Birth seasonality of childhood central nervous system tumors: Analysis of primary data from 16 Southern-Eastern European population-based registries.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys <5 years born during summer seemed to be at a lower risk of embryonal tumors (IRR: 0.73, 95% CI: 0.54-0.99). A clustering of astrocytomas was also found among girls (0-14 years) born during spring (IRR: 1.23, 95% CI: 1.03-1.46). Although the present exploratory results are by no means definitive, they provide some indications for age-, gender- and histology-related seasonal variations of CNS tumors. Expansion of registration and linkage with cytogenetic reports could refine if birth seasonality is causally associated with CNS tumors and shed light into the complex pathophysiology of this lethal disease.

Endocrine treatment and incidence of relapse in women with oestrogen receptor-positive breast cancer in Europe: a population-based study.

PURPOSE: Endocrine therapy (ET) is the mainstream adjuvant treatment for ER-positive breast cancer (BC). We analysed 9293 ER-positive BC patients diagnosed in nine European countries in 2009-2013 to investigate how comorbidities at diagnosis, age, stage and subtype affected ET use over time, and relapse. METHODS: Adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) of receiving ET were estimated according to Charlson comorbidity, age, stage and subtype using logistic regression. The 2-year cumulative incidence and adjusted sub-hazard ratios (SHRs) of relapse were estimated using competing risk analysis, with all-cause death as the competing event. The z-test was used to assess differences in the proportion of patients receiving ET in 1996-1998 and 2009-2013. RESULTS: Ninety percent of the patients started adjuvant ET, range 96% (Belgium, Estonia, Slovenia, Spain)-75% (Switzerland). ORs of starting ET were lower for women aged > 75 years, with severe comorbidities, or luminal B HER2-positive cancer. The factors independently increasing the risk of relapse were: not receiving ET (SHR 2.26, 95%CI 1.02-5.03); severe comorbidity (SHR 1.94, 95%CI 1.06-3.55); luminal B, either HER2 negative (SHR 3.06, 95%CI 1.61-5.79) or positive (SHR 3.10, 95%CI 1.36-7.07); stage II (SHR 3.20, 95%CI 1.56-6.57) or stage III (SHR 7.41, 95%CI 3.48-15.73). ET use increased significantly but differently across countries from 51-85% in 1996-1998 to 86-96% in 2009-2013. CONCLUSIONS: ER-positive BC patients in Europe are increasingly prescribed ET but between-country disparities persist. Older women and women with severe comorbidity less frequently receive ET. ET omission and severe comorbidity independently predict early disease relapse.

Comorbidities, age and period of diagnosis influence treatment and outcomes in early breast cancer.

Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 stage I/IIA cases diagnosed in 9 European countries in 2009-2013, and 4 STs: surgery; breast-conserving surgery plus radiotherapy (BCS + RT); reconstruction after mastectomy; and prompt treatment (≤6 weeks after diagnosis). Covariate-adjusted models estimated odds of receiving STs and risks of death/relapse, according to comorbidities. Pearson's R assessed correlations between odds and risks. The z-test assessed the significance of time-trends. Most women received surgery: 72% BCS; 24% mastectomy. Mastectomied patients were older with more comorbidities than BCS patients (p < 0.001). Women given breast reconstruction (25% of mastectomies) were younger with fewer comorbidities than those without reconstruction (p < 0.001). Women treated promptly (45%) were younger than those treated later (p = 0.001), and more often without comorbidities (p < 0.001). Receiving surgery/BCS + RT correlated strongly (R = -0.9), but prompt treatment weakly (R = -0.01/-0.02), with reduced death/relapse risks. The proportion receiving BCS + RT increased significantly (p < 0.001) with time in most countries. This appears to be the first analysis of the influence of comorbidities on receiving STs, and of consequences for outcomes. Increase in BCS + RT with time is encouraging. Although women without comorbidities usually received STs, elderly patients often received non-standard less prompt treatments, irrespective of comorbidities, with increased risk of mortality/relapse. All women, particularly the elderly, should receive ST wherever possible to maximise the benefits of modern evidence-based treatments.

Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US.

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including - for the first time - the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1,859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared to those of SEER/US (N = 3,166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one-third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress.

Malignant central nervous system tumors among adolescents and young adults (15-39 years old) in 14 Southern-Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns.

BACKGROUND: Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15-39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern-Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program. METHODS: Malignant CNS tumors diagnosed in AYAs during the period spanning 1990-2014 were retrieved from 14 population-based cancer registries in the SEE region (n = 11,438). Age-adjusted mortality rates were calculated and survival patterns were evaluated via Kaplan-Meier curves and Cox regression analyses, and they were compared with respective 1990-2012 figures from SEER (n = 13,573). RESULTS: Mortality rates in SEE (range, 11.9-18.5 deaths per million) were higher overall than the SEER rate (9.4 deaths per million), with decreasing trends in both regions. Survival rates increased during a comparable period (2001-2009) in SEE and SEER. The 5-year survival rate was considerably lower in the SEE registries (46%) versus SEER (67%), mainly because of the extremely low rates in Ukraine; this finding was consistent across age groups and diagnostic subtypes. The highest 5-year survival rates were recorded for ependymomas (76% in SEE and 92% in SEER), and the worst were recorded for glioblastomas and anaplastic astrocytomas (28% in SEE and 37% in SEER). Advancing age, male sex, and rural residency at diagnosis adversely affected outcomes in both regions. CONCLUSIONS: Despite definite survival gains over the last years, the considerable outcome disparities between the less affluent SEE region and the United States for AYAs with malignant CNS tumors point to health care delivery inequalities. No considerable prognostic deficits for CNS tumors are evident for AYAs versus children. Cancer 2017;123:4458-71. © 2017 American Cancer Society.

Mortality and survival patterns of childhood lymphomas: geographic and age-specific patterns in Southern-Eastern European and SEER/US registration data.

Childhood (0-14 years) lymphomas, nowadays, present a highly curable malignancy compared with other types of cancer. We used readily available cancer registration data to assess mortality and survival disparities among children residing in Southern-Eastern European (SEE) countries and those in the United States. Average age-standardized mortality rates and time trends of Hodgkin (HL) and non-Hodgkin (NHL; including Burkitt [BL]) lymphomas in 14 SEE cancer registries (1990-2014) and the Surveillance, Epidemiology, and End Results Program (SEER, United States; 1990-2012) were calculated. Survival patterns in a total of 8918 cases distinguishing also BL were assessed through Kaplan-Meier curves and multivariate Cox regression models. Variable, rather decreasing, mortality trends were noted among SEE. Rates were overall higher than that in SEER (1.02/106 ), which presented a sizeable (-4.8%, P = .0001) annual change. Additionally, remarkable survival improvements were manifested in SEER (10 years: 96%, 86%, and 90% for HL, NHL, and BL, respectively), whereas diverse, still lower, rates were noted in SEE. Non-HL was associated with a poorer outcome and an amphi-directional age-specific pattern; specifically, prognosis was inferior in children younger than 5 years than in those who are 10 to 14 years old from SEE (hazard ratio 1.58, 95% confidence interval 1.28-1.96) and superior in children who are 5 to 9 years old from SEER/United States (hazard ratio 0.63, 95% confidence interval 0.46-0.88) than in those who are 10 to 14 years old. In conclusion, higher SEE lymphoma mortality rates than those in SEER, but overall decreasing trends, were found. Despite significant survival gains among developed countries, there are still substantial geographic, disease subtype-specific, and age-specific outcome disparities pointing to persisting gaps in the implementation of new treatment modalities and indicating further research needs.

Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US.

