A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.

The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.

Metastasis of high grade renal cell carcinoma, clear cell type, in fibrous dysplasia with superimposed giant cell reparative granuloma.

A case of monostotic fibrous dysplasia in a 54-year-old male complaining of severe pain in the right hip is presented. Imaging findings demonstrated an extremely aggressive lesion involving bones, liver, lungs, and lymph nodes, and suggested the possibility of sarcomatous transformation. Histological examination established a diagnosis of metastatic high-grade renal carcinoma, clear cell type, and demonstrated the presence of superimposed giant cell reparative granuloma. This latter is a rare example of giant cell reparative granuloma arising in a long bone and in association with fibrous dysplasia. The clinical, radiographic, and histopathologic features of fibrous dysplasia and giant cell reparative granuloma are discussed.

Metastatic angiosarcoma of the kidney: a case report with treatment approach and review of the literature.

Angiosarcomas are rare soft tissue malignancies. Typically they originate from the skin of the scalp or face, whereas visceral sarcomas are very rare. We report the case of a 67-year-old man affected by a large angiosarcoma of the kidney. After surgical removal, a rapid peritoneal, visceral and cutaneous diffusion developed. Palliative chemotherapy, based on anthracycline and ifosfamide, which are normally used to treat all other high-grade spindle cell sarcomas, was totally inactive. On the basis of these results and of the biological characteristics of these rare neoplasms it is mandatory to develop other therapeutic approaches. Antiangiogenetic agents are of interest for this disease due to the peculiar origin of the cells of these sarcomas.

Asbestos exposure in malignant mesothelioma of the pleura: a survey of 557 cases.

A series of 557 malignant mesotheliomas of the pleura diagnosed in the Trieste-Monfalcone area, Italy, in the period 1968-2000 were reviewed. The series included 492 men and 65 women, aged between 32 and 93 years (median age 69 years). Necropsy findings were available in 456 cases (82%). Occupational histories were obtained from the patients themselves or from their relatives by personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 442 cases. In 109 cases isolation and counting of asbestos bodies were performed. A majority of people had histories of working in the shipyards. Asbestos bodies were observed in lung sections in 67% of the cases. Lung asbestos body burdens after isolation ranged between 20 bodies and about 10 millions of bodies/g dried tissue. Latency periods (time intervals between first exposure to asbestos and death) ranged between 14 and 75 years (mean 48.8 years, median 51.0). Latency periods among insulators and dock workers were shorter than among the other categories. High asbestos consumption occurred in many countries in the 1960s and in the 1970s. The data on latency periods obtained in the present study suggest that a world mesothelioma epidemic has to be expected in the coming decades.

Asbestos exposure in a shipyard area, northeastern Italy.

The Monfalcone area, northeastern Italy, is a small industrial district (population 60,000), with a large shipyard. In order to monitor asbestos exposure in this area, a series of 3,640 necropsies, carried out at the Monfalcone Hospital between October 1979 and September 1998, were investigated. The thoracic cavities were examined for pleural plaques; these were classified into three classes (small, moderate, large). Routine histological sections of lung tissue were examined for asbestos bodies. Isolation and counting of asbestos bodies were performed in 1,075 cases. Lifetime occupational data were collected in 1,277 cases. Pleural plaques were observed in 70.5% among men and in 23.8% among women. The prevalences of pleural plaques did not show significant variations during the study period. Asbestos bodies were found on routine lung sections in 23.7% of men and 3.0% of women. The shipyard workers, the most numerous category in the series, were characterized by high prevalence of pleural plaques (total 86.7%, large 32.4%), high prevalence of asbestos bodies on routine lung sections (35.3%), and high amounts of lung asbestos bodies after isolation. The present data indicate that asbestos exposure may reach alarming levels in the shipyard areas.

Malignant mesothelioma in central and Eastern Europe.

