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To describe fatal cases of gestational trophoblastic neoplasia (GTN) over four decades and evaluate whether treatment was given according to the protocol and reveal possible implications for future management.Retrospective cohort study.The Netherlands.Women who died from GTN from 1971 to 2011.Records from the Dutch Central Registry for Hydatidiform Moles and the Working Party on Trophoblastic Disease were used to identify fatal cases of GTN.Disease extent, risk classification, treatment regimens and cause of death.Twenty-six women died from GTN. In five cases GTN developed after a hydatidiform mole and in 19 cases following term pregnancy. Half of the women died between 1971 and 1980, when women were not yet classified as having low-risk or high-risk disease and were therefore not yet treated accordingly. A major decline in the number of deaths was seen after the first decade, with a further decrease from 1981 to 2011. Early death occurred in nine women. In four of these women, death was treatment-related. Women who died more than 4 weeks after the start of treatment mostly died from metastatic tumour (n = 14).The yearly number of women who died from GTN decreased considerably over the last four decades. Appropriate risk classification is essential to start optimal initial therapy and to prevent therapy resistance. Women with post-term choriocarcinoma represented a large proportion of the dead women and we propose that these women are considered as having high-risk disease.

To evaluate the diagnostic additional value of routine alpha-foetoprotein (AFP) assessment in amniotic fluid for the detection of neural tube defects (NTDs), compared with week 20 ultrasonographic examination.Retrospective.We retrospectively determined AFP concentrations in amniotic fluid obtained from 7981 women who had undergone amniocentesis for karyotyping and AFP assessment. An AFP concentration greater than 2.5 times the median was considered abnormal. Women were categorised into 4 groups based on the indication for invasive prenatal diagnostic assessment: advanced maternal age (group I; n = 6179), increased risk of foetal NTDs (group II; n = 258), ultrasonographically confirmed foetal NTDs (group III; n = 55) or other indications (group IV; n = 1489).In group I, 18 of 6179 samples had increased AFP levels (0.3%), 2 of which were associated with NTDs. In group II, 2 of 258 samples had increased AFP levels (0.8%); both were associated with NTDs. Increased AFP levels were found in 44 of 55 samples from group III (80%), and 223 of 1489 samples from group IV (15.0%).Routine assessment of AFP in amniotic fluid based on advanced maternal age provides little additional value in the detection of NTDs beyond that of week 20 ultrasound.

Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Studies on hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen, ITA) in PTD are limited. In serum samples taken before evacuation of molar pregnancies we measured the concentrations of free hCG beta-subunit (free hCGbeta), "total" hCG (hCG+hCGbeta) and ITA, and determined whether ITA, the two other hCG analytes, or the calculated ratios of hCGbeta/hCG+hCGbeta, hCGbeta/ITA and hCG+hCGbeta/ITA could predict the later development of PTD.A retrospective study based on blood specimens collected in the Dutch Central Registry for Hydatidiform Moles. The study group comprised 97 patients with hydatidiform moles who did not develop PTD after mole evacuation and 33 patients who did develop PTD.Serum samples from 130 patients with hydatidiform mole with or without PTD were assayed using specific (radio)immunoassays for free hCGbeta, total hCG, and ITA. From these analytes we also calculated the ratios hCGbeta/hCG+hCGbeta, hCGbeta/ITA, and hCG+hCGbeta/ITA. To predict the development of PTD from these analytes and parameters we performed receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curve (AUCs) that represented the diagnostic accuracy which was rated in a range from excellent (AUC0.9 or0.1) to poor (AUC 0.4-0.6).The diagnostic accuracy of ITA was moderate (0.618) and not different from that of free hCGbeta (0.610) and hCG+hCGbeta (0.622).ITA as well as the other analytes and parameters in serum taken prior to evacuation from patients with molar pregnancies cannot be used to predict the subsequent development of persistent trophoblastic disease.

