Gestational trophoblastic disease: management, the European way.
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Female↗
Biomedical subjects
P Kenemans
Publications and source records attributed to P Kenemans.
[The pill and cancer of the female sex organs and breast].
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Breast Neoplasms↗
Comparative evaluation of diagnostic methods in ovarian carcinoma with emphasis on CT and MRI.
A prospective study was performed in 64 patients suspected of having primary or recurrent ovarian epithelial cancer. Physical examination (PE), ultrasonography (US), computer tomography (CT), and magnetic resonance imaging (MRI) were performed and CA 125 serum levels (CA 125) were determined. This evaluation was followed within 3 weeks by laparotomy, which served with the pathology data as the gold standard. Both CT and MRI were, independently, evaluated by two experienced radiologists. The accuracy in diagnosing ovarian carcinoma of both CT (70 and 91%) and MRI (64 and 88%) in patients suspected of primary and recurrent cancer grouped together differed between the two radiologists, but for each radiologist no difference in overall accuracy between CT and MRI was observed. The accuracy of PE was 64%, of US, 67%, and of CA 125, 72%. At surgery, 132 separate tumor locations were present. With CT, 41 and 69% and with MRI, 44 and 56% of these lesions were recognized by the two radiologists, respectively. This was the case in 27% with PE and 34% with US. We conclude that in our setting MRI had no additional value over CT. The interobserver variability was high for both MRI and CT. MRI and CT are both useful diagnostic methods in the diagnosis of ovarian carcinoma.
Adult↗
Prognostic significance of serum fragments of cytokeratin 19 measured by Cyfra 21-1 in cervical cancer.
Pretreatment sera of 78 patients with squamous cell cervical cancer were tested for the presence of cytokeratin 19 (CK 19) fragments to determine the relationship among this parameter, tumor stage, various histopathologic characteristics, and prognosis. For the quantitative determination of CK 19 fragments in serum, the enzyme assay Cyfra 21-1 was used. This assay, based on the simultaneous sandwich principle, utilizes two different monoclonal antibodies. The test was considered positive when levels of Cyfra 21-1 were > or = 1.2 micrograms/liter. Cyfra 21-1 was positive in the majority of patients and in all patients with advanced disease (FIGO III or IVa). A highly significant relationship was found between pretreatment Cyfra 21-1 level and FIGO stage (P < 0.0001). Mean Cyfra 21-1 concentration was elevated in the case of macroinvasive disease (FIGO Ib, IIa, IIb, III, IVa). A distinct relationship was found between tumor size (P < 0.001; r = 0.73) and Cyfra 21-1 level. In the univariate Cox analysis Cyfra 21-1 level was significantly related to both disease-free interval (P < 0.0001) and survival (P < 0.0001) of patients. Patients with an increased Cyfra 21-1 level had a significantly worse prognosis. However, in the stepwise Cox regression analysis, these variables had no additional value over known prognostic factors such as FIGO stage and tumor size. It is concluded that Cyfra 21-1 may be of significance as an additional marker in the management of patients with cervical cancer, but further investigation is needed.
Adult↗
Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours.
In previous studies we have shown down-regulation of class I major histocompatibility complex (MHC) expression in a significant proportion of primary cervical carcinomas, which was found to be strongly correlated with loss of expression of the transporter associated with antigen presentation (TAP). By contrast, class II MHC expression was frequently up-regulated on neoplastic keratinocytes in these malignancies. In order to investigate whether these changes are associated with biological behaviour of the tumours, 20 cervical carcinomas were analyzed for MHC (HLA-A, HLA-B/C, HLA-DR) and TAP-1 expression in the primary tumours and in lymph node metastases by immunohistochemistry. The results showed a significant increase in the prevalence of HLA-A and HLA-B/C down-regulation in metastasised neoplastic cells as compared with the primary tumour (P = 0.01). In all cases this was accompanied by loss of TAP-1 expression. Up-regulated HLA-DR expression was found exclusively in primary tumours and was absent in the corresponding metastases (P = 0.002). These data are consistent with the hypothesis that loss of TAP-1 and the consequent down-regulation of class I MHC expression provides a selective advantage for neoplastic cervical cells during metastasis. Furthermore, the lack of class II MHC expression in metastasised cells either reflects a different local lymphokine production or indicates that these cells may have escaped CD4+ cytotoxic T-lymphocyte (CTL)-mediated killing.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Estrogen replacement therapy continuously combined with four different dosages of dydrogesterone: effect on calcium and lipid metabolism.
