcoma: a bibliometric analysis

Background: Osteosarcoma or “osteogenic sarcoma” is the most common neoplasm of the bone in children and young adults. This research is premised upon a citation analysis of the top 100 most-cited articles on osteosarcoma. Materials and Methods: This research is dependent upon the use of SCOPUS database. Using the search strategy “osteosarcoma” on this database yielded 12,107 articles. After filtering for relevant articles, the top 100 most-cited articles were retrieved for descriptive and statistical analysis. Results: The most-cited paper was “A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma” by Friend and colleagues published in 1986 with 1888 citations. The publication years ranged from 1967 to 2014. The United States was the most productive country in terms of research output, followed by Italy. Institution-wise, the Memorial Sloan-Kettering Cancer Centre contributed the most articles. However, the most prolific author was from Italy. Majority of the publications were level IV studies Conclusions: Although citation analysis is not entirely flawless, this is a comprehensive list of the top 100 most-cited articles significantly impacting osteosarcoma knowledge and research over time. Future studies need to cater toward maximizing high-quality evidenced articles.

Chondromyxoid Fibroma Arising in Craniofacial Sites: A Clinicopathologic Analysis of 25 Cases.

Chondromyxoid fibroma (CMF) is a rare benign tumor, usually arising in the metaphysis of long bones in young adults. Occurrence in craniofacial bones presents a particular diagnostic challenge given its unusual location and resemblance to malignant mimics. We describe the clinicopathologic features of 25 cases of craniofacial CMF identified between 1999 and 2017. Patients were 14 men and 11 women, with median age of 44 years (range, 5 to 83 y). Sites of involvement were sphenoid (7), ethmoid (5), maxilla (3), occipital (2), nasal septum (2), palatine (2), temporal (2), orbit (1), and undisclosed skull (1). Tumor size ranged from 0.8 to 6.0 cm (median, 2.0 cm). Of the 21 tumors with available radiology, 15 arose on the bone surface with expansion into adjacent sinuses; 6 were intraosseous. Bony erosion/destruction was present in most (13/16) cases, and 7/12 showed calcification on imaging. Microscopically, most tumors showed a lobulated growth pattern with hypocellular central chondromyxoid areas and peripheral hypercellularity, though many samples were fragmented. Tumor cells had ovoid to tapered nuclei and abundant palely eosinophilic cytoplasm, frequently with stellate cell processes. Mitoses ranged from 0 to 2 per 10 high-power fields (median count, 0). None showed necrosis. Significant atypia was present in 2 cases, 1 of which was a previously radiated recurrence. Bone infiltration was present in 6 cases. Thirteen tumors had focal calcification, and 2 had foci of hyaline cartilage. All tumors were negative for keratin and GFAP (0/24), with frequent positivity for SMA (7/7) and occasional staining for EMA (5/24) and S-100 (2/24). Most patients underwent piecemeal excision or curettage (5/5 positive margins when reported). Follow-up data were available for 15 patients, and 5 suffered local recurrence. Craniofacial CMF poses diagnostic pitfalls including frequent aggressive radiologic features and lack of a specific immunophenotype. Tumors may recur, largely due to the difficulty of obtaining clear surgical margins in this anatomic region. Furthermore, propensity for local destruction and invasion can create significant morbidity.