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This study was funded by the Compagnia di San Paolo, the Cariplo Foundation and the European Commission (grant number 801520 HP-JA-2017, Innovative Partnership for Action Against Cancer, iPAAC Joint Action). The sources of the funding played no role in designing the study, collecting, analyzing, or interpreting the data, writing the report, or deciding whether or not to submit the article for publication. This research was (partially) funded by Italian Ministry of Health "Ricerca Corrente" funds. Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15-64 years) diagnosed in 2000-2006 vs. 2007-2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

ObjectiveThe impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.DesignWe defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.ResultsIn 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).ConclusionThe AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

Objective The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years. Design Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change. Results We retrieved data on 143.7 million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20–29 years from 2004 to 2016. The increase in the age group of 30–39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40–49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20–29 years, and 10–20 years later in those aged 30–39 and 40–49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30–39 years and 40–49 years, respectively. Conclusion CRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered.

this paper is based upon work from COST Action ICSHNet. Children's environmental health is on the 2030 Agenda for Sustainable Development. The incidence of childhood cancer is increasing worldwide and in Europe. Yet, the aetiology of most childhood cancers, including the role of environmental carcinogens, is still largely unknown. Contaminated areas, especially of industrial origin, are of high concern due to complex mix of hazardous pollutants and their potential health impacts on human populations, notably in children.to describe cancer risk in children and young adults (YA) residing in national priority contaminated sites (NPCSs) in Italy and to provide a suitable framework for a development of cancer surveillance in industrially contaminated sites (ICSs) in Europe.this study is based on a collaborative work of the Italian Institute of Health (ISS) and the Italian Association of Cancer Registries (AIRTUM), in the context of the SENTIERI project (Epidemiological study of residents in National Priority Contaminated Sites). Incidence rates were standardised according to the European standard population. The number of observed cases was compared to the expected cases derived from the age-, sex-, and cancer-specific incidence rates of the national pool of AIRTUM registries for the period 2006-2013. Standardized incidence ratios (SIRs) and 90% confidence intervals (CIs) were computed. The study reports the cancer profile in all combined 28 NPCSs covered by 22 cancer registries.1,050 cases of malignant tumours (MTs) were recorded among 3,161,786 person-years in people aged 0-29 years in 28 NPCSs (SIR: 1.03; 90%CI 0.98-1.09), with an age-standardised incidence rate of 317 per million. Excess risks were observed for: MT of the central nervous system in the age-group1 year (SIR: 3.2; 90%CI 1.4-6.3); soft tissue sarcoma in the age-group 0-14 years (SIR: 1.6; 90%CI 1.1-2.3); acute myeloid leukaemia in the agegroup 0-14 years (SIR: 1.7; 90%CI 1.1-2.4); non-Hodgkin lymphoma in the age-group 20-24 years (SIR 1.5; 90%CI 1.1-2.1), and germ cell tumours of male gonads in the age-group 20-29 years (SIR: 1.33; 90%CI 1.1-1.5). A deficit of cases was observed for Hodgkin lymphomas in the age-group 20-29 years (SIR 0.8; 90%CI 0.6-1.0).this study, which is based on standardized methods and accredited information sources, supports the hypothesis that living in an NPCS increases the risk of some cancer types in children and young adults. Further work will concern groups of NPCSs characterised by common sources of contamination/key carcinogenic pollutants. In fact, in a novel project proposal we aim to monitor the cancer profile in children living in ICSs in Europe. The new project, based on the SENTIERI-AIRTUM methodology, will build on the networking activities of the COST Action on Industrially Contaminated Sites and Health Networking (ICSHNet) and childhood cancer studies coordinated by the International Agency for research on Cancer (IARC).

