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Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus that causes pelvic pain and infertility. We used the Global Burden of Disease Study (GBD) 2017 to comprehensively analyze the burden of endometriosis between 1990 and 2017. DisMod-MR 2.1 was used to estimate the incidence and prevalence in some countries/territories with sparse or absent data. Annual percent changes were calculated to quantify endometriosis burden estimate trends. Furthermore, the sociodemographic index (SDI) was used to assess the relationship between endometriosis burden estimates and development level. Between 1990 and 2017, endometriosis age-standardized incidence and prevalence and years of life lived with disability (YLDs) decreased globally by 0.21% (95% confidence interval (CI): -0.23% to -0.20%), 0.29% (95% CI: -0.31% to -0.28%), and 0.28% (95% CI: -0.30% to -0.27%) per year, respectively. Apart from the high SDI quintiles with increasing trends of endometriosis incidence rate, prevalence rate, and YLDs, decreasing trends were observed in all SDI quintiles for all burden estimates. In conclusion, it appears that all endometriosis burden estimates have decreased globally between 1990 and 2017. However, these results are based on limited data and highlight the need for increased data collection on the incidence and prevalence of endometriosis.

BackgroundCurrent literature describes limited and controversial evidence on the associations between maternal preconception and first trimester exposure to particulate matter with a diameter ≤10 µm (PM10) and the risk of oral cleft (OC).MethodsWe conducted a case–control study involving 3086 OC cases and 7950 controls, registered in the Maternal and Child Health Certificate Registry in Liaoning Province between 2010 and 2015. PM10 concentrations were obtained from the Environment Protection Bureau. The exposure windows included the 3 months before pregnancy, the first trimester and the individual months. Unconditional logistic regression model was performed to estimate the OR and 95% CI for the association between PM10 exposure and the risk of OC, cleft lip only (CLO), cleft palate only (CPO), and cleft lip and palate (CLP).ResultsMaternal PM10 exposure was positively associated with an increased risk for OC during the 3 months preconception (per 10 µg/m3 increment: OR=1.04, 95% CI 1.01 to 1.07; highest vs lowest quartile: OR=1.23, 95% CI 1.04 to 1.45) and the first trimester (per 10 µg/m3 increment: OR=1.05, 95% CI 1.02 to 1.08; highest vs lowest quartile: OR=1.37, 95% CI 1.15 to 1.64). Analyses based on individual months presented similar positive associations, particularly in the second month of pregnancy (OR=1.77, 95% CI 1.51 to 2.09) for highest versus lowest quartile. In the subtype analysis, stronger associations were observed for CLO, whereas there was negligible evidence for CPO and CLP. Sensitivity analyses using propensity score matching generated similar findings.ConclusionsOur study provides evidence that PM10 exposure during the 3 months preconception and the first trimester increases the risk of OC.

Epidemiological studies have investigated the relationship between infertility and the risk of ovarian cancer (OC); however, the results have been inconsistent. We therefore conducted the first meta-analysis to update and quantify the aforementioned association based on prospective cohort studies. Studies were identified by searching PubMed, EMBASE and Web of Science databases up to January 8, 2020. We extracted data from the studies and performed quality assessments. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias, and subgroup, meta-regression and sensitivity analyses were also conducted. Nine prospective cohort studies with a total of 10 383 OC cases and 6 278 830 participants were included in the present study. The summary RR of the association between infertility and the risk of OC was 1.51 (95% CI: 1.35-1.69), with low heterogeneity. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, duration of follow-up, study quality, causes of infertility, invasiveness of OC, infertility treatment status and adjustment of potential confounding parameters. No significant publication bias was detected. Our findings suggest that infertility in women were associated with an increased risk of OC.

To provide comprehensive estimates of the global, regional, and national burden of infertility from 1990 to 2017, using findings from a 2017 study on the global burden of disease (GBD), we assessed the burden of infertility in 195 countries and territories from 1990 to 2017. DisMod-MR 2.1 is a Bayesian meta-regression method that estimates non-fatal outcomes using sparse and heterogeneous epidemiological data. Globally, the age-standardized prevalence rate of infertility increased by 0.370% per year for females and 0.291% per year for males from 1990 to 2017. Additionally, age-standardized disability-adjusted life-years (DALYs) of infertility increased by 0.396% per year for females and 0.293% per year for males during the observational period. An increasing trend to these burden estimates was observed throughout the all socio-demographic index (SDI) countries. Interestingly, we found that high SDI countries had the lowest level of prevalence and DALYs in both genders. However, the largest increasing trend was observed in high-SDI countries for females. By contrast, low-SDI countries had the largest increasing trend in males. Negative associations were observed between these burden estimates and the SDI level. The global disease burden of infertility has been increasing throughout the period from 1990 to 2017.

Objectives The burden of gout has been increasing globally. However, little is known about the global, regional and national distribution and time trend of this disease. We present a comprehensive analysis of the Global Burden of Disease Study 2017 on gout burden estimates for 195 countries or territories between 1990 and 2017. Methods Age-standardized prevalence and disability-adjusted life-years of gout were reported between 1990 and 2017 in 195 countries and territories, and associations between these estimates and sociodemographic index (SDI) were further explored. Total and annual percent change between 1990 and 2017 were calculated to quantify the time trends of gout burden. Results Age-standardized prevalence rates (95% uncertainty interval) per 100 000 persons were 790.90 (706.10–881.90) and 253.49 (225.69–284.02) in 2017 in males and females, respectively. The annual percent change in age-standardized prevalence (males, 0.22%; females, 0.38%) and disability-adjusted life-years (males, 0.21%; females, 0.38%) of gout increased every year from 1990 to 2017, globally. The highest increase was detected in high-SDI countries, especially in high-income North America. A non-linear association was observed between burden of gout and SDI, with the lowest estimates of gout burden when SDI value was about 0.6. High BMI was the leading risk factor for the burden of gout. Conclusion These study results suggest a globally rising trajectory of gout burden between 1990 and 2017. More effective interventions, such as detailed and intensive dietary managements and other prevention strategies for reducing obesity, should be carried out to reverse this trend, especially in females and high-SDI countries.

