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ORAL CONTRACEPTIVES AND HEALTH
350 The files of the University Hospital were searched back to 1938 and no other example of this type of tumour was found in women of this age. There was only one liver cancer of any type: an anaplastic cholangiocarcinoma.
Apparently we are seeing a true increase in the frequency of this disease. Projection from the number of liver cancers at these ages compared to those in older women in accumulated series suggest that only about one liver " cancer " should have been expected in Iowa during the three years surveyed instead of the four observed. Without knowledge of the fraction of Iowa women taking oral contraceptives we cannot estimate the risk to users. Family-planning data counted 22,400 Iowa women in their programme taking oral contraceptives. If these were the only Iowa women on the pill the mortality figure would be about 5 per 100,000 women per year as an upper bound to risks. This is less than other causes of death in these women3 and in fact it should be noted that the cited figures show a lower mortality from neoplasms for users than for non-users; the protection against breast cancer may be greater than the liver-tumour risk. What is most disturbing is the risk in the future; most human cancers caused by chemicals appear only after longer exposures. In animal tests " be" nign hepatomas antedate the appearance of fully malignant tumours. Though they are uncommon, early fatalities may be harbingers of a much more serious problem. Department of Preventive Medicine, University of Iowa, Iowa City, Iowa 52242, U.S.A. Mercy Hospital, Pathology Department, Davenport, Iowa. Department of Pathology, University of Iowa. Pathology Department, Finley Hospital, Dubuque, Iowa.
JOHN W. BERG.
physicians and has been reinforced by new data using radioactive fibrinogen and other techniques. The clinical features of deep-vein thrombosis may be subtle and the diagnosis difficult, so that one might expect a considerable degree of bias to operate according to the degree of clinical suspicion. Deep-venous thrombosis is suspected more frequently in oral-contraceptive users with minimal clinical signs with the result that definitive tests are ordered. Thus, the basis on which the authors of the R.C.G.P. study draw their conclusions regarding an association between oral contraceptives and thrombosis is invalid. The problem of bias in the retrospective studies has been That both the R.C.G.P. and discussed elsewhere.6,7 retrospective studies agree on the increased incidence of deep-vein thrombosis in pill users may be merely due to the operation of the same degree of bias generated by the higher index of clinical suspicion. Moreover, the incidence of superficial thrombophlebitis in the more recent study shows only a very slight increase, whereas the pill is indeed thrombogenic, one would have thought its thrombogenicity would be operative in superficial as in deep-vein thrombosis. Other findings, such as alterations in blood coagulation and platelet indicesand in venous tone and possible blood-vessel changes cannot be considered as evidence that the pill is thrombogenic for reasons outlined previously.6 Department of Pathology, University of California, San Diego, La Jolla, California 92037, U.S.A.
CECIL HOUGIE NOEL CLARKE.
ROBERT J. KETELAAR.
GERIATRICS EARL F. ROSE. ROBERT G. VERNON.
SIR,-Like Dr Brandon LushII (as a very new geriatrician) have hesitated to enter into the correspondence your editorial Geriatrics is Medicine.10 But I accept the challenge in Incompatible Physicians (July 20, p. 139) that " general physicians are virtually silent this statement does not give the respect though I suggest that due to Dr Crockett land Dr Staffurth 12 for their admirable contributions. I must also confess, however, that I am a mule-a hybrid in that I was a very general physician until, eighteen months ago, I devoted myself entirely to the geriatric service of the Salisbury Hospital Group (now District). Apart from the challenge, my reason for now writing is that I think we, in Salisbury, have three suggestions which have not yet been made:
following must
ORAL CONTRACEPTIVES AND HEALTH
SiR,—The report of the Royal College of General Practitioners on oral contraceptives and health4 finds that there is a very small increased risk of superficial venous thrombosis in oral-contraceptive users in contrast to a sixfold increase in the incidence of deep-vein thrombosis (an increase which accords with earlier retrospective studies 5). The report recognises that, since an association between thrombosis and pill usage has been generally accepted, doctors would be more likely to diagnose these conditions in takers than in the controls. However, it argues " that bias would be expected to operate particularly in the minor, borderline lesions and that the results show that, on the contrary, the difference between the takers and controls is much less in the mild superficial lesions than in the more dramatic and serious deep thrombosis." On this basis it concludes that the degree of bias must then be very small. Assuming that the " minor, borderline lesions " refer to superficial-vein thrombosis-since deep-vein thrombosis can never be considered minor and is always serious even if not dramatic-the clinical diagnosis of superficial thrombophlebitis is usually unequivocal; the pain is localised, superficial, and associated with obvious findings that the patient quickly recognises so that there is little room for bias on the part of the physician. By contrast most episodes of deep-vein thrombosis are clinically silent. This has been recognised for years by both pathologists and 3. Beral, V. ibid. 1974, i, 1280. 4. Oral Contraceptives and Health: An interim report from the Oral Contraception Study of the Royal College of General Practitioners. London, 1974. 5. Vessey, M. P., Doll, R. Br. med. J. 1969, ii, 651.
