Ovadia Abulafia

Cancer risk among participants in the women's interagency HIV study.

Background:The HIV epidemic has been associated with an increased incidence of specific cancers. However, less is known about cancers occurring in HIV-infected women than men. Methods:To determine the risk of cancer among HIV-infected and at-risk HIV-uninfected women, cancer incidence data from the Women’s Interagency HIV Study (WIHS) were compared with data from the population-based United States Surveillance, Epidemiology, and End Results (SEER) registry. Age- and race-adjusted standardized incidence ratios (SIRs) were computed and exact statistical tests were used to measure significance. Results:Among the 1950 women participants (1554 HIV infected, 391 HIV uninfected, and 5 HIV seroconverters), 48 cancers were diagnosed during study follow-up. Among HIV-infected women, significantly (P < 0.05) increased incidence rates were observed for all cancer types (SIR = 1.9), Kaposi sarcoma (SIR = 213.5), non-Hodgkin lymphoma (NHL) (SIR = 19.0), and lung cancer (SIR = 6.3) when compared with SEER rates. Lung cancer incidence was also elevated (P = 0.07) among the HIV-uninfected women (SIR = 6.9), when compared with SEER rates, and was similar to the SIR for HIV-infected women. While the incidence rate of NHL among HIV-infected women was significantly lower during the era of highly active antiretroviral therapy (HAART) compared with the pre-HAART era (relative risk = 0.15, P = 0.005), the incidence of NHL among HIV-infected WIHS participants remained significantly higher than in the US population (SIR = 6.4, 95% CI = 1.3–15.5). Conclusion:In the HAART era, the higher rates of cancer among HIV-infected women, coupled with increased life expectancy, should lead to more intensive cancer screening and prevention efforts in this population.

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 (r = 0.49) and the manufacturing byproduct ∑-3′-chloro-TCC C (r = 0.79), and ∑-2′-hydroxy-TCC correlated strongly with ∑-3′-hydroxy-TCC (r = 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.

Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer

OBJECTIVE A phase II trial was performed to evaluate the efficacy and safety of the tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER2, lapatinib, and to explore EGFR, HER2 (EGFR2), phosphorylated ERK MAP kinase (pERK), and Ki67 expression, as well as EGFR mutations in persistent/recurrent endometrial cancer (EC). METHODS Women with histologically-confirmed, measurable, persistent/recurrent EC following one or two prior regimens were eligible and treated with 1500 mg oral lapatinib daily until progression or severe toxicity. A 2-stage group sequential design was used to evaluate the regimen with 6 month PFS as the primary endpoint. The trial had a 10% type I error rate with 90% power. EGFR, HER2, pERK, and Ki67 were evaluated by immunohistochemistry (IHC) from hysterectomy specimens, pre-treatment biopsies, and post-treatment biopsies (when available). Exons 18-21 of EGFR were sequenced. RESULTS Three patients of 30 evaluable had PFS ≥6 months, one had a partial response, seven had stable disease, 21 had progressive disease and one was indeterminate. Three mutations in EGFR were identified. Two of these, L688F and K754E, were not associated with response or PFS. However, a newly identified mutation in exon 18, E690K, occurred in the patient with a partial response and progression-free survival extending past six months. CONCLUSION While lapatinib has limited activity in unselected cases, the identification of a previously unreported mutation in EGFR (E690K) with a response suggests that lapatinib may be beneficial in some cases of EC.

Early-stage carcinosarcoma of the uterus: the significance of lymph node count

Carcinosarcoma is a rare tumor of the uterus with a poor prognosis, even when identified and treated at an early stage. The purpose of this study was to identify and analyze prognostic pathologic features and treatment outcomes in patient with stages I and II carcinosarcoma of the uterus. Patients with carcinosarcoma of the uterus who received primary surgical treatment between 1984 and 2004 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/II disease following hysterectomy and selective pelvic and para-aortic lymph node sampling. Regression analysis was used to determine risk factors for recurrence and survival. Disease-free and overall survival were then determined using Kaplan–Meier analysis. Forty-seven patients with stages I and II carcinosarcoma of the uterus were identified. Age, heterologous or homologous histology, and type of adjuvant treatment were not associated with recurrence or survival. Depth of myometrial invasion was found to correlate to disease-free survival but not overall survival. The number of lymph nodes collected correlated to risk of recurrence and survival. Disease-free and overall survival were greater in patients with higher lymph node count. We conclude that the number of lymph nodes collected was the only risk factor that was found to be correlated to recurrence and survival in patients with early-stage carcinosarcoma. These results support mounting evidence that lymphadenectomy is crucial in patients with carcinomas of the uterus in order to discover occult metastatic disease and potentially provide patients with a therapeutic benefit

Prognostic significance of preoperative thrombocytosis in patients with endometrial carcinoma in an inner-city population.