Hyponatremia is an emerging issue in cancer patients. However, few studies have explored the prognostic value of preoperative hyponatremia in epithelial ovarian cancer (EOC) patients. We conducted a retrospective study of women diagnosed with EOC at Shengjing Hospital from 2011 to 2015. Preoperative serum sodium levels were measured and classified as normal (136-145 mmol/L) or hyponatremic (≤135 mmol/L) according to the average/most recent measurements of this biomarker. Multivariable Cox proportional hazard regression models were applied to determine the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of preoperative hyponatremia with progression-free survival (PFS) and overall survival (OS). We identified 607 EOC patients meeting the inclusion criteria with a median age of 51 years (inter-quartile range: 47-59 years). The median follow-up duration was 3.1 years (inter-quartile range: 2.2-4.2). The recurrence and mortality rates were 56.8% (345/607) and 38.4% (233/607), respectively. Among the patients, 81 (13.3%) were observed as hyponatremic. Preoperative hyponatremia was associated with poorer PFS (HR=1.51; 95%CI=1.07-2.15) as well as OS (HR=1.47; 95%CI=1.03-2.11) after adjusting for potential confounders. Notably, results were in line with the main findings only when using the most recent serum sodium levels before treatment, with corresponding HRs of 1.58 (95%CI=1.12-2.23) for PFS and 1.45 (95%CI=1.02-2.07) for OS. Preoperative hyponatremia is an independent prognostic factor of EOC. Further studies are warranted to confirm our findings as well as to determine whether correction of preoperative hyponatremia may alter clinical outcomes in these patients.

Background and Aims: The dietary inflammatory index (DII) is associated with non-communicable disease. We conducted an umbrella review to systematically evaluate meta-analyses of observational studies on DII and diverse health outcomes.Methods: We comprehensively searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses of observational studies. Those investigating the association between DII and a wide range of health outcomes in humans were eligible for inclusion. For each meta-analysis, we estimated the summary effect size by using fixed and random effects models, the 95% confidence interval, and the 95% prediction interval. We assessed heterogeneity, evidence of small-study effects, and excess significance bias.Results: The umbrella review identified 35 meta-analyses assessing associations between DII and various health outcomes: cancer (n = 24), mortality (n = 4), metabolic (n = 4), and other (n = 3). The methodological quality was high or moderate. Of the 35 meta-analyses, we observed highly suggestive evidence for harmful associations between digestive tract cancer, colorectal cancer, overall cancer, pharyngeal cancer, UADT cancer, and CVD mortality. Moreover, 11 harmful associations showed suggestive evidence: hormone-dependent cancer, rectal cancer, colon cancer, breast and prostate cancer, gynecological cancer, breast cancer, ovarian cancer, colorectal cancer, prostate cancer, all-cause mortality, and depression.Conclusion: DII is likely to be associated with harmful effects in multiple health outcomes. Robust randomized controlled trials are warranted to understand whether the observed results are causal.Systematic Review Registration: CRD42021218361

PurposeThe evidence of adherence to cancer prevention guidelines and endometrial cancer (EC) risk has been limited and controversial. This study summarizes and quantifies the relationship between adherence to cancer prevention guidelines and EC risk.Materials and MethodsThe online databases PubMed, Web of Science, and EMBASE were searched for relevant publications up to June 2, 2020. This study had been registered at PROSPERO. The registration number is CRD42020149966. Study quality evaluation was performed based on the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity among studies. Egger’s and Begg’s tests assessed potential publication bias. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between adherence to cancer prevention guidelines score was assigned to participants by summarizing individual scores for each lifestyle-related factor. The scores ranged from least healthy (0) to most healthy (20) and the EC risk was calculated using a randomeffects model. ResultsFive prospective studies (four cohort studies and one case‑cohort study) consisted of 4,470 EC cases, where 597,047 participants were included. Four studies had a low bias risk and one study had a high bias risk. Summary EC HR for the highest vs. lowest score of adherence to cancer prevention guidelines was 0.54 (95% CI, 0.40 to 0.73) and had a high heterogeneity (I2=86.1%). For the dose-response analysis, an increment of 1 significantly reduced the risk of EC by 6%. No significant publication bias was detected.ConclusionThis study suggested that adherence to cancer prevention guidelines was negatively related to EC risk.

Background: Ovarian cancer (OC) has the highest mortality among gynecological malignancies, and resistance to chemotherapy drugs is common. We aim to develop a machine learning approach based on gut microbiota to predict the chemotherapy resistance of OC. Methods: The study included patients diagnosed with OC by pathology and treated with platinum and paclitaxel in Shengjing Hospital of China Medical University between 2017 and 2018. Fecal samples were collected from patients, and 16S rRNA sequencing was used to analyze the differences in gut microbiota between OC patients with and without chemotherapy resistance. Nine machine learning classifiers were used to derive the chemotherapy resistance of OC from gut microbiota. Results: A total of 77 chemoresistant OC patients and 97 chemosensitive OC patients were enrolled. The gut microbiota diversity was higher in OC patients with chemotherapy resistance. There were statistically significant differences between the two groups in Shannon indexes (P

Background: Pancreatic cancers are the common digestive system tumors with poor prognosis and due to its late diagnosis, surgical resection does not remain a viable treatment option in about 80% of patients. Amongst different treatment options, radioactive 125I seed implantation therapy has also emerged as a good alternative in non-resectable pancreatic cancer patients.Purpose: The present review describes the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers in preclinical and clinical studies.Results: In this technique, small radioactive particles are implanted inside the tumor cells to produce the sustain effects. Due to the short radial distance of these radiations, there is a selective and efficient killing of cancer cells without any significant injury to the neighboring cells. Amongst the different methods for implanting 125I seeds in the pancreatic tissues, CT scan or ultrasound-guided percutaneous seed implantation is preferred as it offers shorter operative time, lesser bleeding, early recovery, lesser complications, and low medical costs. The clinical studies have shown that radioactive 125I seed implantation is a good option for the management of local tumor growth, pain palliation, and improvement in the life span of patients suffering from unresectable pancreatic cancer.Conclusion: It may be employed either alone or in combination with cryotherapy, existing chemotherapy, bypass surgery or radiations to achieve the optimal results in these patients. Nevertheless, there is a need to formulate a uniform dose and procedure to achieve homogeneity and develop references for clinical practices.

