Epithelial ovarian cancer and the ability to conceive.

Relationships between ovarian cancer and ability to conceive were explored in a case-control study of 188 women with histologically confirmed epithelial ovarian cancer and 539 control women in the San Francisco Bay Area. Control women consisted of two groups: those hospitalized without cancer, matched to cases by age, race, and hospital of diagnosis (n = 280); and those selected from the general population by random digital dialing, matched to cases by age, race, and telephone prefix (n = 259). Ovarian cancer risk among nulliparous (but not parous) women was positively associated with a history of unsuccessful attempts to conceive, of physician-diagnosed infertility, and of doubts about ability to conceive. Among all women, risk increased with increasing years of unprotected intercourse (P value for trend = 0.02). Risk among women having 10 or more yr of unprotected intercourse was 1.8 relative to that among women having less than 2 such yr (P = 0.01). This association was independent of parity, oral contraceptive use, and estimated years of ovulation, each associated with ovarian cancer. Further, duration of unprotected intercourse combined multiplicatively with each of these latter characteristics in increasing ovarian cancer risk. For example, while cancer risk exhibited a 2-fold range from lowest to highest years of unprotected intercourse and a 4-fold range from lowest to highest years of ovulation, risk among women in the highest joint category of these characteristics was 8 times that of women in the lowest category. We believe that some abnormality of ovulation that reduces the likelihood of conception plays a role in epithelial ovarian cancer.

Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary.

Nine women with germ-cell tumors of the ovary (three endodermal sinus tumors, four immature teratomas, and two mixed germ-cell tumors) were treated with cisplatin, vinblastine, and bleomycin (PVB) chemotherapy after cytoreductive operations. Five patients were stage I, three were stage III, and one patient had recurrent disease. All nine women are alive and without evidence of disease with a median follow-up of 31 months from diagnosis and 27 months since completion of PVB. Treatment toxicity although occasionally severe was rapidly reversible.

Advanced epithelial ovarian cancer: salvage whole abdominal irradiation for patients with recurrent or persistent disease after combination chemotherapy.

Between 1979 and 1984, 53 patients received whole abdominal irradiation in a curative salvage effort for residual (32 patients) or recurrent (21 patients) epithelial ovarian cancer after combination chemotherapy (cisplatin-based in 48 patients). Residual cancer less than or equal to 2 cm in diameter was confirmed at operation in all patients before irradiation consisting of 2,550 to 3,000 rad to the whole abdomen with partial liver/kidney shielding and boosting of the dose to the diaphragmatic/paraaortic nodal regions and pelvis to approximately 4,000 and 5,000 rad, respectively. Twelve patients (23%) did not complete therapy as a result of hematologic intolerance. Actuarial overall and disease-free survival at 3 years are 35% and 30%, respectively, with follow-up for disease-free patients ranging from 30 to 79 months (median, 43 months). Twenty-seven of 36 relapses (75%) occurred within the irradiated abdomen alone. At 3 years, 70% of patients with well- or moderately-differentiated tumors were disease-free v 10% of those with poorly differentiated tumors (P less than .001). Among prognostic factors evaluated, including grade, initial residual disease before chemotherapy, residual disease at time of irradiation, age, chemotherapy response v progression, and completion of irradiation, only grade and initial residual disease before chemotherapy were statistically significant in multivariate analysis (both P less than .01). Patients with the combination of high-grade tumor, initial residual disease greater than 2 cm before chemotherapy, and macroscopic disease after "second-look" laparotomy do not benefit from irradiation. Eleven patients (21%) developed an apparent treatment-related bowel obstruction after completion of irradiation. Selected subsets of patients do well; however, the role of irradiation in this setting can be confirmed only with randomized clinical study.

High-dose megestrol acetate therapy of ovarian carcinoma: a phase II study by the Northern California Oncology Group.

The activity of high-dose megestrol acetate was studied in 47 patients with epithelial ovarian cancers after failure of initial chemotherapy. The dose of megestrol acetate was 800 mg/d orally (PO) for 4 weeks and then 400 mg/d until tumor progression. Patients generally had far-advanced disease. Prior therapy included cisplatin, doxorubicin, and cyclophosphamide (PAC) or other cisplatin-containing regimens in 37, other combinations in eight, and single agents in only two patients. Seventeen patients (36%) developed intestinal obstructions within the first 2 months on study. Tumor histology was serous in 37, endometrioid in six, and clear-cell in two. Two thirds of the tumors were histologic grade 3, and the others were grade 2. Complete remission was obtained in one patient, with time to progression of 4 months. There were three partial remissions, with times to progression of 4, 5, and 18 months. The overall response rate (complete and partial) was 8%. Three additional patients had minor remissions (3, 5, and 8 months), and five had stable disease, for 3, 4, 5, 6, and 9 months. There was no correlation of response with grade, histologic type, or site of disease, but responding patients had a longer survival from diagnosis to protocol entry and from protocol failure to death than did nonresponding patients. The major side effect of megestrol acetate was increased appetite, which caused one patient to withdraw from the study, and resulted in a 10- to 20-kg weight gain in five patients. Plasma levels of megestrol acetate averaged 600 ng/mL in the first month of therapy and decreased to approximately 400 ng/mL at 8 and 12 weeks, after the drug dosage had been reduced. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were markedly lower during megestrol therapy compared with pretreatment values. Megestrol acetate at 1 microgram/mL in vitro inhibited soft agar colony formation from one of 17 specimens of ovarian carcinomas. We conclude that megestrol acetate in high doses has modest, but definite, palliative effects in some patients with advanced ovarian carcinoma in whom chemotherapy has failed. A controlled trial of megestrol plus combination chemotherapy as first-line treatment of advanced ovarian carcinoma should be considered.