Renata Conforti,1 Mario Cirillo,2 Valeria Marrone,1 Rosario Galasso,1 Guglielmo Capaldo,3 Teresa Giugliano,4 Assunta Scuotto,1 Giulio Piluso,4 Mariarosa AB Melone3,51Neuroradiology Unit, Department of Clinical and Experimental Medicine and Surgery, 2Radiology Unit, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, 3Division of Neurology, Department of Clinical and Experimental Medicine and Surgery, 4Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy; 5Institute of Protein Biochemistry, National Research Council, Naples, ItalyAbstract: Neurofibromatosis type 1 (NF1) is a relatively common single-gene disorder, and is caused by heterozygous mutations in the NF1 gene that result in a loss of activity or in a nonfunctional neurofibromin protein. Despite the common association of NF1 with neurocutaneous features, its pathology can extend to numerous tissues not derived from the neural crest. Among the rare cerebrovascular abnormalities in NF1, more than 85% of cases are of purely occlusive or stenotic nature, with intracranial aneurysm being uncommon. Predominantly, the aneurysms are located in the internal carotid arteries (ICAs), being very rare bilateral aneurysms. This report describes a very unusual case of fusiform aneurysms of both ICAs in a Caucasian NF1 patient, with a new pathogenic intragenic heterozygous deletion of the NF1 gene, presenting at age 22 years with Tolosa–Hunt syndrome, because of partial thrombosis of the left giant intracavernous aneurysm. Medical treatment with anticoagulant therapy allowed a good outcome for the patient. In conclusion, early identification of cerebral arteriopathy in NF1 and close follow-up of its progression by neuroimaging may lead to early medical or surgical intervention and prevention of significant neurologic complications.Keywords: neurofibromatosis type 1, NF1 gene, multiplex ligation-dependent probe amplification (MLPA), intracranial aneurysms, Tolosa–Hunt syndrome

Purpose: Alcohol intake may adversely affect the concentrations of endogenous sex hormones, and thus increase the risk of endometrial cancer. However, epidemiologic studies have provided conflicting results. Therefore, we investigated the association between alcohol intake and endometrial cancer risk a large, multicenter, prospective study. Methods: From 1992 through 2010, 301,051 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed for incident endometrial cancer (n = 1382). Baseline alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. Results: The multivariable HRs (and 95% CIs) compared with light drinkers (0.1-6 g/d) were 1.03 (0.88-1.20) for 0 g of alcohol per day at baseline, 1.01 (0.86-1.17) for 6.1-12 g/d, 1.03 (0.87-1.22) for 12.1-24 g/d, 1.07 (0.87-1.38) for 24.1-36 g/d, and 0.85 (0.61-1.18) for more than 36 g/d (ptrend = 0.77). No association was observed among former drinkers (OR, 1.28; 95% CI, 0.98-1.68 compared with light drinkers). Null associations were also found between alcohol consumption at age 20 years, lifetime pattern of alcohol drinking, and baseline alcohol intake from specific alcoholic beverages and endometrial cancer risk. Conclusions: Our findings suggest no association between alcohol intake and endometrial cancer risk. © 2013 Elsevier Inc.

OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS: The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS: This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.

Androgen deprivation therapy still remains the gold standard in the treatment of advanced prostate cancer. Unfortunately, patients with metastatic prostate cancer treated with androgen deprivation therapy frequently develop androgen-independent prostate cancer. Cytotoxic chemotherapy has not been used routinely and the current standard regimens have not demonstrated any significant alteration in the development of hormone-refractory disease. Recent phase III randomized clinical trials have suggested that docetaxel-based therapy, demonstrating a real increase of survival in treated patients, could represent the new standard treatment for metastatic patients. There is also promising activity of new drug combinations, such as taxanes plus vinca alkaloids, and of classic chemotherapeutic agents plus biological drugs. This review focuses on the current therapies for the treatment of HRPC.

Objective: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24- h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods.Design: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included.Results: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R-partial(2) = 17.2%) for beta-cryptoxanthin, total carrots (R-partial(2) = 13.4%) and root vegetables (R-partial(2) = 13.3%) for alpha-carotene, and tomato products (R-partial(2) = 13.8%) for lycopene. For 24HDR, the highest R-partial(2) was for fruits in relation to beta-cryptoxanthin (7.9%).Conclusions: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

