346
nine years or more. Such figures sound daunting, but the actual number of women likely to be affected is probably extremely small. After combining data from two large family planning surveys based on nearly 45 000 women-years of oral contraceptive use and two population studies including six million individuals Vessey et a 15 could find only one case of primary hepatic neoplasm. Possibly, however, now that women are increasingly tending to take the pill continuously and for a long time, the full scale of the problem has not yet come to light. Unfortunately we have no simple screening test for diagnosing liver tumours, since conventional liver function tests are unhelpful (as is measuring alphafetoprotein), and hepatic scintiscanning will miss smaller tumours.2 Grey scale ultrasound may prove useful, as it has been in screening for hepatic fibrosis and angiosarcoma in vinyl chloride workers,16 but the role of this remains to be assessed. Meanwhile, a high index of suspicion should be maintained in all women on the pill who have unexplained enlargement of the liver or upper abdominal pain. 1 Baum, J K, et al, Lancet, 1973, 2, 926. 2 Nissen, E D, et al, Obstetrics and Gynecology, 1976, 48, 49. 3 O'Sullivan, J P, and Wilding, R P, British Medical Journal, 1974, 3, 7. 4 Christopherson, W M, Mays, E T, and Barrows, G H, Obstetrics and Gynecology, 1975, 46, 221. Mays, E T, et al, J7ournal of the American Medical Association, 1976, 235, 730. Edmondson, H A, Henderson, B, and Benton, B, New England Journal of Medicine, 1976, 294, 470. 7 Christopherson, W M, and Mays, E T, Journal of the National Cancer Institute, 1977, 58, 167. 8 Davis, M, et al, British Medical Journal, 1975, 4, 496. 9 Yanoff, M, and Rawson, A J, Archives of Pathology, 1964, 77, 159. '° British Medical Journal, 1975, 3, 209. 15 Model, D G, Fox, J A, and Jones, R W, Lancet, 1975, 1, 865. 12 Edmondson, H A, Tzumors of the Liver and Intrahepatic Bile Ducts, p 18. Washington DC, Armed Forces Institute of Pathology, 1958. 13 Committee on the Safety of Medicines, Carcinogenicity Tests of Oral Contraceptives. London, HMSO, 1975. 14 Lancet, 1973, 2, 1481. 5 Vessey, M P, et al, British MedicalyJournal, 1977, 1, 1964. 16 Taylor, K J W, et al, Proceedings of the Royal Society of Medicine, 1976, 69, 292,
Adverse effects of lithium treatment Cade' first introduced lithium for the control of mania 30 years ago, and it is now also used to control both unipolar and bipolar manic depressive states. Short-term adverse effects include nausea and tremor, while acute lithium intoxication may result in seizures or coma. Adverse reactions may also be associated, however, with long-term lithium treatment even when plasma concentrations are maintained within the therapeutic range of 0-8-1 2 mEq/l.2 The effects of lithium on the thyroid3 were first described in 1968. Patients taking lithium carbonate or sulphate may become hypothyroid, and these compounds have occasionally been used for treating thyrotoxicosis4 -though there is at least one report of lithium-induced thyrotoxicosis.5 The incidence of thyroid deficiency, often accompanied by goitre, in patients taking lithium may be as high as 150 6 but most reports7 8 put the figure at 5-90'o. Hypothyroidism is more likely in women than in men and may be accompanied by raised serum calcium and magnesium concentrations. 9 All these changes have been attributed to interference with para-
BRITISH MEDICAL JOURNAL
6 AUGUST 1977
thyroid hormone rather than to the action of lithium directly on the thyroid, but there is some evidence to the contrary."0 Clinicians who believe that hypothyroidism is a serious complication suggest that treatment with lithium should always be preceded by an evaluation of thyroid function.1" Nephrogenic diabetes insipidus12 13 with polydipsia and polyuria has often been observed in patients taking lithium, and these effects are likely to be due to interference with the action of the antidiuretic hormone. Thus lithium antagonises the hormone's stimulation of adenylcyclase, and the increase in cyclic AMP which would normally increase the permeability of the collecting tubule to water does not occur. Whether similar effects occur in the skin is less certain, though exacerbation of psoriasis has