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Second-trimester diagnosis of most open neural tube defects has become clinically feasible in the past five years. Alpha fetoprotein is the common denominator in a two-stage screening program. Maternal serum analysis identifies high-risk pregnancies; amniotic fluid analysis is diagnostic. The biochemical basis for these tests and findings of clinical studies are reviewed.

During chemical carcinogenesis by N-2-fluorenylacetamide, the hormonal status of female Sprague Dawley rats is largely modified. Thyroids present a modified activity which is evidenced by the histological study as well as T4 and T3 assays. In hypophysis, thyrotropic cells were found in an hyperactive state, a fact which is in agreement with the changes observed in thyroid follicles size and epithelial cells demonstrating an hyperactivity of thyroid glands. Despite this histological result, T4 serum level was lowered. T3 level was also decreased but to a lesser extent. We suggest that the low thyroid hormone level play a role in the relative protection of females versus males toward liver cancer induction by chemicals.

170 patients with testicular germ cell tumours (88 seminomas and 82 non-seminomas) were examined with immunologic techniques for the presence of the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in tumour tissue and preoperative serum samples. Patients with pure seminomas had AFP negative tumour tissue and normal levels of serum AFP, whereas 13% had HCG demonstrated in the tumour tissue, mainly in syncytiotrophoblast-like cells (STLC), and 9% had raised serum HCG. 55% of patients with HCG positive seminomas had raised serum HCG. HCG positive seminomas did not occur in higher frequency in metastatic disease than in localized. 65% of patients with non-seminomas had AFP positive tumour tissue and 66% had raised serum AFP. 85% of the former group had raised serum AFP and 83% of the latter had AFP demonstrated in the tumour tissue. 69% of the patients with raised serum AFP had a positively stained yolk sac tumour (YST) component, while 15% had positively stained tumour components other than YST, inclusive teratoma components. Although 71% of patients with metastatic disease had raised serum AFP, AFP positive tumours with or without raised serum AFP did not occur with higher frequency in metastatic than in localized disease at the time of diagnosis. 46% of patients with non-seminomas had HCG positive tumours and 29% had raised serum HCG. 61% of the former group had raised serum HCG and 96% of the latter had HCG demonstrated in the tumour tissue. HCG positive tumours with or without raised serum HCG did not occur more frequently in metastatic than in localized disease at the time of diagnosis. 28% of patients with non-seminomas had raised serum AFP as well as HCG, whereas 23% had neither AFP nor HCG in tumour tissue and serum. A search for new tumour markers in this rather large marker negative group of patients is recommended.

Fetoplacental function and maternal nutritional condition were assessed in order to clarify the mechanism of retarded fetal growth in pregnant women who smoked. Dehydroepiandrosterone sulfate (DHA-S) loading tests and measurements of cotinine, which is a major metabolite of nicotine, were also made. In heavy smokers, urinary estriol and serum levels of human placental lactogen (hPL) were lower than those in nonsmokers. There was no difference in maternal nutrition between smokers and nonsmokers. Heavy smokers demonstrated a lower conversion of DHA-S to estradiol than did nonsmokers. Levels of cotinine in maternal blood and umbilical cord blood of heavy smokers were remarkably higher than those in nonsmokers. Microscopic examination showed atrophic and hypovascular changes in placental villi from mothers who smoked. These results suggest that retarded fetal growth in heavy smokers is due to impairment of uteroplacental circulation as a result of the vasoconstricting effect of nicotine.

En bloc resection of the inferior vena cava (IVC) has been demonstrated to be of benefit in removing bulky retroperitoneal testicular tumor metastases. The major indications for its use have been to increase the amount of tumor resected, to allow access to large amounts of tumor located posterior to the aorta which would otherwise be inaccesible, to diminish the possibility of massive pulmonary embolism from clot or tumor located in the IVC, and to decrease the risk of major hemorrhage from injury to the IVC, aorta, or one of their branches. To date the surgical morbidity has been acceptable, and no direct mortality has been associated with it.

