Amy LaLonde

MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions

Summary Minichromosomal maintenance (MCM) proteins are participants of DNA replication and may represent more accurate markers in determining the proliferative fraction within a tumor than proliferative marker Ki-67. Our study investigated the correlation between MCM4 and MCM7 expression and Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. MCM4 and MCM7 expression had similar distribution as Ki-67 and Bmi1 expression in esophageal carcinoma and pre-cancerous lesions. The mean percentage of MCM4, MCM7, and Ki-67 expression increased from squamous epithelium (5.5%, 7.3%, and 5.9%, respectively), to columnar cell metaplasia (11.2, 13.5%, and 3.4%), Barretts esophagus (27.7%, 35.3%, and 8.3%), low-grade dysplasia (42.6%, 52.2%, and 12.9%), high-grade dysplasia (63.2%, 77.7%, and 29.6%), adenocarcinoma (61.3%, 75.5%, and 24.5%), and squamous cell carcinoma (74.1, 85.4%, and 36.3%). The percentages of MCM4 and MCM7 expression were significantly higher than Ki-67 expression. Using univariate analysis we found a high percentage of MCM4 expression (>70%) to be significantly associated with lymph node metastasis and shorter survival in the adenocarcinoma group. We also demonstrated the percentage of MCM4 and MCM7 expression to be significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal carcinoma and precancerous lesions. MCM4 and MCM7 may serve as more sensitive proliferative markers for the evaluation of esophageal lesions.

Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences

Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions. We analyzed genomic DNA from 116 EACs for copy number aberrations via Affymetrix SNP6.0 microarrays. The TGR5 gene locus was amplified in 12.7% (14/116) of the EACs. The TGR5 protein expression was also assessed using immunohistochemistry from tissue microarrays, including Barrett’s esophagus (BE), low-(LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CM), squamous epithelium (SE), EAC and squamous cell carcinoma. The TGR5 protein was highly expressed in 71% of EAC (75/106), 100% of HGD (11/11), 72% of LGD (13/18), 66% of BE (23/35), 84% of CM (52/62), and 36% of SE (30/83). The patients with high expression of TGR5 exhibited significantly worse overall survival compared to the patients with nonhigh expression. TGR5 high expression was significantly increased in the males compared to the females in all cases with an odds ratio of 1.9 times. The vitamin D receptor (VDR) was significantly correlated with TGR5 expression. Our findings indicated that TGR5 may play an important role in the development and prognosis of EAC through a bile acid ligand. Gender differences in TGR5 and VDR expression may explain why males have a higher incidence of EAC compared to females.

151 Race and Insurance Status Are Associated With Higher Charges in Patients Having Pituitary Tumor Surgery in New York State.

INTRODUCTION Cost of care can be influenced by factors unrelated to quality. We previously demonstrated that, for patients undergoing pituitary tumor surgery, hospital costs, charges, and length of stay (LOS) across New York State were significantly affected by surgeon volume and geographic location. To identify factors that may have gone unnoticed, we conducted further analysis to identify patient-related factors present in low- vs high-charging hospitals. METHODS We performed cost analysis on pituitary tumor surgery cases previously identified in the New York State inpatient database (SPARCS 2006-2012). Controlling for surgeon volume, hospital location, and LOS, a Bayesian model-based clustering method segregated hospitals into low, medium, and high charging; subsequent analysis of variance (ANOVA) and linear regression identified patient factors that were statistically different between these groups. RESULTS Two thousand seven hundred eighty-four surgeries were performed in New York (2006-2012), 63% of patients were white, and 66% were privately insured, with Medicare/Medicaid covering 32%. Among low (6), medium (31), and high charge hospitals (32), median charges were

Placental concentrations of essential, toxic, and understudied metals and relationships with birth outcomes in Chattanooga, TN

10 740,

Using the Seychelles child development study to cluster multiple outcomes into domains to improve estimation of the overall effect of mercury on neurodevelopment

24 221, and

Obesity candidate genes, gestational weight gain, and body weight changes in pregnant women

43 520, respectively. Mean percentages of white patients were 14%, 48%, and 54%; mean percentages of privately insured patients were 28%, 40% and 60%. The association between race, insurance status and hospital charges was significant using both one-way ANOVA (race, P = .047; insurance status P = .011) and linear regression (race, P = .035; insurance status, P = .003). Costs and LOS were not different between low-, medium-, and high-charging hospitals. CONCLUSION When studying patients having pituitary tumor surgery, high-charging hospitals had a statistically significant increased proportion of white and privately insured patients, even though the cost of providing the service and the LOS (an indirect proxy for quality) was no different from low-charging hospitals. Understanding the forces that influence hospital charges will be important to improve health care quality and cost effectiveness.