Topical 5-fluorouracil in the treatment of intraepithelial neoplasia of the vagina.

Twelve patients with vaginal intraepithelial neoplasia received topical therapy with 5% 5-fluorouracil cream. Six patients had carcinoma in situ, 5 had moderate dysplasia, and 1 had mild dysplasia. Five patients responded to 1 treatment course. Six patients required 2, and 1 patient required 3 courses of therapy to respond. Three patients developed recurrent vaginal intraepithelial neoplasia 11-16 months after therapy and were retreated with topical 5-fluorouracil. Vaginal irritation occurred in all patients but was limited to the duration of the treatment course.

Reticuloendothelial neoplasia of the female genital tract.

Twelve patients thought to have gynecologic tumors subsequently were found to have lymphoma or leukemia. Eleven tumors involved the genital organs; one involved the retroperitoneal pelvic lymph nodes. A lymphoma originated in the genital tract in 7 patients, and secondary involvement occurred in 2 patients. One patient with a previously treated lymphoma and 1 with leukemia in remission developed ovarian tumors as the first sign of relapse. The difficulty in diagnosis, need for appropriate treatment, and prognostic importance of the genital organs affected are discussed.

Survival after extraperitoneal pelvic and paraaortic lymphadenectomy and radiation therapy in cervical carcinoma.

Clinical staging, bipedal lymphangiography, and extraperitoneal pelvic and paraaortic lymphadenectomy were performed in 95 patients with invasive squamous carcinoma of the cervix. Radiation therapy was modified on the basis of findings at operative staging. Patients have been followed from 16 to 91 months, with a mean of 41 months. The accuracy of clinical staging and the relative abilities of lymphangiography and lymphadenectomy to assess the retroperitoneal lymph nodes have been determined. Five-year survival with respect to stage of disease and status of the pelvic and paraaortic lymph nodes was calculated by the life-table method. Seventy-five percent of patients with no lymph node metastases are projected to be alive at 5 years without recurrence. Fifty-six percent with pelvic lymph node metastases and 23% of those with paraaortic lymph node involvement are projected to be free of disease at 5 years. The risk of lymph node metastases increases with either the stage of disease or the volume of the primary tumor independently of stage. The presence of lymph node metastases adversely affects survival regardless of the stage of the primary tumor. Clinical staging as accepted by FIGO is inadequate in that it ignores patients with pelvic or paraaortic lymph node metastases. The accuracy of detection in the individual patient does not increase with the addition of lymphangiography. Operative staging can be performed safely by the extraperitoneal route and radiation therapy can be modified on the basis of the true extent of disease. Radiation therapy fails to cure patients because of distant dissemination of disease as well as an inability of conventional radiotherapeutic techniques to sterilize a large primary tumor volume.

Conservative treatment of borderline ovarian tumors.

Of 61 patients with stage IA borderline ovarian tumors, 41 were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, and 20 were treated by a variety of more limited operations, including cystectomy with (one patient) and without (three patients) a contralateral ovarian wedge biopsy, and unilateral salpingo-oophorectomy with (six patients) and without (ten patients) a contralateral wedge biopsy. In the group treated conservatively, there were 11 serous, seven mucinous, and two mixed seromucinous borderline tumors, whereas in the total abdominal hysterectomy and bilateral salpingo-oophorectomy treatment group there were 26 serious, 12 mucinous, and three mixed seromucinous borderline tumors. After a mean follow-up of 89 months (range 36 to 244 months), subsequent borderline neoplasms had developed in three patients (15%) with serious borderline tumors initially treated conservatively and in two patients (5%) with serous or mixed seromucinous borderline tumors initially treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patient with a mucinous borderline tumor treated either conservatively or with total abdominal hysterectomy and bilateral salpingo-oophorectomy developed a subsequent neoplasm. All 61 patients in the study group are alive and free of disease, including those who developed recurrent neoplasm.

Use of an immunoradiometric assay and a radioimmunoassay for the detection of free beta-human chorionic gonadotropin.

An immunoradiometric assay and a radioimmunoassay (RIA) were used to quantitate human chorionic gonadotropin (hCG) in the sera of ten pregnant women at term and of six women with gestational trophoblastic neoplasia. The two techniques show good correlation (Pearson correlation coefficient .96) in the assay of pregnancy serum. Because only the RIA, and not the immunoradiometric assay, measures the free beta-subunit of hCG, a comparison of the results obtained by the two immunoassay methods permits a semi-quantitative assessment of the free beta-subunit. The numerical results may not reflect the actual concentration of free beta-subunit in that two different immunoassay methods are used.

