1360 PUBERTAL FAILURE IN CONGENITAL ADRENAL HYPOPLASIA
WHICH MEDICINE?
SIR,-Your editorial (Dec 10, p. -1215) accurately
repre-
the situation but draws limited conclusions. That practitioners feel they are unable to obtain unbiased assessment of a new drug highlights their ignorance of’ the numerous regional, area, district, and hospital drug information services throughout the country, staffed by pharmacists who are able to supply such information. Practitioners choose not to use these resources. Pharmacists are also sceptical about the value of information provided by drug-company representatives, but why do prescribing figures contlnually show how successful this method is at selling the product to the medical practitioner? We accept that clinical information is of extreme importance but it is only one half of the total picture. The drug information services are already able to provide much of the necessary information-i.e., the best treatment for a particular condition, the correct administration of the drug, and the potential dangers and necessary precautions. A publication such as the one you mention would be invaluable, but when will the medical profession learn to respect and make use of the many services that pharmacists make available to them? sents
Pharmacy Department, St George’s Hospital, London SW1
WILLIAM M. PATE
SiR,-Your editorial perpetuates the myth of vast numbers of medicines available to the prescribed The figure of 30 000 you cite relates to the 36 000 products registered under the Medicines Act 1968. Only a fraction of these are prescribable. The current Chemist & Druggist monthly price list gives less than 2000 names (some repetitively) in its therapeutic index. The product (brand) index of the monthly index MIMS is of similar magnitude (2350 at the last count). Whilst this does not invalidate your case it does illustrate the misuse or misunderstanding of much data on pharmaceuticals. It is surprising how few are aware that the drug bill is currently only 8% of the total N.H.S. costs. Will your proposed information system really be either more efficient or less expensive than that provided by the industry? After all, the pharmaceutical industry has to be cost conscious and work efficiently in competition. What nationalised service-including the N.H.S.-has similar stimulants? 14
Marlborough Close, D. G. HIGGINS
on decision making in prescribing is members of the medical profession. We must the money we spend. Pharmacy information centres, as you mention, can be of great value but only if under the direct guidance of the medically qualified. You are of the opinion that the present British National Formulary is out of date, but this is bound to be the case with such a publication, useful though it is. What is required is a more up-to-date information system that guides us as to which drugs to choose (or more important which not to use) from the constant flow of those appearing. You did not mention the Drug & Therapeutics Bulletin, an admirable publication of the independent Consumers’ Association. The circulation of about 18 000 now includes 11 000 trainee and recently qualified doctors (whose subscriptions are paid for by the D.H.S.S.). Its conclusions are usually pithy, to the point, and often (to the pharmaceutical industry) painful. If a didactic summary could be circulated to all doctors this would be most useful.
SiR,-Your editorial
important to all have regard for
Department of Medical Microbiology, Dudley Road Hospital, Birmingham B18 7QH
Middlesex Hospital, London W1N 8AA
*** This letter has been shown -ED.L.
C. G. D. BROOK
to
Dr
Hay, whose reply follows.
