News Article | December 19, 2016
Other factors -- such as weight loss, a healthy diet and ceasing to smoke -- remain the top risk-reduction strategies both for developing cancer and premature cancer-related deaths COLUMBUS, Ohio - Regular use of over-the-counter non-steroidal inflammatory drugs (NSAIDs) such as aspirin and ibuprofen is associated with an increased risk of dying in patients diagnosed with Type 1 endometrial cancers, according to a new population-based study led by The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). In this observational study, a multi-institutional team of cancer researchers sought to understand the association of regular NSAID use and the risk of dying from endometrial cancer among a cohort of more than 4,000 patients. They found that regular NSAID use was associated with a 66 percent increased risk of dying from endometrial cancer among women with Type 1 endometrial cancers, a typically less-aggressive form of the disease. The association was statistically significant among patients who reported past or current NSAID use at the time of diagnosis, but it was strongest among patients who had used NSAIDs for more than 10 years in the past but had ceased use prior to diagnosis. Use of NSAIDs was not associated with mortality from typically more aggressive, Type 2 cancers. "There is a increasing evidence that chronic inflammation is involved in endometrial cancer and progression and recent data suggests that inhibition of inflammation through NSAID use plays a role," says Theodore Brasky, PhD, co-lead author of the study and a cancer epidemiologist with the OSUCCC - James. "This study identifies a clear association that merits additional research to help us fully understand the biologic mechanisms behind this phenomenon. Our finding was surprising because it goes against previous studies that suggest NSAIDs can be used to reduce inflammation and reduce the risk of developing or dying from certain cancers, like colorectal cancer." Researchers point out that information about specific dosages and NSAID use after surgery was not available in the current study, which represents a significant limitation. "We are continuing to analyze the biologic mechanisms by which inflammation is related to cancer progression in this specific cohort of patients," adds Ashley Felix, PhD, co-lead author of the study and cancer epidemiologist with the OSUCCC - James and College of Public Health. They report their findings in the Dec. 16, 2016, issue of the Journal of the National Cancer Institute. "These results are intriguing and worthy of further investigation," says David Cohn, MD, gynecologic oncology division director at the OSUCCC - James and co-author of the study. "It is important to remember that endometrial cancer patients are far more likely to die of cardiovascular disease than their cancer so women who take NSAIDs to reduce their risk of heart attack -- under the guidance of their physicians -- should continue doing so. While these data are interesting, there is not yet enough data to make a public recommendation for or against taking NSAIDS to reduce the risk of cancer-related death." Cohn says any woman concerned about the risks of long-term NSAID use should consult with her physician. For this study, researchers analyzed information from 4,374 endometrial cancer patients who previously participated in a national clinical trial (NRG Oncology/GOG 210). All of the women were eligible for surgery and had not undergone prior surgery or radiation at the time of enrollment. Participants were followed for an average of five years after enrollment. Study participants were asked at the beginning of the study to complete a questionnaire prior to surgery to capture information about previous and current NSAID use including aspirin, non-aspirin NSAIDs (ibuprofren, naproxen, indomethacin, piroxicam, sulinadac) and COX-2 inhibitors. Researchers collected information about duration of use -- ranging from less than one year to more than 10 years -- and whether that use was previous or current. Daily frequency of NSAID use, NSAID dosage, and use after surgery were not available. Researchers also collected clinical data (cancer stage, pathology, and treatment), demographic data (age, race, annual income, education) and information about established endometrial cancer risk factors, including body weight/height, reproductive and menstrual characteristics, history of hormone therapy, smoking status and other medical conditions. Researchers used regression models to statistically account for the influence of these additional factors on the association between NSAID use and endometrial cancer mortality. Funding for this research comes from grants to the NRG/Gynecologic Oncology Group (CA 27469, CA 37517, 1 U10 CA180822 and U10 CA180868); National Cancer Institute and National Institutes of Health. Additional collaborators in this study include Louise A. Brinton, PhD, of the National Cancer Institute; D. Scott McMeekin, MD, and Joan Walker, MD, of the University of Oklahoma; David Mutch, MD, and Premal Thaker, MD, Washington University School of Medicine; William Creasman, MD, Medical University of South Carolina; Richard Moore, MD, Women and Infants Hospital/Brown University; Shashikant Lele, MD, and John Boggess, MD, University of North Carolina; Saketh Guntupalli, MD, University of Colorado Cancer Center; Levi Downs, MD, University of Minnesota; Christa Nagel, MD, Case Western Reserve University; Michael Pearl, MD, State University of New York; Olga Ioffe, MD; University of Maryland; and Shamshad Ali, Roswell Park Cancer Institute. More than 60,000 women are diagnosed with endometrial cancer in the United States annually, making it the fourth most common cancer in women and sixth leading cause of cancer death. The cancer begins in the lining of the uterus and grows outward to surrounding organs. Type 1 tumors are less aggressive and are typically confined to the uterus at the time of diagnosis, whereas Type 2 tumors tend to be aggressive and are at greater risk of spreading. The disease is most common in women over age 60. Aside from aging, excess body weight, diabetes, certain hormone therapies, a family history of endometrial cancer or personal history of endometrial hyperplasia, breast cancer or ovarian cancer are associated with increased risk of the disease. The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs. As the cancer program's 306-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. For more information, please visit cancer.osu.edu.
