Search

Objective: To determine whether differences in tumor vessel architecture influence the entry of tumor-associated antigens into the circulation., Study Design: Using an image analysis system, nine vascular parameters in samples of endometrial carcinomas stained for factor VIII-related antigen were evaluated. These were related to groups with, respectively, normal and elevated serum values for two different serum tumor markers: one with low tissue polypeptide-specific antigen (TPS) and one with high molecular weight (CA-125)., Results: Lumen area, lumen perimeter and maximum lumen diameter appeared to differentiate between the normal and elevated TPS group; the higher lumen values occurred in the latter (Mann and Whitney U test: P = .021, .013 and .014, respectively). For CA-125 a higher number of vessels per square millimeter after correction for the epithelium-stroma ratio was found to differentiate between the normal and elevated group (P = .011). The other parameters did not show differentiation between the groups., Conclusion: Distension of vessels appears to be related to the TPS serum level; that might be explained by the presence of endothelial gaps, permitting passive passage of the small TPS molecules. Vascular density appears to be related to the CA-125 serum level. However, whether this relation is real remains to be determined.

Although the nature of the cancer antigen 125 leaves many questions unanswered, the use of serum measurements as a means to assess the response to surgery and chemotherapy in ovarian cancer is now well documented. Good prognostic significance is attributed to a rapid decline in cancer antigen 125 levels after chemotherapy in patients with advanced ovarian cancer. Pre-operative serum cancer antigen 125 levels may successfully discriminate benign from malignant adnexal masses in postmenopausal women, but in women in their reproductive years the specificity is low. In stage I ovarian cancer patients, high preoperative cancer antigen 125 levels are reported to lead to a sixfold increase in the risk of dying from the disease. Low expectations on the specificity and outcome of cancer antigen 125-based screening of asymptomatic women are contradicted by the first results of screening programmes for postmenopausal women. Large, randomized, controlled studies will assess if survival can be improved by early detection of ovarian cancer. Experimental immunotherapy by activation of the idiotypic network directed against cancer antigen 125 may offer new possibilities to prolong survival in advanced ovarian cancer.

Elevated serum levels of the beta-subunit of human chorionic gonadotrophin (hCG) were measured in 50% of patients with locoregional recurrences or progressive vulvar carcinoma (n = 14). At diagnosis of vulvar cancer, however, the incidence of elevated serum levels was low (5%) in 104 patients. The rising serum levels during progression of disease indicate that the synthesis of the beta-subunit hCG can be increased in vulvar carcinoma.

Background: The feasibility of concurrent chemotherapy and radiotherapy for advanced primary carcinoma of the cervix was evaluated and the results were compared to historical controls., Patients and Methods: In a single institution study, patients (n = 74) with primary cervical carcinoma received 3 cycles carboplatin/5-fluorouracil concurrent with radiotherapy followed by salvage hysterectomy (group I). Treatment results were compared with those of a historical control group (n = 39) (group II), treated similarly but without chemotherapy., Results: In group I median follow-up is 28 months (12-68+) and in group II 23 months (14-90+ months). The 5-year overall survival, progression-free survival and local recurrence free survival for group I and II are, respectively, 69% versus 38% (P < 0.003), 67% versus 38% (P < 0.005) and 84% versus 43% (P < 0.0001). Two patients in each group developed posttreatment enteritis., Conclusions: Radiotherapy with concurrent carboplatin and 5-fluorouracil resulted in a better overall survival, disease free survival and local disease free survival compared to historical controls. The toxicity of this schedule did not exceed that of radiation alone in historical controls.

To investigate the role of neutrophils in the efficacy of photodynamic therapy (PDT) in rhabdomyosarcoma-bearing rats, the number of these circulating phagocytes was decreased or increased before interstitial PDT by use of rabbit anti-rat neutrophil serum or granulocyte colony-stimulating factor, respectively. After administration of the antiserum, the number of circulating neutrophils decreased by 99.9%. However, the number of monocytes, lymphocytes, and platelets decreased as well (by 100%, 80%, and 25%, respectively). Under these conditions, PDT did not retard tumor growth at all. However, after cessation of the antiserum treatment 5 days after PDT, a striking decrease in the growth rate occurred subsequent to an increase above the normal range of the number of circulating neutrophils. Administration of the granulocyte colony-stimulating factor led to a specific 4-fold increase in the number of circulating neutrophils. In these rats, the tumor growth at day 2 after PDT was retarded as compared with PDT-treated rats that received saline only. Statistical evaluation of both experimental conditions showed that the efficacy of PDT, expressed as the percentage of change in tumor volume at day 2 after treatment, was dependent on the number of circulating neutrophils present at the day of PDT (P = 0.001; r2 = 0.482). Apparently, neutrophils are indispensable for successful PDT in vivo.