(1) The situation in smaller district hospitals is fundamentally different from that in hospitals serving large conurbations, and in the former it is much more appropriate to retain an integrated service in general and geriatric medicine than in the larger hospitals ; indeed it is much more difficult to do otherwise. (2) The increasing contribution of district hospitals to undergraduate teaching should/could/will foster the initial interest of students in geriatric special problems and skills and prevent the present predominant change in their attitude during their student career described by Gale and Livesley 13 in the teaching hospitals of the past. (3) I would suggest that the most economical way to provide specialist geriatric advice of the highest calibre in small districts might be by redeployment of experienced geriatric physicians from special geriatric units in large centre of population to work for their final years in close collaboration with the general physicians of the smaller district hospitals. There can be no doubt that many of us find thirty-odd years in one post rather a long time. It becomes difficult to maintain youthful enthusiasm 6. Hougie, C. Am. Heart J. 1973, 85, 538. 7. Feinstein, A. R. Clin. Pharmac. Ther. 1973, 14, 291. 8. Poller, L. in Recent Advances in Thrombosis (edited p. 181. London, 1973. 9. Lush, B. Lancet, 1974, i, 1052. 10. ibid. p. 663. 11. Crockett, G. S. ibid. p. 804. 12. Staffurth, J. S. ibid. p. 985. 13. Gale, J., Livesley, B. Age and Aging, 1974, 3, 49.
by L. Poller) ;
Apparently we are seeing a true increase in the frequency of this disease. Projection from the number of liver cancers at these ages compared to those in older women in accumulated series suggest that only about one liver " cancer " should have been expected in Iowa during the three years surveyed instead of the four observed. Without knowledge of the fraction of Iowa women taking oral contraceptives we cannot estimate the risk to users. Family-planning data counted 22,400 Iowa women in their programme taking oral contraceptives. If these were the only Iowa women on the pill the mortality figure would be about 5 per 100,000 women per year as an upper bound to risks. This is less than other causes of death in these women3 and in fact it should be noted that the cited figures show a lower mortality from neoplasms for users than for non-users; the protection against breast cancer may be greater than the liver-tumour risk. What is most disturbing is the risk in the future; most human cancers caused by chemicals appear only after longer exposures. In animal tests " be" nign hepatomas antedate the appearance of fully malignant tumours. Though they are uncommon, early fatalities may be harbingers of a much more serious problem. Department of Preventive Medicine, University of Iowa, Iowa City, Iowa 52242, U.S.A. Mercy Hospital, Pathology Department, Davenport, Iowa. Department of Pathology, University of Iowa. Pathology Department, Finley Hospital, Dubuque, Iowa.
JOHN W. BERG.
physicians and has been reinforced by new data using radioactive fibrinogen and other techniques. The clinical features of deep-vein thrombosis may be subtle and the diagnosis difficult, so that one might expect a considerable degree of bias to operate according to the degree of clinical suspicion. Deep-venous thrombosis is suspected more frequently in oral-contraceptive users with minimal clinical signs with the result that definitive tests are ordered. Thus, the basis on which the authors of the R.C.G.P. study draw their conclusions regarding an association between oral contraceptives and thrombosis is invalid. The problem of bias in the retrospective studies has been That both the R.C.G.P. and discussed elsewhere.6,7 retrospective studies agree on the increased incidence of deep-vein thrombosis in pill users may be merely due to the operation of the same degree of bias generated by the higher index of clinical suspicion. Moreover, the incidence of superficial thrombophlebitis in the more recent study shows only a very slight increase, whereas the pill is indeed thrombogenic, one would have thought its thrombogenicity would be operative in superficial as in deep-vein thrombosis. Other findings, such as alterations in blood coagulation and platelet indicesand in venous tone and possible blood-vessel changes cannot be considered as evidence that the pill is thrombogenic for reasons outlined previously.6 Department of Pathology, University of California, San Diego, La Jolla, California 92037, U.S.A.
