Antiestrogens sensitize human ovarian and lung carcinomas for lysis by autologous killer cells.

BACKGROUND: The antiestrogens tamoxifen (TX) and toremifene (TO) were shown previously to enhance the lysis of target cells by natural killer cells (NK), lymphokine activated killer (LAK) cells, and by cytotoxic T lymphocytes (CTL). MATERIALS AND METHODS: CTL were cultured from lung cancer tissue and from ascites fluid of ovarian carcinoma patients with the aid of human recombinant interleukin-2 (hrIL-2). The target, effector or both cell populations were pretreated by TX, TO and/or with human recombinant interferon-alpha (IFN-alpha). RESULTS: Significant enhancement of cytotoxicity occurred when the tumor targets or both the target and effector cells were treated with TX, TO or when these drugs were used in combination with IFN-alpha. The lytic activity of CTL cultured from draining lymph nodes of lung cancer patients, was also observed after similar treatment. The lytic effect of autologous LAK cells derived from peripheral blood was increased to a lesser extent, which could be amplified by additional treatment with IFN-alpha. CONCLUSIONS: The antiestrogens TX and TO and IFN-alpha enhance the lysis of autologous tumor cells by CTL and LAK effectors.

Clinically apparent early stage invasive epithelial ovarian carcinoma: should all be treated similarly?

OBJECTIVES: The role of adjuvant therapy in patients with early stage ovarian carcinoma has not been clearly defined. Most randomized trials examining this issue have not used the vigorous staging exploration accepted as today's standard. This report examines the natural history of patients after surgically documented stage 1 ovarian carcinoma followed expectantly. METHODS: A retrospective chart review was carried out using strict criteria to include only patients who had an adequate staging procedure performed by gynecologic oncologists following a fixed protocol from 1987 to 1997. Patients' demographic data as well as current disease status were abstracted and analyzed. RESULTS: A total of 80 comprehensive surgical staging procedures were carried out over a 10-year period for apparent stage 1 ovarian cancer at the time of exploratory laparotomy. Fifty cases were true surgicopathological stage 1. It was found that serous and anaplastic tumors were more likely than other subtypes to be upstaged by the procedure. Further follow-up confirmed the excellent prognosis of early stage serous, endometrioid, and mucinous tumor with only one recurrence noted in an extraabdominal location in a patient with serous histology with no postoperative adjuvant therapy. Clear cell histology stands out as a significant recurrence risk (33%) despite an initially negative surgical assessment. CONCLUSION: Careful surgical exploration can identify a group of patients with early stage epithelial ovarian carcinoma who will benefit little from further adjuvant therapy. Patients with clear cell histology prove to be at a high risk for recurrence even at an early stage such that chemotherapy should be considered.

Does debulking surgery improve survival in biologically aggressive ovarian carcinoma?

Aggressive tumor reduction surgery has been widely used in patients with advanced stage epithelial ovarian carcinoma before initiation of cytotoxic chemotherapy. No randomized controlled trial has been carried out to confirm the benefits of such procedures. To examine the role of cytoreductive surgery in the management of stage 2 and 3 patients with epithelial ovarian carcinoma treated with postoperative adjuvant platinum-based chemotherapy, survival analysis was carried out on patients with initial microscopic disease documented on staging laparotomies, patients with large volume of disease at time of exploration and tumor reduced to microscopic residuals, and patients who were suboptimally debulked with more than 2-cm residual disease. Twenty-four, 81, and 191 patients were identified from a computerized data base, respectively. Kaplan-Meier survival estimates showed that 62% with initial microscopic residual are alive with no evidence of disease at 5 years and 56% of patients left with microscopic residuals after tumor reduction are alive and well at 5 years. There was no statistical significant difference between these two groups. The groups are equivalent with respect to known adverse prognostic factors. In contrast, 5-year survival in the suboptimal debulked group was significantly lower at 15%. Debulking surgery to achieve microscopic residual disease improved the prognosis in patients with initial large volume of disease. Survival was similar to survival in patients with microscopic disease at time of exploration. The beneficial effect may be attributed to the removal of chemoresistant clones in bulky tumors. Tumor reduction surgery remains important in the management of advanced stage epithelial ovarian carcinoma.

Malignant mixed mesodermal ovarian tumor treatment and prognosis: a 20-year experience.

