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Biomedical subjects

J T Soper

Publications and source records attributed to J T Soper.

At least 109 records · Page 6Linked to original sources

Metastatic gestational trophoblastic disease: prognostic factors in previously untreated patients.

From 1966-1982, 138 previously untreated patients with metastatic malignant gestational trophoblastic disease received primary chemotherapy at the Southeastern Regional Trophoblastic Disease Center. Fifty-six (41%) had poor-prognosis metastatic gestational trophoblastic disease, and 51 (91%) of these patients were initially treated with multiagent chemotherapy. Sustained remissions were achieved in 128 patients (93%). Patients who had metastatic involvement of more than one anatomic site, disease duration of greater than four months, antecedent nonmolar pregnancy, or clinicopathologic diagnosis of choriocarcinoma were at significantly increased risk for failure to achieve sustained remission compared with patients who lacked these clinical features. Initial human chorionic gonadotropin level and site of metastasis had no significant effect on survival in these previously untreated patients. Patients with disease duration of greater than four months who had an antecedent nonmolar pregnancy were at significantly increased risk, with only 12 of 20 (60%) surviving, versus all of 85 patients with short duration of disease and antecedent molar pregnancy, and 32 (94%) of 34 patients with other combinations of these factors (P less than .001). Initial therapy for patients with metastatic gestational trophoblastic disease should be selected on the basis of prognostic factors that predict a high probability of failure with single-agent chemotherapy alone. Patients with prolonged duration of disease and nonmolar antecedent gestation are at high risk for failure using traditional forms of methotrexate and actinomycin D-based combination chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Renal metastases of gestational trophoblastic disease: a report of eight cases.

Between 1968-1984, eight women with renal metastases of gestational trophoblastic disease were treated at the Southeastern Regional Trophoblastic Disease Center. Two (1.3%) of 154 patients referred for primary therapy and six (14%) of 42 patients referred for secondary therapy of metastatic gestational trophoblastic disease had renal metastases. All eight had coexistent pulmonary metastases. Four had central nervous system and other systemic metastases. All had high-risk metastatic gestational trophoblastic disease by assessment of individual risk factors and analysis of a prognostic index score. Three women with limited systemic tumor burden are alive after receiving multiagent chemotherapy and nephrectomy.

Female↗

Nonmetastatic gestational trophoblastic disease.

Nonmetastatic gestational trophoblastic disease encompasses a variety of related neoplasms of the human placenta. With the advent of effective chemotherapy, nearly all of these patients can be cured using a variety of regimens with acceptable toxicity. Hysterectomy is useful in selected patients to decrease the amount of chemotherapy required to produce remission and to salvage patients who have failed initial chemotherapy. The majority of patients can retain child-bearing capacity and often have normal pregnancies after therapy.

Combined Modality Therapy↗

Immunochemical characterization and radioimmunometric detection of molecules shed by human ovarian cancer.

Monoclonal antibodies (MAbs) OC125, MOv2 and MOv8 recognize the CA125, CAMOv2 and CAMOv8 epitopes, respectively, which are associated with human ovarian carcinomas and are shed by these tumors. The biochemical analysis of the recognized antigens and epitopes has been performed to investigate the possibility of exploiting their expression, if any, on the same molecules. Cross-competition experiments clearly indicated that the 3 epitopes are distinct. Biochemical analysis was performed on a cyst fluid from an ovarian cystadenoma. Heat treatment and periodate oxidation indicated that CAMOv2 and CAMOv8 are saccharidic and suggested that CA125 is a conformational epitope to which both saccharides and the protein backbone could contribute. By gel-filtration chromatography CA125 activity was eluted into 2 peaks of high molecular weight, whereas CAMOv2 and CAMOv8 activities were associated with a single broad peak which included CA125-positive fractions. Isopycnic centrifugation showed that CA125, CAMOv2 and CAMOv8 carrying molecules had the same high density (1.46 g/ml) in the first peak, whereas CA125 molecules had a lower density (1.41 g/ml) in the second peak. Double-determinant immunoradiometric assays, carried out using different combinations of the MAbs, indicated that in the cyst fluid molecules expressing both CAMOv2 and CAMOv8 could be detected, whereas CA125 was carried by different molecules. CAMOv2 and CA125 could however be expressed on the same molecule in 2 out of 9 ascitic fluids from ovarian carcinoma patients. Taken together, these data indicate that CA125 and CAMOv2-CAMOv8 were only occasionally expressed on the same molecules. Therefore, the use of the CA125-CAMOv2 combination could not increase the sensitivity achievable by using each respective simultaneous immunoradiometric assay.