CECIL HOUGIE NOEL CLARKE.
ROBERT J. KETELAAR.
GERIATRICS EARL F. ROSE. ROBERT G. VERNON.
SIR,-Like Dr Brandon LushII (as a very new geriatrician) have hesitated to enter into the correspondence your editorial Geriatrics is Medicine.10 But I accept the challenge in Incompatible Physicians (July 20, p. 139) that " general physicians are virtually silent this statement does not give the respect though I suggest that due to Dr Crockett land Dr Staffurth 12 for their admirable contributions. I must also confess, however, that I am a mule-a hybrid in that I was a very general physician until, eighteen months ago, I devoted myself entirely to the geriatric service of the Salisbury Hospital Group (now District). Apart from the challenge, my reason for now writing is that I think we, in Salisbury, have three suggestions which have not yet been made:
following must
ORAL CONTRACEPTIVES AND HEALTH
SiR,—The report of the Royal College of General Practitioners on oral contraceptives and health4 finds that there is a very small increased risk of superficial venous thrombosis in oral-contraceptive users in contrast to a sixfold increase in the incidence of deep-vein thrombosis (an increase which accords with earlier retrospective studies 5). The report recognises that, since an association between thrombosis and pill usage has been generally accepted, doctors would be more likely to diagnose these conditions in takers than in the controls. However, it argues " that bias would be expected to operate particularly in the minor, borderline lesions and that the results show that, on the contrary, the difference between the takers and controls is much less in the mild superficial lesions than in the more dramatic and serious deep thrombosis." On this basis it concludes that the degree of bias must then be very small. Assuming that the " minor, borderline lesions " refer to superficial-vein thrombosis-since deep-vein thrombosis can never be considered minor and is always serious even if not dramatic-the clinical diagnosis of superficial thrombophlebitis is usually unequivocal; the pain is localised, superficial, and associated with obvious findings that the patient quickly recognises so that there is little room for bias on the part of the physician. By contrast most episodes of deep-vein thrombosis are clinically silent. This has been recognised for years by both pathologists and 3. Beral, V. ibid. 1974, i, 1280. 4. Oral Contraceptives and Health: An interim report from the Oral Contraception Study of the Royal College of General Practitioners. London, 1974. 5. Vessey, M. P., Doll, R. Br. med. J. 1969, ii, 651.
(1) The situation in smaller district hospitals is fundamentally different from that in hospitals serving large conurbations, and in the former it is much more appropriate to retain an integrated service in general and geriatric medicine than in the larger hospitals ; indeed it is much more difficult to do otherwise. (2) The increasing contribution of district hospitals to undergraduate teaching should/could/will foster the initial interest of students in geriatric special problems and skills and prevent the present predominant change in their attitude during their student career described by Gale and Livesley 13 in the teaching hospitals of the past. (3) I would suggest that the most economical way to provide specialist geriatric advice of the highest calibre in small districts might be by redeployment of experienced geriatric physicians from special geriatric units in large centre of population to work for their final years in close collaboration with the general physicians of the smaller district hospitals. There can be no doubt that many of us find thirty-odd years in one post rather a long time. It becomes difficult to maintain youthful enthusiasm 6. Hougie, C. Am. Heart J. 1973, 85, 538. 7. Feinstein, A. R. Clin. Pharmac. Ther. 1973, 14, 291. 8. Poller, L. in Recent Advances in Thrombosis (edited p. 181. London, 1973. 9. Lush, B. Lancet, 1974, i, 1052. 10. ibid. p. 663. 11. Crockett, G. S. ibid. p. 804. 12. Staffurth, J. S. ibid. p. 985. 13. Gale, J., Livesley, B. Age and Aging, 1974, 3, 49.
by L. Poller) ;