Clinical Outcomes of Thermal Ablation Re-Treatment of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.

Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000-2021).

Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014-2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000-2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies.

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.

Children exposure to inorganic and organic arsenic metabolites: A cohort study in Northeast Italy.

The aim of this study was to provide urinary levels of total arsenic (TAs) and As species as arsenobetaine (AsB), arsenocholine (AsC), inorganic As (i.e., [As(III)+As(V)]), methylarsonic acid (MMA) and dimethylarsinic acid (DMA) in 7 year-old-children (n = 200) enrolled in the Northern Adriatic Cohort II (NACII), a prospective cohort in a coastal area of Northeast Italy. TAs was determined by sector field-inductively coupled plasma mass spectrometry (SF-ICP-MS) and AsB, AsC, As(III), As(V), MMA and DMA by ion chromatography coupled to ICP-MS (IC-ICP-MS). The geometric mean (GM) for TAs was 12.9 µg/L and for [iAs + MMA + DMA] was 4.26 µg/L. The species AsB (GM of 5.09 µg/L) and DMA (GM of 3.20 µg/L) had the greatest percentage contribution to TAs levels; a greater percentage contribution from AsB is seen at TAs >10 µg/L and from DMA at TAs <10 µg/L. Urinary [iAs + MMA] levels were positively associated with [iAs + MMA + DMA] and DMA with AsB levels. Fish, shellfish and crustaceans consumption increased the AsB and TAs levels, while rice intake, mothers' education level and selenium (Se) concentration influenced the DMA concentration. Children have a high capacity to metabolize and detoxify the iAs because of the higher secondary methylation index (ratio DMA/MMA) with respect to primary methylation index (ratio MMA/iAs). In addition, the median level of [iAs + MMA + DMA] in the whole population of children was lower than the Biomonitoring Equivalent (BE) value for non-cancer endpoints. Also the Margin of Safety (MOS) value based on the population median was greater than 1, thus the exposure to the toxicologically relevant As species was not likely to be of concern.

Urinary metabolites of organophosphate and pyrethroid pesticides in children from an Italian cohort (PHIME, Trieste).

Urinary metabolites of organophosphate (OP) and pyrethroid (PYR) pesticides from seven years old children of a birth cohort study (n=199; PHIME cohort of Trieste, Italy) have been measured. Six OP and two PYR metabolites have been investigated, 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY, pirimiphos metabolite) was the one found at higher concentrations, median 3.4 ng/mL specific gravity adjusted (SG adjusted), followed by 4-nitrophenol (PNP, median 1.4 ng/mL SG adjusted) and 3,5,6-trichloro-2-pyridinol (TCPY, median 0.36 ng/mL SG adjusted), parathion and chlorpyriphos metabolites, respectively. TCPY concentrations were low in comparison to other distributions of OP metabolites in children from other studies. Accordingly, the PHIME cohort showed a distinct OP metabolite distribution with high concentrations of pirimiphos and parathion. Another specific characteristic of this cohort was the high concentration of 3-phenoxybenzoic acid (3-BPA, median 0.36 ng/mL SG adjusted), a general metabolite of PYR pesticides. Evaluation of anthropometric and socio-demographic characteristics of children and families only showed a positive association between family educational level and urinary concentrations of DEAMPY metabolite (p<0.05), which could reflect distinct dietary habits depending on the educational level. Estimated daily intakes were evaluated, all studied metabolites were found within safe levels.

Mid-term outcome after arthroscopic treatment of femoroacetabular impingement: development of a predictive score.

PURPOSE: To build a post-arthroscopy outcome-predictive score (POPS) associated with the likelihood of lasting benefit after arthroscopic treatment of femoroacetabular impingement (FAI) and based solely on unambiguous preoperative information. METHODS: A population of 220 FAI patients, operated on with standard techniques by orthopaedic surgeons trained in hip arthroscopy in 6 different centres, was evaluated physically or by telephone interview 2 to 5 years after surgery. The criteria of successful mid-term outcome (SMO) were agreed upon by all authors. A multivariate logistic regression, adjusted for patient's age and centre, was applied to predict SMO. In the model, the variables associated with the outcome were included and the relative ORs (odds ratios) were used to compute the FAI-POPS (FAI - post-arthroscopy outcome-predictive score). A ROC (receiver operating characteristic) curve was plotted and the optimum cut-off was calculated. RESULTS: 155 patients out of 220 showed a successful mid-term outcome. The optimum cut-off of FAI-POPS was calculated to be 6.3 and with this threshold it proved a sensitivity of 0.66 and a specificity of 0.69, a positive predictive value of 0.84 and a negative predictive value of 0.46. CONCLUSIONS: The standard arthroscopic treatment of FAI resulted in satisfactory persistent symptom relief for about 70% of patients. No or minimal osteoarthritis, short time elapsed from the appearance of symptoms and high preoperative modified Harris Hip Score are independent predictive factors of SMO. The FAI-POPS is obtained as sum of 3 odds ratios corresponding to the above prognostic factors and is a useful predictor of mid-term outcome after conventional arthroscopic FAI treatment.

Impact of low-dose computed tomography screening on lung cancer mortality among asbestos-exposed workers.

