Document KGq2kdOORZBaznRN4JzK3NVp2

Gastrointestinal Carcinoma and Occurrence of Pleural Plaques on Pulmonary X-Ray Gunnar Hillerdal, M.D. In many studies of persons exposed to asbestos an overrepresentation of gastrointestinal carcinomas has been found. So called "pleural plaques" (PP) are hyaline or calcified formations of the parietal pleura which are caused mainly by exposure to asbestos. If sufficiently large, they can be seen on a chest roentgenogram. It was therefore decided to investigate whether in a population of patients with gastrointestinal carcinoma these forma tions were more commonly found on the chest roentgen ograms than would be expected. Subjects and Methods . A list of all patients from the county of Uppsala with gastrointestinal tumors (esophagus, stomach, small and large intestine and rectum) diagnosed during the five-year period from 1968 to 1972 was obtained from the Swedish Cancer Registry. All cancers are reported to this registry as a matter of routine both by clinicians and by patholo gists, and the register is considered to contain 97 to 100% of all diagnosed cases. The latest available data year from this registry was 1972. Miniature chest films'of the pa tients were sought in the archives of the General Health Survey of the county. This health survey has been in oper ation since the early 1960s and all persons of age 15 and above living in the county are invited to take part every second to third year. The participation rate is between 65 and 75%. The miniature chest film is of very good quality, and in the author's experience pleural changes are just as easily diagnosed in these small films as in full size roent genograms. For every patient whose films were found, three controls were chosen. The archive is organized ac cording to date of birth and the controls comprised the nearest persons with a film taken the same year as the latest film available for the cancer patient (later films be ing left in the file) and of the same sex. Thus, all the con trols were born in the same year, usually in the same From the Department of Lung Medicine. University Hospital. Uppsala. Sweden. 806 month, and in many cases even on the same day as the patients. They were taken randomly from one or both sides of the patients in the archive (i.e., somewhat younger or older) and were examined by the author with out knowledge as to which films represented carcinoma patients and which did not . Only PP fulfilling the criteria in Table 1 were accepted."* For almost all male cases their occupation was stated on the card accompanying the x-ray, and this was recorded. Results . Male Cases. -- There were 482 men in the list from the Cancer Registry, 61 with benign lesions only (Table 2). Miniature films were found for 386 (80.1%) of them and thus there were 1,158 controls. The number of persons with PP among the tumor patients was 13 (3.4%) and among the controls 20 (1.7%j, the difference being signifi cant. at the 2% level (chi-square test). The distribution among the different gastrointestinal regions is given in Table 3. Female Cases. -- Of the 420 women in the Cancer Registry? 320 with chest x-rays were found, giving 960 con trols. Two women with PP were found, one patient and one control. No conclusions could be drawn from these findings. Discussion The etiology of the various forms of gastrointestinal cancer is far from clear. Epidemiological data, however, point to some external agent(s) as being responsible. Cancer of the colon, on the one hand, is common in Scot land, Denmark, Canada and New Zealand, while it is rare in Chile, Finland, Japan and Israel.1 On the other hand, cancer of the stomach is common in Finland, Chile, Japan and Iceland.2 2 If Japanese, who run the Japanese high risk of cancer of the stomach and low risk of cancer of the colon, move to the U.S. and in the process also modi fy their food habits, they will tend to have children with risks more similar to those of the U.S., i.e., the gastric Table 1. -- The Roentgenological Criteria* lor Definite Pleural Plaques Used in This Study. Table 2. -- Total Population Distribution by Gastrointestinal Region and Sex. 1. Bilateral Changes 2. Typical Changes, i.e., uneven, situated mainly in the flanks and the diaphragm. If only seen in the (tanks, at least 5 mm thick on a normal-sized chest x-ray. Oiaphragmal plaques, if the only find ing. not accepted unless bilaterally calcified 3. Clear costodiaphragmatic sinuses 4. Progression in a 5-year