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Biomedical subjects

R S Berkowitz

Publications and source records attributed to R S Berkowitz.

At least 127 records · Page 7Linked to original sources

Persistent gestational trophoblastic tumor after partial hydatidiform mole.

The current study investigates the clinical characteristics of patients with partial molar pregnancy who developed persistent gestational trophoblastic tumor (GTT). Between January 1979 and January 1989, 16 of 240 (6.6%) patients, who were followed for partial mole, developed persistent GTT. Fifteen (94%) patients were diagnosed as having a missed abortion before evacuation and only 1 patient presented with excessive uterine size and theca lutein ovarian cysts and was felt to have molar disease. No patient presented with toxemia, hyperemesis, or hyperthyroidism. All 16 patients developed nonmetastatic GTT. Fifteen patients achieved complete remission with methotrexate-citrovorum factor and only 1 patient required combination chemotherapy to attain remission. None of the patients had histologic evidence of choriocarcinoma. Patients with partial mole who developed persistent GTT did not have clinical or pathological characteristics that distinguished them from other patients with partial mole. All patients with partial mole should be followed with measurement of hCG levels to assure gonadotropin remission.

Adult↗

Localization of leukocytes and cytokines in chorionic villi of normal placentas and complete hydatidiform moles.

Monoclonal antibodies were used to localize and characterize leukocytes and cytokines in chorionic villi of normal placenta and complete mole. OKT4a reacted with Hofbauer cells in first-, second-, and third-trimester placentas. HLA-DR was expressed on second- and third-trimester placental Hofbauer cells but was not detected in the first trimester. The cytokines, gamma-interferon, granulocyte-macrophage colony-stimulating factor, interleukin-1 alpha, and tumor necrosis factor alpha, were all detectable on Hofbauer cells in first-, second-, and third-trimester placentas. None of the tested cytokine antibodies reacted with cellular constituents in complete molar chorionic villi. The absence of cytokine-positive cells in molar chorionic villi may be related to the hyperplastic and unregulated growth of molar villous trophoblast.

Antibodies, Monoclonal↗

Epithelial ovarian tumors of borderline malignancy.

Between January 1975 and January 1987, 80 patients underwent primary surgery at Brigham and Women's Hospital for epithelial ovarian tumors of borderline malignancy. Surgical staging revealed 52 (65%) patients with stage IA, 2 (2.5%) with stage IB, 10 (12.5%) with stage IC, 4 (5%) with stage II, 11 (13.8%) with stage III, and 1 (1.2%) with stage IV. All 37 patients with mucinous tumors had stage I disease, whereas 13 (33%) of 39 patients with serous tumors had stage II-IV disease. The mean sizes of mucinous and serous ovarian tumors were 18.7 and 10 cm, respectively. At initial surgery, 48 (60%) patients had a total abdominal hysterectomy with bilateral salpingo-oophorectomy and 16 (20%) had an oophorectomy. Sixteen (20%) patients underwent cystectomy, 6 (37.5%) of whom subsequently had an oophorectomy. All 10 patients treated by cystectomy alone have remained disease free. CA-125 levels were normal in 5 patients with stage I disease, but were elevated in 6 of 8 patients with more advanced tumors. Current disease status was determined in 72 patients (90%); 69 (95.8%) are alive and disease free, 1 (1.4%) patient is alive with tumor, and 2 (2.8%) patients died, free of disease.

Adult↗

Vinblastine, cisplatin and bleomycin as salvage therapy for refractory high-risk metastatic gestational trophoblastic disease.

Vinblastine, cisplatin and bleomycin (VPB) were utilized as salvage therapy in seven women with high-risk metastatic gestational trophoblastic tumors resistant to prior treatment with triple therapy (methotrexate, actinomycin D and cyclophosphamide) or the modified Bagshawe protocol. While four patients (57%) achieved sustained remission with VPB, surgery was performed on two of them to remove sites of resistant disease. The mean prognostic score for the patients who achieved remission was 10 versus 17 for those who died (P less than .05). Although severe hematologic toxicity occurred in five patients (71%), no deaths were attributable to toxicity. Since VPB has limited activity when used as salvage therapy, alternate chemotherapy protocols need to be developed for patients with refractory gestational trophoblastic disease.

Antineoplastic Combined Chemotherapy Protocols↗

Sonographic diagnosis of partial hydatidiform mole.