Paepe M.E.D.,Women and Infants Hospital |
Paepe M.E.D.,Brown University
Seminars in Perinatology | Year: 2015
Twin birth rates have increased dramatically over the past three decades, and twins currently account for 3% of all pregnancies. Twin pregnancies of any type are at risk for prematurity. In addition, monochorionic twin pregnancies (25-30% of all twin pregnancies) are predisposed to a specific set of complications, including twin-to-twin transfusion syndrome (TTTS), twin reversed arterial perfusion syndrome (TRAP), malformations, and intertwin growth discordance. This article reviews the basic mechanisms underlying the twinning process, the relationship between zygosity and chorionicity, and the various types of twinning. We describe the major complications of monochorionic twinning in association with their reported placental characteristics (or lack thereof). Finally, a rational, evidence-based approach to examination of the twin placenta is presented. It is essential for the pathologist to understand the value, strengths, and limitations of examination of the twin placenta in order to provide a meaningful clinicopathological correlation in complicated (monochorionic) twin pregnancies. © 2014 Elsevier Inc.
Maccani M.A.,Brown University |
Padbury J.F.,Women and Infants Hospital |
Marsit C.J.,Brown University
PLoS ONE | Year: 2011
Background: Novel research has suggested that altered miRNA expression in the placenta is associated with adverse pregnancy outcomes and with potentially harmful xenobiotic exposures. We hypothesized that aberrant expression of miRNA in the placenta is associated with fetal growth, a measurable phenotype resulting from a number of intrauterine factors, and one which is significantly predictive of later life outcomes. Methodology/Principal Findings: We analyzed 107 primary, term, human placentas for expression of 6 miRNA reported to be expressed in the placenta and to regulate cell growth and development pathways: miR-16, miR-21, miR-93, miR-135b, miR-146a, and miR-182. The expression of miR-16 and miR-21 was markedly reduced in infants with the lowest birthweights (p<0.05). Logistic regression models suggested that low expression of miR-16 in the placenta predicts an over 4-fold increased odds of small for gestational age (SGA) status (p = 0.009, 95% CI = 1.42, 12.05). Moreover, having both low miR-16 and low miR-21 expression in the placenta predicts a greater increase in odds for SGA than having just low miR-16 or miR-21 expression (p<0.02), suggesting an additive effect of both of these miRNA. Conclusions/Significance: Our study is one of the first to investigate placental miRNA expression profiles associated with birthweight and SGA status. Future research on miRNA whose expression is associated with in utero exposures and markers of fetal growth is essential for better understanding the epigenetic mechanisms underlying the developmental origins of health and disease. © 2011 Maccani et al.