period if x-rays are available "All criteria must be fulfilled (except number 4, if no earlier x-rays are available) cancer rate will go down2 and the colon cancer will go up.4 Many investigations have revealed a higher rate than that expected for gastrointestinal cancers among persons exposed to asbestos. As early as in 1951 Cloyne5 reported 102 autopsy cases of asbestosis collected over some de cades, and there were eight cases of gastrointestinal cancer included among them even though the average age of the patients was only 35.5 years. In 1964 Selikoff, Churg and Hammond* reported on 632 insulation workers who had been followed from 1943 to 1962. Among them there were 29 with gastrointestinal cancer, while the ex pected number was 9.4. These workers have been fol lowed further, and in 1973, 41 deaths of gastrointestinal cancer had occurred against 13 expected, i.e., 2 to 3 times the expected figure.7 The time from first exposure to asbestos to diagnosis of the cancer was more than 20 years in most cases. Specifically, gastric cancers were six times as numerous as expected, and cancer of colon three times as numerous.* Mancuso,* in 1965, also found an approximately dou bled risk for asbestos workers in a U.S. plant manufactur ing asbestos brake linings, and Newhouse10 found a signif icant increase of gastrointestinal cancers in males in a London asbestos textile factory. In 170 male insulation workers from Belfast followed from 1940 to 1960, Elmes and Simpson" likewise found an increase in the incidence of gastrointestinal cancer, and in Russia Kogan et al13 reported the same. An increasing number of gastrointes tinal cancers with increasing exposure to asbestos has also been noted in Canada.11 A tendency to a higher mor tality has been found in Sweden'4 as well as in U.S. dis tricts with shipyards, where especially during World War II, asbestos has been used extensively.1* In reviews of the above articles and others, Schneiderman1* and Miller17 concluded that there are no doubts about the increased risk of gastrointestinal cancer among persons exposed to Esophagus Stomacn Small intestine Large intestine Rectum Total Male'*{6enign) Female (Benign) Male/Female 30 (2) 9 183 (3) 137 11 (0) 6 133 (14) 182 125 (32) 86 482 (61)' 420 (0) (1) (0) (10) (20) (31) 3.3 1.3 1.8 0.7 1.5 1.1 asbestos, and that the induction period is usually more than 20 years. The occurrence of PP may be regarded as indirect proof of exposure to asbestos. With strict roentgenolog ical definitions of PP (Table 1), 80% of PP carriers will readily admit to asbestos exposure, and of the rest a large portion will probably have been exposed unknowingly.'* Very few false positive cases will be found with these cri teria if comparison is made with the autopsy findings, but on the other hand a large portion will be missed." The cri teria have been used in earlier investigations and in one patient group with bronchial carcinomaTM and in one with laryngeal carcinoma21 a highly significant increase of PP carriers was found. Thus, if exposure to asbestos does have any influence on the occurrence of gastrointestinal malignancies, there ought to be a higher frequency among such patients than among controls. Since the oc currence of PP differs in different age groups, and the in cidence is rising," the controls are very important In the present investigation there were three controls of the same sex and age with a roentgenogram taken In the same year, and the films were scrutinized without knowl edge as to which represented cancer patients and which represented controls. The frequency of PP among the male controls, 1.7%, is similar to the expected value from 1976 in the county.20 Among the patients with gastrointes tinal cancer the frequency of PP was 3.4% and the differ ence is statistically significant at the 2% level. As for the different gastrointestinal regions, there was a tendency to wards higher figures for the esophagus and the stomach. Apart from the total figures, it was only for cancer of the stomach that the differences were statistically significant How does asbestos reach the gastrointestinal tract? The most plausible way Is, of course, by swallowing, and the major part of any inhaled dust deposited in the upper di gestive tract will be quickly transported to the gastroin testinal regions.22 Evans and Morgan and co-workers2124 showed that 30 to 68% of inhaled radioactively-labelled Table 3. The Distribution of All Male Patients with Available