We undertook a study to determine whether partial hydatidiform mole could be distinguished from other cases of first-trimester missed abortion using ultrasound. Scans from 22 cases of pathologically proved partial hydatidiform mole and 33 cases of first-trimester missed abortion were independently reviewed by three radiologists, each unaware of the final pathologic diagnosis. Using a standard data form, each radiologist recorded the dimensions, shape, and contents of the gestational sac, the sonographic appearance of the decidual reaction/placenta and myometrium, and the presence or absence of adnexal cysts. The following two criteria were found to be significantly associated (P less than .05) with the diagnosis of partial mole: 1) ratio of transverse to anteroposterior dimension of the gestational sac greater than 1.5, and 2) cystic changes, irregularity, or increased echogenicity in the decidual reaction/placenta or myometrium. There was high interobserver correlation for both criteria, as measured by the kappa statistic. In 50% of the cases, either both or neither of these criteria were met. When both criteria were met, the frequency of partial mole was 87%; when neither criterion was met, the frequency of missed abortion was 90%. These results indicate that ultrasound can be of value in predicting a high likelihood of partial mole prior to curettage.

Abortion, Missed↗

Repetitive complete and partial hydatidiform mole.

Fifteen patients with repetitive hydatidiform mole were followed at the New England Trophoblastic Disease Center between 1965-1988. The medical records were examined to determine the patients' age, gravidity, parity, clinical presentation, development of post-molar tumor, and subsequent pregnancy experience. Each molar tissue was reviewed pathologically. Seven patients had repetitive complete hydatidiform mole and three developed persistent post-molar disease after their later mole. Five patients had an initial complete hydatidiform mole followed by a partial hydatidiform mole; two developed persistent post-molar disease after the partial mole. One patient had an initial partial hydatidiform mole followed by a complete hydatidiform mole and required chemotherapy after her complete mole. Two patients had repetitive partial hydatidiform mole, and neither developed post-molar disease. Four of the patients with repetitive mole later achieved a normal viable pregnancy. Molar pregnancies must be categorized as either complete or partial to provide meaningful data concerning repetitive hydatidiform mole.

Adolescent↗

Effects of products of activated leukocytes (lymphokines and monokines) on the growth of malignant trophoblast cells in vitro.

Supernatants from activated leukocyte cultures and individual lymphokines and monokines were added to cultures of JEG-3 human gestational choriocarcinoma cells in vitro, and effects on cell proliferation were measured. Activated leukocyte culture supernatants, recombinant gamma-interferon, tumor necrosis factor, and colony-stimulating factor significantly inhibited JEG-3 proliferation. In contrast, high doses of both interleukin 1 and 2 stimulated JEG-3 proliferation. Low doses of B cell growth factor stimulated JEG-3 proliferation, whereas the highest dose was inhibitory. Further understanding of the effects of lymphokines and monokines on trophoblastic growth may provide important insights into immunologic mechanisms affecting early pregnancy development and tumor-host interactions in gestational trophoblastic neoplasia.

Biological Products↗

Cross-reactivity of monoclonal antibodies directed against lymphocyte markers with trophoblast cells of normal placenta, hydatidiform mole, and gestational choriocarcinoma.

The current study was undertaken to characterize the expression of trophoblast-lymphocyte cross-reactive antigens on normal, molar, and malignant trophoblast. A panel of monoclonal antibodies directed against lymphoid cell markers were tested in immunofluorescence assay on cryostat sections of placenta and mole and on monolayers of choriocarcinoma cells. NKH-1, a monoclonal antibody to natural killer cells, reacted with both molar and placental villous trophoblast and with two choriocarcinoma cell lines. NKH-2, a monoclonal antibody reactive with a subset of natural killer cells, did not react with placental villous trophoblast but reacted with molar villous trophoblast in three of five moles tested and with both choriocarcinoma cell lines. B5, a monoclonal antibody which reacts with activated B cells, reacted with both choriocarcinoma cell lines but did not react with normal placental or molar trophoblast. MY7, a monoclonal antibody to myeloid colony-forming cells, reacted with only one of the choriocarcinoma cell lines. Trophoblast-lymphocyte cross-reactive antigens may be important in the immunobiology of gestational trophoblastic disease by modulating interactions between the trophoblast and the maternal immune system.

Antibodies, Monoclonal↗

Analysis of treatment failure in high-risk metastatic gestational trophoblastic disease.