SIR,-Dr Brook raises two important points-the possible worth of adrenal androgen therapy in congenital adrenocortical hypoplasia (C.A.H.) and the difference in pubertal behaviour between patients with C.A.H. and those with adrenocortical atrophy acquired in childhood. Adrenal androgen therapy is based on the assumption that the cause of pubertal failure lies essentially within the adrenal cortex. In the panhypoadrenocortical circumstance of C.A.H. one is already replacing the glucocorticoid and mineralocorticoid requirements, and to mimic the well-recognised prepubertal steroid hormonal profile’ it seems only logical to add adrenal androgens to the regimen. The hope of such a therapy would be that, once primed, the hypothalamic "gonadostat"2 would function autonomously and that puberty would proceed without intervention with exogenous gonadotrophin. As Brook has pointed out, the hypothalamic priming "must take place early in life,"3 and ideally adrenal androgen replacement should start about the age of 7 (i.e., at a time when, physiologically, the output of adrenal androgens begins its progressive
rise4.5) . Little information is available about any difference in adrenal androgen status between patients with C.A.H. and those with childhood Addison’s disease. The excretion of ll-deoxy-17-oxosteroids, the urinary metabolites of adrenalderived dehydroepiandrosterone and androstenedione, has, however, been measured both in a child with idiopathic adrenocortical atrophy6 and in the oldest surviving and first reported case of familial cytomegalic C.A.H.’ In the addisonian boy, who showed normal growth and skeletal maturation, the urinary metabolites, although low, were always measurable between one and two standard deviations below the mean. On the other hand, in the boy with C.A.H., the urinary products, when measured on six occasions between the of 5 and 15, were refound to be at the limit peatedly of detectability.8 The development of specific radioimmunoassays has allowed the direct measurement of serum levels of adrenal androgens, and Sizonenko et awl. have shown that in four boys with Addison’s disease aged 7-15 years the serum concentrations of both dehydroepiandrosterone and its sulphate were consistently lower than normal. In my own case of C.A.H.IO the plasma level of androstenedione has been estimated in a specific radioimmunoassay and found to be undetectable (assay sensitivity 5 ng/dl) at a chronological age of 17.6 years. In childhood Addison’s disease it is possible that the levels of adrenal androgens, although low, remain adequate for the initiation of puberty. However, in C.A.H. there appears to be
ages
Tytherington, Macclesfield SK10 2LA
SIR,--Why does Dr Hay (Nov. 12, p. 1035) think it "worthwhile to try adrenal androgens in [prepubertal] patients with familial congenital adrenal hypoplasia" when patients with Addison’s disease go into puberty spontaneously?
RICHARD WISE
1. Hopper, B. R., Yen, S. S. C. J. clin. Endocr. Metab. 1975, 40, 458. 2. Grumbach, M. M., Grave, C. D. Mayer, F. E Control of the Onset of Puberty. New York, 1974. 3. Black, S., Brook, C. G. D., Cox, P. J. N. Br med. J. 1977, ii, 996. 4. Savage, D. C. L., Forsyth, C. C., McCafferty, E., Cameron, J. Acta endocr. 1975, 79, 551. 5. Ducharme, J. R., Forest, M. G., De Peretti, E., Sempe, M., Collu, R., Bertrand, J. J. clin. Endocr. Metab., 1976, 42, 468. 6. Forsyth, C. C., Forbes, M., Cumings, J. N. Archs Dis. Childh. 1971, 46, 273. 7. Mitchell, R. G., Rhaney, K Lancet, 1963, ii, 1065. 8. Forsyth, C. C. Personal communication. 9. Sizonenko, P. C., Paunier, L., Carmignac, D. Hormone Res. 10. Hay, I. D. Lancet, 1977, ii, 1035.
1976, 7, 288.
1361 adrenal
androgen production and, perhaps spontaneous onset of puberty.
no
as a
University Department of Medicine, Royal Infirmary, Glasgow G4 0SF
result,
no
IAN D. HAY
TREATMENT OF CRYPTORCHIDISM BY SYNTHETIC LUTEINISING-HORMONE-RELEASING HORMONE
SIR,-We were interested in the article by Dr Illig and colleagues (Sept. 10, p. 518) and in the letter by Dr Hadziselimovic and co-workers (Nov. 26, p.1125) since we have been using synthetic lutenising-hormone-releasing hormone (L.H.R.H.) in cryptorchidism. 4 boys aged 7i-152 years were given L.H.R.H. subcutaneously; 3 received 500 fLg every 8 h for 3 days and 1 received 100 g every 8 h for 3 days. In 2 boys, 1 aged 15 a with
’
