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Objectives Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM). Materials and methods A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area. Results Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 ( p < 0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone. Conclusions Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases. [ABSTRACT FROM AUTHOR]

With the regional law n. 26 of December 30, 2020, the Friuli Venezia Giulia Region wanted to promote the establishment of the Regional Register of Sudden Cardiac Death, with the aim of favoring the study of all those deaths that occurred suddenly and unexpectedly under the age of 50 years in which it is not possible to trace the cause of death with certainty. Such dramatic events, difficult to quantify considering the complexity of data collection, are often accepted with resignation without any further investigation of the possible causes. The Regional Register of Sudden Cardiac Deaths of Friuli Venezia Giulia was born from this premise and from the awareness of the importance of going back with a rigorous scientific methodology and through a multidisciplinary approach, to the diagnosis of hereditary heart diseases which, when determined, allow the enrollment of relatives in a cardiological screening process and, therefore, primary prevention of potentially fatal events. The authors describe the operating procedures feeding the Regional Register and present the results of the first year of activity on 26 cases.

Purpose: Monitoring mutation status in circulating free DNA (cfDNA) during target therapy could hold significant clinical importance in non-small cell lung cancer (NSCLC). Our aim is to establish if EGFR mutational status change on cfDNA has predictive value that can impact clinical management of NSCLC patients care., Methods: This study included 30 patients with EGFR-mutated NSCLC. Blood samples were collected at diagnosis (T0) and in 19 patients during therapy (T1)., Results: Concordance between T0 and T1 EGFR mutation status for patients evaluable for both samples (n = 19) was 79%, with a sensitivity of 100% (95% CI: 55.5-100.0) and specificity of 60.0% (95% CI: 26.2-86.8). For the patients in oncological therapy with targeted drug and with T1 sample available (n = 18), survival outcomes were evaluated. For both mutation-negative T0 and T1 patients, 12-month progression-free survival (PFS) was 66.7% (95% CI: 27.2-100.0) and 12-month overall survival (OS) was 100% (95% CI: 1.00-1.00); for patients mutated both at T0 and T1, PFS was 22.2% (95% CI: 6.5-75.4%) and OS was 55.6% (95% CI: 20.4-96.1%)., Conclusion: EGFR mutation status can be assessed using cfDNA for routine purposes and longitudinal assessment of plasma mutation is an easy approach to monitor the therapeutic response or resistance onset.

Purpose: Prediction algorithms estimating survival rates for breast cancer (BC) based upon risk factors and treatment could give a help to the clinicians during multidisciplinary meetings. The aim of this study was to evaluate accuracy and clinical utility of three different scores: the Clinical Treatment Score Post-5 Years (CTS5), the PREDICT Score, and the Nottingham Prognostic Index (NPI)., Methods: This is a retrospective cohort analysis conducted on prospectively recorded databases of two EUSOMA certified centers (Breast Unit of Trieste Academic Hospital and of Cremona Hospital, Italy). We included patients with Luminal BC undergone to breast surgery between 2010 and 2015, and subsequent endocrine therapy for 5 years for curative intent., Results: A total of 473 patients were enrolled in this study. ROC analysis showed fair accuracy for NPI, good accuracy for PREDICT, and optimal accuracy for CTS5 (AUC 0.7, 0.76, and 0.83, respectively). The three scores seemed strongly correlated in Spearman's rank correlation coefficient analysis. PREDICT partially overestimated OS in patients undergone to mastectomy, and in pT3-4, G3 tumors. Considering DRFS as a surrogate of OS, CTS5 showed women in intermediate and high risk class had shorter OS too (respectively p = 0.001 and p < 0.001). Combining scores does not improve prognostication power., Conclusion: Mathematical models may help clinicians in decision making (adjuvant therapies, CDK4/6i, genomic test's gray zones). CTS5 has the higher prognostic accuracy in predicting recurrence, while score predicting OS did not show substantial advances, proving that pN, G, and pT are still the most important variables in predicting OS.

