Search PubMed⌕ Search

Biomedical subjects

R S Berkowitz

Publications and source records attributed to R S Berkowitz.

At least 109 records · Page 6Linked to original sources
PubMed1993

Sex chromosome composition of complete hydatidiform moles: relationship to metastasis.

OBJECTIVE: Complete hydatidiform moles have a substantial risk for subsequent development of persistent or metastatic gestational trophoblastic tumor. We evaluated the hypothesis that presence of a Y chromosome in a complete hydatidiform mole confers an increased risk for developing metastatic gestational trophoblastic tumor. STUDY DESIGN: The polymerase chain reaction was applied to archival paraffin-embedded molar-tissue to identify Y chromosome-positive dispermic moles in patients who did or did not develop metastatic disease. To reduce the chances of analytic error, consensus polymerase chain reaction primers directed at homologous but different genes present on both X and Y chromosomes were used. RESULTS: Y-chromosome sequences were identified in 7.7% (1/13) of the metastatic group and 9.1% (2/22) of the nonmetastatic group, a statistically insignificant difference. CONCLUSION: We are unable to confirm any increased risk for metastasis in Y chromosome-positive compared with Y chromosome-negative complete hydatidiform mole.

Base Sequence↗
PubMed1993

Cost-effectiveness of strategies to evaluate postmenopausal bleeding.

OBJECTIVE: To identify an optimal evaluation strategy for patients of various ages and risks for endometrial cancer and for complex hyperplasia who present with a first episode of postmenopausal bleeding. METHODS: We constructed a decision-analytic model to assess the life expectancy, effectiveness, cost, and cost-effectiveness of four options for the initial evaluation of postmenopausal bleeding: office endometrial biopsy, D&C, hysterectomy, and observation unless bleeding recurred. We considered patients at different ages and risks for cancer and for complex hyperplasia. RESULTS: Life expectancy was similar for all four strategies, but overall expected costs varied markedly. Compared with the other procedures, office biopsy was the most cost-effective initial strategy, costing less than $41,000 per year of life saved for patients at moderate combined risk (ie, 10%) of cancer or complex hyperplasia. However, for patients at low risk (ie, 5%), even office biopsy was relatively costly in certain age groups, with costs as high as $205,000 per additional year of life saved for 80-year-old patients. Both D&C and hysterectomy were more costly and no more effective than office biopsy as initial evaluation strategies in all patient groups over a wide range of changes in baseline assumptions. CONCLUSIONS: Office biopsy is always preferred over D&C or hysterectomy for the initial evaluation of patients with postmenopausal bleeding. However, one may consider delaying a biopsy unless and until bleeding recurs for patients who are at low risk (5% or less) for cancer and complex hyperplasia by clinical criteria.

Aged↗
PubMed1992

Molar villous fluid suppresses mononuclear cell cytotoxicity.

Complete molar pregnancy tissue is an allograft to the mother because all molar chromosomes are of paternal origin. Interactions between molar tissue and the maternal immune system may be important in the natural history of complete molar pregnancy. Molar villous fluid (MVF) has previously been demonstrated to suppress both mitogen and interleukin-2-induced T lymphocyte proliferation. The current study was undertaken to evaluate the potential effect of MVF on the cytotoxic activity of mononuclear cells (MNC) and lymphokine-activated mononuclear cells (LA-MNC). Sera and molar villous fluid were obtained from four women at the time of molar evacuation. K-562 erythroblastoid cells were used as target cells for MNC-mediated lysis, and JEG-3 choriocarcinoma cells were used as targets for LA-MNC-mediated lysis in a 51Cr release assay. Relative to patient sera, all MVF tested significantly inhibited both MNC and LA-MNC lysis of target cells (48.3 and 91% mean inhibition, respectively; P < 0.05). This study provides additional evidence that molar gestational tissue produces factor(s) that suppress maternal immunologic responses. Potential therapies may become available to reduce or eliminate the immunosuppressive effects of molar gestations resulting in a more favorable clinical outcome in patients with complete molar pregnancy and postmolar gestational trophoblastic tumors.

Choriocarcinoma↗
PubMed1992

The role of cytoreductive surgery in the management of stage IV epithelial ovarian carcinoma.