Antigens, Neoplasm↗

Intraperitoneal chromic phosphate P 32 as salvage therapy for persistent carcinoma of the ovary after surgical restaging.

From 1977 through 1984, 23 patients with persistent epithelial carcinomas of the ovary received intraperitoneal instillation with chromic phosphate P 32 suspension as salvage therapy after second- or third-look laparotomy. Patients received a median 10 cycles of chemotherapy before chromic phosphate P 32. Disease consisted of microscopic residual only in 10 patients (43%), macroscopic residual that was completely resected in eight (35%), and macroscopic residual disease in which the largest diameter was less than 0.5 cm in five patients (22%). Ten patients are free of disease at 13 to 94 months after chromic phosphate P 32 salvage therapy. Life table survival is 75% at 2 years and 57% at 4 years, with a disease-free survival rate of 54% at 2 years and 27% at 4 years. Patients with no gross residual disease had median disease-free survival of 27 months versus 9 months for patients with macroscopic residual disease (p greater than 0.1). Only three patients (13%) developed surgical bowel complications related to chromic phosphate P 32. Compared with previous studies, intraperitoneal chromic phosphate P 32 as salvage therapy for patients with minimal residual ovarian carcinoma defined at secondary surgical evaluation results in comparable survival and fewer complications than does salvage abdominopelvic irradiation and should be considered as an option to further chemotherapy in selected patients.

Actuarial Analysis↗

Total parenteral nutrition in poor prognosis gestational trophoblastic disease.

From 1978 through 1984, 35 women received therapy for poor prognosis gestational trophoblastic disease (GTD) at Duke University Medical Center. Total parenteral nutrition (TPN) was utilized in nine patients (26%) for reasons including inadequate oral intake, nutritional depletion, and/or bone marrow suppression. Overall survival with follow-up ranging from 12 to 78 months was 88% for the TPN group and 70% for the non-TPN group (P = 0.38). Median duration of TPN therapy was 4 weeks (2-46 weeks). Intensity of therapy was comparable between the groups. Median weight gain of 0.15 kg/week for the TPN group was significantly greater than the 0.18/kg/week weight loss in the non-TPN group (P less than 0.001). Severe nutritional depletion represented by both low serum albumin (less than or equal to 2.5 gm/dl) and weight loss greater than or equal to 10% had a higher mortality rate than when only one of these factors existed (P = 0.006). Future studies need to further define the proper role of TPN in patients with poor prognosis GTD especially in those with severe nutritional deficits.

Adolescent↗

Long-term effects on bladder function following radical hysterectomy with and without postoperative radiation.

Sixty-one patients with Stage IB cervical carcinoma treated initially by Type III radical hysterectomy underwent water cystometry 6 or more months after surgery. Adjunctive pelvic radiation in 10 patients was associated with significantly more contracted (P less than 0.001) and unstable (P less than 0.01) bladders than surgery alone. The necessity for bladder drainage 30 or more days after surgery alone in 17 patients was associated with significantly worse (P less than 0.05) long-term post-void residual and total bladder capacity as well as volume for first urge to void compared to 34 patients treated only with surgery who required short-term drainage. Management of bladder drainage following radical hysterectomy is discussed.

Adult↗

Endometrial adenocarcinoma estrogen receptor content: association of clinicopathologic features with immunohistochemical analysis compared with standard biochemical methods.