been reported, with change to a form more resistant to treatment.'4 Nevertheless, we still do not know whether this and other dermatological disorders reported were due to the lithium treatment or were associated with the primary disorder itself. Psychiatric disorders are known to be associated with a higher incidence of psoriasis.'5 Adverse effects of lithium on the heart seem to have occurred with plasma concentrations well within the recommended therapeutic range. Reversible T-wave changes (flattening or inversion) are the most frequently reported,16 17 attributed to replacement of cell potassium by lithium, which is then only slowly extruded. A similar mechanism has been proposed to account for two cases of myocarditis,'819 but again no clear link with lithium was established. Arrhythmias have occasionally been encountered, and the use of lithium should be carefully controlled in patients with existing arrhythmias. On balance, however, there is probably wide acceptance of the view of Tilkian"2 that there is insufficient evidence "to contraindicate the administration of lithium to patients with heart disease when there are clear psychiatric indications for its use." Severe adverse effects of combined lithium-haloperidol treatment were reported by Cohen and Cohen21 in four patients whose plasma lithium concentrations were above 1 2 mEq 1. Louden and Waring22 also recorded this interaction: their seven patients with bipolar mania were given lithium and haloperidol and showed extrapyramidal symptoms for a longer period than would have occurred had haloperidol been given alone. The plasma lithium concentrations were between 0-6 and 1-5 mEq 1, and when haloperidol was given rigidity, tremor, confusional states, and dystonia became evident. Assessing the adverse effects of any drug has to include teratogenicity. Lithium crosses the placental barrier readily,23 and treatment is usually said to be contraindicated during the first trimester of pregnancy11; thereafter it should be carefully appraised. Nevertheless, from a follow-up study of 60 "lithium babies" born with no obvious abnormalities to mothers who had taken lithium during the first trimester, Schou24 concluded that there was no increased frequency of either physical or mental abnormalities in the children. Again, we need more evidence, and as the indications for lithium treatment continue to expand we should have regular reviews to weigh the incidence of adverse reactions against its value in the individual case. Cade, J F J, Medical Journal of Australia, 1949, 2, 349. Ashcroft, G W, Today's Treatment, 1976, 1, 262. 3Schou, M, et al, British Medical_Journal, 1968, 3, 710. 4 Lazarus, J H, et al, Lancet, 1974, 2, 1160. 4 Franklin, L M, New Zealand Medical Journal, 1974, 79, 782. 6 Lindstedt, G, et al, British J7ournal of Psychiatry, 1977, 130, 452. 7 Lazarus, J H, and Bennie, E H, Acta Endocrinologica, 1972, 70, 266. 8 Brownlie, B E W, Australian and New Zealand J7ournal of Medicine, 1976, 6, 223. 9 Christiansen, C, et al, Neuropsychobiology, 1975, 1, 344.
2
BRITISH MEDICAL JOURNAL
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6 AUGUST 1977
'l Perez, G 0, et al, Clinical Pharmacology and Therapeutics, 1977, 21, 449. Glen, A I M, in Topics in Therapeutics, vol 2, ed P Turner. Tunbridge Wells, Pitman Medical, 1976. 12Schou, M, Acta Pharmacologica et Toxicologica, 1958, 14, 70, 85. 13 Singer, I, et al,3ournal of Clinical Investigation, 1972, 51, 1081. 14 Bakker, J B, and Pepplinkhuizen, L, Psychosomatics, 1976, 17, 143. 15 Wittkower, E, and Russell, B, Emotional Factors in Skin Diseases, p 190. London, Cassells, 1953. 16 Jaffe, C M, American Journal of Psychiatry, 1977, 134, 88. 1 Demers, R G, and Heninger, G R, Diseases of the Nervous System, 1970, 31, 674. 18 Tseng, H, Archives of Pathology, 1971, 92, 444. 19 Swedberg, K, and Winblad, B, Acta Medica Scandinavica, 1974, 196, 279. 21\ Tilkian, A G, et al, American Journal of Medicine, 1976, 61, 665. 21 Cohen, W J, and Cohen, N H,Journal of the American Medical Association, 1974, 230, 1283. 22 Loudon, J B, and Waring, H, Lancet, 1976, 2, 1088. 23 Schou, M, and Amdisen, A, American3Journal of Obstetrics and Gynecology, 1975, 122, 541. 21 Schou, M, Acta Psychiatrica Scandinavica, 1976, 54, 193.
