Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen-biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (< 25 kg/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast (CLS-B) which are comprised of dead or dying adipocytes surrounded by macrophages. Severity of inflammation was measured as CLS-B/cm2. The primary objective was to determine if breast WAT inflammation is associated with aromatase expression and activity. Secondary objectives included assessment of circulating factors and breast adipocyte size. Breast WAT inflammation was present in 39% of women. Median BMI was 23.0 (range 18.4 to 24.9) in women with breast WAT inflammation versus 21.8 (range 17.3 to 24.6) in those without inflammation (P=.04). Breast WAT inflammation was associated with elevated aromatase expression and activity, which increased with severity of inflammation (P<.05). Breast WAT inflammation correlated with larger adipocytes (P=.01) and higher circulating levels of C-reactive protein, leptin, insulin, and triglycerides (P≤.05). A subclinical inflammatory state associated with elevated aromatase in the breast, adipocyte hypertrophy, and systemic metabolic dysfunction occurs in some normal BMI women and may contribute to the pathogenesis of breast cancer.
Multidisciplinary simulation-based team training is feasible and well received by surgical teams. Non-technical skills can be assessed alongside technical skills, and differences in performance indicate where there is a need for further training. Future work should focus on developing team performance measures for training and on the development and evaluation of systematic training for technical and non-technical skills to enhance team performance and safety in surgery.
Background
Obesity, a cause of subclinical inflammation, is associated with increased risk of high grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown.
Methods
In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives were to explore the clinical and systemic correlates of periprostatic WAT inflammation. Tumor characteristics and host factors including BMI, adipocyte diameter, and circulating levels of lipids, adipokines, and other metabolic factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher’s exact tests, and generalized linear regression were used to examine the association between WAT inflammation and tumor and host characteristics.
Results
Periprostatic fat was collected from 169 men (median age 62 years; median BMI 28.3). Periprostatic WAT inflammation was identified in 49.7% of patients and associated with higher BMI (P=0.02), larger adipocyte size (P=0.004), and Gleason grade groups IV/V tumors (P=0.02). The relationship between WAT inflammation and high Gleason grade remained significant after adjusting for BMI (P=0.04). WAT inflammation correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to those without WAT inflammation (P’s <0.05).
Conclusions
Periprostatic WAT inflammation is common in this cohort of men with PC and is associated with high grade PC.
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