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BILLROTH-I GASTRIC RESECTION
387 From in the determination of 17-kotogonic steroids. each sample aliquots were taken for the types of treatment specified in the accompanying table. The results, presented in the table, clearly show that the low recoveries of cortisone and cortisol by the M.R.C. method are due to incomplete extraction of formed 17-ketosteroids by carbon tetrachloride, since continued extraction with the same solvent still yields substantial quantities of 17-ketosteroids. On the other hand, a single extraction with ethylene dichloride (Drekter’s technique) is suflicient to account satisfactorily for the added quantities of cortisone and cortisol. The failure of carbon tetrachloride to extract quantitatively 17-ketosteroids from urine assayed for 17-ketogenic steroids is attributed to the presence of acetic acid. This is confirmed by experiments in which four 11-oxygenated 17-ketosteroids were distributed between equal volumes of 25% acetic acid and carbon tetrachloride or ethylene dichloride. The following proportions of
androst-4-ene-3:11:17-trione, llp-hydroxyandrost-4-ene3 :17-dione, 3oc-hydroxytestane-11:17-dione, and 3ot:llp-
dihydroaytestan-17-one were found in the organic phase : using carbon tetrachloride 46, 20, 53, and 33% re8pectively, using ethylene dichlorido 98, 85, 104, and 90% respectively. From the evidence presented we conclude that, contrary to what has been implied in your leading article, Brooks and Clayton’s interesting findings in no way reflect on the value or reliability of the method for the determination of urinary 17-ketogenic steroids. Chemical Research Laboratory, Rheumatism Research Unit, Nether Edge Hospital, Sheffield.
J. K. NORYMBERSKI R. D. STUBBS.
BILLROTH-I GASTRIC RESECTION
Sip,—I learned the good qualities and technique of this fine operation from Professor John Morley in 1932 and later from Dr. Schoemacher and Dr. Ten Kate of The Hague. They fired me with enthusiasm for it, and in 1937-38 I performed it for all gastric and duodenal ulcers and occasionally for cancer of the stomach. In 1940-41 those patients in whom it had been done for a duodenal ulcerneededre-operation because ofre-ulceration. This taught me that it is not a good operation for this condition. I have now done over 405 of this type of partial gastrectomy, and time has confirmed its value for gastric ulcer ; for coincidental gastric and duodenal ulcers when the latter is small ; for anastomotic -ulcers after gastro-enterostomy, provided that the duodenal ulcer is very little scarred ; for cases in which a small duodenal ulcer has bled or in which the acid content of the gastric juice is low ; and occasionally for a small gastric cancer when no secondaries are detected. Regarding the technique, the stomach is mobilised to the cardio-oesophageal junction on the lesser curve and up to the last vasa brevia at the upper pole of the spleen. The second and third parts of the duodenum are mobilised. The stomach is resected from just below the cardio-cesophageal junction to the lower pole of the spleen, whilst if there is a duodenal ulcer or scar it is removed also. The anastomosis is made by interrupted sutures without the use of clamps (the duodenum is fragile compared with the stomach). Care is taken not to make too wide a flange between the stomach and duodenum lest it delay postoperative gastric emptying. Recovery is usually uneventful : an occasional patient has gastric retention for 7-12 days, but this has rarely happened since the duodenum has been mobilised. The risk of injury to the common bile-duct is a real but slight one : to be aware of it is usually to avoid it. The mortality is around 4%. After the operation, discomfort after food is very unusual and can always be controlled by the simple expedient of taking the meals dry, drinking 2-3 hours
later. Postoperative annomia, when it occurs, is an exception to the rule. These patients enjoy a slightly higher level of vigour and weight than those treated by resection of the stomach and gastrojejunostomy. Because of the recurrence of ulceration when the operation is done for a duodenal ulcer, I formed the opinion that in some patients the duodenum may be a defective structure, for there is no doubt that they do well after the Polya-Balfour resection whether the anastomosis bo anterocolic or posterocolic. In both procedures I excise the same amount of stomach. HAROLD DODD. Jjondcn W.I. SiR,—I read with special interest the article by Dr. Schmitz and his colleagues in your issue of July 3, since we also have some experience of this operation. Over 1000 Billroth-i resections have been done at Whipps Cross Hospital by my colleague, Mr. W. E. Joseph, and myself. Most of these operations have been performed by Mr. Joseph who uses the B.I for nearly all gastric and duodenal ulcers, whereas for duodenal ulcers I use the B.i more selectively. We agree with the writers that there is less postprandial trouble, and better nutrition, after the B.I than after the B.n operation. But, after all, this is to be expected since a closer approximation to normal function is achieved by the B.I. Again any surgeon who has experience of both operations can be in little doubt that it is the preferable procedure for gastric ulcers since it is more simply and quickly