Pregnancy specific beta 1 glycoprotein (PS beta 1G), human choriogonadotropin (hCG), alpha-foetoprotein (AFP) and carcinoembryonic antigen (CEA) were measured simultaneously in 58 patients with a progressive germinal testicular tumour, and in 20 patients in complete remission. All markers were negative in all the cases in remission, and in 1 case of progressive teratoma. The specificity of the association of these 4 markers was 76 p. 100, higher than any of them measured alone. There was no correlation between individual markers with respect to histological classification. The highest diagnostic specificity was obtained with hCG in all types of tumours. PS beta 1G was associated with hCG but with a lower specificity. AFP is mainly related to embryonic carcinoma but may be raised in all forms of tumour, except seminomas. CEA was positive less often, irrespective of the type of tumour, and never alone. The value of measuring these tumour markers is double: on the one hand it allows better characterisation of the tumour, and on the other, the clinical course and efficacy of treatment can be followed-up more closely and tumour recurrence may be diagnosed at an early stage.

Malignant ovarian tumors only account for 3 per cent of all malignancies under 15 years of age, and more than two third of them are of germ cell origin. Abdominal mass and/or pains are the usual revealing symptoms and abnormal sexual prematurity is infrequently encountered. Diagnostic ultrasonography is currently the most useful imaging investigation. Alpha-foeto-protein (alpha-FP) serum determination is mandatory before surgery to indicate the presence of endodermal sinus tumor cells. Surgical procedure is in childhood usually restricted to unilateral salpingo-oophorectomy, if allowed by tumoral spreading which is carefully searched in the abdominal cavity. Thus will be defined, along with the post-operative lymphangiography, the extension of the tumor, according to the staging system of Wollner (Memorial Hospital NY) more than the FIGO. Malignant teratomas are the most frequent malignant germ cell ovarian tumors in young females. They may realize pure or mixed pathological types of immature teratoma, embryonal carcinoma, endodermal sinus tumor and very seldom choriocarcinoma. Serial assays of serum alpha-FP are of utmost value to follow therapeutic progress or detect recurrences. Since new sequential multidrug protocol including, vincristine, actinomycin D, cyclophosphamide, adriamycin, méthotrexate and cis-platinum, protracted survivals are to be expected in a higher number of patients with localized stages and even in some with advanced disease. Value of extended pelvi-abdominal and/or lymph node radiotherapy is still under evaluation. Ovarian dysgerminomas are radiosensitive tumors in which chemotherapy is as a rule not indicated. Relapses may be most often prevented by a prophylactic irradiation of iliac ipsilateral, lumboaortic, mediastinal and supraclavicular nodes. Among functional ovarian tumors, mainly granulosa cell types with isosexual precocity, malignant tumors are so rarely encountered that no complementary treatment has to be performed after a complete resection. Cystadenocarcinoma or borderline ovarian epithelial tumors occur after puberty and require the same treatment as in adult though keeping a conservative view. Ovarian deposits of Burkitt's tumor may account in some exposed african areas for most ovarians malignancies in childhood. Gonadoblastomas with both stromal and germ cell elements are exclusively to be found in dysgenetic gonads.

The tumor markers alpha-fetoprotein and human chorionic gonadotropin have proved to be useful in staging disease in patients with testicular carcinomas. Moreover, their detection has often had a bearing on the therapeutic regimen selected. The nature and value of these tumor markers are discussed in detail, and other potentially useful oncofetal gene products are reviewed.

This paper describes a 50-year-old woman with an unusual malignant tumour of the liver. Poorly differentiated liver cells, tubular structures and spindle cells in abundant intercellular ground substance characterized the tumour. Extremely high serum concentration of alpha-fetoprotein was present. The spindle cells showed strong immunoreactivity against this antigen and vimentin. Both the spindle and epithelial cells showed negative immunoreactivity against desmin, epithelial membrane antigen and keratin. Markers for low molecular cytokeratin (MAK-6, CAM 5.2) were demonstrated in both cell types. Ultrastructurally the neoplastic epithelial cells showed frequent intercellular spaces and well-formed brush borders suggestive of differentiation towards hepatocytes and bile duct epithelium. The immunohistological findings established the epithelial nature of the spindle cells thus distinguishing the tumour from hepatoblastoma.

