Breast cancer in women younger than 35 years old.

PURPOSE: Women ≤ 35 years old with breast cancer constitute a special group. Considering the impact of the disease and its prognosis, these patients face some specific problems that are not present in older women. What are the prognostic features of the survival rate in very young women with breast cancer? METHODS: Retrospective analysis of very young women with breast cancer from the Surgical-Oncologic Breast Cancer Department at "Theagenio" Anticancer Hospital, 2003-2016. Patient and tumor characteristics, treatment options and follow-up information were collected. Univariate-multivariate analyses were conducted and survival rates were calculated. RESULTS: The median age was 34 years old. 53 patients (41%) had T1, 36 (28%) had T2, 7 (5.4%) had T3 and 33 (25.6%) had T4 stage tumors. Most women, 114 (88.4%), had ductal carcinoma in their histology. Furthermore, positive axillary lymph nodes were present in 62 women (48%). In the immunochemistry report, 91 patients (70.5%) were hormone receptor positive, HER2 was overexpressed in 32 patients (24.8%) and 27 patients presented with triple-negative subtype. Out of 65 patients tested for Ki-67, 51 (78.5%), had a high expression (cut-off value of 20%). After adjusting for all possible factors, the risk of recurrence and death was six times higher in the positive lymph node group, (p < 0.001). The median disease-free and overall survival was 133 and > 173 months, respectively. CONCLUSION: Breast cancer in very young women appears with large size and high-grade tumors, high incidence of infiltrated axillary lymph nodes, high Ki-67 expression and intrinsic subtypes with poor prognosis. As a result, these women need to be treated by a multidisciplinary team.

Protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) in endometriosis and normal endometrium.

Given the involvement of different extracellular matrix (ECM) metalloproteinases (MMPs) in endometriosis, the protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) was analyzed in this study in endometriosis and normal endometrium. Tissue samples were collected prospectively from 64 premenopausal patients undergoing operative laparoscopy. Protein expression of TIMP3 was analyzed immunohistochemically in endometriotic lesions (n = 30) and normal eutopic endometrium from patients with (n = 35) and without (n = 29) endometriosis. Comparison between the three different groups of tissue samples showed that TIMP3 was differentially expressed between the three groups (p = .04). Pair-wise comparisons showed that TIMP3 expression was lower in endometriotic lesions as compared with normal eutopic endometrium from controls (p = .006); the same non-significant trend was found, in the comparison between endometriosis lesions and matched eutopic endometrium. There were no differences in TIMP3 expression in the normal eutopic endometrium between patients with and without endometriosis. In conclusion, TIMP3 seems to be involved in the pathogenesis, pathophysiology, and maintenance of endometriosis and it might be useful as a diagnostic and prognostic marker of endometriosis. Future studies should further investigate this issue, as well as the interplay between TIMPs and different extracellular MMPs in endometriosis.

Cavernous Breast Hemangioma Mimicking an Invasive Lesion on Contrast-Enhanced MRI.

Hemangiomas are vascular lesions, which are only rarely located in the breast. Larger breast hemangiomas may be detected by clinical examination, mammography, and breast ultrasound, whereas smaller lesions are usually incidental findings. We present a rare case of a 43-year-old woman with a cavernous hemangioma of the breast, presenting only on MRI and evading mammographic and ultrasonographic imaging. On breast MRI, a small lesion with irregular margins was detected in the right breast, and following gadolinium contrast medium administration, a type 3 curve, with rapid initial rise, followed by reduction in enhancement (washout) in the delayed phase was noted, raising suspicion for malignancy. The lesion could not be visualized on second-look targeted breast ultrasound and full-field digital mammography. A wide local excision was performed after 3 T MRI-guided hook wire localization and diagnosis of cavernous hemangioma was established histologically. Cavernous hemangioma is a rare breast lesion, with only few cases reported in the literature, and this is the first case with a presentation mimicking an invasive tumor on contrast-enhanced MRI.

Split Hand Foot Malformation Syndrome: A Novel Heterozygous FGFR1 Mutation Detected by Next Generation Sequencing.

