Correlation between outcome and extent of residual disease in the sentinel node after neoadjuvant chemotherapy in clinically fine-needle proven node-positive breast cancer patients.

BACKGROUND: Whether the extent of residual disease in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC) influences the prognosis in clinically node-positive breast cancer (BC) patients remains to be ascertained. METHODS: One hundred and thirty-four consecutive cN+/BC-patients received NAC followed by SLN biopsy and axillary lymph node dissection. Cumulative incidence of overall (OS) and disease-free (DFS) survival, BC-related recurrences and death from BC were assessed using the Kaplan-Meier method both in the whole patient population and according to the SLN status. The log rank test was used for comparisons between groups. RESULTS: The SLN was identified in 123/134 (91.8%) patients and was positive in 98/123 (79.7%) patients. Sixty-five of them (66.3%) had other axillary nodes involved. SLN sensitivity and false-negative rate were 88.0% and 2.0%, Median follow-up was 10.2 years. Ten-year cumulative incidence of axillary, breast and distant recurrences, and death from BC were 6.5%, 11.9%, 33.4% and 31.3%, respectively. Ten-year OS and DFS were 67.3% and 55.9%. When stratified by SLN status, 10-year cumulative incidence of BC-related and loco-regional events, and death from BC were similar between disease-free SLN and micrometastatic SLN subgroups (28.9% vs 30.2%, p = 0.954; 21.6% vs 13.4%, p = 0.840; 12.9 vs 24.5%, p=0.494). Likewise, 10-year OS and DFS were comparable (80.0% vs 75.5%, p=0.975 and 68.0% vs 69.8, p=0.836). Both OS and DFS were lower in patients presenting a macrometastatic SLN (60.2% and 47.5%). CONCLUSION: Outcome of patients with micrometastatic SLN was similar to that of patients with disease-free SLN, which was more favorable as compared to that of patients with macrometastatic SLN.

Mortality among workers exposed to asbestos at the shipyard of Genoa, Italy: a 55 years follow-up.

BACKGROUND: Exposure to asbestos remains a global issue due to its massive use in the twentieth century and its long environmental persistence. Exposure to asbestos still occurs during dismantling of ships and vessels, buildings renovation, mining operations, and is reported in developing countries. Current estimate report exposure of hundreds of million people in occupational settings in countries where its use remains unregulated. METHODS: We conducted a historical prospective cohort mortality study aimed at estimating mortality from specific causes, the temporal changes of pleural and lung cancer mortality, and the attributable fraction (AF) of lung cancer deaths following asbestos exposure. The study included 3984 shipyard workers employed at the shipyard of Genoa, Italy, between 1960 and 1981 and followed up to December 2014. Standardized Mortality Ratios (SMR) and their 95% confidence intervals (95%CI) were computed. RESULTS: Overall deaths recorded were 3331 (83.6%). Excess mortality was observed for all cancers (SMR = 127, 95%CI:120-134), pleural mesothelioma (575, 469-697), cancers of the larynx (183, 134-244) and of the lung (154, 139-170), and for respiratory tract diseases (127, 114-141), including asbestosis (2277, 1525-3270). Ninety out of 399 deaths (22.6%) from lung cancer were attributed to asbestos exposure. The estimated lung cancer AF was 49.3% in workers with the highest SMR for pleural cancer. Median latency times for pleural and lung cancer were 42.8 years (minimum latency: 9.3 years) and 38.7 years (minimum latency: 6 years). The peak of mesothelioma incidence, expected in Italy in the period 2015-2024, was confirmed. CONCLUSIONS: The long follow-up period of our study allowed the detection of a substantial disease burden following asbestos exposure. These findings support the urgent need for the prevention of asbestos related diseases through the implementation of asbestos ban worldwide, including those countries where asbestos is still mined, manufactured and used.

Prognostic Significance of VEGF after Twenty-Year Follow-up in a Randomized Trial of Fenretinide in Non-Muscle-Invasive Bladder Cancer.

Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive disease, but no effective preventive treatments are available. In addition, no reliable prognostic biomarkers have been identified. We assessed the long-term effect of the oral retinoid fenretinide and the prognostic value of circulating VEGF levels. We updated through the Tumor Registry the vital status of 99 patients with resected Ta/T1 bladder tumors who were recruited in a randomized trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels measured at baseline and 12 months were available in a subgroup of 62 patients. After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or bladder cancer survival (BCS) was affected by fenretinide (log-rank P ≥ 0.2). DNA aneuploidy in bladder washing was associated with shorter OS (P = 0.02), CS (P = 0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top quintile (≥350 pg/mL) had a significantly shorter OS (P = 0.01), CS (P = 0.02), and BCS (P = 0.008). The trend across quintiles of VEGF was significant for BCS (P = 0.007). Multivariate analyses showed that, in addition to smoking status, VEGF level in the top quintile was an independent prognostic factor for OS (HR = 2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR = 8.9; 95% CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with NMIBC. High serum VEGF level was a significant predictor of overall and cancer death and may help to identify high-risk subjects who may benefit from a preventive therapy. Cancer Prev Res; 9(6); 437-44. ©2016 AACR.

Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Early-Stage Breast Cancer: 15-Year Follow-Up Update of a Randomized Clinical Trial.

BACKGROUND: Sentinel lymph node biopsy (SLNB) allows for staging of the axillary node status in early-stage breast cancer (BC) patients and avoiding complete axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is proven to be free of disease. In a previous randomized trial we compared SLNB followed by ALND (ALND arm) with SLNB followed by ALND only if the SLN presented metastasis (SLNB arm). At a mid-term of ≈ 6 years median follow-up, the two strategies appeared to ensure similar survival and locoregional control. We have revised these previous findings and update the results following a 15-year observation period. METHODS: Patients were randomly assigned to either the ALND or SLNB arm. The main endpoints were event-free survival (EFS), overall survival (OS), and axillary disease recurrence. EFS and OS were assessed using Kaplan-Meier analysis and the log-rank test. RESULTS: The ALND and SLNB arms included 115 and 110 patients, respectively. At 14.3 years median follow-up, 39 primary BC-related recurrences occurred, 22 (19 %) of which occurred in the ALND arm and 17 (16 %) occurred in the SLNB arm (p = 0.519). No axillary relapse developed in the SLNB arm, while two were observed in the ALND arm. OS (82.0 vs. 78.8 %) and EFS (72.8 vs. 72.9 %) were not statistically different between the ALND and SLNB arms (p = 0.502 and 0.953, respectively). CONCLUSIONS: SLNB is a safe and efficacious component of the surgical treatment of early-stage BC patients. In the long-term, SLNB is equivalent to ALND in terms of locoregional nodal disease control and survival in this subset of patients.

Lifestyle factors and risk of leukemia and non-Hodgkin's lymphoma: a case-control study.

PURPOSE: Risk factors for leukemia and lymphomas in adults are largely unknown. This study was aimed at evaluating the association between lifestyle factors and the risk of hematological malignancies in an adult population. METHODS: Data were drawn from a population-based case-control study carried out in Italy and included 294 cases (199 lymphoid and 95 myeloid) and 279 controls. Analyses were performed using standard multivariable logistic regression. RESULTS: Hair dye use for at least 15 years was associated with a higher risk of lymphoid malignancies among females (OR 2.3, 95 % CI 1.0-4.9, p = 0.036, test for trend). Furthermore, a protective effect of a moderate to heavy tea consumption on the risk of myeloid malignancies was observed (OR 0.4, 95 % CI 0.2-0.9, p = 0.017). No association was found for the use of alcoholic beverages and tobacco smoking. CONCLUSIONS: Our results confirm the potential carcinogenic effect of prolonged hair dye use observed in previous investigations. The excess risk could be explained by exposure to a higher concentration of toxic compounds in hair products used in the past. The protective effect of regular tea consumption observed in an area with a very high prevalence of black tea consumers deserves further investigation.

[Air pollution and mortality in twenty-five Italian cities: results of the EpiAir2 Project]. / Inquinamento atmosferico e mortalità in venticinque città italiane: risultati del progetto EpiAir2.