Various anastomotic coupling systems have been developed aiming to facilitate microvascular anastomoses. Of these only the 3M Precise Microvascular Anastomotic System (MAS) has recently gained increasing popularity. However, clinical studies on the use of the MAS are sparse. We report our clinical experience with the MAS in a two-centre study between 1991 and 1996. Of the 96 MAS coupling rings used, 50 were accessible for final analysis, and a 100% patency rate was obtained. The main indication is venous end-to-end anastomosis in vessels of minimal discrepancy. In selected cases in head and neck surgery even end-to-side venous anastomoses appear to be feasible. Although it is not universally applicable for microvascular anastomoses, we conclude that, if appropriate, the MAS coupling device leads to a reliable venous anastomosis in a greatly reduced operating time of less than 4 minutes.

We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal antibodies against CA125. Information on relative affinities and epitope similarities was obtained from a parallel immunochemical study. Antibodies were tested at concentrations of 10 and 1 micrograms/ml on frozen and paraffin sections. Paraffin sections were stained according to the streptavidin-biotin complex protocol, and frozen sections according to a two-step immunoperoxidase technique. Aminoethylcarbazole served as the chromogen. The tissues were from normal proliferative endometrium (formalin-fixed paraffin-embedded) material and clear-cell adenocarcinoma of the ovary (formalin-fixed paraffin-embedded and frozen material). Sections were scored for staining in epithelial cells, basal, apical and diffuse cytoplasmic and in stromal components. Intensity was graded as 1, 2 or 3 for epithelial cells and as -1, -2 or -3 for stroma. The cumulative scores for each antibody expressed the discriminative properties of specific epithelial staining against background. M11 and M11-like antibodies, as well as OC125 and OC125-like antibodies, in general showed good staining results. Although there was a trend for high-affinity antibodies to show higher scores, there was no clear relationship between affinity and staining result. For nine antibodies (ZR45, MA602-1, K102, K94, K90, OV185, K97, K96, OV198), the reactions in paraffin and frozen sections were of similar intensity. Most of these were of low affinity with one exception: antibody ZR45, a rat monoclonal antibody (MAb) which had a high relative affinity. For eight antibodies (M11, K101, MA602-6, ZS33, B27.1, B43.13, K93, OC125), a loss of specific staining was observed in frozen sections. All but two of these antibodies (MA602-6 and OC125) were of high relative affinity. With four antibodies (K91, ZR38, K95, K100), the reverse situation was observed. One (K100) was of low affinity, two (K95 and K91) of high affinity and the fourth (ZR38) was a rat MAb of high affinity. Mainly due to the increased cytoplasmic staining in carcinoma, the reactivity in paraffin sections was less extensive in normal endometrium compared to ovarian carcinoma for the majority of antibodies, irrespective of their affinity or epitope group. The IH characterization of these antibodies may be of help in selecting antibodies with specific properties for further comparative studies. The reactivity of normal endometrium with all useful antibodies makes it a good candidate for standard external IH tissue control.

The aim of the study is to review the mechanisms of resistance to four classes of drugs that are widely used in ovarian carcinoma: platinum (cisplatin/carboplatin) compounds, classical alkylating agents (cyclophosphamide/melphalan), natural drugs (doxorubicin), and "new drugs" (taxol and taxotere). Both platinum and classical alkylating agents mediate their cytotoxicity by the formation of drug-DNA adducts, resulting in DNA damage. Therefore, drug resistance mechanisms are (in part) comparable. In ovarian carcinoma cell lines increased repair of DNA damage and increased detoxification by binding of drugs to glutathione, possibly catalyzed by glutathione S-transferases, have been identified as the most prominent resistance mechanisms to these drugs. Studies on the role of DNA repair mechanisms and glutathione in human ovarian carcinoma are hampered by the complexity of enzyme systems involved in DNA repair and intratumor heterogeneity for glutathione. Resistance to doxorubicin appears to be mediated by enhanced efflux from the cell by increased expression of membrane glycoproteins acting as a drug efflux pump, such as P-glycoprotein. Resistance to doxorubicin can also be due to quantitative and/or qualitative changes in the nuclear target of doxorubicin, topisomerase (Topo) II. Finally, resistance to taxol may be mediated by enhanced expression of P-glycoprotein, while presumed other mechanisms such as alterations in tubulin structure, the cellular "target" of taxol, and changes in polymerization of tubulin are still largely unresolved. Several ways to modulate the reviewed resistance mechanisms are also described. In conclusion, this review shows that many cell biological factors may be involved in drug resistance. The relevance of the identification of most of these factors in ovarian carcinoma patients however remains to be established.

