Phase II multicenter open-label study of karenitecin in previously treated epithelial ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study.

The topoisomerase I agents are established as a therapy in recurrent ovarian cancer. Karenitecin, an analog of topotecan with solubility and pharmacologic advantages, was tested in a phase II trial in previously treated patients with recurrent or persistent ovarian cancer. The drug was administered intravenously over 1 h at a dose of 1.0 mg/m(2) daily for 5 days every 21 days. Patients were treated until disease progression, intolerable toxicity, or voluntary withdrawal. Response was evaluated according to modified RECIST criteria. Twenty-seven patients were entered into the study. One patient was inevaluable for not receiving any treatment. Of the 26 evaluable patients, there were two partial responses and one complete response for a total response rate of 12%. This response rate was insufficient to justify accrual to the second stage. The most common grade 3 or 4 toxicities were neutropenia (19%) and gastrointestinal (15%). Karenitecin is a well-tolerated topoisomerase compound but has minimal activity in extensively pretreated ovarian cancer with the dose-schedule employed.

Loss of heterozygosity and mutational analysis of the PTEN/MMAC1 gene in synchronous endometrial and ovarian carcinomas.

Mutations of the human putative protein tyrosine phosphatase (PTEN/MMAC1) gene at chromosome 10q23 have been found frequently in type I endometrial carcinomas. Endometrioid adenocarcinoma is the most frequent histology seen in patients with clinically determined synchronous endometrial and ovarian carcinomas. We report a high incidence of PTEN/MMAC1 mutations and 10q23 loss of heterozygosity (LOH) in patients with synchronous endometrial and ovarian carcinomas. Paraffin-embedded precision microdissected tumors were analyzed for 10 matched synchronous endometrial and ovarian cancers and 11 matched control metastatic endometrial cancers. Single-stranded conformation polymorphism analysis was used to screen for mutations in all tumors and corresponding normal lymphocyte DNA. LOH was determined using a panel of four microsatellite markers within the PTEN/MMAC1 locus. PTEN/MMAC1 mutations were found in 43% (9 of 21) of the endometrial cancers studied, similarly represented in the clinically synchronous group (5 of 10 or 50%) and the advanced metastatic group (4 of 11; 36%; P = 0.53). In two of the five cases of clinically synchronous cancers, identical or progressive PTEN mutations were found in both the endometrial and ovarian cancers, suggesting that the ovarian tumor is a metastasis from the endometrial primary. PTEN/MMAC1 mutations in the advanced endometrial cancers were similar in the corresponding metastases. In one case, the mutation was seen in only one of two metastatic lymph nodes. The LOH analysis demonstrated 55% LOH in at least one PTEN/MMAC1 marker. These findings suggest that the putative tumor suppressor gene PTEN/MMAC1 may be a viable molecular marker to differentiate synchronous versus metastatic disease in a subset of clinically synchronous endometrial and ovarian carcinomas.

Endometrial carcinoma: the relevance of cervical cytology.

In patients with endometrial carcinoma, preoperative identification of poor prognostic factors is helpful in planning therapy. Extended surgical staging, including pelvic and periaortic node dissection, is indicated in patients with deep myometrial invasion or high-grade tumor, or when other risk factors for extrauterine spread are present. In this study, cervical cytology was reviewed in 86 patients with endometrial carcinoma, all of whom underwent surgical staging, to correlate the cytologic results with surgical and pathologic findings. Cervical cytology was normal in 20 patients (23%), whereas suspicious or malignant endometrial cells were present in 23 and 43 cases (27 and 50%), respectively. Suspicious or malignant cervical cytology was associated with deeper myometrial invasion (P = .011), higher postoperative tumor grade (P = .006), positive peritoneal washings (P = .012), and more advanced stage by International Federation of Gynecology and Obstetrics criteria (P = .024). When compared with patients with normal cervical cytology, those who had malignant endometrial cells had over twice the risk of deep myometrial invasion (67 versus 30%), twice the risk of grade 2 or 3 tumor (60 versus 30%), and three times the risk of positive peritoneal washings (33 versus 10%). Seventy-four percent of patients with malignant cervical cytology were stage IC or more. In contrast, 70% of patients with normal cervical cytology were stage IA or IB. Patients with endometrial carcinoma who have malignant endometrial cells detected by cervical cytology are at increased risk of having a deeply invasive, high-grade, advanced-stage tumor, and therefore are more likely to require extended surgical staging.