unilateral cryptorchidism and a very retractile testis on 500 g L.H.R.H. and 1 boy aged 7t on 100 pg L.H.R.H. who had one inpalpable testis and one highly retractile testis, there was testicular descent within 3 days of the initiation of therapy and cessation of retractility. Both children had an impaired gonadotrophin response to a standard 100 fLg L.H.R.H. test with no change in L.H. levels and a blunted follicle-stimulating hormone (F.S.H.) response. The 2 other boys, 1 aged 10 years with small inguinal testes and the other aged 13tyears with one impalpable and one retractile testis, showed no improvement after L.H.R.H. Both had a normal gonadotrophin response to 100 g of L.H.R.H., but no testosterone response to stimulation with human chorionic gonadotrophin (H.C.G.). The speed of response in the first 2 boys supports the suggestion that gonadotrophins themselves are responsible for testicular descent, though perhaps only if a testis is potentially fully functional. The descent is unlikely to be due to any systemic rise in androgen production directly relating to the gonadotrophin therapy as gonadotrophins may cause testicular descent in unilateral cryptorchidism where androgen levels are comparatively normal.’ H.C.G. has been the gonadotrophin of choice in the management of crytorchidism but there had been no general agreement about the age at which it should be given. Scorer2 noted in a large prospective series that 3.4% of testes were undescended at birth; half of these were descended at the end of the first month and at the end of the first year only 0.7% were undescended, a figure that remained virtually unchanged into adult life. Ehrlich et al.,3 reviewing management with H.C.G. therapy in 350 undescended testes, found the best response (38% success-rate) in the 2-5-year age-group compared with an overall response of 23% and only 14% in boys aged 6-13. In unilateral cryptorchidism there is evidence that the normal testis undergoes compensatory hypertrophy and normal development through puberty. There is also evidence of testosterone responsiveness to x.c.G.4 but in cases of bilateral cryptorchidism both the baseline testosterone and the response to H.C.G. stimulation are overall significantly lower than normal.l.5.6 This suggests that cryptorchidism itself leads to testicular dysfunction regardless of hypothalamic-pituitarygonadal axis status,7 although histological findings in such cases may be normal. In view of the above findings we suggest that a definite decision on the management of cryptorchidism should be made at the time the condition is first noted, even as early as 12 months of age. Therapy could begin at 12 months as the likelihood of success is probably greatest at this time. Patients who do not respond may have either primary testicular disease or ’
1. Walsh, P. C., and others. J, clin. Endocr. Metab. 1976, 42, 52. 2. Scorer, C. G. Lancet, 1957, ii, 1123. 3. Ehrlich, R. E., and others. J. Urol. 1969, 102, 793. 4. Laron, Z., Silka, E. J. clin. Endocr.Metab. 1969, 29, 1409. 5. Rivarola, M. A., Bergada, C., Cullen, M. ibid. 1970, 31, 526. 6. Cacciari, E., and others Acta endocr. Copenh. 1976, 33, 182. 7. Charny, C. W. J. Urol. 1960, 83, 607.
significant local mechanical obstruction to descent; a worsening of the obstruction or acquired testicular dysfunction may account for the increasing failure of response to gonadotrophins in the older age-group. Surgery should be contemplated for such patients but not later than the age of 10 because of the risk of permanent damage to the spermatogenic epithelium. The use of gonadotrophins after correction of cryptorchidism should not be contemplated until puberty because of the danger of premature androgenisation. Cryptorchid testes exposed to gonadotrophins following7 orchidopexy may show more rapid degeneration and sclerosis. Although L.H.R.H. treatment is a priori more physiological than H.c.G., the latter is favoured now on grounds of cost. However, our use of a 3-day subcutaneous L.H.R.H. regimen (by contrast with a month of snuff) permits speedy decisions about surgery or other investigations, and this treatment could therefore prove cheaper in the long run. Department of Endocrinology, Royal Free Hospital, London NW3 2QG
M. C. WHITE
JEAN GINSBURG
NEEDLE BIOPSY IN OVARIAN CARCINOMA
SIR,-Accurate histological classification of ovarian carcinoma may aid the choice of therapy but has been limited by the absence of a method of obtaining a sufficiently large tumour specimen. Vaginal fine-needle aspiration biopsy is widely used and has few complications1,2 but provides only enough material for cytology. I describe here a procedure in which the tumour biopsy is done first with a fine needle and immediately afterwards with a needle of large gauge similar to that used in percutaneous liver and kidney biopsy,’providing enough material for histological investigation. Before biopsy, the bladder is emptied and the vagina cleaned with antiseptic solution. The tumour should be palpable directly, with no suspicion of visceral interposition. A fine needle (0.8 mm diameter) is inserted into it via the vagina, suction applied with a Franzen syringe, and the needle moved in and out of the tumour. Suction is released when the tip is just below the vaginal mucosa. The material in the needle is ejected on to microscope slides