BACKGROUND: Split-hand/foot malformation syndrome is a rare, clinically and genetically het-erogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. It may occur as an isolated abnormality or it may be associated with a genetic syn-drome. CASE REPORT: In the present case, isolated split-hand/split-foot malformation was diagnosed by prenatal ultrasound at 24 weeks in a male singleton fetus, with deep median cleft of the right hand, syndactyly and hypoplasia of phalanges in both hands, and oligodactyly of the right foot. During consultation, the father of the fetus revealed that he also had an isolated right foot dysplasia. The parents chose elective termination and autopsy confirmed prenatal ultrasound findings. Genetic testing of the aborted fetus with QF-PCR analysis for common aneuploidies and array comparative genomic hybridization (aCGH) showed a male genomic pattern, without aneuploidies or chromosomal imbalances. Further investigation with next generation sequencing of 49 clinically relevant genes revealed a novel heterozygous FGFR1 mutation c.787_789del (p.Ala263del) in the fetus; the father was heterozygous to the same mutation. CONCLUSION: A novel heterozygous FGFR1 mutation causing split-hand/foot malformation syndrome is reported. Accurate genetic diagnosis allowed detailed counseling to be provided to the couple, including the underlying cause, recurrence risks, and detailed management plan with preimplantation genetic diag-nosis for future pregnancies.

Regulation of basal metabolic rate in uncomplicated pregnancy and in gestational diabetes mellitus.

Basal metabolic rate (BMR) is one of the major components of total energy expenditure (TEE). It is affected by various factors, such as body weight, body composition, age, race/ethnicity, gender, biochemical parameters, physical activity, and health status. Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy and it increases the risk for health complications, such as stillbirth, diabetes mellitus, and cardiovascular disease in later life. Both BMR and GDM have been linked with gestational weight gain (GWG), a fact suggesting a possible association between them. However, assessing BMR is a complex procedure, which becomes more complicated when additional parameters, such as pregnancy and GDM, are taken into consideration. The present review summarizes the current knowledge on factors affecting BMR and its regulation in relation to pregnancy and GDM. Future research addressing these associations should thoroughly consider other factors that affect BMI when designing such studies and/or discussing the BMR outcome results.

Amniotic Fluid and Maternal Serum Metabolic Signatures in the Second Trimester Associated with Preterm Delivery.

Preterm delivery (PTD) represents a major health problem that occurs in 1 in 10 births. The hypothesis of the present study was that the metabolic profile of different biological fluids, obtained from pregnant women during the second trimester of gestation, could allow useful correlations with pregnancy outcome. Holistic and targeted metabolomics approaches were applied for the complementary assessment of the metabolic content of prospectively collected amniotic fluid (AF) and paired maternal blood serum samples from 35 women who delivered preterm (between 29 weeks + 0 days and 36 weeks +5 days gestation) and 35 women delivered at term. The results revealed trends relating the metabolic content of the analyzed samples with preterm delivery. Untargeted and targeted profiling showed differentiations in certain key metabolites in the biological fluids of the two study groups. In AF, intermediate metabolites involved in energy metabolism (pyruvic acid, glutamic acid, and glutamine) were found to contribute to the classification of the two groups. In maternal serum, increased levels of lipids and alterations of key end-point metabolites were observed in cases of preterm delivery. Overall, the metabolic content of second-trimester AF and maternal blood serum shows potential for the identification of biomarkers related to fetal growth and preterm delivery.

Sorafenib in breast cancer treatment: A systematic review and overview of clinical trials.

