Surgery in advanced epithelial ovarian cancer.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Biomedical subjects
M S Piver
Publications and source records attributed to M S Piver.
Epidemiologic differences between women with colorectal cancer and women with ovarian cancer.
BACKGROUND AND OBJECTIVES: The difference between the epidemiologic features of women with colorectal cancer and those with ovarian cancer has not been thoroughly studied. The aim of this study is to review the epidemiologic features of women with colorectal cancer and compare them with those of women with ovarian cancer. METHODS: The epidemiologic features of 705 women with colorectal cancer were compared with those of 503 women with primary epithelial ovarian cancer. Both groups included all women with the confirmed respective histologic diagnoses admitted to Roswell Park Cancer Institute between 1982 and 1996 who returned a voluntary self-administered epidemiologic questionnaire. RESULTS: Women with ovarian cancer were significantly younger, had higher education and income, had fewer children, and were more likely to have never been married and nulligravid than those with colorectal cancer. There was a significant difference in the contraceptive history between both groups among women > or = 45 years of age. More women with ovarian cancer had a family history of ovarian cancer and more women with colorectal cancer had a family history of colorectal cancer. CONCLUSIONS: The epidemiologic features of women with colorectal cancer are different from those with ovarian cancer. The difference between both groups might indicate difference in the environmental or genetic etiology of both cancers.
Colorectal Neoplasms↗
Regular use of analgesic drugs and ovarian cancer risk.
Analgesics have been shown to reduce risk for colorectal cancer. Results from three recent reports (D. W. Cramer et al., Lancet, 351: 104-107, 1998; C. Rodriguez et. al., Lancet, 352: 1354-1355, 1998; L. Rosenberg et al., Cancer Epidemiol. Biomark. Prev., 9: 933-937, 2000) suggest that these drugs might be associated with decreased risk for ovarian cancer. In this hospital-based case-control study, we compared 547 patients with ovarian cancer to 1094 age-matched patients with nonneoplastic conditions. All of the participants received treatment at the Roswell Park Cancer Institute between 1982 and 1998 and completed a comprehensive epidemiological questionnaire that included information on demographics, life-style factors, and reproductive characteristics as well as frequency and duration of aspirin and acetaminophen use. Women who reported that they had used one or more of these agents at least once a week for at least 6 months were classified as analgesic users. Logistic regression was used to compute crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Aspirin users were not at reduced risk of ovarian cancer compared with nonusers (adjusted OR, 1.00; CI, 0.73-1.39). There was also no evidence of a decrease in risk as a function of greater frequency of use or prolonged duration of use. Regular acetaminophen use was associated with a reduced risk (adjusted OR, 0.56; 95% CI, 0.34-0.86), and risk reductions were observed for women with the greatest frequency of use (adjusted OR, 0.32; 95% CI, 0.09-1.08) and longest duration of use (adjusted OR, 0.51; 95% CI, 0.27-0.97). These data suggest that regular use of acetaminophen, but not aspirin, may be associated with lower risk of ovarian cancer.
Acetaminophen↗
Ovarian carcinoma in situ with germline BRCA1 mutation and loss of heterozygosity at BRCA1 and TP53.
BACKGROUND: The two-hit hypothesis for the genesis of cancer predicts that cancer can develop when the wild-type allele of a tumor suppressor gene is lost in an individual with a germline mutation in that gene. Neither loss of heterozygosity (LOH) for BRCA1 nor mutations of the TP53 (also known as p53) gene have been documented prior to invasion in ovarian cancers arising in women with germline BRCA1 mutations. Such documentation is difficult because lesions are rarely identified in ovarian epithelium. We, therefore, looked for LOH at microsatellite polymorphisms linked to the BRCA1 and TP53 tumor suppressor loci in an incidental carcinoma in situ of the ovary removed prophylactically from a woman with a germline BRCA1 mutation. METHODS: By use of laser-capture microdissection, we obtained pure populations of atypical ovarian epithelial cells and normal stromal cells. DNA was extracted, amplified with primers flanking polymorphic microsatellites linked to BRCA1 (D17S855 and D17S579) and TP53 (TP53 and D17S786), and analyzed for LOH at these microsatellites. We also tested for p53 expression in the abnormal epithelium by immunohistochemistry. RESULTS: Both of the markers linked to TP53 showed LOH, as did an intragenic BRCA1-linked marker (D17S855). The other microsatellite marker for BRCA1 was uninformative. Immunohistochemical staining with an antibody to p53 showed strong immunoreactivity confined to the atypical epithelium. CONCLUSIONS: BRCA1, as well as TP53, can undergo LOH prior to stromal invasion in BRCA1-associated ovarian cancer. Strong immunoreactivity for p53 suggests the presence of mutated p53 in these cells as well. These findings suggest that loss of function of these two tumor suppressor genes occurs early in ovarian carcinogenesis in BRCA1 mutation carriers.