Caskey M.,Women and Infants Hospital |
Stephens B.,Community Medical Center |
Tucker R.,Women and Infants Hospital |
Vohr B.,Women and Infants Hospital
Pediatrics | Year: 2014
OBJECTIVE: The goal of this study was to test the association of mean adult word counts at 32 and 36 weeks' postmenstrual age in the NICU with Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), cognitive and language scores. It was hypothesized that preterm infants exposed to higher word counts would have higher cognitive and language scores at 7 and 18 months' corrected age. METHODS: This prospective cohort study included 36 preterm infants with a birth weight ≤1250 g. Sixteen-hour recordings were made in the NICU by using a digital language processor at 32 and 36 weeks' postmenstrual age. Regression analyses were performed on adult word count per hour, with Bayley-III measures correcting for birth weight. RESULTS: Adult word counts in the NICU were positively correlated with 7- and 18-month Bayley-III scores. For the 32-week recording, in regression analyses adjusting for birth weight, adult word count per hour independently accounted for 12% of the variance in language composite scores (P = .04) and 20% of the variance in expressive communication scores at 18 months (P = .008). For the 36-week recording, adult word count per hour independently accounted for 26% of the variance in cognitive composite scores at 7 months (P = .0049). CONCLUSIONS: Increased amount of parent talk with preterm infants in the NICU was associated with higher 7- and 18-month corrected age Bayley-III language and cognitive scores. These findings offer an opportunity for language intervention starting in the NICU. Copyright © 2014 by the American Academy of Pediatrics.
Caskey M.,Women and Infants Hospital |
Vohr B.,Women and Infants Hospital
Acta Paediatrica, International Journal of Paediatrics | Year: 2013
Language delays are common among premature infants and children with hearing loss. There are multiple tools and reports for assessing language in young children. Assessing early language and providing intervention is key to improving outcomes. Conclusion We conclude that utilization of a new tool, Language Environment Analysis digital language processor (LENA™), to assess the natural language environment of high-risk infants and children in a variety of settings including the neonatal intensive care unit and home, provides the opportunity to access and identify key features of the early language environment. ©2013 Foundation Acta Pædiatrica. Published by Blackwell Publishing Ltd.
Vohr B.,Women and Infants Hospital
Clinics in Perinatology | Year: 2013
At present, moderate preterm (MPT) infants born at 32 to 33weeks' gestation and late preterm (LPT) infants born at 34 to 36weeks' gestation make up the largest subgroup of preterm infants and contribute to more than 80% of premature births in the United States. There is increasing evidence that both MPT and LPT infants are at increased risk of neurologic impairments, developmental disabilities, school failure, and behavior and psychiatric problems. Population studies suggest that for each 1week decrease in gestational age below 39weeks, there are stepwise increases in adverse outcomes after adjusting for confounders. © 2013 Elsevier Inc.
Wenstrom K.D.,Women and Infants Hospital
American Journal of Obstetrics and Gynecology | Year: 2014
The Food and Drug Administration and Environmental Protection Agency recently issued an updated draft of advice on fish consumption for pregnant and breastfeeding women, after survey data indicated that the majority of pregnant women do not eat much fish and thus may have inadequate intake of the omega 3 fatty acids eicosapentaenoic acid [EPA] and ducosahexaenoic acid [DHA]. Omega 3 fatty acids are essential components of membranes in all cells of the body and are vitally important for normal development of the brain and retinal tissues (especially myelin and retinal photoreceptors) and for maintenance of normal neurotransmission and connectivity. They also serve as substrates for the synthesis of a variety of antiinflammatory and inflammation-resolving mediators, favorably alter the production of thromboxane and prostaglandin E2, and improve cardiovascular health by preventing fatal arrhythmias and reducing triglyceride and C-reactive protein levels. Maternal ingestion of adequate quantities of fish (defined in many studies as at least 340 g of oily fish each week) has been associated with better childhood IQ scores, fine motor coordination, and communication and social skills, along with other benefits. Although the FDA did not clarify which fish to eat, it specifically advised against eating fish with the highest mercury levels and implied that fish with high levels of EPA and DHA and low levels of mercury are ideal. The FDA draft did not recommend taking omega 3 fatty acid or fish oil supplements instead of eating fish, which is advice that may reflect the fact that randomized controlled trials of DHA and EPA or fish oil supplementation generally have been disappointing and that the ideal daily dose of DHA and EPA is unknown. It seems safe to conclude that pregnant and nursing women should be advised to eat fish to benefit from naturally occurring omega 3 fatty acids, to avoid fish with high levels of mercury and other contaminants, and, if possible, to choose fish with high levels of EPA and DHA. © 2014 Elsevier Inc.
