Cancer and Pregnancy: Estimates in Italy from Record-Linkage Procedures between Cancer Registries and the Hospital Discharge Database.

The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15-49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC.

Pediatric Version of the Nurse Caring Behavior Scale: A Cross-Sectional Study in Pediatric Hemato-Oncology Centers.

Background and Purpose: Caring is an essential value in nursing, it's crucial in pediatric hemato-oncology: we tested the Nurse Caring Behavior Scale (NCBS) in this setting. Methods: The NCBS is a 14-item validated psychometric questionnaire: caregivers and nurses adapted versions were used. Descriptive statistics and exploratory factor analysis (EFA) were used. Results: The questionnaires were completed by 188 caregivers and 193 nurses. The two data sets were suitable for EFA and fitted with one-solution factor analysis; factor loading showed values >0.40 (>0.60 for caregivers). The mean scores were: 4.5 (range: 1-5) for caregivers and 4.7 (range: 1-5) for nurses. Conclusion: The two validated versions can be used on a wider nurses and caregivers sample and provide an instrument for the development of nursing protocols based on caring.

Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

BACKGROUND: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. METHODS: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. RESULTS: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. CONCLUSIONS: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

Impact of Rhabdomyosarcoma Treatment Modalities by Age in a Population-Based Setting.

Purpose: Rhabdomyosarcoma (RMS) has a worse prognosis in adults than in children, but there is evidence of a better outcome in the former if treated using a pediatric-like approach. This study describes treatment for RMS in patients more than 10 years old and examines to what extent treatment contributes to explain the different age-related survival observed and to what extent treatment centers impact treatment appropriateness. Methods: A retrospective population-based study was developed considering 104 RMS cases (excluding the pleomorphic subtype) diagnosed in Italy between 2000 and 2015. Patients were grouped by age (10-19 vs. 20-60 years old) and scored according to whether or not their chemotherapy was consistent with the schemes used in pediatric protocols (score 1 = chemotherapy in line with pediatric protocols). Treatment centers were grouped according to whether or not they have a pediatric-dedicated unit affiliated to the national pediatric oncology network (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]). Results: Older patients were more likely to have tumors at unfavorable sites (p = 0.045). A treatment score of 1 was assigned to 85% of younger patients, but only to 32% of older patients (p < 0.001). Furthermore, the proportion of score 1 was higher in younger patients treated in centers with an AIEOP Unit. A multivariate model confirmed age as a significant prognostic factor (Hazard rate ratio [HR] = 2.06; p = 0.04) and showed a significant impact of treatment on survival (HR = 2.13; p = 0.03). Conclusions: Adult RMS patients are still relatively unlikely to be treated with pediatric protocols and in centers with a pediatric oncology expertise. This may explain the survival gap between older and younger patients.

Adolescent and Young Adult Cancer Survivors: Design and Characteristics of the First Nationwide Population-Based Cohort in Italy.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

Cancer Risk and Multiple Sclerosis: Evidence From a Large Italian Cohort.

Introduction: The complexity of understanding cancer risk in MS is increased by inconsistencies in study design, and the lack of age-, sex-, and ethnicity-specific risk estimates. Aims of our study were to estimate the incidence of cancers in the MS population of Catania (Italy) and to evaluate the impact of disease-modifying treatments (DMTs) in cancer risk. Materials and Methods: We screened 2,730 PwMS according to the MS criteria of Mc Donald 2010 referring to MS center of Catania in the period between 2003 and 2013. We matched database of MS patients with the Integrated Cancer of Catania-Messina-Siracusae-Enna. We calculated age and sex specific standardized incidence ratios (SIR) and the relative risk (RR) of developing cancer in MS patients treated with at least two different DMTs compared to who received one or no treatment. Results: Out of 2,730, 1,180 MS patients (67.1% females; mean age 41.2 ± 12.9) were enrolled. We found 36 cancers. Global SIR was 1.18 (CI95% 0.78-1.58), with a significantly higher risk in men with a range age of 20 to 50 years [2.84; (CI95% 1.59-4.09)] and in women over 50 years [1.82 (CI95% 1.08-2.55)]. RR of developing cancer was 1.99 (CI95% 1.14-3.45) in MS patients switching one DMT and 3.38 (CI95% 1.83-6.22) in who switched at least twice. Discussion: Our results demonstrated that cancer risk was not increased in our MS population; but age and sex different distribution may partly drive cancer risk. Higher cancer risk in MS patients switching more than two DMTs should take into account in treatment decision making.

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020.