Miconazole: a new antimycotic drug Whereas bacterial infections are often transmitted from man to man this rarely happens with the mycoses. Fungal infections are usually due to inhaling or the inoculation of spores, widespread in the environment, most of which are common animal pathogens. Candida albicans is an exception, for it is part of the normal flora of the gastrointestinal tract. How these organisms establish themselves in the body is obscure. Some fungi require a local alteration in the host, such as a cavity for Aspergillus to grow within, or a generalised disturbance, such as immunosuppression. Another feature of the disease process is the development of hypersensitivity, sometimes localisedas in the allergic pneumonitis associated with aspergillosisand sometimes more generalised, provoking a reaction such as
erythema nodosum. Many of the fungal infections such as blastomycosis, coccidioidomycosis, histoplasmosis, and sporotrichosis described in the textbooks are rare in Britain. Nevertheless, cryptococcosis should always be included in the differential diagnosis of meningitis, particularly if it starts insidiously. Candida infections, on the other hand, are common: as well as the typical oral or vaginal thrush this yeast-like organism may cause chronic paronychia, membranous oesophagitis, and more serious systemic infections. The treatment of systemic candidiasis and other deep fungal infections remains difficult. Nystatin is not absorbed from the intestinal tract. Amphotericin B may be given intravenously and, though effective,' it is toxic and may affect the kidneys and the heart as well as causing fever, nausea, or vomiting.2 A less toxic alternative is 5-fluorocytosine, which can be given by mouth, but resistant organisms may emerge when it is used in the long-term treatment of chronic conditions such as cryptococcosis and systemic candidiasis. Clotrimazole is highly active,3 well absorbed, and gives sustained blood levels, but up to 180X,, of patients tolerate it poorly.4 For these reasons an agent combining safety with high efficacy would be a welcome addition to the antimicrobial armament. Miconazole is a contender for this role. Like clotrimazole, it is an imidazole derivative, and it is active against a wide range of fungi including dermatophytes and yeasts5; some strains of aspergillus are not very sensitive. The drug is absorbed moderately well from the intestinal tract, or
it may be given intravenously. There is some evidence that miconazole acts by inhibiting peroxidative enzymes, at least in C albicans. The first clinical reports described experience with miconazole as a topical agent in vaginal candidiasis6 and skin infections.7 Nevertheless, we now have some information on its systemic use,8 which has included the treatment of mycotic infections such as coccidioidomycosis, South American blastomycosis, and aspergillosis, as well as systemic candida infections. Commonly these conditions are associated with some underlying disorder that weakens the host's resistance, and here miconazole performed fairly well, even though treatment had to be prolonged in many cases. Side effects were infrequent, diarrhoea being the most often reported, and one case of drug-induced thrombocytopenic purpura was seen. Assessment of any new antimycotic drug is always difficult, since any one investigator can treat only a limited number of the rare systemic infections. At this stage, however, miconazole looks a promising newcomer and further reports will be of wide interest. Sarosi, G A, et al, Annals of Internal Medicine, 1969, 71, 1079. 2 Miller, R P, and Bates, J H, Annals of Internal Medicine, 1969, 71, 1089. Holt, R J, and Newman, R L,Journal of Clinical Pathology, 1972, 25, 1089. 4 Weuta, H, Postgradtuate Medical Journal, 1974, 50, suppl 1, 45. 5 van Cutsem, J M, and Theinpont, D, Chemotherapy (Basle), 1972, 17, 392. 6 Godts, P, Vermylen, P, and van Cutsem, J M, Arzneimittelforschung, 1971, 21, 256. Botter, A A, Mykosen, 1971, 14, 187. 8 Proceedings of the Royal Society of Medicine, 1977, 70, suppl 1. 3