A synthetic peptide comprising amino acids 6-35 of HPV-16 E7 was used in an ELISA to screen sera taken from 31 cervical carcinoma patients. Sera obtained before and during treatment, and in follow-up, were tested for the presence of antibodies to this peptide. Sixteen patients with negative pretreatment serum determination remained negative during treatment and follow-up. Of the 15 patients with positive pretreatment sera, 12 showed a decrease in anti-E7 6-35 antibody level during treatment. During follow-up an increase in anti-E7/6-35 antibody level was observed in 6 out of 7 patients with progressive or recurrent disease, whereas all patients who remained in complete remission showed stable or further decreasing antibody levels. During the course of disease of the 15 seropositive patients, serum anti-E7/6-35 antibody levels were compared with serum squamous cell carcinoma antigen (SCC-Ag) profiles, a clinically useful tumor marker in the management of cervical cancer patients. Similar patterns were observed in 10 out of 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured the maternal serum cancer antigen 125 (MS-CA 125) levels in 98 nonpregnant women, 765 first- and second-trimester pregnancies with chromosomally-normal fetuses, and 54 chromosomally-abnormal pregnancies. To determine the MS-CA 125 concentration, we used a new automated microparticle enzyme immunoassay with low inter-assay variability. The median MS-CA 125 level decreased from the first to the second trimester of pregnancy and was higher than that in non-pregnant women. We found no difference between normal and Down's syndrome (n = 29) pregnancies (t-test: t = 0.57, p > 0.5). The MS-CA 125 levels in pregnancies with other chromosomal abnormalities showed no difference either, compared with the normals. We conclude that MS-CA 125 is not a useful marker for fetal Down's syndrome, nor for other chromosomal disorders in pregnancy.

A new surface plasmon resonance microscope is described that can operate at different resonance angles. The lateral resolution in the surface plasmon resonance microscope depends on the orientation of the edge of the object relative to the plasmon direction. By rotating the object it is possible to reach a resolution of the order of the wavelength. The equipment is described, and it is shown that a resolution of 1.5 microm is obtained for a silver-air interface with 675 nm. Some pictures of biological cells are presented.

The CA 195 levels in ovarian cyst fluids from malignant mucinous tumours (median 2,300,000 U/ml) were significantly higher than the levels in benign mucinous tumours and malignant non-mucinous tumours (medians of 26,800 and 1,700 U/ml, respectively, p = 0.039 and 0.011). Also, the carcinoembryonic antigen (CEA) and tumour-associated trypsin inhibitor (TATI) levels in cyst fluid from mucinous tumours were much higher than those in non-mucinous tumours. Pretreatment serum CA 195 levels were found to be elevated (> 10.5 U/ml) in 72% of the patients with malignant mucinous tumours (n = 25), compared with 35% in malignant non-mucinous tumours and 28% in benign mucinous tumours. The positivity rate shown for serum CA 195 in malignant mucinous tumours was higher than that measured for serum TATI, CA 125 or CEA (60, 53 and 42%, respectively). Measurement of serum CA 195 can be valuable in the clinical management of patients with mucinous ovarian cancer.

Objective: To review the use of a membrane-free haemolysate prepared from maternal blood to distinguish the amniotic sacs at amniocentesis in twin gestation., Setting: University Hospital, Groningen., Method: Haemoglobin solution prepared from maternal blood., Subjects: 63 twin pregnancies having amniocentesis., Results: The fetal loss before 28 weeks was 4%. There was no perinatal mortality. Dye was detected in the second sac in 9 of 24 women tested before 1985 and none of the 39 women since, no malformations could be ascribed to the use of the haemolysate., Conclusion: The use of the membrane-free haemolysate is safe, but the technique will probably gradually become redundant because of improved ultrasound.

Serum alpha-fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24-year-old female in week 17 of pregnancy. After surgery, chemotherapy was postponed. In week 28 levels of serum alpha-fetoprotein increased, but delivery was delayed until 33 weeks' gestation. After delivery, the patient received four chemotherapy courses (cisplatin, etoposide, and bleomycin). Mother (24 months after last chemotherapy) and child are doing well.

