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RADIATION-INDUCED BREAST CANCER
297 tuition. We wish
Letters
to
the Editor
RADIATION-INDUCED BREAST CANCER on the report by Wanebo et al. that the incidence of breast cancer is increased in atom-bomb survivors,2 and on Mackenzie’s conclusion that there is an excess of breast cancer in women who have been exposed to X-rays during fluoroscopic control of pneumothorax therapy for pulmonary tuberculosis.3 The results of both studies were statistically highly significant. We, like Stewart and Kneale,4and Court Brown and Doll,6 have concluded that radiation carcinogenesis occurs in proportion to the spontaneous incidence of cancer in a given tissue-thus, the dose required to double the incidence of cancer in one organ also doubles the incidence in other tissues. Our analysis of Wanebo’s data indicates that, over the dose-range 40-300 rads, the dose required to double the incidence of spontaneous breast cancer is approximately 20 rads.7 Our estimate of Mackenzie’s data-based on the author’s estimate that each patient who received pneumothorax therapy had approximately 150 fluoroscopic examinations-suggests that the dose received was 900-1200 rads, and that the doubling dose was 20-50 rads.’In view of the very different nature of these epidemiological studies, the agreement between these estimates is remarkable. Further, because the doubling dose is so low, the situation is
SiR,—You have commented editorially1
extremely worrying. We know of no reported studies similar to that of Mackenzie. Yet the records of patients who have had pneumothorax therapy (controlled by fluoroscopy) in tuberculosis sanitoria between- 1930 and 1950 are all available, and the latent period for cancer development is essentially over. Thus, a worldwide effort to study these records together with the subsequent occurrence of breast cancer, presents one of the most remarkable medical opportunities in history. The issue of radiation-induction of cancer has everything to do with the radiation standards associated with atomicenergy development throughout the world. Carefully conducted searches of the records of tuberculosis hospitals should increase the data available on radiation-induced breast cancer at least a hundredfoldand probably give much more information than we can hope for from projected Japanese studies. Indeed, if there are enough well-kept fluoroscopy records it may well be possible to describe the dose-response curve for radiationinduction of breast cancer for a wide range of doses. We urge such studies. Bio-Medical Research Division, Lawrence Radiation Laboratory, University of California, Livermore, California.
ARTHUR R. TAMPLIN JOHN W. GOFMAN.
SIMPLIFIED PERITONEAL DIALYSIS SIR,-Peritoneal dialysis is becoming a widely used method of treatment in general hospitals throughout the country, both for acute renal failure and, increasingly, for maintenance dialysis in patients waiting for a place on a hsemodialysis programme. Unlike hxmodialysis, it is a treatment which can be carried out efficiently by any medical and nursing staff on any ward after a short period of skilled 1. Lancet, 1968, ii, 1229. 2. Wanebo, C. K., Johnson, K. G., Sato, K., Thorslund, T. W. New Engl. J. Med. 1968, 279, 667. 3. Mackenzie, I. Br. J. Cancer, 1965, 19, 1. 4. Stewart, A., Kneale, G. W. Lancet, 1968, i, 104. 5. Brown, W. M. C., Doll, R. Br. med. J. 1965, ii, 1327. 6. Gofman, J. W., Tamplin, A. R. Congressional Record, 1969, 194,
11,338. 7.
Tamplin, A. R., Gofman, J. W. Testimony submitted to the Federal Radiation Council, January, 1970. (GT-107-70) no. 6.