for later cytological investigation. If it is solid and free of blood, urine or fluid from a cyst or the intestine, a second biopsy is done immediately, using a modified Iverson-Roholm needle (length 150 mm, outer diameter 2.0 mm, inner diameter 1.7 mm with a sharp right-angled tip without notches V The trocar is inserted through the vaginal puncture canal, the stylet withdrawn, and suction applied using a syringe with lock. The needle is pushed into the tumour with a rotating movement, one or more times. The needle is withdrawn with sustained suction and the fragments of tissue it contains are placed immediately in fixative. This technique should be used only in patients with advanced tumours where the alternative is a biopsy obtained by laparotomy, a procedure with a significant associated mortality. Laparotomy also has a high risk of disseminating the tumour. With needle biopsies, this risk is probably low even when a large-gauge needle is used. In my experience, the technique is safe and reliable.6 Department of Obstetrics
and Gynaecology, Central Hospital, DK-4800 Nykøbing Falster, Denmark
1. 2.
J. SERUP
Jensen, H. K., Gram, N. C., Francis, D. Ugeskr. Lœg. 1974, 136, 586. Kjellgren, O., Angstrøm, T., Bergman, F., Wiklund, D.-E. Cancer, 1971, 28, 967.
Menghini, G. Gastroenterology, 1958, 35, 190 4. Iversen, P., Brun, C. Am. J. Med. 1951, 11, 324. 5. Brun, C. in Nefro-urologi (edited by S.-E. Bergentz, E. Brodwall, p. 39. Copenhagen, 1973. 6. Serup, J. Ugeskr, Lœg. (in the press). 3.
Fl.
Lund);
WHICH MEDICINE?
SIR,-Your editorial (Dec 10, p. -1215) accurately
repre-
the situation but draws limited conclusions. That practitioners feel they are unable to obtain unbiased assessment of a new drug highlights their ignorance of’ the numerous regional, area, district, and hospital drug information services throughout the country, staffed by pharmacists who are able to supply such information. Practitioners choose not to use these resources. Pharmacists are also sceptical about the value of information provided by drug-company representatives, but why do prescribing figures contlnually show how successful this method is at selling the product to the medical practitioner? We accept that clinical information is of extreme importance but it is only one half of the total picture. The drug information services are already able to provide much of the necessary information-i.e., the best treatment for a particular condition, the correct administration of the drug, and the potential dangers and necessary precautions. A publication such as the one you mention would be invaluable, but when will the medical profession learn to respect and make use of the many services that pharmacists make available to them? sents
Pharmacy Department, St George’s Hospital, London SW1
WILLIAM M. PATE
SiR,-Your editorial perpetuates the myth of vast numbers of medicines available to the prescribed The figure of 30 000 you cite relates to the 36 000 products registered under the Medicines Act 1968. Only a fraction of these are prescribable. The current Chemist & Druggist monthly price list gives less than 2000 names (some repetitively) in its therapeutic index. The product (brand) index of the monthly index MIMS is of similar magnitude (2350 at the last count). Whilst this does not invalidate your case it does illustrate the misuse or misunderstanding of much data on pharmaceuticals. It is surprising how few are aware that the drug bill is currently only 8% of the total N.H.S. costs. Will your proposed information system really be either more efficient or less expensive than that provided by the industry? After all, the pharmaceutical industry has to be cost conscious and work efficiently in competition. What nationalised service-including the N.H.S.-has similar stimulants? 14
Marlborough Close, D. G. HIGGINS
on decision making in prescribing is members of the medical profession. We must the money we spend. Pharmacy information centres, as you mention, can be of great value but only if under the direct guidance of the medically qualified. You are of the opinion that the present British National Formulary is out of date, but this is bound to be the case with such a publication, useful though it is. What is required is a more up-to-date information system that guides us as to which drugs to choose (or more important which not to use) from the constant flow of those appearing. You did not mention the Drug & Therapeutics Bulletin, an admirable publication of the independent Consumers’ Association. The circulation of about 18 000 now includes 11 000 trainee and recently qualified doctors (whose subscriptions are paid for by the D.H.S.S.). Its conclusions are usually pithy, to the point, and often (to the pharmaceutical industry) painful. If a didactic summary could be circulated to all doctors this would be most useful.