Two recently developed monoclonal antibody (MAb)-based anti-mucin assays, CA M26 and CA M29, were studied in 250 cancer patients and compared to 3 well-established marker tests, viz., CA 125, CA 15.3 and SCC, in order to assess their clinical usefulness as serum tumor markers. Pre-treatment sera were obtained from patients with predominantly low-stage epithelial malignancies comprising 200 adenocarcinomas (of the ovary, endometrium, breast and large intestine) and 50 squamous-cell carcinomas (of the uterine cervix). Pretreatment sera of 50 patients with benign ovarian tumors were included to evaluate levels in benign disease, CA M26 and CA M29 cut-off levels were established in 89 healthy controls. In patients with adenocarcinomas, overall positivity for CA M29 was 24%, ranging from 10% in breast cancer to 60% in ovarian cancer. Overall positivity was highest for CA 125 (30%) and lowest for CA M26 (18%) with CA M29 (24%) being similar to CA 15.3 (25%). In adenocarcinomas the combined CA M26-CA M29 assays equalled results obtained with the CA 125-CA 15.3 combination (33% vs. 36%). Elevation of 2 or more markers was highly indicative of advanced disease (p less than 0.025). A majority of positive patients showed either CA M26 or CA M29 elevations, indicating that both antibodies detect distinct epitopes. After adjustment for tumor site and stage, the profile of CA M26 as a single marker differed significantly from the profiles of CA 125 and of CA M29. CA M26 was frequently (32%) elevated in patients with squamous-cell carcinoma of the cervix and CA M26 levels were often independently elevated. CA M26 seems to be valuable as an additional marker in breast cancer and perhaps as a new marker in cervical cancer. CA M29 may be useful in ovarian cancer in addition to CA 125.

Between 1978 and 1989, 451 patients with cervical squamous cell carcinoma were referred to our department, of whom 143 experienced persistent or recurrent disease. Serial serum samples of the patients were analyzed for the presence of squamous cell carcinoma antigen (SCC). The incidence of elevated pretreatment serum SCC levels ranged from 37% in stage IB (N = 173) to 90% in stage IV (N = 19). Multivariate analysis showed that deep stromal infiltration and lymph node metastases were associated with significantly higher serum SCC levels. Serum SCC trends correlated with the course of disease: after treatment the sensitivity (percentage positive results in patients with persistent disease) was 79% and the specificity (percentage negative results in patients with no evidence of disease) was 91%. During follow-up, the sensitivity of the assay was 85.5% in patients with recurrent disease. However, the positive predictive value of a single serum SCC value greater than 2.5 ng/ml for tumor recurrence was only 49%. This figure rose to 76% when two consecutive elevations were determined. Stage and pretreatment serum SCC level were the only factors found to influence survival, using Cox's regression analysis with five pretreatment variables.

The CA 125 assay is used to monitor the course of disease in women with adenocarcinoma of the genital tract. We measured serum CA 125 levels longitudinally in three different groups of patients who had normal serum CA 125 levels (less than or equal to 16 U/ml) before extensive intraperitoneal abdominal surgery (group 1, second-look laparotomy in 28 women with ovarian cancer; group 2, radical hysterectomy in 42 patients with cervical cancer; group 3, 13 men and one woman who had aortic surgery for atherosclerotic occlusive disease or aneurysm formation). Following surgery, rising serum CA 125 levels were observed in 69 out of the 84 patients (82%), irrespective of the primary diagnosis, type of operation or sex. The highest levels were found during the second week after the operation (range 3-336 U/ml) and decreased gradually thereafter, to become normal at 8 weeks after surgery. It was concluded that abdominal surgery interferes with the specificity of CA 125 as a tumour marker during the early postoperative period.

We describe a patient whose both hands were amputated at the level of the wrist in an accident with a farm machine. Both hand were replanted. In spite of an extremely severe injury and consequently a bad prognostic situation an acceptable functional result was obtained. This patient is capable of performing his daily activities reasonably well. He can also ride a bicycle and drive his car.

In a group of 20 asymptomatic women at increased risk for ectopic pregnancy, serum analyses were conducted prospectively early in pregnancy (amenorrhea less than or equal to 45 days) at 2-4-day intervals, to examine the rate of increase in hCG values. The initial serum hCG level, which was determined at the time of the first transvaginal ultrasound examination, was below the discriminatory zone of 1000 IU/l (2nd International Standard). In 8 out of the 9 women who were ultimately diagnosed as having an ectopic pregnancy, the increase in hCG progressed only slowly, with a doubling time exceeding 2.2 days. This slow hCG increase occurred in 2 out of the 11 women who were ultimately diagnosed as having an intra-uterine pregnancy; both women subsequently had an early spontaneous abortion. When Lindblom's hCG score was applied retrospectively to distinguish between intra-uterine and ectopic pregnancies, the hCG increase in all the ectopic pregnancies was below 190 IU/l per day and in 10 of the 11 women with an intra-uterine pregnancy above 190 IU/l per day. A slower rate of increase was observed in only one woman with an intra-uterine pregnancy; she had a spontaneous abortion. The doubling time of hCG and the hCG score are useful diagnostic aids in cases where transvaginal ultrasound has not (yet) given a definite answer regarding the presence of an intra-uterine pregnancy.

