Response to Chemotherapy in Overweight/Obese Patients With Low-Risk Gestational Trophoblastic Neoplasia

Objective Despite rising global obesity rates, the impact of obesity on gestational trophoblastic neoplasia (GTN) remains uninvestigated. This study aimed at investigating whether overweight/obesity relates to response to chemotherapy in low-risk GTN patients.Methods This nonconcurrent cohort study included 300 patients with International Federation of Gynecology and Obstetrics-defined postmolar low-risk GTN treated with a single-agent chemotherapymethotrexate or actinomycin-D (actD)between 1973 and 2012 at the New England Trophoblastic Disease Center. Chemotherapy dosing was based on actual body weight regardless of obesity status, except for 5-day courses or pulse regimens of actD. Patients were classified as overweight/obese (body mass index [BMI] 25 kg/m(2)) or non-overweight/obese (BMI <25 kg/m(2)). Information on patient characteristics and response to chemotherapy (need for second-line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles, need for combination chemotherapy, and time to human chorionic gonadotropin remission) was obtained.Results Of 300 low-risk GTN patients, 81 (27%) were overweight/obese. Overweight/obese patients were older than the non-overweight/obese patients (median age: 30 vs 28 years, P = 0.004). First-line therapy using actD was more frequent in overweight/obese patients (6.2% vs 1.4%, P = 0.036). Resistance and toxicity were similar between groups. No significant difference in the number of chemotherapy cycles needed for remission or time required to achieve remission was found between groups.Conclusions No association between overweight/obesity and low-risk GTN outcomes was found. Current chemotherapy dosing using BMI seems to be appropriate for overweight/obese patients with low-risk GTN.

Gestational protein malnutrition impairs c-myc and p63 protein expression, increases prostatic intraepithelial neoplasia incidence and prostatitis aggressiveness in adult male offspring subjected to hormonal handling

Background: Prostate cancer is the second most common cancer diagnosed in men; however its etiology remains unknown. Previous studies have shown that environmental adverse factors, such as maternal nutritional status during pregnancy, can influence fetal development and predispose people to diseases in adult life. The feeding of low-protein diets to pregnant rats result in fetal growth disturbance, androgen/estrogen unbalance and changes in the expression and sensibility of hormone receptors in male offspring. These alterations can promote permanent changes in androgen dependent organs, such as in the prostate. In this sense, we hypothesized that the hormonal unbalance that occurs during aging can lead to an increase in the susceptibility to prostatic disorders. Aim: To evaluate our hypothesis, malnourished male rat offspring were submitted to simultaneous estrogen and testosterone exposure in adulthood, to drive lesions in the rat ventral prostate gland (VP). Methods: 17 week-old Wistar rats (n=48) that received in utero normal protein diet (NP group, AIN93G=17% protein) or low protein diet (RP group, AIN93G modified=6% protein) were given implants with 17β-estradiol plus testosterone administration (NPH and RPH groups) for 17 weeks. The animals were killed at the age of 34 weeks and the VP were excised, weighted and processed for histopathological, immunohistochemical (Ki67, AR, p63, e-caderin, laminin, c-myc and GSTP), biochemical and ultrastructural analysis. Results: Both absolute and relative VP weight from NPH animals were about 30% higher than RPH. Serological data showed that estradiol levels were similar in both groups, but testosterone levels were lower in the RPH male offspring. The steroid hormone exposure in adult life promoted prostate lesions in both RPH and NPH offspring associated with reactive stroma. VP from RPH group exhibited heightened susceptibility to prostatic intraepithelial neoplasia (mainly cribriform and signet ring-cell patterns) and increased the incidence and aggressiveness of prostatitis. In this group, a higher proportion of basal cells, increased proliferation index, lower expression ofthe androgen receptor and increased focus of collagenous micronodules closely associated to epithelial neoplasias were also observed. Conclusion:These observations suggest that maternal protein restriction alters adult prostate response to androgen/estrogen handling and increases susceptibility to prostate diseases. Ethical protocol:CEEA,476/2013 IBB-UNESP; Funding Support: 2009/50204-6 and 2013/09649-0.

