Gestational trophoblastic disease: does central nervous system chemoprophylaxis have a role?
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In the UK there are standardized surveillance procedures for gestational trophoblastic disease. However, there are differences in practice between the two treatment centres in terms of definition of persistent gestational trophoblastic disease, prognostic risk assessment and chemotherapeutic regimens. The role of prophylactic chemotherapy for cerebral micrometastatic disease in persistent gestational trophoblastic disease is unclear. We have analysed the outcome of 69 patients with lung metastases who elsewhere might have received prophylactic intrathecal chemotherapy. Of the 69 patients, 67 received intravenous chemotherapy only. The other two patients had cerebral metastases at presentation. One patient who received only intravenous chemotherapy subsequently developed a cerebral metastasis, but this patient's initial treatment was compromised by non-compliance. This experience supports our current policy of not treating patients with pulmonary metastases, without clinical evidence of central nervous system (CNS) involvement, with prophylactic intrathecal therapy. (+info)
Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG.
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Human chorionic gonadotropin (hCG) exhibits molecular heterogeneity in both its protein and carbohydrate moieties. This communication describes changes in hCG isoforms detected directly in clinical samples. These isoforms, quantified in blood or urine specimens, show a progression of change throughout normal pregnancy. Early pregnancy produces a type of hCG that resembles, in terms of immunoreactivity, a major form of hCG excreted in choriocarcinoma. The isoforms predominate for the first 5-6 weeks of gestation and then diminish, being replaced with the hCG isoforms which predominate throughout the remainder of pregnancy. The alteration in hCG isoform content occurs in both blood and urine. The progression of isoforms is best delineated by calculating the change in the ratio of the two forms, as many hCG assays either do not detect or fail to discriminate among these isoforms. An analogous pattern of hCG isoforms was observed in patients with in vitro fertilization pregnancies. hCG isolated from the pituitary displayed binding characteristics similar to those of the hCG derived from normal pregnancy urine. The early pregnancy hCG isoforms appear to have a differential expression in normal pregnancy as opposed to pregnancies which will not carry to term, suggesting that a determination of the relative balance of hCG isoforms may have diagnostic application in predicting pregnancy outcome. (+info)
Oral contraceptive use and risk of gestational trophoblastic tumors.
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BACKGROUND: Gestational trophoblastic disease refers to a spectrum of rare benign and malignant gynecologic disorders whose pathogenesis is not well understood. Recent studies from China and the United States have raised the hypothesis that long-term use of oral contraceptives before conception may increase the risk of gestational trophoblastic tumors. A multicenter case-control study of gestational trophoblastic tumors was undertaken to test this hypothesis. METHODS: Telephone interviews were conducted with 235 case patients, including 50 with gestational choriocarcinoma, and 413 control subjects matched on recentness of pregnancy, age at pregnancy, and area of residence. Relative risks (odds ratios) were computed by conditional logistic regression. Reported P values are two-sided. RESULTS: The relative risk estimate for ever having used oral contraceptives before the index pregnancy was 1.9 (95% confidence interval [CI] = 1.2-3.0), and the risk increased with duration of use (P for trend = .05). The estimate was highest for women who used oral contraceptives during the cycle in which they became pregnant (relative risk = 4.0; 95% CI=1.6-10), but there was no consistent pattern according to the time interval since last use. Separate analyses of choriocarcinoma and persistent mole yielded similar results, i.e., the relative risk estimates for oral contraceptive use were 2.2 (95% CI=0.8-6.4) and 1.8 (95% CI=1.0-3.0), respectively. Control for the number of sexual partners, which was independently associated with risk (P for trend = .05), did not materially change the results. CONCLUSIONS: This study, the largest to date, indicates that long duration of oral contraceptive use before conception increases the risk of gestational trophoblastic tumors. These findings may provide clues to the pathogenesis of this rare disease. Changes in use of oral contraceptives are not warranted, however, because the incidence attributable to oral contraceptive use is very low. (+info)
Structure, pathology and function of the N-linked sugar chains of human chorionic gonadotropin.
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Human chorionic gonadotropin (hCG) contains five acidic N-linked sugar chains, which are derived from three neutral oligosaccharides by sialylation. Each of the two subunits (hCGalpha and hCGbeta) of hCG contain two glycosylated Asn residues. Glycopeptides, each containing a single glycosylated Asn, were obtained by digestion of hCGalpha with trypsin, and of hCGbeta with chymotrypsin and lysyl endopeptidase. Comparative study of the sugar chains of the four glycopeptides revealed the occurrence of site-directed glycosylation. Studies of the sugar chains of hCGs, purified from urine of patients with various trophoblastic diseases, revealed that choriocarcinoma hCGs contain sialylated or non-sialylated forms of eight neutral oligosaccharides. In contrast, hCGs from invasive mole patients contain sialyl derivatives of five neutral oligosaccharides. The structural characteristics of the five neutral oligosaccharides, detected in choriocarcinoma hCGs but not in normal placental hCGs, indicate that N-acetylglucosaminyltransferase IV (GnT-IV) is abnormally expressed in the malignant cells. This supposition was confirmed by molecular biological study of GnT-IV in placenta and choriocarcinoma cell lines. The appearance of tumor-specific sugar chains in hCG has been used to develop a diagnostic method of searching for malignant trophoblastic diseases. In addition, a summary of the current knowledge concerning the functional role of N-linked sugar chains in the expression of the hormonal activity of hCG has been presented. (+info)
Serosal complications of single-agent low-dose methotrexate used in gestational trophoblastic diseases: first reported case of methotrexate-induced peritonitis.