The influence of time to chemotherapy (TTC) on recurrence and survival among epithelial ovarian cancer (EOC) patients still remains unknown. This single center retrospective cohort study was conducted on 489 EOC patients who underwent surgery followed by taxane- plus platinum-based chemotherapy in the Shengjing Hospital of China Medical University between 2011 and 2015. The Multivariate cox proportional regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) after adjustment for potential confounders. The median follow-up duration was 2.97 years (inter-quartile range from 2.11 to 4.13 years). The recurrence and mortality rate of the all patients was 50.9% (249/489) and 43.6% (213/489), respectively. Having comorbidity, residual disease, ascites, and advanced FIGO stage (III-IV) was associated worse PFS and OS of EOC patients. Compared to TTC less than 14 days, delayed TTC (more than 28 days) was associated with a worse PFS (HR=1.36; 95%CI: 0.96-1.92) and OS (HR=1.38; 95%CI: 0.95-2.00). Notably, in EOC patients with advanced stage, delayed TTC (more than 28 days) was associated with worse PFS (HR=1.51; 95%CI: 1.02-2.24) and OS (HR=1.53; 95%CI: 1.01-2.32) when comparing to TTC less than 14 days. In conclusion, delayed TTC was associated with higher rates of EOC recurrence and survival among these patients with advanced stage. The findings of the present study may provide evidence for gynecologist as well as these ovarian cancer patients to make further decision for the treatment.

Objectives Cisplatin is commonly applied as anticancer agent for various cancers, including ovarian cancer. Unfortunately, the drug resistance frequently occurred which obstructing the effect of cisplatin on tumors. The goal of our research was to investigate the reversal actions and the potential mechanisms of sulforaphane (SFN) on cisplatin resistance in ovarian carcinoma. Methods The A2780 and IGROV1 cells and their cisplatin resistance cells A2780/CP70 and IGROV1-R10 were used in this study. Cell viability was detected by CCK-8. The DNA repair was measured by comet assay. The cisplatin transporter proteins were measured with western blotting. The concentration of intracellular cisplatin was detected by HPLC. The luciferase activity assay was applied to determine the target site of miR-30a-3p on the 3′UTR of ERCC1 and ATP7A. A2780/CP70 and IGROV1-R10 xenograft mouse model were established to confirm the antineoplastic action of SFN combined with cisplatin. Results SFN reversed the resistance of A2780/CP70 and IGROV1-R10 ovarian carcinoma cells to cisplatin through inducing DNA damage and accumulation of intracellular cisplatin. SFN treatment notably increased miR-30a-3p expression, which was decreased in cisplatin-resistant cells. Moreover, overexpressed miR-30a-3p enhanced the sensitivity of A2780/CP70 and IGROV1-R10 cells to cisplatin treatment, and inhibiting miR-30a-3p activity abated the reversal actions of SFN on cisplatin resistance. The luciferase assay findings showed that miR-30a-3p binds to ERCC1 and ATP7A which are the key regulators for DNA repair and cisplatin transportation. Conclusions Our findings indicated that SFN could enhance cisplatin sensitivity of ovarian carcinoma cells through up-regulating miR-30a-3p to induce DNA damage and accumulation of intracellular cisplatin.

Endometrial cancer (EC) is the most common malignancy affecting women in developed countries. Recently, the EC disease burden has changed; therefore, the Global Burden of Disease (GBD) 2017 was used to comprehensively analyze the global, regional, and national burden of EC between 1990 and 2017. General GBD cancer estimation methods were used with the data input from vital registration systems and cancer registries. Annual percent changes were calculated to quantify the trends of EC burden estimates during the study period. Furthermore, the sociodemographic index (SDI) was used to assess the relationship between the EC burden estimates and development level. From 1990 to 2017, the age-standardized incidence and prevalence rate of EC increased globally by 0.58 and 0.89% per year, respectively. In contrast, the age-standardized death rate and disability-adjusted-life years (DALYs) decreased by 1.19 and 1.21% per year, respectively. Increasing trends in both the incidence and prevalence were observed in all SDI quintiles, except for the low SDI quintiles, whereas decreasing trends were observed in all SDI quintiles for mortality and DALYs. Additionally, a non-linear association existed for the level of mortality rate, DALYs, and SDI. Of note, there was a strong positive association between a high body mass index and DALYs across all SDI quintiles. In conclusion, EC incidence and prevalence rates are growing globally, whereas the death rate and DALYs decreased between 1990 and 2017. Greater efforts, particularly detailed prevention strategies for reducing obesity, should be performed to reverse this phenomenon.

Ovarian cancer (OC) is one of the most common gynecologic malignancies with poor survival rate, and Iberin is a member of isothiocyanate family with anti-tumor activity. However, the role of Iberin in OC development has not been reported yet. In this study, A2780 and OVCAR-3 cells were treated with gradient concentrations of Iberin to investigate the effect of Iberin on OC in vitro. Meanwhile, the in vivo tumorgenesis experiment was performed using female BALB/c nude mice treated with Iberin. Iberin inhibited cell proliferation, induced G2 cell cycle arrest and promoted cell apoptosis in OC cells. Besides, Iberin reduced GSH/GSSG level, enhanced ROS accumulation, and activated MAPK signaling in OC cells. More interestingly, ROS scavenger (NAC) compensated the anti-proliferative and pro-apoptotic effects of Iberin on OC cells, suggesting the involvement of ROS in the regulation of Iberin on OC cell growth. Notably, Iberin induced down-regulation of glutathione peroxidase-1 (GPX1), and over-expression of GPX1 reversed Iberin-mediated alterations in the proliferation, apoptosis and ROS accumulation of OC cells. The in vivo tumorgenesis study further evidenced the protection of Iberin against OC development. Besides, Iberin displayed a synergistic effect on the enhancement of chemo-sensitivity in OC cells. In summary, our study demonstrates the anti-tumor effect of Iberin on OC and its potential as a therapeutic agent against OC in the future.

