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CERVICAL SMEARS—WHEN AND HOW OFTEN?
1297
electron-microscope investigations need to be extended. We know virtually nothing of possible predisposing factors in these patients. Impaired delayed hypersensitivity has been demonstrated in a few cases, but the detailed pathogenesis of this (presumptive) lymphoma has still to be unravelled. THE HAZARDS OF THOROTRAST THE radioactive contrast medium ’Thorotrast’
(a
col-
loidal suspension of thorium dioxide), introduced in
1928,’ was reported as early as 1933 to produce serious toxic side-effects. Martland2 had already recorded the drastic and fatal acute haematological effects of radium in U.S. luminous-dial painters, and his early paper on unrecognised dangers of radioactive substances refers particularly to retention of insoluble radium and thorium compounds in the reticuloendothelial system. Thorotrast is an excellent radiological contrast medium-still perhaps the best. But as the reports of serious sideeffects accumulated it became ever less attractive. Until the late 1950s most of the reports were of single cases, and these were collated in a bibliography published by the International Atomic Energy Agency in 1964.3 Since then, the long-term effects of thorotrast have come under scrutiny-notably, in series from Denmark4 and Portugal.5 Now Johnson and others,6 describing possible long-term effects in six cases, point out that as lately as 1975 thorotrast was advocated for localisation of brainstem abscesses. Cavett et al. argued that, once injected, thorotrast remains "radioactively static" and contributes to its own encapsulation. But this proposition is incorrect, since, although deposits do become encapsulated, the decay of thorotrast involves the physical translocation of alpha and beta emitting daughter-product radioisotopes and the fate of the individual cells and tissues . irradiated is determined by biological transport mechanisms and equations as yet imperfectly understood. The main long-term sequelae of thorotrast are local effects and tumours at the site of injection and/or deposit, hxmangioendotheliomas (previously called thorotrastomas) or haEmangiosarcomas and fatal blood dyscrasias, including leuksemia and aplastic anaemias.* The marrow dyscrasias typically arise after a latent period of 20 years or so, and the risk of acquiring a total blood dyscrasia is increased 12-16-fold (as compared with the 6-8-fold increase over the natural risk observed in irradiated patients with ankylosing spondylitis).9 The risk of fatal blood dyscrasia with thorotrast is therefore much greater than that after any other form of radiation reported in man. Since there are adequate alternauves, administration of this potent carcinogen and leuksemogen seems undesirable. Horta, Abbatt, Motta, and 15
Shillitoe,
E. J.,
Lehner, T., Lessof, M. H., Harrison, D. F. N. Lancet, 1974,
, 281. 1. Ferves, C. Roentgenpraxis, 1933, 5, 207. 2 Martland, H. S., Conlon, P., Knef, J. P. J.Am. med. Ass. 1925, 85, 1769. 3. Thorotrast: a bibliography of its diagnostic use and biological effects. International Atomic Energy Agency, Vienna, 1964. (see also supplement,
June, 1965). 4. Faber, M. Ann. N. Y. Acad. Sci. 5. Horta, J. da S., Abbatt, J. D.,
1967, 145, 843. Cayolla da Motta, L., Roriz,
M. L. Lancet, 1965, ii, 201. 6. Johnson, S. A. N., Bateman, C. J. T., Beard, M. E. J., Whitehouse, J. M. A., Waters, A. H. Q. Jl. Med. 1977, 46, 259. 7. Cavett, M. R., Jr., Stern, W. E., Brown, J., Greenfield, M. A., Bentson, J. R.Surg.Neurol. 1975, 3, 153. 8. Abbatt, J. D. Ann. N.Y. Acad. Sci. 1967, 145, 766. 9 Horta, J. da S., Abbatt, J. D., Cayolla da Motta, L., Tavares, M. H. Z. Krebsforsch, 1972, 77, 202.
"the use of thorotrast as a is never justified in people medium radiological contrast with a life expectation of more than two years".