AIM: To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer. METHODS: An extensive search of the literature until March 2016 was carried out in Medline and clinicaltrials.gov, by using the search terms "sorafenib" and "breast cancer". Papers found were checked for further relevant publications. Overall, 21 relevant studies were found, 18 in advanced breast cancer (16 in stage IV and two in stages III-IV) and three in early breast cancer. RESULTS: Among studies in advanced breast cancer, there were two trials with sorafenib as monotherapy, four trials of sorafenib in combination with taxanes, two in combination with capecitabine, one with gemcitabine and/or capecitabine, one with vinorelbine, one with bevacizumab, one with pemetrexed and one with ixabepilone, three trials of sorafenib in combination with endocrine therapy and two trials in women with brain metastases undergoing whole brain radiotherapy. In addition, there was one trial of sorafenib added to standard chemotherapy in the adjuvant setting, and two trials in the neoadjuvant setting. In general, sorafenib was well tolerated in breast cancer patients, though its dosage had to be adjusted in some trials, and discontinuation rates were high, particularly for the combination of sorafenib with anastrozole. Sorafenib monotherapy and combinations with taxanes, bevacizumab and ixabepilone showed inadequate efficacy, while efficacy results from combinations with gemcitabine and/or capecitabine and possibly tamoxifen were more promising. CONCLUSION: At present, sorafenib should not be used for the treatment of breast cancer outside of clinical trials and more clinical data are needed in order to support its standard use in breast cancer therapy.

Quality-of-life changes over time in breast cancer patients undergoing breast-conserving surgery: a prospective study in Greece.

AIM: The aim of the present study was to evaluate quality of life (QL) over time in patients undergoing breast-conserving surgery, due to primary operable breast cancer, in Greece. MATERIALS AND METHODS: This was a prospective, questionnaire-based study in women with primary operable breast cancer. A Greek version of the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire was used. Patients filled out all six subscales of FACT-B, initially 24 h prior to and then 3-7 days and 9-12 months after breast-conserving surgery. All participants received standard adjuvant therapy. Patients with metastatic disease, psychiatric comorbidities and those treated with neoadjuvant therapy were excluded. Data were statistically analyzed using parametric and nonparametric tests as indicated. RESULTS: In total, 155 women, with a mean age of 59.2 years (range 30-80 years), filled out the study questionnaire. Patients' social/family well-being improved 3-7 days and 9-12 months after the operation as compared with the preoperative period (p < 0.05). Patient-doctor relationship and functional well-being deteriorated (p < 0.05), while physical well-being improved (p < 0.05) 9-12 months after surgery than prior to or 3-7 days postoperatively. Finally, emotional well-being and "additional concerns" and overall QL were all better 3-7 days postoperatively than prior to or 9-12 months after the operation (p < 0.05). Among demographic factors, patient age and place of residence did not appear to have any effect on QL, in contrast to marital status, with married women having better QL in the social/family subscale (p < 0.05). With respect to histopathological factors, patients with ER- and/or PR-positive tumors had better QL in the physical well-being but worse in the functional subscale, 9-12 months after surgery. No significant correlation was found between QL and other histopathological factors. CONCLUSION: In the long term, patients' QL deteriorates with respect to functional and emotional well-being, "additional concerns" and patient-doctor relationship. Hence, specific interventions should aim to improve these aspects of QL in breast cancer patients undergoing breast-conserving surgery.

Immunohistochemical expression pattern of metastasis suppressors KAI1 and KISS1 in endometriosis and normal endometrium.

OBJECTIVE: To analyze the expression pattern of metastasis suppressors KAI1 and KISS1 in the endometrium of patients with and without endometriosis. STUDY DESIGN: In this pilot study, tissue samples were prospectively collected from 38 patients with endometriosis and 29 without endometriosis, undergoing operative laparoscopy in the proliferative phase of the menstrual cycle; diagnosis or absence of endometriosis was confirmed histologically. Protein expression of KAI1 and KISS1 were analyzed immunohistochemically in endometriotic lesions and the eutopic endometrium of patients with endometriosis and without endometriosis. RESULTS: KAI1 expression was significantly decreased in the glandular eutopic endometrium of endometriosis patients as compared with that of patients without endometriosis (p=0.008). On the other hand, in endometriosis patients, KAI1 expression was significantly increased in the ectopic as compared with the eutopic endometrial stroma (p=0.021). There were no other significant differences in KAI1 expression between different groups. KISS1 expression in the ectopic glandular endometrium was significantly increased as compared with the eutopic glandular endometrium from patients with (p=0.004) and without endometriosis (p=0.008). There was no significant difference in KISS1 protein expression in the stromal endometrium between the three groups. CONCLUSIONS: KAI1 and KISS1 are implicated in the pathogenesis and maintenance of endometriosis. Future studies should investigate whether KAI1 and KISS1 could be used as markers for early and minimally invasive detection of endometriosis based on their differential protein expression pattern in the eutopic endometrium of patients with and without endometriosis.

