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

Unselected autopsy findings of nonagerians reviewed by the authors in the last 20 years, confirm a decline in malignant tumors at very old ages. Two main factors are thought to be responsible for this evidence: a less aggressive biological behavior of cancer in the oldest old; the crucial role played by comorbidity as the cause of death.

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.

In Italy, 28% of all deaths are due to cancer. Of the 15% of the population that is 65 years or older, 65% of cancer deaths occur in men and 69.5% in women. The proportional mortality and incidence of cancer in Italy varies with increasing age. All patients over 65 years are found to be at increased risk for intestinal cancers. In older men, the proportion of lung and urinary tract cancers decreases, while prostate, intestinal and gastric cancers increases. Prostate cancer predominates in men over 85 years and intestinal and gastric cancers are relatively more common than lung cancer. In women over age 74, intestinal cancer is most common. Breast, genital and lung cancers decrease rapidly with age, while stomach, liver, gallbladder and pancreatic cancers increase with age. The ratio of incidence to mortality for all cancers studied is shown to equalize with increased age, the probable result of lower hospitalization rates and less adequate cancer therapy for the elderly.

A case-control study of lung cancer and occupational exposure was conducted in a coastal area of Northeastern Italy where metallurgical and mechanical industries, docks and shipyards are located. Cases comprised 756 men who died of primary lung cancer in a 5-year period. Controls comprised 756 male subjects dying from other causes during the same period. Occupational exposures to lung carcinogens were assessed according to a job title-based approach, using two separate lists of industries/occupations recognized as being causally associated (list A) or suspected of being causally associated (list B) with lung cancer in humans. Exposure to asbestos was classified as absent, possible, or definite. After adjustment for cigarette smoking and place of residence, a significant association was found between lung cancer and occupations in both list A [relative risk (RR) = 2.25, 95% confidence interval (CI) = 1.68-3.03] and list B (RR = 1.33, 95% CI = 1.03-1.71). A significant excess risk was found for workers with definite exposure to asbestos as compared to those with no exposure to lung carcinogens (RR = 1.98, 95% CI = 1.42-2.75). Among occupations with recognized exposure to lung carcinogens other than asbestos, a significant excess risk for lung cancer was observed in iron and metalware workers. In occupational groups with definite exposure to asbestos, elevated risk estimates were found for shipyard workers, dockworkers, carpenters, and electricians. The combined effect of smoking and asbestos was found to be compatible with that expected under a multiplicative model. The overall population-attributable risk (ARp) for cigarette smoking was found to be 87.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the relationship between occupation and lung cancer, a case-control study was performed in the province of Trieste, Italy, where metallurgical and mechanical industries, dock activities and shipbuilding and ship repairing are predominant. Through the local Cancer Registry, pathology records of 938 men who died of primary lung cancer (ICD 162) in a five-year period were examined. Residential, smoking and occupational histories were obtained from interviews of next of kin of 756 cases and 756 age-matched male controls (+/- 2 years). Occupational exposures to lung carcinogens were assessed according to a job-title based approach, identifying industries/occupations with well-recognized lung carcinogen exposures (list A) and industries/occupations with suspected lung carcinogen exposures (list B). Exposure to asbestos was classified as absent, possible or definite. After adjustment for cigarette smoking (four levels) and residence (three levels), a significant association was found between lung cancer and occupations in list A (RR = 2.28, 95% CI = 1.70-3.07) and in list B (RR = 1.33, 95% CI = 1.04-1.71). A significant excess risk was found for workers with definite exposure to asbestos when compared to those with no exposure to lung carcinogens (RR = 1.99, 95% CI = 1.43-2.76). A very high relative risk was observed among heavy smokers with definite exposure to asbestos (RR = 42.8). A stratified analysis showed that the combined effect of asbestos and smoking was compatible with that expected under a multiplicative model. The overall attributable risk in the population (ARp) for cigarette smoking was found to be 87.6%. The ARp fraction for occupations with well-established exposures to lung carcinogens (list A) was 16.2%. The ARp fraction increased to 25.5% (85% CI = 1.4-34.6) when occupations with suspected exposure to lung carcinogens (list B) were included. The ARp fraction for possible or definite exposure to asbestos was 20.1% (95% CI = 11.6-28.6).