OBJECTIVES: this study aims at presenting the results from the Italian EpiaAir2 Project on the short-term effects of air pollution on adult population (35+ years old) in 25 Italian cities. DESIGN: the short-term effects of air pollution on resident people died in their city were analysed adopting the time series approach. The association between increases in 10µg/m(3) in PM10, PM2.5, NO2 and O3 air concentration and natural, cardiac, cerebrovascular and respiratory mortality was studied. City-specific Poisson models were fitted to estimate the association of daily concentrations of pollutants with daily counts of deaths. The analysis took into account temporal and meteorological factors to control for potential confounding effect. Pooled estimates have been derived from random effects meta-analysis, evaluating the presence of heterogeneity in the city specific results. SETTING AND PARTICIPANTS: it was analysed 422,723 deaths in the 25 cities of the project among people aged 35 years or more, resident in each city during the period 2006-2010. MAIN OUTCOME MEASURES: daily counts of natural, cardiac, cerebrovascular, and respiratory mortality, obtained from the registries of each city. Demographic information were obtained by record linkage procedure with the civil registry of each city. RESULTS: mean number of deaths for natural causes ranged from 513 in Rovigo to 20,959 in Rome. About 25% of deaths are due to cardiac diseases, 10% to cerebrovascular diseases, and 7% to respiratory diseases. It was found an immediate effect of PM10 on natural mortality (0.51%; 95%CI 0.16-0.86; lag 0-1). More relevant and prolonged effects (lag 0-5) have been found for PM2.5 (0.78%; 95%CI 0.12-1.46) and NO2 (1.10%; 95%CI 0.63-1.58). Increases in cardiac mortality are associated with PM10 (0.93%; 95%CI 0.16-1.70) and PM2.5 (1.25%; 95%CI 0.17-2.34), while for respiratory mortality exposure to NO2 has an important role (1.67%; 95%CI 0.23-3.13; lag 2-5), as well as PM10 (1.41%; 95%CI - 0.23;+3.08). Results are strongly homogeneous among cities, except for respiratory mortality. No effect has been found for cerebrovascular mortality and weak evidence of association has been observed between ozone and mortality. CONCLUSIONS: a clear increase in mortality associated to air pollutants was observed. More important are the effects of NO2 (on natural mortality), mostly associated with traffic emissions, and of PM2.5 (on cardiac and respiratory mortality). Nitrogen dioxide shows an independent effect from the particulate matter, as observed in the bi-pollutant models.

[«Bridge Coding¼ ICD-9, ICD-10 and effects on mortality statistics]. / Il passaggio da ICD-9 a ICD-10 per le statistiche di mortalità.

OBJECTIVE: This study evaluates the impact of the introduction of ICD-10 on mortality statistics in Italy. DESIGN: «Bridge-Coding¼ analysis carried out by a working group that has coded a number of death certificates using both ICD-9 and ICD-10 versions. In 2006, a training project was launched in order to allow the group to standardize the coding procedures. SETTING: The study was carried out by professionals from the following regions: Emilia-Romagna, Veneto, Tuscany, Liguria; and from the towns of Biella and Milan. The analysis included 74,525 Death Certificates produced in the aforementioned areas. RESULTS: A limited variability was observed for the most important groups of diseases (diseases of the circulatory system and neoplasms), with low impact on mortality statistics. The variability was higher for "minor" diseases like infectious and respiratory diseases, and dementia. The variability was similar but not identical to that observed in other national and international studies. The «Bridge-Coding¼ analysis has a local impact. Furthermore, changes depending on the variation in the selection rules are impossible to predict or to correct with the trans-coding procedure. CONCLUSIONS: In some cases, the changes determined by the implementation of ICD-10 are not completely corrected by the transcoding procedure, even applying appropriate Comparability Ratios (CR) from «Bridge Coding¼ analysis like this. Studies on respiratory diseases, or dementia and some neoplasms require new coding procedures in only one ICD version. Quality and accuracy of the compilation of death certificates have more effect than a correct coding, though more casual and less evaluable by means of comparability studies like this one.

A historical mortality study among bus drivers and bus maintenance workers exposed to urban air pollutants in the city of Genoa, Italy.

OBJECTIVE: A historical mortality cohort study was conducted in Genoa, Italy among public transport workers ever employed between 1949 and 1980, to estimate overall and cause-specific mortality from January 1970 to December 2005 and to examine associations between exposure to urban air pollutants and overall and cause-specific mortality. METHODS: Causes of death for 9267 males (6510 bus drivers, 2073 maintenance workers and 601 white collar workers) were coded according to ICD-9. Standardised mortality ratios (SMRs) and 95% CIs were computed by applying Italian and regional male death rates to person-years of observation for the entire cohort and following stratification by longest held job title and length of and time since first employment using the Poisson regression model. RESULTS: There were 2916 deaths and 230,009 person-years of observation; 17 subjects were lost to follow-up. SMRs for all causes, diseases of the circulatory, respiratory, digestive and genitourinary systems, and for accidents were lower than expected. SMRs (95% CI) were increased for lung cancer (1.16, 1.05 to 1.28), non-Hodgkin's lymphoma (1.23, 0.85 to 1.78), Hodgkin's lymphoma (2.14, 1.19 to 3.87) and diabetes mellitus (1.16, 1.05 to 1.28). The SMR for leukaemia was 0.77 (0.51 to 1.16). Hodgkin's lymphoma mortality was significantly increased among bus drivers (1.62, 1.37 to 5.04). Lung cancer risk was significantly increased among all workers after 30 years' employment and among maintenance workers. CONCLUSIONS: The study failed to show any increased risk for leukaemias. The increased mortality from Hodgkin's lymphoma and lung cancer may be associated with long-term exposure to urban air pollution.