Fetal nasal bone length in the second trimester: comparison between population groups from different ethnic origins.

OBJECTIVE: To compare normal ranges of ultrasonographically measured fetal nasal bone length in the second trimester between different ethnic groups. METHOD: A prospective, non-interventional study in order to establish normal ranges of fetal nasal bone length in the second trimester in a Greek population was conducted in 1220 singleton fetuses between 18 completed weeks and 23 weeks and 6 days of gestation. A literature search followed in order to identify similar studies in different population groups. Fetal nasal bone length mean values and percentiles from different population groups were compared. RESULTS: Analysis of measurements in the Greek population showed a linear association, i.e., increasing nasal bone length with increasing gestational age from 5.73 mm at 18 weeks to 7.63 mm at 23 weeks. Eleven studies establishing normal ranges of fetal nasal bone length in the second trimester were identified. Comparison of fetal nasal bone length mean values between the 12 population groups showed statistically significant differences (P<0.0001). CONCLUSION: Normal ranges of fetal nasal bone length in the second trimester vary significantly between different ethnic groups. Hence, distinct ethnic nomograms of fetal nasal bone length in the second trimester should be used in a given population rather than an international model.

Screening performance of different methods defining fetal nasal bone hypoplasia as a single and combined marker for the detection of trisomy 21 in the second trimester.

OBJECTIVE: To evaluate different methods of defining fetal nasal bone hypoplasia in the second trimester for the detection of trisomy 21. METHODS: Prospective study in Greek women undergoing anomaly scan between 18 + 0 and 23 + 6 weeks. The following methods of defining nasal bone hypoplasia were evaluated, either as a single marker or in combination with others: (1) BPD to nasal bone length (NBL) ratio; (2) multiples of the median (MoM) of NBL, according to normal curves from a Greek population; (3-4) NBL < 2.5 percentile according to normal curves (3) commonly used internationally curves and (4) curves from a Greek population. RESULTS: In total, 1301 singleton fetuses were evaluated - 10 with trisomy 21. The best detection rate of trisomy 21 was achieved when the applied method was nasal bone percentiles adjusted to maternal ethnicity, in combination with other markers (<2.5 percentile according to normal curves from a Greek population; p < 0.001; sensitivity 50%; specificity 94.8%; false-positive rate 5.2%; positive likelihood ratio 9.6). CONCLUSION: Screening performance of fetal nasal bone hypoplasia in detecting trisomy 21 varies according to the method applied. The best screening performance is achieved by using percentiles adjusted to maternal ethnicity in combination with other markers of aneuploidy.

Distinct demographic factors influence the acceptance of vaccination against HPV.

PURPOSE: To investigate the possible effect of demographic factors on HPV vaccination acceptance in Greece. METHODS: Analysis was performed on data from the "LYSISTRATA" project, a prospective, cross-sectional study, focusing on questions regarding the acceptance of HPV vaccination among Greek women for themselves, and their 13-year-old daughter or son. In total, 5,379 women participated in the study, between 2005 and 2011. RESULTS: Women born and raised in Greece were more likely to accept HPV vaccination for themselves (aOR = 4.1, 95 % CI 2.9-5.8), their daughter (aOR = 3.3, 95 % CI 2.3-4.7) and son (aOR = 3.3, 95 % CI 2.3-4.8), compared with immigrants. Similarly, women who had a Papanicolaou's test were more likely to accept vaccination for themselves (aOR = 1.8, 95 % CI 1.4-2.3), their daughter (aOR = 1.5, 95 % CI 1.2-1.9) and son (aOR = 1.4, 95 % CI 1.1-1.7) than those never tested. Smokers were less likely to accept HPV vaccination for themselves (aOR = 0.8, 95 % CI 0.6-0.9); however, such an association was not documented concerning their children. Educational level had a rather inconsistent impact on HPV vaccination acceptance. The effect of womens' age, monthly income, residence, profession and marital status on HPV vaccination acceptance for themselves was different than that for their daughters, and even more for their sons. CONCLUSIONS: There are distinct demographic factors that influence HPV vaccination acceptance. Women's perception that male vaccination is not as necessary may lead to lower acceptance of HPV vaccination for young boys and men.