// Ting-Ting Gong 1 , Qi-Jun Wu 2 , Yan-Ling Chen 3 , Cheng-Zhi Jiang 4 , Da Li 1 , Jing Li 5 , Li-Li Li 6 , Chen Zhou 7 and Yan-Hong Huang 5 1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China 3 Liaoning Women and Children’s Health Hospital, Shenyang, China 4 School of Environmental and Chemical Engineering, Shenyang Ligong University, Shenyang, China 5 Department of Science and Education, Shenyang Women and Children Health Care Centre, Shenyang, China 6 Department of Children’s Health Prevention, Shenyang Women and Children Health Care Centre, Shenyang, China 7 Department of Information Statistics, Shenyang Women and Children Health Care Centre, Shenyang, China Correspondence to: Qi-Jun Wu, email: wuqj@sj-hospital.org Keywords: anencephaly, Liaoning province, prevalence, time trend Received: November 04, 2016 Accepted: February 22, 2017 Published: April 26, 2017 ABSTRACT The goal of this study was to assess the prevalence and trends of anencephaly on the basis of a large population-based cases identified by the Liaoning Birth Defects Registry, which included 14 cities over a 10-year period. Anencephaly prevalence, percent change, average changeand the contribution rates of each city were calculated. Statistical analysis was undertaken on the basis of a Poisson regression model. A total of 1600 anencephaly cases were collected during the observational period (4.92/10,000 live births). On average, the prevalence decreased 10.15% each year; this overall time trend was statistically significant (P

// Gen Ba 1 , Qi-Jun Wu 2 , Yan-Ling Chen 3 , Yan-Hong Huang 4 , Ting-Ting Gong 5 1 Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China 3 Liaoning Women and Children’s Health Hospital, Shenyang, China 4 Department of Science and Education, Shenyang Women and Children Health Care Centre, Shenyang, China 5 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China Correspondence to: Qi-Jun Wu, email: wuqj@sj-hospital.org Keywords: Liaoning Province, prevalence, spina bifida, time trend Received: October 04, 2016 Accepted: January 08, 2017 Published: January 27, 2017 ABSTRACT The present study sought to assess the time trends of spina bifida on the basis of cases identified by the Liaoning Birth Defects Registry in 14 cities from 2006 to 2015. We calculated the prevalence of spina bifida, percent and average change of time trends, and contribution rates of each city. Poisson regression model was used to find the line of best fit for spina bifida prevalence by year, with year as a continuous independent variable. From 2006 to 2015, a total of 2,029 spina bifida cases were identified from 3,248,954 live births (6.25/10,000 live births). We observed statistically significant decreasing trend of overall time trend (11.57% each year). Chaoyang, Fuxin, and Huludao were the top three leading cities, with 14.30/10,000 live births, 9.70/10,000 live births, and 9.20/10,000 live births, respectively. Inversely, the bottom three cities with lowest prevalence were Anshan (2.64/10,000 live births), Dandong (3.43/10,000 live births), and Dalian (3.45/10,000 live births). Of note, we observed significant decreasing trends in over half of these cities ( n = 8). In addition, the decreasing trend of overall time trend could be mainly attributed to cities of Shenyang, Fushun, and Jinzhou which accounted for nearly one third. In summary, our study suggested a decreasing time trend of spina bifida during the past decade in the Liaoning province. The findings of this study provide evidence that the nationwide folic acid supplement program has been an effective strategy to prevent spina bifida.

Aim To perform a meta-analysis of available cohort studies on the association between sertraline use by pregnant women in the first trimester and the findings of congenital anomalies in infants. Methods A comprehensive search of articles published from the index date up to 31st December 2015 investigating the aforementioned associations was conducted on PubMed and Web of Science. Mesh headings used included the terms "serotonin reuptake inhibitor," "sertraline," "congenital anomalies" and "obstetrical outcome." Results Twelve cohort studies that involved 6 468 241 pregnant women were identified. We summarized odds ratios (ORs) and 95% confidence intervals (CIs) of congenital anomalies using the random-effects model. Pregnant women who used sertraline in the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (OR = 1.36; 95% CI = 1.06-1.74; I2 = 64.4%; n = 12) as well as atrial and/or ventricular septal defects (OR = 1.36, 95% CI = 1.06-1.76; I2 = 62.2%; n = 8). Additionally, positive but nonsignificant associations between sertraline use and congenital anomalies of the nervous system (OR = 1.39; 95% CI = 0.83-2.32; I2 = 0%; n = 5), digestive system (OR = 1.23; 95% CI = 0.76-1.98; I2 = 0%; n = 5), eye, ear, face and neck (OR = 1.08; 95% CI = 0.33-3.55; I2 = 32.1%; n = 3), urogenital system (OR = 1.03; 95% CI = 0.73-1.46; I2 = 0%; n = 5), and musculoskeletal system (OR = 0.97; 95% CI = 0.69-1.36; I2 = 0%; n = 5) were observed. Conclusion This meta-analysis suggested that the use of sertraline use by pregnant women in the first trimester had an increased risk of cardiovascular-related malformations as well as atrial and/or ventricular septal defects in infants. Meanwhile, nonsignificant associations between sertraline use and other congenital anomalies were found. More cohort studies are warranted to provide detailed results of other congenital anomalies.

Observational studies have reported inconsistent results on the association between fruit and vegetable intake and the risk of pancreatic cancer. We carried out a meta-analysis of epidemiological studies to summarize available evidence. We searched PubMed, Scopus, and ISI Web of Science databases for relevant studies published until the end of January 2015. Fixed-effects and random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs) for the associations between fruit and vegetable intake and the risk of pancreatic cancer. A total of 15 case-control studies, eight prospective studies, and one pooled analysis fulfilled the inclusion criteria. The summary RR for the highest versus the lowest intake was 0.73 (95% CI=0.53-1.00) for fruit and vegetables, 0.73 (95% CI=0.63-0.84) for fruit, and 0.76 (95% CI=0.69-0.83) for vegetables, with significant heterogeneities (I=70.5, 55.7, and 43.0%, respectively). Inverse associations were observed in the stratified analysis by study design, although the results of prospective studies showed borderline significance, with corresponding RR=0.90 (95% CI=0.77-1.05) for fruit and vegetable intake, 0.93 (95% CI=0.83-1.03) for fruit intake, and 0.89 (95% CI=0.80-1.00) for vegetable intake. Besides, significant inverse associations were observed in the majority of other subgroup analyses by study quality, geographic location, exposure assessment method, and adjustment for potential confounders. Findings from the present meta-analysis support that fruit and vegetable intake is associated inversely with the risk of pancreatic cancer. However, study design may play a key role in the observed magnitude of the aforementioned association. Future well-designed prospective studies are warranted to confirm these findings.

