Aberrant lipid homeostasis is a feature of diabetes and obesity. This metabolic imbalance is associated with excessive levels and/or actions of glucocorticoids (GCs) and contributes to dyslipidemia including elevated hepatic triglyceride (TG)-rich very low-density lipoprotein (VLDL-TG) secretion. The mediobasal hypothalamus (MBH) is a nutrient and hormone sensing brain region that regulates whole-body lipid metabolism and VLDL-TG secretion. We aimed to assess GC action in the MBH in regulating VLDL-TG secretion in health and diet-induced hyperlipidemia. Sprague Dawley rats received stereotaxic MBH cannulation and vascular catheterizations to enable direct MBH infusions, intravenous injections, and blood sampling. Plasma TG levels and the rate VLDL-TG secretion were measured in 10h-fasted rats following intravenous poloxamer injection with concomitant MBH infusions. In healthy rats, direct MBH GC infusion increased VLDL-TG secretion compared to controls. MBH GC action is mediated via its receptor (GR) since mifepristone (GR antagonist) co-infusion, chronic inhibition of GRs in the MBH with GR shRNA, or inhibition of heat shock protein 90 (required for in vivo GR function) negated the MBH GC-induced increases in VLDL-TG secretion rate. High-fat diet-fed rats had both elevated basal plasma GC levels and hepatic TG secretion compared to healthy rats. Remarkably, chronic MBH GR loss-of-function lowered VLDL-TG secretion in high-fat diet-induced hyperlipidemic rats, independent of changes in body weight. Here, we provide novel in vivo evidence that MBH GC action modulates VLDL-TG secretion and suggest that blocking excessive GC action in the brain improves lipid homeostasis in diet-induced hyperlipidemic rats. These findings may provide insight on lowering lipid levels in diabetes and obesity. Disclosure M. Cardoso: None. M. Wang: None. E. Ling: None. H. Lee: None. E. Beaulieu-Bayne: None. J.T. Yue: None. Funding Diabetes Canada; Natural Sciences and Engineering Research Council of Canada; Canadian Lipoprotein Conference
e22511 Background: Since 2006 breast cancer has been the main cause of cancer mortality in Mexican women representing 14% of cancer related deaths. In Mexico the incidence and mortality of breast cancer have increased in recent decades and will continue to rise. Despite the vast information media on the prevention of this cancer the diagnosis of between 50 - 70% of cases is carried out in advanced stages probably due to a limited understanding of knowledge and practices of early prevention for breast cancer. Methods: The study universe was 375 Mexican women between 30 - 58 years of age of any socioeconomic level in the open population of Orizaba Veracruz who signed the informed consent form. The socioeconomic level was determined with the index of the Asociación Mexicana de Inteligencia de Mercado y Opinión Pública. The level of knowledge was determined by means of a 10 question survey type test on knowledge and practices of early prevention of breast cancer, based on Norma Oficial Mexicana 041. Period: March-May 2019. Results: Of the 375 women, 145-38.7% corresponded to high, 109-29.1% to medium high, 62-16.5% to medium, 26-6.9% to medium low, 17-4.5% to upper low and 16-4.3% to low socioeconomic levels, respectively. Mean age: 43.17 +7.82. Levels of knowledge were high in 28-7.5%, medium in 211-56.3%, low in 134-35.7% and null in 2-0.5% women respectively. 360-96% received information about prevention of breast cancer . 248-66% knew 1 to 3 risk factors, 101-27% >4 risk factors and 26-7% no risk factors. 338-90% know where to go in case of finding an abnormality in their breasts. 272-72% know the age at which they should perform the first self examination, 76-20% know the age at which they should go with trained health personnel for the exploration of their breasts. 233-62% know the age at which the first mammogram should be performed, 91-24% know the age at which the last mammogram should be performed and 8-22% know the frequency of time that a mammogram should be performed. 247-65% have had the 2 corresponding mammograms in the last 4 years. We recognize that this study may have as a limitation that the sample of patients comprises a specific group of Mexican women, however, due to its heterogeneity, its demographic characteristics could be applicable to Mexico and Latin America. Conclusions: Knowledge of the prevention of breast cancer is medium observing a direct relationship between the socioeconomic level and the level of knowledge. Effective communication between health professionals and women must take into account the socioeconomic level of patients in order to achieve a greater understanding of it and potentially reduce the incidence and mortality rate of breast cancer. It is important not to stop emphasizing the importance of continuing medical education and patient education programs for the early detection of breast cancer by patients and first contact physicians as well as primary and secondary prevention strategies which are vitally important in developing countries.
