Citations

AbstractDespite improvements in operative strategies for esophageal resection, anastomotic leaks, fistula, postoperative pulmonary complications, and chylothorax can occur. Our review seeks to identify potential risk factors, modalities for early diagnosis, and novel interventions that may ameliorate the potential adverse effects of these surgical complications following esophagectomy.

PurposeTo build and evaluate a small‐footprint, lightweight, high‐performance 3T MRI scanner for advanced brain imaging with image quality that is equal to or better than conventional whole‐body clinical 3T MRI scanners, while achieving substantial reductions in installation costs.MethodsA conduction‐cooled magnet was developed that uses less than 12 liters of liquid helium in a gas‐charged sealed system, and standard NbTi wire, and weighs approximately 2000 kg. A 42‐cm inner‐diameter gradient coil with asymmetric transverse axes was developed to provide patient access for head and extremity exams, while minimizing magnet‐gradient interactions that adversely affect image quality. The gradient coil was designed to achieve simultaneous operation of 80‐mT/m peak gradient amplitude at a slew rate of 700 T/m/s on each gradient axis using readily available 1‐MVA gradient drivers.ResultsIn a comparison of anatomical imaging in 16 patients using T2‐weighted 3D fluid‐attenuated inversion recovery (FLAIR) between the compact 3T and whole‐body 3T, image quality was assessed as equivalent to or better across several metrics. The ability to fully use a high slew rate of 700 T/m/s simultaneously with 80‐mT/m maximum gradient amplitude resulted in improvements in image quality across EPI, DWI, and anatomical imaging of the brain.ConclusionsThe compact 3T MRI system has been in continuous operation at the Mayo Clinic since March 2016. To date, over 200 patient studies have been completed, including 96 comparison studies with a clinical 3T whole‐body MRI. The increased gradient performance has reliably resulted in consistently improved image quality.

Abstract The trend toward precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration-resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer–related genes. CTCs were isolated from the whole blood of mCRPC patients (n = 41) and multiplex qPCR was performed to evaluate expression of prostate cancer–related target genes (n = 78). A large fraction of patients (27/41, 66%) had detectable CTCs. Increased androgen receptor (AR) expression (70% of samples) and evidence of Wnt signaling (67% of samples) were observed. The TMPRSS2:ERG fusion was expressed in 41% of samples, and the aggressive prostate cancer–associated long noncoding RNA SChLAP1 was upregulated in 70%. WNT5a [HR 3.62, 95% confidence interval (CI), 1.63–8.05, P = 0.002], AURKA (HR 5.56, 95% CI, 1.79–17.20, P = 0.003), and BMP7 (HR 3.86, 95% CI, 1.60–9.32, P = 0.003) were independently predictive of overall survival (FDR < 10%) after adjusting for a panel of previously established prognostic variables in mCRPC (Halabi nomogram). A model including Halabi, WNT5a, and AURKA expression, termed the miCTC score, outperformed the Halabi nomogram alone (AUC = 0.89 vs. AUC = 0.70). Understanding the molecular landscape of CTCs has utility in predicting clinical outcomes in patients with aggressive prostate cancer and provides an additional tool in the arsenal of precision-based therapeutic approaches in oncology. Implications: Analysis of CTC gene expression reveals a clinically prognostic “liquid biopsy” signature in patients with metastatic castrate-resistance prostate cancer. Mol Cancer Res; 16(4); 643–54. ©2018 AACR.

AbstractObjectivesHigh body mass index (BMI) often predicts truncated breastfeeding, although why is unclear. We test a proposed mediating role of body concerns on breastfeeding initiation and child's age at weaning using longitudinal data for 55,522 mothers from the Norwegian Mother and Child Cohort Study (MoBa).MethodsA linear regression‐based mediation analysis with bootstrapping estimates the indirect effects of BMI on breastfeeding decisions (ever‐initiation of breastfeeding, child's age at weaning, and duration of any breastfeeding beyond six months) through the variables of concern around prepregnancy weight and weight gains due to pregnancy.ResultsContrary to prediction, Norwegian mothers with greater prepregnancy weight concerns had a higher likelihood of initiating breastfeeding. Concerns about weight gain during pregnancy, however, predicted earlier weaning. This relationship was the same for higher and lower BMI mothers.ConclusionIn this very large sample, body image affects some breastfeeding decisions. However, this effect is independent of mother's body size.

Tumor heterogeneity of a target molecule could contribute to failure of the targeted therapy. We investigated the heterogeneity of MET expression within same primary gastric cancer (GC) and between primary and corresponding secondary GC lesions using immunohistochemistry (IHC). Intratumoral heterogeneity was defined as discordant MET status among 3 tissue microarray cores (3 different areas of same tumor). IHC 3+ was considered positive for MET overexpression. MET overexpression was observed in 2.7% (50/1869) of all examined cores and 5.3% (33/623) of primary GCs. When we compared MET IHC results between 3 cores from each tumor, intratumoral heterogeneity was identified (65.0% in total 623 cases; 84.4% in 480 cases with any staining intensity; 84.9% in 251 cases with moderate to strong intensity; 90.9% in 33 cases with strong intensity). Of 33 MET-overexpressed GCs, the average proportion of strongly stained area was 19.6% in the whole sections. Of 269 cases with primary GC and regional lymph node metastasis, 17 (6.3%) showed MET positivity in which 9 (52.9%) were discordant (negative conversion). In 123 cases with primary and corresponding local recurrent/distant metastatic GC, 3 (2.4%) showed MET positivity in which 2 (66.7%) were discordant (positive conversion). In the survival analysis, MET IHC 3+ in lymph node metastases was an independent negative prognostic factor for overall survival. We found that MET overexpression is uncommon and highly heterogeneous in GC. This severe heterogeneity of MET status should be considered in tissue sampling and development of biomarkers for anti-MET therapy.