593 INTRAPLEURAL B.C.G. IMMUNOSTIMULATION IN LUNG CANCER
follow-up of our preliminary compublished year ago.’ In that report we recorded our experience with the first 60 patients to enter a randomised prospective study of the influence of intrapleural B.C.G. immunonostimulation after surgery for lung cancer. Treatment with extraordinarily large doses of B.C.G., who have become serstrain) followed by oral isoniazid seemed to improve survival in stage-I patients when compared with survival in controls StR,—This letter
munication
is
a
a
treated with isoniazid alone. 101 patients have now been entered into the study. The median duration of observation is 640 days, and the longest follow-up is 1400 days. The results continue to support the view that intrapleural B.C.G. is effective in stage-I lung cancer but ineffective in more advanced disease. The accompanying table summarises the number of patients free of cancer as a proportion of the number of patients studied:
The survival curve of the isoniazid-treated controls is identical with that of a historical control population at our own hospital and with the survival of a larger population of 330 surgically resected stage-i2 lung-cancer patients treated at the M.D. Anderson Hospital. We have seen no serious complications from this treatment when administered in the manner described in our original reports.’3 We know of 3 patients, treated at other institutions with extraordinarily large doses of B.C.G., who have become seriously ill from this treatment. All of these patients received 50 x 107 colony-forming units (the entire contents of an ampoule and, therefore, fifty times the recommended dose of intrapleural B.C.G. 1 patient developed miliary B.c.G. infection with splendomegaly, positive bone-marrow cultures, and numerous draining sinuses and granulomas, and 1 had a transient but severe miliary infection with B.C.G. Both of these patients were controlled by intensive antituberculous therapy. 1 patient died from mycobacterial empyema. We emphasise that this treatment is effective in the proper dose range and dangerous when larger doses are given. Excessive doses of B.C.G. seem to increase the growth of transplanted tumours in laboratory animals.
Supported in part by N.I.H. grants R01-CA-17346, MOI-RROO749 and NOI-CB-53940, and by the New York State Kidney Disease Institute.
Division of Cardio-Thoracic Albany Medical College of Union University, Albany, N.Y. 12208, U.S.A.
Surgery,
MARTIN F. MCKNEALLY CAROLE M. MAVER HARVEY W. KAUSEL
Ultrasound appearances. A=anterior uterine wall; P=posterior uterine wall; Pl=placenta; L=liquor; N=tip of amniocentesis needle; SP=spurt of fetal blood arising from puncture site.
The fetus was an anencephalic of 20 weeks’ gestation. The placenta was situated upper posteriorly with paracentral insertion of the umbilical cord. A suitable echo-free area was located and the skin was anaesthetised with a 1% procaine infiltration. A 20-gauge amniocentesis needle was introduced into the amniotic cavity. The tip of the needle, which will appear as a dot of echoes on the monitor confirming its proper direction, was moved towards a lateral section of the placenta. The needle tip was then gently placed just inside the chorionic membrane; 1 ml of blood was aspirated and the needle was subsequently moved into the amniotic cavity, and this procedure was done four times. The first three blood-samples contained 30%, 25%, and 19% HbF, respectively. The liquor stayed clear. After withdrawal of the needle for the fourth time ultrasonic visualisation revealed small spurts synchronous with the fetal heart-rate (120 beats/min) arising from the puncture site into the amniotic cavity, indicating the escaping of blood from a fetal artery (see figure). This sample contained 62% HbF. The spurts lasted for about 20 s. By now the liquor had become slightly bloodstained; 10 ml was sampled. Total fetal blood-loss was estimated at 3 ml; this was based on fetal haemoglobin content in the last liquor sample, liquor volume (about 500 ml at 20 weeks), and the amount of fetal blood aspirated. Fetal heart action remained normal throughout the procedure and afterwards. Induction of abortion with intramuscular 15-methylprostaglandin F2cx was started 4 h later. The placenta showed four puncture sites close together on the chorionic membrane, about 5cm from the umbilicalcord insertion. One of the punctures was in a medium-sized fetal artery. It seems that real-time scanning with a dynamically focusing system, is a promising tool in the further development of fetal
blood-sampling techniques. REAL-TIME SCANNING AND TRANSABDOMINAL FETAL BLOOD-SAMPLING
SIR,-Increasing interest in the diagnosis of inherited and acquired fetal diseases has lead to the search of methods of viewing the fetus and of obtaining fetal blood-samples and skin-biopsy samples 4-6 We have obtained a fetal blood-sample from a placental vessel under real-time ultrasound visualisation, using a newly developed dynamically focused multiscan
system.’ 1 McKneally, M. F., Maver, C. M., Kausel, H. W. Lancet, 1976, i, 377. 2. Mountain, C. F., and others. Unpublished. 3. McKneally, M. F., Maver, C., Kausel, H. W., Alley, R. D. J. thor. cardiovasc. Surg. 1976, 72, 333. 4 Hobbins, J. C., Mahoney, M. J. Lancet, 1975, ii, 107. 5 Hobbins, J. C., Mahoney, M. J. Clin. Obst. Gynec. 1976, 19, 341. 6 Golbus, M. S., Kaw, Y. W., Naglich-Craig, M. Am. J. Obstet. Gynec. 1976, 124, 653. 7. Ligtvoet, C. M., Ridder, J., Lancée, C. T., Hagemeyer, F., Vletter, W. B.
