Reproductive performance after molar pregnancy and gestational trophoblastic tumors.
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Biomedical subjects
Publications and source records attributed to R S Berkowitz.
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A new anatomic staging system has been developed for gestational trophoblastic tumors. The use of this system, it is hoped, will permit the development of prospective, multiinstitutional treatment trials to assess current and new forms of therapy and to suggest new areas for clinical and basic research.
Because all the chromosomes in complete molar pregnancy are of paternal origin, complete moles are complete allografts (transplants). Complete moles may therefore be expected to induce a vigorous maternal host immunologic response. Further understanding of the relationships between the normal placenta, mole and choriocarcinoma may provide important insights into the basic mechanisms of teratogenesis and carcinogenesis.
The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas. An assay has been developed to detect CA 125 in serum. By this assay, only 1 per cent of 888 apparently healthy persons and 6 per cent of 143 patients with nonmalignant disease had serum CA 125 levels above 35 U per milliliter. In contrast, 83 of 101 patients (82 per cent) with surgically demonstrated ovarian carcinoma had elevated levels of antigen. In 38 patients with epithelial ovarian carcinoma monitored on 2 to 18 occasions during 2 to 60 months, antigen levels ranged from less than 1 to more than 8000 U per milliliter. Rising or falling levels of CA 125 correlated with progression or regression of disease in 42 of 45 instances (93 per cent). Determination of CA 125 levels may aid in monitoring the response to treatment in patients with epithelial ovarian cancer.
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Pelvic ultrasonography was performed in 33 patients with persistent gestational trophoblastic disease (GTD) and the sonographic findings were compared in all patients with laparoscopic findings and histologic material from endometrial curettage and/or hysterectomy. Ultrasonography indicated trophoblastic uterine involvement in 17 patients (51.5%) and the ultrasound interpretation was histologically confirmed in all 17 patients by endometrial curettage and/or hysterectomy. Among the 16 patients in whom the uterus appeared normal by ultrasound, endometrial curettings demonstrated scanty fragments of trophoblastic tumor in 6 patients (37.5%). Furthermore, in all 16 patients in whom the uterus appeared normal by ultrasound, laparoscopy also revealed no uterine abnormalities. Ultrasonography appears to be accurate in detecting extensive trophoblastic uterine involvement and helpful in identifying resistant uterine foci. Pelvic ultrasonography should be an integral part of the pretreatment assessment of patients with persistent GTD.
Circulating immune complex levels were measured in patients with molar pregnancy to investigate the relationship between circulating immune complex and trophoblastic tumor burden. When 27 (87%) of 31 patients with molar pregnancy were first seen, circulating immune complex values were in the normal range. Three of the 4 patients with elevated levels had concurrent medical illness. Eighteen patients were followed with serial measurements until gonadotropin remission was achieved and all 18 patients developed increased levels as they entered remission (P less than .001). Circulating immune complex values remained elevated during gonadotropin remission from 6 to 16 weeks and then declined to initial levels. Further investigation should be undertaken to evaluate possible interactions between circulating immune complex and host immune defenses.
Corynebacterium parvum has been administered i.p. to 14 patients with advanced ovarian cancer. Two patients had responded completely to cytoreductive surgery and combination chemotherapy prior to immunotherapy, and one patient with residual disease had received only a single course of C. parvum due to i.p. catheter malfunction. Among the 11 patients with residual disease evaluable for response, from three to eight i.p. treatments with C. parvum produced surgically confirmed tumor regression in five patients (45%) with three partial responses and two complete responses of 5 and 12 months duration. All responders had (a) multiple tumor nodules less than 0.5 cm at the initiation of immunotherapy, and (b) severe abdominal pain and fever after C. parvum injection. Overall, 58 courses of immunotherapy were associated with abdominal pain (91%), fever (67%), nausea (52%), vomiting (31%), and hypotension that responded promptly to i.v. infusion of fluids (10%). Use of i.p. cathethers was associated with two episodes each of infection and intraabdominal bleeding. Administration of C. parvum i.p. has augmented the ability of human peritoneal cells to lyse human ovarian carcinoma cell lines in the presence of specific rabbit heteroantiserum. C. parvum administered i.p. has inhibited the growth of human ovarian carcinoma and may prove useful for modulating the activity of human effectors for antibody-dependent cell-mediated cytotoxicity.
The implantation sites of 11 molar pregnancies were examined for the deposition of immunoglobulin and complemented by direct immunofluorescence. None of the 10 women experiencing their first molar pregnancy had immunoglobulin or complement deposition in the implantation site. The one patient with immunoglobulin and complement deposition in the implantation site was aslo the only patient experiencing a second molar pregnancy. Immunofluorescent staining for IgG, IgM, and C3 was confirmed to the decidual arteries in this patient and was unassociated with endovascular trophoblastic deposits. While only one of the 10 women with their first molar pregnancy had focal vasculitis at the implantation site, the patient with her second consecutive mole had diffuse vasculitis. Because molar implantation sites are generally free of immunoglobulin and complement deposition, molar pregnancies do not appear to induce a vigorous host humoral immune response at the time of presentation at the molar implantation site.
Methotrexate with citrovorum rescue (MTX-CF) was administered as primary treatment in 106 patients with gestational trophoblastic disease (GTD). Ninety-six patients (90.6%) achieved complete remission with MTX-CF and 77 of these patients (80.2%) required only one course of MTX-CF to attain remission. MTX-CF induced sustained remission in 89 (94.7%) of 94 patients with nonmetastatic GTD and in seven (59.3%) of 12 patients with low-risk metastatic GTD. Resistance to MTX-CF was more common in patients with disseminated disease and with pretreatment hCG titers greater than or equal to 50,000 milliIU/ml. Following MTX-CF, granulocytopenia, thrombocytopenia and hepatotoxicity was observed in only seven (6.6%), three (2.8%), and ten (9.4%) patients, respectively. MTX-CF should be the preferred primary treatment in nonmetastatic and low-risk metastatic GTD.
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One hundred patients, managed for molar pregnancy at the New England Trophoblastic Disease Center, were selected at random to determine if the contraceptive method following molar evacuation influenced the incidence of postmolar trophoblastic disease. Following molar evacuation, 58 (58%) patients used oral contraceptives and 42 (42%) patients used barrier methods (foam, condom, and/or diaphragm). Postmolar trophoblastic disease developed in 11 (18.9%) patients using oral contraceptives and in 6 (14.3%) patients using barrier methods (P greater than .10). The mean human chorionic gonadotropin (hCG) regression time after molar evacuation was 7.0 weeks in patients using oral contraceptives and 7.2 weeks in patients using barrier methods. The 2 groups of patients were comparable in age, gravidity, molar histology, pretreatment hCG titers, and exposure to prophylactic chemotherapy. Oral contraceptives do not appear to increase the risk of postmolar trophoblastic tumors and therefore may be safely prescribed after molar evacuation during the entire interval of gonadotropin monitoring.
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