Endometrial adenocarcinomas from 96 patients were studied for their biochemical estrogen receptor content as well as immunohistochemical localization of estrogen receptor. A well-characterized specific monoclonal antihuman estrogen receptor antibody (H222 sp gamma) as amplified by peroxidase/antiperoxidase techniques was used for immunohistologic localization. Immunohistochemical evaluation incorporated both the intensity and distribution of staining into a semiquantitative analysis (HSCORE). The total HSCORE was the sum of the relative contributions of the four histologic components: benign epithelium, malignant epithelium, stroma, and myometrium. These results were compared with clinicopathologic features of the tumors. Excellent sensitivity (91.5%) and specificity (93.1%) were observed for immunohistochemical analyses as compared with the biochemical analysis of estrogen receptor for these tissues. The cancer component HSCORE correlated better with grade than did the biochemical estrogen receptor determination. Correlation was also observed between surgical stage and estrogen receptor content. Decreasing biochemical estrogen receptor content predicted advanced surgical stage (p = 0.0003), as did the total HSCORE (p = 0.003); however, the HSCORE of the cancer component only did not correlate with advanced surgical stage (p = 0.11). Although immunohistochemical analyses predicted biologic differentiation better than did the biochemical technique, stage correlated better with biochemical estrogen receptor analysis and total HSCORE than did the cancer component HSCORE. The HSCORE of the cancer component may better predict biologic behavior and therefore identify cancers more likely to respond to hormonal therapy.

Adenocarcinoma↗

Histologic composition of endometrial carcinomas analyzed for steroid receptor content.

One hundred endometrial carcinoma specimens were analyzed for estrogen receptor content and histologic composition. Benign tissue elements were identified in the majority of tissue sections. Histologic control of endometrial carcinoma specimens submitted for steroid receptor analysis is critical, because biochemical assays of whole tissue homogenates cannot determine receptor localization among tissue components.

Female↗

Role of surgical therapy and radiotherapy in gestational trophoblastic disease.

Surgical procedures and radiotherapy continue to play a significant role in the management of gestational trophoblastic disease (GTD) despite continuing advances in chemotherapy. Suction curettage and hysterectomy are preferred techniques for evacuation of hydatidiform mole. Although primary chemotherapy alone is usually successful in women with nonmetastatic or good-prognosis metastatic GTD, hysterectomy is useful in selected patients to decrease the amount of chemotherapy required to produce remission or as salvage therapy in patients who have failed primary chemotherapy. Even among patients with poor-prognosis metastatic GTD, such adjunctive surgical procedures as hysterectomy, thoracotomy and craniotomy may be useful. Whole brain and liver irradiation is employed as adjuvant therapy to reduce hemorrhagic complications of brain and liver metastases.

Brain Neoplasms↗

Radical hysterectomy as therapy for early carcinoma of the cervix.

During a 13-year period, 268 radical hysterectomies and pelvic lymphadenectomies were performed for Stage IB and IIA carcinoma of the cervix at Duke University Medical Center. Fifteen percent of patients had lymph node metastasis. Substage, histologic features, grade, capillary-like space involvement, and lesion size did not appear to affect nodal status. Survival was related to lymph node metastasis, status of surgical margins, and lesion size. Judicious use of radiation therapy after hysterectomy may have improved survival in high-risk patients. These does not appear to be any contraindication to operation in this group of patients as long as the condition is deemed medically operable.

Adenocarcinoma↗

Vulvar dystrophies.

Vulvar dystrophy is a relatively frequent gynecologic problem in postmenopausal women and may cause disabling discomfort. All patients with vulvar dystrophy should be carefully evaluated at the time of initial presentation and during therapy. Biopsies of vulvar lesions should be used liberally to define optimal therapy and to exclude atypia or malignancy, not only at the initial visit but also when lesions persist during therapy. In the absence of atypia, the patient can be reassured about the malignant potential of her disease. Most symptoms are relieved with conservative therapy alone.

Aged↗

Role of computed axial tomography of the chest in staging patients with nonmetastatic gestational trophoblastic disease.

