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Biomedical subjects

J T Soper

Publications and source records attributed to J T Soper.

At least 73 records · Page 4Linked to original sources

Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease.

Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer.

Adenocarcinoma↗

The role of partial sigmoid colectomy for debulking epithelial ovarian carcinoma.

Forty women underwent partial sigmoid colectomy during cytoreductive surgery for advanced epithelial ovarian carcinoma. Twenty-one (53%) and nineteen (47%) received this as part of primary or secondary debulking procedures, respectively. Fifty-four percent had postoperative residual disease less than 1 cm in largest diameter. Even though multiple surgical procedures were performed in conjunction with sigmoid colectomy, 75% of the patients had no significant postoperative morbidity. Postoperative mortality was 2.5%. Seventy-eight percent avoided permanent colostomy. Despite the above morbidity rate and aggressive postoperative therapy, the median survival for the entire group was only 14.5 months, with no significant differences between groups of patients who were categorized by primary or secondary debulking, histologic grade, amount of preoperative disease, ascites, or extent of postoperative residual disease. Although a partial sigmoid colectomy can be performed with a reasonable morbidity rate as part of debulking for ovarian cancer, and probably provides significant palliation of symptoms from large pelvic tumors, it must be used judiciously in selected patients.

Carcinoma↗

Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer.

Previous studies in breast and bladder cancer have suggested that epidermal growth factor receptor is expressed by only a proportion of cancers and is associated with poor clinical outcome. We used a monoclonal antibody specifically reactive with the extracellular domain of the epidermal growth factor receptor to localize this receptor immunohistochemically in frozen sections of normal ovary and epithelial ovarian cancer. Normal ovarian epithelium was found to express epidermal growth factor receptor in all cases. Among 87 ovarian cancers, however, 23% did not express immunohistochemically detectable receptor. Epidermal growth factor receptor expression was not related to histologic grade or stage, but was associated with poor survival (p less than 0.05). The median length of survival of patients with tumors that did not express epidermal growth factor receptor was 40 months compared with 26 months in patients with tumors that did express epidermal growth factor receptor. As in breast and bladder cancer, expression of epidermal growth factor receptor in ovarian cancer appears to be a poor prognostic factor.

Antibodies, Monoclonal↗

Hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy: correlation with histology and steroid receptor content.

Endometriosis is rare after hysterectomy and oophorectomy for conditions unrelated to endometriosis. We present a case of delayed development of aggressive, hormone-resistant endometriosis temporally remote from hysterectomy and oophorectomy performed for chronic pelvic inflammatory disease. Treatment with depo-medroxyprogesterone acetate resulted in continued growth of the retroperitoneal endometrioma and necessitated posterior exenteration because of the endometrioma's location. Estrogen and progesterone receptor levels were measured to clarify why this woman's endometriosis was resistant to hormone therapy. Despite administration of large amounts of depo-medroxyprogesterone acetate, the progesterone receptor content was elevated while the estrogen receptor content was undetectable. Why this patient developed this particular type of aggressive endometriosis is unclear, but the lack of down-regulation of progesterone receptors in response to high-dose progestin therapy may indicate an alteration in basic regulatory and cellular processes within the endometriotic implant.

Adult↗

Necrotizing fasciitis in irradiated tissue from diabetic women. A report of two cases.

Two diabetic women with pelvic malignancies developed necrotizing fasciitis within the irradiation fields. Despite aggressive surgical and medical therapy, both died when their health became too unstable for them to tolerate further surgery to resect the residual infection. We attribute their poor outcome to several factors. First, postradiation tissue changes obscured the early clinical findings necessary for a prompt diagnosis and made the identification of adequate surgical margins difficult. Second, diabetic patients have increased susceptibility to this infection. Third, the cumulative effects of radiation, diabetes mellitus and other factors that are common in patients with gynecologic malignancy (advanced age, vascular disease, obesity) favor the development, progression and persistence of necrotizing fasciitis. Radiographic studies were helpful in defining the extent of the infection in one patient.

Aged↗

Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center.

Between 1968 and 1985, 28 patients with recurrent gestational trophoblastic disease (GTD) were treated at the Southeastern Regional Trophoblastic Disease Center. Sixteen patients received primary therapy at this center and had recurrence diagnosed by re-elevation of human chorionic gonadotropin (hCG) levels after three consecutive negative levels: five (2.5%) of 204 patients with nonmetastatic GTD, three (3.7%) of 81 with good prognosis metastatic disease, and eight (13%) of 61 with poor prognosis disease. The remaining 12 patients were referred for therapy after receiving primary therapy elsewhere. All episodes of recurrence were observed within 36 months of remission with 50% and 85% before 3 and 18 months, respectively. Fourteen (56%) of 25 patients who achieved secondary remission developed a second recurrence and five (45%) of 11 surviving a second recurrence developed one or more further episodes of recurrent GTD. Nineteen patients (68%) have sustained remission 18 months following therapy for recurrent GTD. Factors relating to development and survival of recurrent disease include: poor prognosis metastatic disease, inadequate initial staging and therapy, lack of adequate maintenance chemotherapy beyond the first negative hCG level, and prolonged intervals between cycles of chemotherapy. Recent regimens introduced have contributed to an increasing salvage rate: 15 of 18 patients treated since 1978 are without evidence of disease whereas only four of ten treated prior to 1978 are currently in remission (P = 0.03).