Poor-risk prostatectomy Is prostatectomy a safe and reliable operation with a trivial mortality? A recent paper from Australia' has raised doubts and has questioned this currently held belief. In a series of cases in an Adelaide teaching hospital Sach and Marshall reported an overall mortality of 2-3%/ at the end of one month, while the mortality rate for the patients aged over 80 was 9% at three months. Perhaps one man in every ten will require a prostate operation sooner or later,2 so that initially these figures seem alarming-and would be were there not some special factors in the Australian series. What must first be questioned is the statement by Sach and Marshall that, while the mortality rate has improved in general, the rate in high-risk patients has reached a plateau. This is surely incorrect when the benefits of skilled anaesthesia, careful selection, accurate haemostasis, and the transurethral operation are considered. Secondly, Sach and Marshall did not indicate how many patients were refused operation because they were unfit; and they did not find any increased mortality in patients with acute retention. Yet comparable figures elsewhere3 record only a 0.75%-10/ mortality for transurethral resection, even though many of the patients were far from ideally fit. In Jameson's series of 1600 consecutive prostatectomies4 onethird had respiratory troubles or had had a coronary thrombosis within two years previously, and a further third were admitted with acute retention. All 1600 patients were followed up for at least nine months to assess results. Jameson also recorded a series of 24 prostatectomies in patients with cardiac pacemakers without any deaths, all being dealt with by transurethral resection, with no patient refused operation. It can be accepted that generally the mortality for transurethral resection is less
nine years or more. Such figures sound daunting, but the actual number of women likely to be affected is probably extremely small. After combining data from two large family planning surveys based on nearly 45 000 women-years of oral contraceptive use and two population studies including six million individuals Vessey et a 15 could find only one case of primary hepatic neoplasm. Possibly, however, now that women are increasingly tending to take the pill continuously and for a long time, the full scale of the problem has not yet come to light. Unfortunately we have no simple screening test for diagnosing liver tumours, since conventional liver function tests are unhelpful (as is measuring alphafetoprotein), and hepatic scintiscanning will miss smaller tumours.2 Grey scale ultrasound may prove useful, as it has been in screening for hepatic fibrosis and angiosarcoma in vinyl chloride workers,16 but the role of this remains to be assessed. Meanwhile, a high index of suspicion should be maintained in all women on the pill who have unexplained enlargement of the liver or upper abdominal pain. 1 Baum, J K, et al, Lancet, 1973, 2, 926. 2 Nissen, E D, et al, Obstetrics and Gynecology, 1976, 48, 49. 3 O'Sullivan, J P, and Wilding, R P, British Medical Journal, 1974, 3, 7. 4 Christopherson, W M, Mays, E T, and Barrows, G H, Obstetrics and Gynecology, 1975, 46, 221. Mays, E T, et al, J7ournal of the American Medical Association, 1976, 235, 730. Edmondson, H A, Henderson, B, and Benton, B, New England Journal of Medicine, 1976, 294, 470. 7 Christopherson, W M, and Mays, E T, Journal of the National Cancer Institute, 1977, 58, 167. 8 Davis, M, et al, British Medical Journal, 1975, 4, 496. 9 Yanoff, M, and Rawson, A J, Archives of Pathology, 1964, 77, 159. '° British Medical Journal, 1975, 3, 209. 15 Model, D G, Fox, J A, and Jones, R W, Lancet, 1975, 1, 865. 12 Edmondson, H A, Tzumors of the Liver and Intrahepatic Bile Ducts, p 18. Washington DC, Armed Forces Institute of Pathology, 1958. 13 Committee on the Safety of Medicines, Carcinogenicity Tests of Oral Contraceptives. London, HMSO, 1975. 14 Lancet, 1973, 2, 1481. 5 Vessey, M P, et al, British MedicalyJournal, 1977, 1, 1964. 16 Taylor, K J W, et al, Proceedings of the Royal Society of Medicine, 1976, 69, 292,
Adverse effects of lithium treatment Cade' first introduced lithium for the control of mania 30 years ago, and it is now also used to control both unipolar and bipolar manic depressive states. Short-term adverse effects include nausea and tremor, while acute lithium intoxication may result in seizures or coma. Adverse reactions may also be associated, however, with long-term lithium treatment even when plasma concentrations are maintained within the therapeutic range of 0-8-1 2 mEq/l.2 The effects of lithium on the thyroid3 were first described in 1968. Patients taking lithium carbonate or sulphate may become hypothyroid, and these compounds have occasionally been used for treating thyrotoxicosis4 -though there is at least one report of lithium-induced thyrotoxicosis.5 The incidence of thyroid deficiency, often accompanied by goitre, in patients taking lithium may be as high as 150 6 but most reports7 8 put the figure at 5-90'o. Hypothyroidism is more likely in women than in men and may be accompanied by raised serum calcium and magnesium concentrations. 9 All these changes have been attributed to interference with para-