// Ting-Ting Gong 1 , Da Li 1 , Qi-Jun Wu 2 , Ya-Zhu Wang 3 1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China 3 Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, China Correspondence to: Ya-Zhu Wang, e-mail: yzwang_first@163.com Keywords: cholesterol, endometrial cancer, epidemiology, meta-analysis Received: October 29, 2015 Accepted: January 29, 2016 Published: March 04, 2016 ABSTRACT In vivo and in vitro studies have indicated the link of cholesterol consumption and endometrial cancer risk, however, previous observational studies have yielded inconsistent results. Additionally, a previous meta-analysis published in 2007 found limited evidence of aforementioned association. Therefore, we performed the dose-response meta-analysis to address this concern. Studies were identified using the PubMed, EMBASE and Web of Science databases from the database inception to the end of June 2015 as well as by examining the references of retrieved articles. Two authors independently performed the eligibility evaluation and data extraction. The summary risk estimates and 95% confidence intervals (CIs) were summarized by the random-effects models. One cohort and nine case-control studies were included in the dose-response analyses. Risk of endometrial cancer increased by 6% for 100 mg/day increment in the dietary consumption of cholesterol (Odds ratio (OR) = 1.06; 95% CI = 1.00–1.12), with significant heterogeneity ( I 2 = 64.2, P = 0.003). When stratified by study design, the result was significant in case-control studies (OR = 1.07; 95% CI = 1.01–1.13). Additionally, although the direction of the associations were consistent in the subgroup analyses stratified by study characteristics and adjustment for potential confounders, not all of them showed statistical significance. In summary, findings of the present dose-response meta-analysis partly support the positive association between dietary cholesterol consumption and risk of endometrial cancer. Since only one cohort study was included, more prospective studies and pooled analysis of observational studies are warranted to confirm our findings in the future.

Background The number of studies on air pollution with birth defects as the primary outcome has increased dramatically over the past two decades, but the potential role of specific air pollutants in congenital limb anomalies remains unclear. Objectives To evaluate associations between preconception and first-trimester PM10 exposure and polydactyly and syndactyly in a population-based case-control study. Methods Polydactyly cases (n = 2605), syndactyly cases (n = 595), and controls without any birth defects (n = 7950) born between 2010 and 2015 were selected from the Maternal and Child Health Certificate Registry of Liaoning Province. The monthly mean PM10 concentrations were obtained from 75 air monitoring stations, and the exposure assessment was based on the mean concentration of all stations in mother's residential city. A multivariable logistic regression model was constructed to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results PM10 exposure was positively associated with the risks of polydactyly (preconception: aORT3 vs. T1 = 1.95, 95% CI 1.56–2.45, aOR = 1.06, 95% CI 1.01–1.10 [per 10-μg/m3 increment]; first-trimester: aORT3 vs. T1 = 2.51, 95% CI 2.00–3.15) and syndactyly (preconception: aORT3 vs. T1 = 2.86, 95% CI 1.98–4.13, aOR = 1.11, 95% CI 1.03–1.20 [per 10-μg/m3 increment]; first-trimester: aORT3 vs. T1 = 3.10, 95% CI 2.11–4.56). Analyses based on single month exposure windows basically showed similar positive associations. Additionally, these findings were robust in sensitivity analyses and broadly consistent across subgroups. Conclusion Our study suggest that preconception and first-trimester PM10 exposures are related to increased risks of polydactyly and syndactyly.

Background In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication. Methods The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs). Results Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32). Conclusions The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy. Electronic supplementary material The online version of this article (10.1186/s12916-018-1193-5) contains supplementary material, which is available to authorized users.

The associations between dietary fat and fatty acid (FA) intakes and epithelial ovarian cancer (EOC) risk have been inconsistent in previous studies. We conducted a meta-analysis of epidemiological studies to evaluate these associations. We identified relevant studies by searching PubMed, EMBASE, and Web of Science databases. We used random-effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Overall, the search yielded 20 studies (1 pooled analysis of 12 cohort studies, 5 cohorts, and 14 case-control studies). The summary RR for EOC for the highest versus lowest categories of total dietary fat intake was 1.12 (95%CI= 0.95-1.33; I2 = 77.4%; n = 14). The RRs were not significant when fats were divided into plant-based fats (RR = 0.93, 95%CI = 0.77-1.13; n = 6), animal-based fats (RR = 1.15, 95%CI = 0.95-1.39; n = 8), dairy-based fats (RR = 1.02, 95%CI = 0.88-1.18; n = 3), saturated FAs (RR = 1.04, 95%CI = 0.93-1.17; n = 12), monounsaturated FAs (RR = 0.98, 95%CI = 0.84-1.13; n = 10), polyunsaturated FAs (RR = 0.96, 95%CI = 0.81-1.12; n = 10), and trans-unsaturated FAs (RR = 1.15, 95%CI = 0.98-1.36; n = 3). Similar non-significant results were also observed in most of the subgroup and sensitivity analyses. The findings of this meta-analysis suggest a lack of evidence for associations between dietary fat and FA intakes and EOC risk. Further analyses should be conducted to assess the associations with other types of fat, and the results should be stratified by tumor invasiveness and EOC histology.

Epidemiological studies have provided controversial evidence of the association between dietary fatty acids intake and endometrial cancer risk. The continuous update project of World Cancer Research Fund failed to focus on this issue. To address this inconsistency, we conducted this dose-response meta-analysis based on epidemiological studies published up to the end of June 2015 identified from PubMed, EMBASE and Web of Science. Two authors independently performed the eligibility evaluation and data extraction. Random-effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Fourteen epidemiological studies (4 cohort and 10 case-control studies) were included in this dose-response meta-analysis. The summary RR for an intake increment of 10g/day was 1.02 (95% CI = 0.97-1.08; I2 = 66.0%) for saturated fatty acids, 0.98 (95% CI = 0.96-1.001; I2 = 0%) for monounsaturated fatty acids, and 1.00 (95% CI = 0.95-1.06; I2 = 0%) for polyunsaturated fatty acids intake. Non-significant results were observed in the majority of subgroup analyses stratified by study characteristics and adjustment for potential confounders in analyses of aforementioned associations. In conclusion, results from this dose-response meta-analysis provided limited evidence that dietary saturated, monounsaturated, and polyunsaturated fatty acids consumption was associated with endometrial cancer risk. Further studies, especial prospective designed or pooled studies are warranted to confirm our findings.