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n = 305,044), while 42% of prevalent women had breast cancer (n = 604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since ≥15 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+ 37% vs 2010). The largest 10-year increases are foreseen for prostate (+ 85%) and for thyroid cancers (+ 79%), and for long-term survivors diagnosed since 20 or more years (+ 45%). Among the population aged ≥75 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation needs.

Histology-based Combination Induction Chemotherapy for Elderly Patients with Clinical Stage III Non-small Cell Lung Cancer.

AIM: To explore the feasibility and activity of a histology-based induction combination chemotherapy for elderly patients with clinical stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged ≥70 years with stage IIIA and IIIB lung squamous cell carcinoma (SCC) or adenocarcinoma were treated with three cycles of carboplatin and gemcitabine or pemetrexed, respectively, followed by definitive radiotherapy or surgery. The primary endpoint was the overall response rate (ORR) following induction. RESULTS: Twenty-seven patients, with a median age of 74 years (range=70-80 years) were treated for adenocarcinoma in 14 (52%) and SCC in 13 (48%), clinical stage IIIA in eight (30%) and IIIB in 19 (70%). Grade 3 or 4 toxicity was reported for five patients (18.5%). The ORR was 46% in 12 (partial responses) out of 26 assessable patients. CONCLUSION: Histology-based induction combination chemotherapy is active and feasible in elderly patients with stage III NSCLC.

Predictive and Prognostic Value of Early Disease Progression by PET Evaluation in Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: To assess the predictive and prognostic value of progressive metabolic disease (PMD) by the use of early 18Fluorodeoxyglucose positron emission tomography (18FDG-PET) in patients with clinical stage IV non-small cell lung cancer (NSCLC) treated with first-line chemotherapy. METHODS: An 18FDG-PET performed following the first cycle of chemotherapy (PET-1) was compared with a pretreatment 18FDG-PET (PET-0) and a computed tomography (CT) scan after the third cycle (CT-3). The primary endpoint was the positive predictive value (PPV) of PMD. Secondary endpoints included the prognostic value of PMD. RESULTS: Eleven of 38 patients (29%) had a PMD by PET-1, and 15 (39%), including all patients with a PMD, experienced a progressive disease by CT-3. The PPV of PMD was 100% according to both the European Organization for Research and Treatment of Cancer (EORTC) criteria and the PET Response Criteria In Solid Tumors (PERCIST) (p value for both, <0.0001). Patients with a PMD by PET-1 had a median overall survival of 7.0 months versus 14.0 months for those without a PMD (p = 0.04, according to the EORTC criteria). CONCLUSIONS: Early 18FDG-PET assessment deserves further investigation for the identification of NSCLC patients who do not benefit from first-line chemotherapy.

Usefulness of SYNTAX score II in complex percutaneous coronary interventions in the setting of acute coronary syndrome.

BACKGROUND: SYNTAX score II (SS II) integrates anatomical SS with clinical characteristics allowing an individualized prediction of long-term mortality. AIMS: We sought to assess to evaluate the usefulness of SS II in a real-world acute coronary syndromes (ACS) population with severe coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: From August 2011 to May 2013, out of 1591 consecutive patients admitted for ACS, 217 (13.6%) showed severe CAD (three-vessel disease and/or left main involvement). Among the latter, 100 patients underwent PCI and were enrolled into the study. SS II was calculated in all patients. One-year clinical follow-up was performed; major adverse cardiac and cerebrovascular events (MACCE) were defined as a composite of death, nonfatal myocardial infarction, stroke, or repeat revascularization. RESULTS: The median SS II was 29 (range, 14-59). Overall, MACCE occurred in 25% of patients (cardiac death 4%, myocardial infarction 4%, stroke 0%, and repeat revascularization 17%). The 1-year MACCE-free survival was significantly lower in patients with SS (⩾29), than in those with SS II (<29) (64.2% vs. 87.2%, respectively; p = 0.007). In multivariate Cox regression analysis, the presence of unprotected left main stenosis [hazard ratio 2.52, 95% confidence interval (CI): 1.02-5.85; p = 0.031] and SS II ⩾29 (hazard ratio 2.74, 95% CI: 1.30-8.21; p = 0.011) were the only predictors of MACCE at 1-year clinical follow-up. The c-index of SS score II was 0.70 (95% CI: 0.58-0.81). For patients who experienced MACCE, the SS II reclassification improved by 36%, while in nonevent patients the reclassification improved by 22%. The net reclassification index was 0.24 (p = 0.09). CONCLUSION: SS II might represent a useful tool to predict clinical events in not only ideal stable patients, but also an unrestricted, real world population of patients with ACS and severe CAD undergoing PCI.