Mixed mesodermal sarcoma of the ovary is a rare clinical entity. To review the epidemiology, prognostic factors, and treatment results related to primary ovarian sarcoma at our center, a retrospective chart review of all patients referred for ovarian cancer was carried out from 1974 to 1994. Cases with confirmed pathologic diagnosis of primary mixed mesodermal ovarian sarcomas were selected, forming the present study group. Thirty-six charts were identified. The median age at presentation was 67.5 years. Findings at laparotomy demonstrated extraovarian metastasis in 33/35 patients. Total abdominal hysterectomy and bilateral salpingo-oophorectomy +/- omentectomy were performed in 34 patients, with 22 patients left with macroscopic residual disease after surgery. Follow-up adjuvant chemotherapy consisting of cisplatin and doxorubicin was administered to 29/36 patients. Follow-ups ranged from 1 to 11 years with a median of 2 years. As with epithelial ovarian cancer, residual disease after initial surgery is an important prognostic factor. Thirteen patients had a second-look laparotomy. Five patients were positive for disease. Eight patients, one of whom recurred, were histologically negative. The patients with positive second-look findings, as well as all those who recurred clinically, subsequently died within 12 months despite trials with different second-line chemotherapeutic agents. Survival analysis showed a median survival of 3 years among patients treated with combination cytotoxic chemotherapy. Primary ovarian sarcomas make up about 2-3% of all ovarian cancer cases seen in our center. These are often very aggressive tumors with widespread metastasis at the time of presentation, making optimal tumor debulking difficult. The combination of cisplatin and doxorubicin appears to have activity resulting in a survival of 35% at 5 years. Second-look surgery offers little helpful information on the management of these tumors.

Early ovarian cancer: value of a negative staging laparotomy.

OBJECTIVE: To assess the risk of recurrence in patients with stage I (negative cytology) epithelial ovarian cancer receiving no adjuvant therapy. METHODS: Between 1976 and 1991, 51 patients with apparent stage I ovarian cancer underwent a comprehensive surgical staging that included: peritoneal cytology, omentectomy, pelvic and para-aortic lumphadenectomy, peritoneal biopsies and either unilateral salpingo-oophorectomy or TAH and BSO. RESULTS: Eleven of 51 patients (22%) were found to have stage II or III disease based on a positive staging laparotomy. Thirty-seven of 40 patients with stage I disease received no further therapy. There was one recurrence (stage 1C - grade 1) in patients with surgical stage 1C while there were no recurrences in patients with either stage 1A or 1B disease. CONCLUSION: This study concludes that surgical staging in apparent early stage ovarian cancer can identify a group of patients that require surgical therapy alone.

Peritoneovenous shunt for palliation of gynecologic malignant ascites.

BACKGROUND: Ascites is a common sequela of advanced or recurrent gynecologic malignancies, such as carcinoma of the ovary, fallopian tube, or endometrium. Symptomatic treatment with repeated paracentesis is the initial management after failure of chemotherapy. STUDY DESIGN: This study was done to evaluate the safety and effectiveness of a peritoneovenous shunt (PVS) in the palliation of these patients with recurrent ascites. A retrospective review of 25 patients having a PVS between 1982 and 1992 was performed. RESULTS: The 25 patients consisted of 21 patients with carcinoma of the ovary, two with primary carcinoma of the peritoneum, one with carcinoma of the endometrium, and one patient with carcinoma of the fallopian tube. The mean weight and abdominal girth decreased after shunt insertion (p < 0.001). Gastrointestinal dysfunction and dyspnea also improved with PVS insertion. There was no change in mean Karnofsky score after placement of a PVS. Two patients died within ten days postoperatively. The median survival period was 80 days and shunt occlusion occurred in four patients. CONCLUSIONS: The insertion of a PVS is effective in relieving refractory malignant ascites in gynecologic malignancies. The impact on quality of life requires further study.

Glassy cell carcinoma of the cervix: a bimodal treatment strategy.

