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TREATMENT OF FEMALE BREAST CARCINOMA
855 an insignificant effect on the initiating somatic mutations. But various infective agents and drugs, atmospheric pollution, cigarette smoking, and severe mental stress, by interfering with an endogenous defence mechanism directed against the forbidden clone, can all shorten the latent period between the last
initinting event and the onset of svmntoms and -,igns.1,559 The General Infirmary
at
Leeds.
P. R. J. BURCH.
APPLE PACKERS WITH BLEEDING NOSES SIR,-Quimby’s observations of the effect of newspaper pulp on the human nose, to which you draw attention in your annotation (Oct. 1, p. 740), are part of the same story as your previous annotation, Led by the Nose ? (Sept. 24, p. 690). Some samples of American newsprint were found by Dr. Carroll Williams and Dr. Karel Slama, of Harvard, to have juvenilehormone activity high enough to stop the maturation of insects.Io Juvenile hormone, which appears to be a steroid, occurs in the adrenal glands of cattle.ll Epistaxis due to vicarious menstruation was recorded in 1892, and testosterone was shown to affect nasal mucosa in 1938.12 Oral contraceptives can cause vasomotor rhinitis,13 though they can also stop it.14 Indeed the mechanism seems to be a primeval one; not only, as you say in your annotation (Sept. 24, p. 690), is the pituitary gland partly nasal in origin, but man retains a pharyngeal hypophysis,l5 and cestrogens cause hyperaemia not only of the nose but of the pituitary gland." Testosterone and several other steroids show fibrino-
lytic activity. 17 A paradox seldom discussed in the published reports is that, just as the oral contraceptives can stop vasomotor rhinitis as well as start it, so they can stop epistaxis even though it can be started by closely related steroids. They have been regarded as specific for hereditary hsemorrhagic telangiectasia, 18 19 but if nasal endometriosis occurs they would be appropriate for that, and they are now used for epistaxis due to any caused Oral contraceptives have been described as specific for congential anbrinogenasmia by Dr. Ozsoylu and Dr. Corbacioglu (July 16, p. 170) and as potent inhibitors of fibrinolysis in many conditions by Mr. Misirlioglu (Aug. 13, p. 392). Summerfield Hospital,
Birmingham
18.
ROBERT J. HETHERINGTON.
TREATMENT OF FEMALE BREAST CARCINOMA SIR,-The outcome of Dr. Brinkley and Mr. Haybittle’s trial, at Addenbrooke’s Hospital, Cambridge, of radical versus conservative surgery for breast cancer, has been awaited with great interest. In a final report (Aug. 6, p. 291) they reach the conclusion: " There were no significant differences in survival or recurrence-free rates between the two treatment groups...". Referring to their trial in your leading article, in 1964,21 you stated: at Cambridge stage-2 breast cancer is being treated alternatively by radical mastectomy or simple mastectomy supplemented by radiation in both groups." It is now revealed, however, that this trial has, in fact, not been one of radical versus simple mastectomy at all. It would be unfortunate if the trial were interpreted as such. The patients who were treated conservatively were a mixed group, sometimes having a simple, and sometimes a modified simple," mastectomy. Thus 89 of 113 " simple " cases had "
"
9. 10. 11.
Burch, P. R. J., Rowell, N. R. Brit. med. J. 1966, i, 1050. Lancet, July 2, 1966, p. 37. Barrington, E. J. W. An Introduction to General and Comparative Endocrinology; p. 349. Oxford, 1963. 12. Fabricant, M. D. Fert. Steril. 1960, 11, 195. 13. Dowie, L. N. Lancet, 1964, i, 726. 14. Mears, E. ibid. p. 981. 15. Turner, C. D. General Endocrinology; p. 474. Philadelphia, 1960. 16. Burrows, H., Horning, E. Œstrogens and Neoplasia; p. 43. Oxford, 1952. 17. Fearnley, G. R. Br. med. Bull. 1964, 20, 188. 18. Lancet, 1957, i, 35. 19. Hetherington, R. J. ibid. 1965, ii, 237. 20. Medical Tribune, Sept. 29, 1966, p.1. 21. Lancet, 1964, i, 367.
