Constantine Dimitrakakis

Absence of Transplacental Passage of the Low Molecular Weight Heparin Enoxaparin

Background: Venous thromboembolism (VTE) during pregnancy and puerperium remains a major cause of maternal morbidity and mortality. The use of low molecular weight heparin (LMWH) constitutes a promising alternative for the prevention of VTE instead of unfractionated heparin as it can be administered subcutaneously once daily and without coagulation measurement. Unfortunately, the safety of LMWHs administration for the mother and fetus has not been well established. Study Design: In order to examine the safety of enoxaparin to the fetus, 24 women were recruited and 40 mg of enoxaparin was administered in 14 of them. All 24 women were going to have an early termination of pregnancy due to major fetal malformations. Maternal blood samples were drawn before and after the injection of enoxaparin, while fetal blood samples were taken only after the drug administration. Anti-IIa and anti-Xa activities were measured. Results: A statistically significant increase of anti-Xa activity in the mothers studied was pointed out, while there was no detection of anti-IIa and anti-Xa activities in the fetuses. Conclusions: Since no anti-IIa and anti-Xa activities were detected in the fetuses’ blood samples, it is concluded that enoxaparin does not cross the placenta and therefore appears safe for the fetus.

Taxanes for breast cancer during pregnancy: a systematic review.

Landmark studies have established taxanes in the treatment of patients with breast cancer; however, recommendations regarding their administration during pregnancy are controversial. The present systematic review aims to synthesize all available data that stem exclusively from breast cancer case series to evaluate the efficacy and safety of taxanes during pregnancy. Overall, 16 studies (50 pregnancies) were eligible for the systematic review according to prisma guidelines. The mean age of patients with breast cancer at pregnancy was 34.6 years. The gestational age (GA) at chemotherapy administration varied from 12 to 36 weeks. The mean GA at delivery was 35.9 weeks. The mean weight of babies at delivery was 2380 g. In 76.7% of cases, a completely healthy neonate was born; in the remaining cases, a neonate who was dystrophic and premature, one with mild hydrocephalus, one with signs of bacterial sepsis, one with hyperbilirubinemia, one with apnea of prematurity, respiratory distress syndrome and gastroesophageal reflux, one with meconium-stained fluid, and another neonate with neutropenia and pyloric stenosis were reported. Ninety percent of children were completely healthy, with a median follow-up of 16 months; in the remaining cases, one child with recurrent otitis media, one with immunoglobulin A deficiency and mild constipation, and another child with delayed speech were reported. In conclusion, available data suggest that taxanes may potentially play a promising role in the optimal therapeutic strategy of patients with breast cancer diagnosed during pregnancy.

Maternal mortality in Greece (1980-1996).

OBJECTIVE To use data from the National Statistical Service of Greece to examine trends in maternal mortality and risk factors for maternal deaths. STUDY DESIGN Maternal mortality in Greece has been studied from years 1980 to 1996 in total, by cause of death, by residency (urban/rural) and by maternal age. The maternal mortality ratio (MMR) has been defined as the number of deaths per 100,000 live births. RESULTS From years 1980 to 1996, there have been 136 maternal deaths (MMR: 7). The number of deaths has significantly decreased during this period and six major causes of death have been identified, resulting in 80% of maternal deaths. A simulation of maternal mortality between urban and rural areas has been achieved during the last decade. Also, maternal mortality rises dramatically with age. CONCLUSIONS Although overall rates of maternal mortality in Greece have been significantly decreased over the last years, an improved recording of maternal deaths is necessary for identifying preventable factors and developing effective interventions.

Cancer in pregnancy: disentangling treatment modalities

Pregnancy-associated cancer constitutes an uncommon and difficult to manage clinical situation. It is defined as the cancer diagnosed from the first day of childbearing to 1 year post partum. Coexistence of cancer with pregnancy adds complexity to treatment recommendations, as both the mother and the fetus may be affected. The optimal therapeutic management of pregnant women with cancer diagnosis should take into account, apart from medical factors, a host of other parameters (ethical, psychological, religious, legal, etc). Unfortunately, this situation becomes more complex as more women delay childbearing, and consequently the incidence of cancer during pregnancy is constantly increasing. This manuscript summarises the general principles in managing pregnant patients with cancer and gives detailed instructions in the management of pregnant patients with breast cancer, ovarian cancer, melanoma, lymphoma, lung cancer, soft-tissue sarcoma and cervical cancer. Of note, management of pregnant women with cancer diagnosis should be performed in specialised centres with experience and all cases should be discussed in multidisciplinary meetings composed of multiple specialists (medical oncologists, obstetricians, surgeons, radiologists and paediatricians).

