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Copyright of Meme Sagligi Dergisi / Journal of Breast Health is the property of Turkish Federation of Breast Diseases Associations and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Chemotherapy for the treatment of maternal cancers during pregnancy has become more acceptable in the past decade; however, the effect of prenatal exposure to chemotherapy on cardiac and neurodevelopmental outcomes of the offspring is still uncertain. We aimed to record the general health, cardiac function, and neurodevelopmental outcomes of children who were prenatally exposed to chemotherapy. METHODS: We did an interim analysis of a multicentre observational cohort study assessing children who were prenatally exposed to maternal cancer staging and treatment, including chemotherapy. We assessed children at birth, at age 18 months, and at age 5-6, 8-9, 11-12, 14-15, or 18 years. We did clinical neurological examinations, tests of the general level of cognitive functioning (Bayley or intelligence quotient [IQ] test), electrocardiography and echocardiography, and administered a questionnaire on general health and development. From age 5 years, we also did audiometry, the Auditory Verbal Learning Test, and subtasks of the Children's Memory Scale, and the Test of Everyday Attention for Children, and we also completed the Child Behavior Checklist. This study is registered with ClinicalTrials.gov, number NCT00330447. FINDINGS: 236 cycles of chemotherapy were administered in 68 pregnancies. We assessed 70 children, born at a median gestational age of 35·7 weeks (range 28·3-41·0; IQR 3·3; 47 women at <37 weeks), with a median follow-up period of 22·3 months (range 16·8-211·6; IQR 54·9). Although neurocognitive outcomes were within normal ranges, cognitive development scores were lower for children who were born preterm than for those born at full term. When controlling for age, sex, and country, the score for IQ increased by an average 11·6 points (95% CI 6·0-17·1) for each additional month of gestation (p<0·0001). Our measurements of the children's behaviour, general health, hearing, and growth corresponded with those of the general population. Cardiac dimensions and functions were within normal ranges. We identified a severe neurodevelopmental delay in both members of one twin pregnancy. INTERPRETATION: Fetal exposure to chemotherapy was not associated with increased CNS, cardiac or auditory morbidity, or with impairments to general health and growth compared with the general population. However, subtle changes in cardiac and neurocognitive measurements emphasise the need for longer follow-up. Prematurity was common and was associated with impaired cognitive development. Therefore, iatrogenic preterm delivery should be avoided when possible. FUNDING: Research Foundation-Flanders; Research Fund-K U Leuven; Agency for Innovation by Science and Technology; Stichting tegen Kanker; Clinical Research Fund-University Hospitals Leuven; and Belgian Cancer Plan, Ministery of Health. [ABSTRACT FROM AUTHOR]

The establishment of enclosed conservation areas are claimed to be the driving force for the long-term survival of wildlife populations. Whilst fencing provides an important tool in conservation, it simultaneously represents a controversial matter as it stops natural migration processes, which could ultimately lead to inbreeding, a decline in genetic diversity and local extinction if not managed correctly. Thus, wildlife residing in enclosed reserves requires effective conservation and management strategies, which are strongly reliant on robust population estimates. Here, we used camera traps combined with the relatively new class of spatially explicit capture-recaptured models (SECR) to produce the first reliable leopard population estimate for an enclosed reserve in Namibia. Leopard density was estimated at 14.51 leopards/100 km 2 , the highest recorded density in Namibia to date. A combination of high prey abundance, the absence of human persecution and a lack of top-down control are believed to be the main drivers of the recorded high leopard population. Our results add to the growing body of literature which suggests enclosed reserves have the potential to harbour high densities and highlight the importance of such reserves for the survival of threatened species in the future., Competing Interests: The authors declare no conflict of interest.

