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Currently, there are more and more requests for a characterization of the health profile by populations living in areas affected by several types of environmental contaminations, notably for the presence of previously unknown and accidentally discovered landfills. The aim of the present paper is to describe the mortality profile of the residents of Piazzola sul Brenta (Veneto Region, Northern Italy). In this area, it was discovered an environmental contamination of the soil in the nearby of a large school building, where was formerly located a phosphate fertiliser plant. Using cause of death data provided by the Italian National Institute of Health, 10th International Classification 2013-2018, standardised mortality ratios (SMRs) and 90% confidence intervals (CIs) were calculated by gender and specific causes of death. Compared to the provincial reference population, no excess was found, for both genders, for all-causes mortality and for circulatory diseases. However, an excess for malignant tumours was found, 523 observed deaths over 498 expected deaths, an SMR of 105 (IC90% 98-113), and 85% probability of excess cancer mortality; lung cancer (SMR 117; IC90% 100-135) and lympho-hematopoietic tumours (in men only, SMR 134; IC90% 101-178).In light of these results and of the potential human exposure to carcinogenic substances, present results support further epidemiological investigations and environmental remediation.

Uncertainty on long-term average radon concentration has a large impact on lung cancer risk assessment in epidemiological studies. The uncertainty can be estimated by year-to-year radon concentration variability, however few data are available. In Italy a study has been planned and conducted to evaluate year-to-year radon variability over several years in normally inhabited dwellings, mainly located in Rome. This is the longest study of this kind in Europe; repeat radon measurements are carried out for 10 years using LR-115 radon detectors in the same home in consecutive years. The study includes 84 dwellings with long-term average radon concentration ranging from 28 to 636 Bq/m3. The result shows that year-to-year variability of repeated measurements made in the same home in different years is low, with an overall coefficient of variation of 17%. This is smaller than most of those observed in studies from other European countries and USA, ranging from 15% to 62%. Influencing factors that may explain the differences between this study and other studies have been discussed. Due to the low yearly variability estimated in the present 10-year study, a negligible impact on lung cancer risk estimate for the Italian epidemiological study is expected.

The ALK gene (anaplastic lymphoma kinase) encodes a highly conserved tyrosine kinase receptor whose physiological function has not yet been fully established; in particular the fusion of ALK (mainly EML4-ALK) is the gene alteration that most frequently involves 3-7% of all non-small cell lung cancers. Neuroblastoma in adults (NB) is a rare tumor that can present somatic activating mutations in the ALK gene in 8-9% of patients (and up to 14% of high-risk NBs); these mutations occur in the tyrosine kinase domain in three key positions (F1174, F1245 and R1275), which account for approximately 85% of all ALK mutations in NB. In this article, we report the case of an adult patient with advanced mutation-positive NB treated with an ALK inhibitor ceritinib showing a therapeutic opportunity due to the molecular diagnostic techniques now available.

The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML’s Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.

The idea of conducting a geographical analysis of cancer incidence in Vercelli, a city with about 46,000 population in the Province of Vercelli (Piedmont, northern Italy), originated from the need to respond to concerns of the population and local administrators regarding the presence of a solid waste incinerator just a few kilometers from the city, and the ongoing intense agricultural activity in the area. The study also aimed to verify the excess risk identified in a similar study on mortality. We obtained census data and mortality data for the years 2002 to 2009, from the Italian Institute of Statistics (ISTAT) and analysed these from both an epidemiological point of view, through standardised mortality rates, and spatial analysis through the use of Bayesian models. Both approaches highlighted an overall increased risk for cancers and increased risks for colorectal and lung cancer, in persons residing south of the capital. They also identified an increased cancer risk in the young adult population of both sexes, which deserves further investigation.

This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.