Introduction: Thrombocytosis is present in a wide range of malignancies, with a reported incidence of 10% to 57%. Several reports have documented thrombocytosis at the time of diagnosis as a poor prognostic indicator. Our study is the first report evaluating the role of preoperative thrombocytosis and its association with survival in a predominantly African American and Caribbean American urban population. Materials and Methods: We retrospectively reviewed the charts of 99 consecutive patients treated for endometrial carcinoma at SUNY Downstate Medical Center. Seventy-seven patients were deemed eligible for the study, and the following clinicopathologic characteristics were recorded from their medical records: age, stage, grade, histological subtype, presence of lymphovascular space invasion, depth of myometrial invasion, intrauterine tumor volume, preoperative prothrombin time, activated partial thromboplastin time, platelet count, progression-free survival (PFS), and overall survival (OS). The data were analyzed using Spearman and Pearson correlations, Student t test, &khgr;2 test, and Fisher exact test. Survival analysis was performed using Kaplan-Meier tables, log-rank test, and Cox proportional hazard model. The 2-tailed value of P < 0.05 was considered significant. Results: Fourteen (18.2%) of 77 patients exhibited thrombocytosis (platelet count, >400 × 109/L). Patients with advanced disease (stages III-IV) had a significantly higher mean preoperative platelet count (359 ± 23.8 × 109/L) in comparison with patients with localized disease (stages I-II, 283 ± 14.3 × 109/L, P = 0.005). The median PFS among patients with stages III and IV without preoperative thrombocytosis was 15.0 ± 4.8 months (n = 21) and with thrombocytosis was 3.0 ± 1.4 months (n = 8, P = 0.032). The median OS in patients without thrombocytosis was 24.0 ± 4.5 months (n = 21) and in patients with thrombocytosis was 7.0 ± 3.8 months (n = 8, P = 0.015). Multivariate analysis was performed using log-rank test and Cox proportional hazard model. The only variables that retained independent prognostic significance were stage (hazards ratio, 3.268; P = 0.040) and preoperative thrombocytosis (hazards ratio, 1.714 per 100 platelets; P = 0.030). Among patients with localized disease, preoperative thrombocytosis was not associated with worsened OS or PFS. Conclusions: Our data indicate that preoperative thrombocytosis among high-risk inner-city patients with stages III to IV endometrial cancer is an independent prognostic indicator. This is the first such report in a predominantly African American and Caribbean American population. Further research is needed to elucidate the mechanisms of thrombocytosis in malignancy. Association of thrombocytosis and aggressive tumor behavior warrants investigation of antiplatelet therapy and its effect on outcome.

Assessment of prenatal mercury exposure in a predominately Caribbean immigrant community in Brooklyn, NY

Prenatal mercury exposure and its fetotoxic effects may be of particular concern in urban immigrant communities as a result of possible contributing cultural factors. The most common source of exposure in these communities is ingestion of fish and shellfish contaminated with methylmercury. Other sources of exposure may occur in ritualistic practices associated with Hispanic and Caribbean-based religions. This study 1) assessed total mercury levels in both random urine specimens from pregnant women, and in cord blood; and 2) examined environmental sources of exposure from a convenience sample in a predominantly Caribbean immigrant population in Brooklyn, New York. A questionnaire designed in collaboration with health professionals from the Caribbean community assessed the frequency of fish consumption, ritualistic practices, occupational exposures, and use of dental amalgams and mercury-containing skin and household products. The geometric mean for total mercury in cord blood was 2.14 μg L(-1) (95%CI: 1.76-2.60) (n = 78), and 0.45 μg L(-1) (95%CI: 0.37-0.55) (n = 183) in maternal urine corrected for creatinine (μg g(-1)). Sixteen percent of cord blood mercury levels exceeded the estimated equivalent of U.S. Environmental Protection Agencys Reference Dose (5.8 μg L(-1) blood). Predictors of cord blood mercury included maternal fish consumption and foreign birth of the mother. Predictors of urine mercury included foreign birth of the mother, number of dental amalgams, and special product use. There were no reports of mercury use in ritualistic practices or in cosmetics; however some women reported use of religious medals and charms. This study characterized risk factors for mercury exposure in a sample of urban, predominantly Caribbean-born blacks. Findings may help target interventions in this population, which might include appropriate fish selection and consumption frequency during pregnancy, and safe handling of mercury-containing products in the home.

A phase II evaluation of weekly gemcitabine and docetaxel for second-line treatment of recurrent carcinosarcoma of the uterus: A gynecologic oncology group study

BACKGROUND The objective of this study was to estimate antitumor activity and toxicity of weekly docetaxel and gemcitabine as second-line chemotherapy for patients with recurrent uterine carcinosarcoma. METHODS Patients with recurrent carcinosarcoma of the uterus who had failed one regimen of chemotherapy, had a Gynecologic Oncology Group (GOG) performance status of 0-2 and had measurable disease were included. Treatment consisted of gemcitabine 600 mg/m(2) and docetaxel 35 mg/m(2) intravenously on days 1, 8 and 15 of a 28-day cycle until disease progression or intolerable adverse effects. This study employed an optimal but flexible two-stage design with an early stopping rule. If more than 3 out of 22-24 or more than 4 out of 25-29 patients responded, accrual to the second stage was to be initiated. RESULTS Twenty-eight patients were enlisted. Three patients were not eligible after pathology review. One patient was never treated. Twenty-four patients were evaluable. Nine patients had previous radiation therapy. There were no complete responses. Partial responses were seen in two patients (8.3%), stable disease in eight (33.3%) and progressive disease in 12 patients (50%). Two patients were not evaluable (8.3%). The median progression-free survival was 1.8 months. The median survival was 4.9 months. The treatment caused myelosuppression, mainly neutropenia, but also thrombocytopenia and anemia. Dose modifications became necessary in the majority of patients. In five patients, treatment was discontinued due to toxicity. CONCLUSIONS This regimen of docetaxel and gemcitabine is not active in patients with recurrent carcinosarcoma of the uterus as second-line chemotherapy.