SiR,-Your editorial
important to all have regard for
Department of Medical Microbiology, Dudley Road Hospital, Birmingham B18 7QH
Middlesex Hospital, London W1N 8AA
*** This letter has been shown -ED.L.
C. G. D. BROOK
to
Dr
Hay, whose reply follows.
SIR,-Dr Brook raises two important points-the possible worth of adrenal androgen therapy in congenital adrenocortical hypoplasia (C.A.H.) and the difference in pubertal behaviour between patients with C.A.H. and those with adrenocortical atrophy acquired in childhood. Adrenal androgen therapy is based on the assumption that the cause of pubertal failure lies essentially within the adrenal cortex. In the panhypoadrenocortical circumstance of C.A.H. one is already replacing the glucocorticoid and mineralocorticoid requirements, and to mimic the well-recognised prepubertal steroid hormonal profile’ it seems only logical to add adrenal androgens to the regimen. The hope of such a therapy would be that, once primed, the hypothalamic "gonadostat"2 would function autonomously and that puberty would proceed without intervention with exogenous gonadotrophin. As Brook has pointed out, the hypothalamic priming "must take place early in life,"3 and ideally adrenal androgen replacement should start about the age of 7 (i.e., at a time when, physiologically, the output of adrenal androgens begins its progressive
rise4.5) . Little information is available about any difference in adrenal androgen status between patients with C.A.H. and those with childhood Addison’s disease. The excretion of ll-deoxy-17-oxosteroids, the urinary metabolites of adrenalderived dehydroepiandrosterone and androstenedione, has, however, been measured both in a child with idiopathic adrenocortical atrophy6 and in the oldest surviving and first reported case of familial cytomegalic C.A.H.’ In the addisonian boy, who showed normal growth and skeletal maturation, the urinary metabolites, although low, were always measurable between one and two standard deviations below the mean. On the other hand, in the boy with C.A.H., the urinary products, when measured on six occasions between the of 5 and 15, were refound to be at the limit peatedly of detectability.8 The development of specific radioimmunoassays has allowed the direct measurement of serum levels of adrenal androgens, and Sizonenko et awl. have shown that in four boys with Addison’s disease aged 7-15 years the serum concentrations of both dehydroepiandrosterone and its sulphate were consistently lower than normal. In my own case of C.A.H.IO the plasma level of androstenedione has been estimated in a specific radioimmunoassay and found to be undetectable (assay sensitivity 5 ng/dl) at a chronological age of 17.6 years. In childhood Addison’s disease it is possible that the levels of adrenal androgens, although low, remain adequate for the initiation of puberty. However, in C.A.H. there appears to be
ages
Tytherington, Macclesfield SK10 2LA
SIR,--Why does Dr Hay (Nov. 12, p. 1035) think it "worthwhile to try adrenal androgens in [prepubertal] patients with familial congenital adrenal hypoplasia" when patients with Addison’s disease go into puberty spontaneously?
