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11.
  • Mavromatis, Ioannis D., et al. (author)
  • Validity of intraoperative gross examination of myometrial invasion in patients with endometrial cancer : a meta-analysis
  • 2012
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 91:7, s. 779-793
  • Research review (peer-reviewed)abstract
    • Objective. The current recommended endometrial cancer surgical treatment is abdominal extrafascial total hysterectomy with bilateral salpingo-oophorectomy followed by pelvic lymphadenectomy if >50% myometrial invasion is estimated by intraoperative gross examination (IGE). This meta-analysis aims to quantify evidence regarding the validity/predictive value of IGE staging compared with final histology. Design. Meta-analysis of studies published until October 2011. Setting. Systematic search, according to PRISMA guidelines, of the six major medical literature databases Medline, Scopus, EMBASE, Google Scholar, Ovid, Cochrane. Population. Sixteen eligible studies including 2567 endometrial cancer patients. Methods. Pooled sensitivity/specificity, accuracy, negative/positive predictive value (NPV/PPV) and diagnostic odds ratio (DOR) of IGE were calculated and the summary receiver operator characteristic (sROC) curve was constructed. A meta-regression analysis was used to explore the role of potential modifiers of sensitivity and specificity. Main outcome measures. Pooled diagnostic measures of IGE indices. Results. Sixteen studies (15 retrospective, one prospective) meeting the inclusion criteria were qualitatively analyzed. Pooled IGE estimates were: sensitivity = 0.75 (95%CI: 0.720.78), specificity = 0.92 (95%CI 0.900.94), accuracy = 0.87 (95%CI 0.860.88), NPV = 0.89 (95%CI 0.870.92), PPV = 0.80 (95%CI 0.760.84) and DOR = 36.9 (95%CI 28.747.4). No significant modifiers were identified for sensitivity or specificity. Conclusions. The synthesized measures presented here for the first time showed that accuracy, sensitivity and specificity of IGE were 87, 75 and 92%, respectively, which indicates that IGE is useful for estimating depth of myometrial invasion and staging of endometrial cancer in clinical practice. The degree to which the relatively low values of some of its performance indicators could be improved remains to be elucidated in order for the values to be comparable with those from frozen section biopsies.
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12.
  • Michelakos, Theodoros, et al. (author)
  • Serum Folate and B12 Levels in Association With Cognitive Impairment Among Seniors : Results From the VELESTINO Study in Greece and Meta-Analysis
  • 2013
  • In: Journal of Aging and Health. - : SAGE Publications. - 0898-2643 .- 1552-6887. ; 25:4, s. 589-616
  • Journal article (peer-reviewed)abstract
    • Objective: To summarize existing evidence on the effect of serum folate and vitamin B12 levels on cognitive impairment among elders via a meta-analysis, also including unpublished data from a cross-sectional study of seniors ( > 65 years) residing in Velestino, Greece. Method: Serum measurements and Mini-Mental State Examination (MMSE) assessments were available for 593 Velestinians. In addition, 12 studies availing data on folate blood levels (N = 9,747) and 9 on B12 (N = 8,122) were identified following a search algorithm; pooled effect estimates were derived. Results: Cognitive impairment (MMSE < 24) among Velestenians was associated with lower education level in both genders; decreased social activity, depressive symptoms and low folate levels in males; older age in females. Meta-analyses showed an adverse effect of low-folate levels on cognition (OR: 1.66, 95% CI: 1.40-1.96); B12 was nonsignificantly associated (OR: 1.11, 95% CI: 0.88-1.40). Discussion: Low folate levels are associated with cognitive impairment of seniors; underlying pathophysiological mechanisms should be further explored.
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13.
  • Panagopoulou, Paraskevi, et al. (author)
  • Parental age and the risk of childhood acute myeloid leukemia : results from the Childhood Leukemia International Consortium
  • 2019
  • In: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 59, s. 158-165
  • Journal article (peer-reviewed)abstract
    • Background:Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent.Aim:To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies.Material/methods: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants < 1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period.Results:Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers >= 40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year.Conclusions:An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.
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14.
  • Petridou, Eleni Th., et al. (author)
  • Advanced parental age as risk factor for childhood acute lymphoblastic leukemia : results from studies of the Childhood Leukemia International Consortium
  • 2018
  • In: European Journal of Epidemiology. - : SPRINGER. - 0393-2990 .- 1573-7284. ; 33:10, s. 965-976
  • Journal article (peer-reviewed)abstract
    • Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1.05, 95% CI 1.00-1.11; ORNCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I (2) = 58%, p = 0.002; ORNCC 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.
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15.