Lipid and bone metabolism was studied in 165 healthy postmenopausal women treated with 2 mg 17 beta-estradiol continuously combined with one of four doses (2.5, 5, 10, or 15 mg) of dydrogesterone in a double blind randomized study design. Fasting blood and urine samples were drawn at baseline and after 3 and 6 months of treatment. Bone remodeling was significantly reduced in all four treatment groups, as indicated by the decrease in serum corrected calcium, phosphate, and alkaline phosphatase and the urinary calcium/creatinine ratio. A dose response of dydrogesterone on these indices was not found. With all four dosages of dydrogesterone, lipid profile (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and apolipoproteins) improved significantly; however, this was less pronounced with the highest dydrogesterone dose. Our data suggest that continuously applied dydrogesterone in combined hormone replacement therapy does not annihilate the beneficial effects on bone remodeling and lipid metabolism induced by estrogens.
Administration, Oral↗
Technical evaluation of three second generation CA 125 assays.
The analytical performance of five CA 125 assays was studied using samples from apparently healthy women (n = 28) and from a group of patients with gynaecological malignancies (n = 260). Investigations were carried out on two homologous sandwich assays using the monoclonal antibody OC 125 (LIA-mat I and IRMA-mat I) and three heterologous assays using the monoclonal antibodies OC 125 and M11, both directed against the carcinoantigen CA 125 (LIA-mat CA 125 II, IRMA-mat CA 125 II, Centocor CA 125 II). The precision of the LIA-mat CA 125 II was better than that of the previously used LIA-mat I, the intra-assay coefficients of variation being 6.5% and 11.6% respectively. Using the new generation CA 125 II assays, only 0.5% of the duplicate measurements had to be rejected. The inter-assay coefficient of variation of the automated LIA-mat CA 125 II ranged from 7.1% to 11.2% while the IRMA-mat CA 125 II inter-assay CV ranged from 11.6% to 13.9%. Serum EDTA or heparin plasma did not give significantly different results. A carry-over of 0.02% was observed using the LIA-mat S 300 system. A high dose hook effect may be observed with concentrations over 20000 kU/l. All assays showed excellent linearity, and there was a good correlation between the assays.
Adult↗
High-dose intensity regimens with epirubicin in ovarian cancer.
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Cisplatin↗
Kinetics and tissue distribution of the radiolabeled chimeric monoclonal antibody MOv18 IgG and F(ab')2 fragments in ovarian carcinoma patients.
Twenty-four patients suspected of having ovarian carcinoma received i.v. injection with a combination of radiolabeled intact IgG (1 mg) and F(ab')2 fragments (1 mg) of the chimeric monoclonal antibody MOv18, each form labeled with 1.85 MBq 131I or 125I. Laparotomy was performed either 2 or 6 days after injection, and the uptake of radioactivity was determined in a total of 329 biopsies of normal and malignant tissues. The mean elimination half life in plasma of cMOv18 IgG and F(ab')2 was 70 +/- 8 (SD) and 20 +/- 5 h, respectively. The mean uptake of IgG in tumor biopsies was 3.6-fold higher two days after injection and 6.9-fold higher than the uptake of F(ab')2 6 days after injection. Uptake in normal tissues was 3.3 and 5.5 times higher for IgG at 2 and 6 days, respectively. Two days after injection, the mean ratio of the uptake in tumor:normal tissue/patient was 3.8 +/- 1.5 and 4.0 +/- 1.8 for radiolabeled cMOv18 IgG and F(ab')2, respectively. Six days after injection, this was 6.7 +/- 4.7 for Ig G and 5.7 +/- 4.1 for F(ab')2. cMOv18 IgG has a longer circulation time in blood, a higher uptake in tumor and normal tissues, and a longer retention time compared to the F(ab')2 fragments. However, the tumor:normal tissue ratios are similar. The results do not warrant a definite conclusion as to which antibody form is most suitable for therapeutic application of antibodies but provide a more firm basis for rational design of therapeutic targeting studies using immunoconjugates.
Adult↗
The cellular composition in the peritoneal cavity and the cytotoxic function of the peritoneal cells from patients with ovarian cancer; effect of tumor necrosis factor-alpha treatment.
