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.

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.

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.

Transcultural Adaptation of the Breast Cancer Awareness Measure in a Rural Border Area of Greece.

BACKGROUND: Breast cancer awareness is a concept suggesting that awareness of signs and symptoms and early seeking of medical advice may decrease mortality, especially in limited resource settings. METHODS: A modified questionnaire based on the breast cancer awareness measure (BCAM) by Cancer Research UK was translated into Greek and used for the first time. Participants were women residing in a rural border area in Greece. For statistical analysis the χ2 goodness-of-fit and Cramer's V test for categorical comparisons were used and Cronbach's alpha for reliability analysis. RESULTS: In total, 110 women filled out and returned the questionnaire. Respondents appeared to be inappropriately informed regarding the less common warning signs of breast cancer, the most common age of breast cancer occurrence, the national screening program, and the less important risk factors of breast cancer. On the other hand, most women appeared to be confident in recognizing breast changes and seeking medical advice if needed. CONCLUSIONS: The translated modified BCAM tool can be used to evaluate breast cancer awareness in Greek women. Future campaigns developed by policymakers should focus on improving breast cancer awareness, especially in socioeconomically deprived areas.

Sonographic vascularity indices' study in ectopic pregnancies, after methotrexate treatment.

Objectives: Ectopic pregnancy is a crucial problem in Gynaecology. Previous studies concerning the medical treatment of ectopic pregnancies, have used only ß-hCG (beta- human chorionic gonadotropin) values, to monitor the successful response to treatment. The current study was a PhD (Doctorate of Philosophy) thesis research, which has evaluated the vascularity indices' changes. The values of vascularity indices could be used, in combination with ß-hCG values and the gestational sac dimensions, in every medically treated ectopic pregnancy. The results could be used, for monitoring the course of all medically treated ectopic pregnancies. Study design: 72 women of reproductive age have taken part in the study. They have been admitted due to secondary amenorrhea, positive ß-hCG test, with or without vaginal bleeding. The participants took part voluntarily and were allocated in two groups. The first group consisted of 37 women, who were possible normal or threatened intrauterine pregnancies (control group). The second group consisted of 35 women, whose sonographic findings suggested ectopic pregnancy, and qualified for methotrexate treatment (study group). Sonographic control and measurement of the vascularity indices (PI - RI) (Pulsatility index - Resistance index) of the ectopic pregnancy was conducted, in combination with ß-hCG values for every admitted or outpatient woman.The dimensions of the gestational sac of both groups were measured during four consecutive periods of time. The control group has shown progressively increasing sac dimensions, whereas, in the study group sac dimensions were more stable or growing gradually smaller. The exception where those ectopic pregnancies that ruptured, which have also shown a gradual enlargement of the sac. Results: The endometrial thickness of the study group was gradually decreasing up to 76 % per day, and the more eminent, but not statistically significant decrease, was observed in the single dose regiment of methotrexate. Moreover, the quantitative PI and RI were evaluated, and the main finding was that there were no statistically significant decreases in any of the two groups. Concerning the study group, methotrexate treatment was successful, since there was a decrease of up to 80 %, whereas a clearly significant correlation was found between the ß-hCG levels and the RI. Conclusion: The vascularity indices could be used safely, in combination with ß-hCG levels and the decrease of the gestational sac dimensions, as criteria for the evaluation of response to medical treatment of ectopic pregnancies.

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.

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.

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.

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.