Antibodies, Neoplasm↗
Flt-3 ligand inhibits growth of human ovarian tumors engrafted in severe combined immunodeficient mice.
OBJECTIVE: The current study evaluated the effects of Flt-3 ligand (FL) on the growth of human malignant ovarian tumors engrafted in severe combined immunodeficient (SCID) mice with particular attention directed at FL's effect on the host natural killer (NK) cell response against ovarian cancer xenografts. METHODS: Equal portions of surgical specimen-derived human ovarian carcinomas were engrafted subcutaneously (SC) into SCID mice. Mice were placed into one of two treatment groups 7 days after the day of implantation. Group 1 received placebo injections SC from Day 1 to Day 20 and group 2 received FL at 10 microg/day SC from Day 1 to Day 20. NK cell depletion was performed on three additional mice from group 2 starting on Day 0 using anti-asialo GM1. Serial tumor volumes were measured. On Day 21, mice from each group were sacrificed, and tumors and spleens were evaluated. Data analysis included chi(2) tests, Student t tests, and analyses of variance when appropriate. RESULTS: FL resulted in tumor growth delay compared with control (P = 0.036). When NK cell activity was depleted prior to FL administration, no tumor growth delay was observed. Spleens from FL-treated mice were larger (P < 0.01) with expanded white pulp compared with controls. Histologic examination of tumor sections from FL-treated mice revealed regions of solid tumor growth with glandular architecture similar to that seen in control tumors; however, there was an obvious increase in regions composed largely of dense fibrosis in the FL-treated tumors. NK cells and other infiltrating cells could be detected in clusters among tumors from mice treated with FL whereas these cells were only occasionally detected in sections of control tumors. CONCLUSION: FL treatment resulted in an antitumor response against human ovarian cancer engrafted in SCID mice and this inhibition appears to be largely host NK cell mediated. The tumor inhibition seen in this model is similar to that previously seen using syngeneic tumors grown in an immunocompetent animal model. Results from this model can potentially be extrapolated to treatment of human ovarian cancer patients.
Animals↗
Comparative study of ovarian cancer histopathology by registry pathologists and referral pathologists: a study by the Gilda Radner Familial Ovarian Cancer Registry.
OBJECTIVE: The aim of this study was to evaluate whether there is a significant difference in the pathology diagnoses of women in the Gilda Radner Familial Ovarian Cancer Registry between the two expert Registry pathologists and the referral pathologist. Inaccuracies in verification that ovarian cancer did occur in family members could lead to unnecessary prophylactic surgery or genetic testing. METHODS: A retrospective review was performed of (1) site of malignancy; (2) histopathology of malignancy; (3) grade of malignancy; and (4) the presence or absence of malignancy between the Registry and referral pathologists. RESULTS: There was 95.3% complete agreement between the Registry and the referral pathologist on site of origin with a major difference in only 1.0% of the cases. In comparison of histopathology, there was a 61.7% complete agreement, and only 1.0% were considered major differences. There was 68.8% complete agreement in grade of the malignancy, whereas 2.3% were considered major differences. CONCLUSION: When constructing a family pedigree, it is important to obtain pathology reports to confirm the index case diagnosis of the presence or absence of ovarian cancer. However, because of the small percentage of major differences in diagnosis between the two Registry pathologists and the multiple referral pathologists, we believe genetic counselors and treating physicians can rely, in most instances, on the original histopathology report of verification of ovarian cancer without review of the original histopathology slides when recommending surveillance, genetic testing, and/or prophylactic surgery.