  • Petridou, Eleni Th., et al. (author)
  • Folate and B12 serum levels in association with depression in the aged : a systematic review and meta-analysis
  • 2016
  • In: Aging & Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 20:9, s. 965-973
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To systematically review and meta-analyse existing evidence on the association between folate/B12, and depression among the aged people.METHODS: Following PRISMA/STROBE guidelines, the Medline abstracts were retrieved using an algorithm comprising relevant MeSH terms. Publications on the association of folate/B12 serum measurements with depression were abstracted independently by two reviewers and included in both gender and gender-specific meta-analyses, following recarculations of published data as appropriate. The Newcastle-Ottawa scale was used to evaluate the quality of included studies.RESULTS: Both gender data were contributed by 11 folate-related (7949 individuals) and 9 B12-related studies (6308 individuals), whereas gender-specific data by 4 folate-related (3409 individuals) and 3 B12-related studies (1934 individuals). A statistically significant overall association between both exposures of interest (low folate and B12 levels) and depression was observed (ORfolate:1.23, 95%CI:1.07-1.43, ORB12:1.20, 95%CI:1.02-1.42). Gender-specific estimates pointed to a statistically significant positive association between low B12 levels and depression only among women (OR:1.33, 95%CI:1.02-1.74); the gender specific associations of low folate levels with depression were, however, non-significant and of counter-direction (ORfemales:1.37, 95%CI:0.90-2.07; ORmales:0.84, 95%CI:0.57-1.25).CONCLUSION: Low folate and B12 serum levels seem to be associated with depression in the aged. The gender-specific analyses are confined to a positive association of low B12 with depression among older women and call for further research in this direction.
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16.
  • Petridou, Eleni Th., et al. (author)
  • In vitro fertilization and risk of childhood leukemia in Greece and Sweden
  • 2012
  • In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 58:6, s. 930-936
  • Journal article (peer-reviewed)abstract
    • Background Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets. Methods. The hospital-based case-control study in Greece derived from the National Registry for Childhood Hematological Malignancies (1996-2008, 814 leukemia and 277 lymphoma incident cases with their 1: 1 matched controls). The Swedish casecontrol study was nested in the Swedish Medical Birth Register (MBR) (1995-2007, 520 leukemia and 71 lymphoma cases with their 5,200 and 710 matched controls) with ascertainment of incident cancer cases in the National Cancer Register. Study-specific and combined odds ratios (OR) were estimated using conditional logistic regression, with adjustment for possible risk factors. Results. Nationwide studies pointed to similar size excess risk of leukemia following IVF, but to a null association between IVF and lymphoma. The proportion of leukemia cases conceived through IVF was 3% in Greece and 2.7% in Sweden; prevalence of IVF in matched controls was 1.8% and 1.6%, respectively. In combined multivariable analyses, the increased risk of leukemia was confined to age below 3.8 years (OR 2.21; 95% confidence interval, CI: 1.27-3.85) and to acute lymphoblastic leukemia (ALL) (OR 1.77; 95% CI: 1.062.95) with no sufficient evidence of excess risk for other leukemias (OR 1.34; 95% CI: 0.38-4.69). Following IVF, OR for ALL was 2.58 (95% CI: 1.37-4.84) before age 3.8 and 4.29 (95% CI: 1.4912.37) before age 2 years. Conclusions. IVF seems to be associated with increased risk of early onset ALL in the offspring. 
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17.
  • Petridou, Eleni Th, et al. (author)
  • Maternal and birth anthropometric characteristics in relation to the risk of childhood lymphomas : a Swedish nationwide cohort study
  • 2015
  • In: European Journal of Cancer Prevention. - 0959-8278 .- 1473-5709. ; 24:6, s. 535-541
  • Journal article (peer-reviewed)abstract
    • This Swedish nationwide cohort study aims to examine the role of maternal characteristics (maternal age, education, smoking, BMI, diabetes, and preeclampsia) and multiple intrauterine growth measures on the risk of childhood lymphomas. A total of 3 444 136 singleton live births registered in the Swedish Medical Birth Register were analyzed, among whom there were 515 incident non-Hodgkin lymphoma (NHL) cases and 169 Hodgkin lymphoma (HL) cases aged 0-14 years at diagnosis (1973-2007) identified through linkage with the Swedish Cancer Register. Proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) of NHL and HL. Male sex (HR=2.00, 95% CI: 1.66-2.41), older maternal age (HR=1.03, 95% CI: 1.00-1.06, per 1-year increase), and large for gestational age compared with appropriate for gestational age (AGA) birth weight (HR=1.83, 95% CI: 1.20-2.79) were correlated with the risk of NHL; of note, in subanalysis by sex, the latter association was confined to girls (HR=3.37, 95% CI: 1.90-5.97, Pinteraction by sex=0.008). The risk of childhood HL overall was more evident among boys (HR=2.03, 95% CI: 1.46-2.81), whereas indices of accelerated fetal growth were not convincingly associated with the risk of HL. Apart from the established association with sex, the findings point to accelerated intrauterine growth as a risk factor for childhood NHL that may differ by sex. Given the rarity of this condition at birth, however, further studies with more elaborate indices are needed to conclude on its association with rare diseases such as HL.