Background: Due to its rarity, there is no standard treatment for tongue cancers that concur with pregnancy. Treatment depends on the stage of cancer, gestational age of the pregnancy, and the wish of the mother to maintain the pregnancy. The purpose of this study was to review the literature and to report 5 new cases., Methods: Twelve cases of tongue cancer during pregnancy were already reported between 1987 and 2009. We report 5 new cases and first administration of concomitant radiochemotherapy for tongue cancer., Results: Median age of the patients was 29 years, 65% of diagnoses were made after the first trimester of pregnancy. Different treatment modalities are used to treat tongue cancer during pregnancy., Conclusion: We hypothesize that tongue cancer treatment adhering to standard protocols provides the best guarantee to cure the mother. Based on a growing experience and insight taking fetal safety into consideration, the available data suggest that standard treatment is a realistic option., (Copyright © 2011 Wiley Periodicals, Inc.)

Chemotherapy and especially anthracyclines are associated to cardiotoxicity. To assess this potential risk during pregnancy a clinical case-control trial was conducted. Maternal cardiac function, fetal Doppler and fetal cardiac function were evaluated before and after chemotherapy. Maternal cardiac function was assessed by echocardiography before and after the third cycle of anthracyclines and compared with a control group of 10 non-pregnant women matched for age, type of cancer and anthracycline treatment. Ten fetuses exposed to chemotherapy were compared with 10 control fetuses matched for gestational age and gender. Biometry, amniotic fluid index, fetal Doppler and cardiac function were assessed before and after each cycle of chemotherapy. In all, 108 fetal ultrasounds scans were performed before and after 36 cycles of chemotherapy. Anthracycline exposure did not result in acute maternal and fetal cardiac dysfunction in this small cohort study., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child., Methods: We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833., Findings: From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1-105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76-1·69]; p=0·539)., Interpretation: Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance., Funding: BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Data on the transplacental transfer of chemotherapeutic agents are lacking. We aimed to measure the maternofetal transfer of cytotoxic drugs in a mouse model., Study Design: The transplacental transfer of doxorubicin (9 mg/kg), epirubicin (11 mg/kg), vinblastine (6 mg/kg), carboplatin (50 mg/kg), paclitaxel (10 mg/kg), and cytarabine (100 mg/kg) was tested in a C57/Bl6J mouse model. Ninety minutes after intravenous (IV) drug injection on gestational day 18.5, maternal and fetal blood were collected simultaneously. Plasma drug levels were determined using high performance liquid chromatography or atomic absorption spectrometry., Results: Fetal plasma concentrations of doxorubicin, epirubicin, vinblastine, and cytarabine were 5.1% ± 0.6% (n = 8), 4.8% ± 3.8% (n = 8), 13.8% ± 5.8% (n = 6), and 56.7% ± 22.6% (n = 6) of the maternal concentrations, respectively. Total platinum passed the mouse placenta easily (117.0% ± 38.9%, n = 6). Paclitaxel could not be detected in fetal plasma samples (n = 6)., Conclusions: Substantial variations in transplacental transfer were noted among the tested drugs. Current findings contribute to the understanding of reported pregnancy outcomes in humans.

Breast cancer during pregnancy is relatively uncommon. However, the incidence is expected to increase as more women delay childbearing. A challenging situation emerges for all persons involved ‑ patient, family and medical care workers ‑ since two lives are at risk with contradicting priorities. Breast cancer treatment is possible during pregnancy. The treatment plan needs to adhere as closely as possible to standardised protocols for nonpregnant patients, with some considerations to minimize fetal exposure and risks. This concerns mainly limiting radiation exposure and timing of chemotherapy to start in the second trimester. The prognosis of pregnant women does not seem to differ from that of nonpregnant patients when matched for age and stage of the disease. This literature review concentrates on the diagnosis, treatment and outcome of patients diagnosed with breast cancer during pregnancy.

