The Philadelphia Pulmonary Neoplasm Research Project. Symptoms in occult lung cancer.

In a prospective study of 6,027 older men screened every six months for ten years by means of chest photofluorograms and questionnaires regarding symptoms, 121 developed lung cancer after the first examination. Eighty-five men with lung cancer had the opportunity to be screened eight times before the tumor was detected by chest x-ray film, but only 33 actually reported that often. These 33 men were compared with matched controls for symptoms before the neoplasm was detected radiologically. The common symptoms of expectoration and chronic cough showed a significant increase in frequency over time in the cases of cancer, while only expectoration showed a slight increase in the controls. Uncommon symptoms more suggestive of lung cancer (hemoptysis and worsening cough) occurred in only four men prior to detection of cancer. Symptoms are seldom useful in the detection of occult lung cancer, but the appearance of expectoration and chronic cough in older male smokers should raise a suspicion of this disease.

Mortality of brain tumors among asbestos insulation workers in the United States and Canada.

Death resulting from brain tumors among workers in the petrochemical industry have called attention to the possibility that these neoplasms may be the result of occupational exposure to carcinogens. We have examined the experience of a cohort of 17,800 insulation workers known to be at significant increased risk of cancer at a number of sites (lung, mesothelioma, gastrointestinal, oral cavity, pharyngeal, larynx, renal) to ascertain whether their asbestos exposure also increased their risk of brain tumors. From 1967 to 1979, there were 24 deaths from primary brain tumors in this cohort, somewhat more than were anticipated (18.0 such deaths were expected based on U.S. general population data, and 20.5 if smoking was taken into account). The excess was not "statistically significant" at the 5% level although this does not rule out the possibility of an etiological association. It was of interest that the observed excess was concentrated (about twice expected) among insulators in the younger ages (those under 50) and during the early period after onset of work (15-24 years), in contrast with age distribution and latency in other asbestos-associated neoplasms. This may have relevance to theoretical concerns about questions of initiation and promotion in the etiology of cancer, particularly with regard to brain tumors.

Mortality experience of a cohort of vinyl chloride-polyvinyl chloride workers.

These data are derived from early follow-up of individuals exposed for 5 or more years to vinyl chloride in a polymerization facility. At least 17 percent of the deaths that occurred were causally related to exposure to vinyl chloride. Longer periods of observation are required to provide information concerning the full spectrum of vinyl chloride-induced malignancies and their incidence among exposed workers. These data speak for the need to prevent exposure to vinyl chloride and for surveillance and early disease detection of those who have experienced vinyl chloride exposures in the past.

Long-term mortality experience of chrysotile miners and millers in Thetford Mines, Quebec.

Among a cohort of 544 men with at least 20 years of employment in chrysotile mining and milling at Thetford Mines, Canada, 16% of the deaths were from lung cancer and 15% from asbestosis. The excess over expected deaths from these causes account for 43 of 178 deaths in the group. The risk of death of asbestosis, at equal times fron onset of exposure, is very similar in miners and millers, factory workmen and insulators. The ratio of observed to expected deaths from lung cancer is similar in the miners and millers and factory workers, but higher in insulators. The risk of death of mesothelioma in miners and millers is decidedly less than the other two groups. The exact causes of the reduced risk in this category are not yet completely clarified.

Amosite mesothelioma in a cohort of asbestos workers.

A cohort of 820 asbestos workers with a short duration of exposure to amosite between 1941 and 1945 was followed. These men were alive five years after starting work and were observed until 1988. Seventeen cases of malignant mesothelioma (eight pleural, nine peritoneal) were found. The mean age at the onset of exposure was 33 years for men with pleural mesothelioma and 30 years for those with peritoneal mesothelioma. Chest pain was the main symptom in pleural mesothelioma and abdominal pain in peritoneal mesothelioma. Open lung biopsy was the most useful diagnostic approach for pleural mesothelioma, whereas for peritoneal mesothelioma it was exploratory laparotomy. Pleural patients died of pulmonary insufficiency, and peritoneal patients of wasting and inanition. In both groups the death certificate diagnosis was less accurate than the clinical diagnosis at death. The mean survival was 12.5 months from first symptom to death for the pleural group and 5.4 months for the peritoneal group.

Mortality experience of styrene-polystyrene polymerization workers. Initial findings.