Simultaneous and equimolar injections of methionine and adenosine 5'-triphosphate significantly accelerated the rapid fall of rat serum alpha-fetoprotein (AFP) concentrations after birth. The results were compared with those obtained by administrations of prednisolone and adult tissue extracts. Correlations between a methionine-related metabolic event(s) and the repression of AFP synthesis were discussed.

alpha-Fetoprotein (AFP) levels have been measured in maternal serum and amniotic fluid in a variety of gastrointestinal abnormalities of the fetus. Maternal serum AFP levels were consistently elevated in abdominal wall defects of the fetus after 15 weeks gestation and the amniotic fluid levels were raised in 3 of the 4 patients measured. In atresia of the gastrointestinal tract and diaphragmatic hernia, serum AFP levels were usually normal unless there was an associated neural tube defect or multiple pregnancy, although the majority were not measured between 15 and 26 weeks gestation. If elevated amniotic fluid levels of AFP are used in the decision to terminate pregnancy on the assumption of a probable neural tube defect of the fetus, a proportion of terminations will be performed because of abdominal wall defects of the fetus.

Sixteen histologically documented testicular cancer specimens obtained at diagnostic procedures following induction chemotherapy with cis-platinum containing regimens were cloned in soft agar. Seven (44%) of the specimens cultured formed colonies with a mean cloning efficiency of .021%. Colony formation was observed with all the common histologic subtypes of testicular cancer (seminoma, embryonal carcinoma, choriocarcinoma and mixed tumors). In vitro drug sensitivity tests were performed using cis-platinum, vinblastine and VP-16. Three of four specimens demonstrated a decrease in colony formation to less than 50% of controls after a 1 h exposure to VP-16 at 300 micrograms/ml. Two of these patients had a response to treatment with a VP-16 based salvage regimen. Immunoperoxidase staining of the colonies for alpha feto protein and human chorionic gonadotropin were correlated with the serum levels of these tumor markers determined at the time the specimen was obtained. In three instances the same markers were elevated in the serum as detected within cells which formed the colonies; however, in two other cases the marker(s) that was elevated in the serum was not expressed in the colonies. In one case a biopsy of a residual retroperitoneal mass following chemotherapy histologically was a teratoma, but it formed colonies in the assay which stained positive for alpha feto protein. This patient subsequently developed an elevated serum alpha feto protein. These studies have demonstrated that (a) testicular cancer can be cloned directly in soft agar; (b) a heterogeneous tumor cell population exists in metastatic testicular cancer specimens; and (c) a dose response exists for VP-16 in relapsed testicular cancer which suggests that increasing the dose of VP-16 may be clinically beneficial.

By means of polyacrylamide gel stage electrophoresis designed by us, serum gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were separated into 9 (I to IX) and 7 (I to VII) isoenzyme bands. The GGT II and ALP I were found only in the sera of patients with primary hepatic carcinoma showing positive rates of 29.5% and 8.5%, respectively. The combined positive rate of the two kinds of isoenzymes was 36.2% which is lower than that of alpha-fetoprotein (AFP) in the liver cancer but it has a higher specificity compared to the latter test. Furthermore, positive GGT II and ALP I may also be present in patients with liver cancer who were negative for AFP. It is obvious that the simultaneous determinations of GGT II, ALP I and AFP are mutually supplementary in the diagnosis of liver cancer.

The AFP concentration in the amniotic fluid is elevated after contamination of the sample with fetal blood during a traumatic amniocentesis. Though the calculation of AFP due to fetal hemorrhage is possible by counting the fetal red cells there may be execssive errors resulting from the variability of fetal red cell count, amniotic volume, fetal serum AFP concentration, AFP concentration in the amniotic fluid changing with fetal age. Therefore it is impossible to interpretate elevated AFP values from a sample stained with fetal blood. A repeated amniocentesis is unavoidable. The correct time to do a second punction is still a matter of question.