Female↗
Insurance policies for prophylactic mastectomy: to cover or not to cover?
Explore the source record for details and available documents.
Breast Neoplasms↗
Microsatellite instability in ovarian and other pelvic carcinomas.
Twenty-six cases of ovarian carcinoma and six cases of other pelvic neoplasms were analyzed for microsatellite instability (MSI) using frozen specimens, fluorescence technology, and four selected markers (D2S123 on chromosome 2, D18S58 on chromosome 18, BAT26 on chromosome 2, and BAT40 on chromosome 1). This procedure also allowed the detection of loss of heterogeneity (LOH) at the four selected loci. One of the cases of ovarian carcinoma exhibited MSI and this was evident at three loci. Of 44 informative loci, 7 exhibited LOH representing 3 cases of ovarian carcinoma, 3 of 4 cases of primary peritoneal carcinoma, and one case of unknown primary. These data support other findings that MSI is not a frequent occurrence in ovarian cancer; however, LOH is a more frequent event and may be a target for the development of diagnostic/prognostic procedures for ovarian and primary peritoneal carcinoma.
DNA, Neoplasm↗
Primary ovarian dysgerminoma in a patient with a germline BRCA1 mutation.
Germline mutations in the BRCA1 tumor suppressor gene are associated with increased risk for the development of ovarian cancer. All such cancers thus far reported have been of the epithelial histologic type. We identified an ovarian dysgerminoma in a 16-year-old woman (proband) with a family history of ovarian cancer during a review of histopathologic characteristics of ovarian cancers from women enrolled in the Gilda Radner Familial Ovarian Cancer Registry. Mutation analysis of DNA from this patient's peripheral blood leukocytes revealed a germline BRCA1 mutation (3312insG). The mutation was also present in the mother with breast cancer, a maternal aunt and a distant cousin with ovarian cancer, and a maternal grandfather and an uncle with skin cancer. The development of the proband's dysgerminoma may be unrelated to her germline BRCA1 mutation. Alternatively, such dysgerminomas may be caused by BRCA1 mutations, but occur so infrequently compared with epithelial cancers that they are seldom identified. Analysis of a larger series of ovarian germ cell tumors may resolve this question.
Adolescent↗
Maintenance chemotherapy in advanced ovarian cancer.
Explore the source record for details and available documents.
Antineoplastic Agents↗
The Gilda Radner Familial Ovarian Cancer Registry 1981-2000.
Explore the source record for details and available documents.
Age of Onset↗
Histopathology of familial ovarian tumors in women from families with and without germline BRCA1 mutations.
Breast cancers from patients with germline BRCA1 mutations show characteristic histopathologic features. However, similar studies of BRCA1-associated ovarian cancers have reported inconsistent findings. Interobserver differences in histopathologic classification are a significant source of variation, and most studies have obtained histopathologic information from pathology reports rather than from review of histopathology slides. We therefore reviewed the histopathology slides and pathology reports to determine histologic type, grade, and stage for cancers of the ovary or peritoneum in 217 women from 126 families enrolled in the Gilda Radner Familial Ovarian Cancer Registry. Peripheral blood DNA from at least 1 affected member of each family was analyzed for BRCA1 mutations, and tumors from BRCA1 mutation-positive families were compared with those from BRCA1-negative families. Of 66 patients from 36 BRCA1-positive families, 64 had ovarian carcinoma, 1 had an ovarian carcinoma in situ, and 1 had a dysgerminoma. Of 151 patients from 90 BRCA1-negative families, 135 had ovarian carcinoma, 10 had ovarian borderline tumors, 3 had ovarian sex cord/stromal tumors, and 3 had primary peritoneal carcinoma. There were fewer grade 1 (P <.001) and stage I (P =.10) cancers in patients from BRCA1-positive families than in patients from BRCA1-negative families. Neither mucinous nor borderline tumors were found in the BRCA1-positive families. Ovarian cancers arising in women from BRCA1-positive families are more likely to be high grade and nonmucinous than cancers arising in women from BRCA1-negative families. The absence of borderline tumors in patients from BRCA1-positive families adds to accumulating evidence that BRCA1 mutations do not play a role in the development of these tumors. HUM PATHOL 31:1420-1424.