Pilocytic astrocytomas (PA) comprise the most common childhood central nervous system (CNS) tumor. Exploiting registry-based data from Southern and Eastern Europe (SEE) and SEER, US, we opted to examine incidence, time trends, survival and tentative outcome disparities of childhood PA by sociodemographic and clinical features. Childhood PA were retrieved from 12 SEE registries (N = 552; 1983-2014) and SEER (N = 2723; 1973-2012). Age-standardized incidence rates (ASR) were estimated and survival was examined via Kaplan-Meier and Cox regression analysis. ASR of childhood PA during 1990-2012 in SEE was 4.2/106, doubling in the USA (8.2/106). Increasing trends, more prominent during earlier registration years, were recorded in both areas (SEE: +4.1 %, USA: +4.6 %, annually). Cerebellum comprised the most common location, apart from infants in whom supratentorial locations prevailed. Age at diagnosis was 1 year earlier in SEE, whereas 10-year survival was 87 % in SEE and 96 % in SEER, improving over time. Significant outcome predictors were age <1 year at diagnosis diagnosis (hazard ratio, HR [95% confidence intervals]: 3.96, [2.28-6.90]), female gender (HR: 1.38, [1.01-1.88]), residence in SEE (HR: 4.07, [2.95-5.61]) and rural areas (HR: 2.23, [1.53-3.27]), whereas non-cerebellar locations were associated with a 9- to 12-fold increase in risk of death. The first comprehensive overview of childhood PA epidemiology showed survival gains but also outcome discrepancies by geographical region and urbanization pointing to healthcare inequalities. The worse prognosis of infants and, possibly, females merits further consideration, as it might point to treatment adjustment needs, whereas expansion of systematic registration will allow interpretation of incidence variations.

Analysis of Conservative Surgical Treatment and Prognosis of Microinvasive Squamous Cell Carcinoma of the Cervix Stage IA1: Results of Follow-Up to 20 Years.

OBJECTIVE: The aim of this study was to evaluate the prognosis and recurrence of microinvasive squamous cervical (MIC) cancer stage IA1 in women treated conservatively or by hysterectomy, and followed-up to 20 years. METHODS: It was studied in a cohort of 139 women with MIC, 41 definitively managed by conization and 98 by hysterectomy from January 1994 to December 2003 and followed-up until 2013. The definitive treatment, age, conization technique (loop electrosurgical excision procedure or cold knife conization), cone margin, residual disease in hysterectomy specimen, and the association with recurrence (intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse, and microinvasive or worse) were analyzed. RESULTS: There were 2.5 times more conservative treatment in younger women than older (>40 years), and high proportion of residual disease in hysterectomy specimens (67% of intraepithelial cervical neoplasia grade 3 or worse), more common if positive cone margin (74% vs 35%, P < 0.002). There were 2.3% (3/133) recurrences detected as microinvasive or worse, and 6% (8/133) recurrences detected as intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse: 7.3% (3/41) in the conization group and 5.4% (5/92) in the hysterectomy group (P = 0.701). Almost all recurrences (88%, 7/8) were diagnosed until 36 months after treatment, and they were not associated with conization technique. There were no differences in risk of recurrence and overall disease-free survival time related to type of treatment. CONCLUSIONS: This study demonstrates the good prognosis of MIC, regardless the treatment. When fertility is not a concern, hysterectomy should be considered as definitive treatment to avoid the risk of residual disease. Regular follow-up for a long period should be maintained.

Incidence and time trends of childhood lymphomas: findings from 14 Southern and Eastern European cancer registries and the Surveillance, Epidemiology and End Results, USA.