To obtain data on mesothelioma incidence in Central and Eastern Europe, a short questionnaire was sent to 83 researchers from 19 countries. The questions referred to the approximate number of mesotheliomas diagnosed per year in the country, degree of asbestos consumption, and percentage of lung carcinomas attributable to asbestos. Answers were received from 12 countries. For some major asbestos producers and/or consumers, such as Russia and Ukraine, mesothelioma data were unavailable or unreliable. In various countries of Central-Eastern Europe, the crude incidence of mesothelioma appeared to be lower than in Western countries. The reported annual numbers of mesotheliomas were 120 in Poland, 133 in Romania, and 78 in Hungary. Among the countries with a population of 5 million or less, the highest incidence was observed in Croatia (46 cases per year, peritoneal tumors not included). Data on the percentage of asbestos-related lung carcinomas are lacking. The knowledge about asbestos related cancer in Central and Eastern Europe remains fragmentary. Further investigations in this relevant area of public health should be encouraged.

Asbestos exposure in lung carcinoma: a necropsy-based study of 414 cases.

BACKGROUND: The prerequisites necessary for attributing lung carcinoma to asbestos, represent a controversial issue. METHODS: Three parameters (occupational history, pleural plaques, and lung asbestos bodies) were investigated in 414 consecutive cases of lung carcinoma, examined at necropsy at the Hospital of Monfalcone, Italy. Occupational data were obtained from the patients' relatives by personal or telephone interviews. Pleural plaques were classified into three classes (small, moderate, large). Routine lung sections were examined for asbestos bodies in all cases; isolation and counting were performed in 408 cases. RESULTS: The series included 353 men, and 61 women, aged between 38 and 97 years. The male patients had worked in industries in 74% of cases (60% in shipbuilding). Men showed pleural plaques in 82% of cases (moderate or large plaques in 58.7%). Asbestos bodies were observed in routine lung sections in 34.8%, and in 31% exceeded the value of 5,000 bodies per gram of dried tissue. Among women the principal features were: history or domestic exposure to asbestos in 36% of the cases, prevalence of pleural plaques 34% (moderate or large plaques 15%), asbestos bodies in routine lung sections in 3.3% and there was no case with an asbestos body burden over 5,000/g. The fraction of asbestos-related carcinomas among male patients varied between 24.7 and 61%, depending on the criteria used for attribution. CONCLUSIONS: Different criteria indicated about 60% of the present lung carcinomas among men as plausibly attributable to asbestos.

Pleural plaques as risk indicators for malignant pleural mesothelioma: a necropsy-based study.

Pleural plaque is recognized as a reliable marker of previous exposure to asbestos. However, it is controversial whether pleural plaque is a risk indicator for asbestos-related malignancies. In the present study, the thoracic cavities were examined for pleural plaques in 3,005 necropsies performed at the Monfalcone Hospital in people aged 15 years or older. Plaques were classified into three classes: 1, small (plaques measuring 1-4 cm in major diameter); 3, large (plaques involving a major part of a hemithorax); and 2, moderate (intermediate conditions). The prevalences of pleural plaques were 70.9% among men, and 24.0% among women. The prevalences of plaques (total plaques, various classes) among subjects with pleural mesothelioma were compared with those observed in the remaining cases. The series included 92 subjects with malignant pleural mesothelioma (82 men and 10 women). Mesothelioma cases showed higher prevalences of total plaques as well as higher prevalences of classes 1, 2, and 3, when compared with controls. These differences reached the statistical significance for total plaques, and classes 2, 3. The present data are consistent with the idea that pleural plaque is a risk indicator for pleural mesothelioma.

Latency periods in asbestos-related mesothelioma of the pleura.

Latency periods (time intervals elapsing between first exposure to asbestos and death) were examined in 421 cases of malignant pleural mesothelioma, diagnosed in the Trieste-Monfalcone area, Italy. Occupational data were collected from the patients or from their relatives by personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 370 cases. Latency periods, calculated in 312 cases, ranged from 14 to 72 years (mean 48.7, median 51). Latency periods differed significantly from one occupational group to another. Mean latency periods were 29.6 among insulators, 35.4 among dock workers, 43.7 in a heterogeneous group defined as various, 46.4 in non-shipbuilding industry workers, 49.4 in shipyard workers, 51.7 among women with a history of domestic exposure to asbestos, and 56.2 in people employed in maritime trades. The ANOVA test indicated a correlation between latency periods and occupational groups. Latency periods in people with asbestos bodies visible in routine lung sections did not differ from those seen in cases with no evidence of asbestos bodies. These data suggest that intensity of exposure is a relevant, but not the only, factor in determining the duration of latency periods.