Breast Neoplasms↗
Treatment of high-risk cervical cancer.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Mutation analysis of BRCA1, TP53, and KRAS2 in ovarian and related pelvic tumors.
Cancer may be viewed as a genetic disease resulting from critical mutations that disrupt normal cell growth. To characterize the involvement of the BRCA1 and TP53 tumor suppressor genes and of the KRAS2 protooncogene in gynecologic cancer, mutation analysis of these genes was conducted in pelvic tumors of 85 patients that included 49 epithelial ovarian carcinoma cases. The 85 pelvic tumors contained 5 tumors with BRCA1 mutations, 33 with TP53 mutations, and 1 with a KRAS2 mutation. Each of the BRCA1 and KRAS2 mutations, and 25 of the TP53 mutations, were in ovarian carcinomas. Four of the BRCA1 mutations were germline and 1 was somatic. The 4 patients with germline BRCA1 mutations had an early age of disease onset (33-48 years) relative to the mean age of onset (58 years) of all 49 ovarian carcinoma patients, and 3 of these 4 patients had a family history of ovarian or breast cancer. None of the 4 tumors with germline BRCA1 mutations had a KRAS2 mutation or a TP53 mutation, despite a 51% frequency of TP53 mutations in the 49 ovarian carcinomas. Three of the 4 tumors with germline BRCA1 mutations retained a wild-type BRCA1 allele. The tumor with the somatic BRCA1 mutation contained a TP53 mutation and had no evidence for wild-type BRCA1 and TP53 alleles. These data suggest that both BRCA1 and TP53 were inactivated in 1 of 49 ovarian carcinomas. Moreover, mutational inactivation of both BRCA1 and TP53 did not occur in 4 tumors with a germline BRCA1 mutation. It has been proposed that tumorigenesis in cells with a heterozygous BRCA1 mutation requires inactivation of the wild-type BRCA1 and TP53 alleles, which results in genomic instability and acquisition of mutations in protooncogenes. Clearly, mutational inactivation of TP53 and the wild-type BRCA1 allele in ovarian tumors with a heterozygous, germline BRCA1 mutation is not an absolute requirement for tumor formation. It is possible that these alleles may be inactivated by nonmutational mechanisms or that other tumor formation pathways exist.
Adult↗
Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma.
BACKGROUND AND OBJECTIVE: The clinical picture, response to therapy, and prognosis of women with diffuse malignant peritoneal mesotheliomas (DMPM) are ill defined. The purpose of this study is to report on the clinical picture, response to therapy, and survival of women with DMPM. METHODS: The study is a retrospective review of 15 women with the confirmed pathologic diagnosis of DMPM treated between 1964 and 1996. Survival curves were constructed according to the Kaplan-Meier method. The effect of different factors on survival was studied using the log-rank test. Two-tailed P values < 0.05 were considered significant. RESULTS: Clinical features included abdominal distension (11/15, 73%), abdominal pain (6/15, 40%), ascites (9/15, 60%), abdominal or pelvic masses (14/15, 93%), elevated CA-125 (4/4, 100%), thrombocytosis (4/ 15, 27%), and thrombo-embolic manifestations (3/15, 20%). The response rate to all first-line chemotherapy regimens was 30%. The response rate to paclitaxel/cisplatin was 66.7% and the toxicity was tolerable. The median survival of all patients was 12.5 months. Patients who underwent cytoreductive surgery survived longer than those who underwent biopsy only (median survival 13.5 vs. 6.0 months, P = 0.24). Patients who received chemotherapy survived significantly longer than those who did not receive chemotherapy (29.0 vs. 1.0 months, P = 0.03). Patients who responded to first-line chemotherapy survived significantly longer than those who did not respond (P = 0.04). CONCLUSIONS: Cytoreductive surgery and chemotherapy, especially with paclitaxel and cisplatin, might be of benefit in women with DMPM.
Abdominal Pain↗
Laparoscopic management of women with a family history of ovarian cancer.