Between 1979 and 1988, 432 cases of previously untreated laryngeal cancers were histologically diagnosed at the Institute of Pathological Anatomy of the University of Trieste. Of these cases, 192 were supraglottic and 182 glottic cancers. The overall crude incidence was 31.06 0/0000 in males and 2.29 0/0000 in females, with a male/female ratio of 10.2:1 for supraglottic cancers vs. 20.4:1 for glottic cancers. Our incidence values for laryngeal cancer, and supraglottic lesions in particular, are similar to those recorded in France, Spain and other areas of Italy, i.e. in nations where wine production and consumption is very high. The 3-year adjusted survival rate was 45.7% for supraglottic and 83% for glottic cancer patients. Subjects with supraglottic cancer often had a poor prognosis because of the high frequency of cervical lymph node involvement, recurrences and visceral metastases; cancers of the aryepiglottic folds presented the worst clinical evolution.

From January 1, 1968 to December 31, 1984, 31,955 autopsies were performed at the Department of Pathology of the University of Trieste. Of these 16,521 were male and 15,434 female which covered about 70% of the population who died in the area over the recent years. Hepatocellular carcinoma (HCC) associated with liver cirrhosis was encountered in 441 cases (380 males and 61 females, M:F ratio 5.8:1) with an overall occurrence of 1.4% in the autoptic population. On the contrary and in the absence of chronic liver disease HCC was only observed in 0.3% of the cases (45 males and 16 females, M:F ratio 2.7:1). Liver cirrhosis accounted for 10% of autopsies (2099 males and 1104 females, M:F ratio 1.8:1). A 15% of cirrhosis was associated with HCC, indicating that major attention should be paid to cirrhotic patients, in particular males after the 5th decade of life. The year distribution of HCC and cirrhosis was fairly constant during the period of time considered. These data suggest that: i) HCC is common in Italy; ii) in the vast majority, HCC occurs in the presence of cirrhosis; and iii) HCC appears to be a rather late disease as it does not reduce the life expectancy of cirrhotic and control populations. Since reliable, nationwide epidemiological data are not available in Italy, it is not known whether these data represent a local realty or whether they may be extrapolated to the entire country. Cooperative and prospective studies appear appropriate in investigating possible geographical differences in HCC distribution and permit a better understanding and prevention of the disease.

Fixed and paraffin-embedded tissues from pathology department archives can be available for RNA expression analysis. In this report, we show that RNA isolated from surgical or autopsy tissues, routinely processed by fixation and paraffin embedding, is not completely degraded. RNA fragments around 100-200 bases in length are still present even in organs late fixed and very rich in RNase, such as the pancreas. Here we describe a general protocol to obtain RNA from single 6-8-microns tissue sections. The RNA extracted can be analyzed for the presence of specific sequences by reverse transcription and amplification with the PCR. We studied the retinoblastoma gene expression in 38 human pancreas specimens from surgical or autopsy origin.

We have compared autopsy results with the diagnosis reported on 759 death certificates for gynaecological cancers. High levels of discrepancies were noted for all sites. Surprisingly, complete agreement between death certificates and autopsy reports was found for only 30% of cervical and corpus tumours and for 50% of ovarian tumours. This low level of agreement was due partly to the poor quality of death certificates of older women. No difference in accuracy was found over the 15-year period considered. The most obvious causes of the discrepancies were of two types. The first was erroneous interpretation of codes; confusion between 180 (cervix) and 182 (corpus) was very frequent. The second type was associated with clinical factors, such as confusion of anatomical site, adjacent organs or metastases being diagnosed as primary tumours. A relatively frequent cause of inaccuracy on death certificates was consideration of patients who had been cured of a cancer as having died of the disease.