Percutaneous Coronary Revascularization for Chronic Total Occlusions: A Novel Predictive Score of Technical Failure Using Advanced Technologies.

OBJECTIVES: The aims of this study were to describe the 10-year experience of a single operator dedicated to chronic total occlusion (CTO) and to establish a model for predicting technical failure. BACKGROUND: During the last decade, the interest in percutaneous coronary interventions (PCIs) of chronic total occlusions (CTOs) has increased, allowing the improvement of success rate. METHODS: One thousand nineteen patients with CTO underwent 1,073 CTO procedures performed by a single CTO-dedicated operator. The study population was subdivided into 2 groups by time period: period 1 (January 2005 to December 2009, n = 378) and period 2 (January 2010 to December 2014, n = 641). Observations were randomly assigned to a derivation set and a validation set (in a 2:1 ratio). A prediction score was established by assigning points for each independent predictor of technical failure in the derivation set according to the beta coefficient and summing all points accrued. RESULTS: Lesions attempted in period 2 were more complex in comparison with those in period 1. Compared with period 1, both technical and clinical success rates significantly improved (from 87.8% to 94.4% [p = 0.001] and from 77.6% to 89.9% [p < 0.001], respectively). A prediction score for technical failure including age ≥75 years (1 point), ostial location (1 point), and collateral filling Rentrop grade <2 (2 points) was established, stratifying procedures into 4 difficulty groups: easy (0), intermediate (1), difficult (2), and very difficult (3 or 4), with decreasing technical success rates. In derivation and validation sets, areas under the curve were comparable (0.728 and 0.772, respectively). CONCLUSIONS: With growing expertise, the success rate has increased despite increasing complexity of attempted lesions. The established model predicted the probability of technical failure and thus might be applied to grading the difficulty of CTO procedures.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

Mutation-Independent Activation of the Anaplastic Lymphoma Kinase in Neuroblastoma.

Activating mutations of anaplastic lymphoma kinase (ALK) have been identified as important players in neuroblastoma development. Our goal was to evaluate the significance of overall ALK activation in neuroblastoma. Expression of phosphorylated ALK, ALK, and its putative ligands, pleiotrophin and midkine, was screened in 289 neuroblastomas and 56 paired normal tissues. ALK was expressed in 99% of tumors and phosphorylated in 48% of cases. Pleiotrophin and midkine were expressed in 58% and 79% of tumors, respectively. ALK activation was significantly higher in tumors than in paired normal tissues, together with ALK and midkine expression. ALK activation was largely independent of mutations and correlated with midkine expression in tumors. ALK activation in tumors was associated with favorable features, including a younger age at diagnosis, hyperdiploidy, and detection by mass screening. Antitumor activity of the ALK inhibitor TAE684 was evaluated in wild-type or mutated ALK neuroblastoma cell lines and xenografts. TAE684 was cytotoxic in vitro in all cell lines, especially those harboring an ALK mutation. TAE684 efficiently inhibited ALK phosphorylation in vivo in both F1174I and R1275Q xenografts but demonstrated antitumor activity only against the R1275Q xenograft. In conclusion, ALK activation occurs frequently during neuroblastoma oncogenesis, mainly through mutation-independent mechanisms. However, ALK activation is not associated with a poor outcome and is not always a driver of cell proliferation and/or survival in neuroblastoma.

[Evaluation of the cancer co-pay fee exemption data source (048 code) to estimate cancer incidence]. / Valutazione del flusso delle esenzioni ticket per neoplasia (codice 048) per stimare l'incidenza dei tumori.

OBJECTIVES: to assess whether the data source of cancer exemption ticket (code 048) correctly estimate the cancer incidence produced by Cancer registries (CR). DESIGN: comparison between incidence estimates produced by cancer exemptions ticket and cases registered by CR. SETTING AND PARTICIPANTS: six CRs provided incidence data for one year in the five-year period from 2007 to 2011 and for the previous five years, the exemptions provided for the same year and for the previous five years. MAIN OUTCOME MEASURES: incidence distribution by gender, age and tumour site, exemptions 048/incident cancers ratio, and trend estimates. RESULTS: out of 14,586 patients with 048 exemption, a first group was present in the CR database in the same reference year (No. 8,015) and a second group in the previous 6 months (No. 1,696). Of the remaining 4,875, only 2,771 were prevalent cases and 2,104 were manually re-valued: 514 non-cancer; 710 non-malignant/noninfiltrating tumours, 250 non-residents, 532 unknown, and 98 lost at CR. The exemption/ tumours ratio was 32%in males and 37% in females. Out of 27,632 cancer patients in CR, only 29% had a 048 exemption. Among linked cases, there is a case-mix problem: the exemptions overestimated the weight of some cancer sites (breast, prostate), but underestimate the weight of other sites (stomach, liver, lung) and the burden of tumours in the elderly.The trend estimated from the exemptions underestimates the true incidence of tumours and presents fluctuations, because of local administrative and organisational issues. CONCLUSIONS: the 048 codes are an accessory source for CRs, but when used as single flow they are not able to estimate the true incidence of tumours and, therefore, do not provide useful information on cancer trends.

