Gynecologic tumors in tamoxifen-treated women with breast cancer.

OBJECTIVES: To present six additional cases of gynecologic tumors in tamoxifen-treated breast cancer patients, review the literature, and recommend measures for surveillance. METHODS: The hospital and office records of patients treated with tamoxifen at the University of Kansas Medical Center and Research Medical Center were analyzed. A comprehensive review of tamoxifen in the English and European literature was performed using MEDLINE and the bibliographies of various articles. RESULTS: From 1985-1992 at our institutions, six tamoxifen-treated breast cancer patients developed gynecologic tumors: three endometrial adenocarcinomas, a mixed müllerian sarcoma, a fallopian tube carcinoma with adenofibroma of the endometrium, and recurrent hyperplastic endometrial polyps. The literature contained 61 cases of adenocarcinoma of the endometrium and possibly four cases of uterine sarcomas in tamoxifen-treated breast cancer patients. The number of gynecologic malignancies reported is now 70. In 35 of the patients, the mean age (+/- standard deviation) was 63.9 +/- 12.0 years, and 61 of 66 patients (92.4%) were postmenopausal. Of the endometrial adenocarcinomas, 25 of 27 (92.6%) were stage I, and 11 of 27 (40.7%) were grade 1. The dose of tamoxifen was 20 mg/day in 15 (23.4%), 30 mg/day in 11 (17.2%), and 40 mg or higher in 38 (59.4%); 57% were treated with tamoxifen for less than 2 years. CONCLUSIONS: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial cancer. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint.

Diagnosis and management of brain metastasis from gestational trophoblastic disease.

Significant advances have been made since the introduction of methotrexate towards the improvement of long-term survival in patients with brain metastases from gestational trophoblastic disease. Early diagnosis via computed tomography of the head and beta-hCG serum testing along with aggressive, multiagent intervention have greatly improved patient prognosis from this once highly fatal condition. Although toxicity is commonly associated with this treatment, death from sepsis or drug reactions is unusual. Surgery has been found useful only to relieve intracranial pressure and is discouraged as part of diagnosis.

Early detection of gynecologic malignancies.

Gynecological malignancies constitute 14% of cancers in women. Failure to control disease is most frequently related to delays in diagnosis, which may be corrected through renewed efforts at patient and physician education as well as the use of diagnostic techniques currently available.

Endometriosis of the bowel.

One hundred sixty-three cases of endometriosis of the bowel (5.4% of 3037 laparotomies for endometriosis at the Ochsner Foundation Hospital) were reviewed to assess the management of this complication. Colon and rectal surgeons performed bowel resections of the colon in 30 cases and resections of the ileum and/or cecum in 11 cases. Gynecologic surgeons resected bowel implants, often multiple, in 153 patients, and also performed other necessary surgery, either ablative (with removal of uterus, tubes, and one or both ovaries; 58.8%) or conservative (with preservation of reproductive potential; 41.2%). The bowel mucosa was opened in 15% of implant resections. Complications included transient pulmonary febrile responses in 43%, two pelvic infections, and one hematoma. Ileus was not a problem, and there were no deaths. Resection of intestinal implants appears to be a safe procedure.

Hepatic metastases of choriocarcinoma: a report of 15 patients.

The presentation of illness, response to treatment, and complications of therapy of 15 patients with hepatic metastases of choriocarcinoma are analyzed. The majority of patients received multiagent chemotherapy concomitantly with whole-liver irradiation. Two patients are now in sustained remission. Hepatotoxicity of this combined treatment regimen directly contributed to only one death in the 13 nonsurviving patients. The diagnosis, management, and prognostic significance of choriocarcinoma metastatic to the liver are discussed.

Human papilloma virus in multifocal, invasive female genital tract malignancy.

Two young patients with multifocal, invasive, verrucoid carcinomas of the lower genital tract are described. Viral particles consistent with human papilloma virus were demonstrated by transmission electron microscopy in areas of koilocytotic malignant and nonmalignant epithelium, and both patients had evidence of impaired immune function. The role of human papilloma virus in genital neoplasia is discussed.

Intracavitary Corynebacterium parvum for treatment of malignant effusions.

Intracavitary instillation of Corynebacterium parvum was used to treat recurrent malignant effusions in 15 patients. Eleven patients were treated for ascites, and four patients were treated for pleural effusion. Six patients (40%) had good response with no recurrence of effusions up to 3 months after treatment. Three patients responded but died before criteria for complete response could be fulfilled. Six patients were judged to have poor response, either because of death from tumor burden before evaluation could be made or because of recurrent effusions. There were no serious side effects directly attributed to intracavitary C. parvum therapy. Analysis of the results in this preliminary study suggests that patients who have had prior good response to chemotherapy, whose performance scale is adequate, whose tumor burden is not preterminal, and who have been previously treated with immunotherapy may be excellent candidates for definitive treatment of malignant effusions with intracavitary C. parvum.

Intensive inpatient therapy and survival in gestational trophoblastic disease.

