Preoperative quality of life and surgical outcomes in gynecologic oncology patients: a new predictor of operative risk?

OBJECTIVE: Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients. METHODS: We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores. RESULTS: Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16). CONCLUSION: Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk.

Spectrum of mutation and frequency of allelic deletion of the p53 gene in ovarian cancer.

BACKGROUND: The p53 gene encodes a nuclear phosphoprotein present in low levels in normal human cells. The wild-type form of this protein functions to restrain inappropriate cellular proliferation. Approximately one half of human epithelial ovarian cancers have mutations in the p53 gene and overexpress the mutant protein product. Deletion of one allele of the p53 gene also frequently occurs in these cancers. PURPOSE: We sought to define the spectrum of mutations in the p53 gene in epithelial ovarian cancer with respect to both the specific codons involved and the type of mutations observed. We also examined the frequency of allelic deletion of the p53 gene in cancers containing p53 gene mutations. METHODS: Tissue samples from the epithelial ovarian cancers of 62 patients were obtained during initial laparotomy. Histologic examination was done to ensure that the experimental samples used in this study contained more than 75% cancer cells. Total RNA was extracted from these samples and separately from matched control noncancerous regions of the surgical specimen or white blood cells. The purified RNAs were reverse transcribed to generate cDNA copies of exons 4-10 of the p53 gene. Two rounds of polymerase chain reaction (PCR) were conducted to produce enough template for DNA sequence analysis of the regions of interest within the p53 gene. Dideoxy sequencing of at least two independent productions of each amplified DNA template was done to confirm the validity of the mutations found. Allelic deletions were identified by PCR and gel electrophoretic techniques to examine three polymorphisms within the p53 gene in cancer-normal DNA pairs. RESULTS: We identified 45 mutations in exons 5-8 of the p53 gene, where mutations frequently have been found in other cancer types. An additional mutation was identified in exon 4. Overall, 72% of the mutations were transitions, 24% transversions, and 4% microdeletions. Allelic deletion of the other p53 allele was seen in 67% of ovarian cancers in which a p53 mutation was present. Germ-line p53 mutations were not found in any patients whose cancers had p53 mutations. CONCLUSIONS AND IMPLICATIONS: Like p53 mutations in other types of human cancers, those in epithelial ovarian cancers are diverse and occur frequently in exons 5-8. The predominance of transition mutations suggests that p53 mutations in ovarian cancer arise because of spontaneous errors in DNA synthesis and repair rather than the direct interaction of carcinogens with DNA. These molecular data are consistent with data from epidemiologic studies that have failed to demonstrate a convincing relationship between exposure to environmental carcinogens and the development of ovarian cancer.

Elevation of multiple serum markers in patients with stage I ovarian cancer.

BACKGROUND: The high overall mortality from ovarian cancer (> 60%) relates, in part, to delays in diagnosis. When ovarian cancer is detected in stage I (International Federation of Gynecology and Obstetrics staging), up to 90% of patients can be cured. Transvaginal sonography can detect early-stage disease with great sensitivity, but it is expensive and lacks specificity. Although serum marker assays could provide a less expensive and more convenient initial screening test, the sensitivity of assays varies. Measurement of serum CA 125 in conjunction with ultrasound screening as a second-line test confers high specificity but detects only about one half of early stage ovarian carcinomas. PURPOSE: The purpose of this retrospective study was to determine whether assays of multiple serum markers would improve sensitivity by detecting a higher percentage of stage I ovarian cancers than the CA 125 assay alone. METHODS: Using immunoradiometric assays, we measured preoperative serum levels of CA 125 tumor-associated antigen, macrophage colony-stimulating factor (M-CSF), and OVX1 in 46 patients with stage I ovarian cancer of different histologies and 237 patients with benign pelvic masses. We also assayed sera from 204 apparently healthy women who had participated in a screening trial and remained free from cancer at 1 year of followup. All specimens were obtained from cryopreserved aliquots. Marker levels were considered to be elevated when levels of CA 125 were greater than 30 U/mL, M-CSF levels were greater than 3.1 ng/mL, or OVX1 levels were greater than 12.1 U/mL. RESULTS: At least one of the serum markers was elevated in 98% of patients with stage I ovarian cancer; CA 125 levels were elevated in 67%. By the same criteria, 11% of healthy individuals and 51% of patients with benign pelvic masses had at least one elevated marker value. Thus, the sensitivity of the combination of assays for the three serum markers was significantly greater than the sensitivity of the CA 125 assay (P < .0005) and specificity was moderate. CONCLUSION: A panel of these three tumor markers can identify early-stage ovarian cancer with extremely high sensitivity and moderate specificity. IMPLICATIONS: Elevation of one or more serum markers should be evaluated further as an indication for transvaginal sonography in apparently healthy women. Such a strategy might substantially reduce the expense and improve the specificity of screening compared to the use of ultrasound alone. Prospective studies with a large cohort of patients at high risk for ovarian cancer will be required to confirm these findings.

Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors.

A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. In all cases H222 Sp gamma localized in the nucleus of target cells. A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues. The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively. HSCORE correlated with tumor grade for breast and endometrial carcinoma. Immunohistochemical evaluation showed no specific staining in melanomas. The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied.

Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody.

Immunohistochemical localization of estrogen receptor (ER) using specific monoclonal anti-human estrogen receptor antibody, H222, with an immunoperoxidase technique was performed on fresh frozen tissue derived from 100 endometrial adenocarcinomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining. In all cases, H222 localized in the nucleus of target cells. A significant quantitative relationship was shown between histological score (H-Score) and the biochemical analysis of ER content in tissue homogenates (r = 0.65, P = 0.00001). Excellent sensitivity (92%) and specificity (93%) were observed for the comparison of H-Score to the biochemical assay. Significant ER localization was present in stromal and myometrial elements, component H-Score of which correlated weakly with component H-Scores of malignant epithelial elements. Divergent receptor localization in stromal and myometrial versus malignant epithelial elements suggests that biochemical assays of endometrial carcinoma specimens may not reflect cancer-relevant receptor content. The data presented here suggest that the immunoassay of ER using H222 monoclonal antibody provides additional histochemical information to complement conventional analyses of endometrial adenocarcinomas.

Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential.

Immunohistochemical localization of CA 125 using murine monoclonal antibody OC 125 was performed on fresh frozen tissue from 44 endometrial adenocarcinomas and 26 benign endometria. Immunohistochemical evaluation incorporated both intensity and distribution of staining (CA 125 HSCORE). Thirty-seven cancers (84%) and 23 benign endometria (88%) expressed immunohistochemically detectable CA 125. Staining was confined to epithelial cells and was present both on the cell membrane and in the cytoplasm. Among the 44 endometrial cancers, CA 125 HSCORE did not correlate with histological grade, depth of myometrial invasion or estrogen/progesterone receptor levels. Following surgical staging, 13 patients (30%) were found to have extrauterine metastatic disease. The median CA 125 HSCORE of patients with metastatic disease (2.25) was significantly higher than that of patients with disease confined to the uterus (0.6) (P less than 0.001). In addition, high CA 125 HSCORE also correlated with the presence of lymph node metastasis (P less than 0.001). The results of this study suggest that high CA 125 expression by endometrial adenocarcinomas is associated with increased metastatic potential.

Coexpression of different antigenic markers on moieties that bear CA 125 determinants.