In 50 patients with a provisional diagnosis of pelvic inflammatory disease (PID), CA 125 concentrations in serum were measured before laparoscopy and during hospitalization, using an enzyme immunoassay. The findings at laparoscopy were graded on the basis of the extent of inflammatory peritoneal involvement (grades 0-3; normal observations having a score of 0). On admission, 66% of the patients had serum CA 125 concentrations in excess of the cut-off value of 16 U/ml (range: 20-1300 U/ml). The serum CA 125 concentration before laparoscopy correlated with the extent of inflammatory peritoneal involvement (eta = 0.74). The predictive value of an elevated serum CA 125 level to indicate the presence of salpingitis (grades 1-3) was 97%. However, the predictive value of a normal CA 125 level indicating normal observations at laparoscopy (grade 0) was only 47%. During treatment and follow-up, the serum CA 125 concentration returned gradually to normal levels. It was concluded that the finding of an elevated serum CA 125 level confirms the diagnosis of peritoneal involvement in patients with a clinical diagnosis of PID.

The combined occurrence of X-linked steroid sulfatase deficiency of the placenta and X-linked ichthyosis is reported in 6 unrelated boys. Placental steroid sulfatase deficiency was diagnosed on the basis of a very low total estrogen excretion (6 cases), verified prenatally by the dehydroepiandrosterone sulfate (DHEAS) loading test in 4 cases and postnatally by clinical investigations (6 cases) and by biochemical investigations (5 cases). In addition, microsomal arylsulfatase C (MAS) could not be detected in the placental homogenate of the five cases investigated. Lysosomal arylsulfatases were within the normal range. All boys developed well except for X-linked ichthyosis. In the 5 cases investigated the skin biopsy showed the same MAS deficiency histochemically in the granular layer of the epidermis as in the trophoblast cells. The same holds true for the skin of carriers. Steroid sulfatase activity of cultured skin fibroblasts from the boys was almost nil (3 cases). The histochemical technique offers a practical approach in the scientific investigation of keratotic conditions.

Our study reports 6 patients with advanced adenocarcinoma of the fallopian tube, with elevated levels of serum CA 125 (greater than 35 U/ml). In two patients the serum CA 125 values were followed during treatment. In one of them the CA 125 values decreased during clinical remission and increased at the time of tumor progression. In the second patient we observed increasing levels of CA 125 preceding clinical evidence of recurrent disease. The possible usefulness of CA 125 for monitoring patients with tubal cancer is discussed.

In this study the clinical significance of serum ferritin (SF) determinations was evaluated in patients with disseminated non-seminomatous germ cell tumors (NSGCT). The SF levels during the presence of active tumor but before institution of combination chemotherapy (cis-platinum, vinblastine and bleomycin, PVB) were within the normal limits in 38/47 NSGCT patients. During PVB treatment peaking SF levels were observed in relationship to the drug administration, whereas alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) serum levels decreased continuously. Other drugs also caused temporary increases in SF levels. Tumor recurrence was not recognized by SF increases in all eight patients tested. Based on the results we conclude that serial SF determinations are of no value in monitoring patients with NSGCT.

Treatment with methotrexate (MTX) for two patients with gestational choriocarcinoma proved to be inadequate; subsequently both patients received a combination of cis-platinum, cyclophosphamide, actinomycin D and etoposide. These histories demonstrate the need for better prediction of the efficacy of MTX treatment. Baghshawe and Goldstein developed scoring systems to recognize patients requiring primary combination chemotherapy. The Dutch Working Group for Trophoblastic Tumors recently introduced a simplified scoring system to classify these patients. In order to compare these three scoring systems to predict the effect of primary treatment with MTX a retrospective study was made of 37 patients. MTX treatment failures were predictable in 8 out of 13 patients using Bagshawe's system and 6 out of 13 by the Dutch scoring system. The specificity was 88 and 92%, respectively. Goldstein's scoring system proved to be the least sensitive, but very specific.