PURPOSE: To describe epidemiologic patterns of childhood (0-14 years) lymphomas in the Southern and Eastern European (SEE) region in comparison with the Surveillance, Epidemiology and End Results (SEER), USA, and explore tentative discrepancies. METHODS: Childhood lymphomas were retrieved from 14 SEE registries (n = 4,702) and SEER (n = 4,416), diagnosed during 1990-2014; incidence rates were estimated and time trends were evaluated. RESULTS: Overall age-adjusted incidence rate was higher in SEE (16.9/106) compared to SEER (13.6/106), because of a higher incidence of Hodgkin (HL, 7.5/106 vs. 5.1/106) and Burkitt lymphoma (BL, 3.1 vs. 2.3/106), whereas the incidence of non-Hodgkin lymphoma (NHL) was overall identical (5.9/106 vs. 5.8/106), albeit variable among SEE. Incidence increased with age, except for BL which peaked at 4 years; HL in SEE also showed an early male-specific peak at 4 years. The male preponderance was more pronounced for BL and attenuated with increasing age for HL. Increasing trends were noted in SEER for total lymphomas and NHL, and was marginal for HL, as contrasted to the decreasing HL and NHL trends generally observed in SEE registries, with the exception of increasing HL incidence in Portugal; of note, BL incidence trend followed a male-specific increasing trend in SEE. CONCLUSIONS: Registry-based data reveal variable patterns and time trends of childhood lymphomas in SEE and SEER during the last decades, possibly reflecting diverse levels of socioeconomic development of the populations in the respective areas; optimization of registration process may allow further exploration of molecular characteristics of disease subtypes.

Sociodemographic determinants of prevalence and incidence of Helicobacter pylori infection in Portuguese adults.

BACKGROUND: Understanding the determinants of Helicobacter pylori infection in adults is essential to predict the burden of H. pylori-related diseases. We aimed to estimate the prevalence and incidence of H. pylori infection and to identify its major sociodemographic correlates in an urban population from the North of Portugal. MATERIAL AND METHODS: A representative sample of noninstitutionalized adult inhabitants of Porto (n = 2067) was evaluated by ELISA (IgG) and a subsample (n = 412) was tested by Western Blot to assess infection with CagA-positive strains. Modified Poisson and Poisson regression models were used to estimate crude and sex-, age-, and education-adjusted prevalence ratios (PR) and incidence rate ratios (RR), respectively. RESULTS: The prevalence of H. pylori infection was 84.2% [95% confidence interval (95%CI): 82.4-86.1]. It increased across age-groups in the more educated subjects, (18-30 years: 72.6%; ≥71 years: 88.1%; p for trend <0.001) and decreased with education in the younger (≤4 schooling years: 100.0%; ≥10 schooling years: 72.6%; p for trend <0.001). Living in a more deprived neighborhood was associated with a higher prevalence of infection, only in the younger (PR = 1.20, 95%CI: 1.03-1.38) and more educated participants (PR = 1.15, 95%CI: 1.03-1.29). Among the infected, the proportion with CagA-positive strains was 61.7% (95%CI: 56.6-66.9). The incidence rate was 3.6/100 person-years (median follow-up: 3 years; 95%CI: 2.1-6.2), lower among the more educated (≥10 vs ≤9: RR = 0.25, 95%CI: 0.06-0.96). The seroreversion rate was 1.0/100 person-years (95%CI: 0.6-1.7). CONCLUSIONS: The prevalence of infection among adults is still very high in Portugal, suggesting that stomach cancer rates will remain high over the next few decades.

Dietary patterns and gastric cancer in a Portuguese urban population.

Dietary patterns analysis is a powerful technique to study the relations between diet and cancer. We aimed to quantify the association between dietary patterns and gastric cancer, by location and histological type, according to Helicobacter pylori infection status. We analyzed 591 incident cases of gastric adenocarcinoma and 1,463 community controls. Dietary intake was assessed using a validated food frequency questionnaire. Principal components and cluster analyses were used to define dietary patterns. Anti-H. pylori IgG was assessed by ELISA. Age-, gender-, education- and total energy intake-adjusted odds ratios (OR) were computed. Three dietary patterns were identified, with the following main characteristics: (I) high consumption of fruits and dairy products, and low consumption of alcoholic beverages; (II) low consumption of fruit, salads, vegetables, dairy products, fish and meat; (III) high consumptions of most food groups and low vegetable soup intake. Compared to pattern I, the risk of gastric cancer was higher for pattern II (OR = 1.68, 95% CI: 1.31-2.14) but not for pattern III (OR = 0.80, 95% CI: 0.57-1.14), with no effect modification by H. pylori infection. The association was similar for cardia and non-cardia gastric cancer, but for tumors of the diffuse Laurén histological type, the association was weaker for pattern II vs. I (OR = 1.32, 95% CI: 0.83-2.08) and a protective effect was observed for pattern III vs. I (OR = 0.43, 95% CI: 0.22-0.87). Our results confirm the protective effect of high fruit and vegetables intake, and show a differential association according to histological type. No effect modification by H. pylori infection was observed.