RICHARD WISE
1. Hopper, B. R., Yen, S. S. C. J. clin. Endocr. Metab. 1975, 40, 458. 2. Grumbach, M. M., Grave, C. D. Mayer, F. E Control of the Onset of Puberty. New York, 1974. 3. Black, S., Brook, C. G. D., Cox, P. J. N. Br med. J. 1977, ii, 996. 4. Savage, D. C. L., Forsyth, C. C., McCafferty, E., Cameron, J. Acta endocr. 1975, 79, 551. 5. Ducharme, J. R., Forest, M. G., De Peretti, E., Sempe, M., Collu, R., Bertrand, J. J. clin. Endocr. Metab., 1976, 42, 468. 6. Forsyth, C. C., Forbes, M., Cumings, J. N. Archs Dis. Childh. 1971, 46, 273. 7. Mitchell, R. G., Rhaney, K Lancet, 1963, ii, 1065. 8. Forsyth, C. C. Personal communication. 9. Sizonenko, P. C., Paunier, L., Carmignac, D. Hormone Res. 10. Hay, I. D. Lancet, 1977, ii, 1035.
1976, 7, 288.
1361 adrenal
androgen production and, perhaps spontaneous onset of puberty.
no
as a
University Department of Medicine, Royal Infirmary, Glasgow G4 0SF
result,
no
IAN D. HAY
TREATMENT OF CRYPTORCHIDISM BY SYNTHETIC LUTEINISING-HORMONE-RELEASING HORMONE
SIR,-We were interested in the article by Dr Illig and colleagues (Sept. 10, p. 518) and in the letter by Dr Hadziselimovic and co-workers (Nov. 26, p.1125) since we have been using synthetic lutenising-hormone-releasing hormone (L.H.R.H.) in cryptorchidism. 4 boys aged 7i-152 years were given L.H.R.H. subcutaneously; 3 received 500 fLg every 8 h for 3 days and 1 received 100 g every 8 h for 3 days. In 2 boys, 1 aged 15 a with
’
unilateral cryptorchidism and a very retractile testis on 500 g L.H.R.H. and 1 boy aged 7t on 100 pg L.H.R.H. who had one inpalpable testis and one highly retractile testis, there was testicular descent within 3 days of the initiation of therapy and cessation of retractility. Both children had an impaired gonadotrophin response to a standard 100 fLg L.H.R.H. test with no change in L.H. levels and a blunted follicle-stimulating hormone (F.S.H.) response. The 2 other boys, 1 aged 10 years with small inguinal testes and the other aged 13tyears with one impalpable and one retractile testis, showed no improvement after L.H.R.H. Both had a normal gonadotrophin response to 100 g of L.H.R.H., but no testosterone response to stimulation with human chorionic gonadotrophin (H.C.G.). The speed of response in the first 2 boys supports the suggestion that gonadotrophins themselves are responsible for testicular descent, though perhaps only if a testis is potentially fully functional. The descent is unlikely to be due to any systemic rise in androgen production directly relating to the gonadotrophin therapy as gonadotrophins may cause testicular descent in unilateral cryptorchidism where androgen levels are comparatively normal.’ H.C.G. has been the gonadotrophin of choice in the management of crytorchidism but there had been no general agreement about the age at which it should be given. Scorer2 noted in a large prospective series that 3.4% of testes were undescended at birth; half of these were descended at the end of the first month and at the end of the first year only 0.7% were undescended, a figure that remained virtually unchanged into adult life. Ehrlich et al.,3 reviewing management with H.C.G. therapy in 350 undescended testes, found the best response (38% success-rate) in the 2-5-year age-group compared with an overall response of 23% and only 14% in boys aged 6-13. In unilateral cryptorchidism there is evidence that the normal testis undergoes compensatory hypertrophy and normal development through puberty. There is also evidence of testosterone responsiveness to x.c.G.4 but in cases of bilateral cryptorchidism both the baseline testosterone and the response to H.C.G. stimulation are overall significantly lower than normal.l.5.6 This suggests that cryptorchidism itself leads to testicular dysfunction regardless of hypothalamic-pituitarygonadal axis status,7 although histological findings in such cases may be normal. In view of the above findings we suggest that a definite decision on the management of cryptorchidism should be made at the time the condition is first noted, even as early as 12 months of age. Therapy could begin at 12 months as the likelihood of success is probably greatest at this time. Patients who do not respond may have either primary testicular disease or ’
1. Walsh, P. C., and others. J, clin. Endocr. Metab. 1976, 42, 52. 2. Scorer, C. G. Lancet, 1957, ii, 1123. 3. Ehrlich, R. E., and others. J. Urol. 1969, 102, 793. 4. Laron, Z., Silka, E. J. clin. Endocr.Metab. 1969, 29, 1409. 5. Rivarola, M. A., Bergada, C., Cullen, M. ibid. 1970, 31, 526. 6. Cacciari, E., and others Acta endocr. Copenh. 1976, 33, 182. 7. Charny, C. W. J. Urol. 1960, 83, 607.