Epidemiology of HPV infection and current status of cervical cancer prevention in Greece: final results of the LYSISTRATA cross-sectional study.

The objective of this study was to assess the overall prevalence of the human papilloma virus (HPV) infection and distribution of high-risk HPV (hrHPV) types in Greece and evaluate the participation of women in primary and secondary cervical cancer prevention. This was a prospective, cross-sectional study carried out between October 2005 and January 2011 in Greece; 5379 women filled out the study questionnaire anonymously. 5107 women underwent cervical HPV-DNA testing, either by Hybrid Capture 2, followed by restriction fragment length polymorphism-PCR, or by the Abbott Real-Time High-Risk HPV test. Overall, 5.8% (295/5107) of women were positive for hrHPV infection. The most common hrHPV type was HPV-16 (24.8% among infected women; 1.4% overall), followed by HPV types 31, 35, 53, 18, 51, 56, 58, 52, 39, 66, 45, 33, 59, and 68. In respect to primary prevention of cervical cancer, acceptance of anti-HPV vaccination appeared to decrease over time (from 85-89.9% annually during 2005-2008 to 64.4-60.5% during 2009-2010, P<0.001). In respect to secondary prevention, only 30.3% of women had regular (annually for more than 5 years) Pap smears; regular gynecologic examinations, Papanicolaou testing, and knowledge of HPV were all associated with various demographic parameters (age, education, place of residence, occupation, and income). The prevalence of hrHPV infection in Greece is similar to that in other European countries; the most common type is HPV-16. The initially relatively high acceptance of HPV vaccination decreased after licensing of the vaccine. Demographic parameters appear to influence participation in cervical cancer screening.

Endometriosis and ovarian cancer risk: a systematic review of epidemiological studies.

BACKGROUND: A possible etiological association between endometriosis and ovarian cancer has been repeatedly reported in the literature. OBJECTIVE: Our aim was to evaluate published epidemiological data on this issue. REVIEW METHODS: We conducted an extensive search of the literature in MEDLINE, of articles ever published until February 2014, using the key-words "endometriosis" and "ovarian" and one of the following terms in the title: "cancer" or "malignancy" or "malignant" or "tumor" or "neoplasia" or "neoplasm" or "transformation." Retrieved papers were checked for further relevant publications. RESULTS: Overall, our search yielded 1 prospective cohort study, 10 retrospective cohort, and 5 case-control studies. A meta-analysis of these studies was not considered to be appropriate, due to differences in data reporting, study design, and adjustment for confounding factors. LIMITATIONS: The main limitation of studies found, with one exception, was the lack of operative confirmation of endometriosis. CONCLUSION: An association of endometriosis with clear-cell and endometrioid ovarian cancer was a consistent finding in most studies. On the other hand, existing epidemiological evidence linking endometriosis with ovarian cancer is insufficient to change current clinical practice. Prospective cohort studies, with prior laparoscopic confirmation, localization, and staging of endometriosis are needed, in order to further clarify this issue.

Prenatal diagnosis of thoracic kidney in the 2nd trimester with delayed manifestation of associated diaphragmatic hernia.

Ectopic kidney is a rare congenital malformation, caused by renal malpositioning during embryogenesis. We report a rare case of ectopic kidney located in the left hemithorax of a male fetus. The unique features in this case were early sonographic prenatal diagnosis of thoracic kidney at 22 weeks' gestation, which was confirmed by fetal MRI, and delayed sonographic manifestation of the associated congenital diaphragmatic hernia at 27 weeks.