In patients with epithelial ovarian cancer (EOC), the cellular composition in the peritoneal cavity and the functional capacities of the peritoneal cells (PC) are unknown. Especially the peritoneal macrophages (m phi) could play an important role in defense against tumor cells. To study the cellular composition in the peritoneal cavity and the functional capacities of PC, these cells were obtained from three patients with EOC. The PC were immunophenotyped and tested functionally in vitro in a cytotoxicity assay. One of the patients was treated intraperitoneally (i.p.) with a single dose of 0.06 mg/m2 tumor necrosis factor-alpha (TNF-alpha). PC were obtained before the treatment, after 24 h and after 1 week. PC from healthy women undergoing laparoscopic sterilization served as controls. It appeared that patients with EOC have a lower percentage of macrophages (m phi) in the peritoneal cavity than healthy persons. These m phi of patients were also less capable of killing U 937 tumor cells as compared to the peritoneal m phi of control persons. However, in the patient treated i.p. with TNF-alpha the cytotoxic capacities of the peritoneal m phi were strongly improved. The percentage cytotoxicity at an effector to target ratio of 10, increased from 17% to 80%. Thus, the peritoneal m phi in this patient were activated in vivo to a tumoricidal state. These findings indicate that PC in patients with EOC differ from controls, but further investigation is necessary to define the contribution of the disease and/or prior chemotherapy to this defect.
Adenocarcinoma↗
Identification of peptide sequences that potentially trigger HLA-A2.1-restricted cytotoxic T lymphocytes.
We used the human processing defective cell line 174CEM.T2 (T2) to identify potential cytotoxic T lymphocyte (CTL) epitopes of human proteins. Exogenously added peptides can increase the number of properly folded HLA-A2.1 molecules on the cell surface of T2 cells, as shown by immunofluorescence measurements using the mouse monoclonal antibody BB7.2 (anti-HLA-A2.1) and fluorescein isothiocyanate-labeled goat anti-mouse F(ab')2 antibody. The peptides were selected on the basis of a computer score derived from the recently described HLA-A2.1 specific motif. Analysis of the influenza matrix protein showed that 15 out of 35 high-scoring peptides up-regulate the expression of HLA-A2.1 molecules on the T2 cell surface. The combination of the computer scoring program and an immunofluorescence-based peptide binding assay allows rapid detection of potential CTL target peptides.
Amino Acid Sequence↗
In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild-type p53.
The central role of the p53 tumor suppressor gene product in oncogenesis is gradually being clarified. Point mutations in the p53 tumor suppressor gene are common in most human cancers and are often associated with p53 protein overexpression. Overexpressed wild-type or mutant determinants of the p53 protein thus represent an attractive target for immunotherapy of cancer directed against a structure involved in malignant transformation. An important step towards this goal is identification of epitopes of p53 that can be recognized by human cytotoxic T lymphocytes. We identified peptides of (mutant) p53 capable of binding to HLA-A2.1 in an in vitro assay. These HLA-A2.1-binding peptides were utilized for in vitro induction of primary cytotoxic T lymphocyte responses using a human processing-defective cell line (174CEM.T2) as antigen-presenting cell. These cells display "empty" HLA class I surface molecules, that can efficiently be loaded with a single peptide. We obtained CD8+ cytotoxic T lymphocyte clones capable of specifically lysing target cells loaded with wild-type or tumor-specific mutant p53 peptides. This strategy allows the in vitro initiation of human cytotoxic T lymphocyte responses against target molecules of choice.
Amino Acid Sequence↗
HPV DNA presence and HPV genotypes as prognostic factors in low-stage squamous cell cervical cancer.
Sixty-four patients with FIGO stages IB and IIA squamous cell carcinoma of the uterine cervix were studied to assess the prognostic potential of the presence of HPV DNA and HPV genotypes in the tumor, as detected by a general primer-mediated polymerase chain reaction followed by a type-specific PCR on paraffin-embedded tissue sections of the primary tumor. The prevalence of various HPV types in 32 patients with positive lymph nodes was compared to the prevalence found in 32 age-matched controls with negative lymph nodes. In both patient groups HPV DNA was found in all cases. The prevalence rates of HPV types 16, 18, and X in the positive and negative lymph node group were 78% versus 72%, 13% versus 9%, and 3% versus 16%, respectively. These differences were not statistically significant. HPV genotypes 6, 11, and 31 were not found. Differences in recurrence rate and 5-year survival rate between the patient groups with different tumor-containing HPV genotypes were not statistically significant. Nor was there any statistically significant relationship between HPV type and other well-known prognosticators. In conclusion, in our study a 100% HPV DNA prevalence was found in squamous cell cervical carcinomas. Neither the presence of HPV DNA nor the HPV genotype appeared to be related to either the presence of lymph node metastases at the time of initial treatment or to 5-year survival.
Adult↗
Discordant serum CA 125 values in commercial immunoassays.