BRITISH MEDICAL JOURNAL
6 AUGUST 1977
thyroid hormone rather than to the action of lithium directly on the thyroid, but there is some evidence to the contrary."0 Clinicians who believe that hypothyroidism is a serious complication suggest that treatment with lithium should always be preceded by an evaluation of thyroid function.1" Nephrogenic diabetes insipidus12 13 with polydipsia and polyuria has often been observed in patients taking lithium, and these effects are likely to be due to interference with the action of the antidiuretic hormone. Thus lithium antagonises the hormone's stimulation of adenylcyclase, and the increase in cyclic AMP which would normally increase the permeability of the collecting tubule to water does not occur. Whether similar effects occur in the skin is less certain, though exacerbation of psoriasis has been reported, with change to a form more resistant to treatment.'4 Nevertheless, we still do not know whether this and other dermatological disorders reported were due to the lithium treatment or were associated with the primary disorder itself. Psychiatric disorders are known to be associated with a higher incidence of psoriasis.'5 Adverse effects of lithium on the heart seem to have occurred with plasma concentrations well within the recommended therapeutic range. Reversible T-wave changes (flattening or inversion) are the most frequently reported,16 17 attributed to replacement of cell potassium by lithium, which is then only slowly extruded. A similar mechanism has been proposed to account for two cases of myocarditis,'819 but again no clear link with lithium was established. Arrhythmias have occasionally been encountered, and the use of lithium should be carefully controlled in patients with existing arrhythmias. On balance, however, there is probably wide acceptance of the view of Tilkian"2 that there is insufficient evidence "to contraindicate the administration of lithium to patients with heart disease when there are clear psychiatric indications for its use." Severe adverse effects of combined lithium-haloperidol treatment were reported by Cohen and Cohen21 in four patients whose plasma lithium concentrations were above 1 2 mEq 1. Louden and Waring22 also recorded this interaction: their seven patients with bipolar mania were given lithium and haloperidol and showed extrapyramidal symptoms for a longer period than would have occurred had haloperidol been given alone. The plasma lithium concentrations were between 0-6 and 1-5 mEq 1, and when haloperidol was given rigidity, tremor, confusional states, and dystonia became evident. Assessing the adverse effects of any drug has to include teratogenicity. Lithium crosses the placental barrier readily,23 and treatment is usually said to be contraindicated during the first trimester of pregnancy11; thereafter it should be carefully appraised. Nevertheless, from a follow-up study of 60 "lithium babies" born with no obvious abnormalities to mothers who had taken lithium during the first trimester, Schou24 concluded that there was no increased frequency of either physical or mental abnormalities in the children. Again, we need more evidence, and as the indications for lithium treatment continue to expand we should have regular reviews to weigh the incidence of adverse reactions against its value in the individual case. Cade, J F J, Medical Journal of Australia, 1949, 2, 349. Ashcroft, G W, Today's Treatment, 1976, 1, 262. 3Schou, M, et al, British Medical_Journal, 1968, 3, 710. 4 Lazarus, J H, et al, Lancet, 1974, 2, 1160. 4 Franklin, L M, New Zealand Medical Journal, 1974, 79, 782. 6 Lindstedt, G, et al, British J7ournal of Psychiatry, 1977, 130, 452. 7 Lazarus, J H, and Bennie, E H, Acta Endocrinologica, 1972, 70, 266. 8 Brownlie, B E W, Australian and New Zealand J7ournal of Medicine, 1976, 6, 223. 9 Christiansen, C, et al, Neuropsychobiology, 1975, 1, 344.