We have studied the sorting and alteration of the thyroglobulin (tg) secreted by well-differentiated carcinomas using a group of anti-tg monoclonal antibodies. A previously described monoclonal antibody, specific for the hormogenic iodinated epitopes, shows that in carcinomas the iodinated tg is not secreted in the colloid as in normal glands but is accumulated in the cytoplasm of the cells. Separation of tg in a concanavalin A column, to isolate the correctly glycosilated protein, reveals that hormogenesis is present only in glycosilated tg with a correct final configuration. An other monoclonal antibody, specific for an epitope connected with the carbohydrate moiety of the tg, reacts with tgs from normal glands and from any thyroid lesion except tg from carcinomas. This tg of carcinomas presents an alteration in the oligosaccharide chains that can be detected by this antibody. The alteration is specific for malignant tumors and could be connected with the missing exocytosis of the iodinated tg in carcinomas.

The true risk population for uterine and ovary cancer have been studied, according to the prevalence of histerectomy and oophorectomy in the Trieste area female population. The calculation of the females at risk for these tumors permits to recalculate the incidence rates that are usually underestimated. This adjustment increases the rates in all genital tract tumors from 14% to 18%, but does not modify the relative frequency per age groups or the incidence in the temporal trends. An exception is represented from the uterine corpus cancer in which the correction of the population modifies the temporal trend for the age group over 60 years. The incidences tend in fact to increase significantly more after the adjustment.

Bilirubin and phthalein dyes are taken up by the liver via a carrier-mediated mechanism operated at least in part by bilitranslocase (BTL). Because they also undergo renal transport, the presence and function of BTL was investigated in rat renal tubular plasma membrane vesicles. Transport of sulfobromophthalein (BSP) was enriched in basolateral domain of plasma membrane and followed the distribution pattern of Na(+)-K(+)-ATPase but not of gamma-glutamyltransferase. BSP uptake was inhibited by addition of monospecific antibodies raised against hepatic BTL. As in liver vesicles, BSP transport was electrogenic, being greatly accelerated by addition of valinomycin in presence of an inwardly directed K+ gradient. Apparent Km of BSP transport was 17 +/- 2 microM (n = 3 expts), one order of magnitude higher than that measured in liver; however, Vmax was similar to that described in liver vesicles (429 +/- 18 nmol BSP.mg protein-1.min-1, n = 3 expts). Competitive inhibition was observed with both unconjugated bilirubin (Ki, 2.9 +/- 0.2 microM) and rifamycin SV (Ki, 76 +/- 10 microM), known competitors for hepatic BTL-mediated transport of BSP. Immunoblotting studies with anti-BTL monospecific antibodies revealed presence of a single positive band only in basolateral-enriched membrane fraction; its apparent molecular mass was 37 kDa, virtually identical to that of hepatic protein. Immunohistochemistry confined presence of BTL to renal proximal tubules (RPT) We conclude that BTL is present in basolateral plasma membrane of RPT cells. Lower affinity of renal, compared with hepatic protein, for substrates might explain the marginal role of kidney in plasma clearance of bilirubin and cholephilic dyes.

The Authors examined the epidemiological behaviour of endometrial carcinoma in the Province of Trieste from 1969 to 1980. In this period a European standard incidence of 14.33(0)/0000 was recorded. The most affected age group is 60 to 69, and the average age is 64 years. A clear increasing trend of this kind of neoplasia was recorded. This increase mainly occurs in younger age groups than those which presently are most affected.

The distribution of counts of asbestos bodies in lung specimens from 25 persons dying of fibrocaseous tuberculosis was essentially identical to that in age- and sex-matched control subjects. Although tuberculosis mortality has been elevated in the past in cohorts of asbestos workers, asbestos exposure at environmental levels found in a region with a history of heavy asbestos use appears to be unassociated with risk of tuberculosis. Potentiation of the risk of death from tuberculosis may require both a high risk of tuberculosis in the general community and intense personal exposure to asbestos.