We performed this meta-analysis of epidemiologic studies to investigate the associations between circulating adiponectin, leptin and adiponectin–leptin (A/L) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random-effects models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned associations. Fourteen manuscripts with 13 studies (five nested case–control and eight case–control studies) cumulatively involving a total of 1,963 endometrial cancer cases and 3,503 noncases were included in the analyses. Overall, comparing persons with circulating concentrations of adiponectin, leptin and A/L ratio in the top tertile with persons with concentrations of these biomarkers in the bottom tertile yielded SORs of 0.47 (95% CI: 0.34–0.65; I2 = 63.7%; n = 13), 2.19 (95% CI: 1.44–3.31; I2 = 64.2%; n = 7),and 0.45 (95% CI: 0.24–0.86; I2 = 90.1%; n = 5), respectively. Notably, there was an 18% reduction in risk for per each 5 μg/mL increment in circulating adiponectin concentrations (SOR = 0.82; 95% CI: 0.74–0.90; I2 = 49%; n = 8). Stratifying by study characteristics and whether these studies considered or adjusted for potential confounders, the findings were robust in the analyses of circulating adiponectin and leptin. No evidence of publication bias was detected. In conclusion, the findings from this meta-analysis suggest that increased circulating adiponectin and A/L ratio or decreased leptin concentrations were associated with reduced risk of endometrial cancer. Further prospective designed studies are warranted to confirm our findings.

Although several studies have previously investigated the association between the initiation time of adjuvant chemotherapy and survival in ovarian cancer, inconsistencies remain about the issue. We searched PubMed and Web of Science through the May 24, 2017 to identify cohort studies that investigated the aforementioned topic. Fourteen studies with 59,569 ovarian cancer patients were included in this meta-analysis. We conducted meta-analyses comparing the longest and shortest initiation time of adjuvant chemotherapy and dose-response analyses to estimate summary hazards ratios (HRs) and 95% confidence intervals (CIs). A random-effects model was used to estimate HRs with 95% CIs. When comparing the longest with the shortest category of initiation time of adjuvant chemotherapy, the summary HR was 1.18 (95% CI: 1.06–1.32; I2 = 17.6; n = 7) for overall survival. Additionally, significant dose-response association for overall survival was observed for each week delay (HR = 1.04; 95% CI: 1.00–1.09; I2 = 9.05; n = 5). Notably, these findings were robust in prospective designed cohort studies as well as studies with advanced stage (FIGO III-IV) patients. No evidence of publication bias was observed. In conclusion, prolonged initiation time of adjuvant chemotherapy is associated with a decreased overall survival rate of ovarian cancer, especially in patients with advanced stage ovarian cancer.

The relationship between selective serotonin-reuptake inhibitors (SSRIs) use during first trimester and cardiovascular-related malformations of infants is still uncertain. Therefore, we conducted this systematic review and meta-analysis to assess the aforementioned association. A systematic literature review identified studies for cohort studies about SSRIs use and cardiovascular-related malformations in PubMed and Web of Science. We summarized relative risk (RRs) and 95% confidence intervals (CIs) of cardiovascular-related malformations using random-effects model, and heterogeneity and publication-bias analyses were conducted. Eighteen studies met the inclusion criteria. Pregnant women who were exposed to SSRIs at any point during the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (RR = 1.26, 95%CI = 1.13–1.39), with moderate heterogeneity (I2 = 53.6). The corresponding RR of atrial septal defects (ASD), ventricular septal defects (VSD), ASD and/or VSD was 2.06 (95%CI = 1.40–3.03, I2 = 57.8), 1.15 (95%CI = 0.97–1.36; I2 = 30.3), and 1.27 (95%CI = 1.14–1.42; I2 = 40.0), respectively. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses. In conclusion, SSRIs use of pregnant women during first trimester is associated with an increased risk of cardiovascular-related malformations of infants including septal defects. The safety of SSRIs use during first trimester should be discussed to pregnant women with depression.

Background: Epidemiologic studies have yielded inconsistent findings between breastfeeding and epithelial ovarian cancer (EOC) risk. Objective: We performed a meta-analysis to summarize available evidence of the association between breastfeeding and breastfeeding duration and EOC risk from published cohort and case-control studies. Design: Relevant published studies were identified by a search of MEDLINE through December 2012. Two authors (T-TG and Q-JW) independently performed the eligibility evaluation and data abstraction. Study-specific RRs from individual studies were pooled by using a random-effects model, and heterogeneity and publication-bias analyses were conducted. Results: Five prospective and 30 case-control studies were included in this analysis. The pooled RR for ever compared with never breastfeeding was 0.76 (95% CI: 0.69, 0.83), with moderate heterogeneity (Q = 69.4, P , 0.001, I 2 = 55.3%). Risk of EOC decreased by 8% for every 5-mo increase in the duration of breastfeeding (RR: 0.92; 95% CI: 0.90, 0.95). The risk reduction was similar for borderline and invasive EOC and was consistent within case-control and cohort studies. Conclusions: Results of this meta-analysis support the hypothesis that ever breastfeeding and a longer duration of breastfeeding are associated with lower risks of EOC. Additional research is warranted to focus on the association with cancer grade and histologic subtypes of EOC. Am J Clin Nutr 2013;98:1020‐31.

To evaluate time trends of exomphalos prevalence using a large population-based study with cases identified by the Liaoning Birth Defects Registry including 14 cities over the course of a 10-year period. Exomphalos prevalence, percent change, annual percent change (APC), and contribution rates of each city were calculated. Additionally, epidemiological characteristics of this malformation were described. We observed 516 cases of exomphalos among 3,248,954 live births. Birth prevalence of exomphalos was 1.59 per 10,000 live births with non-significant change during the observational period (APC = −1.19%, P = 0.48). However, significantly decreasing trends were noticed in three cities: Fushun (APC = −9.15%, P = 0.03), Benxi (APC = −11.49%, P = 0.05), and Yingkou (APC = −16.47%, P = 0.04), contributing 62.77% of the decreasing trend of overall prevalence. The mean maternal age, gestational age, and birth weight was 28.4 years (standard deviation [SD], 6.1 years), 25.6 weeks (SD, 8.6 weeks), and 1236.2 gram (SD, 1164.4 gram). For time of diagnosis, 79.8% (n = 412) cases were diagnosed during pregnancy. In summary, the prevalence of exomphalos in Liaoning province did not change remarkably during 2006 to 2015. Future studies are warranted to investigate the risk factors and create prevention strategies for this disease.