Inhibin is a peptide hormone normally produced by ovarian granulosa cells. It reaches a peak of 772 +/- 38 U per liter in the follicular phase of the menstrual cycle and is undetectable in the serum of menopausal women. To determine whether measurements of serum inhibin levels would provide a biochemical marker of the presence or progression of ovarian granulosa-cell tumors and their metastases, we measured the serum immunoreactive inhibin concentrations in six women with such tumors. Three women had been treated by hysterectomy and bilateral salpingo-oophorectomy. In the two women with residual or recurrent disease, the serum inhibin levels were abnormally elevated 5 and 20 months before the clinical manifestations of recurrence became evident. The maximal concentrations approached 3000 U per liter. The serum inhibin level remained undetectable in one patient who was disease-free for 11 years. Serum inhibin concentrations were also elevated in three women with amenorrhea and infertility that resulted from small granulosa-cell tumors. After the removal of the tumors, the serum inhibin levels in these women became normal, and fertility returned. There was a significant negative correlation between the serum concentrations of inhibin and follicle-stimulating hormone, in a manner consistent with the autonomous production of inhibin by granulosa-cell tumors. We conclude that granulosa-cell tumors produce inhibin. Since serum inhibin levels reflect the size of the tumor, measurements of inhibin can be used as a marker for primary as well as recurrent disease.

Serum SP-1 levels were measured serially in 94 patients with non-seminomatous germ cell tumors to evaluate its clinical significance as a tumor marker. In 12 out of 80 patients (15%) with active tumors serum SP-1 was found to be elevated, whereas serum HCG and AFP in the same sample were raised in 53 and 45% respectively. Elevation of serum SP-1 levels was always associated with raised HCG levels, and with AFP in 7 patients. During chemotherapy, serum SP-1 and HCG disappeared when a complete remission was obtained. In contrast to HCG, serum SP-1 failed to detect tumor progression in two patients. Serum HCG and AFP are superior as tumor markers to serum SP-1.

Pre-operative serum CA 125 levels were elevated (greater than 35 U/ml) in 44 of 46 (96%) patients with epithelial ovarian cancer. Their serum CA 125 levels ranged from 36 to 8670 U/ml and a correlation with tumour stage was found. Also, during progressive disease, 49 of 53 patients showed elevated levels. At the time of second-look operations, elevated serum CA 125 levels indicated the presence of tumour. However, the presence of small tumour residues (less than 2 cm) and of microscopically detectable tumour in biopsies were not associated with raised CA 125 levels, only a few patients (2 of 13 and 2 of 17, respectively) showed levels higher than 35 U/ml before the second-look operation. Rising levels preceded the clinical discovery of a relapse in 15 of the 22 patients with a median lead time of 3.5 months (1-17 months), and in three patients rising levels were found at the time the tumour recurrence was detected. It is concluded that CA 125, despite its general usefulness, is unable to detect tumour nodules of less than 2 cm in size, but it proved to be a sensitive and early indicator of tumour recurrence and progression.

The presence of the tumor marker CA 125 was studied in the cervices of healthy women. Immunohistochemical staining of normal cervical tissue demonstrated the presence of CA 125 in the tall columnar cells of the endocervical epithelium but not in the ectocervical squamous epithelium. We measured very high levels of CA 125 in liquefied cervical mucus from women with regular menstrual cycles. At midcycle, levels ranged from 14,200 to 153,000 U/ml (n = 13) in cervical mucus, while normal levels less than 35 U/ml were found in the corresponding serum samples. Levels of CA 125 in cervical mucus are comparable to the high levels found in cyst fluids from ovarian tumors (median 24,600 U/ml, n = 25). When secretion of cervical mucus was stimulated by ethinyl estradiol, equally high levels were found (7900 to 138,000 U/ml, n = 10). We conclude that the tumor marker CA 125 is synthesized and secreted by normal endocervical cells. Apparently an effective barrier exists between the endocervical mucosa and the circulation.

In a retrospective study 121 patients with endometrial cancer were examined. In addition, 20 primary endometrial adenocarcinomas were tested immunohistochemically for CA 125. All tumor tissues were demonstrated to contain CA 125. However, only 25% of 110 patients had elevated CA 125 levels in serum before treatment. The incidence of elevated CA 125 serum levels increased with higher tumor staging up to 55% and 86% in surgical Stages III and IV, respectively. In Stage I and II disease (International Federation of Gynecology and Obstetrics) elevated serum levels before treatment correlated with the presence of tumor tissues outside the uterine body or outside the uterus, respectively, as was determined histopathologically after operation. In addition a close correlation between elevated levels and vessel invasion of tumor cells was revealed. Serum levels of CA 125 paralleled the clinical course of disease. Tumor recurrence in the abdomen can be preceded by an increase of serum CA 125 levels.

