Biomedical subjects
Publications and source records attributed to J T Chambers.
Two cases of torsion of the normal fallopian tubes during the third trimester of pregnancy are presented. The etiology and clinical features of this complication are discussed. Although uncommon, it should be included in the differential diagnosis of abdominal pain in pregnancy.
In a 20-year-old man, computed tomography revealed that an orbital mass in the region of the lacrimal gland fossa had low density attenuation values (below water), indicating a fat-containing tumor. At surgery, we found a dermoid cyst of the oil cyst type.
A pilot study investigated topotecan (Hycamtin, GlaxoSmithKline, Philadelphia, PA), a topoisomerase I inhibitor, in treating uterine serous carcinoma, a typically unresponsive aggressive tumor. Fifteen patients were surgically staged, then treated with topotecan (1.5 mg/m2, Days 1-5 every 21 days) as first-line therapy (n = 12) or secondary to platinum failure (n = 3). Patients received topotecan through six courses, disease progression, or unacceptable toxicity. Grade 3/4 hematologic toxicity prompted dose adjustments. Thirteen patients exhibited no gross evidence of residual disease postoperatively. At topotecan initiation, one patient had 5-cm and one had < 1-cm residual disease. Seventy-eight courses (median, six) were administered; 12 (80%) patients completed the specified protocol. Common serious toxicities included grade 3 neutropenia (33%), anemia (13%), and thrombocytopenia (13%). Eight patients received erythropoietin and/or granulocyte colony-stimulating factor. Median follow-up for 14 evaluable patients was 26 months (range, 13-40). Of 11 evaluable first-line topotecan patients, nine were alive at follow-up; five were disease-free. Of three second-line topotecan patients, two died and one was alive with disease 31 months post-treatment. One patient with measurable disease achieved a complete and one a partial response as assessed by computed tomography scan. Median progression-free survival was 25 months; median survival has not been reached at 26 months. Although topotecan's antitumor activity cannot yet be quantified, disease-free interval and survival outcomes compare favorably with other therapies in uterine serous carcinoma. Further evaluation of topotecan in this population is warranted.
Ovarian cancer has received national attention as a highly virulent disease. Its lack of early warning symptoms and the failure to develop highly sensitive screening tests have led some physicians to recommend prophylactic oophorectomies to women with relatives who have had ovarian cancer. Others have recommended routine screening of otherwise normal women for CA 125, a circulating tumor marker, and ultrasound examinations. Each of these techniques is associated with substantial false-positive rates that could lead to unnecessary surgery. A review of epidemiologic data suggests that familial ovarian cancer kindreds are rare, but women with first-degree relatives who have had ovarian cancer have a significant risk themselves for developing ovarian cancer. In addition, women with a great number of ovulatory cycles are at an increased risk for the disease. Circulating tumor markers are frequently elevated in women with advanced ovarian cancer, but their value in early detection of ovarian cancer has yet to be established. Advances in endovaginal ultrasound and color Doppler flow technology have significantly improved our ability to assess pelvic organs. This article presents the background, rationale, and structure of the Yale Early Detection Program for ovarian cancer, whose goals are to identify the best techniques for diagnosing ovarian cancer in an early stage, to determine the frequency with which such tests should be employed, to assess false-positive results, and to identify women who might benefit from prophylactic oophorectomies.
Eighty-four women at high risk for ovarian cancer by having first-degree relatives with epithelial ovarian cancer participated in a newly established, early ovarian cancer detection program at Yale University. Participants were to be evaluated with physical examinations and circulating tumor markers at entry and every six months thereafter. Endovaginal ultrasound and color Doppler flow studies were to be performed at three and nine months following entry into the program. In addition, women were encouraged to follow American Cancer Society guidelines for mammography. Stool was checked for occult blood. Endometrial sampling was offered to post-menopausal women. No participant has developed an ovarian cancer since entering the program. One woman has been diagnosed to have breast cancer. False-positive levels of circulating tumor markers (CA 125, 4/84 [4.8 percent]; lipid-associated sialic acid in plasma, 13/84 [15.5 percent]; NB/70K, 4/84 [4.8 percent]; and urinary gonadotropin fragment, 1/65 [1.5 percent]) were observed on entry into the program. Low resistive indices (less than 0.5) were documented in 8/91 (8.8 percent) ovaries studied by the color Doppler flow technique. One participant underwent a laparotomy based on a false-positive endovaginal ultrasound examination. Tests now being employed in community practice have a high likelihood of being associated with false-positive results. Therapeutic interventions based on isolated abnormal tumor markers or ultrasound studies obtained from women with family histories of ovarian cancer may lead to inappropriate surgery. It is necessary for cancer centers to develop expertise in ovarian cancer detection techniques to advise physicians in their geographic areas appropriately about the significance of the abnormal screening test.
Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment.
Endometrial cancer contains estrogen and progestin receptor proteins. The receptor content inversely correlates with histologic differentiation. The correlation between receptor content and histologic subtype and stage of the disease may depend upon the degree of differentiation of the tumor. The status of the peritoneal cytology and depth of myometrial invasion by tumor do not correlate with the receptor status. In general, patients with receptor-rich tumors have a better prognosis than those without receptors and respond favorably to progestin therapy. The level of the receptor protein in the tumor may also influence survival.
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