Chorionic Gonadotropin↗

Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer.

Previous studies have suggested that overexpression of HER-2/neu oncogene occurs in 15-40% of breast cancers and that overexpression is associated with poor prognosis. In the present report, we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of HER-2/neu to study expression of HER-2/neu in frozen sections of normal ovary and advanced epithelial ovarian cancer. The intensity of staining for HER-2neu was always moderate or less (0-2+) in normal ovarian epithelium. Among 73 ovarian cancers, 50 (68%) had staining similar to that for normal ovarian epithelium (0-2+) while 23 (32%) stained heavily (3+). Survival of the 23 patients with high HER-2/neu expression (median, 15.7 months) was significantly worse (P = 0.001) than that of the 50 patients (median, 32.8 months) with normal HER-2/neu expression. In addition, patients whose tumors had high HER-2/neu expression were significantly less likely to have a complete response to primary therapy (P less than 0.05) or have a negative second-look laparotomy when serum CA 125 levels were normal preoperatively (P less than 0.05). These findings suggest that HER-2/neu deserves further evaluation as a prognostic marker in epithelial ovarian cancer.

Female↗

The prognostic significance of CA 125 half-life in patients with ovarian cancer who have received primary chemotherapy after surgical cytoreduction.

Fifty-four patients with advanced epithelial ovarian cancer were monitored with serial serum CA 125 levels after surgical cytoreduction and during multi-agent chemotherapy with cisplatin-containing regimens. CA 125 half-life of less than 20 days was associated with prolonged overall survival (p less than 0.015). In those patients who eventually were found to be disease-free at surgical surveillance procedures, normalization of serum CA 125 levels to less than 35 U/ml within 65 days of primary operation also suggested an improved survival (p less than 0.059).

Adenocarcinoma, Mucinous↗

Preoperative evaluation of serum CA 125, TAG 72, and CA 15-3 in patients with endometrial carcinoma.

We evaluated 109 women with endometrial carcinoma to determine the accuracy of preoperative tumor-associated antigen levels (CA 125, CA 72, CA 15-3) for prediction of extrauterine disease and whether TAG 72, CA 15-3, or both would improve the predictive value of CA 125 alone. Eleven (12%) of 80 patients with disease confined to the uterus or positive cytologic findings had CA 125 values greater than 35 U/ml versus 12 (65%) of 20 patients with extrauterine metastasis. Therefore CA 125 values had sensitivity of 65% and specificity of 88%. The TAG 72 level was elevated (greater than 6 U/ml) in 4% of patients with localized disease and 30% with metastasis. CA 15-3 was elevated (greater than 30 U/ml) in 17% and 65% in these categories, respectively. TAG 72 or CA 15-3 levels did not improve the combination of sensitivity and specificity of CA 125 alone. In addition, only one of 10 patients with microscopic metastasis (three cases) or positive peritoneal cytology (seven) had elevation of any of these tumor-associated antigen levels. Failure to detect occult metastasis and a high false-positive rate limit the role of these tumor-associated antigen assays in the preoperative evaluation of patients with endometrial carcinoma.

Antigens, Neoplasm↗

Heterogeneity of antigen expression in advanced epithelial ovarian cancer.

Immunohistochemical techniques were used to evaluate the expression of six antigens (CA 125, TAG 72, CA 19-9, OVTL3, DF3, and transferrin receptor) in frozen sections from the primary tumor and metastases of 20 patients with epithelial ovarian cancer. Heterogeneous expression of most antigens was observed within a given tumor nodule, but in each patient the proportion of cells expressing an antigen was similar in the primary tumor and metastases. To explore the stability of the antigenic phenotype of individual cells, we studied CA 125 expression in an ovarian cancer cell line. Cells were separated into CA 125-positive and -negative groups using fluorescence-activated cell sorting. After the two groups of cells were recultured separately, only 38% of cells originally sorted as CA 125 positive still expressed CA 125, whereas 27% of cells sorted as CA 125 negative expressed CA 125. That cells may gain or lose CA 125 expression in culture suggests that expression of CA 125 by ovarian cancer cells is not a stable trait.

Adenocarcinoma↗

Estrogen and progesterone receptor content of endometrial carcinomas: comparison of total tissue versus cancer component analysis.