The CA 125 assay is from a clinical point of view very well suited to monitor ovarian cancer patients. Although most commercial assay systems include as standards CA 125 preparations derived from the OVCA 433 cell line, the various assay configurations do not produce identical results. The so called cut-off value of 35 U/ml obtained in the original Centocor CA 125 assay appears to be equivalent to CA 125 values ranging as low as 18 U/ml and as high as 53 U/ml in other commercial CA 125 assays now available. Because of these dissimilar results, obtained with different immunoassays, switching from one assay to another during follow-up, should not be tolerated. The newly introduced second generation Centocor CA 125 II IRMA was shown to retain the cut-off values of 35 U/ml and 65 U/ml as defined with the original CA 125 IRMA.
Animals↗
CA 125 in gynecological pathology--a review.
The original CA 125 serum tumor marker test is a homologous double-determinant (OC 125 monoclonal antibody based) assay for the quantification of tumor associated mucin-like CA 125 molecules present in the serum. Commercial kits, now supplied by various manufacturers (and in different versions, e.g. IRMA, EIA, etc.) are currently widely applied in the following clinical situations: (i) Monitoring of disease. Doubling or halving of CA 125 serum values correlated (in 87% of all cases) with tumor progression or regression, respectively. (ii) Early prediction of outcome. Deviation from the ideal CA 125 regression curve predicts poor outcome within 3 months of cytostatic treatment. (iii) Tumor status after completion of therapy. Patients with CA 125 > 35 U/ml have (in 95% of all cases) still tumor present (at second look surgery). However, patients with CA 125 < 35 U/ml have in 50% (mostly minimal) residual disease. (iv) Early detection of recurrence. After a complete remission, a rise in CA 125 precedes tumor recurrence in 75% of all patients, with lead times up to more then 1 year, surpassing the CT-scan in cheapness and accuracy. (v) Diagnosis and differential diagnosis. Only when used in combination with other markers, do CA 125 determinations have a value as a diagnostic adjunct in the discrimination of ovarian cancer patients from those with benign ovarian tumors and from those with advanced colon cancer. Today, optimal management of ovarian cancer patients can only be provided using the CA 125 serum test.
Antigens, Tumor-Associated, Carbohydrate↗
Efficacy of a synthetic mesh sling in keeping the small bowel in the upper abdomen to prevent radiation enteropathy in gynecologic malignancies.
Radiation therapy in gynecological malignancies is limited by the frequent occurrence of radiation enteropathy at effective dose levels of 45 Gy and higher. Elevation of the small bowel out of the true pelvis should enable doses of up to 60-70 Gy to be given without damaging the small bowel. We report a feasibility study concerning elevation of the small bowel out of the true pelvis, by creating an intra-abdominal sling with a synthetic mesh. Twelve patients with pelvic gynecological malignancies were included since 1986. In all patients peroperative application of the mesh was possible. In ten patients adequate elevation of the small bowel was achieved. Two patients showed a right-sided herniation of a small bowel loop on a control barium opacification, performed 1 week postoperatively. In one of these a fistula occurred after resecuring the mesh. The most important problem in this study, as has also been reported elsewhere, was a herniation of a small bowel loop. The incidence is probably inversely correlated with the skill of the surgeon and will therefore be reduced with increasing experience. Future long-term studies should address the issue whether or not radiation enteropathy can be prevented by this method.
Abdomen↗
Identification of patients with persistent trophoblastic disease by means of a normal human chorionic gonadotropin regression curve.
OBJECTIVE: Data from the Dutch Central Registry of Hydatidiform Mole were used to establish a reference human chorionic gonadotropin regression curve after molar pregnancy. STUDY DESIGN: A normal serum human chorionic gonadotropin regression corridor was constructed after fitting data from 130 patients with uneventful human chorionic gonadotropin regression after evacuation of a complete hydatidiform mole. Retrospectively, data from 77 patients with persistent trophoblastic disease were analyzed by means of this normal corridor. Measurements were performed with a radioimmunoassay for both native and free human chorionic gonadotropin beta-subunits. RESULTS: Human chorionic gonadotropin disappearance curves showed a biphasic decline with median serum half-lives of 1.8 and 12.8 days. Median time until normalization was 74 days (range 28 to 430). With the 95th percentile line, 71 of 77 patients (92%) with persistent trophoblastic disease could be identified. In > 50% of cases this could be achieved within 6 weeks from evacuation. CONCLUSION: The normal regression corridor allows identification of patients with persistent trophoblastic disease and an expectant attitude within the limits of the corridor.
Chorionic Gonadotropin↗