Metronomic cyclophosphamide with bevacizumab provides disease stabilization in patients with advanced uterine cancer

• We present two cases of advanced uterine cancer that were treated with the combination of metronomic cyclophosphamide and bevacizumab. • Targeting angiogenesis can provide disease control in patients with advanced uterine cancer. • Randomized controlled trials comparing metronomic and conventional regimens in advanced uterine cancer are required

Performance of ThinPrep liquid-based cervical cytology in comparison with conventionally prepared Papanicolaou smears: a quantitative survey. Gynecol Oncol 2003;90:137–44

Abstract Objective. The goal of this study was to evaluate the performance of ThinPrep, a liquid-based cytology preparation technique, in comparison with conventionally prepared Papanicolaou smears in detecting cervical pathology. Methods. Forty-seven English-language articles published between January 1990 and September 2002 were identified through Medline and manual searches. After elimination of 5 nonprimary articles, 10 unpaired studies, 5 descriptive articles with insufficient or no data, and 3 articles with data that could not be recast into a consistent format, there remained 24 usable articles. Seventeen articles contained data comparing ThinPrep with conventional cytology for 35,172 patients; and 10 articles compared cytology with histology or other gold standard diagnoses for 21,752 patients. Three of these articles contained both types of comparisons. The standard cytology classification into negative, atypical, low-grade (LGSIL) and high-grade (HGSIL) squamous intraepithelial lesions, and carcinoma was applied; other categorization schemes were recoded as necessary. Concordance estimates, based on five-way and dichotomous (normal/abnormal) classifications, were obtained from the 17 studies containing paired cytology data. Sensitivity and specificity rates were obtained from the 10 studies with paired cytology and histology data. Results. The two methods tend to agree in 89 and 92% of cases based on the five-level and dichotomous classifications, respectively. ThinPrep was reported as normal in 93.5% of cases of normal conventional smears. The remaining 6.5% of ThinPrep slides were classified as follows: atypical, 4.55%; LGSIL, 1.56%; HGSIL, 0.36%; invasive cancer, 0.007%. Sensitivity rates, relative to histology, were 68% (conventional) and 76% (ThinPrep), and specificity rates were 79% (conventional) and 86% (ThinPrep). Conclusion. ThinPrep tends to be more sensitive and specific than conventional smears in detecting cervical dysplasia. The increased sensitivity of ThinPrep results in increased cytologic diagnosis of cervical atypia, LGSIL, HGSIL, and invasive cervical carcinoma

Peripartum Primary Prophylaxis Inferior Vena Cava Filter Placement in a Patient with Stage IV B-Cell Lymphoma Presenting with a Pathologic Femur Fracture

Abstract Background Pulmonary embolus (PE) remains a leading etiology of maternal mortality in the developed world. Increasing utilization of retrievable inferior vena cava (IVC) filter placement currently includes pregnant patients. Case A 22-year-old woman at 27 weeks' gestation was diagnosed with Stage IV high-grade malignant B cell lymphoma following pathologic femur fracture. Significant risk factors for PE led to placement of primary prophylaxis IVC filter before cesarean delivery, open reduction and internal fixation of the fractured femur, and chemotherapy. Conclusion This case supports that primary prophylaxis placement of IVC filters in highly selected pregnant patients may assist in decreasing PE-associated maternal mortality

Sonographic Findings of Medullary Thyroid Carcinoma Leading to Diagnosis of Multiple Endocrine Neoplasia Type 2a during Pregnancy

Multiple endocrine neoplasia (MEN) type 2a (Sipple's syndrome) is characterized by medullary thyroid carcinoma and pheochromocytoma, and in a smaller percentage of cases, multiglandular parathyroid hyperplasia. This autosomal-dominant syndrome is due to a mutation in the rearranged during transfection (RET) proto-oncogene located on chromosome 10cen–10q11.2 and rarely complicates pregnancy. We present an unusual case in a patient with an enlarged thyroid with sonographic findings characteristic of thyroid cancer, which led to diagnosis and subsequent management of RET proto-oncogene-positive MEN type 2a complicating pregnancy