Multiple primary malignant tumors in patients with hepatocellular carcinoma. A review of 29 patients.

BACKGROUND: The study of patients with hepatocellular carcinoma (HCC) and multiple primary malignant tumors (MPMTs) is interesting from an etiopathogenetic as well as from a clinical point of view. There are few studies dealing with this topic. METHODS: Smoking habits, alcohol intake, HBsAg status, alpha-feto-protein serum concentration, presence of liver cirrhosis, type of associated cancers, treatment, and survival were evaluated in 29 patients (25 men and 4 women; median age 73 years) with histologically confirmed HCC and MPMTs. All patients were examined between January 1980 and February 1995 at the General Hospital of Monfalcone, in northeastern Italy. In the same period there were 143 patients with HCC. RESULTS: Tumors associated with HCC were located in: prostate (9 cases), colon-rectum (5), bladder (3), lung (3), stomach (2), gallbladder (2), and brain, breast, oesophagus, pancreas, thyroid, larynx, pleura, small intestine, kidney (1 each). In 25 patients there was a single, and in 4 patients two associated malignancies. A diagnosis in vita of the associated malignancy was made in 15 cases. Cirrhosis was present in 90% of patients and HBsAg was positive in 15%. Mean survival time from diagnosis was 5.5 weeks (0-150) in patients with MPMTs and 6.8 weeks (0-221) in patients with HCC only. The cause of death was HCC in 18 patients, the associated tumor in 8, and non-neoplastic diseases in 2. Treatment of the associated tumors was performed in 8 cases. CONCLUSIONS: In this study the prevalence of MPMTs in patients with HCC is high (20.3%) in accordance with other autopsy series. Mean survival time in patients with MPMTs was similar to that in patients with HCC only. From a clinical point of view, attention must be paid to the diagnosis of hepatic lesions in patients affected with cirrhosis and extrahepatic cancer.

[Human subcutaneous dirofilariasis: 8 more cases in Italy]. / Dirofilariasi umana sottocutanea: 8 ulteriori casi in Italia.

Eight new cases of Human Subcutaneous Dirofilariasis due to Dirofilaria repens in subjects aged 14 to 83 years, 5 men and 3 women, are recorded. The patients were living in Piedmont (5 cases), Tuscany (1), Friuli-Venetia Julia (1) and Apulia (1). The nematodes were immature in 6 cases (2 males and 4 females) and adults in 2 (both females). Microfilariae in the uterus of one of them were detected.

Diagnosis of malignant tumor: comparison between clinical and autopsy diagnoses.

A review was made of the results of 1,036 consecutive autopsies (average patient age, 75 years; 617 male and 419 female patients; autopsy rate, 40.2%) done at the Hospital of Monfalcone from January 1986 through December 1991. In 457 autopsies (44%) one or more malignant neoplasms were found (single tumor in 382, dual tumor in 69, and triple tumor in six) for a total of 538 tumors. In the corresponding death certificates the clinical diagnosis of malignancy was found in 302 autopsies for a total of 310 tumors (single in 294 and dual in eight). The number of clinically unrecognized malignancies was 228 (42%) and the number of patients with undiagnosed tumors was 155 (34%). The neoplasms were subdivided into four stages according to their extension at autopsy: stage 0 (85 tumors), microscopic neoplasm; stage I (146 tumors), neoplasm localized at the site of origin; stage II (43 tumors), local advanced neoplasm; and stage III (264 tumors), neoplasm with metastases. The rate of correct clinical diagnoses increased according to the level of stage; (stage 0, 1%; stage I, 40%; stage II, 58%; and stage III, 66%). The greatest numbers of tumors found at autopsy were located in the gastroenteric apparatus (170), the respiratory apparatus (149), and the urogenital apparatus (130). The number of clinically undiagnosed neoplasms was high with respect to the urogenital apparatus (77% overall and 51% excluding stage 0) and the gastroenteric apparatus (41% and 38% excluding stage 0); in contrast, the number was low for the respiratory apparatus (17%). The rate of correct diagnoses was higher in patients younger than 65 years (65%) than in those older than 65 (54%), but the difference was not significant. The duration of hospitalization in the 12 months before death was statistically higher (P < .001) in patients with a correct diagnosis (36 days) than in undiagnosed patients (14 days). Even taking into account the biases that affect selection of patients for autopsy, the notable discrepancy found between clinical and autopsy diagnoses underlines the fact that autopsy, despite improvements in diagnostic techniques, maintains its fundamental importance in assessing the reliability of clinical diagnoses and furthermore shows the underestimation of the incidence of tumors in epidemiological studies based solely on death certificates.

