Relation of adrenal-derived steroids with bone maturation,mineral density and geometry in healthy prepubertal and early pubertal boys

BackgroundLittle is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys.ObjectiveTo study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys.Methods98 healthy prepubertal and early pubertal boys (aged 6–14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand.ResultsAdrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD).ConclusionIn healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys.     

A comparison of patient-centered economic and clinical outcomes of post-mastectomy breast reconstruction between obese and non-obese patients

BackgroundThe objectives of this study were to compare, by patient obesity status, the contemporary utilization patterns of different reconstruction surgery types, understand postoperative complication profiles in the community setting, and analyze the financial impact on health care payers and patients.MethodsUsing data from the MarketScan Health Risk Assessment Database and Commercial Claims and Encounters Database, we identified breast cancer patients who received breast reconstruction surgery following mastectomy between 2009 and 2012. The Cochran-Armitage test was used to evaluate the utilization pattern of breast reconstruction surgery. Multivariable logistic regressions were used to estimate the association between obesity status and infectious, wound, and perfusion complications within one year of surgery. A generalized linear model was used to compare total, complication-related, and out-of-pocket costs.ResultsThe rate of TE/implant-based reconstruction increased significantly for non-obese patients but not for obese patients during the years analyzed, whereas autologous reconstruction decreased for both patient groups. Obesity was associated with higher odds of infectious, wound, and perfusion complications after TE/implant-based reconstruction, and higher odds of perfusion complications after autologous reconstruction. The adjusted total healthcare costs and out-of-pocket costs were similar for obese and non-obese patients for either type of breast reconstruction surgery.ConclusionsA greater likelihood of one-year complications arose from TE/implant-based vs autologous reconstruction surgery in obese patients. Given that out-of-pocket costs were independent of the type of reconstruction, greater emphasis should be placed on conveying the surgery-related complications to obese patients to aid in patient-based decision making with their plastic surgeons and oncologists.     

Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression

BackgroundAt diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients.Patients and methodsSpecimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62%) remained disease-free and 41 (38%) relapsed (median follow-up: 67 months, range 9–241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients.ResultsHigh expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67.ConclusionsBy demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.     

Best practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.     

The clinicopathologic relevance of RECK gene polymorphisms in ameloblastoma

ObjectiveTo investigate the relationship between RECK gene polymorphisms and the clinicopathologic features of ameloblastoma.DesignNormal gingival mucosa specimens were obtained from 10 healthy volunteers. Ameloblastomas were surgically removed from 30 patients and part of the tumor specimens were used to detect RECK gene polymorphisms by using PCR-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing analysis. Expression of RECK and MMP-9 protein was measured using western blot.ResultsThe overall SNP rate was 46.7% (14/30). Four polymorphisms were detected in exon 9, 11, 13, 15 of the RECK gene: two synonymous (P520P and R625R) and two missense SNPs (V275I and I395 V). RECK protein expression in specimens with minor RECK SNPs was lower than that in specimens without RECK SNPs (P < 0.05), and, RECK protein expression in specimens with and without RECK SNPs was lower than that in the normal gingiva specimens (P < 0.05). MMP-9 protein expression in specimens with minor RECK SNPs was higher than that in specimens without RECK SNPs (P < 0.05), and MMP-9 protein expression in specimens with and without RECK SNPs was higher than that in normal gingiva specimens (P < 0.05). RECK gene polymorphisms were closely associated with active proliferation, capsular invasion, and clinical recurrence of ameloblastoma.ConclusionThe rs16932912(G/A) SNP in the RECK gene was closely associated with active proliferation, capsular invasion, and clinical recurrence of ameloblastoma. RECK protein expression was closely associated with the presence of the rs16932912(G/A) SNP.