Document J0nN9zja6rYLGe4ODazxpDOa

Jan76 # TexcfsMedicinel PLAINTIFFS EXHIBIT ! SH-1903 as bes tos (asbes'tos, az-), n. 1. Mineral, a. a fibrous amphibole, used for making incombustible or fireproof .articles, b. the mineral chrysolite, similarly used. 2 a .fabric woven from asbestos fibers, used for theater cur tains, firemen's gloves, etc. 3 Theat. a fireproof cur tain. Also, asbes'tus. [t. L, t. Gk.: unquenchable; r. ME asbeston, t. OF] --bestine (&s bes'tYn, Hz-), adj. DPMC-01771 ## Reprinted from Texas Medicine, January, 1976, Vol. 72, No. 1, pp. 39-43 Sputum cytopathological findings in former asbestos workers S. Donald Greenberg, MD; George A. Hurst, MD; William T. Matlage, MD; Charles S. Christianson, MD; Irby J. Hurst, MD; Linda C. Mabry, CT Cigarette smoking asbestos workers con stitute a high-risk group for the potential development of lung cancer. The Tyler Asbestos Workers Program was begun in July 1974 to examine 890 former asbes tos workers, approximately 90% of whom are cigarette smokers. As of April 1975, 456 former workers had been studied by sputum cytopathology; 217 (48%) were found to have mild squamous epithelial atypias, 20 (4%) severe atypias, and 1 (0.3%) malignant cells of a squamous carcinoma. Sputum cytopathology has been found to be an excellent, simple, noninvasive, painless, and inexpensive means of early detection of premalignant and malignant lesions of the lungs. One-third (33%) of these former as bestos workers had ferruginous bodies in their sputum. The ferruginous bodies were most numerous in aerosol-induced sputa specimens and could be readily identified by the routine Papanicolaou stain. Introduction The Tyler Asbestos Workers Program has been developed for former asbestos workers in order to provide them the most up-to-date care for the early detection and treatment of pulmonary diseases, par ticularly carcinoma. Approximately 90% of these men are also cigarette smokers, and this along with their previous occupa tional asbestos exposure renders them 90 times more likely than the general popu lation to develop carcinoma of the lung.1-2 The cohort for the program is composed From the Department of Pathology, Baylor College of Medicine, and the East Texas Chest Hospital, Tyler, Texas. Supported in part by Contract No. l-CN-45066 of the National Cancer Institute, Division of Cancer Control and Rehabilitation to the Texas Chest Foundation. of 890 former amosite asbestos workers, most of whom still live within a 150-mile radius of Tyler, Texas. The plant operated between 1954 and 1972. The program began in July 1974, and is ongoing. Each former worker is scheduled for a complete interview, physical examination, and lab oratory diagnostic studies including com plete blood count and urinalysis, roent genogram of the chest, electrocardiogram, spirometry, and sputum cytopathology which serves as the heart of the program. Through April 1975, 1,184 sputum speci mens from 456 workers had been studied and the results serve as the basis of this report. Material and Methods Sputum is collected by both aerosol inhalation duringthe initial clinic visit and early morning cough at home. All sputa are collected directly into 60% alcohol which serves as an instant fixative. Three sequential early morning home-col lected sputa are mailed to the cytopatho logy laboratory and pooled into one. Spu tum induction is carried out by transoral inhalation of a few breaths of an ultrasonic aerosol mist of 8% solution of sodium chloride in water. After inhaling as few as three to five breaths, the patient yields an adequate specimen which is collected directly into 60% alcohol in the sputum container. The sputum specimens are poured into a Petri dish and the cytotechnologist, using curettes, selects out portions of cellular aggregates, debris, and particulate matter and transfers them onto four prelabeled microscopic slides which have been coated with a thin layer of albumin. The cellular material is spread thinly and evenly over the slide by a sec ond slide which is not albumin coated. The DPMC-01772 008289 slides to be stained are then placed in 95% ethyl alcohol in a Coplin jar and subsequently stained in the routine man ner by the Papanicolaou technique. The remainder of the specimen is utilized for preparation of a cell block. The sediment for the cell block is placed into a tissue embedding bag, passed through the rou tine