axillary glands removed, while the remaining 24 had the breast only resected. It is therefore evident that the only constant feature of the " simple " group has been the leaving in situ of the pectoral muscles; it appears to be this step which has been contrasted with standard radical mastectomy. There is no clear definition of the exact operative procedure which was employed in the non-radical group, although, except in a minority of cases, it was certainly not a simple mastectomy. In fairness to Dr. Brinkley and Mr. Haybittle, it must be stated that at no time in their report do they claim that this was a study of radical versus simple mastectomy, as this latter term is usually interpreted. There is now general recognition of the fact that a very complete axillary-gland clearance can be obtained without sacrificing the pectoral muscles. Since lymphography studies have provided objective evidence of this, Patey’s operation has enjoyed, deservedly, an increased popularity, because it is, for practical purposes, as radical as the Halsted operation as far as the axilla is concerned It is difficult to imagine that the cases described as having had " accessible axillary glands " removed were not those in which clinically invaded glands were mobile, and invitingly low in the axilla. Now if there is indeed any advantage to be derived from radical surgery, it is surely most likely to be shown in cases with limited and low axillary invasion. Thus, if a " modified simple mastectomy " includes removal of such glands, it is scarcely to be expected that this operation would produce results appreciably inferior to the standard radical operation. It seems therefore that Dr. Brinkley and Mr. Haybittle’s article gives some support to the Patey method of dealing with operable breast cancer. It must be clearly understood, however, that this article provides no evidence whatever in favour of the operation generally envisaged by the term " simple mastectomy ". Were this report to be so misinterpreted, existing confusion on this matter would be augmented. Breast Service, Peter MacCallum Clinic, THOMAS H. ACKLAND. Melbourne, Australia.
FLUORIDATION SIR,-The exchange of views on the effect(s) of fluoride on the locomotor system 12 indicates that more unexpected cases of toxicity may well occur in future. This is particularly so, in view of the demonstrated effects of fluoride in cases of postparathyroidectomy,3-5 multiple myeloma,6 and pyelorlephritiS. 78 Even the widely hailed concept that fluoride may be beneficial to the bones of those with " rarefaction " ailments9 10 has now been disputed,U-13 and it has been conceded that the new bone produced following this treatment is fluorotic.14 13 In view of the expressed willingness to re-evaluate the role of fluoride in cases of unexpected toxicities,16 the findings of Fedorov 17 18 assume added significance, for they present an alternative, non-toxic means of reducing dental caries. Fedorov has shown that, as a caries-preventive, calcium glycerophos1. 2. 3. 4.
Lancet, 1966, i, 1194. Sauerbrunn, B. J. L. ibid. Aug. 27, 1966, p. 497. Spira, L. J. Hyg., Camb. 1942, 42, 500. Yates, C., Doty, S., Talmadge, R. V. Proc. Soc. exp. Biol. Med. 1964,
115, 1103. 5. Geall, M. G., Beilin, L. J. Br. med. J. 1964, ii, 355. 6. Cohen, P., Gardner, F. H. New Engl. J. Med. 1964, 271, 1129. 7. Sauerbrunn, B. J. L., Ryan, C. M., Shaw, J. F. Ann. intern. Med. 1965, 63, 1074. 8. Call, R. A., Greenwood, D. A., Le Cheminant, W. H., Shupe, J. L., Nielsen, H. M., Olson, L. E., Lamborn, R. E., Mangelson, F. L., Davis, R. V. Publ. Hlth Reps, Wash. 1965, 80, 529. 9. Purves, M. J., Lancet, 1962, ii, 1188. 10. Rich, C., Ensinck, J., Ivanovich, P. J. clin. Invest. 1964, 43, 545. 11. Higgins, B. A., Nassim, J. R., Alexander, R., Hile, A. Br. med. J. 1965, i, 1159. 12. Rose, G. A. Proc. R. Soc. Med. 1965, 58, 436. 13. Adams, P. H., Jowsey, J. Ann. intern. Med. 1965, 63, 1151. 14. Rich, C., Ivanovich, P. ibid. p. 1069. 15. Cass, R. M., Croft, J. D., Perkins, P. Nye, W., Waterhouse, C., Terry, R. Archs intern. Med. 1966, 118, 111. 16. Arnold, F. A., Jr. Quoted in Br. dent. J. 1963, 114, 491. 17. Fedorov, Y. A. Dokl Akad. Nauk SSSR, 1961, 137, 1481. 18. Fedorov, Y. A. ibid. 1965, 161, 244.
initinting event and the onset of svmntoms and -,igns.1,559 The General Infirmary
at
Leeds.