Chorionic villus sampling (CVS) is a recent advance in prenatal diagnosis in the first trimester. maternal serum alpha fetoprotein (AFP) screening for neural tube defects is done from 14-17 weeks gestation. Previous studies have shown an elevation of AFP levels following amniocentesis. The aim of this study was to determine the effect of CVS on AFP levels immediately following this procedure. CVS was performed under sonographic guidance on 22 patients between 6 and 12 weeks gestation undergoing elective termination of pregnancy. A Portex catheter was used for obtaining villi. Maternal serum AFP levels were ascertained before and after CVS by radioimmunoassay. In the group of patients 8 weeks or less, no change in AFP levels was seen; in patients greater than 8 weeks gestation, a significant rise in post-biopsy AFP level was noted in 7 of 14 patients. Further studies are planned to clarify the effect of CVS on AFP levels in patients with ongoing pregnancies. Clarification of this issue is important to the role of CVS in prenatal screening.

Representation of the clinical significance of the tumor markers CEA, HCG-beta and alpha 1-fetoprotein (AFP) of the basis of the relevant literature and of own studies. As a marker for tumors of the urogenital tract, CEA is at present of very little value as it is too unspecific. HCG-beta and AFP, on the other hand, are important new parameters for both the demonstration of so-called subclinical metastases (staging) and clinical case control, particularly with malignant nonseminomatous tumors of the testicles. Over a period of four years we found in 62 out of 85 patients with nonseminomatous testicle tumors that -- in accordance with the literature -- simultaneous determination by the two markers (85% positive) is decidedly superior to the determination by one marker only. Out of 23 patients with a histologically classified seminoma, one patient (i.e. 4.4%) was HCG-beta positive. So far, the prognostic significance of such findings has generally not been clarified. It is shown here that exclusively "marker-oriented" therapy planning and case control without the clinical examination methods used so far are not yet justified because of the inadequate specificity and sensitivity of these two markers as well as of more recent ones (SP-1, TPA). Nevertheless, HCG-beta and AFP are at present important new methods in the areas of diagnosis (staging), therapy planning and case control as primarily increased marker values, or marker values increased during or after therapy clearly indicate metastasizing or renewed tumor activity, respectively.

Proteins, which are elevated in their blood concentration in pregnant women and patients suffering from malignant tumours, are reported because of their growing significance for the clinical practice. At present mainly are the following "pregnancy" proteins of clinical relevance: human chorionic gonadotrophin (HCG), human placental lactogen (HPL), placental heatstable alkaline phosphatase (HAP), pegnancy-associated alpha2-glycoprotein ("pregnancy zone" protein, PZ), socalled pregnancy-specific beta1-glycoprotein (SP1) and alpha1-fetoprotein (AFP). Applications to the clinical practice may be the surveillance of normal pregnancy, the recognition of dangerous conditions for mother and fetus, the inhibition of graft rejection, the induction of abortion, antibodies against pregnancy proteins as abortifacient and antifertilizer as well as the tumour diagnosis including the control of treatment and recognition of recidives.

The risk of having a Down's syndrome term pregnancy was estimated using maternal age and the results of two maternal serum alpha-fetoprotein (AFP) tests carried out between 14 and 20 weeks gestation. The estimates of risk were derived from published data and the AFP results from nine affected and 145 unaffected pregnancies in which repeat testing had been carried out. Repeat AFP testing is unjustified in antenatal screening programmes for Down's syndrome, but if a second test happens to have been done, the appropriate estimate of risk that would be applicable when counselling individual patients depends on both results. For example a woman aged 35 years and 6 months with a first AFP level of 0.50 multiples of the normal median (MoM) was estimated to have a risk of 1:172. If a second test were done on a fresh sample and the AFP level were 0.80 MoM then the estimated risk would be 1:216 which is higher than the estimated risk of 1:353 obtained if the second test were regarded as the only result. Estimates of risk are given for maternal serum AFP results in first and second tests ranging from 0.40 to 2.50 MoM.