Metastatic gestational trophoblastic disease may be categorized into "good prognosis" and "poor prognosis" groups on the basis of the level of the pretreatment human chorionic gonadotropin titer, the location of metastases, the duration of disease, type of antecedent gestation, and the response of prior therapy. One hundred twenty-six patients with metastatic disease were treated from 1966 through 1979. All patients were treated as inpatients. Sixty-three "good prognosis" patients required an average of 65 days of intensive inpatient chemotherapy and all achieved sustained remission. Sixty-three "poor prognosis" patients were treated. Thirty-eight patients achieved sustained remission after an average of 112 days of intensive chemotherapy. Twenty-five patients (40%) succumbed to disease, after an average of 162 days of therapy. The probability of successful outcome of therapy falls rapidly after 150 days of treatment. Toxicity and deaths are reviewed.

Treatment of nonmetastatic gestational trophoblastic disease: results of methotrexate alone versus methotrexate--folinic acid.

Two treatment regimens for nonmetastatic gestational trophoblastic disease are compared in this retrospective study. The course of 39 patients with nonmetastatic gestational trophoblastic disease treated with methotrexate alone is contrasted to that of 29 patients with nonmetastatic gestational trophoblastic disease who were treated with methotrexate alternated with folinic acid. Of those patients initially treated with methotrexate alone, 7.7% developed methotrexate-resistant disease and required a change in chemotherapy for induction of remission. In contrast, 27.5% of patients initially treated with methotrexate and folinic acid developed methotrexate-resistant disease and required a change in chemotherapy to achieve remission. Ultimately, remission was achieved in all patients. Methotrexate as single-agent chemotherapy was found to be consistently more toxic than methotrexate alternated with folinic acid. It is concluded that methotrexate with folinic acid at the dosage used in this study, while less toxic than methotrexate alone, is less effective than methotrexate alone in the induction of remission of nonmetastatic gestational trophoblastic disease.

A trial of prophylactic cefamandole in extended gynecologic surgery.

A double-blind randomized trial of antibiotic prophylaxis was performed with 49 patients undergoing extended pelvic surgery for adenocarcinoma of the endometrium. In this series infections of the Hemovac drain site(s) were most common (8 of 10 infections); only 1 serious infection, pelvic cellulitis, occurred. Short-term perioperative cefamandole therapy significantly reduced infections and febrile morbidity in these patients as compared with patients who received a placebo. The average postoperative hospital stay for patients in the cefamandole group was 1 day less than for patients in the placebo group, but the difference was not statistically significant. The presence of 10 colony-forming units or more of a potential pathogen in lymph fluid collected through the Hemovac drains correlated with clinical infection. The low incidence of serious infection in this study precludes any conclusion regarding the impact of antibiotic prophylaxis in preventing serious infection after operation for gynecologic malignancy.

Chemotherapy with the modified Bagshawe protocol for poor prognosis metastatic trophoblastic disease.

The Southeastern Regional trophoblastic Disease Center has treated 126 patients with metastatic gestational trophoblastic disease from 1966 through 1979. Sixty-three cases were categorized as having a poor prognosis on the basis of criteria published previously. Since 1976, 18 patients have been treated with a modification of Bagshawe's multiagent chemotherapy protocol. Ten of 18 patients (56%) have achieved sustained remission. Seventy-eight percent of these patients encountered serious myelosuppression (white blood count 1000 cells or fewer) and 39% suffered severe thrombocytopenia (platelet count 50,000 or fewer). There were no deaths related to drug toxicity. The courses of therapy and complications of modified Bagshawe chemotherapy are reviewed.

Prognostic significance of peritoneal cytology in patients with endometrial cancer and preliminary data concerning therapy with intraperitoneal radiopharmaceuticals.

One hundred sixty-seven patients with clinical State I carcinoma of the endometrium were treated primarily by operation consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and para-aortic lymphadenectomy, and cytologic testing of peritoneal washings. Twenty-six (15.5%) of the 167 patients had malignant cells identified on cytologic examinations of peritoneal washings. Recurrence developed in 10 of these 26 (34.0%) compared to 14/141 (9.9%) patients with negative cytologic testing. Of the 26 patients, 13 (50%) had disease outside of the uterus at operation and seven have died of disease (54%). Thirteen patients had malignant cells in the peritoneal washings but no disease outside of the uterus and six (46%) of these have died of disseminated intra-abdominal carcinomatosis. On the basis of the poor outcome of those patients who had malignant cells in the peritoneal washings in the 167 patients studied, a plan of treating such patients with intraperitoneal radioactive chromic phosphate suspension (P-32) was instituted. Twenty-three subsequent patients with clinical Stage I carcinoma of the endometrium were found to have malignant cells in the peritoneal fluid. All 23 received intra-abdominal P-32 suspension instillation after operation. There have been three recurrences with two patients dying of disease. All of the three recurrences appeared at sites distant from the abdominal cavity. Peritoneal cytologic examination appears to be an important factor in the prognosis of endometrial cancer and, when the washings are positive for malignant cells, intraperitoneal chronic phosphate therapy appears to be efficacious.

Gestational trophoblastic neoplasia.

As a result of modern diagnostic and therapeutic techniques, nearly 100 percent of patients with GTN can be cured of a disease thay only a few years ago had a high death rate. To achieve this, skillful mixing of chemotherapy, surgery, and irradiation, as well as supportive therapy, are necessary. Understanding and utilizing the HCG assay to monitor disease status is vital. With this approach, essentially all of these patients should survive, many to have successful future pregnancies.