Effect of oral sodium bicarbonate on fibroblast growth factor-23 in patients with chronic kidney disease: A pilot study

Background: Comprehensive examinations of placental metal concentrations and correlations with infant parameters are under‐investigated. Chattanooga, Tennessees consistently high incidence of low birth weight and potential for metal exposure provides an ideal opportunity to investigate potential correlations. Objectives: To investigate the associations between a wide variety of metals in placental tissue and multiple infant parameters. Methods: A total of 31 elements were screened via ICP‐MS in 374 individual placental samples. Of those, 14 were quantifiable in > 86% of the samples. We examined correlations between metal concentrations and infant parameters (birth weight, gestational age, birth weight centile, placental weight, birth length and head circumference). We fit multivariable regression models to estimate the covariate‐adjusted associations of birth weight with ln‐transformed concentrations of each of the 14 metals and used generalized additive models to examine nonlinear relationships. Results: Some of the strongest relationships with infant parameters came from several lesser‐studied metals. Placental rhodium concentrations were negatively correlated with almost all infant parameters. In the fully adjusted regression model, birth weight was significantly associated with several metals. On an IQR (25th to the 75th percentile) basis, estimated changes in birthweight were: for cobalt (82.5 g, IQR=6.05 &mgr;g/kg, p = 0.006), iron (−51.5 g, IQR = 171800 &mgr;g/kg, p = 0.030), manganese (−27.2 g, IQR=152.1 &mgr;g/kg, p = 0.017), lead (−72.7 g, IQR=16.55 &mgr;g/kg, p = 0.004) and rhodium (−1365.5 g, IQR = 0.33 &mgr;g/kg, p < 0.001). Finally, a generalized additive model showed significant nonlinear relationships between birth weight and concentrations of Co and Rh. Conclusions: Our comprehensive examination of placental metals illustrate many strong associations between lesser‐studied metals and infant parameters. These data, in combination with our correlations of well‐studied metals, illustrate a need to consider in utero exposure to a broad array of metals when considering fetal development.

Geographic variation in cost of care for pituitary tumor surgery.

Environmental exposure effects on human development can be small and difficult to detect due to the nature of observational data. In the Seychelles Child Development Study, researchers examined the effect of prenatal methylmercury exposure using a battery of tests measuring aspects of child development [23, 25]. We build a multiple outcomes model similar to that of the previous analyses (see [23, 25]); however, our multiple outcomes model makes no assumptions of relationships between the testing outcomes. Instead, the nesting of outcomes into domains is a clustering problem we address with a Dirichlet process mixture model implemented through a Bayesian MCMC approach [16]. This model provides inference for the methylmercury exposure effect as well as greater insight into the similarities and differences across the outcomes.

Sa1918 TGR5, a Bile Acid Receptor, Is Highly Expressed in Esophageal Adenocarcinoma and Precancerous Lesions Significantly Associated With Worse Overall Survival and Gender Difference

OBJECTIVE To examine the associations of two obesity-associated genes, FTO (rs9939609) and GNB3 (rs5443) single nucleotide polymorphisms (SNPs), with early pregnancy body mass index, gestational weight gain, and postpartum weight retention. METHODS Secondary data analysis of self-identified white (n = 580) and black (n = 194) women who participated in a randomized controlled trial (2009-2014) and provided a saliva sample of DNA. Bivariate relationships were assessed using analysis of variance. Multiple regression models assessed the relationship between outcomes and gene SNPs, controlling for income, parity, and smoking status. RESULTS FTO and GNB3 gene associations with pregnancy weight were different by racial group and early pregnancy body mass index. Obese black women homozygote for the FTO risk allele (AA) had a higher gestational weight gain compared with non-risk homozygotes (TT) (P = 0.006). GNB3 non-risk CC homozygotes tended to have a lower gestational weight gain compared with heterozygotes (P = 0.05). White GNB3 C carriers tended to be heavier in early pregnancy (P <0.1) and GNB3 homozygote (TT) overweight women tended to have lower postpartum weight retention than C carriers. CONCLUSIONS The FTO gene and possibly the GNB3 gene are associated with high gestational weight gain in obese black women. Obese carriers of the FTO risk allele gained 4.1 kg (AT) and 7.6 kg (TT) more than those without risk alleles. Overweight GNB3 heterozygotes (CT) gained 6.6 kg less than homozygotes (CC). Overweight or obese black women who have either risk variant are at risk for high gestational weight gain.