The clinical significance of serum ferritin as a serological marker of hepatocellular carcinoma (HCC) was studied. Fasting serum ferritin levels were measured in 343 patients with diseases of the liver, using a radioimmunoassay ferritin kit. Elevated ferritin levels were obtained in various liver diseases but hyperferritinemia could be more clearly interpreted by classifying ferritin levels according to serum iron or transaminase values. Significantly higher values were obtained in HCC than liver cirrhosis. Sensitivity for diagnosis of HCC increased by serial and simultaneous determinations of ferritin and alpha-fetoprotein because high ferritin levels were observed more often in low alpha-fetoprotein-producing HCC and also in HBsAg negative, alcohol related, small-sized HCC. Therefore, simultaneous determination of alpha-fetoprotein and ferritin seems to be useful for detection of HCC in high risk patients such as those with liver cirrhosis.

Morphometric, immunohistochemical, and electron-microscopic studies were undertaken in an attempt to identify the types of hepatoblastoma cellular elements responsible for the synthesis of alpha-fetoprotein (AFP), and to see how they may relate to serum AFP levels and the metastatic spread and prognosis of the hepatoblastoma. Morphometric studies of 21 hepatoblastomas with statistical treatment of the results revealed a moderately strong reliable correlation of the AFP serum titer with the volume ratio of embryonal tumor cells and with that of those tumor elements of endodermal hepatic diverticulum which are similar to the latter cells with regard to degree of differentiation. Also, a consistent, reliable negative correlation was demonstrated between serum AFP titer and the volume of fetal hepatoblastoma cells. The volume ratio of stromal elements was found to be subject to chance variations and not to correlate with serum AFP level. Immunohistochemical and electron-microscopic studies confirmed the morphometric findings and showed AFP synthesis to be effected by poorly differentiated hepatoblastoma cells--by endodermal hepatic diverticulum elements at first and by embryonal and intermediate tumor cells later--and to decrease as the liver tumor cells differentiate further. It is concluded that a high serum AFP level is, generally, an indication that the hepatoblastoma is an extensive one and consists of poorly differentiated cells so that the prognosis is unfavorable.

Radio-immunologic measurement of alpha-fetoprotein is possible in small amounts of blood and amniotic fluid. During the first half of pregnancy the AFP values in maternal serum are lowered when there is fetal abnormality (hydatid cyst, immnent abortion). In the second half of pregnancy high values of AFP also indicate danger to the fetus (Rh-incompatibility). The older the pregnancy the AFP values in amniotic fluid fall. In pathologic pregnancy (hydramnion, anencephaly, trisomy) AFP concentration was normal or raised. Measurement of the AFP level in umbilical cord -- blood provides further diagnostic chances: assessment of the duration of pregnancy and, therefore, of fetal maturity.

Open neural tube defects have been associated with elevated levels of alpha-fetoprotein in maternal serum and amniotic fluid. In the present study, specimens were collected during 14 to 20 weeks of gestation in five laboratories. Dates were confirmed by ultrasound. Among 1,049 subjects included in total serum alpha-fetoprotein determinations, 25 infants were born with neural tube defects, one patient had intrauterine fetal demise, and 1,023 delivered normal infants. The false-negative rate for serum alpha-fetoprotein was 0.38%, and the false-positive rate was 0.29%. For the total 1,211 amniotic fluid specimens, 23 infants were born with neural tube defects. The false-negative rate for amniotic fluid alpha-fetoprotein was 0.25%. All were closed lesions. There were no false-positive values. This study reaffirms the value of screening for neural tube defects by means of serum alpha-fetoprotein RIA. It also negates the argument that serum screening would promote excessive amniocentesis.