BACKGROUND AND OBJECTIVE: The safety of laparoscopic surgery in women with a family history of ovarian cancer predicted to have benign disease has not been established. The objective of this study was to evaluate the feasibility and complications of operative laparoscopy and to describe the pathologic findings in this patient population. METHODS: Sixty-two consecutive women with a family history of ovarian cancer who elected prophylactic oophorectomy or had predicted benign adnexal disease were offered laparoscopic surgery. Patient characteristics, details of laparoscopic surgery, operative and postoperative complications, and histopathologic findings were recorded. RESULTS: Laparoscopy was converted to laparotomy in 2 patients (3.2%); 1 patient (1.6%) had an operative vascular complication, and 1 patient (1.6%) had postoperative bleeding. Median (range) estimated blood loss, operative time, and hospital stay were 50 ml (50-1,500), 120 min (60-290), and 1 day (0-9), respectively. Histopathologic findings included normal ovaries (n = 20), corpus luteum cyst (n = 16), follicular cyst (n = 8), endometriotic cyst (n = 7), serous cystadenoma (n = 5), epithelial hyperplasia (n = 4), dermoid cyst (n = 1), and fibrothecoma (n = 1). CONCLUSIONS: Laparoscopic surgery is feasible and safe in women with a family history of ovarian cancer predicted to have benign disease and is associated with low blood loss and short hospital stay. Most ovaries removed are either normal or have benign disease.
Adult↗
Role of salvage chemotherapy with topotecan and cisplatin in patients with paclitaxel- and platinum-resistant recurrent ovarian or primary peritoneal cancer: a phase II pilot study.
BACKGROUND AND OBJECTIVES: We assessed the role of salvage chemotherapy with topotecan and cisplatin in patients with platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer, based on the reported in vivo and in vitro synergism between these two drugs. METHODS: Twenty patients were entered in this phase II trial from November 1997 to November 1998. They received cisplatin at 50 mg/m(2) on day 1 with topotecan at 0.6 mg/m(2) from day 1 to 5 every 28 days. In 70% of patients (14/20), this combination represented at least a third line of therapy. RESULTS: A clinical response rate of 13.3% (two partial responses) was obtained in the 15 patients with evaluable disease. Sixty percent of patients (9/15) had stable disease and 26.7% (4/15) had progression. The median progression-free interval and survival were 4 months and 7 months, respectively. The 20 patients evaluable for toxicity received a mean of four chemotherapy cycles. Dose reductions were required in 45% of patients despite the administration of growth factors. The major dose-limiting toxicity was a 50% occurrence (10/20) of grade 4 thrombocytopenia and 30% (6/20) grade 4 neutropenia. There was one septic death. CONCLUSIONS: These data suggest that combination therapy with topotecan and cisplatin has minimal activity in platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer at the doses utilized in this trial.
Adult↗
Characterization of human ovarian carcinomas in a SCID mouse model.
This study characterizes a murine model which is promising for the study of the growth and natural history of ovarian cancer and for testing of new therapies for its treatment. Intact portions of 20 different human ovarian cancer surgical specimens were implanted in over 60 severe combined immunodeficient (SCID) mice using techniques previously developed in our laboratory. Growth of xenografts was evaluated by gross examination and histopathologic analysis. Confirmation of the human origin of the tumor outgrowth was obtained using in situ hybridization analysis. By histological evaluation, all of the patients' tumors showed evidence of invasive growth in at least 1 of the mice implanted with portions of each surgical specimen and these tumors remained morphologically similar to the parent tumors for a long period of time. Furthermore, 65% (13/20) of the xenografts grew rapidly enough (i.e., reached a diameter of 1-2 cm within 2-6 months) to allow passage to subsequent SCID mice. Among the passaged xenografts, 3 eventually developed metastases in a distribution pattern similar to that of naturally occurring ovarian cancer and 2 developed ascites without evidence of further metastatic spread. Upon evaluation of sera from tumor-bearing mice, human antibodies presumably derived from immunoglobulin-secreting cells present in the original tumor specimen were identified. In support of this, human B cells and plasma cells could be seen within the tumor xenograft for more than 6 months following implantation. In summary, transplantation of surgical specimens from ovarian cancer patients into SCID mice results in an attractive model for the study of the natural history of ovarian cancer and may also be useful for analysis or new experimental therapeutic approaches for the treatment of this disease.
Animals↗