Background: The paucity of data on fetal effects of prenatal exposure to chemotherapy prompted us to study the transplacental transport of commonly used anticancer agents in a pregnant baboon model., Methods: Single or combination chemotherapy with paclitaxel, docetaxel, carboplatin, and trastuzumab was administered to 9 baboons at a mean (SD) gestational age of 117 (26) days (paclitaxel, 100 mg/m2 [n = 2]; docetaxel, 100 mg/m2 [n = 2]; paclitaxel, 175 mg/m2 with carboplatin, area under the curve of 6 at standard dosage [n = 2] and 50% dosage [n = 1]; docetaxel, 75 mg/m2 with carboplatin, area under the curve 6 [n = 1]; and docetaxel, 75 mg/m2 with trastuzumab, 8 mg/kg [n = 1]). Serial fetal and maternal blood samples, amniotic fluid, maternal urine, and fetal and maternal tissue samples were collected for the first 76 hours after drug infusion. Levels of carboplatin were determined by atomic absorption spectrometry, docetaxel and paclitaxel by high-performance liquid chromatography, and trastuzumab by enzyme-linked immunosorbent assay., Results: Fetal plasma concentrations of carboplatin averaged 57.5% (14.2%) of maternal concentrations (n = 7). Fetal plasma concentrations were 1.5% (0.8%) of maternal concentrations (n = 7). Immediately after ending the infusion, paclitaxel was not detectable in fetal tissues, whereas, after 3 hours, fetal tissues contained 15% of maternal tissue concentrations.Docetaxel could not be detected in fetal blood samples (n = 9). In the first 3 hours after docetaxel infusion, fetal tissues contained 5.0% to 50.0% of maternal tissue concentrations, whereas equal fetal and maternal tissue concentrations were found after 26 and 76 hours.The transplacental passages of trastuzumab were 85.0% and 3.0%, 2 and 26 hours after trastuzumab infusion, respectively. After 26 hours, amniotic fluid contained 36.4% of the fetal plasma concentration. Fetal tissue concentrations varied between 5.0% and 14.0% of the maternal concentration., Conclusion: Variable plasma and/or tissue concentrations of taxanes, carboplatin, and trastuzumab were encountered in the fetal compartment. These data are important when cancer treatment is considered during pregnancy and underline the need for long-term follow-up of children after prenatal exposure to these cytotoxic agents.

Objective: To determine the impact of physiologic changes of pregnancy on pharmacokinetics of chemotherapeutic agents., Design: A preclinical and a clinical case-control trial., Setting: Institute of Primate Research Nairobi and collaborating hospitals in Belgium, the Netherlands and Czech Republic., Population: Pregnant and nonpregnant women and baboons receiving chemotherapy., Methods: Chemotherapy pharmacokinetics was compared between the pregnant and nonpregnant state. Standard-dosed chemotherapy regimens were administered in pregnant and nonpregnant baboons/women, followed by serial blood samplings. Drug plasma levels were determined using high performance liquid chromatography and atomic absorption spectrometry., Main Outcome Measures: Area under the curve (AUC), maximal plasma concentration, terminal elimination half-life, clearance and distribution volume of each drug in pregnant and nonpregnant state., Results: Intraindividual comparative pharmacokinetic data were obtained for doxorubicin and paclitaxel/platinum in three and two baboons, respectively. In the clinical trial, two patients were exposed to doxorubicin and one patient was exposed to paclitaxel/platinum during and after pregnancy. Furthermore, a pooled analysis was performed based on 16 cycles of pregnant and 11 cycles of nonpregnant women. Numbers of pregnant/nonpregnant patients were 5/2, 7/5, 4/4 and 2/2 for paclitaxel, doxorubicin, epirubicin and platinum, respectively. For all drugs tested in the preclinical and clinical study, a decreased AUC and maximal plasma concentration and an increased distribution volume and clearance were observed in pregnancy., Conclusions: Although numbers were too small for statistical significance, pregnancy-associated physiologic alterations appear to lead to a decrease in plasma exposure of chemotherapeutic drugs. The importance of long-term follow-up of women treated with chemotherapy during pregnancy is underscored.