Il grafico, basato sui dati AIRTUM 1992- 2007,mostra l’andamento dell’incidenza di tumore del polmone nei giovani adulti di età 20-49 anni in entrambi i sessi. I

The purpose of our study was to retrospectively evaluate the feasibility, safety and effectiveness of microwave ablation (MWA) in nine patients with unresectable lung tumour.Ten lesions were treated in ten ablation sessions in nine patients. The treatments were performed with a microwave generator with 45 W and 915 MHz connected to a 14.5-gauge antenna for 10 min. Antenna placement was performed with computed tomography (CT) fluoroscopy guidance or XperGuide. All patients underwent CT follow-up at 1, 3 and 6 months from the procedure.Technical success was obtained in all cases; mortality at 30 days was 0%.This study shows that in selected patients, MWA is a valid alternative to other ablative techniques. Further studies are required to demonstrate the short- and long-term effects of this technique and to make a comparison with other available ablation systems, especially with radiofrequency.

Computed tomography (CT) is the most sensitive imaging technique for detecting lung nodules, and is now being evaluated as a screening tool for lung cancer in several large samples studies all over the world. In this report, we describe a semiautomatic method for 3-D segmentation of lung nodules in CT images for subsequent volume assessment. The distinguishing features of our algorithm are the following. 1) The user interaction process. It allows the introduction of the knowledge of the expert in a simple and reproducible manner. 2) The adoption of the geodesic distance in a multithreshold image representation. It allows the definition of a fusion--segregation process based on both gray-level similarity and objects shape. The algorithm was validated on low-dose CT scans of small nodule phantoms (mean diameter 5.3--11 mm) and in vivo lung nodules (mean diameter 5--9.8 mm) detected in the Italung-CT screening program for lung cancer. A further test on small lung nodules of Lung Image Database Consortium (LIDC) first data set was also performed. We observed a RMS error less than 6.6% in phantoms, and the correct outlining of the nodule contour was obtained in 82/95 lung nodules of Italung-CT and in 10/12 lung nodules of LIDC first data set. The achieved results support the use of the proposed algorithm for volume measurements of lung nodules examined with low-dose CT scanning technique.

A-4 . ST2151 . Spindle assembly checkpoint . Mitotic catastrophe . Caspase-3 Combretastatin A-4 (CA-4), a natural stilbenoid isolated from Combretum caffrum, is a new vascular targeting agent (VTA) known for its antitumor activity due to its anti-tubulin properties. We investigated the molecular mechanisms leading to cell death in non-small cell lung cancer H460 cells induced by natural (CA-4) and synthetic stilbenoids (ST2151) structurally related to CA-4. We found that both compounds induced depolymerization and rearrangement of spindle microtubules, as well as an increasingly aberrant organization of metaphase chromosomes in a dose- and time-dependent manner. Prolonged exposition to ST2151 led cells to organize multiple sites of tubulin repolymerization, whereas tubulin repolymerization was observed only after CA-4 washout. H460 cells were arrested at a pro-metaphase stage, with condensed chromosomes and a triggered spindle assembly checkpoint, as evaluated by kinetochore localization of Bub1 and Mad1 antibodies. Persistent checkpoint activation led to mitochondrial membrane permeabilization (MMP) alterations, cytochrome c release, activation of caspase-9 and -3, PARP cleavage and DNA fragmentation. On the other hand, caspase-2, and -8 were not activated by the drug treatment. The ability of cells to reassemble tubulin in the presence of an activated checkpoint may be responsible for ST2151-induced multinucleation, a recognized sign of mitotic catastrophe. In conclusion, we believe that discovery of new agents able to trigger mitotic catastrophe cell death as a result of mitotic block and prolonged spindle checkpoint activation is particularly worthwhile, considering that tumor cells have a high proliferative rate and mitotic failure occurs irrespective of p53 status.