Patients with Stage IV epithelial ovarian carcinoma are generally treated in the same manner as are patients with disease confined to the abdomen--cytoreductive surgery followed by combination chemotherapy. Between 1980 and 1990, 35 women with histologically or cytologically documented Stage IV ovarian carcinoma were treated in this fashion. Sixteen women (45%) underwent optimal initial cytoreductive surgery, defined as less than 2 cm maximum residual disease. Eleven of the 19 women undergoing suboptimal initial procedures underwent interval cytoreduction after two to four cycles of chemotherapy, with 7 achieving an optimal status after the interval procedure. Overall, 23 of 35 patients (66%) were successfully cytoreduced to less than 2 cm either initially or at an interval procedure. Thirty-one of the 35 patients received combination regimens containing platinum as part of their initial therapy. Kaplan-Meier survival curves demonstrated no significant difference in survival between those groups of women cytoreduced intervally or initially, or between those groups of women optimally cytoreduced at some point during their initial therapy and those who were not. The 5-year survival for the entire group was less than 5%, with no significantly prolonged survival seen in those patients undergoing successful cytoreduction.

Chemotherapy, Adjuvant↗
PubMed1992

Preoperative serum CA-125 levels in borderline tumors of the ovary.

Preoperative serum CA-125 levels were evaluated in 38 patients who underwent primary surgery for epithelial ovarian tumors of borderline malignancy at the Brigham and Women's Hospital and Massachusetts General Hospital between 1981 and 1990. Surgical staging was Stage I in 25 (66%) patients, Stage II in 2 (5%) patients, Stage III in 10 (26%) patients, and Stage IV in 1 (3%) patient. The mean sizes of mucinous and serous ovarian tumors were 21.9 and 10.3 cm, respectively (P = 0.0002). All 13 patients (100%) with mucinous tumors had Stage I disease, while 12 (50%) of 24 patients with serous tumors were Stage I. Combining all cell types, 10 (40%) of 25 patients with Stage I disease had an elevated preoperative CA-125 level, while 2 (100%) of 2, 9 (90%) of 10, and 1 (100%) of 1 patient with Stage II, III, and IV disease, respectively, had increased preoperative levels. Among patients with serous tumors, 3 (25%) of 12 Stage I patients had an elevated preoperative CA-125 level, while 11 (92%) of 12 Stage II-IV tumors had elevated levels (P less than 0.001). These data suggest that preoperative CA-125 level correlates with stage of disease in patients with serous borderline ovarian tumors.

Adult↗
PubMed1992

Interferon-gamma receptors on human gestational choriocarcinoma cell lines: quantitative and functional studies.

OBJECTIVES: This study was performed to further define the effects of interferon-gamma on choriocarcinoma cell lines and to determine whether variations in response among cell lines are attributable to quantitative differences in interferon-gamma receptors. STUDY DESIGN: Interferon-gamma receptors were quantified on BeWo, JEG-3 and Jar choriocarcinoma cell lines by a radiolabeled interferon-gamma ligand binding assay. The response of these cell lines to interferon-gamma was measured in two functional assays: a cell proliferation assay and a cell lysis assay after exposure to interferon-gamma with and without actinomycin-D. RESULTS: The number of interferon-gamma receptors on BeWo, Jar, and JEG-3 cells did not differ significantly (650, 560, and 420 interferon-gamma receptors per cell, respectively). Proliferation of all three choriocarcinoma cell lines was significantly inhibited to a similar extent by interferon-gamma. After treatment with interferon-gamma actinomycin-D, each choriocarcinoma cell line exhibited dose-dependent cell lysis; lysis of Jar was significantly less than that of either BeWo or JEG-3. CONCLUSION: These data further document variations in the response of choriocarcinoma cell lines to interferon-gamma and indicate that these differences are not the result of interferon-gamma receptor number but of postreceptor mechanisms.

Binding Sites↗
PubMed1992

A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy.