Dizon D.S.,Women and Infants Hospital
Gynecologic Oncology | Year: 2010
Objective: Endometrial carcinoma is the most common malignancy of the female reproductive tract. Most cases are diagnosed at an early stage due to the appearance of symptoms such as postmenopausal bleeding. However, endometrial carcinoma carries a poor prognosis when it recurs after previous definitive treatment or when diagnosed at an advanced stage. Here, treatment options for advanced endometrial carcinoma are evaluated. Methods: Literature review was performed to determine current therapy options, with a focus on the treatment landscape for women with recurrent, advanced, or metastatic disease. Results: Combination chemotherapy is being used more frequently as first-line treatment of advanced disease, consisting of cisplatin/doxorubicin/paclitaxel, if tolerated, or the doublet of carboplatin/paclitaxel. Options following disease progression after first-line treatment are extremely limited, particularly with the increasing use of active agents in the adjuvant setting. Fortunately, several new cytotoxic and biologic therapies appear promising for women who have progressed on first-line treatment. Conclusions: Clinical trials are planned to further explore how to best incorporate novel agents into the current treatment algorithm with the aim to improve the options in both first- and second-line treatments for women with endometrial adenocarcinomas. © 2010 Elsevier Inc. All rights reserved.
Klatsky P.C.,Women and Infants Hospital
Obstetrics and Gynecology | Year: 2010
Objective: To compare the risk of gestational hypertension and preeclampsia in pregnancies conceived through standard in vitro fertilization (IVF) using autologous oocytes with pregnancies conceived using donated oocytes. Methods: We conducted a retrospective, matched cohort study of women undergoing IVF using autologous compared with donor oocytes between 1998 and 2005. Women with live births resulting from oocyte donor pregnancies were matched for age and plurality (singleton or twin) with women undergoing autologous IVF. Primary outcomes were the incidence of preeclampsia or gestational hypertension (with and without proteinuria) in the third trimester. Data on preterm delivery, low birth weight, and embryo cryopreservation were also recorded. Results: Outcome data were available for 158 pregnancies, including 77 ovum-donor recipient pregnancies and 81 pregnancies using autologous oocytes. There were no differences in age, parity, and gestational type between the two cohorts. The incidence of gestational hypertension and preeclampsia was significantly higher in ovum-donor recipients compared with women undergoing autologous IVF (24.7% compared with 7.4%, P<.01, and 16.9% compared with 4.9%, P=.02, respectively). Ovum-donor recipients were more likely than women undergoing autologous IVF to deliver prematurely (34% compared with 19%). This association remained after controlling for multiple gestation (odds ratio 2.6, 95% confidence interval 1.04-6.3). Sixteen pregnancies from cryopreserved embryos were more likely to have hypertensive disorders of pregnancy (odds ratio 5.0, 95% confidence interval 1.2-20.5). Conclusion: Pregnancies derived from donor oocytes and cryopreserved-thawed embryos may be at a higher risk for hypertensive disorders of pregnancy. These findings inform future research and help counsel women using assisted reproductive technology. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.
De Paepe M.E.,Women and Infants Hospital
Experimental lung research | Year: 2010
Preterm infants exposed to oxygen and mechanical ventilation are at risk for bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disorder characterized by arrested alveolar development and nonsprouting, dysmorphic microvascular angiogenesis. The molecular regulation of this BPD-associated pathological angiogenesis remains incompletely understood. In this study, the authors used focused microarray technology to characterize the angiogenic gene expression profile in postmortem lung samples from short-term ventilated preterm infants (born at 24 to 27 weeks' gestation) and age-matched control infants. Microarray analysis identified differential expression of 13 of 112 angiogenesis-related genes. Genes significantly up-regulated in ventilated lungs included the antiangiogenic genes thrombospondin-1, collagen XVIII alpha-1, and tissue inhibitor of metalloproteinase-1 (TIMP1), as well as endoglin, transforming growth factor-alpha, and monocyte chemoattractant protein-1 (CCL2). Increased expression of thrombospondin-1 in ventilated lungs was verified by real-time polymerase chain reaction (PCR) and immunolocalized primarily to intravascular platelets and fibrin aggregates. Down-regulated genes included proangiogenic angiogenin and midkine, as well as vascular endothelial growth factor (VEGF)-B, VEGF receptor-2, and the angiopoietin receptor TEK/Tie-2. In conclusion, short-term ventilated lungs show a shift from traditional angiogenic growth factors to alternative, often antisprouting regulators. This angiogenic shift may be implicated in the regulation of dysmorphic angiogenesis and, consequently, deficient alveolarization characteristic of infants with BPD.