Post-hysterectomy fallopian tube carcinoma presenting with a positive Papanicolaou smear.

BACKGROUND: Fallopian tube carcinoma is a rare gynecologic malignancy. The majority of women present with vaginal bleeding and have advanced disease. CASE: A 76-year-old woman presented 34 years after vaginal hysterectomy with a routine Papanicolaou smear showing adenocarcinoma. Rectovaginal examination was remarkable for thickening at the vaginal apex. Colposcopy found a pinpoint opening in this area, and a cytobrush passed through the opening confirmed adenocarcinoma. Pelvic ultrasound, computed tomography scan, and CA 125 were normal. At laparotomy, the right fallopian tube and ovary were adherent to the vaginal apex. A grade II papillary serous adenocarcinoma confined to the tube was discovered. CONCLUSION: According to a MEDLINE search, this is the third report detailing a unique presentation of fallopian tube carcinoma after hysterectomy and possibly the first detected with positive Papanicolaou cytology.

Colposcopic biopsies versus loop electrosurgical excision procedure cone histology in human immunodeficiency virus-positive women.

OBJECTIVE: To compare the discrepancy between colposcopically directed punch biopsy and excisional cone biopsy in human immunodeficiency-positive (HIV+) vs. HIV-negative (HIV-) women. STUDY DESIGN: We performed a case-control analysis of women treated with excisional cone biopsy after an abnormal colposcopic punch biopsy. Punch and cone biopsy histology were compared in 29 HIV+ (mean CD4 = 251 cells/mm3, 10 with the acquired immunodeficiency syndrome) and 31 HIV- women. Only patients with no prior treatment for cervical dysplasia, satisfactory colposcopy and cervical cytologic smears concordant with colposcopic biopsies were included. RESULTS: Disagreement between punch biopsy and cone histology was evident in 41% (12/29) of HIV+ patients and 48% (15/31) of seronegative women (chi 2, P = .78). The cone specimen had a higher grade lesion than the punch biopsy in 38% (11/29) of HIV+ patients and 32% (10/31) of seronegative women (P = .65). Overall, patients with HPV, cervical intraepithelial neoplasia (CIN) I or II on punch biopsy had CIN III on 30% of cone biopsies (5/23 HIV+ vs. 9/23 HIV-women, P = .2). In HIV+ women with HPV or CIN I on punch biopsy, 50% (9/18, 95% confidence interval 26-74%) had CIN II or III on the excisional cone vs. 18% (2/11) HIV-patients (Fisher's test, P = .13). However, in HIV+ patients with CIN II or III on cone biopsy, 47% (9/19) had only CIN I or human papillomavirus on punch biopsy as compared to 9% (2/22) HIV-patients (chi 2, P = .01). CONCLUSION: Colposcopically directed punch biopsies are poor predictors of cone histology in both HIV+ and HIV-patients. Based on confidence intervals, at least 26% and as many as 74% of HIV+ women with CIN I on punch biopsy may have a significantly worse lesion on cone biopsy despite satisfactory colposcopy. Though CIN I may be observed in immunocompetent women, due to the likelihood of a more advanced lesion, observation may not be justified in HIV+ women.

Paclitaxel-associated hypersensitivity reaction despite high-dose steroids and prolonged infusions.

The development of paclitaxel-containing chemotherapeutic regimens has been hindered by the frequent occurrence of allergic-type reactions to the drug or its diluent. Fortunately, current pretreatment regimens are associated with a reduced risk of major hypersensitivity reactions. However, there is still a group of patients that may experience these reactions from Taxol despite the use of prechemotherapy steroids and antihistamines. In a recent report, patients with prior reactions to Taxol were successfully retreated utilizing 24 hr of high-dose steroids and a very prolonged infusion regimen. We now report on two patients with major hypersensitivity reactions despite the use of this regimen. We conclude that not all Taxol-associated hypersensitivity reactions are preventable with current drug regimens. In addition, there is little evidence to support continued or exclusive use of the suggested rechallenge premedication schedule or the prolonged infusion rate.

Adrenal function following high-dose steroids in ovarian cancer patients.