The aim of this study was to analyze the concentrations of different components of the plasminogen activation system in cyst fluid from malignant, borderline and benign ovarian tumors and to compare these results with clinicopathological characteristics (FIGO staging, histological grading, residual tumor, ascites, tumor recurrence and disease-free survival).One hundred and seven cyst fluid samples were enrolled from 25 malignant, 12 borderline and 70 benign ovarian tumors. Determination of uPA, tPA, PAI-1, PAI-2, uPA:PAI-1 complex and tPA:PAI-1 complex was performed by specific double determinant ELISAs based on the concept described previously by Grebenschikov et al. With these ELISAs both complexes of the activators (uPA, tPA) with their inhibitor (PAI-1) can be measured as a separate component.Significant differences were found in median cyst fluid concentrations of uPA, PAI-1, uPA:PAI-1 and tPA:PAI-1 from malignant, borderline and benign ovarian tumors, with the highest levels in malignant ovarian tumors. Cystic endometriosis seems to be a special entity within the benign subclass. To achieve better discrimination between malignant and benign cases we introduced a new malignancy index: ([uPA:PAI-1]+[tPA:PAI-1])x [PAI-1]. The area under a Receiver Operating Characteristic (ROC) curve amounted to 0.80. Significantly higher concentrations were found in FIGO stages II-III-IV compared with stage I for uPA (p0.05), tPA (p0.05), uPA:PAI-1 (p0.01) and tPA:PAI-1 (p0.05).Concentrations of plasminogen activation system markers in cyst fluid from ovarian tumors are related to histological subtype. The most significant components are uPA, PAI-1 and the complexes uPA:PAI-1, tPA:PAI-1. The prognostic value of the components seems to be limited but might be important in detecting high-risk borderline or low stage patients.

Item does not contain fulltext Serum determinations of tumor markers are indispensable in the diagnosis and management of cancer, and therefore play an important role in clinical practice. After a short historical survey, we systematically review a number of contemporary aspects of serum tumor markers related to various organ systems, and briefly indicate possible future developments.

The human anti-mouse antibody (HAMA) response was determined in the serum of patients suspected of having ovarian cancer who underwent radioimmunoscintigraphy with either 99 Tc m -OV-TL 3 Fab' In = 20) or 111 In-DTPA-OV-TL 3 F(ab') 2 (n = 73). Blood samples were collected prior to and at several time points post-intravenous injection. The detection of HAMA was performed with an in-house OV-TL 3 F(ab') 2 -based sandwich-type immunoradiometric assay (IRMA). The homologous IRMA demonstrated that 8 of 20 (40%) patients had developed HAMA responses after injection of Fab' fragments and that 14 of 73 (19%) patients had developed HAMA responses after F(ab') 2 administration. The subclass of the measured HAMA was analysed in a limited number of samples, showing IgG or IgM as well as mixed responses. The kinetics of the HAMA responses varied greatly. Our study showed the relevance of the sampling time and frequency : HAMA responses can be easily underestimated with a low sampling frequency. The homologous IRMA described in this study was able to quantify the OV-TL 3-specific HAMA responses. With additional assays, the subclass of the HAMA could be further analysed. Remarkably, the fraction of HAMA responders after injection of OV-TL 3 Fab' fragments was in the same range as the proportion of HAMA responders after F(ab') 2 administration.

A time-resolved immunofluorometric assay (IFMA) is described for quantifying the ovarian carcinoma-associated antigenic determinant CA 125 in human serum. Monoclonal antibody to CA 125 is immobilized onto a microtiter well, and the same antibody labeled with a europium chelate is used as a tracer. After the immunoreaction the bound portion of the labeled antibody is quantified by dissociating the Eu3+ in a fluorescence-enhancement solution and measuring its fluorescence with a time-resolved fluorometer. The detection limit of the IFMA is 1.5 arb. units/mL, being about the same as that of a commercially available immunoradiometric assay (IRMA) for CA 125 (1.4 arb. units/mL). The analytical range of the IFMA extends to 2000 arb. units/mL, whereas the range of the IRMA is 500 arb. units/mL. For 29 serum samples from ovarian-cancer patients measured simultaneously in the IFMA and IRMA, orthogonal regression analysis gave the equation CA 125 (IFMA) = 0.9937 CA 125 (IRMA) - 1.211 arb. units/mL (Syx = 6.8681, r = 0.9932). Apparently, the IFMA for CA 125 is a convenient alternative to the IRMA for CA 125 because of short counting times, the use of nonradioactive, stable reagents, and the much-extended measuring range. Additionally, the microtiter format should lend itself to more fully automated procedures in laboratories doing many such analyses.

Serum levels of estradiol (E2), progesterone (P), prolactin (Prl), monkey chorionic gonadotropin (mCG), dehydroepiandrosterone sulfate (DHEAS), and cortisol (C) in pregnant cynomolgus monkeys are described. mCG, E2, and Prl patterns resembled those of pregnant rhesus monkeys. P patterns differed from data from the literature. DHEAS patterns did not follow E2 patterns. C levels did not change during pregnancy.