Introduction: To the best of our knowledge, soft tissue sarcomas have not prevously been reported as a complication during pregnancy., Case Presentation: A 28-year-old Caucasian woman was diagnosed with a transperitoneal sarcoma during pregnancy. Morphological, immunohistochemical, chromosomal and mutational analyses pointed towards a high-grade endometrial stromal sarcoma. Although surgery and chemotherapy are possible during pregnancy, we were unable to perform these in this case., Conclusion: The potential to treat gynecological cancer during pregnancy should always be assessed individually.

Purpose: The aim of this study was to assess the management and the obstetrical and neonatal outcomes of pregnancies complicated by cancer., Patients and Methods: In an international collaborative setting, patients with invasive cancer diagnosed during pregnancy between 1998 and 2008 were identified. Clinical data regarding the cancer diagnosis and treatment and the obstetric and neonatal outcomes were collected and analyzed., Results: Of 215 patients, five (2.3%) had a pregnancy that ended in a spontaneous miscarriage and 30 (14.0%) pregnancies were interrupted. Treatment was initiated during pregnancy in 122 (56.7%) patients and postpartum in 58 (27.0%) patients. The most frequently encountered cancer types were breast cancer (46%), hematologic malignancies (18%), and dermatologic malignancies (10%). The mean gestational age at delivery was 36.3 +/- 2.9 weeks. Delivery was induced in 71.7% of pregnancies, and 54.2% of children were born preterm. In the group of patients prenatally exposed to cytotoxic treatment, the prevalence of preterm labor was increased (11.8%; P = .012). Furthermore, in this group a higher proportion of small-for-gestational-age children (birth weight below 10th percentile) was observed (24.2%; P = .001). Of all neonates, 51.2% were admitted to a neonatal intensive care unit, mainly (85.2%) because of prematurity. There was no increased incidence of congenital malformations., Conclusion: Pregnant cancer patients should be treated in a multidisciplinary setting with access to maternal and neonatal intensive care units. Prevention of iatrogenic prematurity appears to be an important part of the treatment strategy.

Background: Gynecologic cancer during pregnancy is a special challenge because cancer or its treatment may affect not only the pregnant women in general but directly involve the reproductive tract and fetus. Currently, there are no guidelines on how to deal with this special coincidence., Methods: An international consensus meeting on staging and treatment of gynecological malignancies during pregnancy was organised including a systematic literature search, and interpretation followed by a physical meeting of all participants with intensive discussion. In the absence of large trials and randomized studies, recommendations were based on available literature data and personal experience thus representing a low but best achievable level of evidence., Findings: Randomized trials and prospective studies on cancer treatment during pregnancy are lacking. Gynecological cancer during pregnancy is a demanding problem, and multidisciplinary expertise should be available. Counseling both parents on the maternal prognosis and fetal risk is needed. When there is a firm desire to continue the pregnancy, gynecological cancer can be treated in selected cases. The staging and treatment should follow the standard approach as much as possible. Guidelines for safe pelvic surgery during pregnancy are presented. Mainly in cervical and ovarian cancer, chemotherapy and an alternative surgical approach need to be considered. Administration of chemotherapy during the second or third trimester may probably not increase the incidence of congenital malformations. Until now, the long-term outcome of children in utero exposed to oncological treatment modalities is poorly documented, but preterm birth on its own is associated with cognitive impairment. Delivery should be postponed preferably until after a gestational age of 35 weeks., Interpretation: Further research including international registries for gynecologic cancer in pregnancy is urgently needed. The gathering of both available literature and personal experience allowed only suggesting models for treatment of gynecologic cancer in pregnancy.

Background: Limited data exist on the efficacy and safety of home intravenous antibiotic (IV-AB) therapy for pulmonary infection specifically in children with cystic fibrosis (CF)., Methods: We report on the outcome of IV-AB in the home vs hospital setting based on retrospective single centre patient data from 1999 to 2004 (age >5 and <18 years). Treatment location was chosen based on estimation of competence, adherence, social background and patient preference. Primary outcome parameter was change in FEV(1). Secondary outcome parameters were weight and IgG as well as occurrence of complications., Results: One hundred and thirty-one treatment observations (TOs) were analysed for 47 patients. Mean age was 13.32 (+/-2.9) years and mean FEV(1) 65 (+/-19) % predicted. Fifty-four (41%) TO's were home and 77 (59%) were hospital treatments. Percent change in FEV(1) and weight gain was comparable in the 2 settings. Complications were rare in both groups., Conclusion: The outcome of IV-AB therapy for lung infection in children with CF was not inferior in the home compared to the hospital setting. In our centre, home IV-AB treatment is a valuable treatment option for children with CF.