A group of 560 individuals has been identified as employed on 1 May 1960 with at least five years seniority in a plant manufacturing styrene and polystyrene. In this plant workplace exposures included styrene, benzene and ethylbenzene, among other materials. All of the 560 individuals have been traced through 1975 and their vital status determined. Expected and observed deaths, by cause, were determined from 1 May 1960 or the tenth anniversary of employment in the plant through 31 December 1975. Over this relatively short period of time a deficit of deaths compared to that of the general population was observed (106.41 expected versus 83 observed). Among the 83 deaths, one was of leukemia, one of lymphoma and an additional death was accompanied by leukemia. A review of 361 additional death certificates revealed five additional cases of leukemia and four of lymphoma. The available information from the limited follow-up in time of the time of the cohort and from the randomly collected death certificates, while suggestive of a possible risk, is not definitive.

Age at exposure versus years of exposure.

The pattern of incidence rates according to age for many forms of cancer has been found to be in reasonable accord with the equation or some modification of it: It = btk, where It is the incidence rate at age t, and b and k are constants. An alternative equation postulates that the risk of cancer is determined not by the age of a person but by the length of time exposed to a carcinogenic agent: It = b(t-w)k, where t-w represents the "effective exposure" between first exposure and clinical evidence of cancer. Mesothelioma rates in asbestos insulation workers were strongly related to time from onset of exposure regardless of age at first exposure. However, the same pattern was not evident for lung cancer mortality in the same workers compared with blue collar worker controls from the American Cancer Society Cancer Prevention Study I. Lung cancer mortality by attained rates and by duration of smoking were shown for current smokers of cigarettes only for the Cancer Society study, classified by age at which they started smoking. Lung cancer results were also given for men who never smoked regularly.

Evaluation of selection bias in a cross-sectional survey.

Selection bias is inherent in all occupational cohorts. Selection bias at entry has long been known and is commonly referred to as a "healthy worker effect." Less well appreciated is selection during the life of a cohort resulting from life-style factors (e.g., cigarette smoking); aging with accompanying chronic diseases, economic and demographic circumstances; and diseases that might result from exposures suffered by the cohort being studied, that influence whether individuals remain in a trade. These factors weigh differently at different times. Thus, at any point in time, "surviving" members of a cohort reflect an amalgam of selection factors. When such groups are studied in cross-sectional surveys there can be uncertainty whether clinical, radiological and physiological findings are necessarily representative for the trade or occupation as a whole. We analyzed the results of a large clinical field survey of long-term asbestos insulation workers to investigate whether the non-participants differed substantially from those who were examined. Five thousand three hundred and fifty-five (5,355) men, of an initial cohort of 17,800 established January 1, 1967, had reached 30 or more years from onset of their work by July 1, 1981. All were invited to come for examination. Two thousand and seventy-seven (2,077) came, and 3,278 did not. We questioned a sample of 1,393 non-responders to see why they failed to appear. The answers did not give evidence of significant health-related selection influence. Sickness only infrequently kept them away. We then followed both groups--those examined and those not examined--to the end of 1987 for their mortality experience. There was no great difference. The non-responders had somewhat fewer deaths overall and proportionately fewer of asbestos-associated cancers, such as mesothelioma and lung cancer. The results indicated that, in this cohort, there did not seem to be health-related selection bias that determined whether or not cohort members responded to invitations for examinations.

Use of death certificates in epidemiological studies, including occupational hazards: variations in discordance of different asbestos-associated diseases on best evidence ascertainment.

There is extensive information on discordance in general between accuracy of medical diagnoses on death certificate categorization of cause of death and available clinical and histopathological data. This is as true for occupational disease as for other conditions. But occupational illnesses bear a special problem. Discordance is not equal across the board--it may vary with each occupationally related disease, and no single formula can be applied. It may be high for angiosarcoma and low for acute hydrogen sulfide poisoning, low for bladder cancer, high for unsuspected methyl mercury poisoning. We have found that for one agent--asbestos--there were different rates of discordance for different asbestos-related diseases (e.g., lung cancer, mesothelioma, asbestosis, kidney cancer) among 4,951 deaths studied prospectively from 1967 to 1986. Caution is therefore required before accepting generalizations concerning (unstudied) discordance in occupational mortality studies, and in their use in risk assessment models.