CA 125 has been extensively evaluated as a serum marker for monitoring patients with epithelial ovarian carcinoma. Recently, consideration has been given to the use of CA 125 as one component in a strategy for early detection of this disease. A number of benign conditions can, however, increase CA 125 in serum, limiting the utility of a single antigen determination for identifying ovarian cancer patients. Coexpression of different epitopes on the high molecular weight complexes that express CA 125 determinants might provide a more specific test for malignant disease, provided that adequate sensitivity were maintained. To determine how frequently determinants are coexpressed, macromolecular moieties containing CA 125 determinants have been isolated from ascites fluid of ovarian cancer patients by immunoaffinity chromatography. CA 125+ moieties have been probed on Western transfers with several murine monoclonal antibodies that recognize distinct tumor-associated epitopes. Marked heterogeneity was observed between patients with regard to antigenic determinants that could be coexpressed with CA 125. A fraction of ascites fluids from different ovarian cancer patients contained moieties which bound to OC 125 on a solid phase immmunoadsorbent and which also bound 125I-labeled monoclonal antibodies NS 19-9, B72.3, DF3, or the novel murine monoclonal antibody OC 3632 in a double determinant immunoradiometric assay. Serum samples were evaluated from patients with ovarian cancer and from apparently healthy individuals. Coexpression of TAG 72 and CA 125 was observed most frequently. When the double determinant assay for coexpression of TAG 72 and CA 125 was compared to assays for the individual antigens, the assay for coexpression was substantially less sensitive than those for the individual markers.

Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer.

Previous studies have suggested that overexpression of HER-2/neu oncogene occurs in 15-40% of breast cancers and that overexpression is associated with poor prognosis. In the present report, we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of HER-2/neu to study expression of HER-2/neu in frozen sections of normal ovary and advanced epithelial ovarian cancer. The intensity of staining for HER-2neu was always moderate or less (0-2+) in normal ovarian epithelium. Among 73 ovarian cancers, 50 (68%) had staining similar to that for normal ovarian epithelium (0-2+) while 23 (32%) stained heavily (3+). Survival of the 23 patients with high HER-2/neu expression (median, 15.7 months) was significantly worse (P = 0.001) than that of the 50 patients (median, 32.8 months) with normal HER-2/neu expression. In addition, patients whose tumors had high HER-2/neu expression were significantly less likely to have a complete response to primary therapy (P less than 0.05) or have a negative second-look laparotomy when serum CA 125 levels were normal preoperatively (P less than 0.05). These findings suggest that HER-2/neu deserves further evaluation as a prognostic marker in epithelial ovarian cancer.

Overexpression and mutation of p53 in endometrial carcinoma.

Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P less than 0.001), and also was associated with nonendometrioid histology (P = 0.008), positive peritoneal cytology (P = 0.01), extrauterine metastases (P = 0.003), and negative progesterone receptor status (P = 0.04). To confirm the relationship between p53 overexpression and mutation, p53 mRNA from 8 cancers was reverse transcribed and amplified using the polymerase chain reaction. DNA sequencing revealed point mutations in each of the 5 cancers that overexpressed p53, whereas the wild-type sequence was found in 3 cancers that did not overexpress the protein. Each of the 5 mutations resulted in an amino acid substitution in a highly conserved region of the p53 gene where mutations have been found in other cancers. Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.

High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: Progestins represent the most widely used form of endocrine therapy in advanced or recurrent endometrial carcinoma. Based on encouraging response rates in breast cancer with high-dose megestrol acetate (MA) 800 mg/d, this phase II trial assessed response rates in patients with endometrial carcinoma treated with high-dose MA. PATIENTS AND METHODS: Sixty-three patients with recurrent or advanced endometrial carcinoma were entered into this Gynecologic Oncology Group (GOG) study. Patients had either failed to respond to or were considered incurable with local therapy and had not received prior cytotoxic or hormonal therapy. MA 800 mg/d was administered orally in divided doses. Standard GOG toxicity criteria were used. RESULTS: Of 63 patients entered, 58 were assessable for toxicity and 54 for response. Of 13 responders (24%), six (11%) had a complete and seven (13%) a partial response. Four of the responses lasted greater than 18 months. Twelve patients (22%) had stable disease. The response rate of patients with grade 1 or 2 lesions (11 of 30, 37%) was significantly higher (P = .02) than that of patients with more poorly differentiated tumors (two of 24, 8%). There was no difference in response rates comparing advanced versus recurrent disease, cell type, including papillary serous lesions, site of disease, prior radiation, age, or weight. The median progression-free survival (PFS) and overall survival intervals were 2.5 and 7.6 months, respectively. Grade 3 weight gain (> 20%) was seen in three patients and grade 3/4 hyperglycemia in three. Three deaths secondary to cardiovascular events were possibly related to therapy; diabetes was also a contributing factor in all three cases. CONCLUSION: High-dose MA is active in endometrial carcinoma, but appears to have no advantage over lower-dose progestins.

Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

PURPOSE: In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. PATIENTS AND METHODS: Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. RESULTS: Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). CONCLUSION: Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

OVX1 radioimmunoassay complements CA-125 for predicting the presence of residual ovarian carcinoma at second-look surgical surveillance procedures.

PURPOSE: At second-look surgical surveillance procedures, normal CA-125 levels can be associated with persistent disease in 50% to 60% of patients. A novel radioimmunoassay (RIA) has been evaluated for the ability to identify patients with persistent disease who have normal levels of CA-125. MATERIALS AND METHODS: The OVX1 double-determinant assay used a murine monoclonal antibody to detect an epitope on a high-molecular weight mucin-like glycoprotein. RESULTS: Apparently healthy individuals had serum OVX1 levels of 2.23 +/- 2.48 U/mL (mean +/- SD). Elevated serum OVX1 levels (> 7.2 U/mL) were found in 5% of 184 normal individuals and in 70% of 93 epithelial ovarian cancer patients with clinically evident disease. Among sera from these ovarian cancer patients, OVX1 was elevated in 68% of 76 samples with CA-125 levels more than 35 U/mL and in 76% of 17 samples with CA-125 levels less than 35 U/mL. In serum samples obtained at the time of positive second-look laparotomy, 59% of 41 patients with CA-125 levels less than 35 U/mL had elevated OVX1 antigen levels, whereas 41% of 22 patients with CA-125 levels more than 35 U/mL had elevated serum OVX1 levels. In patients with negative second-look laparotomies, false-positive results were eliminated by increasing the threshold of OVX1 to 10.5 U/mL. At this level, 32% of 41 patients with positive second-look operations had an elevated OVX1 level, despite a normal CA-125 level. When used in combination, CA-125 (> 35 U/mL) and OVX1 (> 10.5 U/mL) detected persistent disease in 56% of 63 patients with positive surveillance procedures, compared with 35% when CA-125 was used alone (P < .05). CONCLUSION: An elevated OVX1 level can alert oncologists to the possibility that ovarian cancer has persisted, despite the return of CA-125 to a normal range.

Improved palliation of cerebral metastases in epithelial ovarian cancer using a combined modality approach including radiation therapy, chemotherapy, and surgery.

PURPOSE: Recent reports suggest an increasing incidence of CNS metastases in patients with ovarian cancer. We reviewed our experience in the management of brain metastases from ovarian carcinoma and merged our results with those of several other series reported in the literature to determine prognostic factors and the role of chemotherapy, radiation therapy, and surgery. PATIENTS AND METHODS: From 1977 to 1990, 15 of 795 patients who were treated for epithelial ovarian cancer at Duke University developed brain metastases. Fourteen of the patients were treated for their brain metastases; this included radiation therapy (RT; four), surgery and RT (one), RT and systemic chemotherapy (six), and all three treatment modalities (three). A meta-analysis was performed that combined the data from the current series with those of several recent clinical series that reviewed patients with brain metastases from ovarian carcinoma (67 patients total) to elucidate the impact of treatment and extent of disease on survival. RESULTS: In the current series, median survival (MS) after the diagnosis of brain metastases was 9 months. For the combined series, MS was 5 months. Thirteen patients who were treated with whole-brain RT and systemic chemotherapy (MS, 7 months), 10 patients who were treated with RT and surgery (MS, 10 months), and nine patients who were treated with all three modalities (MS, 16.5 months) had significantly longer survival than 19 patients who were treated with RT alone (MS, 3 months) (P = .05, P = .01, and P < .001, respectively). In a multivariate analysis, the only variable that provided prognostic information was treatment, namely the addition of systemic chemotherapy or surgery to RT for the treatment of brain metastases. CONCLUSION: Multimodal treatment of patients with brain metastases from ovarian cancer can result in significant palliation.

Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group.

PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.

Transperineal templates for brachytherapy treatment of pelvic malignancies--a comparison of standard and customized templates.

A technique is described for the design and construction of customized templates for transperineal implants and interstitial hyperthermia of pelvic malignancies. The design of the template and the distribution of the transperineal Iridium-192 seed ribbons are based on prior optimization of the dose distribution. The target volume is defined by means of pelvic examination and pertinent radiographic studies including a CT. The pelvic CT study is obtained with a plastic obturator in the rectum or the vagina. The obturator is used as a reference structure for aligning the target contour from each image plane to form a composite 2-dimensional contour of maximum tumor extent in a plane perpendicular to the obturator. Dose distributions are calculated to determine the placement of the Iridium-192 seed ribbons in the template. Laparoscopic guidance is used for actual placement of brachytherapy source needles together with a rectal or vaginal obturator to stabilize the template and to assure that the needle placement conforms with the planned geometry. Dose distributions for 10 consecutive patients calculated for customized templates as well as for five commercially available standard templates show that the customized templates are superior to standard templates in that the planned dose distribution matches the configuration of the target volume and is more uniform than with standard templates.

Adjuvant therapy with intraperitoneal chromic phosphate (32P) in women with early ovarian carcinoma after comprehensive surgical staging.

From 1974-1990, 23 women with stage I and five with stage II epithelial ovarian carcinoma received intraperitoneal chromic phosphate (32P) as the only form of adjuvant therapy after complete debulking and comprehensive surgical staging laparotomy. Surgery consisted of total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, peritoneal washings for cytology, multiple biopsies of pelvic and abdominal peritoneum, and selective pelvic and para-aortic lymphadenectomy. Intraperitoneal 32P therapy was administered a median of 7 days after laparotomy. Significant toxicity was minimal; none of these patients required surgery for bowel obstruction. Overall 5-year survival was 90 and 100%, but disease-free survival was only 65% (95% confidence interval [CI] 36-86%) and 60% (95% CI 12-81%) for patients with stage I and II disease, respectively. Two patients developed intraperitoneal and six systemic relapses; all patients received cisplatin regimens after relapse. Univariate analysis of age, stage, histology, Ovarian Cancer Study/Gynecologic Oncology Group risk status, lesion size, and presence or absence of capsular adhesions revealed that only an age of 50 or more years had an adverse effect on disease-free survival (P less than .03). This study suggests that determination of early-stage disease and host-tumor biology may be the most important factors in determining the survival of women with early ovarian cancer defined by comprehensive surgical staging. Intraperitoneal 32P does not appear to be effective adjuvant therapy in these women.

Metastatic gestational trophoblastic disease: prognostic factors in previously untreated patients.

From 1966-1982, 138 previously untreated patients with metastatic malignant gestational trophoblastic disease received primary chemotherapy at the Southeastern Regional Trophoblastic Disease Center. Fifty-six (41%) had poor-prognosis metastatic gestational trophoblastic disease, and 51 (91%) of these patients were initially treated with multiagent chemotherapy. Sustained remissions were achieved in 128 patients (93%). Patients who had metastatic involvement of more than one anatomic site, disease duration of greater than four months, antecedent nonmolar pregnancy, or clinicopathologic diagnosis of choriocarcinoma were at significantly increased risk for failure to achieve sustained remission compared with patients who lacked these clinical features. Initial human chorionic gonadotropin level and site of metastasis had no significant effect on survival in these previously untreated patients. Patients with disease duration of greater than four months who had an antecedent nonmolar pregnancy were at significantly increased risk, with only 12 of 20 (60%) surviving, versus all of 85 patients with short duration of disease and antecedent molar pregnancy, and 32 (94%) of 34 patients with other combinations of these factors (P less than .001). Initial therapy for patients with metastatic gestational trophoblastic disease should be selected on the basis of prognostic factors that predict a high probability of failure with single-agent chemotherapy alone. Patients with prolonged duration of disease and nonmolar antecedent gestation are at high risk for failure using traditional forms of methotrexate and actinomycin D-based combination chemotherapy.