A comparison of assay design, sensitivity and specificity is given for 10 urinary human chorionic gonadotrophin (hCG) test kits for early pregnancy diagnosis. One slide test applies a polyclonal anti-hCG serum, while nine, more recently developed, tube and slide tests use one or more monoclonal antibodies toward intact hCG or its free subunits. Colour development for five immunoenzymetric (IEMA) ‘sandwich’ assays, or (haem/latex) agglutination (HA, LA)-inhibition (HAI, LAI) for the other systems provide assay sensitivities from 1000–50 IU/L within 3–120 min. The ‘best’ slide-(i.e., LA, LAI), haem-(i.e., HA, HAI) and IEMA-tests detect respectively 500, 75 and 50 IU/L within 2·5, 120 and 3 min. Assay specificities (i.e., as false-positive and false-negative test results) are studied using intact hCG, hLH and their free α- and β-subunits. The presented assays are improved, perform more sensitively at shorter reaction times with increased specificity, and may, therefore, establish pregnancy at an earlier stage with greater reliability.

Human term placenta tissue homogenates were subjected to differential centrifugation procedures. The composition of the subcellular fractions was monitored with a number of marker enzymes and the effectiveness of these enzyme systems was evaluated. The subcellular fractions were tested for their 17β-hydroxy dehydrogenase activity on testosterone, oestradiol and the synthetic substrate retrotestosterone. Buffer medium composition showed a direct influence upon enzyme distribution patterns of all fractions during the same differential centrifugation procedure. All enzyme activities tested became less sedimentable when glycerol was present in the fractionation buffer. Glycerol stabilized soluble 17β-hydroxy dehydrogenase activity during fractionation. The activity of steroid-converting enzymes was inhibited by the presence of glycerol in the medium. Subcellular distribution of marker enzymes did not sustain the presence of mitochondrial 17β-hydroxy dehydrogenase but related it to microsomal contamination. In general the proportion of 17β-hydroxy dehydrogenase activity in the particulate fractions showed a decrease in the substrate order retrotestosterone > testosterone > oestradiol which was independent from the buffer medium used. Specific activities for both particle-bound and soluble 17β-hydroxy dehydrogenase increased in the substrate order retrotestosterone < testosterone < oestradiol. The particulate enzyme activity was maximal with NAD+ for the three substrates tested, but in the cytosol fraction NADP+ was the preferential co-enzyme only when oestradiol was used as the substrate.

Fifteen immunoassay kits for serum hCG(-β) measurements have been compared for their analytical characteristics and clinical usefulness in tumour monitoring. Three out of 13 radioimmunoassays and two sandwich hCG immunoassays represent the ‘one-component’ techniques for intact hCG detection since they are based on antiserum raised against intact hCG. Within this group, method-comparison slopes ranged between 0·149 and 0·374. The remaining 10 radioimmunoassays all apply antiserum against hCG-β and are designated ‘two (or more)–component’ assays since they detect both intact hCG and the free β-subunit (‘total hCG’). For this reason these assays are of potential value for tumour monitoring. Additional criteria for this are: (1) the expression of assay results in terms of 1st IRP-hCG instead of the unstructured use of the 2nd IS or the 1st IRP-hCG-β; (2) documentation of cross-reactivities especially for the free β-subunits of hCG and hLH which are almost completely lacking; (3) establishment of the minimum detectable dose in the presence of normo-to-hypergonadotrophic hLH levels in serum (the ‘clinical sensitivity’) to allow the follow-up of tumour regression especially in the low-dose region. Method-comparison analysis for these assays revealed regression slopes between 0·001 and 0·873.

A clinical study of intravesical prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) in the treatment of 13 female patients with difficulties in emptying their bladder is reported. Urodynamic investigations were performed before and after instillation of the drug. Although 3 patients had some reduction in residual urine volume, the remainder showed no obvious change and no patient experienced subjective improvement. In 6 patients, biopsies of the vesical mucosa were taken before and after instillation in order to measure the uptake of prostaglandin by the mucosa, but no conclusions could be drawn from these measurements. Although prostaglandins are known to have contractile effects on the detrusor muscle, the results of this study suggest that intravesical PGE2 and PGF2 alpha have no therapeutic value in the treatment of voiding dysfunction and residual urine.