The role of polyamines in cartilage is not known: they may be somehow related to the mechanism of calcification. In epiphyseal cartilage from calf scapulas, they are more concentrated in the ossifying area, where calcification takes place, than in the resting region. Spermidine is present in greater amounts than spermine and putrescine. Since ornithine decarboxylase (EC 4.1.1.17) is measurable only in the resting region of the tissue, it is in this area that polyamine biosynthesis occurs, while they accumulate in the ossifying area. Immunohistochemical evidence is obtained that only in the ossifying zone is spermidine extracellular. It is at this level that the matrix is rearranged to become calcified, and proteoglycans are dissociated and partially removed. The effect of polyamines on solutions of proteoglycan subunits has been studied in vitro by following variations of turbidity and viscosity. While in the presence of putrescine the specific viscosity decreases to asymptotic values, in the presence of either 30 mM spermidine or 2.5-10 mM spermine, the decrement is more marked. At the same concentrations, increase of the turbidity of proteoglycan subunit solutions was observed. Only spermidine showed the capacity of displacing proteoglycan subunits from a column of Sepharose 4B-type II collagen: at 15 mM concentration, about 90% of proteoglycans were removed from the column. Alkaline phosphatase activity, which plays an important role in calcification, is enhanced by spermidine and spermine. These results obtained in vitro support the hypothesis that polyamines may be related to calcification of preosseous cartilage.

The purpose of our study was to compare the ultrasound findings in malignant breast masses (which underwent biopsy) with their histological appearance. In our activity of breast sonography, we observed that the same histological type of breast cancer often shows a different ultrasonic image. The main difference concerns the sonic attenuation or increase through the neoplastic mass. The histological examination took into account the amount of stroma and cells and the architectural pattern of the lesion. Comparing these features with the ultrasonic image, it has been shown that sonic transmission is related more to the architectural pattern than to the fibrous content of the neoplastic tissue.

Metastasis to the uterus from distant primary neoplasms are rare: this report is an analysis of 20 cases. The primary tumors arose in the breast (12 cases), pancreas (3 cases), stomach (2 cases), lung (2 cases) and gallbladder (1 case). The corpus uteri (and namely the myometrium) is more often involved than cervix. The mean age of the patients is 71 years (range 42-84). Metastases caused abnormal uterine bleeding in only 2 cases; in the others cases no symptoms were observed and so they were unexpected autopsy findings.

The epidemiological behaviour of the invasive cancer of the uterine cervix in the Province of Trieste is analysed. During this study period, 488 cases of this neoplasia were diagnosed with an incidence rate standardized for the European population of 20.25 degrees/0000. This value is within the average ones recorded in other geographic regions. The age group which is most affected is that from 60 to 64 years. By analyzing the overall incidence rate of the first two years if compared with the last two years of our study period, a 29% decrease is recorded, with an annual average decrease of 2.6%. This value is one of the highest reported in the literature. This decrease is recorded in the age groups over 40, while no decrease is recorded in women under age 40.

In elderly males hormonal changes occur, that are believed to cause benign prostatic hyperplasia (BPH). These are decreased testosterone production, an increased testosterone SHBG and a slightly increased estradiol production. Liver cirrhosis in males causes similar endocrine changes. We carried out a post mortem study evaluating the prostates of 51 men who died with liver cirrhosis compared with a similar group without any hepatic disease. The occurrence of BPH in cirrhotic subjects was diminished and delayed compared to total population. Furthermore in cirrhotic men BPH is more common as early nodular hyperplasia (early stage) or stromal hyperplasia (suggesting estrogenic prevalence), while in the general population stromal and epithelial hyperplasia (androgenic stimulation), were almost equally present.