Zoonotic filaria of possible American origin in Italy.

From a 31 year old man, resident in Monfalcone (Venezia Giulia) a nodule in the right temporal region was surgically removed in January 1992 containing a filiform living nematode. On the basis of the morphological characters, the nematode proved to be Dirofilaria sp. subgenus Nochtiella but the exact species was not possible to define. The medical history indicated that the patient had spent the last summer in Florida.

[Dementia in Friuli-Venice Giulia: hospital diagnosis]. / Le demenze nel Friuli-Venezia Giulia: diagnosi ospedaliere.

Discharge diagnoses made in the large hospitals of Friuli-Venezia Giulia during a 3-year period (1989-91) were collected. Diagnoses with ICD-9 codes 290, 290.0-4, 290.8-9, 331, 331.0-9, and 437.0 were selected, and analyzed. Discharge diagnoses including one of the above ICD-9 codes were found in 6,647 cases. ICD-9437.0 (brain arteriosclerosis) was by far the most frequent code (4,731 cases). When the present results are examined in the light of literature data as well as of previous research performed at the Monfalcone Hospital, it emerges that in the hospitals of Friuli-Venezia Giulia, dementia is a strongly underestimated condition. In addition the present data suggest that in these hospitals most dementia cases are misdiagnosed as vascular dementias.

Asbestos-related mesothelioma in Monfalcone, Italy.

The Monfalcone area, in northeastern Italy, is a small industrial territory (population about 60,000), with a large shipyard. Between October 1979 and April 1992, ninety-two malignant mesotheliomas were diagnosed at the Monfalcone Hospital. The series included 84 men and 8 women, aged 42 to 89 years (median age 68 years). There were 89 pleural and 3 peritoneal tumors. Seventy patients (69 men and 1 woman) had worked in the shipyards; six were seamen, and four insulators. Five men had been exposed to asbestos in various industries; six women had histories of domestic exposure, and one woman had a history of possible environmental exposure. The latency periods (intervals between first exposure to asbestos and diagnosis of the tumor) ranged from 20 to 65 years (median 52 years). Latency periods among insulators were significantly lower than among shipyard workers, as well as lower than among the other categories (p < 0.01). Lung asbestos bodies were isolated after chemical digestion in 73 cases at necropsy, and in two cases at surgery. In necropsy cases, asbestos body burdens ranged between 100 and 10,000,000 bodies per gram of dried tissue (median 11,000). Pleural plaques were observed at necropsy in 62 out of 73 cases, and in two cases at surgery. In the time period we considered, the annual incidence rates for pleural mesothelioma were very high among male Monfalcone residents, being 189 per 100,000 among people aged 75 years or more. On the basis of occupational data and of objective signs (lung asbestos bodies, pleural plaques), all the cases of the present series but one (that with possible environmental exposure) were considered as asbestos-related. The role of co-factors in the development of asbestos-related mesothelioma is suggested.

Prognostic factors of malignant mesothelioma of the pleura.