performed, is equally safe, and restores normal continuity of the What controversy that exists, alimentary tract. therefore, centres round the duodenal ulcer. I agree with Mr. Capper and Mr. Welbourn (July 24) that the B .1 is at its best for duodenal ulcers, as a limited gastrectomy with vagotomy. It has already been sufficiently shown that stomal ulcer is prohibitively common if B.i resection is carried out. The problem really lies in the grossly adherent duodenal ulcer. Here, the more skilled the surgeon and the more he practises, the more duodenectomies he can do and complete satisfactorily by a gastroduodenostomy; and in certain cases, if this is impracticable, the von Haberer modification helps out well, particularly if the B.n is being converted into a B.I. But although Schmitz et al. and other surgeons, like my colleague, have achieved a low mortality and morbidity using the B.I operation and although I have a high regard for the operation myself, I am doubtful whether it would be a sound policy for all surgeons to strive to use the B.i for all duodenal ulcers. It is, perhaps, well to remember that the present safety of modern B.n operations has been hard won during the past decade or-so, and to jettison its safety for a slight improvement in function may be losing perspective. When faced with a large duodenal ulcer fixed to the posterior wall of a fat abdomen, I have blessed the Bancroft manoeuvre for its simplicity and security. Surely to attempt a B.I anastomosis in such a case would be to ignore Billroth’s own assessment of his two operations : "My heart draws towards the Billroth-i, my " and, no doubt, Billroth experience to Billroth-n ; himself was as technically skilled as the best today. Finally, a word must be said for’the B.II. Sir Heneage Ogilvie is constantly reminding us that if certain desiderata are fulfilled (and these have been recently most ably summarised by Mr. Daintree Johnson 1) over 85% who have had this operation are restored to health and good eating. This is in accord with the experience of all my colleagues who use the B.n operation exclusively. It is difficult to understand, therefore, why somewhat bizarre methods are put forward from time to time as alternative procedures. In 1952, in your columns,2 Mr. Grayton Brown and his colleagues
inadequate
1. Postgrad, med. J. June, 1954. 2. Lancet, 1852, ii, 1145.
388 described a method of irradiation of the cells of the stomach to reduce acid secretion in conjunction with When there is available a simple and antrectomy. certain method of reducing gastric secretion by vagotomy, is it justifiable to injure the potentially unstable cells of the stomach-and, who knows, those of the pancreas and kidneys We were assured that the dose was small and harmless but it seems to me a sinister coincidence that I have seen two cases of carcinoma of the cardia appear within eighteen months of irradiation of the lower dorsal spine for arthritis. Moreover, should the acini recover their normal powers of secretion, these patients would seem to be likely candidates for stomal ulceration. I submit that progressive investigation must not be confused with change for the sake of change, and that, used selectively in chronic peptic ulcer, the B.I and B.n operations can give a high degree of satisfaction to patients and surgeons alike. D. LANG STEVENSON. Ilford. Essex. SASKATCHEWAN AND SHEFFIELD SiR, Your editorial of July 3 naturally attracted our attention and I wish to thank you for the recognition given to our efforts here to provide needed hospital care to the population of this rural province. At the same time, it may be useful to correct certain minor errors in your account and to offer certain explanations of the unusually high volume of hospital care in Saskatchewan. As to the errors, the Saskatchewan Hospital Services Plan provides for hospitalisation of unlimited duration within the province : the only condition is that the attending physician declares the patient to need the hospital care. The limitation of 60 days per year applies only to hospitalisation of beneficiaries outside of this province, which accounts for less than 3% of cases. The exclusion of care for tuberculosis, mental disease, and blood for transfusions is due, of course, to the fact that these needs are met by other public programmes. Outpatient services, however, are not now covered, except in one area of the province, with 50,000 population, which enjoys a comprehensive medical-care insurance programme. The increase in hospital beds since 1947 has been great, but not quite so great as that implied by the figures you published. The bed capacity in 1947 was 3966, rather than 2966, a figure which rose to 5692 in 1952. It is not quite correct, however, to speak of " beds in existence," since these figures apply to what we speak of as " rated capacity," which is a measure of the number of
hospital can physically accommodate within proper hygienic and medical standards. Because of the high demand for hospitalisation in this prairie region, the beds actually set up in our hospitals have always been somewhat higher-and even more so since the inauguration of our hospital insurance plan. At the end of 1953, for example, the beds actually in existence in general hospitals, or our " bed complement " as we call it, was
beds
a
6211 beds.