We showed previously that p53 mutations play a role in cigarette smoke-related carcinogenesis not only in humans but also in A/J mice. In fact, (UL53–3 × A/J)F1 mice, carrying a dominant-negative germ-line p53 mutation, responded to exposure to environmental cigarette smoke more efficiently than their wild-type (wt) littermate controls in terms of molecular alterations, cytogenetic damage, and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA array the expression of 1,185 cancer-related genes in the lung of the same mice. Neither environmental cigarette smoke nor the p53 status affected the expression of the p53 gene, but the p53 mutation strikingly increased the basal levels of p53 nuclear protein in the lung. Environmental cigarette smoke increased p53 protein levels in wt mice only. The p53 mutation enhanced the expression of positive cell cycle regulators in sham-exposed mice, which suggests a physiologic protective role of p53. In environmental cigarette smoke-exposed mice, the p53 mutation resulted in a lack of induction of proapoptotic genes and in overexpression of genes involved in cell proliferation, signal transduction, angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted to environmental cigarette smoke in a similar manner regarding genes involved in metabolism of xenobiotics, multidrug resistance, and protein repair. Irrespective of the p53 status, environmental cigarette smoke poorly affected the expression of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these findings may explain the increased susceptibility of p53 mutant mice to smoke-related alterations of intermediate biomarkers and lung carcinogenesis.

This paper reviews the literature on the influence of metabolic and DNA repair polymorphisms of biological indicators of genotoxic risk commonly used in biomonitoring occupational exposure to carcinogens. Genetic polymorphisms which influence biomarkers (urinary metabolites, protein and DNA adducts), include P450 cytochromes (CYPs) and glutathione S-transferases (GSTs) in exposure to polycyclic aromatic hydrocarbons (PAHs), and acetyltransferases (NATs) in exposure to aromatic amines (AAs). As regards exposure to benzene, also relevant is the influence of epoxydohydrolase (EPHX) and NAD(P)H quinone oxidoreductase (NQO1) on the urinary excretion of t,t-muconic and phenylmercapturic acids. With respect to occupational exposure to styrene, EPHX significantly influences the levels of Chromosome Aberrations (CAs), strongly predictive genotoxic biomarkers of cancer risk. Some recent studies examine the role of polymorphisms linked to DNA repair genes in the modulation of genotoxic risk associated with PAH exposure, both for life-style (dietary and smoking behaviour) and for occupational reasons. In addition, molecular epidemiology studies (case/control studies) of lung cancer in smokers published since 2000 may also be viewed as representing models of effects due to exposure to carcinogenic mixtures, some of which are present in the working environment (e.g., BaP, benzene, AAs). Almost all studies show the clearcut influence (i.e., increased lung cancer risk with ORor = 2) of genetic polymorphisms linked to PAH metabolism (in particular, CYPIA1, GSTM1 and P1). Among the risk factors are the different mutagen sensitivity towards, for instance, bleomycin and BaP (tested in vitro), the reduced repair capacity to DNA damage induced by BaP, and increases in some biomarkers of early biological effect (DNA adducts and stable CAs). Other risk factors, such as heredity (siblings of cancer patients have a risk factoror = 3 with respect to the general population), ethnicity (ChileansCaucasians; JapaneseAmericans) and gender (womenmen), have still not been clearly characterized and these are also reported in this paper. It is clear from the above that genetic differences underlie individual susceptibility to lung cancer, whether caused by exposure to tobacco smoke or to occupational carcinogens like PAHs. Some of these indicators of exposure/individual susceptibility can be evaluated in groups at high risk of occupational lung cancer, such as coke-oven and aluminium workers and those exposed to coal tar fumes and soot, etc., with the aim of identifying subjects who are susceptible due to the high concentrations of carcinogens found in their working environment.

The Authors report the case of a patient who underwent video-thoracoscopic resection of a solitary pulmonary metastasis. She presented, after about two years, a local relapse (implantation) in the trocar site. Pathogenesis and surgical therapeutic problems are discussed as well.