Unpublished.
and Gynæcology, Academisch Ziekenhuis Rotterdam-Dijkzigt, Rotterdam-3002, Netherlands
Department of Obstetrics
J. W. WLADIMIROFF M. C. J. JAHODA
IRRADIATION OF THE THYROID AS A CAUSE OF PARATHYROID ADENOMA
SIR,-Hyperparathyroidism, once considered a rare disease, is now being diagnosed more often. In a few patients it is clear that parathyroid adenomas develop after a prolonged stimulus to hyperplasia-tertiary hyperparathyroidism.’ While it has been suggested that a surprisingly high proportion of adenomas may be associated with microscopic hyperplasia, it is generally accepted that most cases of hyperparathyroidism are due to single adenomas arising in glands that are otherwise apparently normal, and that their pathogenesis is unknown. 1. St. Goar, W. T. New Engl. J. Med. 1963, 268, 943. Haff, R. C., Black, W. C., Ballinger, W. F. Ann. Surg. 1970, 171, 85.
2.
follow-up of our preliminary compublished year ago.’ In that report we recorded our experience with the first 60 patients to enter a randomised prospective study of the influence of intrapleural B.C.G. immunonostimulation after surgery for lung cancer. Treatment with extraordinarily large doses of B.C.G., who have become serstrain) followed by oral isoniazid seemed to improve survival in stage-I patients when compared with survival in controls StR,—This letter
munication
is
a
a
treated with isoniazid alone. 101 patients have now been entered into the study. The median duration of observation is 640 days, and the longest follow-up is 1400 days. The results continue to support the view that intrapleural B.C.G. is effective in stage-I lung cancer but ineffective in more advanced disease. The accompanying table summarises the number of patients free of cancer as a proportion of the number of patients studied:
The survival curve of the isoniazid-treated controls is identical with that of a historical control population at our own hospital and with the survival of a larger population of 330 surgically resected stage-i2 lung-cancer patients treated at the M.D. Anderson Hospital. We have seen no serious complications from this treatment when administered in the manner described in our original reports.’3 We know of 3 patients, treated at other institutions with extraordinarily large doses of B.C.G., who have become seriously ill from this treatment. All of these patients received 50 x 107 colony-forming units (the entire contents of an ampoule and, therefore, fifty times the recommended dose of intrapleural B.C.G. 1 patient developed miliary B.c.G. infection with splendomegaly, positive bone-marrow cultures, and numerous draining sinuses and granulomas, and 1 had a transient but severe miliary infection with B.C.G. Both of these patients were controlled by intensive antituberculous therapy. 1 patient died from mycobacterial empyema. We emphasise that this treatment is effective in the proper dose range and dangerous when larger doses are given. Excessive doses of B.C.G. seem to increase the growth of transplanted tumours in laboratory animals.
Supported in part by N.I.H. grants R01-CA-17346, MOI-RROO749 and NOI-CB-53940, and by the New York State Kidney Disease Institute.
Division of Cardio-Thoracic Albany Medical College of Union University, Albany, N.Y. 12208, U.S.A.