Zinc and selenium status was assessed in 30 non-pregnant women, 69 women during normal pregnancy, six with a fetus with a neural tube defect (NTD) and 16 who had a raised plasma alpha-fetoprotein (AFP) but no detectable fetal abnormality. Plasma zinc and selenium concentrations were significantly reduced in the second trimester of normal pregnancy compared with non-pregnant levels. A significant decrease in concentrations of zinc in plasma and selenium in plasma and leucocytes was observed in women in the third trimester compared with women in the second trimester. Women with a fetal NTD and women with an unexplained elevation of plasma AFP had significantly lower leucocyte concentrations of zinc and of selenium. Mean values for plasma zinc, plasma and erythrocyte selenium, and for the activity of glutathione peroxidase in whole blood did not differ from those for normal pregnancy.

HBsAg producing cell-lines of human primary hepatocellular carcinomas express a multitude of differentiated hepatocyte functions. They also grow in hypothymic (nude) mice as solid tumours. Here we describe the subcutaneous injection of cell-lines PLC/PRF/5, Hep 3B and Mahlavu (HBsAg negative) into hypothymic mice to produce a high tumour take without prior immunosuppressive treatment. Serial transplantation of tumour fragments into new animals allows the development of large homogeneous experimental groups and a substantial multiplication of tumour cell mass. The transplanted tumours from PLC/PRF/5 and Hep 3B cells continue to synthesize HBsAg and alpha-fetoprotein, and they secrete these proteins into the blood of their hosts. Fibrinogen and alpha 1-antitrypsin can be demonstrated in the cells of these two tumours but not in tumours originating from Mahlavu cells. This model offers experimental conditions to study the function of solid human primary liver cell carcinomas under the influence of an intact organism.

In the present study we have investigated the influence of pregnancy on the induction and development of experimental autoimmune encephalomyelitis (EAE) in rabbits in relation to the time of gestation. Randomly bred rabbits were immunized with encephalitogenic bovine brain homogenate in complete Freund's adjuvant before or during pregnancy. The appearance of EAE was delayed and occurred only after delivery, abortion, or fetal resorption. The incidence of the disease was lower and the duration longer. The levels of antibodies to myelin basic protein, an autoantigen of EAE, as measured by solid phase radioimmunoassay, were lower in the pregnant rabbits as compared to the nonpregnant animals. The suppressive influence of pregnancy on the induction and the development of EAE confirms previous reports demonstrating amelioration of autoimmune diseases and other immunological reactions during the second half of human pregnancy. This effect might be partially attributed to the increased level of alpha-fetoprotein (AFP) and/or other pregnancy-associated factors in maternal serum.

Low maternal serum alpha-fetoprotein values during the second trimester of pregnancy are associated with an increased risk of Down syndrome in the fetus. In this study a sensitive, monoclonal-based radioimmunoassay for alpha-fetoprotein was used to determine whether such an association also applies to the first trimester and if maternal serum alpha-fetoprotein screening could successfully detect a significant number of pregnancies in which the fetus had a trisomy or other chromosome disorder. Sera were obtained prospectively from 540 women just before chorionic villus sampling for prenatal diagnosis of chromosome defects (largely because of advanced maternal age) at 8 to 12 weeks' fetal age and assayed for alpha-fetoprotein under code without knowledge of the cytogenetic results. Eight of 27 (29.6%) of all serious chromosome defects were associated with low maternal serum alpha-fetoprotein values (less than or equal to 0.6 multiples of the median). Overall, 59 of 540 patients (10.9%) had maternal serum alpha-fetoprotein values less than or equal to 0.6 multiples of the median, eight of whom had a fetus with a serious chromosome defect. Women whose maternal serum alpha-fetoprotein value was less than or equal to 0.6 multiples of the median had one in eight odds of carrying a fetus with a trisomy and one in seven odds of the fetus having any serious chromosome defect. From this study of a group of women at higher risk, we conclude that first-trimester maternal serum alpha-fetoprotein screening for chromosome defects is feasible. A prospective study to determine detection efficiency is now required of a consecutive routine pregnancy population in whom gestational age is determined by menstrual dates as is usually the case in clinical practice.