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18.
  • Petridou, Eleni Th., et al. (author)
  • Sun exposure, birth weight, and childhood lymphomas : A case control study in Greece
  • 2007
  • In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 18:9, s. 1031-1037
  • Journal article (peer-reviewed)abstract
    • Objectives  To explore whether the inverse association of sun exposure with non Hodgkin lymphoma among adults is also evident among the childhood population and test the specificity of the relation by contrasting the findings to those for Hodgkin lymphoma. Methods  A total of 87 cases of childhood (0–14 years) with non Hodgkin lymphoma and 71 with Hodgkin lymphoma, diagnosed in Greece through the national network of childhood Hematology-Oncology Units, during a 7-year period, along with 164 age- and gender-matched control children were enrolled in the study. The guardians of all eligible children were interviewed in person on the basis of a structured questionnaire covering socio-demographic, anthropometric, and perinatal characteristics. Average time of sunbathing per year at a seaside resort was used as a proxy variable of exposure to sun controlling for use of sun protection measures. Results  The estimated incidence of 10.2 cases per 1,000,000 children-years {95% Confidence Intervals (CI), 8.4–12.1} for NHL during the study period in Greece is around the average figure in countries of the European Union. There was an inverse association of sun exposure with Non Hodgkin lymphoma, namely, for an increment of 15 days of sunbathing at seaside resorts children had almost 40% lower risk (Odds Ratio: 0.60, 95% CI: 0.43–0.83), whereas no such association was evident for Hodgkin lymphoma. The risk for non Hodgkin lymphoma has been found to be statistically and significantly higher in birth weight (Odds ratio: 1.42 and 95% CI, 1.04–1.92, for every 500 g increment), whereas there was no substantial indication that maternal education or maternal smoking during the child’s life were important risk factors for the disease. Conclusions  This is the first study to provide epidemiological evidence that increased sun exposure of children may also be associated with a decreased risk of developing childhood non Hodgkin, but not Hodgkin lymphoma.  
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19.
  • Sergentanis, Theodoros N., et al. (author)
  • IVF and breast cancer : a systematic review and meta-analysis
  • 2014
  • In: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 20:1, s. 106-123
  • Research review (peer-reviewed)abstract
    • BACKGROUNDThe effects of controlled ovarian hyperstimulation (COH) for IVF in terms of breast cancer risk remain controversial, despite the hormone-dependent nature of the latter.METHODSEligible studies up to 15 February 2013 were identified and pooled effect estimates for relative risk (RR) were calculated separately for the investigations using the general population and those using infertile women, as a reference group. Fixed- or random-effects models were implemented and subgroup analyses were performed, as appropriate.RESULTSEight cohort studies were synthesized, yielding a total cohort size of 1 554 332 women among whom 14 961 incident breast cancer cases occurred, encompassing 576 incident breast cancer cases among women exposed to IVF. No significant association between IVF and breast cancer was observed either in the group of studies treating the general population (RR = 0.91, 95% confidence interval (CI): 0.74–1.11) or infertile women (RR = 1.02, 95% CI: 0.88–1.18), as a reference group. Of note were the marginal associations, protective for pregnant and/or parous women after IVF (pooled effect estimate = 0.86, 95% CI: 0.73–1.01) and adverse for women <30 years at first IVF treatment (pooled effect estimate = 1.64, 95% CI: 0.96–2.80).CONCLUSIONSAt present, COH for IVF does not seem to impart increased breast cancer risk. Longer follow-up periods, comparisons versus infertile women, subgroup analyses aiming to trace vulnerable subgroups, adjustment for various confounders and larger informative data sets are needed before conclusive statements for the safety of the procedure are reached.
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20.
  • Siristatidis, Charalampos, et al. (author)
  • Controlled ovarian hyperstimulation for IVF : impact on ovarian, endometrial and cervical cancer-a systematic review and meta-analysis
  • 2013
  • In: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 19:2, s. 105-123
  • Research review (peer-reviewed)abstract
    • BACKGROUND: In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer. METHODS: Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed-or random-effects models as appropriate. RESULTS: Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17-1.92) and endometrial (RR = 2.04, 95% CI: 1.22-3.43), but not cervical (RR = 0.86, 95% CI: 0.49-1.49)cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR=1.26, 95% CI: 0.62-2.55 RR=0.45, 95% CI: 0.18-1.14 and RR= 5.70, 95% CI: 0.28-117.20, respectively). CONCLUSIONS: IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.
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