Ribonucleotide reductase inhibition restores platinum-sensitivity in platinum-resistant ovarian cancer: a Gynecologic Oncology Group Study

Abstract Background The potent ribonucleotide reductase (RNR) inhibitor 3-aminopyridine-2-carboxyaldehyde-thiosemicarbazone (3-AP) was tested as a chemosensitizer for restored cisplatin-mediated cytotoxicity in platinum-resistant ovarian cancer. Methods Preclinical in vitro platinum-resistant ovarian cancer cell survival, RNR activity, and DNA damage assays were done after cisplatin or cisplatin plus 3-AP treatments. Six women with platinum-resistant ovarian cancer underwent four-day 3-AP (96 mg/m2, day one to four) and cisplatin (25 mg/m2, day two and three) infusions every 21 days until disease progression or adverse effects prohibited further therapy. Pre-therapy ovarian cancer tissues were analyzed by immunohistochemistry for RNR subunit expression as an indicator of cisplatin plus 3-AP treatment response. Results 3-AP preceding cisplatin exposure in platinum-resistant ovarian cancer cells was not as effective as sequencing cisplatin plus 3-AP together in cell survival assays. Platinum-mediated DNA damage (i.e., γH2AX foci) resolved quickly after cisplatin-alone or 3-AP preceding cisplatin exposure, but persisted after a cisplatin plus 3-AP sequence. On trial, 25 four-day overlapping 3-AP and cisplatin cycles were administered to six women (median 4.2 cycles per patient). 3-AP-related methemoglobinemia (range seven to 10%) occurred in two (33%) of six women, halting trial accrual. Conclusions When sequenced cisplatin plus 3-AP, RNR inhibition restored platinum-sensitivity in platinum-resistant ovarian cancers. 3-AP (96 mg/m2) infusions produced modest methemoglobinemia, the expected consequence of ribonucleotide reductase inhibitors disrupting collateral proteins containing iron. Trial registry ClinicalTrials.gov NCT00081276</p

Human Fetal Exposure to Triclosan and Triclocarban in an Urban Population from Brooklyn, New York

Triclosan (TCS) and triclocarban (TCC) are antimicrobial agents formulated in a wide variety of consumer products (including soaps, toothpaste, medical devices, plastics, and fabrics) that are regulated by the U.S. Food and Drug Administration (FDA) and U.S. Environmental Protection Agency. In late 2014, the FDA will consider regulating the use of both chemicals, which are under scrutiny regarding lack of effectiveness, potential for endocrine disruption, and potential contribution to bacterial resistance to antibiotics. Here, we report on body burdens of TCS and TCC resulting from real-world exposures during pregnancy. Using liquid chromatography tandem mass spectrometry, we determined the concentrations of TCS, TCC, and its human metabolites (2′-hydroxy-TCC and 3′-hydroxy-TCC) as well as the manufacturing byproduct (3′-chloro-TCC) as total concentrations (Σ−) after conjugate hydrolysis in maternal urine and cord blood plasma from a cohort of 181 expecting mother/infant pairs in an urban multiethnic population from Brooklyn, NY recruited in 2007–09. TCS was detected in 100% of urine and 51% of cord blood samples after conjugate hydrolysis. The interquartile range (IQR) of detected TCS concentrations in urine was highly similar to the IQR reported previously for the age-matched population of the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004, but typically higher than the IQR reported previously for the general population (detection frequency = 74.6%). Urinary levels of TCC are reported here for the first time from real-world exposures during pregnancy, showing a median concentration of 0.21 μg/L. Urinary concentrations of TCC correlated well with its phase-I metabolite ∑-2′-hydroxy-TCC (<i>r</i> = 0.49) and the manufacturing byproduct ∑-3′-chloro-TCC C (<i>r</i> = 0.79), and ∑-2′-hydroxy-TCC correlated strongly with ∑-3′-hydroxy-TCC (<i>r</i> = 0.99). This human biomonitoring study presents the first body burden data for TCC from exposures occurring during pregnancy and provides additional data on composite exposure to TCS (i.e., from both consumer-product use and environmental sources) in the maternal–fetal unit for an urban population in the United States