Carcinoids are neuroendocrine neoplasms. Bronchial carcinoids are unusual, malignant primary neoplasms that characteristically involve the central airways and typically exhibit well-defined margins and bronchial-related growth. Bronchial carcinoids include low-grade typical carcinoids and the more aggressive atypical ones. They usually affect patients in the 3rd through the 7th decade of life who are often symptomatic with cough, hemoptysis or obstructive pneumonia. Rarely, the initial symptoms are related to the secretion of hormones causing carcinoid or other endocrine syndromes. Bronchial carcinoids radiologically manifest as hilar or perihilar masses, with or without associated atelectasis, pneumonia or bronchiectasis. At CT-scan the relationship of these tumors with the bronchial tree is usually seen, and they show contrast enhancement or calcification. Even if the radiological signs may be suggestive for bronchial carcinoid, the definitive diagnosis is reached only by the tissue sampling. Bronchoscopic biopsy is the more effective way to identify the nature of carcinoid tumors because of their frequent central location. The treatment of choice is the surgical resection which should be carried out with maximum respect for the residual lung and bronchial tissues. Endoscopic ablations in well defined cases, bronchotomy and lung resections with or without bronchoplastic procedures have been described. Hilar and mediastinal lymph node sampling and examination should be ever performed during open procedures. Positivity of the nodal tissues could influence the resection procedure and is related with the prognosis, specially for the atypical carcinoids. Chemo- and radiation therapy are not effective in improving the long-term outcome in those patients with advanced disease. The long-term outcome is strictly related with the histological subtype and the lymph node status. Local recurrences and distant metastases are more frequent in the atypical carcinoids which manifest a more aggressive behavior. During the last decade, the importance of the use of somatostatine analogues (octreotide) in the staging, early detection of the recurrent disease and its management such as that of the associated carcinoid syndrome became clear.

Lung surgery in the elderly, once considered a major risk, to be avoided if possible has become more popular in recent years as a result of many factors. First: lung cancer incidence has increased significantly in every age group but mostly in the elderly. Second: diagnosis at an early stage of the disease is higher in patients over 70 due to more frequent medical control in old subjects. Third: we now have more and more humans over 80 and a life expectancy increasing over the years. Fourth: preoperative, operative and postoperative medical supports are now safer and more reliable than previously. Operability criteria in the elderly are substantially the same as in younger group of patients for lung cancer. There are no reasons to refuse surgery in a subject over 80 because he is old. Lobectomy is the procedure of choice for lung cancer even in the elderly. Pneumonectomy must be avoided preferring a less radical procedure (wedge resection) so avoiding the risk of a postoperative respiratory failure that is often fatal for a patient with in border line functional respiratory tests, as often happens in the elderly. Thoracoscopic atypical resections must be considered in patients when a wedge resection is indicated preoperatively and almost always metastatic pulmonary lesion.

The study evaluates the role of radio-guided surgery (RGS) with 111In-octreotide in the treatment of lung neoplasms. RGS with octreotide appears to be useful in surgery, above all during the intraoperative staging of the tumour; it can define with greater precision the extent of the resections extended towards the lung wall and ensure a radical approach in minimal lung resections.

Many studies have investigated locoregional immune responses and long-term survival in various types of cancer; few have focused on lung cancer. This study was designed to assess the prognostic value of immunomorphologic changes in locoregional lymph nodes in patients resected for bronchogenic carcinoma.In a retrospective analysis, immune responses in locoregional lymph nodes were studied histologically in 172 selected patients. Lymph node morphology was studied according to the system of Cottier et al.: sinus histiocytosis (SH) and paracortical lymphoid cell hyperplasia (PCA) were considered as a cellular immune response, and follicular hyperplasia of the cortical area (CA) as a humoral reaction. The survival rate was estimated by the Kaplan-Meier product-limit method. Log-rank test and Cox proportional-hazards model were used to determine statistical significance in univariate and multivariate survival analysis.35.5% of the patients had no evident response in regional nodes; 19.8% had a marked cellular response; 11% a marked humoral response; and 33.7% a mixed cellular-humoral response. A nodal cellular response improved long-term survival rates even in patients with regional node metastases. Multivariate analysis identified an independent variable as having high prognostic value: lymph node immunoreactivity.Lymph node immunoreactivity significantly influences long-term survival after curative surgery for lung cancer and may be useful in stratifying patients for prospective trials of adjuvant treatment including immunotherapy.