Hydropic placentas may be classified by histopathology into hydropic abortus, partial hydatidiform mole, and complete hydatidiform mole. We studied 142 hydropic placentas: 39% were complete hydatidiform moles, 35% partial hydatidiform moles, and 26% hydropic abortuses. Villous vesicle size was predictive of histologic diagnosis. We determined DNA ploidy in 137 cases. Seventy-three percent of hydropic abortuses were diploid and 11% were triploid. Ninety percent of partial moles were triploid or near-triploid; one partial mole was haploid and one diploid. Of the complete moles, 50% were diploid, 43% were tetraploid, 3.6% polyploid, and 1.7% triploid. Partial moles had lower pre-evacuation beta-hCG levels than complete moles. Persistent tumor followed 33% of complete moles and 12% of partial moles. Although the numbers were small, no patient with a diploid, tetraploid, aneuploid, or haploid partial mole developed persistent disease. Among complete moles, the pre-evacuation beta-hCG level was not predictive of persistence (P = .15). Subdividing complete moles by ploidy, we found that tetraploid moles were associated with higher pre-evacuation beta-hCG levels than were diploid moles. However, tetraploidy was not associated with increased persistent tumor among complete moles. Although most partial moles were triploid and most complete moles were diploid or tetraploid, there was wider DNA heterogeneity among molar gestations than previously reported. In this series, DNA ploidy was not an independent predictor of persistence in complete moles.

Adolescent↗
PubMed1992

Gestational trophoblastic diseases: recent advances in the understanding of cytogenetics, histopathology, and natural history.

Our understanding of gestational trophoblastic diseases has progressed considerably in recent years in terms of our knowledge of their cytogenetic origin, histopathology, and natural history. Advances in molecular biology have been applied to the study of gestational trophoblastic diseases, providing new insights into their pathogenesis. Molecular biologic studies have now clearly demonstrated that complete molar pregnancies result from fertilization of an anuclear, "empty" ovum. Improved understanding of the cytogenetics and biology of gestational trophoblastic diseases may well contribute to further advances in patient care.

Cytogenetics↗
PubMed1991

Flow cytometric analysis of DNA content in partial hydatidiform moles with persistent gestational trophoblastic tumor.

Hydatidiform moles may be classified as partial or complete based on genetic and pathologic criteria. Between January 1979 and January 1990, 17 (5.5%) of 310 patients followed for partial mole developed persistent gestational trophoblastic tumor. Tissues from 14 partial moles were available for flow cytometric analysis of DNA content. Eleven partial moles (85%) were triploid, two (15%) were diploid, and one DNA histogram was uninterpretable. All patients with triploid partial moles achieved complete remission with one course of single-agent chemotherapy. The two with diploid partial mole required multiple courses of chemotherapy to achieve gonadotropin remission. Although the DNA content of most partial moles with persistent gestational trophoblastic tumor was triploid, diploid partial moles with persistent tumor were less sensitive to single-agent chemotherapy.

DNA, Neoplasm↗
PubMed1991

Pathologic features of sharp curettings in complete hydatidiform mole. Predictors of persistent gestational trophoblastic disease.

The medical records and pathologic specimens were reviewed from 33 patients with complete molar pregnancy at Brigham and Women's Hospital between 1980 and 1989. Two pathologists (D.R.G. and R.W.R.) reviewed all slides from the original sharp curettage to identify pathologic features that may be associated with persistent gestational trophoblastic tumor (GTT). The pathologic features evaluated were implantation site, presence of myometrium, presence of villi, presence and degree of atypia in cytotrophoblast, syncytiotrophoblast and intermediate trophoblast, presence of fibrinoid, presence of implantation site inflammatory cells, volume of tissue and area of trophoblastic tissue. Only one pathologic feature, fibrinoid deposits, identified in sharp curettings was associated with the development of persistent GTT. While 12 (48%) of 25 patients who attained remission without chemotherapy had fibrinoid deposits, only 1 (12.5%) of 8 patients who developed persistent GTT had them (P less than .10).

Adult↗
PubMed1991

Management of low-risk metastatic gestational trophoblastic tumors.

The clinical course of 48 patients with low-risk metastatic gestational trophoblastic tumors (GTTs) treated with primary single-agent chemotherapy was reviewed. All patients achieved sustained remission, although 25 (51%) required a second single-agent regimen, and 7 (14%) needed combination chemotherapy to achieve it. An average of 3.4 courses of chemotherapy were necessary to achieve remission, and 6 patients (12%) underwent resection of resistant tumor foci. Primary single-agent chemotherapy is a reasonable treatment option in patients with low-risk metastatic GTT.

Aspartate Aminotransferases↗
PubMed1991

Evolving concepts of molar pregnancy.

Molar pregnancy is composed of two distinct clinical and pathologic entities, complete and partial mole. Knowledge of the cytogenetic origin, natural history and treatment of complete and partial hydatidiform mole is evolving.