tissue fixatives, and embedded in paraffin. The paraffin blocks of the sedi ment are sectioned and stained with hema toxylin and eosin and Prussian blue for iron. Screening of the Papanicolaou-stain ed sputum smears averages five to seven minutes per slide. Black ink dots are placed by atypical cells and green ink dots by ferruginous bodies. The total number of ferruginous bodies per specimen (four slides) is reported as follows: few, 1 to 14; moderate, 15 to 29; and many, more than 30. For quality control, the cytopathology slides of 10% of all negative sputa specimens are rescreened. The sputa specimens are reported as unsatisfactory (saliva), no atypia, mild atypia, severe atypia, and positive for carcinoma. Free alveolar macrophages must be identified in order for the speci men to be considered adequate; other wise it is presumed to be unsatisfactory. Mild atypias include squamous metaplasia and mild dysplasias. Severe atypias in clude moderate and severe dysplasias. The term ``dysplasia" is used to imply dyskaryosis. The squamous metaplasia and the dysplasias are thought to be re versible atypias of the bronchial epitheli um. ``Positive for carcinoma" includes both carcinoma in situ and invasive carci noma. We are applying this nomenclature of descriptive terminology to represent the progression of epithelial atypias from the mildest change of simple squamous metaplasia to the development of frank squamous carcinoma. Results Ferruginous bodies have been found in the sputa of approximately one-third of the former asbestos workers. Less than 1. Photomicrograph of sputum showing a dumbbellshaped ferruginous body. Note the adjacent cluster of free alveolar macrophages. Papanicolaou stain, X 260. 2. Photomicrograph of sputum showing a lance shaped ferruginous body. Papanicolaou stain, X 260. [2] DPMC-01773 LAM 008290 %t i 1 % of those tested have failed to produce covered, the carcinoma was considered i satisfactory specimens. Thus far, only to be unresectable and the operation was one former worker has been found to have terminated. The patient refused both radi cells positive for squamous carcinoma in ation therapy and chemotherapy, and his sputa. He was a 76-year-old Cau died of probable ventricular fibrillation casian man who had worked in the as six months after diagnosis. Necropsy re bestos plant from 1954 to 1961. He was vealed the squamous cell carcinoma of also a chronic cigarette smoker of 180 the bronchus intermedius (Fig 5) with pack years.* Initial sputum examination metastases to right bronchial lymph nodes, disclosed both ferruginous bodies (Figs right visceral pleura, and pericardium. 1, 2) and malignant cells of squamous Asbestosis with interstitial fibrosis was carcinoma (Fig 3). A roentgenogram of present in both lower lobes of the lungs the chest showed reticular infiltrates con (Figs 6, 7) and centrilobular emphysema sistent with interstitial fibrosis in the low was present in the upper lobes. er lobes of both lungs; however, no local Twenty former workers (4%) have had izing lesion was seen. Fiberoptic bron sputa with severe epithelial atypias, and choscopy revealed an ulcerating lesion of 48% have had mild atypias, the majority the bronchus intermedius which, by brush of which are squamous metaplasia. ing, washing, and biopsy, was positive In the group of former workers whose for squamous carcinoma (Fig4). Media sputa has yielded ferruginous bodies, the stinoscopy and other routine laboratory aerosol method of sputum specimen in studies showed no metastasis, and a right duction has provided for more frequent exploratory thoracotomy was performed. recovery of the bodies than spontaneous When visceral pleural metastases were dis- sputa alone. Also, by our methods of quantitation, the aerosol-induced sputa Three packs of cigarettes/day/50 years. specimens contain a larger number of Ii 3. Photomicrograph of sputum revealing two large 4. Photomicrograph of the tissue preparation of the bronchial biopsy. Note nest of malignant cells malignant cells of squamous carcinoma. Papani of squamous carcinoma. Hematoxylin and eosin j colaou stain, X 260. stain, X145. 1i [3] DPMC-01774 LAM 008291 5. Gross photograph of a coronal section of the right lung. Note the irregular white squamous carcinoma (arrow) involving the bronchus intermedius. 