Screening for colorectal cancer in Italy: 2011-2012 survey.

We utilised the IMPATTO study's archives to describe the 2000-2008 colorectal cancer (CRC) incidence rate trends in Italy, once screening programmes based on the faecal immunochemical test were implemented in different areas. Data on CRCs diagnosed in Italy from 2000 to 2008 in subjects aged 40-79 years were collected by 23 cancer registries. Incidence rate trends were evaluated as a whole and by macro-area (North-Centre and South-Islands), presence of a screening programme, sex, ten-year age class, anatomic site, stage at diagnosis, and pattern of diagnosis (screen-detected, non-screen-detected). The annual percent change (APC) of incidence rate trends, with 95% confidence intervals (95%CI), were computed. The study included 46,857 CRCs diagnosed in subjects aged 40-79 years, of which 2,806 were screen-detected. The incidence rates in the North-Centre were higher than in the South and on the Islands. During the study period, screening programmes had been implemented only in the North-Centre and had a significant effect on incidence rates, with an initial sharp increase in incidence, followed by a decrease that started in the 3rd-4th years of screening. These incidence rate trends were exclusively due to modifications in the rates of stage I cases. After screening programmes started, incidence increased in all anatomic sites, particularly in the distal colon. The differential figures introduced by the implementation of screening programmes warrant a continuous surveillance of CRC incidence and mortality trends to monitor the impact of screening at a national level.

Retrograde Recanalization of Chronic Total Occlusions in Europe: Procedural, In-Hospital, and Long-Term Outcomes From the Multicenter ERCTO Registry.

BACKGROUND: A retrograde approach improves the success rate of percutaneous coronary interventions (PCIs) for chronic total occlusions (CTOs). OBJECTIVES: The authors describe the European experience with and outcomes of retrograde PCI revascularization for coronary CTOs. METHODS: Follow-up data were collected from 1,395 patients with 1,582 CTO lesions enrolled between January 2008 and December 2012 for retrograde CTO PCI at 44 European centers. Major adverse cardiac and cerebrovascular events were defined as the composite of cardiac death, myocardial infarction, stroke, and further revascularization. RESULTS: The mean patient age was 62.0 ± 10.4 years; 88.5% were men. Procedural and clinical success rates were 75.3% and 71.2%, respectively. The mean clinical follow-up duration was 24.7 ± 15.0 months. Compared with patients with failed retrograde PCI, successfully revascularized patients showed lower rates of cardiac death (0.6% vs. 4.3%, respectively; p < 0.001), myocardial infarction (2.3% vs. 5.4%, respectively; p = 0.001), further revascularization (8.6% vs. 23.6%, respectively; p < 0.001), and major adverse cardiac and cerebrovascular events (8.7% vs. 23.9%, respectively; p < 0.001). Female sex (hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.33 to 3.18; p = 0.001), prior PCI (HR: 1.73; 95% CI: 1.16 to 2.60; p = 0.011), low left ventricular ejection fraction (HR: 2.43; 95% CI: 1.22 to 4.83; p = 0.011), J-CTO (Multicenter CTO Registry in Japan) score ≥3 (HR: 2.08; 95% CI: 1.32 to 3.27; p = 0.002), and procedural failure (HR: 2.48; 95% CI: 1.72 to 3.57; p < 0.001) were independent predictors of major adverse cardiac and cerebrovascular events at long-term follow-up. CONCLUSIONS: The number of retrograde procedures in Europe has increased, with high percents of success, low rates of major complications, and good long-term outcomes.

[Potential exposure to carcinogens in low-melting alloys processing]. / Potenziale esposizione a cancerogeni nella lavorazione di leghe bassofondenti.