In recent studies a new method has been proposed to detect circulating melanoma cells in the peripheral blood of patients, based on the amplification of the mRNA for tyrosinase, an enzyme involved in melanin biosynthesis that is expressed only by melanocytic cells. The sensitivity and clinical relevance of this method are still controversial. In the present study, 596 blood samples from 186 melanoma patients at various clinical tumour stages, together with samples from 25 healthy volunteers, were analysed with the aim of investigating the value of tyrosinase detection in predicting melanoma recurrence. We suggest a possible role for this marker in the monitoring of melanoma patients after the excision of regional lymph node metastases, and provide evidence that tyrosinase is related to the status of disease in advanced metastatic patients. Moreover, chemotherapy administration appeared to influence tyrosinase determination and may explain the discrepancies in the reported percentages of positive samples.

To review the patients treated at our Institute over the past 22 years and to evaluate the behaviour of 14 atypical carcinoids on the basis of Capella's classification (1994), defining the most suitable surgical approach.A total of 118 patients undergoing surgery for lung neuroendocrine tumours were reanalyzed on the basis of their anatomic and pathological characteristics, surgical treatment and survival.The 5-year survival rate was 96.5% for typical forms and 74.5% for atypical forms; the 10-year survival rate was 92.4% for typical forms and 49.8% for atypical forms (p0.001). Lymph node metastatic involvement was also an important contributing factor for survival (p0.05). A review of the series of 19 patients treated over the past 6 years, diagnosed with so-called atypical carcinoid based on Capella's anatomic and pathological classification, showed that 5 were well differentiated neuroendocrine tumours (WDNT), 8 well differentiated neuroendocrine carcinomas (WDNC) and 1 small-cell lung neuroendocrine carcinoma (SLCL). From a surgical point of view, 10 cases underwent demolitive surgery and 9 conservative surgery. The overall actuarial survival rate in this series was 78% at 5 years, 100% for WDNT and 75% for WDNC. The only case of SCLC died after a few months.The authors conclude that the 5 and 10-year probability of survival are closely linked to the histological type of the lung neuroendocrine tumour and the presence of lymph node metastasis. Capella's new anatomic and pathological classification helps to establish a more precise prognosis for so-called atypical carcinoids. Lastly, given the malignant potential of these tumours, preference should be given to radical exeresis.

After the liver, the lungs represent the most frequent site of metastasis from primary tumours. Surgical treatment of lung secondary neoplasms leads to a significant improvement in survival.Between 1960-1997, 178 patients with lung metastases underwent surgery at the Thoracic Surgery Department of Turin University in a total of 193 operations. A retrospective study was made in order to identify the prognostic factors which influenced final survival in this population.Overall survival was 47% after 2 years and 20% after five years. Prognosis was not influenced by the size of metastases, the type of surgery, adjuvant therapy and the number of operations on the same patient. On the other hand, useful prognostic factors were found to be the histological type of the primary tumour, the original site of the neoplasm, the number of metastases and, above all, the disease-free interval (DFI).Lung metastasectomy is an important therapeutic aid in selected patients, whereas the preoperative evaluation of the above prognostic factors enables a reasonably precise prognosis to be made in most patients.