Amniotic fluid alpha-fetoprotein (AFP) concentrations were measured in 2180 patients at risk of fetal abnormality because of previous history, family history, advanced maternal age, suspected fetal growth retardation and hydramnios. In 12 patients investigated before 20 weeks gestation, pregnancy was terminated because of a raised amniotic fluid AFP-level: 11 fetuses had neural tube defects (NTDs) and one had a congenital nephrosis. There were no false negative results in the 1927 patients tested before 20 weeks and with a pregnancy of known outcome. In patients tested after 20 weeks, the amniotic fluid AFP concentration was raised in 20 cases of anencephaly, in 9 fetuses with severe congenital malformations without NTD and in one apparently normal fetus. Of 428 patients with a previous offspring who had a NTD, only 8(1.9 per cent) again had a fetus with a NTD.

The mean serum high density lipoprotein cholesterol (HDL-C) concentration proved to be significantly lower in 23 women taking depot-medroxyprogesterone acetate (DMPA) as a twelve-weekly injectable contraceptive for at least 1 year, as compared to 23 IUD users. In the DMPA group, no significant difference was found in the mean serum HDL-C concentration, when measured 2, 6 and 12 weeks after a DMPA injection.

The serum enzyme activities of gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), serum glutamyl oxalate transaminase (sGOT) and serum glutamyl pyruvate transaminase (sGPT) were determined longitudinally in 51 patients with a disseminated non-seminomatous testicular tumor. Elevated levels of one or more enzymes before chemotherapy were observed in 13 patients, all with stage III disease. If, after two cycles of chemotherapy, the established tumor markers alpha-fetoprotein (AFP), human chorionic-gonadotropin (HCG) and/or lactate dehydrogenase (LDH) were normalized, the initially increased enzyme activities were declined to normal values as well. Peaking concentrations of one or more of the tumor markers during induction chemotherapy, probably due to tumor cell lysis, were found in 34 of 45 marker-positive patients (76%). In addition, increases of one or more of the investigated enzyme activities were also noticed in 20 patients. In 76% of these patients the highest point of the tumor marker concentration coincided well with that of the enzyme activities. Indications are given that the peak activities were probably not caused by liver damage. Enzyme elevations were also found in 3 out of 7 patients with progressive disease. The behaviour of the enzyme activities of GGT, AP, sGOT and sGPT in patients with a disseminated non-seminomatous testicular tumor coincided with the known tumor markers. It favors the hypothesis that these enzymes are synthesized in the tumor. The mortality amongst stage III patients with or without initially raised GGT levels differed significantly (P less than 0.02). Finally, it is concluded that in patients with a non-seminomatous testicular tumor, sGOT, sGPT, GGT and AP cannot be used to diagnose liver function.

The decline of serum levels of AFP or HCG in 26 patients with disseminated non-seminomatous germ cell tumors during chemotherapy showed two different patterns: a linear decline or an increasing apparent half life (AHL). The initial AFP half life in 13 patients with a linear decline was 7.2 +/- 1.8 days, and did not differ from the initial half life in 5 patients with a curvi-linear pattern. HCG half life was 3.0 +/- 0.5 days in 10 patients with a linear AHL, and was not different from the initial half life in 6 patients with delayed marker disappearance. Based on the half life pattern of AFP or HCG the result of chemotherapy was predicted. When AFP or HCG showed a linear decline, all viable tumor appeared to be eliminated in 38 and 40% respectively of the patients. An increasing AHL indicated the presence of active tumor, mostly mature teratoma, in 60% of the patients with AFP and in 83% of the patients with HCG. Thus, the pattern of AFP or HCG half life does not predict the eventual outcome of chemotherapy with certainty.

In 82 patients with non-seminomatous germ cell tumors, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) were determined to find if there was a relation to clinical stage. Only two out of 34 patients could be restaged as a result of the presence of elevated marker levels. Markers were present in 12% of patients with stage IIA, 67% with stage IIB and 85% with stage III. In contrast to HCG, the initial levels of LDH and AFP were related to tumor stage. A return of marker levels to normal during chemotherapy always meant tumor regression and indicated complete remission in 42% of patients. Initial marker levels did not correlate with the eventual destructionn of all tumor by chemotherapy. A rise in marker levels always correlated with tumor progression. In conclusion, tumor markers have only a limited value in clinical staging. Disappearance of markers during chemotherapy does not always indicate destructio of all viable tumor, probably because non-producing cell lines such as mature teratoma may persist after chemotherapy.