The objective in our study was to evaluate the worker's exposition to lead and cadmium in 32 radiology technicians in an eastern Sicily hospital in workers of low melting point alloy of lead, tin, cadmium and bismuth (league that can be melted at 73 degrees C as CERROBEND). Such alloy is used for the fabrication of objects used for the personal protection of cancer patients subject to high energy treatment. The parameters taken into consideration for this study were sex, age and smoking habits. In the test subject's working cycle reported in our case, there were traces of smoke formation containing lead, tin, bismuth and cadmium. Cadmium is a substance considered by IARC to be cancerous and can be found in both work and living environments, therefore it is often difficult to establish rather its presence in the organism is due to working activities and/or the living environment. In these cases it is necessary to evaluate whether the work represents an added risk to develop neoplasia, compared to the consequences due to normal environmental exposure. The added risk linked to work is evaluated comparing the concentration of toxic substances found in the living environments (Environmental Reference Value) with the toxic and/or metabolite found in the working environment, and comparing the biological reports of the population not directly exposed by work (Biological Reference Value) and those exposed. We performed a biological monitoring for lead and cadmium on the workers examined. The Italian Legislature, aside from lead, has not yet issued guidelines pertaining to professional exposure to cadmium, and therefore it is mandatory to take reference to the American Hygienist's charts both for environmental exposure (TLVs) andfor biological monitoring (BEI). Biological monitoring, which allows to evaluate the absorption by both inhalation and gastrointestinally, was performed through measuring the levels of lend and cadmium in the bloodstream (PbB and CdB) and the Cd in urine (CdU). The results show that in no case the levels of lead in the bloodstream (PbB) were above the reference value and BEI. The levels of cadmium urine (CdU) weren't above the reference level and the BEI, while the haematic levels of cadmium (CdB) were higher than the reference value in 8 subjects, each long time smokers, each of about 20 cigarettes a day. This data shows how, in the evaluation of exposition to cadmium, aside from the exam of data pertaining to work, the study of ways of absorption and the interpretation of the results of environmental and biological monitoring, it is important to consider the possibility of intoxication outside of the workplace. Cigarette smoke, as already indicated by other authors, is also confirmed in our studies as one of the major fonts of non professionally linked inhalation of cadmium.

Screening patterns within organized programs and survival of Italian women with invasive cervical cancer.

OBJECTIVES: To evaluate screening patterns within organized cervical screening programs (OCSPs) and survival of women with invasive cervical cancer (ICC). METHODS: A population-based study was conducted in Italian areas covered by cancer registries and OCSPs. The study included all women aged 25-65 years diagnosed with ICC between 1995 and 2008, and their screening histories within OCSPs were retrieved. Hazard ratios (HR) of death and 95% confidence intervals (CI) were computed according to screening pattern, using Cox models adjusted for age, ICC stage, and major confounders. RESULTS: Among 3268 women with ICC, 20% were never-invited to OCSP, 36% were never-compliant with OCSP's invitation, 33% were compliant and had a screen-detected ICC within OCSP (i.e., after a positive cytology), and 11% were compliant but had a non-screen-detected ICC. Screen-detected ICCs were more frequently micro-invasive (42%) compared to non-screen-detected ones (14%). Compared to women with screen-detected ICC, the adjusted HRs of death were 1.9 (95% CI 1.5-2.4) for those never-invited, 2.0 (95% CI 1.6-2.5) for never-compliant, and 1.7 (95% CI 1.3-2.4) for compliant women having non-screen-detected ICC. CONCLUSION: Prolonged survival, beyond down-staging, of women with ICC detected within OCSPs in Italy, further calls for improvements of OCSPs' invitational coverage and participation.

Rare hepatic metastases of colorectal cancer in livers with symptomatic HBV and HCV hepatitis.

AIM: The liver is the most common site of metastases in colorectal cancer but metastases seem to be less common in patients with a chronically liver damage. The aim of our study was to assess the development of metachronous liver metastases in patients affected by HBV or HCV related liver diseases. MATERIAL OF STUDY: We retrospectively evaluated above all the development of liver metastases and the 5-year disease free in 457 patients radically treated for colorectal cancer with healthy liver and in 31 patients radically treated for colorectal cancer affected by liver damage (HBV or HCV related). RESULTS: Overall incidence of liver metastases was 9% (44/488), in particular 3.2% in infected patients and 9.4% in non-infected patients (p= 0.34). Our results revealed that there is no statistically significant difference between the number of positive lymph nodes of primary colorectal cancer and the number of indifferentiated cancers in infected compared with non-infected patients (29% vs 34.1% and 9.7% vs 13.6% respectively), and the 5-year disease free is better for infected patients (93% and 80%, p = 0.17). DISCUSSION: In infected patients we registered a better crude 5-year disease free interval and a fewer incidence of metachronous liver metastases. This difference is in agreement with other results mentioned in literature. CONCLUSION: In the light of the reported data, the authors consider that the recent pathogenetic theory of the "metalloproteinase inhibitor" should be taken in account.