Serum samples from 20 patients with acute exacerbation of chronic hepatitis due to hepatitis B virus and 20 patients with hepatocellular carcinoma arising from B viral cirrhosis with elevated levels of alpha-fetoprotein (AFP) were analyzed by affinity column chromatography for concanavalin A binding. Serum AFP was tested at regular intervals in all of these patients. Acute exacerbation was defined as elevation of serum transaminase greater than 300 IU/L in patients with chronic hepatitis B. In hepatocellular carcinoma, serum AFP levels fluctuated but remained higher than 92 ng/ml, whereas, in acute exacerbation of chronic hepatitis B, serum AFP levels returned to normal within 3-12 months of follow-up. The results of concanavalin A-binding assay revealed that AFP from both these groups had a high affinity for concanavalin A, and this assay could not be used to discriminate between the two conditions.

The value of ultrasonography and serum alpha foetoprotein assay in the detection of hepatocellular carcinoma was evaluated in a retrospective study of 217 patients, (135 men and 82 women; mean age 58 years) who had been hospitalized for 18 months. Cirrhosis was of alcoholic origin in 76 per cent of the cases and complicated by ascites in 54 per cent. Twenty-four patients (11 per cent) had hepatocellular carcinoma diagnosed at ultrasonography in 20 cases. The carcinoma was diffuse in 7 cases, focal in 13 cases and less than 3 cm in diameter in 3 cases. A second ultrasonography diagnosed hepatocellular carcinoma in 4 cases. In 25/217 patients (11.5 per cent) the focal lesion seen at sonography was obviously not a carcinoma. Among the 207 patients who had a serum alpha foetoprotein assay, the result was normal in 167 (81 per cent) and 4 of these had a carcinoma. Among the 40 patients with an abnormal level of alpha foetoprotein, 19 had a carcinoma. This study confirms the good sensitivity of ultrasonography in the detection of hepatocellular carcinoma, but it also shows its low specificity, especially in cases with focal lesions. Ultrasonography and serum alpha foetoprotein assay should be used to detect hepatocellular carcinomas in cirrhotic patients who may benefit from surgical treatment. In the other patients, ultrasonically-guided biopsy should provide a firm diagnosis of carcinoma before undertaking other treatments, such as chemoembolization.

Monospecific anti-rat serum alpha-fetoprotein (AFP) IgG was coupled to cyanogen bromide-activated Sepharose-4B (4.5 mg/ml packed volume of gel) to yield an immunoaffinity matrix. The immunoaffinity column was used to isolate AFP from feto-neonatal rat brain. The purified AFP was immunologically and electrophoretically similar to serum AFP. It yielded a single band with a molecular weight of 70,000 on sodium dodecyl sulphate polyacrylamide gel electrophoresis. Polyacrylamide gel electrophoresis of the protein under nondenaturing conditions yielded two charge variants of AFP, reminiscent of AFP from feto-neonatal rat serum. The AFP was observed to bind estradiol with Ka = 5.8 X 10(8) M -1 and 1.3 X 10(8) M -1 by dextran-coated charcoal adsorption and Sephadex gel filtration techniques, respectively. Newborn rat brain cells linearly incorporated [14C]leucine into immunoprecipitable AFP during 6 h in culture. It is, therefore, concluded that feto-neonatal rat brain contains AFP similar to that present in fetal serum and that it may arise in brain as a result of its in situ synthesis.

The blood levels of tumour markers (alpha-foetoprotein and human chorionic gonadotropin) were determined and serial chest X-rays were obtained from 11 patients with germ cell tumours to study the growth of the tumours. Assuming an exponential growth pattern, the tumour marker levels and diameters of lung metastases were analysed. The use of a simple model made it possible to describe the time course of the change of tumour marker levels in blood before and during treatment. The analysis provided estimates of doubling times for marker-positive subpopulations, which were generally in accordance with the doubling times for lung metastases. The estimated doubling times had a log-normal mean value of 21.3 days, in agreement with the 19.5 days for embryonic tumours obtained in other studies.