RorizS put it
more
bluntly:
CERVICAL SMEARS—WHEN AND HOW OFTEN? WHEN health authorities are determining priorities for all aspects of health care,1.2 this is a good moment to reassess practice in cervical cytology. The council of the British Society for Clinical Cytology has just done SO.3 In a policy document the society points out that the maximum prevalence-rate for positive cervical smears is at ages 35-39 years 4.5 but at present in some areas 65% of tests are undertaken in women below this age. Although positive smears are commonly seen in women under 30, a proportion of these lesions will spontaneously regress and, anyway, the in-situ stage lasts 10-20 years. The report suggests that it is both wasteful of resources and a cause of needless anxiety to perform a biopsy in those under 25 years who have positive smears. On the contrary, according to Knox6 and the Walton report4 screening should be prolonged at the other end of the age-scale. The society’s main recommendations are that screening should not start until the age of 25 years; that the interval between tests should be 5 years (as recommended in the existing national programme) ; that in women over 35 years the first test should be followed by a second test a year later (to reduce the false-negative rate’ at a period of maximum prevalence); and that screening should continue up to the age of 70 years. These proposals should go a long way to making better use of resources in this area of preventive medicine. Would it not, however, cause less confusion if the first two smears were taken within a year in all women entering the scheme? The report might also have pointed out that, even if women do not attend for regular testing, one smear, especially in those over 35 years, is better than no smear at all. The recommendations do not unfortunately overcome the greatest obstacle to a substantial lowering of mortality from cervical cancer-namely, the reluctance of the high-risk groups of women to come forward for testing. There must be few areas like Aberdeeng where 99% of women in the 20-60 years agegroup have been tested. In most areas of Great Britain the figure is probably nearer that of one London borough where some 60% of women in the 20-60 year agegroup were tested in a 5-year period. However, the report does find some cheer in the fact that the present cohort of older women in need of tests will be replaced by a new generation who, though exposed at an earlier age to known risk factors, will be accustomed to regular prophylactic testing. Should we not now make it clear to this new generation and the ones that come after that cervical cancer is a sexually transmitted disease?9 1. Priorities for Health and Social Services in England. H.M. Stationery Office 1976. 2. Prevention and Health—Everybody’s Business. H.M. Stationery Office, 1976. 3. British Society for Clinical Cytology. Br. med. J. 1977, i, 1516. 4. Cervical Cancer Screening Programme. Can. med. Ass. J. 1976, 114, 1003. 5. Fidler, H. K., Boyes, D. A., Worth, A. J. J. Obstet. Gynaec. Br. Commonw.
1968, 75, 392. 6. Knox, E. G. Br. J. Cancer 1976, 34, 444. 7. Yule, R. Acta cytol. 1972, 16, 389. 8. Macgregor, J. E., Fraser, M. E., Mann, E. M. F. Acta 9. Doll, R. E. Jl R. Coll. Physcns. 1977, 11, 136.
cytol. 1972, 16,
14.
°
electron-microscope investigations need to be extended. We know virtually nothing of possible predisposing factors in these patients. Impaired delayed hypersensitivity has been demonstrated in a few cases, but the detailed pathogenesis of this (presumptive) lymphoma has still to be unravelled. THE HAZARDS OF THOROTRAST THE radioactive contrast medium ’Thorotrast’
(a
col-
loidal suspension of thorium dioxide), introduced in
1928,’ was reported as early as 1933 to produce serious toxic side-effects. Martland2 had already recorded the drastic and fatal acute haematological effects of radium in U.S. luminous-dial painters, and his early paper on unrecognised dangers of radioactive substances refers particularly to retention of insoluble radium and thorium compounds in the reticuloendothelial system. Thorotrast is an excellent radiological contrast medium-still perhaps the best. But as the reports of serious sideeffects accumulated it became ever less attractive. Until the late 1950s most of the reports were of single cases, and these were collated in a bibliography published by the International Atomic Energy Agency in 1964.3 Since then, the long-term effects of thorotrast have come under scrutiny-notably, in series from Denmark4 and Portugal.5 Now Johnson and others,6 describing possible long-term effects in six cases, point out that as lately as 1975 thorotrast was advocated for localisation of brainstem abscesses. Cavett et al. argued that, once injected, thorotrast remains "radioactively static" and contributes to its own encapsulation. But this proposition is incorrect, since, although deposits do become encapsulated, the decay of thorotrast involves the physical translocation of alpha and beta emitting daughter-product radioisotopes and the fate of the individual cells and tissues . irradiated is determined by biological transport mechanisms and equations as yet imperfectly understood. The main long-term sequelae of thorotrast are local effects and tumours at the site of injection and/or deposit, hxmangioendotheliomas (previously called thorotrastomas) or haEmangiosarcomas and fatal blood dyscrasias, including leuksemia and aplastic anaemias.