P. R. J. BURCH.
APPLE PACKERS WITH BLEEDING NOSES SIR,-Quimby’s observations of the effect of newspaper pulp on the human nose, to which you draw attention in your annotation (Oct. 1, p. 740), are part of the same story as your previous annotation, Led by the Nose ? (Sept. 24, p. 690). Some samples of American newsprint were found by Dr. Carroll Williams and Dr. Karel Slama, of Harvard, to have juvenilehormone activity high enough to stop the maturation of insects.Io Juvenile hormone, which appears to be a steroid, occurs in the adrenal glands of cattle.ll Epistaxis due to vicarious menstruation was recorded in 1892, and testosterone was shown to affect nasal mucosa in 1938.12 Oral contraceptives can cause vasomotor rhinitis,13 though they can also stop it.14 Indeed the mechanism seems to be a primeval one; not only, as you say in your annotation (Sept. 24, p. 690), is the pituitary gland partly nasal in origin, but man retains a pharyngeal hypophysis,l5 and cestrogens cause hyperaemia not only of the nose but of the pituitary gland." Testosterone and several other steroids show fibrino-
lytic activity. 17 A paradox seldom discussed in the published reports is that, just as the oral contraceptives can stop vasomotor rhinitis as well as start it, so they can stop epistaxis even though it can be started by closely related steroids. They have been regarded as specific for hereditary hsemorrhagic telangiectasia, 18 19 but if nasal endometriosis occurs they would be appropriate for that, and they are now used for epistaxis due to any caused Oral contraceptives have been described as specific for congential anbrinogenasmia by Dr. Ozsoylu and Dr. Corbacioglu (July 16, p. 170) and as potent inhibitors of fibrinolysis in many conditions by Mr. Misirlioglu (Aug. 13, p. 392). Summerfield Hospital,
Birmingham
18.
ROBERT J. HETHERINGTON.
TREATMENT OF FEMALE BREAST CARCINOMA SIR,-The outcome of Dr. Brinkley and Mr. Haybittle’s trial, at Addenbrooke’s Hospital, Cambridge, of radical versus conservative surgery for breast cancer, has been awaited with great interest. In a final report (Aug. 6, p. 291) they reach the conclusion: " There were no significant differences in survival or recurrence-free rates between the two treatment groups...". Referring to their trial in your leading article, in 1964,21 you stated: at Cambridge stage-2 breast cancer is being treated alternatively by radical mastectomy or simple mastectomy supplemented by radiation in both groups." It is now revealed, however, that this trial has, in fact, not been one of radical versus simple mastectomy at all. It would be unfortunate if the trial were interpreted as such. The patients who were treated conservatively were a mixed group, sometimes having a simple, and sometimes a modified simple," mastectomy. Thus 89 of 113 " simple " cases had "
"
9. 10. 11.
Burch, P. R. J., Rowell, N. R. Brit. med. J. 1966, i, 1050. Lancet, July 2, 1966, p. 37. Barrington, E. J. W. An Introduction to General and Comparative Endocrinology; p. 349. Oxford, 1963. 12. Fabricant, M. D. Fert. Steril. 1960, 11, 195. 13. Dowie, L. N. Lancet, 1964, i, 726. 14. Mears, E. ibid. p. 981. 15. Turner, C. D. General Endocrinology; p. 474. Philadelphia, 1960. 16. Burrows, H., Horning, E. Œstrogens and Neoplasia; p. 43. Oxford, 1952. 17. Fearnley, G. R. Br. med. Bull. 1964, 20, 188. 18. Lancet, 1957, i, 35. 19. Hetherington, R. J. ibid. 1965, ii, 237. 20. Medical Tribune, Sept. 29, 1966, p.1. 21. Lancet, 1964, i, 367.
