Acral myxoinflammatory fibroblastic sarcoma with hybrid features of hemosiderotic fibrolipomatous tumor occurring 10 years after renal transplantation.

Myxoinflammatory fibroblastic sarcoma is a rare malignant soft tissue neoplasm that typically arises on the distal extremities of adults. It usually behaves in a low-grade manner and its characteristic histology is of a lobulated proliferation of moderately atypical spindled to epithelioid cells, vacuolated cells, and enlarged or bizarre cells with prominent nucleoli, dispersed within myxoid stroma containing a mixed inflammatory cell infiltrate. The etiology of myxoinflammatory fibroblastic sarcoma remains unknown with no definite causal factors identified. We describe a case of myxoinflammatory fibroblastic sarcoma arising in the foot of a 77-year-old female, which rapidly recurred locally after initial excision and which arose 10 years after renal transplantation. The neoplasm also showed intermingled areas of hemosiderotic fibrolipomatous tumor. The patient also had multifocal areas of squamous cell carcinoma in situ of the foot and hand, in keeping with the clinical context of immune deficiency. This is the second case of myxoinflammatory fibroblastic sarcoma reported to occur after transplantation, but additionally shows hybrid features of hemosiderotic fibrolipomatous tumor, highlights immunocompromise/immunosuppressive therapy as a possible etiologic factor in their development, and adds to the growing number of myxoinflammatory fibroblastic sarcoma that has demonstrated aggressive behavior

OX40 and 4-1BB delineate distinct immune profiles in sarcoma.

Systemic relapse after radiotherapy and surgery is the major cause of disease-related mortality in sarcoma patients. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates. However, the immune contexture of sarcoma is understudied. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data. We explore therapeutic targets of relevance to sarcoma, using genomics and multispectral immunohistochemistry to provide insights into the tumor immune microenvironment across sarcoma subtypes. Differential gene expression between radioresponsive myxoid liposarcoma (MLPS) and more radioresistant undifferentiated pleomorphic sarcoma (UPS) indicated UPS contained higher transcript levels of a number of immunotherapy targets (CD73/NT5E, CD39/ENTPD1, CD25/IL2RA, and 4-1BB/TNFRSF9). We focused on 4-1BB/TNFRSF9 and other costimulatory molecules. In TCGA data, 4-1BB correlated to an inflamed and exhausted phenotype. OX40/TNFRSF4 and 4-1BB/TNFRSF9 were highly expressed in sarcoma subtypes versus other cancers. Despite OX40 and 4-1BB being described as Treg markers, we identified that they delineate distinct tumor immune profiles. This was true for sarcoma and other cancers. While only a limited number of samples could be analyzed, spatial analysis of OX40 expression identified two diverse phenotypes of OX40+ Tregs, one associated with and one independent of tertiary lymphoid structures (TLSs). Patient stratification is of intense interest for immunotherapies. We provide data supporting the viewpoint that a cohort of sarcoma patients, appropriately selected, are promising candidates for immunotherapies. Spatial profiling of OX40+ Tregs, in relation to TLSs, could be an additional metric to improve future patient stratification

Associations of infant milk feed type on early postnatal growth of offspring exposed and unexposed to gestational diabetes in utero

10.1007/s00394-015-1057-0European Journal of NutritionGUSTO (Growing up towards Healthy Outcomes

Associations of Maternal Dietary Patterns during Pregnancy with Offspring Adiposity from Birth Until 54 Months of Age

10.3390/nu9010002Nutrients91article no. 2GUSTO (Growing up towards Healthy Outcomes

Associations of gestational glycemia and prepregnancy adiposity with offspring growth and adiposity in an Asian population

10.3945/ajcn.115.117614American Journal of Clinical Nutrition10251104-1112GUSTO (Growing up towards Healthy Outcomes

Determinants of cord blood adipokines and association with neonatal abdominal adipose tissue distribution

Background Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother-offspring cohort. Methods Growing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother-offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed. Results Indian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only. Conclusions Cord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.Peer reviewe

Associations of maternal retinal vasculature with subsequent fetal growth and birth size

10.1371/journal.pone.0118250PLoS ONE104e0118250GUSTO (Growing up towards Healthy Outcomes

Supervised Machine-Learning Enables Segmentation and Evaluation of Heterogeneous Post-treatment Changes in Multi-Parametric MRI of Soft-Tissue Sarcoma.

Background: Multi-parametric MRI provides non-invasive methods for response assessment of soft-tissue sarcoma (STS) from non-surgical treatments. However, evaluation of MRI parameters over the whole tumor volume may not reveal the full extent of post-treatment changes as STS tumors are often highly heterogeneous, including cellular tumor, fat, necrosis, and cystic tissue compartments. In this pilot study, we investigate the use of machine-learning approaches to automatically delineate tissue compartments in STS, and use this approach to monitor post-radiotherapy changes. Methods: Eighteen patients with retroperitoneal sarcoma were imaged using multi-parametric MRI; 8/18 received a follow-up imaging study 2-4 weeks after pre-operative radiotherapy. Eight commonly-used supervised machine-learning techniques were optimized for classifying pixels into one of five tissue sub-types using an exhaustive cross-validation approach and expert-defined regions of interest as a gold standard. Final pixel classification was smoothed using a Markov Random Field (MRF) prior distribution on the final machine-learning models. Findings: 5/8 machine-learning techniques demonstrated high median cross-validation accuracies (82.2%, range 80.5-82.5%) with no significant difference between these five methods. One technique was selected (Naïve-Bayes) due to its relatively short training and class-prediction times (median 0.73 and 0.69 ms, respectively on a 3.5 GHz personal machine). When combined with the MRF-prior, this approach was successfully applied in all eight post-radiotherapy imaging studies and provided visualization and quantification of changes to independent STS sub-regions following radiotherapy for heterogeneous response assessment. Interpretation: Supervised machine-learning approaches to tissue classification in multi-parametric MRI of soft-tissue sarcomas provide quantitative evaluation of heterogeneous tissue changes following radiotherapy

Ethnic differences in effects of maternal prepregnancy and pregnancy adiposity on offspring size and adiposity

10.1210/jc.2015-1728The Journal of Clinical Endocrinology & Metabolism100103641–3650GUSTO (Growing up towards Healthy Outcomes