to
suggest
some
modifications of the
com-
monly practised method which we believe would, if widely adopted, allow a considerable saving of N.H.S. money as well as nurses’ time. As nursing staff shortages become more acute, this factor assumes greater importance. Peritoneal-dialysis solutions, whether supplied commercially or prepared by the hospital pharmacist, normally conform to the official B.P.C. formulation. To these must be added heparin (100-200 units per litre) to discourage fibrin occlusion of the catheter orifices, and potassium chloride, usually in a concentration of 3-4 meq. per litre, once the initial hyperkalaemia has been corrected. These additions are normally made with separate disposable syringes by injection through the rubber cap of the dialysis-fluid bag or bottle. The injections are tedious and time-consuming and must inevitably increase the chance of introducing infection into the peritoneal cavity. For the past six months in our hospital we have used dialysis solution prepared in the hospital pharmacy to our own specifications, using an acetate formulation. Each litre of dialysis solution contains 200 units of heparin and 2-5 meq. of potassium. The addition of heparin effectively prevents fibrin plugging of the catheter, and the presence of 2-5 meq. per litre of potassium has allowed quite satisfactory and prompt reduction of serum-potassium in hyperkalarmic patients without causing hypokalxmia. The only additions to the fluid which have to be made are supplements of antibiotic in occasional cases of peritonitis. The fluid is not prewarmed, but is heated to body temperature by passage through a coil in a warming bath, as described by Kerr and Douglas.! By these modifications the nurse’s role is greatly simplified, so that she has more free time for the treatment of other patients. The peritoneal-dialysis solutions used are isotonic, containing 18.9 g. dextrose monohydrate per litre, or hypertonic, containing 70 g. per litre. In addition the following are present in both solutions: sodium chloride 5-56 g., sodium acetate 4-76 g. (giving 35 meq. per litre HC03 as acetate), calcium hydrate 0-33 g., magnesium chloride 0-15 g., potassium chloride 0-186 g., heparin 200 units, sodium metabisulphite 0-15 g. per litre. The solutions are sterilised by autoclaving at 115°C for half an hour in a rapidcooling steriliser. The acetate formula has a pH of about 5-9 in contrast to the lactate formulation, in which the pH does not normally exceed 5-5. This is an advantage because the higher pH is near the point of optimum stability of heparin at the sterilisation temperature of 115°C, as shown by Pritchard.2 Sterilisation should not be undertaken in a since this normally four-fold increase in the content of 5-hydroxymethylfurfural (5-H.M.F.) and related substances in the sterilised solution compared with the quantities produced in a rapid-cooling steriliser. Our earlier experience showed that the higher 5-H.M.F. content resulted in several cases of sterile inflammatory peritonitis (mainly lymphocytes in the peritoneal fluid) which ceased when all solutions were sterilised in the rapid-cooling steriliser. We are now using solutions at the rate of 18,000 litres a year, and have completely eliminated the expenditure on syringes and injections of potassium chloride used to supplement the fluids previously used. This results in an annual saving of E750. The gross cost of production of our fluids also results in a further saving of 5s. per litre as compared with purchase from commercial sources, making a total annual saving to the hospital of E4500 per year. We suggest that these modifications are worth a trial in any large regional dialysis centre in order to save money and nurses’time. WILLIAM T. WING Newcastle General Hospital, ROBERT ULDALL. Newcastle upon Tyne.
downward-displacement autoclave,
results in
a
Kerr, D. N. S., Douglas, A. P. A Short Textbook of Kidney Disease; p. 108. London, 1968. 2. Pritchard, J. J. Pharm. Pharmac. 1964, 16, 487. 1.
Letters
to
the Editor
RADIATION-INDUCED BREAST CANCER on the report by Wanebo et al. that the incidence of breast cancer is increased in atom-bomb survivors,2 and on Mackenzie’s conclusion that there is an excess of breast cancer in women who have been exposed to X-rays during fluoroscopic control of pneumothorax therapy for pulmonary tuberculosis.3 The results of both studies were statistically highly significant. We, like Stewart and Kneale,4and Court Brown and Doll,6 have concluded that radiation carcinogenesis occurs in proportion to the spontaneous incidence of cancer in a given tissue-thus, the dose required to double the incidence of cancer in one organ also doubles the incidence in other tissues. Our analysis of Wanebo’s data indicates that, over the dose-range 40-300 rads, the dose required to double the incidence of spontaneous breast cancer is approximately 20 rads.7 Our estimate of Mackenzie’s data-based on the author’s estimate that each patient who received pneumothorax therapy had approximately 150 fluoroscopic examinations-suggests that the dose received was 900-1200 rads, and that the doubling dose was 20-50 rads.’In view of the very different nature of these epidemiological studies, the agreement between these estimates is remarkable. Further, because the doubling dose is so low, the situation is
SiR,—You have commented editorially1
extremely worrying. We know of no reported studies similar to that of Mackenzie. Yet the records of patients who have had pneumothorax therapy (controlled by fluoroscopy) in tuberculosis sanitoria between- 1930 and 1950 are all available, and the latent period for cancer development is essentially over. Thus, a worldwide effort to study these records together with the subsequent occurrence of breast cancer, presents one of the most remarkable medical opportunities in history. The issue of radiation-induction of cancer has everything to do with the radiation standards associated with atomicenergy development throughout the world. Carefully conducted searches of the records of tuberculosis hospitals should increase the data available on radiation-induced breast cancer at least a hundredfoldand probably give much more information than we can hope for from projected Japanese studies. Indeed, if there are enough well-kept fluoroscopy records it may well be possible to describe the dose-response curve for radiationinduction of breast cancer for a wide range of doses. We urge such studies. Bio-Medical Research Division, Lawrence Radiation Laboratory, University of California, Livermore, California.
ARTHUR R. TAMPLIN JOHN W. GOFMAN.
