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PROBLEM Cervical cancer screening strategies in the United States include cotesting (human papillomavirus (HPV) with cytology), primary HPV with genotyping and reflex cytology, and cytology alone. An ongoing challenge is the appropriate triage of patients to colposcopy to those at highest risk. We investigated whether incorporation of p16INK4a immunodetection by enzyme-linked immunosorbent assay (ELISA) on fresh cervical samples obtained at the time of screening could improve appropriate referral to colposcopy. METHOD OF STUDY A derivation group comprised of cervical swabs collected from subjects with high-grade dysplasia or cancer (positive control) and from subjects with negative screening history (negative control). Samples collected from colposcopy were used to evaluate the existing screening strategies individually and with incorporation of p16INK4a ELISA. Histology was used as the gold standard. RESULTS Among 163 subjects recruited, 138 were included. In the derivation group, mean p16INK4a level was 2.86 ng/mL (n = 31) and 0.58 ng/mL (n = 20) among positive and negative controls respectively (p = 0.002) with an area under the receiver operator characteristic curve of 0.79 (p

BACKGROUND Uterine leiomyosarcoma (ULMS) is identified in 0.1% to 0.2% of hysterectomy specimens of presumed leiomyoma. To date, there is no preoperative technique that reliably differentiates ULMS from uterine leiomyoma. Increasing use of minimally invasive approaches for the management of leiomyomas may result in inadvertently morcellated ULMS with resultant intraperitoneal dissemination of tumor. The objective of this study was to assess the impact of intraperitoneal morcellation on the outcomes of patients with ULMS. METHODS In this retrospective cohort study, all patients with ULMS who attended the authors' institutions from 2007 to 2012 were reviewed. Demographics and outcomes were compared between those who underwent morcellation or total abdominal hysterectomy (TAH) as their first surgery for uterus-limited ULMS. RESULTS In total, 58 patients were identified, including 39 who underwent TAH and 19 who underwent intraperitoneal morcellation. Intraperitoneal morcellation was associated with a significantly increased risk of abdominal/pelvic recurrences (P = .001) and with significantly shorter median recurrence-free survival (10.8 months vs 39.6 months; P = .002). A multivariate adjusted model demonstrated a >3 times increased risk of recurrence associated with morcellation (hazard ratio, 3.18; 95% confidence interval, 1.5-6.8; P = .003). CONCLUSIONS Intraperitoneal morcellation of presumed leiomyoma worsens the outcomes of women with ULMS. Because there are no reliable preoperative techniques to distinguish ULMS from benign leiomyoma, all efforts to minimize intraperitoneal uterine morcellation should be considered. [See editorial on pages 000-000, this issue.] Cancer 2014;120:3154–3158. © 2014 American Cancer Society.

Purpose To identify a combination of sonographic features that best predicts ovarian malignancy. Methods Subjects included 249 women who had a transvaginal sonogram for a pelvic mass at Brigham and Women's Hospital between December 2005 and February 2010. Subjects underwent surgery for removal of the mass and pathologic diagnosis was available. Images were reviewed retrospectively by one sonologist blinded to diagnosis and clinical information. Twelve sonographic features were scored for each mass. The dataset was divided into training (n = 149) and testing (n = 100) sets. Within the training set, a stepwise logistic regression was used to weigh each variable and combination of features to identify those associated with malignancies. Using the results from the logistic regression analyses, we created a three-level risk stratification that was applied to the sonograms of subjects in the testing set to assess its ability to distinguish benign lesions from invasive and borderline cancers. Results High risk lesions included all masses with internal vascularity. In our testing set, this feature was present in 9 out of 12 (75%) invasive cancers, 1 out of 6 (16.7%) borderline lesions, and 9 out of 82 (11%) benign masses. The intermediate risk level included lesions with a thick wall or thick septa without internal blood flow. This combination of features identified one additional invasive cancer and 5 out of 6 (83.3%) borderline tumors. Masses with low risk features had a 2/49 (4.0%) incidence of malignancy. Conclusions In the absence of high or intermediate risk sonographic features, the risk of malignancy is low. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 41:269–274, 2013

Disseminated peritoneal leiomyomatosis (DPL) is a rare condition characterized by scattered smooth muscle nodules over the peritoneal surfaces. The pathogenesis of DPL remains unclear. Herein, we report a case of DPL occurring 7 years after laparoscopic supracervical hysterectomy with morcellation for uterine leiomyomata (UL). We analyzed both the original UL and the subsequent DPL by molecular cytogenetics to assess the role of chromosomal abnormalities in DPL pathobiology. Interestingly, all of the chromosomal aberrations detected in this case of DPL, including r(1)(p34.3q41), del(3)(q23q26.33), and t(12;14)(q14.3;q24.1), are characteristic chromosomal abnormalities detected in UL. Fluorescence in situ hybridization analysis of the initial UL confirmed an interstitial deletion spanning at least 3q24 and 3q25.1, suggesting that functional alteration of a potential gene in this chromosomal region may play a role in DPL development from UL. With the increasing rate of hysterectomy through laparoscopic approach to UL, the unique complications of laparoscopy with morcellation, especially seeding and proliferation of tumor cells over abdominal organs and peritoneum, are becoming more significant and may necessitate review of current surgical protocols to prevent future seeding of the pelvic region with tumor particles.