significant local mechanical obstruction to descent; a worsening of the obstruction or acquired testicular dysfunction may account for the increasing failure of response to gonadotrophins in the older age-group. Surgery should be contemplated for such patients but not later than the age of 10 because of the risk of permanent damage to the spermatogenic epithelium. The use of gonadotrophins after correction of cryptorchidism should not be contemplated until puberty because of the danger of premature androgenisation. Cryptorchid testes exposed to gonadotrophins following7 orchidopexy may show more rapid degeneration and sclerosis. Although L.H.R.H. treatment is a priori more physiological than H.c.G., the latter is favoured now on grounds of cost. However, our use of a 3-day subcutaneous L.H.R.H. regimen (by contrast with a month of snuff) permits speedy decisions about surgery or other investigations, and this treatment could therefore prove cheaper in the long run. Department of Endocrinology, Royal Free Hospital, London NW3 2QG
M. C. WHITE
JEAN GINSBURG
NEEDLE BIOPSY IN OVARIAN CARCINOMA
SIR,-Accurate histological classification of ovarian carcinoma may aid the choice of therapy but has been limited by the absence of a method of obtaining a sufficiently large tumour specimen. Vaginal fine-needle aspiration biopsy is widely used and has few complications1,2 but provides only enough material for cytology. I describe here a procedure in which the tumour biopsy is done first with a fine needle and immediately afterwards with a needle of large gauge similar to that used in percutaneous liver and kidney biopsy,’providing enough material for histological investigation. Before biopsy, the bladder is emptied and the vagina cleaned with antiseptic solution. The tumour should be palpable directly, with no suspicion of visceral interposition. A fine needle (0.8 mm diameter) is inserted into it via the vagina, suction applied with a Franzen syringe, and the needle moved in and out of the tumour. Suction is released when the tip is just below the vaginal mucosa. The material in the needle is ejected on to microscope slides for later cytological investigation. If it is solid and free of blood, urine or fluid from a cyst or the intestine, a second biopsy is done immediately, using a modified Iverson-Roholm needle (length 150 mm, outer diameter 2.0 mm, inner diameter 1.7 mm with a sharp right-angled tip without notches V The trocar is inserted through the vaginal puncture canal, the stylet withdrawn, and suction applied using a syringe with lock. The needle is pushed into the tumour with a rotating movement, one or more times. The needle is withdrawn with sustained suction and the fragments of tissue it contains are placed immediately in fixative. This technique should be used only in patients with advanced tumours where the alternative is a biopsy obtained by laparotomy, a procedure with a significant associated mortality. Laparotomy also has a high risk of disseminating the tumour. With needle biopsies, this risk is probably low even when a large-gauge needle is used. In my experience, the technique is safe and reliable.6 Department of Obstetrics
and Gynaecology, Central Hospital, DK-4800 Nykøbing Falster, Denmark
1. 2.
J. SERUP
Jensen, H. K., Gram, N. C., Francis, D. Ugeskr. Lœg. 1974, 136, 586. Kjellgren, O., Angstrøm, T., Bergman, F., Wiklund, D.-E. Cancer, 1971, 28, 967.
Menghini, G. Gastroenterology, 1958, 35, 190 4. Iversen, P., Brun, C. Am. J. Med. 1951, 11, 324. 5. Brun, C. in Nefro-urologi (edited by S.-E. Bergentz, E. Brodwall, p. 39. Copenhagen, 1973. 6. Serup, J. Ugeskr, Lœg. (in the press). 3.
Fl.
Lund);