To identify trends in the prevalence of gastroschisis on the basis of a large population-based observation study with cases identified by the Liaoning Birth Defects Registry including 14 cities over the course of a 10-year period. Data were obtained from the aforementioned registry which was maintained by the Liaoning Women and Children’s Health Hospital, a comprehensive care institution as well as being responsible for the women’s and children’s health care guidance in this province. Gastroschisis prevalence, percent change, annual percent change (APC), and contribution rates of each city were calculated. We observed 747 cases of gastroschisis among 3,248,954 live births, for a prevalence of 2.30 per 10,000 births. The gastroschisis prevalence significantly decreased by 12.63% per year in Liaoning Province. Although the decreasing trends were observed in all these 14 cities, significant results were only observed in Shenyang (APC = −16.31%), Tieling (APC = −20.23%), and Chaoyang (APC = −13.50%). Notably, Tieling, Shenyang, and Yingkou were the three major cities which contributed almost 37.17% of the decreasing trend of gastroschisis in Liaoning Province. In conclusion, our findings demonstrate that the prevalence of gastroschisis has been decreasing during the recent decade among 14 cities in Liaoning Province.

Previous studies investigating the relationship between passive maternal smoking and preterm birth reveal inconsistent results. We conducted the current meta-analysis of observational studies to evaluate the relationship between passive maternal smoking and preterm birth. We identified relevant studies by searching PubMed, EMBASE, and ISI Web of Science databases. We used random-effects models to estimate summary odds ratios (SORs) and 95% confidence intervals (CIs) for aforementioned association. For the analysis, we included 24 studies that involved a total of 5607 women who experienced preterm birth. Overall, the SORs of preterm birth for women who were ever exposed to passive smoking versus women who had never been exposed to passive smoking at any place and at home were 1.20 (95%CI = 1.07-1.34,I(2) = 36.1%) and 1.16 (95%CI = 1.04-1.30,I(2) = 4.4%), respectively. When we conducted a stratified analysis according to study design, the risk estimate was slightly weaker in cohort studies (SOR = 1.10, 95%CI = 1.00-1.21,n = 16) than in cross-sectional studies (SOR = 1.47, 95%CI = 1.23-1.74,n = 5). Additionally, the associations between passive maternal smoking and preterm birth were statistically significant for studies conducted in Asia (SOR = 1.26, 95%CI = 1.05-1.52), for studies including more than 100 cases of preterm birth (SOR = 1.22, 95%CI = 1.05-1.41), and for studies adjusted for maternal age (SOR = 1.27,95%CI = 1.09-1.47), socioeconomic status and/or education (SOR = 1.28, 95%CI = 1.10-1.49), body mass index (SOR = 1.33, 95%CI = 1.04-1.71), and parity (SOR = 1.27, 95%CI = 1.13-1.43). Our findings demonstrate that passive maternal smoking is associated with an increased risk of preterm birth. Future prospective cohort studies are warranted to provide more detailed results stratified by passive maternal smoking during different trimesters of pregnancy and by different types and causes of preterm birth.

Epidemiological studies have provided controversial evidence of the association between dietary fat intake and endometrial cancer (EC) risk. To address this inconsistency, we conducted this dose-response meta-analysis by total dietary fat intake, based on epidemiological studies published up to the end of June 2015 identified from PubMed, EMBASE and Web of Science. Two authors (RH and Q-JW) independently performed the eligibility evaluation and data extraction. All differences were resolved by discussion with the third investigator (LJ). Random-effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Overall, the search yielded 16 studies (6 cohort and 10 case-control studies) that involved a total of 7556 EC cases and 563,781 non-cases. The summary RR for EC for each 30g/day increment intake was 0.98 (95%CI = 0.95–1.001; I2 = 0%; n = 11) for total dietary fat. Non-significant results were observed in plant-based fat (summary RR = 1.05, 95%CI = 0.94–1.18; I2 = 0%; n = 5) and animal-based fat (summary RR = 1.17, 95%CI = 0.92–1.36; I2 = 85.0%; n = 6). Additionally, the null associations were observed in almost all the subgroup and sensitivity analyses. In conclusion, findings of the present meta-analysis suggested a lack of association between total dietary fat intake and EC risk. Further studies, especially prospective designed studies are warranted to confirm our findings.

// Jun Wei 1 , Cai-Xia Liu 1 , Ting-Ting Gong 1 , Qi-Jun Wu 2 , Lang Wu 3 1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China 3 Center for Clinical and Translational Science, Mayo Clinic, Rochester, MN, USA Correspondence to: Qi-Jun Wu, e-mail: wuqj@sj-hospital.org Keywords: cigarette smoking, meta-analysis, preeclampsia, risk factor Received: August 13, 2015 Accepted: October 06, 2015 Published: October 20, 2015 ABSTRACT Although evidence from epidemiological studies evaluating the association between cigarette smoking during pregnancy and preeclampsia risk has been systematically reviewed, the findings have been out of date. To further clarify the relationship, we conducted this comprehensive meta-analysis of prospective studies. We searched PubMed and Web of Science up to August 2015 to identify prospective studies that evaluated the association between cigarette smoking during pregnancy and preeclampsia risk. Random-effects models were used to estimate summarized relative risk (RR) and 95% confidence intervals (CIs). Seventeen prospective studies involving 62,089 preeclampsia patients from a total of approximately 1.8 million subjects were included. Overall, there was a significant negative association between smoking during pregnancy and incidence of preeclampsia ( RR = 0.67, 95% CI: 0.60–0.75), with significant heterogeneity ( I 2 = 91.7%). Such an inverse association was also detected in strata of subgroup analyses according to study location, study sample size, parity of populations, singleton pregnancy, and adjustment for potential confounders including maternal age, diabetes mellitus, chronic hypertension, body mass index, and gender of infant. In summary, this meta-analysis suggests that smoking during pregnancy is inversely associated with incidence of preeclampsia. Further large scale multi-center prospective studies are warranted to validate our findings.