SIMPLIFIED PERITONEAL DIALYSIS SIR,-Peritoneal dialysis is becoming a widely used method of treatment in general hospitals throughout the country, both for acute renal failure and, increasingly, for maintenance dialysis in patients waiting for a place on a hsemodialysis programme. Unlike hxmodialysis, it is a treatment which can be carried out efficiently by any medical and nursing staff on any ward after a short period of skilled 1. Lancet, 1968, ii, 1229. 2. Wanebo, C. K., Johnson, K. G., Sato, K., Thorslund, T. W. New Engl. J. Med. 1968, 279, 667. 3. Mackenzie, I. Br. J. Cancer, 1965, 19, 1. 4. Stewart, A., Kneale, G. W. Lancet, 1968, i, 104. 5. Brown, W. M. C., Doll, R. Br. med. J. 1965, ii, 1327. 6. Gofman, J. W., Tamplin, A. R. Congressional Record, 1969, 194,
11,338. 7.
Tamplin, A. R., Gofman, J. W. Testimony submitted to the Federal Radiation Council, January, 1970. (GT-107-70) no. 6.
to
suggest
some
modifications of the
com-
monly practised method which we believe would, if widely adopted, allow a considerable saving of N.H.S. money as well as nurses’ time. As nursing staff shortages become more acute, this factor assumes greater importance. Peritoneal-dialysis solutions, whether supplied commercially or prepared by the hospital pharmacist, normally conform to the official B.P.C. formulation. To these must be added heparin (100-200 units per litre) to discourage fibrin occlusion of the catheter orifices, and potassium chloride, usually in a concentration of 3-4 meq. per litre, once the initial hyperkalaemia has been corrected. These additions are normally made with separate disposable syringes by injection through the rubber cap of the dialysis-fluid bag or bottle. The injections are tedious and time-consuming and must inevitably increase the chance of introducing infection into the peritoneal cavity. For the past six months in our hospital we have used dialysis solution prepared in the hospital pharmacy to our own specifications, using an acetate formulation. Each litre of dialysis solution contains 200 units of heparin and 2-5 meq. of potassium. The addition of heparin effectively prevents fibrin plugging of the catheter, and the presence of 2-5 meq. per litre of potassium has allowed quite satisfactory and prompt reduction of serum-potassium in hyperkalarmic patients without causing hypokalxmia. The only additions to the fluid which have to be made are supplements of antibiotic in occasional cases of peritonitis. The fluid is not prewarmed, but is heated to body temperature by passage through a coil in a warming bath, as described by Kerr and Douglas.! By these modifications the nurse’s role is greatly simplified, so that she has more free time for the treatment of other patients. The peritoneal-dialysis solutions used are isotonic, containing 18.9 g. dextrose monohydrate per litre, or hypertonic, containing 70 g. per litre. In addition the following are present in both solutions: sodium chloride 5-56 g., sodium acetate 4-76 g. (giving 35 meq. per litre HC03 as acetate), calcium hydrate 0-33 g., magnesium chloride 0-15 g., potassium chloride 0-186 g., heparin 200 units, sodium metabisulphite 0-15 g. per litre. The solutions are sterilised by autoclaving at 115°C for half an hour in a rapidcooling steriliser. The acetate formula has a pH of about 5-9 in contrast to the lactate formulation, in which the pH does not normally exceed 5-5. This is an advantage because the higher pH is near the point of optimum stability of heparin at the sterilisation temperature of 115°C, as shown by Pritchard.2 Sterilisation should not be undertaken in a since this normally four-fold increase in the content of 5-hydroxymethylfurfural (5-H.M.F.) and related substances in the sterilised solution compared with the quantities produced in a rapid-cooling steriliser. Our earlier experience showed that the higher 5-H.M.F. content resulted in several cases of sterile inflammatory peritonitis (mainly lymphocytes in the peritoneal fluid) which ceased when all solutions were sterilised in the rapid-cooling steriliser. We are now using solutions at the rate of 18,000 litres a year, and have completely eliminated the expenditure on syringes and injections of potassium chloride used to supplement the fluids previously used. This results in an annual saving of E750. The gross cost of production of our fluids also results in a further saving of 5s. per litre as compared with purchase from commercial sources, making a total annual saving to the hospital of E4500 per year. We suggest that these modifications are worth a trial in any large regional dialysis centre in order to save money and nurses’time. WILLIAM T. WING Newcastle General Hospital, ROBERT ULDALL. Newcastle upon Tyne.
downward-displacement autoclave,
results in
a
Kerr, D. N. S., Douglas, A. P. A Short Textbook of Kidney Disease; p. 108. London, 1968. 2. Pritchard, J. J. Pharm. Pharmac. 1964, 16, 487. 1.