As for the reason for our high supply of general hospital beds-which incidentally is the highest of any province or State on this continent-special factors are relevant. Most important, without a doubt, is the system of universal hospital insurance which has covered our population since 1947-the first such programme on this continent. This has made it possible for hospitals to operate and expand, with financial security. Along with this has been an energetic effort on the part of provincial and local governments to support hospital construction and expansion, with some financial aid from the national government since 1948. (The great majority of construction costs, however, are borne by the local people in the communities where our 160 hospitals have been built.) Highly important, however, is the nature of our population settlement and the role played by the hospital in
this setting. Our 861,000 residents are extremely thinly settled on these vast wheat-growing plains ; the density is 3.04 persons per sq. mile. Doctors likewise are thinly settled and most of them practise in isolation or with only one, two, or three colleagues in the community. Under these circumstances, the hospital is used for the treatment of illness, and must be so used, much more frequently than in a highly urban setting like Sheffield With distances or almost any community in England. so great, it is extremely difficult for the doctor to treat a seriously ill patient at home and equally difficult for such a patient to make frequent visits to the doctor’s surgeryor his " office " as we would say. In our urban centres In 1952, we find the rate of hospitalisation much lower. the rate of hospital discharges per 1000 population in our cities (places of 5000 population or more) was 172 per 1000, compared with 216 per 1000 in the rest of the province. And, incidentally, even with our 7-2 beds per 1000 population and 2139 days of patient care per 1000 population per year, many of our hospitals have waitinglists. We are still seeking the answer on the absolute need for hospital beds. Any advice would be appreciated, as would any visitors from Sheffield or elsewhere in Britain who would like to come over and studv our efforts to find the answer. Provincial Health Building
F. B. ROTH
Regina, Saskatchewan, Canada.
Deputy Minister, Saskatchewan.
CYANACETIC ACID HYDRAZIDE
SiR,-The report from the Continent of the tuberculostatic effect of cyanacetic acid hydrazide (C.À.H.),1--3and its clinical trial in this country, prompt us to give a brief account of our own observations. We have studied the in-vitro and in-vivo action of the drug against Jtfycobacterium tuberculosis, using both H37Rv and isoniazidresistant strains. In Dubos-Middlebrook medium containing albumin and ’Tween 80,’ we found the minimum inhibitory concentration of c.A.H. against the normal strain of H37Rv to be about 3 !J.g. per ml. Under the same conditions the minimum inhibitory concentration of p-a.minosalicylic acid is about 10 !J.g. per ml. and that"of isoniazid about 0-03 &mgr;g. per ml. Against a resistant strain, the be of which could inhibited by 7 (Ag. of isoniazid growth per ml., a concentration of 30 jig. of C.A.H. per ml. was required for inhibition of growth. The in-vivo activity of the substance was measured by survival and corneal tests in mice. Using an isoniazidsensitive strain, concentrations of up to 0-04% of C.A.H. in the diet of infected mice had no protective action against the infection, whereas 0-004% of isoniazid protected 80-100% of the animals. Using an isoniazidresistant strain, C.A.11. was similarly ineffective. The toxicity of c.A.ri. was investigated on mice, rats, and guineapigs. The approximate acute oral LD50 for mice was found to be 250 mg. per kg. body.weight (agreeing with published figures) and the comparable figure for isoniazid was 140 mg. From chronic toxicity tests, it appeared that 80 mg. per kg. is a toxic dose of C.A.H. in all three species of animal and that isoniazid is less toxic in rats and guineapigs and rather more toxic in mice. Summarising our results, it seems that cyanacetic acid hydrazide is considerably less active than isoniazid against ]}I. tuberculosis H37Rv and has very little activity against an isoniazid-resistant strain of the organism. Its toxicity is of the same order as that of isoniazid, being somewhat dependent upon the species of animal used. "
Valdecasas, F., Salva, J. A., Puig Muset, P. 1952, 19, 275. 2. Hartl, W. Schweiz. Zschr. Tuberk. 1954, 11, 65. 3. Scheu, H. Ibid, p. 77. 1. Garcia
Med. clin.