An anticorpal panel formed by Calretinin, Ber-EP4, Keratin and CD 68 has been applied to differentiate mesothelial hyperplasia/mesothelioma from metastastic carcinoma in cavity effusions. The study was performed in 86 cases in which paraffinated cell-blocks were obtained. All cases positive for malignancy had histological confirmation. The series included 2 malignant mesothelioma, 54 reactive mesothelial hyperplasia, and 30 metastatic carcinoma. All cases of reactive mesothelial showed strong cytoplasmatic positivity for Calretinin, and hyperplasia negativity for Ber-EP4. The 2 cases of mesothelioma were positive for Calretinin and negative for Ber-EP4. In contrast, all cases of metastatic carcinoma had membrane or cytoplasmatic positivity for Ber-EP4. The sensitivity (100%) and specificity (100%) of reactivity for Calretinin and Ber-EP4 showed that the immunocytochemical results on paraffin embedded material from cavity effusions are very reliable, so that the tested immunocytochemical panel can be useful in cytological differential diagnosis between reactive mesothelial hyperplasia/mesothelioma and metastatic carcinoma.

Sixty-one patients undergoing pulmonary resection were studied pre- and post-operatively by spirometry, arterial gas determination, and quantitative ventilation/perfusion lung scanning. Our results showed that ventilation and/or perfusional scintigraphic scanning is currently the most reliable method in identifying patients at risk for postoperative respiratory insufficiency. Specifically, this technique was successful in detecting pulmonary areas other than those to be resected presenting ventilation or perfusional abnormalities. Therefore, the technique is particularly useful in predicting residual pulmonary function.

Personal experience on the use of 111In-DTPA-octreotide scintigraphy (Octreoscan) in the staging of neuroendocrine and non-neuroendocrine tumors of the lung is reported. From July 1995 to May 1996 26 scintigraphic studies were performed in patients affected by lung cancer at the Department of Thoracic Surgery and at the Service of Nuclear Medicine of the University of Turin. The scintigraphy allowed to detect the lesion in all the neuroendocrine tumors and in 63.2% of the non neuroendocrine ones. Their preliminary results are discussed and stress is laid on the importance of this scintigraphic procedure in the staging and the follow-up of neoplastic patients.

Over the past years, a number of serum components have been confirmed as useful biological markers of lung cancer. Although none have been sensitive or specific enough to enable early diagnosis, they do seem to facilitate the monitoring and prediction of disease prognosis. We studied tumor markers in 66 patients with lung cancer: serum levels of ferritin, carcinoembryonic antigen (CEA), alpha-fetoprotein (alpha-FP); tissue polypeptide antigen (TPA), cytocheratin fragment 19, 21-1 (CYFRA 21-1) and carbohydrate antigen 125 (CA 125) levels were measured and correlated to tumor stage and histological type. Postulating a specificity of 95% versus benign diseases of the lung, we confirmed the following diagnostic sensitivity for the markers: ferritin = 39.3%; CEA = 42.4%; alpha-FP = 5.1%; TPA = 57.5%; CYFRA 21-1 = 65.1%; CA 125 = 46.9%. CYFRA 21-1 showed significantly higher sensitivity in non small cell lung cancer patients than in those with small cell lung cancer (Wilcoxon, p = 0.02). Moreover since survival time was significantly shorter in patients with high serum CYFRA 21-1, these levels seemed to be correlated with the prognosis.

To investigate the relationship between air pollution and histologic type of lung cancer we conducted a case-control study among deceased men in Trieste, Italy. 755 cases of lung cancer and 755 controls were identified through the local autopsy registry. Information on smoking habits, occupation and place of residence was obtained from the subject's next-of-kin. Air pollution at the residence of each subject was estimated from the average value of total particulate at the nearest monitoring station. Spatial models and logistic regression were used to evaluate the effect of residence and air pollution on LC after adjustment for age, smoking habits, likelihood of exposure to occupational carcinogens and social group. The risk of lung cancer increased with increasing level of air pollution for all types of lung cancer combined (P = 0.022), for small cell carcinoma (P = 0.016) and for large cell carcinoma (P = 0.049). Compared with inhabitants of the residential area, residents of the rural area had a relative risk (RR) of 0.6 (95% confidence interval (CI): 0.4-1.0). The RR was 1.5 (1.0-2.2) for residents of the center of the city and 1.4 (1.0-2.1) for residents of the industrial area. In the center of the city the excess risk was almost completely restricted to small cell carcinoma (RR = 2.0) and to large cell carcinoma (RR = 2.6). In the industrial area the risk was increased especially for adenocarcinoma (RR = 2.1). These results provide evidence that air pollution is a moderate risk factor for certain histologic types of lung cancer.