Objective To develop and validate a parent-centered and a child-centered composite disease assessment index for juvenile idiopathic arthritis (JIA): the Juvenile Arthritis Parent Assessment Index (JAPAI) and the Juvenile Arthritis Child Assessment Index (JACAI), respectively. Methods The JAPAI and the JACAI include 4 measures: parent/child rating of overall well-being, pain, physical function, and health-related quality of life (HRQOL). Validation analyses were conducted on nearly 5,000 patients and included assessment of construct validity, discriminant validity, responsiveness to change, and reliability. Besides the 4-item version, a 3-item version of both indices, which did not include HRQOL, was tested. Results The JAPAI and the JACAI demonstrated good construct validity, yielding high correlations with the Juvenile Arthritis Disease Activity Score and moderate correlations with physician global rating and joint counts. Correlations obtained for the JAPAI and the JACAI and for the 4-item and the 3-item versions were comparable. Factorial analysis by principal component analysis showed that both indices are monodimensional. Both the JAPAI and JACAI discriminated well between different disease states and courses and between different levels of American College of Rheumatology Pediatric criteria in a clinical trial, and revealed fair responsiveness to clinical change. Internal consistency was satisfactory, with a Cronbach's alpha of >0.80 in all but 1 of the patient samples tested. Conclusion The JAPAI and the JACAI were found to be valid instruments for assessment of disease status in JIA and suitable surrogates of physicians' evaluations. Both indices are potentially applicable in clinical practice, observational studies, and therapeutic trials. Copyright © 2011 by the American College of Rheumatology.

Objectives To determine whether baseline demographic, clinical, articular and laboratory variables predict methotrexate (MTX) poor response in polyarticular-course juvenile idiopathic arthritis. Methods Patients newly treated for 6 months with MTX enrolled in the Paediatric Rheumatology International Trials Organization (PRINTO) MTX trial. Bivariate and logistic regression analyses were used to identify baseline predictors of poor response according to the American College of Rheumatology pediatric (ACR-ped) 30 and 70 criteria. Results In all, 405/563 (71.9%) of patients were women; median age at onset and disease duration were 4.3 and 1.4 years, respectively, with anti-nuclear antibody (ANA) detected in 259/537 (48.2%) patients. With multivariate logistic regression analysis, the most important determinants of ACR-ped 70 non-responders were: disease duration >1.3 years (OR 1.93), ANA negativity (OR 1.77), Childhood Health Assessment Questionnaire (CHAQ) disability index> 1.125 (OR 1.65) and the presence of right and left wrist activity (OR 1.55). Predictors of ACR-ped 30 non-responders were: ANA negativity (OR 1.92), CHAQ disability index> 1.14 (OR 2.18) and a parent's evaluation of child's overall wellbeing

Objectives Multiple aspects of the metabolic syndrome (MetS) remain problematic. Here we assess the association between epidemic obesity and the other MetS traits, and MetS utility for cardiovascular disease (CVD) risk assessment. Methods Italian population-based Progetto CUORE data were used: 17 252 women and men ages 35–69 years, baseline 1984–1993, mean follow-up of 10 years, for nonfatal plus fatal CVD events. NCEP-ATP III criteria defined MetS. Results Epidemic obesity was strongly related to epidemic rates of the four other MetS traits. Only four of 16 possible MetS trait combinations were common; their CVD hazard ratios ranged from 1.21 to 1.70. In multivariate analyses MetS was no better than the sum of its parts in predicting CVD, important information was lost due to omission of non-HDL-C and smoking, and from considering MetS traits as yes/no variables. CVD risk prediction by MetS was less strong for men and no stronger for women than by classical risk factors (blood pressure, diabetes, serum cholesterol, smoking, overweight/obesity). Conclusions These findings are concordant with the inference that epidemic obesity importantly influences epidemic occurrence of the other MetS traits; they also indicate that use of MetS for CVD risk assessment has limitations and needs critical reconsideration.

Intracranial lipomas are very rare congenital malformative lesions, being less than 0.1% of intracranial tumors. They originate from abnormal differentiation of mesenchimal tissue of meninx primitiva. Most of cases are asymptomatic pericallosal lesions, often associated with other defects of differentiation of the midline. Association with hypogenesis/agenesis of corpus callosum is frequent, being present in 90% of anterior lipomas and in 30% of posterior lipomas. We report a case of asymptomatic lipoma of corpus callosum associated with hypogenesis of corpus callosum, accidentally found, during diagnostic imaging of a female patient with early headache and no neurologic symptoms. Corpus callosum pure lesions are asymptomatic, that is they don’t affect commisural functions, so there’s no indication to surgical treatment. Other midline defects, that can be associated with pericallosal lipomas, are most frequently symptomatics. In lipomas of corpus callosum prognosis and symptoms depends on associated malformations.