Thirty-nine women with nonmetastatic gestational trophoblastic disease as determined by conventional staging studies were prospectively evaluated with computed axial tomography (CAT) of the lungs. Sixteen patients (41%) had pulmonary micrometastases detected by CAT, which were not detected by routine chest x-ray. Eight patients (20.5%) had indeterminate scans, and only 15 patients (38%) had negative scans. Eight of 16 patients (50%) with pulmonary micrometastases failed initial therapy with methotrexate-folinic acid rescue while one of eight (12.5%) patients in the indeterminate group and one of 15 (6.7%) patients in the true nonmetastatic group failed initial therapy (P less than .006). All patients who failed methotrexate-folinic acid rescue ultimately achieved prolonged remission with actinomycin D. Time to remission was significantly decreased in patients without evidence of pulmonary micrometastases (P = .03), but the total number of courses of chemotherapy was not significantly different (P = .06). No life-threatening toxicity occurred. Pulmonary micrometastases detected by CAT but not chest x-ray are predictive of an increased risk of methotrexate-folinic acid therapy failure. Computed axial tomography of the lungs identifies a group of patients at high risk for failure of methotrexate-folinic acid rescue, and, therefore, may be indicated for routine staging of patients with otherwise nonmetastatic gestational trophoblastic disease.

Adolescent↗

Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors.

A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. In all cases H222 Sp gamma localized in the nucleus of target cells. A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues. The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively. HSCORE correlated with tumor grade for breast and endometrial carcinoma. Immunohistochemical evaluation showed no specific staining in melanomas. The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied.

Antibodies, Monoclonal↗

Steroid receptors and endometrial cancer.

Like breast carcinomas, endometrial carcinomas are derived from sex steroid target tissue. Progress and research directed into the clinicopathologic relationship of steroid receptors and endometrial carcinomas have been hampered by many factors, including: limited numbers of patients with advanced-stage disease compared to the number with breast carcinoma; contamination of specimens with surrounding benign endometrial components which may contribute to total steroid binding; and amount of tissue required for standard biochemical assays. Nevertheless, several clinicopathological associations have been made for steroid receptor content of endometrial carcinomas. Receptor content appears to correlate with histological differentiation in that well-differentiated lesions have higher mean levels of receptor and more receptor 'positive' lesions than do poorly differentiated lesions. Furthermore, receptor levels and status appear to correlate with prognosis of primary endometrial carcinomas and response to hormonal therapy of advanced endometrial carcinoma. Newer techniques utilizing monoclonal antibodies to directly localize receptor in tissue specimens may lead to a greater understanding of the dynamics of receptor physiology in endometrial carcinomas, and may make possible more accurate predictions of clinical behavior by allowing the direct analysis of the receptor content of the malignant component within a tissue specimen.

Antibodies, Monoclonal↗

Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody.

Immunohistochemical localization of estrogen receptor (ER) using specific monoclonal anti-human estrogen receptor antibody, H222, with an immunoperoxidase technique was performed on fresh frozen tissue derived from 100 endometrial adenocarcinomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining. In all cases, H222 localized in the nucleus of target cells. A significant quantitative relationship was shown between histological score (H-Score) and the biochemical analysis of ER content in tissue homogenates (r = 0.65, P = 0.00001). Excellent sensitivity (92%) and specificity (93%) were observed for the comparison of H-Score to the biochemical assay. Significant ER localization was present in stromal and myometrial elements, component H-Score of which correlated weakly with component H-Scores of malignant epithelial elements. Divergent receptor localization in stromal and myometrial versus malignant epithelial elements suggests that biochemical assays of endometrial carcinoma specimens may not reflect cancer-relevant receptor content. The data presented here suggest that the immunoassay of ER using H222 monoclonal antibody provides additional histochemical information to complement conventional analyses of endometrial adenocarcinomas.

Adenocarcinoma↗

Assessment of the contemporary management of germ cell malignancies of the ovary.

Fortunately germ cell cancers of the ovary are infrequent. Modern therapy has changed an almost universally fatal disease to one that is highly curable. Conservative surgical procedures and intensive short-term chemotherapy appears to be the treatment of choice. In this young population subsequent pregnancies are a reality. Contemporary management is discussed.

Antineoplastic Combined Chemotherapy Protocols↗