The state of the art of cancer control in 30 European countries in 2008.

Inequalities in cancer incidence, mortality and survival represent a major challenge for public health. Addressing this challenge requires complex and multidisciplinary approaches. Sharing successful experiences from across Europe may therefore be of benefit. We describe the state of the art of cancer control structures in the 27 European Union countries, plus Iceland, Norway and Switzerland, at the beginning of 2008. Information on cancer plans, cancer registries, cancer screening, Human Papillomavirus (HPV) vaccination and smoking restrictions in each country was identified through PubMed, the official websites of national and international organizations and Google searches. Experts and/or health authorities from each country completed and validated the information. Sixteen countries had implemented national cancer plans in 2008. Twenty four countries had population-based cancer registries with 100% coverage. The exceptions were Greece and Luxembourg (no population-based registry yet), France, Italy and Spain (<50%), and Switzerland (62%). In 9 countries, population coverage of breast cancer screening was 100% with participation ranging from 26 to 87%; 8 countries did not have organized programmes. Seven countries had cervical cancer screening programmes with 100% coverage with participation ranging from 10 to 80%; 8 countries had no organized programme. Nine countries had announced national HPV vaccination policies by early 2008. Six countries had organized colorectal cancer screening programmes. Five countries had complete bans on smoking in public places. There is wide international heterogeneity in cancer control structures in Europe. This provides considerable scope and motivation for cooperation and sharing of experience.

Lung Cancer: A Nationwide Study to Characterize Sex Differences, Incidence, and Spatial Patterns in Portugal.

BACKGROUND/AIM: This study characterized lung cancer (LC) in Portugal, to capture sex differences, regional variation, and spatial distribution. PATIENTS AND METHODS: Variables: age, sex, vital status, region of residence, degree of urbanization, histologic types and stage at diagnosis. Spatial analyses conducted to identify high (HIC) and low incidence (LIC) clusters. RESULTS: In total, 11,642 cases were diagnosed (76.6% male, 23.4% female), with a similar mean age at diagnosis. There were 23,6% locally advanced and 58.4% metastatic disease cases, with 13.4% alive five years after diagnosis. Non-small-cell LC accounted for 77.3% of which 40.8% was adenocarcinoma and 22.7% was squamous cell carcinoma. Standardized incident rate (IR) was 37.5/105, 65.2/105 in males, and 15.7/105 in females, with four HIC (urban) clusters and four LIC (non-urban). CONCLUSION: This study highlighted the sex differences in incidence, mortality, histology, and geographic distribution of LC in Portugal. Considering the advanced stages and the poor overall survival, understanding sex and geographic differences is important for public health interventions.

Regional differences in tobacco smoking and lung cancer in Portugal in 2018: a population-based analysis using nationwide incidence and mortality data.