Chest Films ________ and Those with PP in Gastrointestinal Regions. Esophagus Stomach Small intestine Large intestine Rectum Total Number of PP Total (Benign) Observed (Benign) 21 (2) 1 (0) 148 (1) 6 (0) 8 (0) 0 108 (13) 3 (2) 101 (30) 3 (0) 386 (46) 13 (2) * - Significance on the 5% level (chi-square test) Journal of Occupational Medicine/Vol. 22, No. 12/December 1980 Expected 0.35 2.5 -- 1.8 1.7 6.6 Obs/Exp 2.8 2.4* -- 1.7 1.8 2* 807 asbestos dust will be deposited in the gastrointestinal tract in rats initially, and after 30 days more than 70% will have been excreted in the feces. Gloyne2' showed that asbestos bodies could be found in the feces of asbestos workers, and since it is hard to imagine asbestos body fornation taking place in the gastrointestinal tract, they must have come from the bronchi. Cunningham and asso ciates2* have shown that the amount of fecal asbestos is significantly increased among asbestos workers. Most of the ingested asbestos fibers traverse the entire tract, but some of them will probably penetrate into the intestinal cells. Webster27 fed asbestos to baboons and found a small portion of it later in their ashed gut. Westlake,2* on feeding rats with asbestos, found asbestos needles in their large intestine cells, and Storeygard and Brown2' found some fibers in rat jejunal wall one hour after asbestos in gestion. After injection into rat stomachs, chrysotile fibers could be isolated two to four days later from many or gans.10 Despite these findings, both Davis31 and Cross et ai,22 stated that asbestos fibers do not penetrate into the gastrointestinal cells. Other authors, however, believe such penetration possible.121114 In a long-term study Gibel and co-workersJ$ showed that rats which consumed asbestos daily had significantly more tumors than did control rats, including carcinoma of the kidney and lung, and papilloma of the stomach. In humans fibers have been demonstrated widely dis seminated in the spleen, liver, kidney and gastrointestinal tract,J`17 but these, of course, might have been trans ported there via the blood from the lungs. Chatel et al3* investigated 42 men occupationally exposed to asbestos and found asbestos fibers in the gastric fluid in five cases. Electron microscopic examination of biopsies obtained at gastroscopy in some of these men gave negative results, but in one case where the whole stomach was available for study after operation for a malignant tumor, many naked small fibers were found. Asbestos bodies are seldom found in the intestinal wall; Rosen et aP' found no such bodies in the colon of 21 patients with primary malignancies of the colon. There has been public anxiety that ingestion of asbes tos in food or drink can occur and lead to gastrointestinal cancer. Asbestos fibers can be found in small quantities in practically all kinds of beverages10 J` even in fresh, unpol luted water near asbestos deposits. Beer and wine are often passed through asbestos filters, and consequently asbestos fibers can be found in the finished products.40 Water polluted from asbestos mining operations or sim ple dumping of asbestos, or from being passed through asbestos pipes, has been shown not to be associated with a higher prevalence of gastrointestinal carcinoma, but the observation time might wefl have been too short41 42 41 Wigle et al44 report that in two communities in Quebec the incidence of cancer of the stomach among men is twice the expected value, but this is explained by prob able occupational exposure to asbestos. Asbestos fibers can also be found as an ingredient in many processed foodstuffs. The most discussed of these is the talc-coating of rice, which is done mainly for aes thetic purposes.4* Merliss144 suggested that it is this coat ing that explains the seven-times greater-than-expected prevalence cancer of the stomach in Japan but Haenszel et al2 found no support for this theory in epidemiological studies. Electron microscopic investigations have re vealed talc, but not asbestos, in gastric carcinoma cells from Japanese patientsjp one study47 and both talc and asbestos, as well as other particulate matter, in another4* but this does not, of course, prove any relationship. There is a correlation between low socioeconomic sta tus and occurrence of gastrointestinal carcinoma.4* For example. Enterline10 reported a doubled incidence of gas trointestinal cancer in a population of coalworkers and related this to socioeconomic factors. If this was the main