Biphasic Synovial Sarcoma of the Extremity: Quadruple Approach of Isolated Limb Perfusion, Surgical Ablation, Adipofascial Perforator Flap and Radiation to Avoid Amputation

Synovial sarcoma is a rare type of soft tissue sarcoma that occurs mostly in young adults, and it is always regarded as a high-grade tumor. Here, we report the case of a 31-year-old German Caucasian male with synovial sarcoma of the wrist who was offered amputation at his local hospital. After referral to our Reference Centre for Soft Tissue Sarcoma, the quadruple approach of isolated limb perfusion, surgical ablation, adipofascial perforator flap and radiation avoided amputation and enabled preservation of good hand function with no evidence of recurrence or metastasis after 1 year

BMI Changes During Childhood and Adolescence as Predictors of Amount of Adult Subcutaneous and Visceral Adipose Tissue in Men: The GOOD Study

Objective. The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how body mass index (BMI) changes during childhood and adolescence predict adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous and visceral fat mass by BMI changes during childhood and adolescence. Research Design and Methods. Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n=612). Body composition was analysed using Dual X-Ray Absorptiometry and adipose tissue areas using abdominal computed tomography at 18-20 years of age. Results. The main finding in the present study was that subjects with increases in BMI Z-score of >1 SD during adolescence had, independent of prepubertal BMI, both larger subcutaneous (+138%; p1 SD during late childhood had larger amount adult subcutaneous adipose tissue (+83%;

Proliferation of Ewing sarcoma cell lines is suppressed by the receptor tyrosine kinase inhibitors gefitinib and vandetanib

<p>Abstract</p> <p>Background</p> <p>Tyrosine kinase inhibitors (TKIs) have gained much attention in recent years as targeted agents for the treatment of a wide range of human cancers. We have investigated the effect of the TKIs gefitinib and vandetanib on tumor cell lines derived from Ewing sarcoma, a highly malignant tumor affecting bone and soft tissue in children and young adults. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase activity (EGFR) and vandetanib selectively targets vascular endothelial growth factor receptor-2 (VEGFR-2) with additional activity against VEGFR-3, EGFR and RET kinase receptors.</p> <p>Results</p> <p>Two Ewing sarcoma cell lines investigated showed high levels of nuclear EGFR expression as well as moderate expression in plasma membrane and cytoplasm. When treated with concentrations of 5 μM and more of either gefitinib or vandetanib, we observed a significant decrease in cell proliferation. However, there were no detectable changes in p44/42 MAPK and Akt-1 phosphorylation, or in the expression of cyclin D1 or c-Myc following gefitinib or vandetanib treatment.</p> <p>Conclusion</p> <p>We conclude that Ewing sarcoma tumor cell proliferation is not highly sensitive to inhibition of EGFR signaling alone or the simultaneous inhibition of VEGFR receptors, EGFR and RET kinase. Decreased tumor cell proliferation could be achieved with gefitinib and vandetanib, but only at higher doses where non-specific effects of the compounds may be overriding. As Ewing tumor cells do not seem to depend on EGFR and VEGFR pathways for survival, other key factors in the cellular signaling of Ewing sarcoma should be targeted in order to obtain a potent therapeutic response.</p

Survival and prognostic factors in conventional G1 chondrosarcoma

Background Chondrosarcoma is the second most frequent malignant bone tumor. Grade I chondrosarcoma (syn.: atypical cartilaginous tumor) is classified as an intermediately and locally aggressive neoplasm and typically is treated less aggressively (i.e., by intralesional curettage). Does the data regarding local recurrence (LR) and metastatic disease justify this? Methods From 1982 to 2014, 37 consecutive patients with G1 chondrosarcoma had been resected or curetted. The margin was defined as R0 (wide resection) or R1 (marginal resection). All patients were followed for evidence of local recurrence or metastatic disease. Overall and recurrence-free survival were calculated, and various potentially prognostic factors were evaluated. Results In 23 patients (62%), the tumor was widely (R0) resected, whereas in 14 patients, (38%) the resection was marginal (R1). Overall survival was 97% after 5 years, 92% after 10 years, and 67% after 20 years. Five-year local recurrence-free survival was 96%. Ten-year local recurrence-free survival was 83%. Local recurrence-free survival showed a significant correlation to margin status but no correlation to location or age. None of the patients with local recurrence died during the follow-up. One patient had metastatic disease at initial presentation, and a further five patients developed metastatic disease during follow-up. Metastatic disease proofed to be a highly significant factor for survival but was not correlated to local recurrence. Conclusions There was no significant correlation between the outcome and the primary tumor location. Marginal resection was a risk factor for LR, but there was no significant difference in the overall survival in patients with or without LR. Metastatic disease (16%) was more common than expected from the literature and a significant predictor for poor overall survival

Genetic Regulation of the Growth Plate

The epiphyseal growth plate consists of a layer of cartilage present only during the growth period and vanishes soon after puberty in long bones. It is divided to three well-defined zones, from epiphyses; resting, proliferative, and hypertrophic zones. Chondrocyte proliferation and differentiation and subsequent bone formation in this cartilage are controlled by various endocrine, autocrine, and paracrine factors which finally results into elimination of the cartilaginous tissue and promotion of the epiphyseal fusion. As chondrocytes differentiate from round, quiescent, and single structure to flatten and proliferative and then large and terminally differentiated, they experience changes in their gene expression pattern which allow them to transform from cartilaginous tissue to bone. This review summarizes the literature in this area and shortly describes different factors that affect growth plate cartilage both at the local and systemic levels. This may eventually help us to develop new treatment strategies of different growth disorders

High penetrances of BRCA1 and BRCA2 mutations confirmed in a prospective series

Penetrances of BRCA1 and BRCA2 mutations have been derived from retrospective studies, implying the possibility of ascertainment biases to influence the results

Lymph Nodes Draining Infections Investigated by PET and Immunohistochemistry in a Juvenile Porcine Model

Background: [(18)F]FDG and [(11)C]methionine accumulate in lymph nodes draining S. aureus -infected foci. The lymph nodes were characterized by weight, [(11)C]methionine- and [(18)F]FDG-positron emissions tomography (PET)/computed tomography (CT), and immunohistochemical (IHC)-staining. Methods: 20 pigs inoculated with S. aureus into the right femoral artery were PET/CT-scanned with [(18)F]FDG, and nine of the pigs were additionally scanned with [(11)C]methionine. Mammary, medial iliac, and popliteal lymph nodes from the left and right hind limbs were weighed. IHC-staining for calculations of area fractions of Ki-67, L1, and IL-8 positive cells was done in mammary and popliteal lymph nodes from the nine pigs. Results: The pigs developed one to six osteomyelitis foci. Some pigs developed contiguous infections of peri-osseous tissue and inoculation-site abscesses. Weights of mammary and medial iliac lymph nodes and their [(18)F]FDG maximum Standardized Uptake Values (SUV(FDGmax)) showed a significant increase in the inoculated limb compared to the left limb. Popliteal lymph node weight and their FDG uptake did not differ significantly between hind limbs. Area fractions of Ki-67 and IL-8 in the right mammary lymph nodes and SUV(Metmax) in the right popliteal lymph nodes were significantly increased compared with the left side. Conclusion: The PET-tracers [(18)F]FDG and [(11)C]methionine, and the IHC- markers Ki-67 and IL-8, but not L1, showed increased values in lymph nodes draining soft tissues infected with S. aureus. The increase in [(11)C]methionine may indicate a more acute lymph node response, whereas an increase in [(18)F]FDG may indicate a more chronic response