androst-4-ene-3:11:17-trione, llp-hydroxyandrost-4-ene3 :17-dione, 3oc-hydroxytestane-11:17-dione, and 3ot:llp-
dihydroaytestan-17-one were found in the organic phase : using carbon tetrachloride 46, 20, 53, and 33% re8pectively, using ethylene dichlorido 98, 85, 104, and 90% respectively. From the evidence presented we conclude that, contrary to what has been implied in your leading article, Brooks and Clayton’s interesting findings in no way reflect on the value or reliability of the method for the determination of urinary 17-ketogenic steroids. Chemical Research Laboratory, Rheumatism Research Unit, Nether Edge Hospital, Sheffield.
J. K. NORYMBERSKI R. D. STUBBS.
BILLROTH-I GASTRIC RESECTION
Sip,—I learned the good qualities and technique of this fine operation from Professor John Morley in 1932 and later from Dr. Schoemacher and Dr. Ten Kate of The Hague. They fired me with enthusiasm for it, and in 1937-38 I performed it for all gastric and duodenal ulcers and occasionally for cancer of the stomach. In 1940-41 those patients in whom it had been done for a duodenal ulcerneededre-operation because ofre-ulceration. This taught me that it is not a good operation for this condition. I have now done over 405 of this type of partial gastrectomy, and time has confirmed its value for gastric ulcer ; for coincidental gastric and duodenal ulcers when the latter is small ; for anastomotic -ulcers after gastro-enterostomy, provided that the duodenal ulcer is very little scarred ; for cases in which a small duodenal ulcer has bled or in which the acid content of the gastric juice is low ; and occasionally for a small gastric cancer when no secondaries are detected. Regarding the technique, the stomach is mobilised to the cardio-oesophageal junction on the lesser curve and up to the last vasa brevia at the upper pole of the spleen. The second and third parts of the duodenum are mobilised. The stomach is resected from just below the cardio-cesophageal junction to the lower pole of the spleen, whilst if there is a duodenal ulcer or scar it is removed also. The anastomosis is made by interrupted sutures without the use of clamps (the duodenum is fragile compared with the stomach). Care is taken not to make too wide a flange between the stomach and duodenum lest it delay postoperative gastric emptying. Recovery is usually uneventful : an occasional patient has gastric retention for 7-12 days, but this has rarely happened since the duodenum has been mobilised. The risk of injury to the common bile-duct is a real but slight one : to be aware of it is usually to avoid it. The mortality is around 4%. After the operation, discomfort after food is very unusual and can always be controlled by the simple expedient of taking the meals dry, drinking 2-3 hours
later. Postoperative annomia, when it occurs, is an exception to the rule. These patients enjoy a slightly higher level of vigour and weight than those treated by resection of the stomach and gastrojejunostomy. Because of the recurrence of ulceration when the operation is done for a duodenal ulcer, I formed the opinion that in some patients the duodenum may be a defective structure, for there is no doubt that they do well after the Polya-Balfour resection whether the anastomosis bo anterocolic or posterocolic. In both procedures I excise the same amount of stomach. HAROLD DODD. Jjondcn W.I. SiR,—I read with special interest the article by Dr. Schmitz and his colleagues in your issue of July 3, since we also have some experience of this operation. Over 1000 Billroth-i resections have been done at Whipps Cross Hospital by my colleague, Mr. W. E. Joseph, and myself. Most of these operations have been performed by Mr. Joseph who uses the B.I for nearly all gastric and duodenal ulcers, whereas for duodenal ulcers I use the B.i more selectively. We agree with the writers that there is less postprandial trouble, and better nutrition, after the B.I than after the B.n operation. But, after all, this is to be expected since a closer approximation to normal function is achieved by the B.I. Again any surgeon who has experience of both operations can be in little doubt that it is the preferable procedure for gastric ulcers since it is more simply and quickly performed, is equally safe, and restores normal continuity of the What controversy that exists, alimentary tract. therefore, centres round the duodenal ulcer. I agree with Mr. Capper and Mr. Welbourn (July 24) that the B .1 is at its best for duodenal ulcers, as a limited gastrectomy with vagotomy. It has already been sufficiently shown that stomal ulcer is prohibitively common if B.i resection is carried out. The problem really lies in the grossly adherent duodenal ulcer. Here, the more skilled the surgeon and the more he practises, the more