A client's emotional experiences and reactions to those experiences are influenced by his/her family of origin and direct or indirect interactions with various family members. Contextual therapists propose that a client's satisfaction with a relationship depends on the equity of his/her emotional interactions with family members. When relationships are inequitable, trust between individuals disintegrates. In order to reestablish trust in a relationship, a balance of interests must be restored. If not, imbalances may be passed down to future generations. A case of a woman with a family history of ovarian cancer is reviewed with the principles of contextual therapy in mind. In her family, several legacies have resulted in unbalanced relationships between family members that lead to difficulty in establishing trust within the genetic counseling session.

BACKGROUND Ifosfamide and paclitaxel are antineoplastic agents with broad activity and with different mechanisms of action. A Phase I trial was conducted to determine the maximum tolerated dose and associated toxicities of these agents when used in combination. METHODS Patients with refractory, incurable solid tumors were entered on a 5-step Phase I trial of ifosfamide, given in doses of 2-3 g/m2 intravenous (i.v.) bolus for 3 days with mesna support, and paclitaxel, given in doses of 135-190 g/m2 i.v. by continuous infusion over 24 hours. Paclitaxel was given after the first dose of ifosfamide on Day 1. RESULTS Twenty-three patients were treated, and the maximum tolerated dose was the highest planned dose level of the trial: ifosfamide, 3 g/m2/day i.v. for 3 days, and paclitaxel, 190 mg/m2 i.v. over 24 hours. Hematologic toxicity was not dose-limiting, and although neutropenia occurred, it was brief (median, 2-4 days) and resulted in hospitalization for neutropenia and fever in only 7 of 111 courses of therapy. For patients treated at the highest dose level, only 1 of 50 courses of therapy resulted in hospitalization for neutropenia and fever. Nonhematologic toxicity also was not severe and no significant neuropathy occurred. Although patients entered into the study were heavily pretreated, responses were observed, particularly in patients with breast or ovarian carcinoma. CONCLUSIONS Ifosfamide and paclitaxel can be administered safely in the doses used in this study and there are indications of significant antitumor effect. Further studies are necessary to explore the antineoplastic activity of this regimen, particularly for patients with breast and ovarian carcinoma. Cancer 1998;82:561-6. © 1998 American Cancer Society.

Conventional therapy for epithelial ovarian cancer, including aggressive cytoreductive surgery followed by combination chemotherapy regimens, has failed to reduce the number of deaths caused by this disease, which remains the most lethal of gynecologic malignancies. Monoclonal antibodies, which offer the promise of high selectivity for detection and therapy, may be targeted to tumor-associated antigens, growth factors, receptors, or oncogenes. They may be used alone as immunotherapeutic agents or conjugated to chemotherapeutic drugs, toxins, or radionuclides. Radioimmunoconjugates may also be used for preoperative or intraoperative tumor localization. The authors focused on the clinical utility, technical limitations, and potential of monoclonal antibodies in the detection and treatment of epithelial ovarian cancer with emphasis on radioimmunodetection and radioimmunotherapy.

Background Although there is a basis for linking pituitary or ovarian hormones with experimentally induced ovarian cancer, establishing their role in women is complicated because the usual case-control methods cannot be applied. In this study, hormonal levels in women with a family history of ovarian cancer (FOC) and who are at higher risk for the disease are compared with women without such a history. Methods The authors studied 106 unrelated women (FOC patients) with at least one primary or two second-degree relatives with ovarian cancer compared with 116 age- and residence-matched controls without a family history of ovarian cancer (FOC control subjects). All women were premenopausal, between the ages of 25 and 49 years, not currently using oral contraceptives, and had blood drawn during the early follicular phase for gonadotropins, estradiol (E2), and CA-125. Results Women with a family history of ovarian cancer and control subjects did not differ significantly in follicle stimulating hormone (FSH) levels, E2, or CA-125. Patients with a family history of ovarian cancer had significantly lower luteinizing hormone (LH) levels compared with control subjects and produced more E2 and FSH relative to their level of LH. The ratios of LH to E2 and LH to FSH were correlated with the enzymatic activity of galactose-1-phosphate uridyl transferase, which was shown previously to differ between FOC patients and control subjects. Conclusion Lower LH and higher E2 are reported in women with breast, endometrial, and ovarian cancer (before surgery). The authors speculate that these observations reflect greater LH binding and estradiol production in ovaries at risk for these cancers--the ovarian cortical hyperplasia postulated in older gynecologic literature as the precursor to estrogen dependent neoplasia.