Objectives: The purpose of this study was to evaluate cell proliferation in platelet-enriched collagen plugs with and without addition of amniotic fluid-derived heterologous foetal cells to seal an iatrogenic membrane defect in the foetal rabbit model., Methods: Amniotic fluid cells were harvested from three donor does at 23 days of gestation (term = 32 days) and labelled with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE). In 42 other does, foetal membrane defects were induced by foetoscopic needle puncture at 23 days of gestation, and closed with either a platelet-enriched collagen plug with (n = 44) or without (n = 32) amniotic fluid cells. At 30 days of gestation, the defects were harvested and assessed microscopically., Results: The plugs enriched with heterologous amniotic fluid cells more commonly had proliferating cells in the centre of the plug than those without cell addition. CFDA-SE labelling confirmed the presence of heterologous amniotic fluid cells over the entire membrane plug. Cell typing showed a mixture of fibroblasts and epithelial cells at the wound edges, whereas in the centre, there was an abundance of fibroblasts., Conclusion: When sealing iatrogenic membrane defects in the foetal rabbit model, enrichment of collagen plugs with platelets and amniotic fluid-derived heterologous foetal cells increases local cell proliferation.

Background and Aim: Kangaroo mother care (KMC) has become the standard of care for low-risk preterm babies born in developing countries. However, the potential risk of nosocomial transmission of Mycobacterium tuberculosis within KMC units, particularly in tuberculosis-endemic areas, has not been explored. We report an infant (sentinel case) who was admitted to our paediatric intensive care unit (PICU) with extensive pulmonary tuberculosis., Methods and Results: When interviewed, the mother reported no household contact with a tuberculosis source case, but mentioned that she shared a KMC room with someone who had symptoms suspicious of tuberculosis. We found molecular evidence that nosocomial transmission of M. tuberculosis occurred within the KMC unit and conducted a contact investigation of all infants exposed to this infectious source case during her stay in the KMC unit., Conclusion: We present the findings of the contact investigation and discuss the implications of these findings for KMC units, particularly in tuberculosis-endemic areas.

Objectives: To review the incidence, clinical features, ventilatory support and outcome of children with tuberculosis (TB) admitted to a Pediatric Intensive Care Unit (PICU) in a region with an high incidence of TB., Materials and Methods: The study was performed in a PICU situated in a province with a extremely high incidence of TB (> 700 new cases/ 100000/year). This is a retrospective descriptive study of TB admissions to the PICU in a 4-year period. Data regarding indications for admission, clinical picture, duration of ventilation, PICU and hospital stay were collected from patient files. Outcome measures included mortality and long term morbidity., Results: Of the 1862 children admitted to the hospital for TB during the 4 years, 57 (3.1%) required PICU admission (1 to 6% of annual admissions). Of these 57 children 41 (72%) were admitted for respiratory failure. In 12 cases TB was the cause of the respiratory failure, 17 cases suffered from other respiratory diseases and in 12 cases the cause was nonrespiratory disease of which TB meningitis (n=8) was the most common. Mechanical ventilation was indicated in 43 (75%) patients who were ventilated for 7.3+/-11.5 days. The duration of PICU admission was 10.2+/-2.4 days whereas the duration of hospitalization was 70.3+/-148.9 days. The PICU mortality was 23% with TB meningitis having the highest mortality of 75%., Conclusions: In a region with a high incidence of TB, tuberculous patients constitute up to 6% of PICU admissions. A high degree of suspicion for the diagnosis is needed because in 30% of our cases the diagnosis was not initially considered.