reason for the higher prevalence of gastrointestinal car cinomas among carriers of PP in the present investigation, it might be expected that there would be some significant differences in the stated occupations between the pa tients and their controls, but with the exception of con struction workers in relation to carcinoma of the stomach this was not the case. Many persons exposed to asbestos are in fact skilled workers and cannot be regarded as a group belonging to a low socioeconomic class. In conclusion, there is a slight but significant excess of typical pleural plaques in patients with gastrointestinal carcinoma, particularly carcinoma of the stomach. This is in accordance with many other reports, in which exposure to asbestos has been linked to an approximately doubled risk of gastrointestinal carcinoma. References 1. Selikoff I): Epidemiology of gastrointestinal cancer. Environ Health Perspect 9:299-305,1974. f 2. Haenszel W, Kurihara M, Segi M. and Lee RKC: Stomach cancer among japanese in Hawaii. I Natl Cancer Inst 49:969-988,1972. 3. Merliss RR: Talc-treated rice and lapanese stomach cancer. Science 173:1141-1142,1971. 4. Glober CA, Nomura A, Kamiyama S. et al: Bowel transit-time and stool weight in populations with different colon-cancer risks. Lancet 2:110-111,1977. 5. Cloyne SR: Pneumoconiosis. A histological survey of necropsy material in 1205 cases. Lancet 1:810-814.1951. 6. Selikoff I). Churg }, and Hammond EC: Asbestos exposure and neoplasia. / Am Med Assoc 1:142-146,1964. 7. Selikoff II. Hammond EC. and Seideman H: Cancer risk of insula tion workers in the United States, in Biological Effects of Asbestos. IARC Sci Publ 8:209-216,1973. 8. Hammond EC and Selikoff IJ: Relation of cigarette smoking to risk of asbestos-associated disease among insulation workers in the United States, in Biological Effects of Asbestos. IARC Sci Publ 8:312-317,^1973. 9. Mancuso TF: In discussion. Ann NY Acad Sci 132:590-592,1965. 10. Newhouse ML: Cancer among workers in the asbestos textile in dustry, in Biological Effects of Asbestos. IARC Sci Publ 8:203-208, 1973. 11. Elmes PC and Simpson MjC: Insulation workers in Belfast 3. Mortality 1940-66. Br I Ind Med 28:226-236. 1971. 12. Kogan FM, Gusel'nikova NA, and Gulevskaya MR: The cancer mortality rate among workers in the asbestos industry in the Urals. Cig Sanit 7:29-32,1972. _ 13. McDonald AD and McDonald JC: etudes epidemiologiques sur les maladies dues a I'amiante au Canada. Rev Fr Ma! Resp (Suppl. 2) 4:25-38, 1976. 14. Ahlmark A: Vi maste leva med asbest Milio i Sverige 5:16-22, 1977. 15. Blot WJ. Harrington JM. Toledo A. et al: Lung cancer after employment in shipyards during World War H. N Engl I Med 299:620-624, 1978. 16. Schneiderman MA: Digestive systsem cancer among persons subjected to occupational inhalation of asbestos particles: A litera ture review with emphasis on dose response. Environ Health Perspect 9:307-311. 1974. 808 Gastrointestinal Carcinoma and Occurrence of Pleural Plaques/Hillerdal 17. Miller AB: Asbestos fiber dust and gastrointestinal malignancies Review of literature with regard to a cause/effect relationship. I Chronic Dis 31:23-33, 1978. 18. Hillerdal C: Pleural plaques in a health survey material. Fre quency. development, and exposure to asbestos. Scand } Respir Dis 39:257-263. 1978. 19. Hillerdal C and Lindgren A: Pleural plaques: Correlation of oc currence at autopsy to radiographic findings and occupational history Accepted for publication, fur / Respir Dis, 1980. 20. Hillerdal C and Nou E: Occupation and bronchial carcinoma. Scand I Respir Dis 60:76-82, 1979. 21. Hillerdal C and Lindholm CE: Laryngeal cancer and asbestos. ORL 42:233-241, 1980. 22. Cross P, Harley RA, et al: Ingested mineral fibers -- Do they penetrate tissue or cause cancer? Arch Environ Health 29:341-347, 1974. 23. Evans JG, Evans R|. et ai: Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and its subsequent clearance using radioactive tracer techniques. I. UICC crocidolite asbestos. Environ Res 6:180-201, 1973. 24. Morgan A, Evans jC, Evans RJ, et al: Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and its sub sequent clearance using radioactive tracer substances. II. Deposition of the UICC standard reference samples of asbestos. Environ Res 10:196-207, 1975. 25. Cloyne SR: The presence of asbestos bodies in the feces in a case of pulmonary asbestosis. Tubercle 12:158-159.1931. 