Search

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. [ABSTRACT FROM AUTHOR]

High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in suppressing the growth of 3D ovarian cancer spheroids or organoids as well as post-treatment cancer recovery through proliferation, migration, invasion, and colony formation assays when compared to the synthetic epigenetic compound Panobinostat with or without standard chemotherapy. Finally, given the regulatory role of the secretome in growth, metastasis, chemoresistance, and relapse of disease, we demonstrate that natural epigenetic compounds can regulate the secretion of protumorigenic growth factors, cytokines, extracellular matrix components, and immunoregulatory markers in human ovarian cancer specimens. While further studies are needed, our results suggest that these treatments could be considered in the future as adjuncts to standard chemotherapy, improving efficiency and patient outcomes.

Program evaluation can identify the successes and challenges of implementing clinical programs, which can inform future dissemination efforts. A cancer genetics improvement program, disseminated from the Lead Team's institution to five health systems (Participating Sites), was genetic counselor led, using virtual implementation facilitation to support Participating Sites' performance of quality improvement (QI) activities over several years. Program implementation and outcome evaluations were performed and included evaluation of program delivery and initial effects of the program on Participating Sites. A logic model guided evaluation of program implementation (inputs, activities, outputs, delivery/fidelity, and coverage/reach) and initial outcomes (short-term and intermediate outcomes). Data were collected from program documents and an Evaluation Survey of Participating Site team members (21 respondents), compared against the Lead Team's expectations of participation, and analyzed using descriptive statistics. All program inputs, outputs, and activities were available and delivered as expected across the five Participating Sites. The most frequently used activities and inputs were facilitation-associated meetings and meeting resources, which were rated as useful/helpful by the majority of respondents. Nearly all respondents noted improvement in short-term outcomes following participation: 82.4% reported increased awareness of clinical processes, 94.1% increased knowledge of QI methods, 100% reported increased perceived importance of QI, 94.1% increased perceived feasibility of QI, and 76.5% reported increased problem-solving skills and self-efficacy to use QI at their site. Intermediate outcomes (identifying barriers, developing interventions, improved teamwork, and capacity) were achieved following program participation as indicated by the results of the program document review and Evaluation Survey responses. Implementation challenges at Participating Sites included staffing constraints, difficulties obtaining buy-in and participation, and developing interventions over time. The multi-site improvement program was delivered and implemented with high levels of fidelity and resulted in improved short and intermediate outcomes. Future research will evaluate long-term, patient-level outcomes associated with site-specific QI interventions., (© 2022 National Society of Genetic Counselors.)

Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients' lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture.

The success of cannabinoids with chronic neuropathic pain and anxiety has been demonstrated in a multitude of studies. With the high availability of a non-intoxicating compound, cannabidiol (CBD), an over-the-counter medication, has generated heightened interest in its use in the field of oncology. This review focuses on the widespread therapeutic potential of CBD with regard to enhanced wound healing, lowered toxicity profiles of chemotherapeutics, and augmented antitumorigenic effects. The current literature is sparse with regard to determining the clinically relevant concentrations of CBD given the biphasic nature of the compound's response. Therefore, there is an imminent need for further dose-finding studies in order to determine the optimal dose of CBD for both intermittent and regular users. We address the potential influence of regular or occasional CBD usage on therapeutic outcomes in ovarian cancer patients. Additionally, as the development of chemoresistance in ovarian cancer results in treatment failure, the potential for CBD to augment the efficacy of conventional chemotherapeutic and epigenetic drugs is a topic of significant importance. Our review is focused on the widespread therapeutic potential of CBD and whether or not a synergistic role exists in combination with epigenetic and classic chemotherapy medications.

Background: This case report draws attention to the debated role of prophylactic oophorectomy in women undergoing definitive surgical resection of colon and rectal cancers. It can be challenging to discern the indications and appropriate patient population for this procedure based on the current literature. Potential benefits include treatment and prevention of metastatic disease, preventing development of primary ovarian cancer, and prolonging survival. Negative effects include an increase in operative time and potential morbidity, development of osteoporosis, the risk of cardiac events, and decreasing sexual function. Multiple patient factors such as age, menopausal status, patient preference, presence of hereditary conditions, exposure to radiation, site, and stage of disease should be considered., Case Presentation: We present a case in which a premenopausal 49-year-old female underwent a prophylactic bilateral salpingo-oophorectomy concurrently with a low anterior resection following neoadjuvant chemoradiation for clinical stage III rectal cancer. On pathologic examination, resection margins and all 14 lymph nodes harvested were negative for malignancy. Interestingly, she was found to have micrometastatic adenocarcinoma in the bilateral ovaries which had appeared grossly normal at the time of surgery., Conclusions: After consideration of the current literature, patient preference, and our clinical judgment, our patient ultimately had a therapeutic effect after undergoing prophylactic bilateral oophorectomy concurrently with a low anterior resection for rectal cancer. The addition of prophylactic oophorectomy in a select population, specifically women 50 years of age or younger and/or women who are in the premenopausal state, may carry a survival benefit in the setting of definitive surgical resection of colon and rectal cancers.

Background: The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS., Methods: Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m 2 as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred., Results: Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS., Conclusion: In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity., (Copyright © 2016. Published by Elsevier Inc.)