New insights of osmoregulatory system changes in ovarian hyperstimulation syndrome.

This study evaluated the osmoregulatory system changes in 39 patients with severe ovarian hyperstimulation syndrome. Plasma osmolality (Posm) less or more than 280 mOsm/kg body weight were associated with inappropriate antidiuretic hormone secretion syndrome and hypovolemia, respectively.

Cervical, uterine corpus, and ovarian cancer mortality in Greece during 1980 to 2005: a trend analysis.

INTRODUCTION: The aim of the present study was to analyze cervical, uterine corpus, and ovarian cancer mortality, between 1980 and 2005, in Greece. METHODS: Mortality data and population age distribution were provided by the National Statistical Service of Greece. Time trends of mortality were calculated for each tumor type per 100,000 women in the whole female population of Greece, and 2 different age groups, that is, women aged 49 years and younger and those 50 years and older. Joinpoint regression was used for further analysis of mortality trends. RESULTS: Overall, cervical and uterine corpus cancer mortality in the whole female population of Greece had a slightly decreasing trend between 1980 and 2005, whereas ovarian cancer mortality rates increased steadily throughout the period studied. Subgroup analyses according to age showed that cervical cancer mortality decreased very slightly only in women older than 50 years, whereas it remained steady in younger women. Uterine corpus cancer mortality decreased slightly in both age groups, but increased during the last years of the study period in the older age group. Ovarian cancer mortality increased in women older than 50 years, whereas it remained steady in the younger age group. Joinpoint regression analysis showed that only the increase after 1997 in the mortality trend for uterine corpus cancer in women 50 years and older was statistically significant (P = 0.0044). CONCLUSIONS: Although our findings regarding cervical cancer mortality in Greece are encouraging, still more efforts are needed, particularly in preventing cervical cancer in younger women. The increasing trend of uterine corpus and ovarian cancer mortality in older women suggests that development of well-organized tertiary centers for the implementation of modern therapeutic modalities is urgently needed.

Levonorgestrel-releasing intrauterine system vs. endometrial thermal ablation for menorrhagia.

OBJECTIVE: To evaluate the efficacy of a Levonorgestrel-releasing Intrauterine System (LNG-IUS) in controlling menorrhagia in comparison with endometrial thermal rollerball ablation. DESIGN: Seventy-nine consecutive patients with menorrhagia underwent either LNG-IUS insertion (n=42) or hysteroscopical endometrial thermal rollerball ablation (n=37) in a prospective, observational, comparative study. Women reported duration of uterine bleeding in days prior to, and six and 12 months after each intervention. Prior to each intervention, endometrial, cervical or other pathological conditions of the genital tract were excluded. GnRH analogues for endometrial suppression were given for ten weeks before endometrial ablation but not prior to LNG-IUS insertion. RESULTS: There were no differences in duration of uterine bleeding before each intervention in the two groups. The duration of uterine bleeding was lower in the LNG-IUS group as compared with endometrial ablation at six (p<0.001) and 12 months (p<0.001) after each intervention. Furthermore, the effect on reduction of bleeding was stronger in the LNG-IUS group as compared with the endometrial ablation group at six (p<0.001) and 12 months (p<0.001). CONCLUSIONS: The LNG-IUS was more efficacious than endometrial thermal ablation in reducing duration of uterine bleeding at six and 12 months post-intervention.

Ultrasound and MR-imaging in preoperative evaluation of two rare cases of scar endometriosis.

Scar or incisional endometriosis is a rare, often misdiagnosed, pathologic condition of the abdominal wall. Two cases of incisional endometriosis are presented. Both patients presented with atypical cyclic pain and palpable nodules on scars of previous cesarean sections. In both cases, the mass was totally excised, after accurate preoperative evaluation with 2-D ultrasound, power Doppler and MRI. Microscopic examination confirmed the preoperatively presumed diagnosis of cutaneous endometriosis. In cases of suspected scar endometriosis, preoperative diagnostic imaging is valuable in determining the extent of disease, thus enhancing accurate and total excision.