Objectives: to evaluate the incidence of advanced-stage breast cancer (BC) - an early surrogate indicator of effectiveness of mammography screening - among women who attended the Friuli Venezia Giulia (FVG) Region (Northern Italy) screening programme compared to women who did not attend., Design: retrospective cohort study. Women invited to the first screening round (2006-2007) were identified from the database of the programme. The cohort was record-linked to the archive of women invited to the second round (2008-2009). The definition of attendance to screening was based on attendance to at least one of the two rounds. The incidence of BC was assessed through record linkage with the FVG cancer registry using an anonymous univocal identifier (end of follow-up: 31st December 2013). Three distinct definitions of advanced stage were used: pT2 or greater (pT2+), positive lymph nodes (pN+), and TNM stage II or greater (stage II+)., Setting and Participants: organized mammography screening programme for women aged 50-69 years in the five regional healthcare districts., Main Outcome Measures: incidence rate ratio (IRR) between attenders and non-attenders, adjusted for age and deprivation index, with 95% confidence interval (95%CI)., Results: the cohort included 104,488 attenders and 49,839 non-attenders. During follow-up (median duration 84 months), 2,717 invasive BCs were diagnosed among attenders and 1,149 among non-attenders. Total incidence rate was 13% higher among attenders (IRR 1.13; 95%CI 1.05-1.21). These, conversely, had a 36% lower rate of pT2+ BC (IRR 0.64; 95%CI 0.56-0.72), a 13% lower rate of pN+ BC (IRR 0.87; 95%CI 0.78-0.98), a 22% lower rate of stage II+ BC (IRR 0.78; 95%CI 0.70-0.87), and a 32% lower rate of mastectomy (IRR 0.68; 95%CI 0.60-0.78)., Conclusions: attenders had lower incidence rates of advanced-stage BC. This early effect is suggestive of a future impact of the screening programme on BC mortality.

Purpose: Radiofrequency ablation has been advocated as an alternative to radioiodine and/or surgery for the treatment of autonomously functioning benign thyroid nodules. However, only a few studies have measured radiofrequency ablation efficacy on autonomously functioning benign thyroid nodules. The aim of this work was to evaluate the 12-month efficacy of a single session of radiofrequency ablation (performed with the moving shot technique) on solitary autonomously functioning benign thyroid nodules., Methods: Thirty patients with a single, benign autonomously functioning benign thyroid nodules, who were either unwilling or ineligible to undergo surgery and radioiodine, were treated with radiofrequency ablation between April 2012 and May 2015. All the patients underwent a single radiofrequency ablation, performed with the 18-gauge needle and the moving shot technique. Clinical, laboratory, and ultrasound evaluations were scheduled at baseline, and after 1, 3, 6, and 12 months from the procedure., Results: A single radiofrequency ablation reduced thyroid nodule volume by 51, 63, 69, and 75 % after 1, 3, 6, and 12 months, respectively. This was associated with a significant improvement of local cervical discomfort and cosmetic score. As for thyroid function, 33 % of the patients went into remission after 3 months, 43 % after 6 months, and 50 % after 12 months from the procedure. This study demonstrates that a single radiofrequency ablation allowed us to withdraw anti-thyroid medication in 50 % of the patients, who remained euthyroid afterwards., Conclusion: This study shows that a single radiofrequency ablation was effective in 50 % of patients with autonomously functioning benign thyroid nodules. Patients responded gradually to the treatment. It is possible that longer follow-up studies might show greater response rates.

In the medical literature, the role of breastfeeding and reproductive factors in the risk of breast carcinoma is still an open debate in premenopausal women. We highlight the role of breastfeeding and reproductive factors in luminal A and luminal B, the most frequent breast cancers. This case-control study analyzes a White premenopausal population of 286 breast cancer patients, divided into molecular subtypes, and 578 controls matched by age. Multivariate logistic regression models were used to assess the relationships of breastfeeding and other reproductive factors (age at menarche, parity, age at first pregnancy, number of children) with the risk of breast cancers. Among the variables examined, reproductive factors did not alter the risk of cancer, whereas breastfeeding up to 12 months was a significant protective factor against luminal B breast cancer (multivariate odds ratio: 0.22, 95% confidence interval: 0.09-0.59, P=0.002). In contrast, luminal A cases did not significantly correlate with breastfeeding or other reproductive factors. Breastfeeding up to 12 months is strongly protective against the more aggressive luminal B, but not against the less aggressive luminal A breast cancer in premenopausal White women.