The course of 51 patients with high-risk metastatic gestational trophoblastic tumor was reviewed. The clinical characteristics and therapy of patients who died were compared to patients who attained remission to identify parameters that are associated with treatment failure. The presence of liver, brain, or intestinal metastases and the failure of prior chemotherapy were found to portend a poor prognosis (P less than 0.001, P less than 0.05). Other high-risk factors such as markedly elevated HCG levels, time interval greater than 4 months from the antecedent pregnancy to treatment, and post-term choriocarcinoma were not independently associated with treatment failure. The mean prognostic score and the mean number of high-risk factors for patients who died were 13 and 3, as compared to 7 and 2, respectively, for patients who achieved remission (P less than 0.001, P less than 0.001). Alternative intensive chemotherapy regimens need to be developed to improve remission rates in patients with liver, brain, or intestinal metastases, failed prior chemotherapy, or a high prognostic score.

Antineoplastic Agents↗

Clinical experience with placental site trophoblastic tumors at the New England Trophoblastic Disease Center.

From 1982-1986, seven patients with pathologically confirmed placental site trophoblastic tumors underwent treatment at the New England Trophoblastic Disease Center. All seven patients presented with nonmetastatic disease; the presenting symptom was vaginal bleeding in six patients and amenorrhea in one patient. Mitotic counts of the tumor may vary among endometrial curettings, hysterectomy specimens, and metastatic lesions. When placental site trophoblastic tumor is diagnosed on endometrial curettage, a thorough metastatic workup should be undertaken. Because of this tumor's poor response to chemotherapy, a diagnosis of nonmetastatic placental site trophoblastic tumor should be followed by prompt hysterectomy.

Adult↗

Diagnosis and management of the primary hydatidiform mole.

Hydatidiform mole may be categorized as either complete or partial on the basis of gross morphology, histology, and karyotype. The diagnosis, natural history, and management of patients with complete and partial moles are reviewed in detail. The controversy concerning chemoprophylaxis at the time of molar evacuation is also discussed. Furthermore, subsequent reproductive outcome in patients with both complete and partial moles is analyzed.

Combined Modality Therapy↗

Persistence of partial mole.

Between January 1979 and August 1984, 8 of 81 patients with partial molar pregnancy who were followed at the New England Trophoblastic Disease Center had persistent trophoblastic tumor develop. No significant clinical differences were noted between such patients and others whose partial moles did not persist. On microscopic examination, none of the initial molar specimens manifested an unusual degree of trophoblastic proliferation or atypia. In six patients, curettage immediately preceding the initiation of treatment for persistent disease revealed viable molar tissue. In four, this was associated with trophoblastic hyperplasia and atypia. All patients who had persistent gestational trophoblastic tumor achieved remission with single-agent chemotherapy. Monitoring of serum human chorionic gonadotropin levels after partial molar pregnancy is recommended to detect persistent disease and effect prompt therapy.

Adult↗

Metastatic gestational trophoblastic disease: experience at the New England Trophoblastic Disease Center, 1965 to 1985.

This report reviews the results of therapy in 93 patients with metastatic gestational trophoblastic tumor treated from 1965-1985. Complete remission was achieved in all 42 patients with low-risk metastatic disease and in 34 of 51 patients (67%) with high-risk metastatic disease. Single-agent chemotherapy induced complete remission in 38 of 42 patients (91%) with low-risk metastatic disease. Survival of high-risk patients has improved markedly over the past two decades; complete remission was attained in 13 of 24 high-risk patients (54%) from 1965-1975, and in 21 of 27 (78%) from 1976-1985. Survival correlated with the number of high-risk factors, the prognostic score, and the type of treatment. From 1965-1975, 54% (13 of 24) of high-risk patients were treated with single-agent chemotherapy alone, while in the last decade only 7% (two of 27) were so treated. Twenty-one patients with traditional high-risk factors had a prognostic score of 7 or less, and all achieved remission, with 67% (14 of 21) treated with primary single-agent chemotherapy. The prognostic scoring system was more effective than traditional high-risk criteria at predicting which patients require intensive combination chemotherapy to attain remission.

Antineoplastic Combined Chemotherapy Protocols↗

Management of complete molar pregnancy.

This review of the current management of complete molar pregnancy is based upon the clinical experience at the New England Trophoblastic Disease Center. Suction curettage is the preferred method of molar evacuation regardless of uterine size in patients who desire to preserve fertility. Prophylactic chemotherapy may be useful in the management of high-risk molar pregnancy, especially when hormonal follow-up is either unavailable or unreliable. All patients must be followed with serial human chorionic gonadotropin levels to ensure that remission has occurred.

Diagnosis, Differential↗