Fast-scan CT is widely and frequently used to guide fine-needle aspiration biopsy (FNAB) of questionable lung nodules. To investigate technical problems, complications, diagnostic accuracy and indications of this technique, the findings were reviewed relative to 118 patients with negative transbronchial biopsy and sputum cytology who underwent CT-guided FNAB of solitary lung lesions. Over a 25-month period, 73 men and 45 women underwent CT-guided FNAB of lung lesions. The CT unit was a GE 9800; 22-gauge 7/9-cm spinal needles were used in most cases, while 22-G 15-cm Chiba needles were used in 6 cases. In 114 patients one FNAB was performed, 4 patients only requiring the maneuver to be repeated. Regarding the malignant nature of the lesions, there were 70 true positive, 36 true negative, 12 false negative and no false positive cytologic findings; sensitivity was 85.36%, specificity and positive predictive value were 100%, negative predictive value was 75% and diagnostic accuracy 89.83%. Only minor complications occurred: 5 cases of hemophtoe, 7 of peripheral bleeding, 4 of chest pain, 4 vagal reactions and 10 cases of pneumothorax, only one of them requiring drainage. In our experience, only one pass per patient is required and the presence of the cytopathologist is unnecessary, since in most of our cases (114/118) the diagnosis was made at the first FNAB performed by the radiologist. CT allowed the lesions to be approached easily and precisely, which is useful especially in small, peripheral or hilar, nodules missed or poorly defined by radiology. To conclude, CT-guided transthoracic FNAB can be suggested as the method of choice to diagnose lung lesions which are difficult to puncture endoscopically because of size or location, and in suspected metastases. Moreover, FNAB can be used as second-line method in the lesions where endoscopic biopsy cannot be performed or whose findings are negative.

The pulmonary hamartoma is a kind of disease frequently shown in elderly. The diagnosis is often difficult and fine needle aspiration (FNA) can be used for histological features. CT scan can be also a such useful technique in differential diagnosis. A case is presented and its problems are discussed.

The authors report their observations on 7 cases of multiple malignant tumors during the period 1988/1992 (frequency of 0.03 x 100). They report that primary malignant tumors involved the laryinx and the wang, and both the lungs in a synchronous or metacronous way. They suggest that pathogenesis of multiple malignant tumors may be very similar to that of multiple endocrinous neoplasms.

Primary lymphoma of the lung is a rare pathological condition arising from mucosa-associated lymphoid tissue (MALT). The lack of specific symptoms and the related diagnostic problems induced the authors to report a clinical case recently observed. Therefore, some histopathologic characteristics useful for a correct differential diagnosis with the pseudolymphoma of the lung and the interstitial lymphocyte pneumonia are analysed.

The Authors describe a case of a 65 year-old man with paraneoplasic syndrome, presenting erythematous-edematous figure lesions. Clinical, histological and immunological features were suggestive of lupus erythematosus.

A brief presentation is made of the theory underlying the multistage model of Armitage and Doll and its implications in assessing the effect of exposure to a carcinogen. The theory foresees different relationships between cancer risk and the dependent time variables (time from beginning of exposure, age at start of employment, duration of exposure and time since end of exposure) according to whether the carcinogen acts in the early or late stages of the process of cell transformation leading to tumour formation. The trend in risk of death from lung cancer was studied in a cohort of workers exposed to hexavalent chromium followed up between 1948 and 1985. The results, referred to the multistage model, indicate that hexavalent chromium probably acts in the later stages of the cell transformation process; the implications of this hypothesis for prevention and/or occupational safety strategies are discussed.