416 Background: The outcomes of patients (pts) with advanced pancreatic cancer (APC) are poor. With the use of currently available multi-agent regimens, median overall survival (mOS) remains < 12 months. Select pts, however, experience a protracted survival. Little is known about the clinical, pathologic and treatment characteristics associated with long term survival (LTS) in APC. Methods: Pooled individual level data from six Canadian cancer centers of pts diagnosed with APC from 2012 to 2016 who received at least one cycle of chemotherapy (CT) were analyzed. Clinical, pathologic and treatment characteristics, as well as survival, were compared between pts who lived < and ≥ 18 months. Multivariable logistic regression was used to identify independent predictors of survival. Results: Of 455 pts, 96% had metastatic disease and 88 (19%) survived ≥ 18 months. Compared to pts who survived < 18 months, those with LTS had lower WBC (p = 0.0025), CA 19-9 (p < 0.001), ALP (p < 0.001) and LDH (p = 0.007) at baseline. Pts with LTS also had higher albumin (p < 0.001) and BMI (p = 0.0268). In addition, they had better ECOG (p < 0.001) and were more likely to have tumors in the head of the pancreas (p = 0.0204). LTS pts were more likely to have a complete response (CR) or partial response (PR) to 1L CT (p < 0.001). The mOS seen with LTS was 29.2 months, compared to 4.3 months (p < 0.001). On multivariable logistic regression, independent predictors of LTS included: primary tumor in the head of the pancreas (OR 3.42 95% CI 1.2-9.76); experiencing a CR or PR to 1L CT (OR 9.19 95% CI 3.78-22.32); and receipt of 2L doublet CT (OR 2.72 95% CI 1.05 to 7.08). Conversely, factors associated with lower likelihood of LTS included: ECOG ≥ 2 (OR 0.32 95% CI 0.11-0.95); and elevated CA 19-9 (OR 0.43 95% CI 0.21-0.9). Conclusions: A select proportion of pts with APC experience LTS and have clinical features which differentiate them from those without LTS. The use of performance status, primary tumor location, pre-treatment CA 19-9, 2L CT type and radiologic response may help identify LTS and inform discussions regarding treatment and prognosis.
650 Background: The survival of patients (pts) with APC (locally advanced/metastatic) is slowly improving; however, in some pts it remains extremely short. Few studies have evaluated the clinical, pathologic and treatment characteristics associated with STS in APC. Methods: Pts with APC (between 2011-2017) were included in the analysis. Descriptive analyses were conducted for demographic, tumor and treatment characteristics between pts who survived ≤ and > 90 days using Wilcoxon rank-sum test and Chi-square test for continuous and categorical variables respectively. Multivariable logistic regression was performed to identify association between pts’ characteristics and STS. Results: A total of 580 pts were included in the analysis: median age 68, 53% male, 92% metastatic and 53% ECOG 0/1. STS ≤90 days occurred in 152 pts (26.2%), with 65.1% not receiving any chemotherapy. Median overall survival for STS was 49 days vs. 276 for non-STS. At least 1 cycle of chemotherapy was administered to 358 pts; mean duration of first-line chemotherapy for pts with STS ≤90 was 1.5(SD 2.5) cycles (N=53), compared to 7.6(SD 11.1) cycles (N=305) for pts surviving > 90 days. Prognostic factors associated with STS <90 days were neutrophil:lymphocyte ratio, LDH, metastatic disease, ECOG and not receiving chemotherapy (Table). Other clinical factors (BMI, smoking history, diabetes) and laboratory values (platelet, baseline CA19-9, estimated GFR) were not prognostic. Conclusions: In a multicenter database of Canadian academic centers, <2/3 of pts received at least 1 cycle of chemotherapy. Prognostic factors associated with STS include routine laboratory values, not receiving chemotherapy, ECOG and the presence of metastatic disease. Further evaluation of factors related to not receiving chemotherapy, and why chemotherapy is discontinued could improve the outcomes of pts with STS. [Table: see text]
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