The operative evaluation of patients with cervical carcinoma by an extraperitoneal approach.

Seventy patients with cervical cancer who were not candidates for primary operative treatment underwent operative evaluation prior to radiation therapy. Thirty-one were explored through a transperitoneal approach and 39 through an extraperitoneal approach. The operative procedure consisted of bilateral pelvic and periaortic lymphadenectomy and exploratory laparotomy, with additional intraperitoneal biopsies taken as indicated by operative findings. Poor correlation was seen between operative findings, lymphangiography, and clinical staging. Radiation therapy was extended to include sites of biopsy proven metastases. The group of patients operated on through a transperitoneal approach experienced a 30% complication rate secondary to small bowel damage following radiation therapy, and 2 patients died as a result of complications. All patients with small bowel complications explored in this manner required surgical correction. The group of patients operated on through an extraperitoneal approach had a 2.5% morbidity secondary to small bowel complications, and there were not deaths or serious complications in these patients. No patients explored in this manner required subsequent operation for complications following radiation therapy.

Continent vesicostomy. Application in a patient.

Continent vesicostomy, as performed in the laboratory animal, allows the severely dysfunctional bladder to be emptied at predetermined intervals by transabdominal catheterization. The formation of a continent vesicostomy in a patient with markedly impaired bladder function secondary to an extended pelvic operation for the treatment of cancer is described. This technique provides a possible alternative to the construction of a urinary conduit in patients disabled from the treatment of a pelvic malignancy.

Myeloblastoma (granulocytic sarcoma) of the ovary.

Myeloblastic neoplasms occur in patients with leukemia. In women, the ovary is a common site. The cells of the tumor are identical histochemically to those in the peripheral blood. The Giemsa stain, PAS stain, and Leder stain assist in the diagnosis. The tumors are responsive to radiation therapy, chemotherapy, and operative removal, but tend to be associated with decreased survival. This report describes a case of myeloblastoma of the ovary in an 18-year-old woman. The clinical and pathologic features of these tumors are described. The literature is reviewed briefly.

Colposcopy in the follow-up of women with lower genital tract or perianal carcinoma.

Colposcopy has gained acceptance in the management of patients with abnormal cytologic smears or visible lesions of the lower genital tract. The well documented potential for the development of multifocal neoplastic disease in these tissues provides the rationale for the suggested use of the colposcope in the follow-up of patients with a previously treated carcinoma of the lower genital or perianal region. The value of colposcopy in such a patient is discussed.

Needle catheter jejunostomy: a controlled, prospective, randomized trial in patients with gynecologic malignancy.

Sixty patients with gynecologic cancer entered a prospective, randomized study of immediate postoperative feeding. Thirty-three women in the study group received an elemental diet (Vivonex HN) delivered through a needle catheter jejunostomy. Twenty-seven patients in the control group were given standard 5% dextrose and electrolyte solutions. Patients in both groups were stratified according to nutritional status as determined by anthropometric evaluation and levels of serum albumin, total protein, and transferrin. These parameters also were measured at intervals throughout the study. Only one catheter-related complication occurred. Patients in the study group received significantly more calories (p = 0.01) and were better able to maintain serum levels of transferrin (p = 0.05) than those in the control group. An elemental diet administered through the needle catheter jejunostomy effectively maintains postoperative nutrition and is associated with few complications.

Separate inguinal incisions in the treatment of carcinoma of the vulva.

A modified surgical technique, using separate incisions for vulvectomy and for each groin, resulted in a low morbidity rate, with no increase in tumor recurrence and no reduction in length of survival time in comparison with previously reported methods of treatment of invasive squamous carcinoma of the vulva. The clinical staging adopted by the International Federation of Gynaecology and Obstetrics accurately predicted survival time for patients in this series as in others. However, in instances in which the histologic status of the nodes differs from the clinical assessment, postsurgical staging with primary importance attached to the histologic evaluation more accurately predicts prognosis.

Partial hydatidiform mole with diploid karyotype: report of three cases.

Recent studies suggest that a partial mole with a triploid karyotype has little tendency to invade and metastasize and usually requires no therapy other than evacuation. This report describes three patients with a mole of normal diploid karyotype coexisting with a living fetus. Each patient had persistent elevation of human chorionic gonadotropin. Two patients required chemotherapy; one of these had invasive mole. The partial mole with normal diploid karyotype is a distinct clinical entity with the potential for malignant sequelae. The possibility of twin gestation cannot be excluded.

Ovarian fibrosarcoma associated with Maffucci's syndrome.

Maffucci's syndrome, a congenital condition of generalized mesodermal dysplasia, is most often associated with multiple enchondromas and soft tissue hemangiomas or lymphangiomas. This case report describes the development of an unusual ovarian fibrosarcoma and subsequent ovarian adenofibroma in a young woman with the syndrome. The importance of aggressive surveillance in this and similar orthopedic syndromes is stressed.