Leo D. Lagasse

Results and complications of operative staging in cervical cancer: Experience of the Gynecologic Oncology Group

Abstract A multiinstitutional study by the Gynecologic Oncology Group (GOG) has confirmed that clinical staging often is inaccurate in determining the extent of disease in patients with cervical cancer. The finding of positive paraaortic nodes in 29% of patients with Stage II, III, and IV tumors supports this conclusion. In this series, the incidence of paraaortic nodal metastases could not be correlated with the histologic grade of the tumors . With positive paraaortic nodes, conventional treatment limited to the pelvis can be expected to fail, but it is still not clear how many patients can be salvaged by treatment to extended paraaortic radiation fields . Longer periods of follow-up in patients whose treatment plans were based on surgical staging information will be required.

Cis‐platinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix: A phase ii study of the gynecologic oncology group

Thirty‐four patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to control with surgery and/or radiotherapy were treated with cis‐platinum 50 mg/m2 intravenously every three weeks. Among 22 patients who had received no prior chemotherapy, three complete and eight partial responses were observed (response rate 50%), whereas only two partial responses were observed among 12 patients who had received prior chemotherapy (response rate 17%). The observed response rate was marginally significantly higher among those with no prior chemotherapy (P = 0.059). The overall frequency of response was 38% (13/34). Responses were observed in those with pelvic (7/20) as well as extrapelvic disease (6/14). Adverse effects included primarily leukopenia (11/34), thrombocytopenia (13/34), nausea and vomiting (29/34), and azotemia (17/34). Adverse effects were generally mild to moderate and hence tolerable. Cis‐platinum thus appears to be a highly active agent in the treatment of squamous cell carcinoma of the cervix at the dose and schedule tested.

Management of Regional Lymph Nodes and their Prognostic Influence on Vulvar Cancer

One hundred thirteen patients with invasive carcinoma of the vulva underwent radical vulvectomy and bilateral inguinal-femoral lymphadenectomy between 1957 and 1978. Eighteen had unilateral pelvic lymphadenectomy. Thirty-one patients (27.4%) had positive lymph nodes. The corrected actuarial five-year survival for patients with negative nodes was 96%, whereas it was 94% for patients with one positive node, 80% for those with two positive nodes, and 12% for those with three or more positive nodes. All patients with positive pelvic nodes or pelvic recurrence had three or more positive unilateral groin nodes, and all had palpably suspicious groin nodes preoperatively. Groin and systemic recurrences occurred in 2.9 and 3.8%, respectively, of patients with fewer than three positive unilateral inguinalfemoral nodes, as compared to 33 and 66%, respectively, of patients with three or more positive nodes. These data do not support routine pelvic lymphadenectomy in patients who have no clinically suspicious groin nodes and fewer than three positive nodes on histologic examination.

Cytoreductive surgery in ovarian carcinoma: feasibility and morbidity.

Between 1974 and 1984, 70 patients underwent primary cytoreductive surgery for ovarian carcinoma at the University of California at Los Angeles. During the period of January 1974 to December 1978, optimal cytoreduction was achieved in 56.4% of the patients. With increased experience, this figure improved to 87.1% in the period of January 1979 to December 1983. The most common morbidity associated with the procedure was fever and prolonged ileus. Bowel resection was required in 20% of the patients and was not associated with increased morbidity. More liberal use of the end-to-end anastomosis stapling device facilitated low colon reanastomosis without colostomy, which contributed to the improved patient acceptance.(Obstet Gynecol 67:783, 1986)

Prognosis and treatment of endometrial cancer

An understanding of the patterns of spread and prognostic factors influencing survival is necessary to develop rational treatment programs for patients with endometrial cancer. The most important risk factors include the stage of tumor, status of pelvic lymph nodes, depth of myometrial penetration, tumor grade, cell type, and patient age. Because of the inherent inaccuracies of staging based on pelvic examination and the inability to assess the status of lymph nodes or myometrial penetration clinically, errors in management often result when radiation therapy is delivered prior to operation. Therefore, a rationale is offered for primary operative management of patients with Stage I disease, with consideration of adjunctive radiation therapy following operation based on extend of disease and a thorough evaluation of the high-risk factors. It is suggested that patients with more advanced stages of disease be considered for pretreatment operative evaluation. Data are presented which refute theoretical objections to this approach.

Serum androgens and estrogens in postmenopausal women with and without endometrial cancer

Thirty-five consecutive patients with adenocarcinoma of the endometrium and an equal number of control subjects matched to the cancer patients for age and percentage of ideal weight were studied prospectively. In the cancer patients, the mean +/- SE serum androstenedione, testosterone, estrone (E1) and estradiol (E2) levels were 503 +/- 34 pg/ml, 224 +/- 22 pg/ml, 38.7 +/- 3.6 pg/ml, and 14.5 +/- 0.9 pg/ml, respectively. Similar concentrations were found in the control subjects. Body weight and percentage of ideal weight showed highly significant correlations (P less than 0.001) with E1 and E2 but not with the androgen concentrations in either group. The heavier patients had higher E1 and E2 levels. Age and years since menopause did not correlate with any of the hormonal levels. The cancer patients with overt diabetes tended to be more obese and have higher estrogen levels than did the nondiabetic subjects. Those with a history of prior estrogen usage were more slender and had lower endogenous estrogens than the nonusers. Twenty-three of the cancer patients (66%) had a presumed risk factor(s) for the development of this tumor, that is, excess body weight, high endogenous estrogen levels, or a history of prior estrogen usage. These data support the concept that conditions which lead to continued, unopposed estrogen stimulation may be associated with malignant transformation of the endometrium.