BACKGROUND Galactose metabolism may be a risk factor for ovarian cancer based upon evidence that galactose causes ovarian failure and that ovarian cancer arises from premature ovarian failure. This study examines galactose-1-phosphate uridyl transferase (GALT) activity in women with a family history of ovarian cancer (FOC) to determine if low GALT activity occurs in women who are at risk for but in whom ovarian cancer has not yet developed. METHODS The authors studied 106 premenopausal women (FOC patients) with one primary or two second-degree relatives with ovarian cancer compared with 116 age matched control subjects without a family history of ovarian cancer (FOC controls). All women completed questionnaires and had blood drawn to measure GALT activity and genotype. RESULTS Mean erythrocyte GALT activity, in micromoles of hexose conversion per hour per gram of hemoglobin was 21.5 in FOC patients, significantly lower than the mean of 23.1 observed in FOC control subjects, (P = 0.001). FOC patients more frequently displayed the Duarte variant of galactosemia as detected by electrophoresis. In a subset of 87 patients and 113 control subjects for whom DNA was available, the allelelic frequency of the Duarte variant based upon molecular genetic detection of the N314D mutation that is associated with the Duarte variant was 15.5% among FOC cases compared with 7.5% among control subjects (P < 0.02). Galactose consumption did not differ between FOC patients and control subjects. CONCLUSION Galactose metabolism differs between women with and without a family history of ovarian cancer, suggesting that it may be a genetic risk factor for ovarian cancer, possibly mediated through oocyte toxicity from galactose.

Patients with Stage IV epithelial ovarian carcinoma are generally treated in the same manner as are patients with disease confined to the abdomen--cytoreductive surgery followed by combination chemotherapy. Between 1980 and 1990, 35 women with histologically or cytologically documented Stage IV ovarian carcinoma were treated in this fashion. Sixteen women (45%) underwent optimal initial cytoreductive surgery, defined as less than 2 cm maximum residual disease. Eleven of the 19 women undergoing suboptimal initial procedures underwent interval cytoreduction after two to four cycles of chemotherapy, with 7 achieving an optimal status after the interval procedure. Overall, 23 of 35 patients (66%) were successfully cytoreduced to less than 2 cm either initially or at an interval procedure. Thirty-one of the 35 patients received combination regimens containing platinum as part of their initial therapy. Kaplan-Meier survival curves demonstrated no significant difference in survival between those groups of women cytoreduced intervally or initially, or between those groups of women optimally cytoreduced at some point during their initial therapy and those who were not. The 5-year survival for the entire group was less than 5%, with no significantly prolonged survival seen in those patients undergoing successful cytoreduction.

Human anti-murine antibody (HAMA) responses were monitored in 23 patients with recurrent or persistent epithelial ovarian carcinoma undergoing single-dose intraperitoneal radioimmunotherapy (RIT) with the murine monoclonal antibody OC-125. Sera of patients receiving escalating doses of OC-125 F(ab')2 (10-70 mg) radiolabeled with 18 to 141 mCi of iodine-131 were assayed for HAMA by a protein A-based radioimmunoassay. Overall, 70% of patients (16/23) developed HAMA within 10 to 46 days (median = 29) postinfusion, with peak values (23 +/- 6 to 325 +/- 10 micrograms/ml) at 32 to 102 days (median = 38). HAMA was undetectable prior to infusion in all cases and persisted up to 76 weeks. Of patients receiving a dose of 123 mCi or less, 80% (16/20) developed HAMA, whereas in the 140-mCi group, none of the three patients had detectable levels. Two patients in the 140-mCi group demonstrated dose-limiting bone marrow toxicity (severe thrombocytopenia and neutropenia). It is concluded that a single intraperitoneal dose of monoclonal antibody leads to a high incidence of HAMA production. The results also suggest that the likelihood of HAMA formation in patients who either had undergone recent chemotherapy or had received the highest dose of the radioimmunoconjugate is reduced. These observations may be of significance in designing multiple-dose therapy trials as HAMA has been demonstrated to decrease antibody-to-tumor binding and may potentially increase renal, hepatic, and hematologic toxicity associated with radioimmunotherapy.