26. Cunningham HM, Pontefract RD, and O'Brien RC: Quantitative relationship of fecal asbestos to asbestos exposure. I Toxicol Environ Health 1:377-379, 1976. 27. Webster ): The ingestion of asbestos fibres. Environ Health Perspect 9:199-202,1974. 28. Westlake CE: Asbestos fibres in th colonic wall. Environ Health Perspect 9:227, 1974. 29. Storeygard AR and Brown AL Penetration of the small intestinal mucosa by asbestos fibres. Mayo Clin Proc 52:809-812,1977. 30. Cunningham HM and Pontefract RD: Symposium on industrial chemicals as food contaminants. Asbestos fibres in beverages, drink ing water, and tissues: their passage through the intestinal wall and movement through the body.J Off Anal Chem 56:976-981.1973. 31. Davis JMC, Bolton RE, and Carrett 1: Penetration of cells by asbestos fibres. Environ Health Perspect 9:255-260,1974. 32. Enticknap JB and Smither WJ: Peritoneal tumors in asbestosis. Bri I Ind Med 21:20-31. 1964. 33. Pontefract RD: Penetration of asbestos through the digestive wall in rats. Environ Health Perspect 9:213.1974. 34. Voikheimer C: Passage of particles through the wall of the gas- trointotin.il tr.ict. Environ Health Perspect 9.21S-225. 1974 35. Cibel W, Lohs K. Horn KH. et al: Tiere.xperimentelle Untersuchungen uber eine kanzerogene Wirkung von Asbestfiltermaterial nach oraler Aufnahme. Arch-Geschwultsforsch 46:437-442. 1976. 36 Borow M, Conston A, Livornese L. and Schalet N: Mesothelioma following exposure to asbestos: A review of 72 cases. Chest 64:641-646.1973. 37. Langer AM: Inorganic particles in human tissues and their asso ciation with neoplastic disease. Environ Health Perspect 9 229-233 1974. 38. Chatel A, Mignon F, Sebastien P, et al: Exploration oeso-gastrique avec recherche de fibres d'amiante chez des malades exposes a I'aminante. Gastroenterol Clin Biol 2:459-464, 1978. 39. Rosen P, Savino A. and Melamed M: Ferruginous (asbestos) bodies and primary carcinoma of the colon. Am I Clin Pathol 61:135-138, 1974. 40. Hillerdal C, Hillerdal O, and Nou E: Radiologically visible pleural plaques in a one year material from a health survey, in press. Eur I Respir Dis (Suppl. 1), 1980. 41. Harrington JM, Craun CF, Meigs )W, et a!: An investigation of the use of asbestos cement pipe for public water supply and the inci dence of gastrointestinal cancer in Connecticut 1935-1973. Am / Epi demiol 107:96-103,1978. 42. Levy BS, Sigurdson E, and Mande)), et al: Investigating possible effects of asbestos in city water Surveillance of gastrointestinal cancer in Duluth. Minnesota. Am I Epidemiol 103:362*368,1976. 43. Masson TJ, McKay FW, and Miller RW: Asbestoslike fibers in Duluth water supply. / Am Med Assoc 228:1019-1020,1974. 44. Wigle DT: Cancer mortality in relation to asbestos in municipal water supplies. Arch Environ Health 32:185*190.1977. 45. Breeling l): Potential hazard from eating rice coated with glucose and talc. / Am Med Assoc 228:101,1974. 46. Merliss RR: Talc and asbestos contaminant of rice. / Am Med Assoc 216:2144, 1971. 47. Matsudo H, Hodgin NM, and Tanaka A: Japanese gastric cancer. Potentially carcinogenic silicates (talc) from rice. Arch Pathol 97:366-368,1974. 48. Henderson W), Evans DMD, Davies ID. and Griffiths K: Analysis of particles in stomach tumors from Japanese males. Environ Res 9:240-249.1975. 49. Williams.RR and Norm JW: Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of pa tients: Interview study from the third national cancer survey. / Natl Cancer Inst 58:525-547,1977. 50. Enterline PE: A review of mortality data for American coal miners, in Coal Workers' Pneumoconiosis. Ann NY Acad Sc/ 200:260-272,1972. Forging New Connections To sustain a balanced effort between the search for new knowledge and uses for the old, we must build a collaborative partnership among research and educational institu tions, the government and the private sector, industry must become a full partner -- not merely a "user" and especially not an adversary. New connections must be forged between academic and industrial research centers. A wide range of cooperative pro grams must be emplaced, and, as in any true partnership, the needs of both parties must be taken into account For healthy science, the vital ingredients in the delicate process of creation (especially freedom of choice and a stable floor of support) must be preserved, and, meanwhile, industry has a right to a fair balance between risk and reward. -- From "Opinion: Epidemic of Life" by James 0. Ebert in Bioscience. August 1980. Journal of Occupational Medicine/Vol. 22, No. 12/December 1980 809