6. Gross photograph of coronal section of right lung. There is diffuse interstitial fibrosis of the lower lobe (arrow). ferruginous bodies. This appears to be even more significant when one considers that the aerosol-induced specimen is a single specimen, while the spontaneous specimen is a pool of three. The sputa specimens with severe epithelial atypias were equally distributed between aerosolinduced and spontaneous specimens. Discussion While the first cases of pulmonary fibrosis caused by asbestos inhalation were report ed in 1929,3 and the first case of lung cancer associated with asbestos in 1935,4 it was not until 19682 that epidemiologic studies established the role of asbestos in the development of lung cancer in ciga rette smoking asbestos workers. The Tyler asbestos plant was in opera tion between 1954 and 1972, employing 890 men who processed amosite asbestos mined in South Africa. For many years, sputum cytopathology has been known to be a useful clinical laboratory means of early detection and diagnosis of lung cancer, yielding positive results in up to 80% of cases.6 Only re cently, however, has the role of fiberoptic bronchoscopy been established in the localization of superficial endobronchial carcinomas. Serial roentgenograms of the chest will not permit truly early detection of lung cancer because such a cancer must grow and double for more than five years before it becomes large enough to be seen by the radiologist.7 Thus far, in the Tyler Asbestos Workers Program, only one of 456 former workers has had a sputum cytopathologic diag nosis of squamous carcinoma. Although the roentgenogram of this man's chest showed no localizing lesion, the cancer found by fiberoptic bronchoscopy in the bronchus intermedius had already metas tasized to the visceral pleura and was nonresectable for cure. Twenty of these 456 former workers have severe atypia of epithelial cells in their sputa. Close clinical and cytologic follow-up of these 20 patients is presently in progress. As the program continues, all 890 former workers will be examined and reexamined [4] DPMC-01775 LAM 008292 routinely at six-month intervals or more often depending upon cytopathologic and clinical findings in each case. As yet, no statistical correlations can be made between the association of fer ruginous bodies (Fig 8) and atypical epithelial cells in the sputa, but in the future, as more data are gained, this will be of great interest. Even now, one can state that the finding of ferruginous bodies in such numbers indicates significant as bestos exposure, because from 1972 to 1975, not one such body had been found in similar cytopathologic examinations of 12,000 sputa specimens from the general public in the Cytopathology Laboratory of the Harris County Hospital District, Hous ton, Texas. Conclusion Sputum cytopathology is an excellent, simple, noninvasive, painless, and inex pensive means for early detection of ma lignant and premalignant lesions of the lung, and no special techniques are neces sary for the identification of ferruginous bodies. 7. Photomicrograph of tissue preparation from right lower lobe of lung showing a deeply stained fer ruginous body with associated free alveolar macro phages and fibroblasts. Prussian blue stain, X170. > References 1. Setikoff, IJ, Churg J, Hammond EC: Asbestos ex posure and neoplasia. JAMA 186:22-26, 1964. 2. Selikoff IJ, Hammond EC, Churg J: Asbestos ex posure, smoking and neoplasia. JAMA 204:106-112, 1968. 3. Cooke WE: Fibrosis of the lungs due to the in halation of asbestos. Br Med J 2:578-580, 1929. 4. Lynch KM, Smith WA: Pulmonary asbestosis: car cinoma of lung in asbestos-silicosis. Am J Cancer 24:56-64, 1935. 5. Russell WO, Neidhardt HW, Mountain CF, et ai: Cytodiagnosis of lung cancer. A report of a four-year laboratory, clinical, and statistical study with a review of the literature on lung cancer and pulmonary cytology. Acta Cytol 7:1-44, 1963. 6. Manals-Estrelia P, Fry WA: Cytologic diagnosis of lung lesions by bronchial brushing. Ann Clin Lab Scl 3:289-295, 1973. 7. Fontana RS: The Philadelphia Pulmonary Neo plasm Research Project. JAMA 225:1373-1374, 1973. Dr. Greenberg, Director of Cytopathology, De partment of Pathology, Baylor College of Medi cine, Texas Medical Center, Houston, Texas 77025. Drs. G. A. Hurst, Matlage, Christianson, I. J. Hurst, and Ms. Mabry, Tyler Asbestos Workers Program, East Texas Chest Hospital, Box 2003, Tyler, Texas 75701. (The authors wish to acknowledge the contributions of the autopsy tissues by Dr. W. T. Sparrow from the labora tories of Dr. V. V. Gonzalez and associates of Tyler, Texas.) 