In our study we analyzed a file of 756 males with lung cancer and an equal number of controls matched by sex, age and year of death. All the subjects were resident in the Trieste area, died between 1979-81 and 1985-86 and underwent autopsy at the Istitute of Pathological Anatomy of the University of Trieste. The aim of the research was to analyze and quantify the risk to develop lung cancer in those exposed to asbestos, and well-recognized carcinogens (list A of I.A.R.C.) or suspected (list B). We have also analyzed the relative risk (R.R.) for lung cancer among those subjects with environmental exposure to air pollution in industrial and urban areas. The study was set up in the Trieste province, a geographic area which is particularly suitable for epidemiological studies. We have demonstrated on excess of risk for males exposed to asbestos (R.R. = 1.99) and to other well known carcinogens (R.R. = 2.28). The capability in differentiating the relative risk of smoking and professional exposure to oncogenetic substances allowed us to detect an excess of risk for people living in industrial and urban areas, when compared to those living in rural and peripheral areas.

A sample of 2,563 cases of liver cirrhosis diagnosed among 26,879 autopsies performed consecutively in the years 1976/85 was considered in order to study the morphologic feature of the liver cirrhosis and their relationship with primary liver cancer (PLC) outbreak. The study showed that age of patients affected by cirrhosis is a significant risk factor for PLC. In fact, in the 10 years considered, the observed mean annual increase of age at death of the cirrhotic patients was associated with an increase in PLC cases. This may be explained as a well known consequence of the conversion of micronodular type of cirrhosis to mixed and macronodular ones (for which cancer complication is more frequent) but also as a statistically significant higher risk of PLC in the older group of patients affected by micronodular cirrhosis. The older age of cirrhotic patients at death observed in the last few years in the Trieste area is probably correlated to a general European trend: our results, although relative to a restricted geographic area, seem to be of interest in order to identify better the patients at risk of PLC among those affected by cirrhosis.

A positive association between alcohol consumption and stroke incidence has been clearly established. The present study evaluated the frequency of stroke in a sample of 500 autopsied patients affected by liver cirrhosis mainly due to chronic alcohol abuse as confirmed by the histologic pattern mostly of mixed and micronodular types. Frequency of stroke was compared to that of 4,741 non-cirrhotic patients autopsied in the same period. Our findings demonstrate that stroke frequency, especially when due to thromboembolism, decreased significantly in cirrhotics. Therefore, hepatopathy is a crucial event in alcoholic patients. Nevertheless the concomitant presence of liver cirrhosis, in studies dealing with this subject, is not being currently evaluated.

This study, aimed at elucidating the epidemiological features of primary liver carcinoma developing in non-cirrhotic livers, was based on 25,103 autopsies performed between 1975 and 1984 in Trieste, Italy. These autopsies correspond to approximately 70% of all deaths that occurred in this area. Various factors allegedly related to carcinomas were analysed in reference to our previous study on cirrhotic livers and in comparison with 5,603 autopsies in Kurume, Japan. There were 28 cases of hepatocellular carcinoma (HCC), 16 of cholangiocellular carcinoma (CCC) not associated with cirrhosis in Trieste, and 48 HCC and 19 CCC in Kurume. On the basis of our findings, it was concluded that cirrhosis, regardless of its cause, is the main pathogenetic factor in HCC; it is responsible for a much higher frequency (14.2:1) than in non-cirrhotic livers, as well as for early occurrence of tumours (an average of 6 years earlier in cirrhotic liver) in Trieste. Patients in Trieste were older than those in Japan, and the frequency of HCC among all autopsies was much greater in the latter. By contrast, the influence of cirrhosis on cholangiocellular carcinoma (CCC) was negligible, as such association appeared purely coincidental or absent. The incidence of CCC among autopsies was greater in Japan. Our data on CCC were not sufficient to demonstrate any clear aetiopathogenetic association between this tumour and alcohol abuse and hepatitis B virus (HBV) infection, except for a possible aetiological role of gallstones. The frequency of CCC relative to HCC was greater in Trieste than in Japan; the incidence of HCC was much less in Trieste, whereas CCC was more frequent in Japan.

The authors report their data on epidemiology of liver cancer (LC) in Trieste. Because of the high autopsy rate in the Province (the ratio autopsies/deaths is about 70%), the findings allow to draw some conclusions which could be regarded as a paradigm, at least in Northern Italy: 1) At autopsy LC prevalence is about 1.8% and the value has been increasing over the last few years; 2) 95.4% of LC are hepatocellular (HCC) and 92.9% of the latter occur in cirrhotic livers. Patients with HCC and cirrhosis are 6 years younger than those affected by HCC alone. On the basis of the above reported conclusions, the role of liver cirrhosis as preneoplastic condition is discussed.