[Health conditions of the general population living near a steel plant]. / Stato di salute dei residenti nei pressi di un'acciaieria.

OBJECTIVE: To evaluate the health conditions (period 1986-2003) of the residents in Cornigliano, a district of Genoa (Italy), exposed to air pollution produced by a steel plant with coke-ovens. MATERIALS AND METHODS: Three epidemiological investigations were performed: on all mortality causes; on tumors incidence; on hospitalizations for respiratory diseases. The studies are based on the Regional Mortality Registry, the Ligurian Tumor Registry and the regional hospital discharge records. We calculated both the standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence limits, and we have compared the hospitalization rates in two Cornigliano subareas with different pollution levels; the "rest of Genoa" represents the general reference. RESULTS: In Cornigliano the total mortality is statistically higher among males (SMR 123; n. 1684) and females (SMR 148; n. 2160); in particular all tumours, prostate, brain and emolymphopoietic system were significantly higher among males, while colon-rectum and NOS intestine tumours were higher among females. SMRs were statistically higher in both genders for degenerative illnesses of the nervous central system, brain circulatory disorders and liver cirrhosis; only in males for respiratory tract illnesses and in females for myocardial heart attacks. The incidence has increased to a statistically significant extent among males for all cancer sites (SIR 110; n. 821), and for larynx, brain and emolymphopoietic system tumours. Hospitalizations for respiratory illnesses appear to be higher in the most polluted area among males (age 0-14), and decreased after closing the coke-oven plant (2002). CONCLUSIONS: Results of these studies suggest that air pollution in Cornigliano may have a role on populations health conditions.

Lung cancer mortality in a district of La Spezia (Italy) exposed to air pollution from industrial plants.

AIMS AND BACKGROUND: In the last decades, many epidemiological studies have implicated outdoor environmental carcinogens in the onset of lung cancer. The present investigation evaluated lung cancer mortality in two areas of the Province of La Spezia (Northern Italy) exposed to environmental pollution emitted by a coal-fired power station and other industrial sources, including a waste incinerator. METHODS: In the two exposed areas, lung cancer mortality risk for the 1988-1996 calendar period was evaluated using the whole Province population as referent. The corresponding relative risks (RR) were estimated after controlling for age structure, urban/rural gradient and deprivation factors (occupation, education, home ownership, housing conditions and family structure) by a Poisson regression modeling. The geographic pattern of risk for the whole province was evaluated via the Besag, York and Mollié (BYM) bayesian model. RESULTS: Persons living in urban areas showed the highest rates in both sexes. No statistically significant risk excess was found in the two exposed areas among males, after excluding rural and semi-rural zones from the analyses (RR = 1.03 and RR = 0.77). In contrast, a risk excess was observed for females in both exposed areas, which remained elevated and statistically significant (P <0.05) after restriction to urban/semi-urban municipalities and after controlling for deprivation factors (RR = 1.54 and RR = 2.14, respectively). Bayesian mapping confirmed the rural/urban gradient and the risk excess observed in females near the industrial sites. CONCLUSIONS: The risk observed among females is consistent with pollution measurements and with other epidemiologic findings, whereas a strong confounding from occupational exposures and smoking habit could account for the lack of an excess risk in males. However, the ecologic nature of this investigation prevented drawing a causal inference. The pollution-related risk observed in the female gender is an important clue that deserves further epidemiologic attention.

Effect of a palliative home care team on hospital admissions among patients with advanced cancer.

This was a quasi-experimental study designed to determine whether, in patients with advanced cancer, a palliative home care team (PHCT) modified hospital utilization in the last six months before death. Of 2503 cancer deaths in the municipality of Genoa, Italy, in 1991, 189 (7.5%) received care from a PHCT. Three hundred and seventy-eight controls matched for primary tumour were selected. The groups were similar in terms of age, gender and most other demographic variables, except that educational level was lower, and times to death, from first diagnosis and from diagnosis of advanced or metastatic cancer, were longer among PHCT patients compared with the controls. Before referral to a PHCT, or a matched time in controls, both groups spent about 15% of days in hospital. After admission to a PHCT, the percentages of days in hospital increased in both groups as death approached, but it was much higher in the control group (30.3%; 95% confidence interval (CI): 26-34) than in the PHCT group (19.0%; 95% CI: 15-23). The difference between groups was most marked in the last month of life, and disappeared among those patients who were in care for more than 120 days (throughout the course of their illness). We conclude that a PHCT appears to reduce days in hospital and allows patients to spend more time at home. Differences in time in care between groups requires further investigations.