Glassy cell carcinoma of the cervix is a distinct clinicopathologic entity. This infrequent pathologic subtype is an aggressive biologic tumor associated with a rapid clinical course and poor outcome with conventional treatment modalities in the majority of cases. In a 12-year period from July 1976 to June 1988, 32 cases of glassy cell carcinoma of the cervix were identified. This accounted for 5.3% of all cervical carcinomas. The mean age was 10 years younger than that of other histologic subtypes. A disproportional number of patients with glassy cell carcinoma had malignancies of early clinical stages. The 5-year survival of patients with Stage IB glassy cell carcinoma of the cervix was 45% when treated with primary radical surgery in contrast to 90% for squamous cell and 78% for adenocarcinoma. When bimodal therapy with radical surgery and radical radiotherapy was used, the survival of patients with Stage IB glassy cell carcinoma improved to 87%. Survival of patients with Stage II glassy cell carcinoma of the cervix improved from 50% to 85% with combined radical surgery and radiotherapy. Despite a combination of radical surgery and radiotherapy, complications were minimal.

Treatment of recurrent and metastatic adenocarcinoma of the endometrium with cisplatin, doxorubicin, cyclophosphamide, and medroxyprogesterone acetate.

We conducted a retrospective review of 44 patients with metastatic or recurrent endometrial carcinoma treated with cisplatin, doxorubicin, cyclophosphamide, and medroxyprogesterone acetate. Thirty-six women had metastatic disease; eight had recurrent disease. In the metastatic group, 12 women had positive peritoneal cytology as the only criterion for metastatic disease. Grade 1 tumors represented 25%, grade 2, 47.7%, and grade 3, 27.3%. The series was divided into four groups based on disease volume before chemotherapy: positive peritoneal cytology only (N = 12), microscopic (N = 11), macroscopic less than 2 cm (N = 6), and macroscopic greater than 2 cm (N = 15). Fifteen patients had measurable disease and eight (53%) had an objective response. The median survival was 31 months for the whole group. Median survivals were not reached for the positive peritoneal cytology only and the microscopic groups. Median survival for the macroscopic less than 2 cm and greater than 2 cm groups were 15 and 10 months, respectively (P less than .0001). The volume of disease was the most important factor in determining survival as well as the time to progression (P less than .0001). The distribution of grade was similar in all groups (P = .88), and grade did not predict survival (P = .80) or recurrence (P = .87). The significant number of low-grade lesions in our series as well as the importance of positive cytology as a predictor of survival underscore the need for surgical pathologic staging in an effort to identify those patients in need of adjuvant therapy.

Prognostic significance of positive peritoneal cytology in endometrial carcinoma.

A retrospective review of 280 patients with endometrial carcinoma who had peritoneal cytologic examination done at the time of laparotomy was undertaken. A positive cytologic finding was the only manifestation of extrauterine disease in 16 patients (6%). Four (25%) of these patients had a recurrence. Only 13 (5%) of 237 patients with negative cytologic findings had a recurrence. Positive peritoneal cytology is a marker for potential recurrence.

Papillary serous adenocarcinoma of the endometrium.

The clinical outcome of 15 women with papillary serous adenocarcinoma of the endometrium is presented. In 14 instances the diagnosis was made by uterine curettage. Eight cases (53.3%) were clinically understaged based on laparotomy findings. Intraoperative assessment for extrauterine spread of disease was infrequently performed. Recurrent disease developed in 12 patients (80.0%) with ten arising within the abdomen either alone or in conjunction with another site. Eleven patients (73.3%) have died of disease and two of the four alive have been treated for a recurrence. The need to determine appropriate adjuvant therapy for patients with this disease exists. A protocol for patient management is proposed.

Results of prior cytologic screening in patients with a diagnosis of Stage I carcinoma of the cervix.

Cervical carcinoma is a disease which lends itself to prevention and diagnosis by cytologic screening. The results of previous Papanicolaou smears were obtained in 84 patients. Of 197 Papanicolaou smear results obtained prior to diagnosis of Stage I carcinoma, 63 (31%) were positive; and of 51 such smears obtained 1 year prior to diagnosis, 30 (59%) were positive. Possible explanations for negative screening prior to development of carcinoma are given. The need for centralized cytologic screening programs on a provincial basis is stressed.

Stage I endometrial adenocarcinoma: treatment results in 835 patients.

A 16-year review of 835 patients with Stage I adenocarcinoma of the uterus revealed histologic grade and depth of myometrial invasion to be salient prognostic factors. Sixteen percent of patients developed recurrent disease and despite aggressive treatment, only 10% of these survived. Preoperative or postoperative radium decreased the incidence of vault recurrence.