Preoperative coagulation testing on a gynecologic oncology service.

OBJECTIVE: To determine the prevalence and clinical significance of abnormalities of preoperative coagulation tests in gynecologic oncology patients. METHODS: Three hundred fifty-one patients presenting for inpatient surgical procedures on the gynecologic oncology service at Duke University Medical Center from January 1, 1990 to December 31, 1990, underwent preoperative coagulation testing. Twenty-nine patients had only prothrombin time (PT) and partial thromboplastin time (PTT) measured; the remaining 322 had preoperative measurement of PT, PTT, fibrinogen, and fragment D-dimer. Outcomes assessed were perioperative hemorrhage resulting in death or reoperation, postoperative hematomas, and need for intraoperative and postoperative transfusion. RESULTS: Twelve of 351 patients (3.4%) had abnormally elevated PT or PTT; six of these were attributable to risk factors unrelated to malignancy. One hundred fifty-six of 322 subjects (48.4%) had abnormal levels of fibrinogen, mostly elevations above 360 mg/dL, and 88 of 322 subjects (27.3%) had positive tests for D-dimer. Fifty-seven (17.7%) had both elevated fibrinogen and positive D-dimer. One hundred eighty-eight of 322 subjects had at least one abnormal test result. There were no perioperative deaths or reexplorations because of hemorrhage. There was one postoperative hematoma. The combination of an elevated fibrinogen and a positive D-dimer test was a significant predictor of perioperative transfusion in a logistic regression model incorporating stage, preoperative hematocrit, and age (odds ratio 1.96, 95% confidence interval 1.03-3.76). However, the attributable risk associated with this abnormality was only 7.7% in patients at highest risk of transfusion. CONCLUSION: Although abnormalities in coagulation are common in patients undergoing surgery for gynecologic malignancy, preoperative testing for occult coagulopathy provides little clinically useful information.

Hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy: correlation with histology and steroid receptor content.

Endometriosis is rare after hysterectomy and oophorectomy for conditions unrelated to endometriosis. We present a case of delayed development of aggressive, hormone-resistant endometriosis temporally remote from hysterectomy and oophorectomy performed for chronic pelvic inflammatory disease. Treatment with depo-medroxyprogesterone acetate resulted in continued growth of the retroperitoneal endometrioma and necessitated posterior exenteration because of the endometrioma's location. Estrogen and progesterone receptor levels were measured to clarify why this woman's endometriosis was resistant to hormone therapy. Despite administration of large amounts of depo-medroxyprogesterone acetate, the progesterone receptor content was elevated while the estrogen receptor content was undetectable. Why this patient developed this particular type of aggressive endometriosis is unclear, but the lack of down-regulation of progesterone receptors in response to high-dose progestin therapy may indicate an alteration in basic regulatory and cellular processes within the endometriotic implant.

Renal metastases of gestational trophoblastic disease: a report of eight cases.

Between 1968-1984, eight women with renal metastases of gestational trophoblastic disease were treated at the Southeastern Regional Trophoblastic Disease Center. Two (1.3%) of 154 patients referred for primary therapy and six (14%) of 42 patients referred for secondary therapy of metastatic gestational trophoblastic disease had renal metastases. All eight had coexistent pulmonary metastases. Four had central nervous system and other systemic metastases. All had high-risk metastatic gestational trophoblastic disease by assessment of individual risk factors and analysis of a prognostic index score. Three women with limited systemic tumor burden are alive after receiving multiagent chemotherapy and nephrectomy.