Breast Disorders in Girls and Adolescents. Is There a Need for a Specialized Service

INTRODUCTION Minor breast concerns in childhood and adolescence are common and lead to increased anxiety among young patients and their families, particularly due to high correlation with breast cancer. However, most breast services aim at managing adults and triaging patients with breast cancer, whereas adolescent medicine specialists or pediatricians are usually not appropriately trained to identify and treat breast pathology. METHODS We reviewed hospital records of all patients attending a pediatric and adolescent gynecology or breast clinic of a tertiary referral hospital, with a breast related symptom, between January 2009 and December 2011. We collected information regarding age at presentation, age at menarche, diagnosis, management and outcome. RESULTS We identified 81 patients of which 11 presented with an abnormal nipple or areolar secretion, 33 had a palpable lump, 20 had mastitis, and 16 had unequal breast development. One patient presented with virginal breast hypertrophy. Three out of 11 of the patients with an abnormal secretion had a cyst identified on ultrasonography. Out of the palpable lumps 12 were fibroadenomas, 3 were phyllodes tumors, and 14 were cystic in nature. The phyllodes tumors and half of the fibroadenomas were removed. The remaining fibroadenomas remain under regular ultrasonographic follow-up. All cases of mastitis were treated conservatively and resolved with broad spectrum antibiotic treatment. CONCLUSION In our series, no malignancies were identified. Although 8 patients required surgical treatment, the majority of cases were treated conservatively.

A Woman with Breast Cancer and Severe Impaired Lactose Tolerance: An Intriguing Therapeutic Dilemma

To the Editor: A variety of prognostic and predictive factors influence the treatment of localized breast cancer since they have a bearing on both prognosis and selection of adjuvant treatment, one of which is the hormone receptor status. Hormonal therapy is directed toward inhibiting estrogen from stimulating the growth of cancer cells that require estrogen to proliferate. Given that hormone receptor (ER and ⁄ or PR)-positive breast cancer requires estrogen to grow, hormonal therapy is effective in hormone receptor-positive breast cases. Data from the Early Breast Cancer Trialists’ Collaborative Group (1), as well from several randomized clinical trials of postmenopausal women with localized hormone receptorpositive breast cancer have shown that adjuvant use of aromatase inhibitors (anastrazole, letrozole, examestane) and tamoxifen reduces the annual risk of breast cancer recurrence by more than 40% and decreases the annual risk of death by more than 35% (2–5). Therefore, it is crucial that women with hormone receptor (ER and ⁄ or PR)-positive breast cancer take hormonal treatment, i.e., tamoxifen or an aromatase inhibitor. Herein, we report a really unusual case of a 50year-old postmenopausal woman with infiltrative lobular carcinoma. The woman had undergone extensive lumpectomy with axillary lymph node dissection, which revealed an infiltrative lobular carcinoma measuring 3.5 cm in its greatest diameter with 13 ⁄ 28 lymph nodes infiltrate, according to the TNM system as T2N3M0. Immunohistochemical examination disclosed a high expression of estrogen receptors (ER: 100%+++) whereas progesterone and HER-2 ⁄ neu expression was negative. Imaging studies did not locate metastatic disease. Regarding breast cancer treatment, the patient underwent irradiation therapy to the remnant breast, received chemotherapy and was prescribed 1 mg of oral anastrazole daily. However, from the first day of treatment the woman experienced grade 3 diarrheas; letrozole (2.5 mg), examestane (25 mg), and tamoxifen (20 mg daily) were used, none of which the woman could tolerate at all. More detailed medical history revealed that the woman had impaired lactose tolerance. Given the necessity for the woman to receive hormonal treatment, fulvestrant 500 mg represents an alternative. Fulvestrant is an R antagonist which, unlike SERMs, has no known agonist effect and downregulates the ER protein (6). It should mentioned that this drug has no indication in the adjuvant setting. But, in two global phase III clinical trials fulvestrant proved to be at least as effective and as equally well tolerated as anastrazole for the treatment of postmenopausal women with advanced and metastatic breast cancer. Taking into consideration that fulvestrant has no lactose excipient and the fact that it is given i.m and not per os, one could consider fulvestrant as an attractive option. Severe impaired lactose tolerance is quite a rare condition; in such cases, aromatase inhibitors as well as tamoxifen are not usually well tolerated. Given the benefit of hormonal treatment to these women, fulvestrant should always be considered as an alternative option.

A unique case of total metastatic lobular breast carcinoma, originating from diffused microcalcifications, presented in a postmenopausal woman, without clinical manifestations

Highlights • The association of LCIS with total metastatic LBC is very rare, presented in mammography as microcalcifications or focal asymmetric densities.• Normal or benign mammographic findings are more frequently reported with ILC than other invasive breast cancers.• LCIS is treated as a benign entity with an associated risk for a future developing carcinoma.

A prepubertal giant juvenile fibroadenoma in a 12-year-old girl: Case report and brief literature review

Highlights • Giant juvenile fibroadenomas are very rare and they have very low prevalence in prepubertal period. Although they should not be ruled out in differential diagnosis in premenarchal period.• Breast examination in premenarchal girls and adolescents plays a pivotal role in order to prevent these peculiar giant lesions.• Another remarkable point is the rapid growth of these breast lesions that should not be ruled out in the diagnostic process of the continuously growth of the adolescent breast.