Objective(s): The Gynecologic Oncology Group (GOG) examined the association between ERBB2 amplification and clinical covariates, tumor response, disease status post-chemotherapy, progression-free survival (PFS), and overall survival (OS) in epithelial ovarian cancer (EOC)., Methods: Women with suboptimally-resected, advanced stage EOC who participated in GOG-111, a multi-center randomized phase III trial of cyclophosphamide+cisplatin versus paclitaxel+cisplatin, and provided a tumor block through the companion protocol GOG-9404 were eligible. ERBB2 amplification was examined using fluorescence in situ hybridization (FISH) with probes for ERBB2 and the centromere of chromosome 17 (CEP17)., Results: ERBB2 amplification, defined as >2 copies of ERBB2/CEP17, was a rare event in EOC with 7% (9/133) of women exhibiting between 2.2 and 33.7 copies of ERBB2/CEP17, and was not associated with patient age, race, GOG performance status, stage, cell type, grade, measurable disease status, volume of ascites, tumor response or disease status post-chemotherapy. Women with >2 verses < or =2 copies of ERBB2/CEP17 did not have a reduced risk of disease progression (hazard ratio [HR]=0.56; 95% confidence interval [CI]=0.27-1.16; p=0.120) or death (HR=0.57; 95% CI=0.26-1.23; p=0.152), and ERBB2 amplification was not an independent prognostic factor for PFS or OS. ERBB2 amplification, defined as >4 copies of ERBB2/nuclei, was observed in 9% (12/133) of women with levels ranging from 4.2 to 49.2 copies of ERBB2/nuclei, and was associated with older age and volume of ascites, but not with the other clinical covariates or outcome., Conclusion(s): ERBB2 amplification is a rare event and has no predictive or prognostic value in suboptimally-resected, advanced stage EOC treated with platinum-based combination chemotherapy.

Objectives: To determine the maximum tolerated dose (MTD) of weekly paclitaxel and cisplatin chemotherapy concurrent with whole pelvic irradiation in women with locally advanced cervical cancer., Methods: Consenting patients with stage IB2, IIA, IIB, IIIB and IVA carcinoma of the cervix (all cell types) were eligible for this phase I/II trial. Chemotherapy agents were administered in escalating doses to cohorts of three patients at each dose level, pending evaluation of toxicities from the previous dose level., Results: Thirty-five eligible women were enrolled on this study, of whom 13 comprised the phase I component. The MTD was determined to be cisplatin 40 mg/m2 and paclitaxel 40 mg/m2 administered weekly for six cycles with external beam radiation therapy. An additional 21 patients were enrolled in the phase II component at the previously determined MTD, yielding a total of 22 patients at the MTD, of whom 19 were evaluable. Among the evaluable patients treated at the MTD, two had grade 3 or 4 gastrointestinal (GI) toxicities (representing 5 of 113 cycles administered to this cohort) and seven experienced grade 3 or 4 neutrophil toxicity, none occurring prior to the fourth cycle. Thrombocytopenia was rare. Radiation therapy was successfully completed in 52% of patients at 8 weeks and in 79% of patients at 9 weeks, with a median of 59 days., Conclusions: Paclitaxel and cisplatin combination chemotherapy concurrent with whole pelvic irradiation can be safely administered at the described MTD.

Purpose: To identify the prevalence of psychological distress among women with ovarian cancer and to examine the association between these symptoms of distress and demographic and medical variables., Patients and Methods: Participants were 143 women with ovarian cancer. Forty-eight percent of participants had been diagnosed with advanced-stage disease (stage III or IV) and most (80%) were currently receiving treatment. Psychological distress was assessed with the following measures: the Beck Depression Inventory, the Mental Health Inventory, the Impact of Events Scale, and a questionnaire regarding mental health service use., Results: Approximately one fifth of women reported moderate to severe levels of distress, and more than half reported high stress responses to their cancer and its treatment. Most participants (60%) were not using any mental health services or psychotropic medications. There was also evidence to suggest that younger patients, patients with more advanced or recurrent disease, and patients who had more recently been diagnosed with ovarian cancer experienced greater psychological distress., Conclusion: These findings indicate that psychological distress and high stress responses to cancer are prevalent among women with ovarian cancer, suggesting they should be carefully evaluated to determine whether treatment for these symptoms is warranted.

Objectives: Docetaxel is an inhibitor of microtubule depolymerization and has demonstrated activity in paclitaxel-resistant breast cancer and gynecologic cancer. The Gynecologic Oncology Group (GOG) conducted a study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma to determine its activity, and nature and degree of toxicity, in this cohort of patients., Methods: Patients with platinum- and paclitaxel-resistant ovarian or peritoneal carcinoma, defined as progression while on or within 6 months of therapy, were eligible if they had measurable disease and had not received more than one chemotherapy regimen. Docetaxel at a dose of 100 mg/m(2) was administered iv over 1 h every 21 days. A prophylactic regimen of oral dexamethasone 8 mg bid was begun 24 h before docetaxel administration and continued for 48 h thereafter. Hepatic function was strictly monitored., Results: Sixty patients were entered and treated with a total of 256 courses, with all 60 evaluable for toxicity and 58 evaluable for response. Responses were observed in 22.4% of patients, with 5.2% achieving complete response and 17.2% achieving partial response (95% CI, 12.5-35.3%). The median duration of response was 2.5 months. The likelihood of observing a response did not appear to be related to the length of the prior paclitaxel-free interval or duration of prior paclitaxel infusions. The principal adverse effect of grade 4 neutropenia occurred in 75% of patients. There was one treatment-related death. Dose reductions were required in 36% of patients., Conclusions: Docetaxel is active in paclitaxel-resistant ovarian and peritoneal cancer but, in view of significant hematologic toxicity, further study is warranted to ascertain its optimal dose and schedule.

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.

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.

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.

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.

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.

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.

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.