BACKGROUND: Pleural mesothelioma is a rare condition with a poor prognosis. The area of Monfalcone, North East Italy, provided a unique opportunity to study the disease because of its past heavy exposure to asbestos in local harbors and shipyards and its high necropsy rates. METHODS: The effects of various patient and tumor characteristics on survival were evaluated in 80 patients (73 males and 7 females; median age, 69) of histologically or cytologically confirmed malignant mesothelioma of the pleura. These patients were examined between October 1979 and October 1991 at the General Hospital of Monfalcone in the Friuli-Venezia Giulia region. Substantial exposures to asbestos were identified in 79 patients. RESULTS: Median survival rate was 13 months (range, 2-44 months), and overall 2- and 5-year survival rates were 23% and 0%, respectively. The factors that exerted a significant favorable influence on survival were as follows: (1) age younger than 65; (2) performance status less than or equal to one; (3) lack of less than or equal to 10% weight loss at any time; (4) Stages I and II; (5) epithelial or mixed histologic type; and (6) presence of pleural fluid with mesothelial cells but without neoplastic cells. When these factors were introduced in a Cox proportional hazard model, age, stage, and histologic type were the only independent prognostic factors. The increased hazards for patients, ages 65-74 (as compared to < 65), and for patients with sarcomatous histologic type (as compared to epithelial type) were 2.6 (95% confidence interval [CI], 1.2-5.7) and 4.5 (95% CI, 1.6-12.8). CONCLUSIONS: Survival rate in 24 untreated patients (median, 10 months) and 56 patients variously treated (median, 15 months) did not differ significantly. The availability of large portions of tumor specimens for histologic examinations in 77 of 80 patients, chiefly from high necropsy rate, strengthens the value of the present analysis of prognostic factors.

Asbestos-related familial mesothelioma.

Familial mesotheliomas are reported in four pairs of patients. The group includes six men and two women, aged between 44 and 84 years. A blood relation (father-son) existed in two pairs only. All the present patients had histories of exposure to asbestos; in five cases exposure had occurred in the shipyards. Familial mesothelioma could represent a useful model for investigating genetic-environmental interactions.

Exposure to asbestos in Monfalcone, Italy. A necropsy-based study.

The Monfalcone area in north-eastern Italy (total population, about 60,000) is a small industrial district in which shipbuilding is the main industry. We examined thoracic cavities for hyaline pleural plaques and routine lung sections for asbestos bodies in 1765 necropsies performed at Monfalcone Hospital. In 553 cases, we also isolated and quantified asbestos bodies in the lungs (Smith-Naylor's method). Occupational histories were obtained from the relatives of 798 patients. The prevalence of pleural plaques was significantly higher (p less than 0.001) among residents of the Monfalcone region (73.6% of men, 26.7% of women) than among nonresidents. Similarly, asbestos bodies were found more frequently in lung sections from residents. A good correlation was observed between pleural plaques and the asbestos body content of the lung (Spearman's correlation coefficient, 0.53). Different occupational groups showed very marked differences in the prevalence of plaques in general, in the prevalence of large plaques and in the numbers of asbestos bodies in the lung. Subjects who had worked in the shipyard or in a sodium carbonate factory had the highest indices. Exposure to asbestos had occurred at work for the large majority of men for whom data on occupation had been collected and through domestic contacts for the large majority of women. In a small portion of cases, environmental exposure could not be excluded as the cause of the objective signs. Pleural plaques, the asbestos body content of the lungs and occupational history must be considered together in monitoring exposure to asbestos in a given geographical area.

Thrombocytosis in malignant pleural mesothelioma.

The prevalence of thrombocytosis (defined as a platelet count above 400,000/mm3 in at least two examinations) and the prevalence of thromboembolism were retrospectively investigated in a series of 41 patients with malignant pleural mesothelioma and in 40 subjects with non small cell lung carcinoma. All the patients were examined at necropsy. The mesothelioma patients showed a higher prevalence of thrombocytosis (56.8% vs 24.2%; p less than 0.01). However, the prevalences of thromboembolism were similar in the two groups of patients (36.6% and 32.5% respectively). Among those with mesothelioma the prevalence of thrombocytosis varied widely from one histological type to another (76.9% in mixed type, 57.1% in the epithelial, and 30% in the sarcomatous type), the difference between mixed and sarcomatous being statistically significant (p less than 0.01). Moreover, the mesothelioma patients of under 70 years had thrombocytosis more often than those over 70 (80% vs 29.4%; p less than 0.01).