The relationship between comorbidity and ovarian cancer survival has been controversial so far. Therefore, we conducted a meta-analysis to summarize the existing evidence from prospective studies on this issue. Relevant studies were identified by searching the PubMed, EMBASE and ISI Web of Science databases through the end of January 2015. Two authors independently performed the eligibility evaluation and data abstraction. Random-effects models were used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival. Eight prospective studies involving 12,681 ovarian cancer cases were included in the present study. The summarized HR for presence versus absence of comorbidity was 1.20 (95% CI = 1.11–1.30, n = 8), with moderate heterogeneity (I2 = 31.2%, P = 0.179). In addition, the summarized HR for the highest compared with the lowest category of the Charlson’s comorbidity index was 1.68 (95% CI = 1.50–1.87, n = 2), without heterogeneity (I2 = 0%, P = 0.476). Notably, a significant negative impact of comorbidity on ovarian cancer survival was observed in most subgroup analyses stratified by the study characteristics and whether there was adjustment for potential confounders. In conclusion, the findings of this meta-analysis suggest that underlying comorbidity is consistently associated with decreased survival in patients with ovarian cancer. Comorbidity should be taken into account when managing these patients.

Evidence between age at menarche and endometrial cancer risk have been controversial. Therefore, we conducted a meta-analysis of prospective studies to analyze the aforementioned association. Relevant studies were identified by searching PubMed and EMBASE databases until the end of June 2015. A random-effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between menarcheal age and endometrial cancer risk. Our meta-analysis included eight prospective studies involving 4553 subjects with endometrial cancer. The summarized RRs of endometrial cancer for menarcheal age were 0.68 (95%CI = 0.58–0.81, I2 = 41.9%, P = 0.099, n = 8) when comparing women with oldest category of menarcheal age with women with youngest category of menarcheal age. Notably, there was an 4% reduction in risk for per 2 years delay in menarcheal age (summarized RR = 0.96; 95%CI = 0.94–0.98, I2 = 45.7%, P = 0.101, n = 6). Additionally, significant inverse associations were consistent within all stratified analyses. There was no evidence of publication bias or significant heterogeneity between subgroups detected by meta-regression analyses. Our findings support the hypothesis that late menarcheal age is inversely associated with endometrial cancer risk. Further larger prospective or pooled studies are warranted to fully adjust for potential confounders and distinguish whether the associations differ by histological subtypes of endometrial cancer.

Background: Observational studies have reported conflicting results between parity and kidney cancer risk. To our knowledge, a comprehensive and quantitative assessment of the association between parity and kidney cancer has not been reported. Thus, we conducted a systematic review and dose–response meta-analysis of published epidemiologic studies to summarize the evidence of this association. Methods: Relevant published studies of parity and kidney cancer were identified using MEDLINE (PubMed) database through end of June 2013. Two authors independently assessed eligibility and extracted data. Six prospective and eight case–control studies reported relative risk (RR) estimates and 95% confidence intervals (CI) of kidney cancer associated with parity or parity number. Fixed- or random-effects models were used to estimate summary relative risk. Results: The summary relative risk of kidney cancer for the parity versus nulliparous was 1.23 (95% CI, 1.10–1.36; Q = 12.41; P = 0.413; I2 = 3.3%). In addition, significant association was also found for the highest versus lowest parity number, with summary RR = 1.36 (95% CI, 1.19–1.56; Q = 8.24; P = 0.766; I2 = 0%). In the dose–response analysis, the summary per one live birth relative risk was 1.08 (95% CI: 1.05–1.10; Q = 9.34; P = 0.500; I2 = 0%), also indicating the positive effect of parity on kidney cancer risk. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses. Conclusions: In summary, findings from this meta-analysis suggest that ever parity and higher parity number is significantly associated with increased risk of kidney cancer. Impact: The present results suggest a positive association between parity and kidney cancer risk. Cancer Epidemiol Biomarkers Prev; 22(12); 2345–53. ©2013 AACR.

Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta-analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T-T.G. and Q-J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random-effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case–control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75–0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case–control studies were 0.89 (95% CI = 0.76–1.03) and 0.84 (95% CI = 0.70–0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta-analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.

Background Distinguishing pancreatic adenocarcinomas from other pancreatic masses remains challenging with current imaging techniques. Contrast-enhanced EUS further improved the efficacy of EUS to characterize pancreatic lesions. Objective To assess the accuracy of contrast-enhanced EUS for diagnosing adenocarcinoma in patients with pancreatic masses by pooling data of existing trials. Design We systematically searched the Medline, PubMed, Web of Science, Embase, and Cochrane Central Trials databases for relevant studies published. Meta-analysis was performed. Pooling was conducted in a fixed-effect model or a random-effects model. Patients Twelve studies involving 1139 patients were included. Intervention Contrast-enhanced EUS. Main Outcome Measurements Meta-analysis and meta-regression analysis. Results The pooled sensitivity of contrast-enhanced EUS for the differential diagnosis of pancreatic adenocarcinomas was 94% (95% CI, 0.91-0.95), and the specificity was 89% (95% CI, 0.85-0.92). The area under the curve under summary receiver operating characteristic was 0.9732. The pooled positive likelihood ratio was 8.09 (95% CI, 4.47-14.64), and the negative likelihood ratio was 0.08 (95% CI, 0.06-0.10). The subgroup analysis by exclusion of the outliers provided a sensitivity of 93% (95% CI, 0.91-0.95) and a specificity of 93% (95% CI, 0.89-0.95) for the differential diagnosis of pancreatic adenocarcinomas. The area under the curve under summary receiver operating characteristic was 0.9745. Limitations A small number of studies met the inclusion criteria. Conclusion Contrast-enhanced EUS is a promising, reliable modality for the differential diagnosis of pancreatic adenocarcinoma in patients with pancreatic mass lesions. The finding of a hypoenhanced lesion was a sensitive and accurate predictor of pancreatic adenocarcinomas. It seems to be a useful tool in clinical practice.

BACKGROUND: Previous epidemiologic studies have reported inconsistent results between parity and pancreatic cancer (PC) risk. To our knowledge, a comprehensive and quantitative assessment of this association has not been conducted. METHODS: Relevant published studies of parity and PC were identified using MEDLINE (PubMed) and Web of Science databases until November 2013. Two authors (H-BG and LW) independently assessed eligibility and extracted data. Eleven prospective and 11 case-control studies reported relative risk (RR) estimates and 95% confidence intervals (CIs) of PC associated with parity. Fixed- and random-effects models were used to estimate the summary RR depending on the heterogeneity of effects. RESULTS: The summary RR for PC comparing the highest versus lowest parity was 0.86 (95% CI: 0.73-1.02; Q = 50.49, P