OBJECTIVES: This study aims to estimate the proportion of lung cancer cases and deaths attributable to tobacco smoking in Portugal in 2018, complemented by trends in incidence and mortality, by sex and region. DESIGN: Cancer cases for 1998-2011 and cancer deaths for 1991-2018 were obtained from population-based registries and Statistics Portugal, respectively. We projected cases for 2018 and used reported deaths for the same year to estimate, using Peto's method, the number and proportion of lung cancer cases and deaths caused by tobacco smoking in 2018. We calculated the age-adjusted incidence and mortality rates in each year of diagnosis and death. We fitted a joinpoint regression to the observed data to estimate the annual percentage change (APC) in the rates. SETTING: Portugal. RESULTS: In 2018, an estimated 3859 cases and 3192 deaths from lung cancer were attributable to tobacco smoking in Portugal, with men presenting a population attributable fraction (PAF) of 82.6% (n=3064) for incidence and 84.1% (n=2749) for mortality, while in women those values were 51.0% (n=795) and 42.7% (n=443), respectively. In both sexes and metrics, the Azores were the region with the highest PAF and the Centre with the lowest. During 1998-2011, the APC for incidence ranged from 0.6% to 3.0% in men and 3.6% to 7.9% in women, depending on region, with mortality presenting a similar pattern between sexes. CONCLUSION: Exposure to tobacco smoking has accounted for most of the lung cancer cases and deaths estimated in Portugal in 2018. Differential patterns of tobacco consumption across the country, varying implementation of primary prevention programmes and differences in personal cancer awareness may have contributed to the disparities observed. Primary prevention of lung cancer remains a public health priority, particularly among women.

Neoadjuvant radiotherapy in the approach of locally advanced breast cancer.

BACKGROUND: Approximately 4% of European patients are diagnosed with locally advanced breast cancer (LABC), a clinical condition commonly associated with poorer prognosis. Systemic therapy is the recommended initial treatment and when inoperability criteria prevails, radiotherapy (RT) should be used for tumour downstaging. This study intends to evaluate the impact of neoadjuvant radiotherapy (NART) in the treatment of inoperable LABC. METHODS: A retrospective study of female patients, submitted to the NART between January 2014 and December 2018 at our institution. The evaluation of pathological response (pR) was made based on Pinder criteria. Primary endpoint: pR. Secondary endpoints: overall survival (OS) and progression-free survival (PFS). OS and PFS were calculated using the Kaplan-Meier method. Differences between groups were compared using Student's t-test, ANOVA (Analysis of variance) and χ2 test. The statistical analyses were performed using Stata (V.13). RESULTS: A total of 76 patients were included, 18% with breast complete response. The 5 years OS was 54% and PFS was 61%. Subgroup analysis showed that pR >90% is correlated with a better OS (p=0.004). Basal-like intrinsic subtype is correlated with worse OS and PFS (p<0.05). No relation was found between response and age, intrinsic subtype, treatment performed and clinical T stage. CONCLUSION: Our study confirms that NART is an effective downsizing treatment in inoperable LABC, allowing for a surgical resection regardless of the systemic treatment performed. Response to NART is independent of the intrinsic subtype and pR >90% is correlated with a better OS. Prospective studies to explore predictive response biomarkers are necessary in order to improve patient selection and optimisation of the treatment.

Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours.

INTRODUCTION: The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERalpha, both encoding for transcription factors with a potential involvement in the ERalpha-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERalpha-negative/poor prognosis breast cancer group. METHODS: We evaluate FOXA1 and GATA-3 expression in 249 breast carcinomas by immunohistochemistry, associating it with breast cancer molecular markers, clinicopathological features and patient's survival. The clinicopathological features and immunohistochemical markers of the tumours were compared using the chi-square test and ANOVA. Disease-free survival was analysed through Kaplan-Meier survival curves and Cox regression. RESULTS: FOXA1 expression was demonstrated in 42% of invasive carcinomas, while GATA-3 was detected in 48% of the cases. FOXA1 expression was inversely associated with tumour size, Nottingham Prognostic Index, histological grade, lymph vascular invasion, lymph node stage and human epidermal growth factor receptor-2 (HER-2) overexpression, while GATA-3 expression showed inverse association with histological grade and HER-2. Both FOXA1 and GATA-3 were directly associated with ERalpha and progesterone receptor. Among FOXA1-positive tumours, 83.1% are comprised in the luminal A subtype, similar to GATA-3 where 87.7% of positive tumours were classified within this molecular subtype. In the subset of ERalpha-negative patients, those who were FOXA1-negative had a 3.61-fold increased risk of breast cancer recurrence when compared with the FOXA1-positive. CONCLUSIONS: FOXA1 was a significant predictor of good outcome in breast cancer, whereas GATA-3 was an important luminal marker. The expression of FOXA1 may be used for risk stratification among ERalpha-negative patients.