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Methotrexate (MTX) is a folate antagonist widely used both as an anticancer drug and as an immunosupressant. Administration of an 8-day methotrexate and folinic acid regime may be associated with pleuritic chest pain and pneumonitis. We have reviewed the toxicity seen in 168 consecutive patients treated with low-dose MTX for persistent trophoblastic disease. Twenty-five per cent of patients developed serosal symptoms, pleurisy was the commonest complaint. The majority of patients had mild to moderate symptoms which were controlled with simple analgesia and did not necessitate a change in treatment; 11.9% had severe symptoms which necessitated a change in treatment. One patient developed a pericardial effusion and a second patient developed severe reversible peritoneal irritation. The possible aetiology and pathophysiology of methotrexate-induced serosal toxicity is discussed. (+info)
Etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EMA) chemotherapy for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine chemotherapy and patients presenting with metastatic placental site trophoblastic tumors.
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PURPOSE: To evaluate the results of etoposide, cisplatin/etoposide, methotrexate, and actinomycin D (EP/EMA) chemotherapy in patients with gestational trophoblastic tumors (GTTs), who have relapsed after or who have become refractory to EMA/cyclophosphamide and vincristine (CO) chemotherapy, and in patients presenting with metastatic placental site trophoblastic tumors (PSTTs). PATIENTS AND METHODS: We have treated a total of 34 patients with GTT and eight patients with metastatic PSTT with the EP/EMA chemotherapy schedule. RESULTS: Twenty-two patients received EP/EMA because of apparent drug resistance to EMA/CO, and because the human chorionic gonadotropin (hCG) was near normal, they were not assessable for response. Twenty-one of these patients (95%) are alive and in remission. In the group where the hCG was high enough to confirm a response (greater than one log fall in hCG) to EP/EMA, all 12 patients responded and nine of these patients (75%) are alive and in remission. We have treated three patients with PSTT where the interval from antecedent pregnancy was less than 2 years, and all patients (100%) are alive and in remission. We have treated five patients where the interval from antecedent pregnancy was greater than 2 years and one fifth (20%) remain in remission. The survival for patients with GTT is 30 (88%) out of 34 patients and four (50%) out of eight patients for PSTT, giving an overall survival for these two cohorts of 34 (81%) out of 42 patients. The toxicity of this schedule is significant, with grade 3 or 4 toxicity (National Cancer Institute common toxicity criteria) recorded in hemoglobin (21%), WBC (68%), and platelets (40%). The role of surgery in this group of patients is important and contributed to sustained remission in five patients (23%) and possibly helped an additional seven patients (32%). CONCLUSION: EP/EMA is an effective but moderately toxic regimen for patients with high-risk GTT who become refractory to or relapse from EMA/CO chemotherapy. Also, EP/EMA clearly has activity in patients with metastatic PSTT. (+info)
Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy.
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Of 4257 patients with gestational trophoblastic disease (GTD) registered between 1986 and 1996 with the Trophoblastic Screening and Treatment Centre, Sheffield, 231 women required chemotherapy; 28 were treated 24 weeks or more after the initial evacuation of products of conception. In 18 patients late treatment was a result of a predetermined watch and wait policy on the part of the Centre; these patients formed the study group. Patients were identified from the Centre's computer database. The time interval from first evacuation (diagnosis) to start of chemotherapy was calculated for each patient. Hospital records were reviewed when the interval of observation was 24 weeks or greater to determine patient characteristics, treatment and outcome. Eighteen women were treated 'late' (according to Centre policy), with a median age of 30 years (range 21-57 years). The interval from diagnosis to treatment ranged from 24 to, in one case, 56 weeks (median 33 weeks). Fourteen of 18 women had complete moles, 3/18 had partial moles and one had unclassified disease. All women had low-risk disease and were treated with single-agent methotrexate; 17 were cured with this regimen, one also required salvage chemotherapy. In conclusion, where a successful surveillance programme is in operation for GTD, a wait and watch policy can be adopted without compromising patients whose definitive treatment is commenced more than 6 months after the initial diagnosis. (+info)
Persistent gestational trophoblastic disease: results of MEA (methotrexate, etoposide and dactinomycin) as first-line chemotherapy in high risk disease and EA (etoposide and dactinomycin) as second-line therapy for low risk disease.
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Persistent gestational trophoblastic disease is potentially fatal, but the majority of patients are cured with chemotherapy. Any developments in treatment are therefore being directed towards maintaining efficacy and reducing toxicity. We evaluated efficacy and toxicity of methotrexate, etoposide and dactinomycin (MEA) as first-line therapy for high risk disease and etoposide and dactinomycin (EA) as second-line therapy for methotrexate-refractory low risk disease in a retrospective analysis of 73 patients (38 MEA, 35 EA) treated since 1986 at a supra-regional centre. The median follow-up period was 5.5 years and the median number of cycles received was 7. The overall complete response rate was 85% (97% for EA, 75% for MEA). Of eight patients who failed to respond, four have since died and four were cured with platinum-based chemotherapy. Alopecia was universal. Grade II or worse nausea, emesis, or stomatitis was observed in 29%, 30% and 37% respectively. Fifty-one per cent experienced grade II/III anaemia, 8% grade II or higher thrombocytopenia and 64% grade III or IV neutropenia; in six cases this was complicated by sepsis. Fifty-four per cent of patients went on to have a normal pregnancy. No patient has developed a second malignancy. In conclusion, the MEA and EA chemotherapy regimens for persistent trophoblastic disease are very well tolerated, do not appear to affect future fertility and are associated with excellent, sustained complete response rates. (+info)