2
BRITISH MEDICAL JOURNAL
347
6 AUGUST 1977
'l Perez, G 0, et al, Clinical Pharmacology and Therapeutics, 1977, 21, 449. Glen, A I M, in Topics in Therapeutics, vol 2, ed P Turner. Tunbridge Wells, Pitman Medical, 1976. 12Schou, M, Acta Pharmacologica et Toxicologica, 1958, 14, 70, 85. 13 Singer, I, et al,3ournal of Clinical Investigation, 1972, 51, 1081. 14 Bakker, J B, and Pepplinkhuizen, L, Psychosomatics, 1976, 17, 143. 15 Wittkower, E, and Russell, B, Emotional Factors in Skin Diseases, p 190. London, Cassells, 1953. 16 Jaffe, C M, American Journal of Psychiatry, 1977, 134, 88. 1 Demers, R G, and Heninger, G R, Diseases of the Nervous System, 1970, 31, 674. 18 Tseng, H, Archives of Pathology, 1971, 92, 444. 19 Swedberg, K, and Winblad, B, Acta Medica Scandinavica, 1974, 196, 279. 21\ Tilkian, A G, et al, American Journal of Medicine, 1976, 61, 665. 21 Cohen, W J, and Cohen, N H,Journal of the American Medical Association, 1974, 230, 1283. 22 Loudon, J B, and Waring, H, Lancet, 1976, 2, 1088. 23 Schou, M, and Amdisen, A, American3Journal of Obstetrics and Gynecology, 1975, 122, 541. 21 Schou, M, Acta Psychiatrica Scandinavica, 1976, 54, 193.
Miconazole: a new antimycotic drug Whereas bacterial infections are often transmitted from man to man this rarely happens with the mycoses. Fungal infections are usually due to inhaling or the inoculation of spores, widespread in the environment, most of which are common animal pathogens. Candida albicans is an exception, for it is part of the normal flora of the gastrointestinal tract. How these organisms establish themselves in the body is obscure. Some fungi require a local alteration in the host, such as a cavity for Aspergillus to grow within, or a generalised disturbance, such as immunosuppression. Another feature of the disease process is the development of hypersensitivity, sometimes localisedas in the allergic pneumonitis associated with aspergillosisand sometimes more generalised, provoking a reaction such as
erythema nodosum. Many of the fungal infections such as blastomycosis, coccidioidomycosis, histoplasmosis, and sporotrichosis described in the textbooks are rare in Britain. Nevertheless, cryptococcosis should always be included in the differential diagnosis of meningitis, particularly if it starts insidiously. Candida infections, on the other hand, are common: as well as the typical oral or vaginal thrush this yeast-like organism may cause chronic paronychia, membranous oesophagitis, and more serious systemic infections. The treatment of systemic candidiasis and other deep fungal infections remains difficult. Nystatin is not absorbed from the intestinal tract. Amphotericin B may be given intravenously and, though effective,' it is toxic and may affect the kidneys and the heart as well as causing fever, nausea, or vomiting.2 A less toxic alternative is 5-fluorocytosine, which can be given by mouth, but resistant organisms may emerge when it is used in the long-term treatment of chronic conditions such as cryptococcosis and systemic candidiasis. Clotrimazole is highly active,3 well absorbed, and gives sustained blood levels, but up to 180X,, of patients tolerate it poorly.4 For these reasons an agent combining safety with high efficacy would be a welcome addition to the antimicrobial armament. Miconazole is a contender for this role. Like clotrimazole, it is an imidazole derivative, and it is active against a wide range of fungi including dermatophytes and yeasts5; some strains of aspergillus are not very sensitive. The drug is absorbed moderately well from the intestinal tract, or