Using affinity chromatography on concanavalin A Sepharose, the authors studied the molecular heterogeneity of the serum alpha-fetoprotein of 53 patients with hepatocellular carcinoma, 16 patients with metastatic tumors to the liver, and 16 patients with germ cell tumors. Mean concanavalin binding of alpha-fetoprotein in the sera of patients with hepatocellular carcinoma was 79%, whereas the mean binding in metastatic tumors was 52% and that of germ cell tumors was 45%. This striking molecular variation of the alpha-fetoprotein produced by these different tumors is helpful in the clinical distinction of these tumors.

The role of second-look laparotomy in the management of patients with endodermal sinus tumor of the ovary is controversial. We report two women who converted to a normal alpha-fetoprotein (AFP) level during treatment with combination chemotherapy, yet were found to have residual endodermal sinus tumor at second-look laparotomy. In view of the limited experience with this rare disease, we continue to recommend second-look laparotomy for patients who have completed chemotherapy for endodermal sinus tumor of the ovary, regardless of the serum AFP level.

Maternal serum alpha fetoprotein (MSAFP) measurement between 16 and 21 weeks gestation is used to define a group of women with an increased risk of fetal abnormality, particularly open neural tube defect. The test is strongly gestation dependent and women with high MSAFP levels require sonar scan examination to define gestation, exclude twins and examine the fetus for obvious malformation or death. It has been reported that women with no primary cause for raised MSAFP have an increased incidence of low birth weight babies. Conflicting reports have separately ascribed these to premature delivery and to intra-uterine growth retardation. We have studied the relationship between MSAFP and low birth weight infants with respect to both prematurity and retarded fetal growth. MSAFP values were expressed as multiples of the appropriate weekly median (MOM) values relating to normal pregnancies with normal outcomes at term. For our normal population an MSAFP value of 2 MOM is the 95% centile, i.e. 5% of normal outcome pregnancies of sure gestation will have MSAFP values in the second trimester which are at or above 2 MOM. Information was available on 389 women whose infants were liveborn singletons weighing 2.5 kg or less. 33 (8.5%) of these women had MSAFP greater than 2 MOM (p less than 0.005) and of the 145 women whose babies weighed less than 2 kg, 17 (11.7%) had MSAFP at this level (p less than 0.001) Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS)

Three human testicular teratocarcinomas were serially passaged following subcutaneous transplantation into nude mice. Tumor cell suspensions from selected passages were injected intraperitoneally. The subcutaneous transplants of each tumor conserved the morphological characteristics of one component of the primary tumor, namely an embryonal carcinoma in one case and a yolk sac tumor in two. The latter maintained the capacity to synthesize alpha-fetoprotein (AFP). After intraperitoneal injection of cell suspensions, tumors, either attached to or even invading abdominal organs or in the form of free-floating tumor spheroids, were observed. AFP could be localized within the attached growths but not in the spheroids. A critical tumor volume and/or vascularization seemed to be necessary for AFP production in tumor cells. In spheroids from one tumor, cytogenetic analysis revealed both human and murine cells. Thus, these spheroids, apparently composed of tumor cells in the center and murine cells at the periphery, can not be considered to be embryoid bodies.

During the last 5 years, radical hepatic resection was performed in 91 patients with hepatocellular carcinoma (HCC). Thirty-one of them had tumour recurrence in the remaining liver during the follow-up period. Second hepatic resection was carried out on nine of them 4-38 months after the first hepatectomy. The ages of these patients ranged from 39 to 65 years with an average of 53.7. There were six men and three women. Eight patients had underlying cirrhosis of the liver and one chronic active hepatitis. Six patients are alive, four being free of HCC and two with disease, for 15-45 months after the first operation. Two patients died of systemic cancer dissemination. The remaining patient had tumour recurrence in the liver again and died of hepatic failure after the third laparotomy. The survival rate of these nine patients was significantly better than that of twenty-two patients who were treated by other palliative methods. The present result shows that a second hepatic resection is a possible and meaningful method of treatment for the patients with recurrent HCCs in the liver remnant.