axillary glands removed, while the remaining 24 had the breast only resected. It is therefore evident that the only constant feature of the " simple " group has been the leaving in situ of the pectoral muscles; it appears to be this step which has been contrasted with standard radical mastectomy. There is no clear definition of the exact operative procedure which was employed in the non-radical group, although, except in a minority of cases, it was certainly not a simple mastectomy. In fairness to Dr. Brinkley and Mr. Haybittle, it must be stated that at no time in their report do they claim that this was a study of radical versus simple mastectomy, as this latter term is usually interpreted. There is now general recognition of the fact that a very complete axillary-gland clearance can be obtained without sacrificing the pectoral muscles. Since lymphography studies have provided objective evidence of this, Patey’s operation has enjoyed, deservedly, an increased popularity, because it is, for practical purposes, as radical as the Halsted operation as far as the axilla is concerned It is difficult to imagine that the cases described as having had " accessible axillary glands " removed were not those in which clinically invaded glands were mobile, and invitingly low in the axilla. Now if there is indeed any advantage to be derived from radical surgery, it is surely most likely to be shown in cases with limited and low axillary invasion. Thus, if a " modified simple mastectomy " includes removal of such glands, it is scarcely to be expected that this operation would produce results appreciably inferior to the standard radical operation. It seems therefore that Dr. Brinkley and Mr. Haybittle’s article gives some support to the Patey method of dealing with operable breast cancer. It must be clearly understood, however, that this article provides no evidence whatever in favour of the operation generally envisaged by the term " simple mastectomy ". Were this report to be so misinterpreted, existing confusion on this matter would be augmented. Breast Service, Peter MacCallum Clinic, THOMAS H. ACKLAND. Melbourne, Australia.
FLUORIDATION SIR,-The exchange of views on the effect(s) of fluoride on the locomotor system 12 indicates that more unexpected cases of toxicity may well occur in future. This is particularly so, in view of the demonstrated effects of fluoride in cases of postparathyroidectomy,3-5 multiple myeloma,6 and pyelorlephritiS. 78 Even the widely hailed concept that fluoride may be beneficial to the bones of those with " rarefaction " ailments9 10 has now been disputed,U-13 and it has been conceded that the new bone produced following this treatment is fluorotic.14 13 In view of the expressed willingness to re-evaluate the role of fluoride in cases of unexpected toxicities,16 the findings of Fedorov 17 18 assume added significance, for they present an alternative, non-toxic means of reducing dental caries. Fedorov has shown that, as a caries-preventive, calcium glycerophos1. 2. 3. 4.
Lancet, 1966, i, 1194. Sauerbrunn, B. J. L. ibid. Aug. 27, 1966, p. 497. Spira, L. J. Hyg., Camb. 1942, 42, 500. Yates, C., Doty, S., Talmadge, R. V. Proc. Soc. exp. Biol. Med. 1964,
115, 1103. 5. Geall, M. G., Beilin, L. J. Br. med. J. 1964, ii, 355. 6. Cohen, P., Gardner, F. H. New Engl. J. Med. 1964, 271, 1129. 7. Sauerbrunn, B. J. L., Ryan, C. M., Shaw, J. F. Ann. intern. Med. 1965, 63, 1074. 8. Call, R. A., Greenwood, D. A., Le Cheminant, W. H., Shupe, J. L., Nielsen, H. M., Olson, L. E., Lamborn, R. E., Mangelson, F. L., Davis, R. V. Publ. Hlth Reps, Wash. 1965, 80, 529. 9. Purves, M. J., Lancet, 1962, ii, 1188. 10. Rich, C., Ensinck, J., Ivanovich, P. J. clin. Invest. 1964, 43, 545. 11. Higgins, B. A., Nassim, J. R., Alexander, R., Hile, A. Br. med. J. 1965, i, 1159. 12. Rose, G. A. Proc. R. Soc. Med. 1965, 58, 436. 13. Adams, P. H., Jowsey, J. Ann. intern. Med. 1965, 63, 1151. 14. Rich, C., Ivanovich, P. ibid. p. 1069. 15. Cass, R. M., Croft, J. D., Perkins, P. Nye, W., Waterhouse, C., Terry, R. Archs intern. Med. 1966, 118, 111. 16. Arnold, F. A., Jr. Quoted in Br. dent. J. 1963, 114, 491. 17. Fedorov, Y. A. Dokl Akad. Nauk SSSR, 1961, 137, 1481. 18. Fedorov, Y. A. ibid. 1965, 161, 244.