* The marrow dyscrasias typically arise after a latent period of 20 years or so, and the risk of acquiring a total blood dyscrasia is increased 12-16-fold (as compared with the 6-8-fold increase over the natural risk observed in irradiated patients with ankylosing spondylitis).9 The risk of fatal blood dyscrasia with thorotrast is therefore much greater than that after any other form of radiation reported in man. Since there are adequate alternauves, administration of this potent carcinogen and leuksemogen seems undesirable. Horta, Abbatt, Motta, and 15
Shillitoe,
E. J.,
Lehner, T., Lessof, M. H., Harrison, D. F. N. Lancet, 1974,
, 281. 1. Ferves, C. Roentgenpraxis, 1933, 5, 207. 2 Martland, H. S., Conlon, P., Knef, J. P. J.Am. med. Ass. 1925, 85, 1769. 3. Thorotrast: a bibliography of its diagnostic use and biological effects. International Atomic Energy Agency, Vienna, 1964. (see also supplement,
June, 1965). 4. Faber, M. Ann. N. Y. Acad. Sci. 5. Horta, J. da S., Abbatt, J. D.,
1967, 145, 843. Cayolla da Motta, L., Roriz,
M. L. Lancet, 1965, ii, 201. 6. Johnson, S. A. N., Bateman, C. J. T., Beard, M. E. J., Whitehouse, J. M. A., Waters, A. H. Q. Jl. Med. 1977, 46, 259. 7. Cavett, M. R., Jr., Stern, W. E., Brown, J., Greenfield, M. A., Bentson, J. R.Surg.Neurol. 1975, 3, 153. 8. Abbatt, J. D. Ann. N.Y. Acad. Sci. 1967, 145, 766. 9 Horta, J. da S., Abbatt, J. D., Cayolla da Motta, L., Tavares, M. H. Z. Krebsforsch, 1972, 77, 202.
"the use of thorotrast as a is never justified in people medium radiological contrast with a life expectation of more than two years".
RorizS put it
more
bluntly:
CERVICAL SMEARS—WHEN AND HOW OFTEN? WHEN health authorities are determining priorities for all aspects of health care,1.2 this is a good moment to reassess practice in cervical cytology. The council of the British Society for Clinical Cytology has just done SO.3 In a policy document the society points out that the maximum prevalence-rate for positive cervical smears is at ages 35-39 years 4.5 but at present in some areas 65% of tests are undertaken in women below this age. Although positive smears are commonly seen in women under 30, a proportion of these lesions will spontaneously regress and, anyway, the in-situ stage lasts 10-20 years. The report suggests that it is both wasteful of resources and a cause of needless anxiety to perform a biopsy in those under 25 years who have positive smears. On the contrary, according to Knox6 and the Walton report4 screening should be prolonged at the other end of the age-scale. The society’s main recommendations are that screening should not start until the age of 25 years; that the interval between tests should be 5 years (as recommended in the existing national programme) ; that in women over 35 years the first test should be followed by a second test a year later (to reduce the false-negative rate’ at a period of maximum prevalence); and that screening should continue up to the age of 70 years. These proposals should go a long way to making better use of resources in this area of preventive medicine. Would it not, however, cause less confusion if the first two smears were taken within a year in all women entering the scheme? The report might also have pointed out that, even if women do not attend for regular testing, one smear, especially in those over 35 years, is better than no smear at all. The recommendations do not unfortunately overcome the greatest obstacle to a substantial lowering of mortality from cervical cancer-namely, the reluctance of the high-risk groups of women to come forward for testing. There must be few areas like Aberdeeng where 99% of women in the 20-60 years agegroup have been tested. In most areas of Great Britain the figure is probably nearer that of one London borough where some 60% of women in the 20-60 year agegroup were tested in a 5-year period. However, the report does find some cheer in the fact that the present cohort of older women in need of tests will be replaced by a new generation who, though exposed at an earlier age to known risk factors, will be accustomed to regular prophylactic testing. Should we not now make it clear to this new generation and the ones that come after that cervical cancer is a sexually transmitted disease?9 1. Priorities for Health and Social Services in England. H.M. Stationery Office 1976. 2. Prevention and Health—Everybody’s Business. H.M. Stationery Office, 1976. 3. British Society for Clinical Cytology. Br. med. J. 1977, i, 1516. 4. Cervical Cancer Screening Programme. Can. med. Ass. J. 1976, 114, 1003. 5. Fidler, H. K., Boyes, D. A., Worth, A. J. J. Obstet. Gynaec. Br. Commonw.
1968, 75, 392. 6. Knox, E. G. Br. J. Cancer 1976, 34, 444. 7. Yule, R. Acta cytol. 1972, 16, 389. 8. Macgregor, J. E., Fraser, M. E., Mann, E. M. F. Acta 9. Doll, R. E. Jl R. Coll. Physcns. 1977, 11, 136.
cytol. 1972, 16,
14.
°