duodenectomies he can do and complete satisfactorily by a gastroduodenostomy; and in certain cases, if this is impracticable, the von Haberer modification helps out well, particularly if the B.n is being converted into a B.I. But although Schmitz et al. and other surgeons, like my colleague, have achieved a low mortality and morbidity using the B.I operation and although I have a high regard for the operation myself, I am doubtful whether it would be a sound policy for all surgeons to strive to use the B.i for all duodenal ulcers. It is, perhaps, well to remember that the present safety of modern B.n operations has been hard won during the past decade or-so, and to jettison its safety for a slight improvement in function may be losing perspective. When faced with a large duodenal ulcer fixed to the posterior wall of a fat abdomen, I have blessed the Bancroft manoeuvre for its simplicity and security. Surely to attempt a B.I anastomosis in such a case would be to ignore Billroth’s own assessment of his two operations : "My heart draws towards the Billroth-i, my " and, no doubt, Billroth experience to Billroth-n ; himself was as technically skilled as the best today. Finally, a word must be said for’the B.II. Sir Heneage Ogilvie is constantly reminding us that if certain desiderata are fulfilled (and these have been recently most ably summarised by Mr. Daintree Johnson 1) over 85% who have had this operation are restored to health and good eating. This is in accord with the experience of all my colleagues who use the B.n operation exclusively. It is difficult to understand, therefore, why somewhat bizarre methods are put forward from time to time as alternative procedures. In 1952, in your columns,2 Mr. Grayton Brown and his colleagues
inadequate
1. Postgrad, med. J. June, 1954. 2. Lancet, 1852, ii, 1145.
388 described a method of irradiation of the cells of the stomach to reduce acid secretion in conjunction with When there is available a simple and antrectomy. certain method of reducing gastric secretion by vagotomy, is it justifiable to injure the potentially unstable cells of the stomach-and, who knows, those of the pancreas and kidneys We were assured that the dose was small and harmless but it seems to me a sinister coincidence that I have seen two cases of carcinoma of the cardia appear within eighteen months of irradiation of the lower dorsal spine for arthritis. Moreover, should the acini recover their normal powers of secretion, these patients would seem to be likely candidates for stomal ulceration. I submit that progressive investigation must not be confused with change for the sake of change, and that, used selectively in chronic peptic ulcer, the B.I and B.n operations can give a high degree of satisfaction to patients and surgeons alike. D. LANG STEVENSON. Ilford. Essex. SASKATCHEWAN AND SHEFFIELD SiR, Your editorial of July 3 naturally attracted our attention and I wish to thank you for the recognition given to our efforts here to provide needed hospital care to the population of this rural province. At the same time, it may be useful to correct certain minor errors in your account and to offer certain explanations of the unusually high volume of hospital care in Saskatchewan. As to the errors, the Saskatchewan Hospital Services Plan provides for hospitalisation of unlimited duration within the province : the only condition is that the attending physician declares the patient to need the hospital care. The limitation of 60 days per year applies only to hospitalisation of beneficiaries outside of this province, which accounts for less than 3% of cases. The exclusion of care for tuberculosis, mental disease, and blood for transfusions is due, of course, to the fact that these needs are met by other public programmes. Outpatient services, however, are not now covered, except in one area of the province, with 50,000 population, which enjoys a comprehensive medical-care insurance programme. The increase in hospital beds since 1947 has been great, but not quite so great as that implied by the figures you published. The bed capacity in 1947 was 3966, rather than 2966, a figure which rose to 5692 in 1952. It is not quite correct, however, to speak of " beds in existence," since these figures apply to what we speak of as " rated capacity," which is a measure of the number of
hospital can physically accommodate within proper hygienic and medical standards. Because of the high demand for hospitalisation in this prairie region, the beds actually set up in our hospitals have always been somewhat higher-and even more so since the inauguration of our hospital insurance plan. At the end of 1953, for example, the beds actually in existence in general hospitals, or our " bed complement " as we call it, was
beds
a
6211 beds.