Impact of risk factors for non-fatal acute myocardial infarction.

The impact of risk factors for acute myocardial infarction (AMI) strongly differs across populations and most studies do not consider age as an effect modifier. This study aims to estimate the population attributable fractions (PAFs) of established risk factors for non-fatal AMI, considering age stratification, within a population-based case-control study of Portuguese men. Cases were male patients consecutively admitted with an incident AMI, during 1999-2003 (n = 638) and controls were a representative sample of the non-institutionalized Porto, Portugal inhabitants (n = 851). PAFs were derived by the equation: PAF = 1 - Sigma (rho/R), in which rho is the proportion of cases in each exposure stratum and R is the adjusted odds ratio. PAFs were obtained for the individual effect of each factor and for combinations of them, after allowance for confounding. High waist-to-hip ratio (> 0.90), smoking and lower education levels (0-4 years) had the highest PAFs among men aged < or = 45 years: 81.2% (95% CI: 71.2-88.2), 63.5% (95% CI: 42.0-80.6) and 53.8% (95% CI: 40.9-66.2), respectively. For the oldest men, high waist-to-hip ratio (PAF = 88.7%, 95% CI: 77.6-94.7) and lack of leisure-time physical activity (PAF = 44.8%, 95% CI: 32.0-58.2) were the risk factors with the highest impact. Lifestyles explained 77.2% (95% CI: 53.4-90.9) of young myocardial infarction cases and 77.6% (95% CI: 65.3-86.4) of the cases aged > 45 years. Preventive targeted interventions to decrease the prevalence of such modifiable risk factors would likely reduce morbidity and mortality of cardiovascular events and related conditions.

Environmental impacts of commuting modes in Lisbon: a life-cycle assessment addressing particulate matter impacts on health.

A life-cycle assessment of commuting alternatives is conducted that compares six transportation modes (car, bus, train, subway, motorcycle and bicycle) for eight impact indicators. Fine particulate matter (PM2.5) emissions and health impacts are incorporated in the assessment using intake fractions that differentiate between urban and non-urban emissions, combined with an effect factor. The potential benefits of different strategies for reducing environmental impacts are illustrated. The results demonstrate the need for comprehensive approaches that avoid problem-shifting among transportation-related strategies. Policies aiming to improve the environmental performance of urban transportation should target strategies that decrease local emissions, life-cycle impacts and health effects.

Human cytotoxicity and octanol/water partition coefficients of fluorinated ionic liquids.

The use of fluorinated ionic liquids (FILs) as novel materials in biological and pharmaceutical applications is an emerging research field. The knowledge of their cytotoxicity and that of 1-octanol/water partition coefficients are essential to assess their environmental risks, to estimate their toxicity and activity, or the hydrophilic/lipophilic balance, as well as to explore their properties as solvents in extraction processes or for successful drug design. The study of the cytotoxicity in four different human cell lines and the experimental measurement of the partition coefficient between 1-octanol and water (Po/w), using the slow-stirring method, were carried out for several FILs. In both studies, the effect of the cation ([C2C1Im]+, [C2C1py]+, [C4C1pyr]+, [N1112(OH)]+, or [N4444]+), the cationic alkyl side-chain length ([CnC1Im]+, with n = 2, 6, 8 or 12), and the anionic fluorinated chain length/anionic fluorinated domain size ([C4F9SO3]¯, [C8F17SO3]¯, or [N(C4F9SO3)2]¯) were analysed. The results reveal that both toxicity and partition properties are mainly influenced by the size of the cationic hydrogenated alkyl side-chain and that of the anionic fluorinated domain. The intrinsic tuneability of the FILs allows for their selection according to the lipophilic or hydrophilic character of the target biological system under consideration. The toxicity studies corroborate the biocompatible nature of some FILs tested in this work. Along, for all the FILs under study Po/w < 1.00. Accordingly, a decadic logarithm of the bioconcentration factor in fish of 0.5 would be estimated, which is below the regulatory endpoint used by regulatory agencies.