Estrogen (ER) and progesterone (PgR) receptor values in 105 endometrial carcinomas were compared using immunocytochemical and standard biochemical techniques. Peroxidase-antiperoxidase staining for location of anti-ER (H222) and anti-PgR (JZB39) primary antibodies was used to generate a semiquantitative (HSCORE) assessment of receptor content in tissue components and the total specimen. Both total HSCORE and cancer component HSCORE correlated with log biochemical assay values for ER and PgR. Biochemical assay values, total HSCORE, and cancer component HSCORES all demonstrated internal correlations between ER and PgR levels. Correlation was somewhat closer for cancer component HSCORE values of ER and PgR than the values for total tissue HSCORE. When receptor content was analyzed by histologic grade, all three estimates of receptor status demonstrated a decreasing proportion of ER and PgR positive lesions with decreasing histologic differentiation; however, the proportion of receptor negative lesions in grade 3 lesions was much higher when using total HSCORE or cancer component HSCORE than when using biochemical assay values (P less than 0.005. Immunocytochemical techniques for localization of ER and PgR in endometrial carcinoma specimens may allow a more focused evaluation of the receptor content in the malignant elements than standard biochemical techniques.

Adenocarcinoma↗

CA 125 in peritoneal fluid and serum from patients with benign gynecologic conditions and ovarian cancer.

CA 125 was measured in peritoneal fluid from 200 patients with primary ovarian malignancies (35) and benign gynecologic conditions (165). In 86 patients CA 125 was measured both in peritoneal fluid and in serum. Patients with ovarian cancer had markedly greater serum CA 125 levels compared to patients with benign disease. CA 125 levels in peritoneal fluid were usually higher than serum levels. Twenty-six (93%) of 28 patients with ovarian cancer had peritoneal fluid levels which exceeded serum levels in paired samples. peritoneal fluid CA 125 values greater than 200 U/ml identified ovarian cancer patients with 96% sensitivity and 99% specificity. Serum CA 125 values greater than 35 U/ml identified ovarian cancer patients bearing ascites with a sensitivity of 99% and specificity of 94%. Only 2 of 165 patients with benign gynecological conditions had peritoneal fluid values above 200 U/ml. By contrast, only two values below 200 U/ml were found in ascitic fluids from 35 patients with ovarian cancer. CA 125 levels in peritoneal fluid deserve further evaluation for follow-up of patients with ovarian cancer.

Animals↗

Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer.

From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.

Adolescent↗

Transperineal templates for brachytherapy treatment of pelvic malignancies--a comparison of standard and customized templates.

A technique is described for the design and construction of customized templates for transperineal implants and interstitial hyperthermia of pelvic malignancies. The design of the template and the distribution of the transperineal Iridium-192 seed ribbons are based on prior optimization of the dose distribution. The target volume is defined by means of pelvic examination and pertinent radiographic studies including a CT. The pelvic CT study is obtained with a plastic obturator in the rectum or the vagina. The obturator is used as a reference structure for aligning the target contour from each image plane to form a composite 2-dimensional contour of maximum tumor extent in a plane perpendicular to the obturator. Dose distributions are calculated to determine the placement of the Iridium-192 seed ribbons in the template. Laparoscopic guidance is used for actual placement of brachytherapy source needles together with a rectal or vaginal obturator to stabilize the template and to assure that the needle placement conforms with the planned geometry. Dose distributions for 10 consecutive patients calculated for customized templates as well as for five commercially available standard templates show that the customized templates are superior to standard templates in that the planned dose distribution matches the configuration of the target volume and is more uniform than with standard templates.

Adult↗

Gestational trophoblastic neoplasia.

In many areas, GTN have become a success story in the field of oncology. It is well known that pregnancies with hydatidiform moles are high risk and carry the potential for the development of malignant forms of GTN. Monitoring with hCG levels has become accepted as the model for a sensitive and specific serum tumor marker. Chemotherapeutic strategies are well documented and are usually successful. However, as the recent literature demonstrates, further basic and clinical research is needed to define the epidemiology of GTN, especially choriocarcinoma resulting from nonmolar gestations. Identification of high-risk patients after evacuation of hydatidiform mole, perhaps using newer hCG subunit assays, might prevent postmolar GTN by identifying patients who would benefit from prophylactic chemotherapy. Because of the high cure rates for nonmetastatic and low-risk metastatic GTN, further research is needed to define cost-effective and efficacious regimens with low toxicity. A uniform system for staging and assessing risk of patients with GTN should be adopted and used by all investigators reporting results of chemotherapy. Although the World Health Organization system is the most widely used prognostic scoring system, further study with large numbers of patients is necessary to validate the weighted scores assigned to each item in the scoring system. Finally, collaborative groups should conduct randomized prospective studies to evaluate newer regimens for high-risk GTN and to develop salvage regimens using rigorously controlled phase II studies.

Antineoplastic Combined Chemotherapy Protocols↗