Immunoglobulin allotypes were examined in the sera of 75 Caucasian patients with epithelial ovarian cancer and of 204 normal individuals. The distribution of the Gm and Km phenotypes in both populations did not differ significantly.

The significance of serum SCC antigen as a tumor marker was investigated in 94 women with squamous cell carcinoma of the vulva. The incidence of elevated serum SCC levels varied from 10% in FIGO stage I to 40% in FIGO stage IV. We did not observe a correlation between elevated pretreatment SCC values and the presence of lymph node metastases. During follow-up, elevated serum SCC values were observed in 8 of 19 patients (42%) with recurrent or progressive disease. It is concluded that the determination of serum SCC levels does not provide additional information in the staging of squamous cell vulvar carcinoma, but can be useful for the early detection of recurrent disease during follow-up in some patients. However, elevated serum SCC levels were also found in 25% of patients without demonstrable tumor activity during follow-up and benign skin disorders were recognized as a cause of false-positive SCC results.

Thirty-three patients with a non-seminomatous germ cell tumor of the testis in clinical stage I were treated only by orchidectomy. The very careful follow-up--with tumor marker assays every 3 weeks, chest X-rays every 6 weeks and CT-scans of the lungs and retroperitoneum every 3 months--revealed metastases in 7 of the patients (21%). All these relapses were diagnosed within 6 months of the orchidectomy. Para-aortic node metastases were found in 5 of the 7 patients, with additional inguinal node metastases in 1 and additional lung metastases in 1; 2 patients had only lung metastases. Six of the 7 patients with a relapse were given chemotherapy (PVB); 1 patient refused chemotherapy. In view of residual disease a surgical excision was performed; it revealed necrosis as well as mature teratoma. All 33 patients are still alive, the post-orchidectomy follow-up period being 12-38 months.

Serum levels of HCG and SP-1 and tissue localization in the primary tumors of these markers were correlated in 41 patients with advanced-stage non-seminomatous germ cell tumors (NSGCT) of the testis. In patients' serum, as well as in the primary tumor tissue, SP-1 positivity was accompanied by a concordant HCG positivity, so that it is concluded that in our patient group SP-1 does not give important additional information with respect to marker positivity not yet provided by HCG. A good correlation was found between serum levels of HCG and SP-1 in advanced-stage disease and the cellular localization of these markers in the primary tumors. Elevated serum SP-1 levels, with concordant elevation of HCG serum levels, were found mainly in cases with a histological diagnosis of choriocarcinoma or an admixture of this component in the primary tumor. Moreover, in cases of choriocarcinoma the presence of SP-1 positive syncytiotrophoblastic cells was very much comparable with the presence of HCG-positive syncytiotrophoblastic cells, whereas in syncytial giant cells associated with embryonal carcinoma HCG-positivity clearly outnumbered SP-1-positivity. This indicates a higher specificity of SP-1 for choriocarcinoma and, therefore, serum levels of this marker may have an important prognostic impact in NSGCT patients with advanced-stage disease. Apart from positivity in syncytiotrophoblastic cells of choriocarcinoma and syncytial giant cells, HCG positivity was incidentally seen in mononuclear embryonal carcinoma cells.

Squamous cell carcinoma antigen (SCC), formerly referred to as TA-4, is a tumor marker for SCC of the uterine cervix. Based on the findings in a patient with complete remission after treatment for cervical carcinoma, the authors decided to analyze the sera from patients with benign dermatoses. It was found that 83% (25/30) of the patients with psoriasis and 80% (12/15) of the patients with eczema had SCC levels in excess of the cut-off value of 2.5 ng/ml. In psoriasis the serum SCC level correlated positively with the body surface area affected by the disease (r = 0.64). Seven patients with miscellaneous skin disorders, all with an inflammatory component, showed high serum SCC levels as well. Thus the existence of an inflammatory skin disease or a hyperkeratotic skin disease with an inflammatory component interferes with the usefulness of the SCC antigen as a tumor marker in SCC of the uterine cervix.

Children and adults with recessive X-linked ichthyosis have elevated levels of cholesterol sulfate, a substrate of the deficient enzyme microsomal sulfatase, in blood, erythrocyte membrane, and ichthyotic scale. We investigated cholesterol sulfate levels in patients with microsomal sulfatase deficiency before birth in amniotic fluid and in maternal plasma and erythrocytes, in cord blood (plasma and erythrocytes), and in plasma in the first month of life before and after onset of skin symptoms. Levels in amniotic fluid and cord blood were elevated. The plasma levels in the first month, before as well as after onset of skin symptoms, were within the range found in older patients with manifest skin symptoms.