8, Artists sketch of a club-shaped ferruginous body with associated free alveolar macrophages. 'Aft- [5] DPMC-01776 LAM 008293 Editorials THE SMALL BEAUTIFUL TIME BOMB The asbestos fibril is such a tiny thing--so tiny that 1 million of them laid side by side will measure only an inch. It resists time, water, acids, fire, and body fluids. And these proper ties make it a time bomb. It enters the body through the nose, throat, or mouth. It lodges in the lung, pleura, pericardium, peritoneum, or gastrointestinal tract. This beautiful mineral (that's what shimmers in tiger's-eye) lies quietly ticking in the body. It may take 20 years for the explosion to occur, but that is not long for asbestos. A Bantu child is made to work filling jute bags with amosite asbestos. Before the age of 12 he will die of pulmonary fibrosis (asbestosis) and cor pulmonale. A native woman has lived near an asbestos mine for 15 years. A mesothelioma develops in her pericardium; the pathologist finds asbestos fibrils (ferruginous bodies) in the resected specimen. In England, workers with more than 20 years' experience in an asbestos-textile factory have 11 times as much cancer as men in the general population. A housewife in Texas gets a chest x-ray. Her doctor finds scars in her lungs and pleurae. No, she never worked with asbestos, "... but my husband has been an insulator (using as bestos) for 20 years. His clothes sure are dusty, and I always shake them out before I wash them." In Pennsylvania, 42 people died of mesothe lioma between 1958 and 1963. Ten of the 42 had known exposure to asbestos. The other 32 were relatives of the workers, lived in the vicin ity of an asbestos factory, or had some minor exposure to asbestos. Now we come to Tyler, Texas, where an as bestos insulation plant opened in 1954. By the time it closed 18 years later, it had employed 890 workers who were exposed to asbestos (amosite) for varying periods. In this issue of Texas Medicine, Greenberg and his co-workers present their account of a continuing evalua tion of the health of these men. This study re ports the results of sputa examinations of 456 former employees. Twenty (4% of those tested) had sputa with severe epithelial atypias, and 217 (48%) had mild atypias of squamous metaplasia. One worker's sputum specimen was reported to be positive for bronchogenic car cinoma. True, one person with lung cancer out of 456 examined is not impressive, but that is only the first sputtering of the time bomb. Usually, 10 to 20 years pass before asbestos affects the body. Pleural effusion and calcifica tion, pulmonary fibrosis, lung cancer, intestinal cancer, and mesothelioma eventually appear. As time passes and the bomb explodes, more of the workers will succumb to incurable di seases--fibrosis and cancer. Deplorable! Were the asbestos workers told their jobs were dangerous? Didn't they know of the danger to others in their households from the asbestos dust that they brought home? Were they provided rooms in which to change clothes? To all of these, the answer is, "No." Was industry informed? From the moment the alarm was sounded at the Tyler plant in 1962 to the day of its closing ten years later, the management denied that asbestos was dangerous. Its scientists and physicians denied that the concentration of asbestos to which the workers were exposed was toxic to the body. The Industrial Hygiene Foundation of America refused to declare the plant safe. The company, nevertheless, fought the Department of Labor and then the Bureau of Occupational Safety and Health. After a long, hard struggle, the plant was forced to close. Whose responsibility is it to keep the air clean of asbestos? The government is ponder ous and irresolute. Industry is more interested in staying in business. To quote Paul Brodeur, science writer for The New Yorker magazine, "The responsibility is clearly up to men and women... who are the independent medical and scientific community. Only you, after evalu ating the problems and after apprising your selves of the dangers of asbestos, can say, `No, I will not countenance such a situation.' " Daniel Jackson, MD, Houston. Quotation from Mr. Brodeur used with permission. COPYRIGHT 1976, TEXAS MEDICAL ASSOCIATION, AUSTIN, TEXAS [7] DPMC-01777 Lam 008294