Hormonal contraceptive use before hCG remission does not increase the risk of gestational trophoblastic neoplasia following complete hydatidiform mole: a historical database review

To re-evaluate the safety of hormonal contraceptives (HC) after uterine evacuation of complete hydatidiform mole (CHM). Historical database review. Charing Cross Hospital Gestational Trophoblastic Disease Centre, London, United Kingdom. Two thousand four hundred and twenty-three women with CHM of whom 154 commenced HC while their human chorionic gonadotropin (hCG) was still elevated, followed between 2003 and 2012. We compared time to hCG remission between HC users and nonusers. The relationship between HC use and gestational trophoblastic neoplasia (GTN) development was assessed. The relationship between HC use and a high International Federation of Gynecology and Obstetrics (FIGO) risk score was determined. Time to hCG remission, risk of developing postmolar GTN and proportion of women with high FIGO risk score. No relationship was observed between HC use with mean time to hCG remission (HC users versus non-users: 12 weeks in both, P = 0.19), GTN development (HC users versus non-users: 20.1 and 16.7%, P = 0.26) or high-risk FIGO score (HC users versus nonusers: 0% and 8%, P = 0.15). Moreover, no association between HC and GTN development was found, even when an age-adjusted model was used (OR = 1.37, 95% CI 0.91-2.08, P = 0.13). The use of current HC is not associated with development of postmolar GTN or delayed time to hCG remission. Therefore, HC can be safely used to prevent a new conception following CHM regardless of hCG level. Non-concurrent cohort study to re-evaluate the safety of low dose HCs after uterine evacuation of CHM.

Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors alpha and beta were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-alpha, CD68, IL-6, IL-8, ER alpha, ER beta) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.

Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood

Background Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood. Methods and Findings A sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures. Conclusions The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.

Management and organisational barriers in the acquisition of computer usage skills by mature age workers

Aim: To investigate workplace cultures in the acquisition of computer usage skills by mature age workers. Methods: Data were gathered through focus groups conducted at job network centres in the Greater Brisbane metropolitan region. Participants who took part were a mixture of workers and job-seekers. Results: The results suggest that mature age workers can be exposed to inappropriate computer training practices and age-insensitive attitudes towards those with low base computer skills. Conclusions: There is a need for managers to be observant of ageist attitudes in the work place and to develop age-sensitive strategies to help mature age workers learn computer usage skills. Mature age workers also need to develop skills in ways which are practical and meaningful to their work.

Maternal age and paternal age are associated with distinct childhood behavioural outcomes in a general population birth cohort

Abstract Background Recent studies show that advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism, bipolar disorder and schizophrenia. A body of evidence also suggests that individuals who develop schizophrenia show subtle deviations in a range of behavioural domains during their childhood. The aim of the study was to examine the relationship between paternal and maternal ages and selected behavioural measures in children using a large birth cohort. Method Participants were singleton children (n = 21,753) drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 7 years. The main analyses examined the relationship between parental age and behavioural measures when adjusted for a range of potentially confounding variables, including age of the other parent, maternal race, socio-economic measures, sex, gestation length, maternal marital status, parental mental illness, and child's age-at-testing. Results Advanced paternal age was associated with a significantly increased risk of adverse ‘externalizing’ behaviours at age seven years. For every five year increase in paternal age, the odds of higher ‘externalizing’ behaviours was increased by 12% (OR = 1.12; 95% CI = 1.03, 1.21, p < 0.0001). The relationship persisted after adjusting for potential confounding factors. ‘Internalizing’ behavioural outcome was not associated with advanced paternal age. In contrast, advanced maternal age was significantly protective against adverse ‘externalizing’ behavioural outcomes, but associated with an increased risk of adverse ‘internalizing’ behavioural outcomes. Discussion The offspring of older fathers show a distinctly different pattern of behaviours compared to the offspring of older mothers. The diverse socio-cultural and biologically-mediated factors that underpin these findings remain to be clarified. In light of secular trends related to delayed parenthood, the mechanisms underlying these findings warrant closer scrutiny.