it may be given intravenously. There is some evidence that miconazole acts by inhibiting peroxidative enzymes, at least in C albicans. The first clinical reports described experience with miconazole as a topical agent in vaginal candidiasis6 and skin infections.7 Nevertheless, we now have some information on its systemic use,8 which has included the treatment of mycotic infections such as coccidioidomycosis, South American blastomycosis, and aspergillosis, as well as systemic candida infections. Commonly these conditions are associated with some underlying disorder that weakens the host's resistance, and here miconazole performed fairly well, even though treatment had to be prolonged in many cases. Side effects were infrequent, diarrhoea being the most often reported, and one case of drug-induced thrombocytopenic purpura was seen. Assessment of any new antimycotic drug is always difficult, since any one investigator can treat only a limited number of the rare systemic infections. At this stage, however, miconazole looks a promising newcomer and further reports will be of wide interest. Sarosi, G A, et al, Annals of Internal Medicine, 1969, 71, 1079. 2 Miller, R P, and Bates, J H, Annals of Internal Medicine, 1969, 71, 1089. Holt, R J, and Newman, R L,Journal of Clinical Pathology, 1972, 25, 1089. 4 Weuta, H, Postgradtuate Medical Journal, 1974, 50, suppl 1, 45. 5 van Cutsem, J M, and Theinpont, D, Chemotherapy (Basle), 1972, 17, 392. 6 Godts, P, Vermylen, P, and van Cutsem, J M, Arzneimittelforschung, 1971, 21, 256. Botter, A A, Mykosen, 1971, 14, 187. 8 Proceedings of the Royal Society of Medicine, 1977, 70, suppl 1. 3
Poor-risk prostatectomy Is prostatectomy a safe and reliable operation with a trivial mortality? A recent paper from Australia' has raised doubts and has questioned this currently held belief. In a series of cases in an Adelaide teaching hospital Sach and Marshall reported an overall mortality of 2-3%/ at the end of one month, while the mortality rate for the patients aged over 80 was 9% at three months. Perhaps one man in every ten will require a prostate operation sooner or later,2 so that initially these figures seem alarming-and would be were there not some special factors in the Australian series. What must first be questioned is the statement by Sach and Marshall that, while the mortality rate has improved in general, the rate in high-risk patients has reached a plateau. This is surely incorrect when the benefits of skilled anaesthesia, careful selection, accurate haemostasis, and the transurethral operation are considered. Secondly, Sach and Marshall did not indicate how many patients were refused operation because they were unfit; and they did not find any increased mortality in patients with acute retention. Yet comparable figures elsewhere3 record only a 0.75%-10/ mortality for transurethral resection, even though many of the patients were far from ideally fit. In Jameson's series of 1600 consecutive prostatectomies4 onethird had respiratory troubles or had had a coronary thrombosis within two years previously, and a further third were admitted with acute retention. All 1600 patients were followed up for at least nine months to assess results. Jameson also recorded a series of 24 prostatectomies in patients with cardiac pacemakers without any deaths, all being dealt with by transurethral resection, with no patient refused operation. It can be accepted that generally the mortality for transurethral resection is less