Severe hypernatremia after cesarean delivery secondary to transient diabetes insipidus of pregnancy

BACKGROUND Transient diabetes insipidus is an uncommon complication of pregnancy, usually manifesting with polydipsia and polyuria. This condition is considered to result from excess placental vasopressinase activity and is managed with deamino D arginine vasopressin. CASE While on restricted oral intake after cesarean delivery, the patient gradually became disoriented and agitated in conjunction with markedly increased urine output disproportional to her intravenous crystalloid fluid intake. Marked hypernatremia of 178 mEq/dL was noted. Urine osmolality was low at 248 mOsm/L. The clinical presentation and electrolyte abnormalities were considered consistent with transient diabetes insipidus of pregnancy. The patient responded well to nasal-spray-administered deamino D arginine vasopressin and increased intravenous fluid intake, with resolution of symptoms and gradual normalization of serum sodium levels. CONCLUSION Transient diabetes insipidus of pregnancy should be considered in the differential diagnosis of severe hypernatremia in obstetric patients with restricted oral intake after operative delivery.

Maternal Mercury Exposure, Season of Conception and Adverse Birth Outcomes in an Urban Immigrant Community in Brooklyn, New York, U.S.A.

Adverse birth outcomes including preterm birth (PTB: <37 weeks gestation) and low birth weight (LBW: <2500 g) can result in severe infant morbidity and mortality. In the United States, there are racial and ethnic differences in the prevalence of PTB and LBW. We investigated the association between PTB and LBW with prenatal mercury (Hg) exposure and season of conception in an urban immigrant community in Brooklyn, New York. We recruited 191 pregnant women aged 18–45 in a Brooklyn Prenatal Clinic and followed them until delivery. Urine specimens were collected from the participants during the 6th to 9th month of pregnancy. Cord blood specimens and neonate anthropometric data were collected at birth. We used multivariate logistic regression models to investigate the odds of LBW or PTB with either maternal urinary mercury or neonate cord blood mercury. We used linear regression models to investigate the association between continuous anthropometric outcomes and maternal urinary mercury or neonate cord blood mercury. We also examined the association between LBW and PTB and the season that pregnancy began. Results showed higher rates of PTB and LBW in this cohort of women compared to other studies. Pregnancies beginning in winter (December, January, February) were at increased odds of LBW births compared with births from pregnancies that began in all other months (OR7.52 [95% CI 1.65, 34.29]). We observed no association between maternal exposure to Hg, and either LBW or PTB. The apparent lack of association is consistent with other studies. Further examination of seasonal association with LBW is warranted.

Maternal and fetal exposure to parabens in a multiethnic urban U.S. population

Fetal exposure to five parabens was investigated due to their endocrine-disrupting potential and possible impact on fetal development. Body burdens occurring from real-world exposures were determined typically as total concentrations after conjugate hydrolysis in 181 maternal urine and 38 umbilical cord blood plasma samples from a multiethnic cohort of 185 predominantly-black, pregnant women recruited in Brooklyn, New York between 2007/9. For 33 participants, both sample types (maternal urine and cord blood) were available. Methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), butyl- (BuPB), and benzylparaben (BePB) were detected in 100, 73.5, 100, 66.3 and 0.0% of the urine samples at median concentrations of 279, 1.44, 75.3, 0.39, and <0.02μg/L, respectively. Median concentrations of MePB and PrPB were, respectively 4.4- and 8.7-fold higher compared to those reported previously for the general U.S. population (NHANES, 2005/6). Listed in the order above, the five parabens were detected in 97.4, 94.7, 47.4, 47.4, and 44.7% of cord blood plasma samples at median total concentrations of 25.0, 0.36, <0.27, <0.09, and <0.10μg/L, respectively. Free MePB, EtPB, and PrPB were detected in a subset of cord blood plasma samples at, respectively, 3.9, 71.7, and 6.4% of their total concentrations, whereas free BuPB and BePB were not detected. Literature data and those reported here show the urban community studied here to rank highest in the world for MePB and PrPB exposure in pregnant women, whereas it ranks among the lowest for EtPB and BuPB. This study is the first to report the occurrence of parabens in human umbilical cord blood. Maternal exposure to parabens is widespread, and substantial differences were found to exist between communities and countries both in the spectrum and degree of paraben exposures.