Background: We previously showed that low-dose computed tomography (LDCT) screening in asbestos-exposed workers is effective in detecting lung cancer (LC) at an early stage. Here, we evaluate whether LDCT screening could reduce mortality from LC in such a high-risk population. Methods: Within a cohort of 2433 asbestos-exposed men enrolled in an Occupational Health surveillance programme, we compared mortality between the participants in the ATOM002 study (LDCT-P, N = 926) and contemporary non-participants (LDCT-NP, N = 1507). We estimated standardized mortality ratios for the LDCT-P and LDCT-NP populations using regional and national rates (SMR_FVG and SMR_ITA, respectively). We compared survival for all causes, all neoplasms, LC and malignant neoplasm of pleura (MNP) between LDCT-P and LDCT-NP using Cox proportional hazard models adjusted for age, smoking history, asbestos exposure level and comorbidities. Results: A reduction in mortality from LC was observed in the LDCT-P group compared with regional and national figures (SMR_FVG = 0.55, 95% confidence interval (CI) 0.24-1.09; SMR_ITA = 0.51, 95% CI 0.22-1.01); this was not the case for the LDCT-NP group (SMR_FVG = 2.07, 95% CI 1.53-2.73; SMR_ITA = 1.98, 95% CI 1.47-2.61). A strong reduction in LC mortality was observed for the LDCT-P compared with the LDCT-NP [hazard ratio (HR) = 0.41, 95% CI 0.17-0.96]. Mortality was also reduced for all causes (HR = 0.61, 95% CI 0.44-0.84), but not for all neoplasms (HR = 0.97, 95% CI 0.62-1.50) and MNP (HR = 0.86, 95% CI 0.31-2.41) within the LDCT-P population. Conclusions: In our cohort, participation in the LDCT screening study was associated with reduced mortality from LC. This finding supports the use of LDCT in surveillance programmes for asbestos-exposed workers.

Cancer incidence in a cohort of asbestos-exposed workers undergoing health surveillance.

OBJECTIVES: To compare a local cohort of 2488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995-2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study. METHODS: Standardized incidence ratios (SIRs), with 95% confidence interval (95% CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974 and 1994. For internal comparisons, we calculated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up. RESULTS: Among cohort members the SIR was 8.82 (95% CI 5.95-12.61) for mesothelioma and 1.61 (95% CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974 and 1984 was 2.09 (95% CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR = 1.53 95% CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost threefold for lung cancer (IRR = 2.94 95% CI 1.01-8.57). CONCLUSIONS: This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974 and 1984.

Mortality in a cohort of asbestos-exposed workers undergoing health surveillance.

BACKGROUND: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health surveillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality. OBJECTIVES: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy. METHODS: Standardized Mortality Ratios (SMR), with 95% Confidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994). RESULTS: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60). CONCLUSIONS: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure.

[Not Available]. / Standardization of incidence rates of mesothelioma in the absence of national standards: sensitivity analysis in a cohort formerly exposed to asbestos.

INTRODUCTION: The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006. OBJECTIVES: To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort. METHODS: We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate. RESULTS: During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively. CONCLUSIONS: Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available.

Low-dose computed tomography screening for lung cancer and pleural mesothelioma in an asbestos-exposed population: baseline results of a prospective, nonrandomized feasibility trial--an Alpe-adria Thoracic Oncology Multidisciplinary Group Study (ATOM 002).

OBJECTIVE: To evaluate the feasibility of using low-dose computed tomography (LDCT) for the early diagnosis of lung cancer and malignant pleural mesothelioma in an asbestos-exposed population. METHODS: Between February 2002 and October 2003, 1,045 volunteers already enrolled in a surveillance program for asbestos-exposed workers and former workers were recruited. The main eligibility criteria were: written informed consent, definite exposure to asbestos, age 40-75, no prior cancer or severe concomitant conditions, no chest CT scan in the past 2 years. A smoking history was not required. After a structured interview, chest X-ray (CXR) and LDCT were performed. Participants with negative examinations were assigned to annual LDCT. Participants with positive findings received high-resolution CT and additional diagnostic workup as appropriate. RESULTS: Baseline characteristics of the screened population were: median asbestos exposure time, 30 years; median age, 58; median pack-years in smokers/former smokers, 18.5. Thirty-four percent had never smoked. On LDCT, 834 noncalcified nodules were identified in 44% of participants, versus 43 nodules in 4% on CXR. Pleural abnormalities were observed in 44% and 70% of participants by CXR and LDCT, respectively. Overall, LDCT identified nine cases of non-small cell lung cancer-eight stage I, one stage IIA-and one thymic carcinoid, corresponding to 1% of the enrolled population. All cases were radically treated. None had been detected by CXR. No pleural mesothelioma was diagnosed. There were 11 false-positive results. CONCLUSIONS: Our findings first suggest that LDCT may be at least as useful in asbestos workers as in heavy smokers for the early diagnosis of lung cancer; this benefit is evident even in a poor-risk population, with low rates of smoking prevalence and a previous history of radiological surveillance. The role of spiral tomography in screening for pleural mesothelioma remains uncertain.