Effect of obesity on survival in epithelial ovarian cancer

Epidemiologic studies suggest that obese women are more likely to die of ovarian cancer than those of ideal body weight, but it is not known whether increased incidence, comorbidities common to obese women, or altered tumor biology is responsible for this difference. The current study attempted to determine the influence of excess body weight on ovarian cancer survival, disease progression, and clinicopathologic factors.

Preoperative radiation therapy for locally advanced vulvar cancer

Eight patients with locally advanced vulvar cancer that would have necessitated pelvic exenteration to encompass the primary tumor were given preoperative radiation therapy in an attempt to shrink the primary tumor and allow more conservative surgery. From 4400 to 5400 rad of external radiation were delivered to the primary tumor, and one patient received an additional 2400 rad from intracavitary therapy. Satisfactory shrinkage of tumor occurred in seven of the eight patients (87.5%), thus allowing conservative surgical excision. In four patients (50%), there was no viable tumor in the surgical specimen. Moist desquamation of the vulva occurred in all patients and was of sufficient severity to require temporary cessation of radiation in four patients (50%). Five received groin radiation, and one (20%) subsequently developed bilateral hip fractures. No other major morbidity occurred. Five of the eight patients (62.5%) are alive without evidence of disease at intervals ranging from 15 months to 10 years. Preoperative radiation in this group obviated the need for pelvic exenteration, resulting in significantly less morbidity without compromising survival.

Steroid hormone effects on the proliferation of human ovarian surface epithelium in vitro

OBJECTIVE The histologically bland-appearing epithelium of the human ovary is responsible for approximately 90% of ovarian cancers. Capitalizing on our ability to propagate this tissue in vitro, we have begun to characterize the steroid hormone responsiveness of the human ovarian surface epithelium. STUDY DESIGN Primary cultures of the human ovarian surface epithelium are characterized as normal epithelium on the basis of morphologic features, normal karyotype, and immunohistochemistry demonstrating AE1/AE3 cytokeratin positivity and factor VIII negativity. Estrogen and progestin receptors were quantitatively analyzed with a standard receptor-ligand binding assay. Cellular proliferation in response to 1 x 10(-7) mol/L 17 beta-estradiol, progesterone, dihydrotestosterone, and dexamethasone were assessed by means of cell counts and a tetrazolium-based colorimetric assay. RESULTS Scatchard analyses identified 8.8 x 10(3) estrogen receptors per cell in the premenopausal human ovarian surface epithelium cells, whereas the postmenopausal cells were negative for estrogen receptors. A total of 3.2 to 13.0 x 10(3) progestin receptors per cell was identified, with variable progestin receptor expression in the postmenopausal cells. No significant effect on cell growth could be demonstrated as a result of any of the steroid hormones investigated under the study conditions. CONCLUSIONS Expression of estrogen and progestin receptors in human ovarian surface epithelium cells may be related to menopausal status. Steroid hormones, however, did not influence cell proliferation under these experimental conditions.

HER-2/neu, P53, and DNA analyses as prognosticators for survival in endometrial carcinoma

Objective To compare the prognostic importance of certain molecular biologic characteristics (HER-2/neu and p53 gene overexpression, DNA ploidy, and the S-phase fraction) to standard clinical-pathologic factors used to predict survival in patients with endometrial carcinoma. Methods We reviewed archival specimens from 128 patients with endometrial cancer diagnosed during the period 1985–1987. One hundred four cases were eligible for inclusion in the study. Immunohistochemistry was used to detect p53 and HER-2/neu overexpression. We used flow cytometry to calculate DNA ploidy and the S-phase fraction. Life-table analysis and Cox multiple regression were used to analyze clinical and molecular data with respect to survival. Results International Federation of Obstetrics and Gynecology stage, nuclear grade, lymph-vascular space invasion, and adverse histopathologic features each significantly correlated with poor outcome (each at P ≤ .001). Overexpression of p53 was demonstrated in 15% of the tumors and was associated with a 12% probability of 5-year survival, compared to a 90% probability of 5-year survival, for the p53-negative cohort (P = .0001). Thirty percent of the tumors were aneuploid, which was also associated with poor prognosis (P = .0003). HER-2/neu overexpression and an S-phase fraction greater than 10% showed similar trends, but were not statistically significant. On multivariate analysis, p53 overexpression was the strongest independent prognosticator of survival (P = .0001). Conclusion Molecular characteristics provide objective data that may be useful in predicting prognosis in patients with endometrial cancer. Further investigation of molecular and genetic characteristics are needed to refine our diagnostic and treatment modalities.