As for the reason for our high supply of general hospital beds-which incidentally is the highest of any province or State on this continent-special factors are relevant. Most important, without a doubt, is the system of universal hospital insurance which has covered our population since 1947-the first such programme on this continent. This has made it possible for hospitals to operate and expand, with financial security. Along with this has been an energetic effort on the part of provincial and local governments to support hospital construction and expansion, with some financial aid from the national government since 1948. (The great majority of construction costs, however, are borne by the local people in the communities where our 160 hospitals have been built.) Highly important, however, is the nature of our population settlement and the role played by the hospital in
this setting. Our 861,000 residents are extremely thinly settled on these vast wheat-growing plains ; the density is 3.04 persons per sq. mile. Doctors likewise are thinly settled and most of them practise in isolation or with only one, two, or three colleagues in the community. Under these circumstances, the hospital is used for the treatment of illness, and must be so used, much more frequently than in a highly urban setting like Sheffield With distances or almost any community in England. so great, it is extremely difficult for the doctor to treat a seriously ill patient at home and equally difficult for such a patient to make frequent visits to the doctor’s surgeryor his " office " as we would say. In our urban centres In 1952, we find the rate of hospitalisation much lower. the rate of hospital discharges per 1000 population in our cities (places of 5000 population or more) was 172 per 1000, compared with 216 per 1000 in the rest of the province. And, incidentally, even with our 7-2 beds per 1000 population and 2139 days of patient care per 1000 population per year, many of our hospitals have waitinglists. We are still seeking the answer on the absolute need for hospital beds. Any advice would be appreciated, as would any visitors from Sheffield or elsewhere in Britain who would like to come over and studv our efforts to find the answer. Provincial Health Building
F. B. ROTH
Regina, Saskatchewan, Canada.
Deputy Minister, Saskatchewan.
CYANACETIC ACID HYDRAZIDE
SiR,-The report from the Continent of the tuberculostatic effect of cyanacetic acid hydrazide (C.À.H.),1--3and its clinical trial in this country, prompt us to give a brief account of our own observations. We have studied the in-vitro and in-vivo action of the drug against Jtfycobacterium tuberculosis, using both H37Rv and isoniazidresistant strains. In Dubos-Middlebrook medium containing albumin and ’Tween 80,’ we found the minimum inhibitory concentration of c.A.H. against the normal strain of H37Rv to be about 3 !J.g. per ml. Under the same conditions the minimum inhibitory concentration of p-a.minosalicylic acid is about 10 !J.g. per ml. and that"of isoniazid about 0-03 &mgr;g. per ml. Against a resistant strain, the be of which could inhibited by 7 (Ag. of isoniazid growth per ml., a concentration of 30 jig. of C.A.H. per ml. was required for inhibition of growth. The in-vivo activity of the substance was measured by survival and corneal tests in mice. Using an isoniazidsensitive strain, concentrations of up to 0-04% of C.A.H. in the diet of infected mice had no protective action against the infection, whereas 0-004% of isoniazid protected 80-100% of the animals. Using an isoniazidresistant strain, C.A.11. was similarly ineffective. The toxicity of c.A.ri. was investigated on mice, rats, and guineapigs. The approximate acute oral LD50 for mice was found to be 250 mg. per kg. body.weight (agreeing with published figures) and the comparable figure for isoniazid was 140 mg. From chronic toxicity tests, it appeared that 80 mg. per kg. is a toxic dose of C.A.H. in all three species of animal and that isoniazid is less toxic in rats and guineapigs and rather more toxic in mice. Summarising our results, it seems that cyanacetic acid hydrazide is considerably less active than isoniazid against ]}I. tuberculosis H37Rv and has very little activity against an isoniazid-resistant strain of the organism. Its toxicity is of the same order as that of isoniazid, being somewhat dependent upon the species of animal used. "
Valdecasas, F., Salva, J. A., Puig Muset, P. 1952, 19, 275. 2. Hartl, W. Schweiz. Zschr. Tuberk. 1954, 11, 65. 3. Scheu, H. Ibid, p. 77. 1. Garcia
Med. clin.