Stress level and quality of life following pediatric cataract surgery / Avaliação do nível de estresse e de qualidade de vida em crianças submetidas à cirurgia de catarata

ABSTRACT Purpose: To evaluate the quality of life and stress level related to visual function following pediatric cataract surgery in a Brazilian public hospital. Methods: This prospective study analyzed children aged 6-14 years old who underwent cataract surgery. The Childhood Stress Scale and Children's Visual Function Questionnaire (CVFQ) were used to assess stress levels and quality of life, respectively. Both instruments were applied by two psychologists before and after the surgery. Eye examination was performed by two ophthalmologists. Preoperative and postoperative data were compared. Results: In total, 23 children (32 eyes) were enrolled in the study, of which 9 had bilateral cataracts. The average age group at the time of surgery was 9.65 ± 2.26 (6-14) years old. One month after the surgery, the spherical equivalent was -0.90 ± 1.66D, and the corrected distance visual acuity was 0.13 ± 0.10 (0-0.3) LogMAR in bilateral cases and 0.50 ± 0.39 (0-1.3) LogMAR in unilateral cases (p<0.01). According to the Childhood Stress Scale, 77.7% of the bilateral cases and 57.1% of the unilateral cases had stable stress levels, and 34.7% of the children improved their stress level. The analysis of the CVFQ was based on scores for general health, general vision health, competence, personality, and treatment. After cataract surgery, 78.2% of the patients had improved or maintained CVFQ scores in the general health domain; 82.6%, general vision health; 95.6%, competence; 56.5%, personality; and 78.2%, treatment. Conclusion: Pediatric cataract surgery improves the visual function and the quality of life even in patients undergoing surgical procedures, without increasing the stress levels.

RESUMO Objetivo: Avaliar a qualidade de vida e o nível de estresse relacionada à função visual após a cirurgia de catarata pediátrica em um hospital público brasileiro. Métodos: Estudo prospectivo em crianças de seis a 14 anos submetidas à cirurgia de catarata. A Escala de Stresse Infantil e o Questionário de Função Visual em Crianças foram usados para avaliar o nível de estresse e a qualidade de vida, respectivamente. Ambos os instrumentos foram aplicados por duas psicólogas antes e após a cirurgia. O exame oftalmológico foi realizado por dois oftalmologistas. Os dados coletados no pré e pós-operatório foram comparados. Resultados: Vinte e três crianças (32 olhos) foram incluídas no estudo, nove delas apresentavam catarata bilateral. A média de idade na cirurgia foi de 9,65±2,26 (6 a 14) anos. Um mês após a cirurgia, o equivalente esférico foi de -0,90 ± 1,66D e a acuidade visual corrigida a distância foi de 0,13 ± 0,10 (0-0,3) LogMAR em casos bilaterais e 0,50 ± 0,39 (0-1,3) LogMAR em casos unilaterais (p<0.01). De acordo com a Escala de Stresse Infantil, 77,7% dos casos de catarata bilaterais, e 57,1% dos casos unilaterais mantiveram o nível de estresse e 34,7% das crianças melhoraram o nível de estresse. A análise do Questionário de Função Visual em Crianças foi baseada em pontuações para saúde geral, saúde geral da visão, competência, personalidade e tratamento. Após a cirurgia de catarata, 78,2% dos pacientes melhoraram ou mantiveram o escore do Questionário de Função Visual em Crianças na saúde geral, 82,6% na saúde geral da visão, 95,6% na competência, 56,5% na personalidade e 78,2% no tratamento. Conclusão: A cirurgia de catarata pediátrica melhora a função visual e a qualidade de vida em pacientes submetidos a procedimento cirúrgico, sem aumentar o nível de estresse.