Evaluation of recombinant human interleukin-12 in patients with recurrent or refractory ovarian cancer: a gynecologic oncology group study.

Objective. The goal of this study was to estimate the antitumor activity and toxicity of recombinant human interleukin-12 (rhIL-12) in patients with recurrent or refractory epithelial ovarian cancer. Methods. From December 1997 to March 1999, patients with recurrent or refractory epithelial ovarian cancer were entered on a Gynecologic Oncology Group phase II study of intravenous rhIL-12. All patients had measurable disease, had a performance status of 0-2, and had failed first-line platinum-based chemotherapy regimen. Eligible patients received rhIL-12, 250 ng/kg IV bolus, as a single dose on Day 1 followed by a 2-week rest period, with subsequent cycles administered daily for 5 days followed by a 16-day rest period per cycle, until disease progression or adverse effects prohibited further therapy. Results. Twenty-eight patients were entered and evaluable for toxicity, while 26 were evaluable for response. The median age was 59.5 years (range: 45-77). The median number of cycles was 2 (range: 1-9). There were no complete responders; however, one patient (3.8%) was a partial responder and 13 patients (50%) had stable disease. Grade 4 myelotoxicity occurred in 21% of patients. Two patients experienced capillary leak syndrome: one grade 2 and one grade 4. Conclusion. As a single agent, rhIL-12 is tolerable and shows a low response rate in recurrent epithelial cancer with measurable disease.

Accuracy of lymph node palpation to determine need for lymphadenectomy in gynecologic malignancies.

OBJECTIVE: To assess the accuracy of intraoperative lymph node palpation for identifying lymph node metastasis in gynecologic malignancies. METHODS: We prospectively evaluated 126 women who had lymphadenectomies for staging of various gynecologic malignancies from August 1995 to June 1997. Surgeries were done by obstetrician-gynecologists with subspecialty certification in gynecologic oncology from the American Board of Obstetrics and Gynecology, who had practiced gynecologic oncology for at least 5 years. Data were collected on gynecologic oncologists' opinions of lymph node status by palpation. Nodes believed to be positive were sent separately. We recorded operating time for lymphadenectomies, and intraoperative and postoperative complications. RESULTS: Mean (range) patient age was 55 (18-83) years. Mean (range) operating time was 188 (85-435) minutes. The mean (range) lymphadenectomy time was 46 (5-150) minutes. The total number of lymph nodes dissected was 2138. One hundred seven of 2138 (5%) nodes were positive for malignancy. Thirty-eight of 107 (36%) positive lymph nodes were missed by palpation. Fifty-six of 2031 (3%) negative lymph nodes were selected as positive. Sixty-nine of 107 (64%) positive lymph nodes were identified correctly. Sensitivity and specificity of palpation were 72% and 81%, respectively. The positive and negative predictive values of lymph node palpation were 56% and 89%, respectively. CONCLUSION: Intraoperative lymph node palpation has low sensitivity and positive predictive value even when done by experienced board-certified gynecologic oncologists.

Does ligation of the hypogastric artery at the time of radical hysterectomy and lymphadenectomy decrease blood loss? Results of a prospective randomized trial.

A prospective, randomized study of patients undergoing radical hysterectomy for gynecologic malignancies was undertaken from 10/95 to 11/96 to determine if ligation of the hypogastric arteries at the time of radical hysterectomy decreases blood loss. Patients were randomized to either ligation of the hypogastric artery (Group 1) or no ligation (Group 2) prior to a standard Piver type III radical hysterectomy. Surgeries were performed by Board certified gynecologic oncologists with gynecologic oncology fellows and/or OB/GYN residents. Patients were analyzed for demographic characteristics and intraoperative and postoperative parameters. Statistical analysis was performed with independent samples t-test, Mann-Whitney rank sum test, Chi square and Fisher exact test. Twenty-one patients were randomized to group 1 and 22 to group 2. Groups were similar with respect to demographics and preoperative parameters except for age. There were no differences among the groups with respect to intraoperative and postoperative parameters. The mean estimated blood loss for group 1 was 600 ml and 550 ml for group 2 (P = NS). Hypogastric artery ligation (HAL) at the time of radical hysterectomy for gynecologic malignancy does not reduce blood loss.

A pilot study utilizing intraoperative lymphoscintigraphy for identification of the sentinel lymph nodes in vulvar cancer.

OBJECTIVE: To identify sentinel lymph nodes using intraoperative lymphoscintigraphy. METHODS: Technetium-99-labeled sulfur colloid was injected at the site of primary vulvar carcinoma. An intraoperative gamma counter was used to identify one or more sentinel lymph nodes. RESULTS: Ten patients underwent bilateral inguinal and femoral lymphadenectomy. The clinical stages are as follows: T1 in 6, T2 in 2, and T3 in 2. A total of four groins (3 patients) were positive for metastases. In one patient only the sentinel node was positive for disease. In a second patient, two unilateral nodes were positive for disease and both were identified with the gamma counter as sentinel nodes. In the third patient, a single sentinel node was positive for malignancy in each groin. Multiple nonsentinel lymph nodes were positive in each groin in this patient. In no case was the sentinel node negative when other nonsentinel nodes were positive. CONCLUSION: Intraoperative lymphoscintigraphy quantitatively identifies one or more sentinel lymph nodes. Since sentinel lymph nodes can be localized transcutaneously, this technique may be useful for selective lymphadenectomy. Larger patient accrual is necessary to verify this technique.