Chorionic Gonadotropin↗
PubMed1991

Gestational trophoblastic disease of the fallopian tube.

Tubal gestational trophoblastic disease (GTD) was diagnosed in 16 (0.8%) of 2,100 women with GTD managed at the New England Trophoblastic Disease Center. Tubal partial mole, complete mole and choriocarcinoma were present in 5, 5 and 6 patients, respectively. Patients with tubal GTD were not clinically distinguishable from those with traditional tubal pregnancies. While only one patient with tubal mole developed metastases, four patients with tubal choriocarcinoma presented with metastases. All the patients achieved complete, sustained remission.

Adolescent↗
PubMed1991

A clinicopathologic study of 153 cases of complete hydatidiform mole (1980-1990): histologic grade lacks prognostic significance.

Although the significance of histologic grading in hydatidiform mole has previously been investigated, most studies evaluated patients treated before 1975. Since 1975, many advances have been made in the understanding and treatment of hydatidiform mole, including the division of molar pregnancy into complete and partial hydatidiform mole. We retrospectively studied 153 cases of complete hydatidiform mole diagnosed and treated at the Brigham and Women's Hospital between 1980-1990 to determine the current prognostic significance of histologic grading in this disease. The histologic grade (based on the criteria of Hertig and Sheldon) was compared with the subsequent clinical course, including the rates of spontaneous remission, persistent gestational trophoblastic tumor, metastatic disease, "high-risk" metastatic disease, chemotherapy resistance, and survival. The histologic grade of the original complete hydatidiform mole did not correlate significantly with any index of clinical outcome evaluated.

Adult↗
PubMed1991

Duplex ultrasonography for persistent gestational trophoblastic tumor.

Duplex ultrasonography was performed on 17 consecutive patients being evaluated for persistent gestational trophoblastic tumor (GTT). All patients had had a prior molar pregnancy evacuated and presented with a rise or plateau in their beta-human chorionic gonadotropin levels. The ultrasonography was considered to be abnormal if the image demonstrated a focal area of altered echogenicity within the uterus or if Doppler scanning revealed a focal area of detectable intrauterine blood flow. The ultrasound findings were compared with the pathologic results from dilation and curettage specimens. Ten of the 17 patients had pathologically proven macroscopic tumor. Of those 10, 7 had an abnormal sonographic image (sensitivity, 70%), and 9 had an abnormal Doppler examination (sensitivity, 90%). In all 10 patients the image and/or Doppler examination was abnormal. Among four patients with microscopic disease, imaging was positive in one case, and the Doppler examination was positive in three. Imaging and Doppler ultrasonography are complementary modalities that can reliably detect persistent uterine GTT, and Doppler ultrasonography appears to be more sensitive than imaging in making this diagnosis.

Dilatation and Curettage↗
PubMed1990

Hepatic scintigraphic changes associated with gestational trophoblastic disease.

We reviewed the results of radionuclide liver imaging in 70 patients newly referred for evaluation and treatment of persistent gestational trophoblastic tumors. Some 58 patients (83%) had abnormal liver scans but no focal defects and no discernible hepatic malignancy. These diffusely abnormal scans may reflect chemotherapeutic and/or hormonal effects on the liver and should not be interpreted as indicative of metastases.

Female↗
PubMed1990

Methotrexate infusion and folinic acid in the primary therapy of nonmetastatic gestational trophoblastic tumors.

Thirty-two patients with nonmetastatic gestational trophoblastic tumors were treated with methotrexate infusion and folinic acid and the results of this therapy were compared to our prior experience with the 8-day methotrexate-folinic acid regimen. Complete remission was achieved in 22 of 32 (68.7%) patients treated with methotrexate infusion and 147 of 163 (90.2%) patients treated with the 8-day regimen (P less than 0.01). One course of chemotherapy induced complete remission in 19 (86.3%) patients treated with methotrexate infusion and 121 (82.2%) patients treated with the 8-day regimen. All 10 patients resistant to methotrexate infusion later achieved remission with other chemotherapy. Following methotrexate infusion, no patient developed myelosuppression, hepatotoxicity, or alopecia. Efforts should continue to identify new chemotherapeutic protocols that maximize remission rates and minimize toxicity and hospitalization.

Antineoplastic Combined Chemotherapy Protocols↗