PURPOSE: Steroid doses similar to those used to prevent paclitaxel-associated hypersensitivity reactions and cisplatin-induced nausea have been associated with hypothalamic-pituitary-adrenal (HPA) axis suppression. We assessed HPA function in patients receiving high-dose steroids as part of their chemotherapy regimen for epithelial ovarian cancer. PATIENTS AND METHODS: From January to July 1994, a cross-sectional study of HPA function was performed on patients receiving dexamethasone (DEX) as part of their paclitaxel and cisplatin chemotherapy regimen (n = 9). Patients received 20 mg of DEX orally, 6 and 12 hr prior to paclitaxel (135 mg/m2) and 10-20 mg intravenously before cisplatin (50-100 mg/m2). In addition, patients received approximately 12 mg/day of DEX orally for 4 days after their chemotherapy as an antiemetic. HPA integrity was evaluated by the administration of synthetic adrenocorticotropic hormone (ACTH). The ACTH stimulation test was performed 11-19 days after the completion of the course of DEX. Patients had fasting baseline cortisol levels drawn at approximately 0800 followed by a 25-unit intravenous injection of ACTH. Post-ACTH cortisol levels were repeated at 30 and 60 min. RESULTS: The mean (+/- SEM) fasting baseline level of cortisol was 12.4 +/- 2.3 micrograms/dl (normal, 7-23 micrograms/dl). At 30 min following ACTH administration, the mean cortisol level rose 17.1 micrograms to 29.5 +/- 1.8 micrograms/dl; at 60 min it rose 21.4 micrograms to 33.8 +/- 2.5 micrograms/dl [P < 0.001] (normal increase 9-39 micrograms). All patients demonstrated a sufficient increase in their plasma cortisol after ACTH stimulation, indicating normal HPA function on the days tested. However, there was a significant trend toward lower increases in plasma cortisol at 30 and 60 min as the interval from ACTH stimulation testing to the DEX regimen decreased (r = 0.986; P < 0.0001). The chemotherapy cycle number had no impact on cortisol response in the multivariate analysis. Based on multiple linear regression, HPA function may be suppressed for approximately 8 days, but up to 14 days from the start of this DEX regimen. CONCLUSION: Current steroid regimens prescribed with chemotherapy transiently decrease HPA function, but do not appear to inhibit the HPA axis long term. HPA function may be suppressed for approximately 8 days from the commencement of chemotherapy cycles involving DEX. Patients presenting within the first 8 days of a chemotherapy cycle using steroids with symptoms attributable to HPA suppression may benefit from HPA axis testing.

Interstitial pregnancy complicated by rectal bleeding.

An interstitial pregnancy complicated by rectal bleeding is described. Despite modern imaging modalities, confounding features made preoperative diagnosis difficult. The pregnancy ruptured into the ileum. Ossified fetal skull bones and degenerated placental tissue were the only remains from the pregnancy.

Recurrent mild abruptio placentae occurring immediately after repeated electroconvulsive therapy in pregnancy.

We present a case in which electroconvulsive therapy was performed repeatedly in pregnancy because of severe depression with psychotic features and failure of chemical treatment. Each electroconvulsive treatment was immediately followed by uterine contractions and active uterine bleeding, possibly representing recurrent abruptio placentae occurring in association with the treatment. Transient acute episodes of maternal hypertension between 180/90 and 190/100 mm Hg, documented within minutes after application of each electroconvulsive treatment, might explain the abruptio placentae manifested by active uterine bleeding and uterine hyperstimulation.

Ovarian cancer: comparison of observer performance for four methods of interpreting CT scans.

PURPOSE: To assess the effects of four interpretative methods on observers' mean sensitivity and specificity by using computed tomography (CT) of ovarian carcinoma as a model. MATERIALS AND METHODS: CT scans in 98 patients with ovarian carcinoma and 49 women who were disease free were retrospectively reviewed by four experienced blinded radiologists to compare single-observer reading, single-observer reading with an anatomic checklist, paired-observer reading (simultaneous double reading), and replicated reading (combination of two independent readings). Confidence level scoring was used to identify three possible disease forms in each patient: extranodal tumor, lymphadenopathy, and ascites. Patient conditions were then categorized as abnormal or normal. RESULTS: There were no significant improvements in sensitivity or specificity for classification of patient conditions as abnormal or normal when comparing single-observer interpretation with single-observer interpretation with a checklist or paired-observer interpretation. Although there was no significant improvement in the mean sensitivity (93% vs 94%) by using the replicated reading method, there was a statistically significant improvement in mean specificity (85% vs 79%) for the replicated readings compared with single-observer interpretations (P < .05). CONCLUSION: Diagnostic aids such as checklists and paired simultaneous readings did not lead to an improved mean observer performance for experienced readers. However, an increase in the mean specificity occurred with replicated readings.