Surgery,
MARTIN F. MCKNEALLY CAROLE M. MAVER HARVEY W. KAUSEL
Ultrasound appearances. A=anterior uterine wall; P=posterior uterine wall; Pl=placenta; L=liquor; N=tip of amniocentesis needle; SP=spurt of fetal blood arising from puncture site.
The fetus was an anencephalic of 20 weeks’ gestation. The placenta was situated upper posteriorly with paracentral insertion of the umbilical cord. A suitable echo-free area was located and the skin was anaesthetised with a 1% procaine infiltration. A 20-gauge amniocentesis needle was introduced into the amniotic cavity. The tip of the needle, which will appear as a dot of echoes on the monitor confirming its proper direction, was moved towards a lateral section of the placenta. The needle tip was then gently placed just inside the chorionic membrane; 1 ml of blood was aspirated and the needle was subsequently moved into the amniotic cavity, and this procedure was done four times. The first three blood-samples contained 30%, 25%, and 19% HbF, respectively. The liquor stayed clear. After withdrawal of the needle for the fourth time ultrasonic visualisation revealed small spurts synchronous with the fetal heart-rate (120 beats/min) arising from the puncture site into the amniotic cavity, indicating the escaping of blood from a fetal artery (see figure). This sample contained 62% HbF. The spurts lasted for about 20 s. By now the liquor had become slightly bloodstained; 10 ml was sampled. Total fetal blood-loss was estimated at 3 ml; this was based on fetal haemoglobin content in the last liquor sample, liquor volume (about 500 ml at 20 weeks), and the amount of fetal blood aspirated. Fetal heart action remained normal throughout the procedure and afterwards. Induction of abortion with intramuscular 15-methylprostaglandin F2cx was started 4 h later. The placenta showed four puncture sites close together on the chorionic membrane, about 5cm from the umbilicalcord insertion. One of the punctures was in a medium-sized fetal artery. It seems that real-time scanning with a dynamically focusing system, is a promising tool in the further development of fetal
blood-sampling techniques. REAL-TIME SCANNING AND TRANSABDOMINAL FETAL BLOOD-SAMPLING
SIR,-Increasing interest in the diagnosis of inherited and acquired fetal diseases has lead to the search of methods of viewing the fetus and of obtaining fetal blood-samples and skin-biopsy samples 4-6 We have obtained a fetal blood-sample from a placental vessel under real-time ultrasound visualisation, using a newly developed dynamically focused multiscan
system.’ 1 McKneally, M. F., Maver, C. M., Kausel, H. W. Lancet, 1976, i, 377. 2. Mountain, C. F., and others. Unpublished. 3. McKneally, M. F., Maver, C., Kausel, H. W., Alley, R. D. J. thor. cardiovasc. Surg. 1976, 72, 333. 4 Hobbins, J. C., Mahoney, M. J. Lancet, 1975, ii, 107. 5 Hobbins, J. C., Mahoney, M. J. Clin. Obst. Gynec. 1976, 19, 341. 6 Golbus, M. S., Kaw, Y. W., Naglich-Craig, M. Am. J. Obstet. Gynec. 1976, 124, 653. 7. Ligtvoet, C. M., Ridder, J., Lancée, C. T., Hagemeyer, F., Vletter, W. B.
Unpublished.
and Gynæcology, Academisch Ziekenhuis Rotterdam-Dijkzigt, Rotterdam-3002, Netherlands
Department of Obstetrics
J. W. WLADIMIROFF M. C. J. JAHODA
IRRADIATION OF THE THYROID AS A CAUSE OF PARATHYROID ADENOMA
SIR,-Hyperparathyroidism, once considered a rare disease, is now being diagnosed more often. In a few patients it is clear that parathyroid adenomas develop after a prolonged stimulus to hyperplasia-tertiary hyperparathyroidism.’ While it has been suggested that a surprisingly high proportion of adenomas may be associated with microscopic hyperplasia, it is generally accepted that most cases of hyperparathyroidism are due to single adenomas arising in glands that are otherwise apparently normal, and that their pathogenesis is unknown. 1. St. Goar, W. T. New Engl. J. Med. 1963, 268, 943. Haff, R. C., Black, W. C., Ballinger, W. F. Ann. Surg. 1970, 171, 85.
2.