Interleukin-12-mediated tumoricidal activity of patient lymphocytes in an autologous in vitro ovarian cancer assay system.

This study was designed to examine if interleukin-12 (IL-12) can induce cytolytic function of lymphocytes from ovarian cancer patients against either an ovarian cancer cell line or their own autologous tumor cells. Lymphocytes were obtained from the peripheral blood or ascites of ovarian cancer patients and activated with IL-12 alone or concomitantly with interleukin 2 (IL-2) for 2 to 3 days. Activation of lymphocytes and assessment of tumoricidal function by a chromium release assay were performed directly in a standard control medium (RPMI 1640 containing 2 mM glutamine, 100 micrograms/ml streptomycin, 100 units penicillin, 5% heat-inactivated human AB serum, and 5 mM 4-(2-hydroxyethyl)-1-piperazinesulfonic acid) and in 50% ascitic fluid (50% by volume filter-sterilized ascites with 50% of the above-mentioned control medium). Target cells were added directly into the medium in which the lymphocytes were activated in order to more closely mimic in vivo conditions. Lymphocytes, activated by IL-12 in 50% ascitic fluid, were able to lyse autologous tumor cells in 3 of 6 assays and were able to lyse SKOV3 cells (an ovarian cancer cell line) in 5 of 7 assays. The results were not significantly different in the control medium. When both IL-2 and IL-12 were used to activate lymphocytes in 50% ascitic fluid, significant cytotoxicity was generated in 6 of 6 autologous assays and in all 7 patient assays using SKOV3 as a target (P < 0.05). Synergy between the two cytokines was seen in all 13 patient assays in ascitic medium compared to only 5 of 13 assays in control medium. Additionally, when lymphocytes were stimulated with both IL-2 and IL-12, significantly greater cytotoxicity was seen in the ascitic fluid medium compared to the control medium in 13 of 14 assays (P < 0.05). No significant tumoricidal activity was seen by lymphocytes maintained in either medium without the addition of IL-2 or IL-12. Ascitic fluid consistently potentiates the synergy between IL-2 and IL-12 in generating cytotoxicity against ovarian cancer cells but does not increase cytotoxicity induced by IL-12 alone. IL-12 by itself activates tumoricidal activity of lymphocytes in ascitic fluid; however, the addition of IL-2 increases the degree and consistency of this effect. These data support the possibility that IL-12 may warrant further investigation as a potential therapeutic agent in the treatment of advanced ovarian cancer.

Sciatic nerve endometriosis treated with a gonadotropin releasing hormone agonist. A case report.

Sciatic nerve endometriosis was previously treated primarily with surgery. Most commonly hysterectomy and bilateral salpingo-oophorectomy have been used; however, two reports also describe successful conservative surgery with resection of the endometriosis from the sciatic nerve. Only one case of sciatic nerve endometriosis has been reported to have responded to medical management. This report details the rapid and complete resolution of sciatica secondary to endometriosis after medical treatment with the gonadotropin releasing hormone analog leuprolide acetate for depot suspension.

Management of chemotherapy in a pregnancy complicated by a large neuroblastoma.

BACKGROUND: The English literature contains infrequent reports of neuroendocrine carcinoma during pregnancy. The chemotherapy for this type of malignancy can cause severe nausea and neutropenia. We used recently developed modalities to ameliorate these side effects. CASE: A 22-year-old woman, gravida 4, para 2-0-1-2, presented at 24 weeks' gestation with a complaint of massive lower-extremity edema. Computed tomography scan delineated a large retroperitoneal mass. Biopsy of a small neck mass revealed a poorly differentiated neuroblastoma. A multidisciplinary approach to therapy was undertaken. The patient received cisplatin and etoposide chemotherapy. Complications of the first course included severe neutropenia and nausea with vomiting. Filgrastim and ondansetron were used to treat these complications. She delivered an 1825-g healthy male by cesarean for fetal distress at 35 weeks. No anomalies were noted at birth. Neonatal hematologic indices were normal CONCLUSION: A multidisciplinary approach to rare malignancies is warranted in pregnancy. Filgrastim and ondansetron are effective agents in the treatment of chemotherapy-associated complications. Their use in pregnancy warrants further investigations.

Upper vaginectomy for in situ and occult, superficially invasive carcinoma of the vagina.

Between Aug. 1, 1985, and July 31, 1990, 32 patients underwent upper vaginectomy for grade 3 vaginal intraepithelial neoplasia. Thirty-one of these patients had undergone hysterectomy, 25 because of cervical neoplasia. Fourteen patients had undergone treatment for vaginal intraepithelial neoplasia. Nine (28%) had invasive cancer on final pathologic examination. Among the remaining 23 patients, recurrence of vaginal neoplasia developed in four (17%), with a mean time to recurrence of 78 weeks, and one was found to have superficial invasion at the time of recurrence. The remaining 19 patients remain alive with no evidence of recurrent disease at a mean follow-up interval of 152 weeks. In our patients upper vaginectomy was efficacious for the diagnosis of occult invasive carcinoma of the vagina and for the treatment of in situ and superficially invasive carcinoma of the vagina.