Immunohistochemical expression pattern of metastasis suppressor KISS-1 protein in adenomyosis lesions and normal endometrium.

OBJECTIVE: Kisspeptins are multifunctional peptides; it has been shown that they act as inhibitors of tumor metastasis in a range of cancers and that they are also involved in cell invasion through regulation of matrix metalloproteinases (MMPs). The aim of this study was to investigate the expression of KISS-1 protein in adenomyosis lesions compared with matched eutopic endometrium, as well as with endometrium from patients without adenomyosis. STUDY DESIGN: In this comparative, non-interventional study, adenomyosis and corresponding eutopic endometrium samples from women with histologically proven adenomyosis after hysterectomy, and eutopic endometrium samples from women without adenomyosis were analysed. Expression of KISS-1 protein was analyzed immunohistochemically in formalin-fixed, paraffin-embedded adenomyotic tissue specimens (n=29), matched eutopic endometrium from the same patients (n=29) and normal endometrium from patients without adenomyosis (n=29). RESULTS: Using a semi-quantitative immunohistochemical score, we found that KISS-1 protein expression was higher in the adenomyotic as compared with matched eutopic glandular endometrium (p<0.05), in which in turn KISS-1 protein expression was higher than those from patients without adenomyosis (p<0.001). The inverse correlation was found in the stroma, between adenomyosis lesions and matched eutopic endometrium (p<0.01), while no statistically significant correlation was found in KISS-1 protein expression in the stroma between patients with and without adenomyosis. CONCLUSIONS: KISS-1 protein expression appears to be up-regulated in adenomyotic as compared with eutopic glandular endometrium of patients with, as well as women without adenomyosis. These findings are suggestive of the involvement of KISS-1 protein in the pathogenesis and maintenance of adenomyosis. Future studies should investigate whether KISS1 protein could be used as a marker for early and minimally invasive detection of adenomyosis, based on its differential protein expression pattern in the eutopic endometrium of patients with and without adenomyosis.

The effect of physical exercise on postpartum fitness, hormone and lipid levels: a randomized controlled trial in primiparous, lactating women.

PURPOSE: To evaluate the effect of an exercise training program combining low-impact dance aerobic, resistance and stretching exercise on physical fitness, hormone and lipid levels of postpartum, primiparous, lactating women. METHODS: Thirty seven primiparous, lactating women were randomly assigned at 4-6 weeks postpartum to either follow an exercise training program of 50-60 min aerobic, strengthening and stretching exercise, 3 days a week, for 12 weeks (interventional group; n = 20) or no training program at all (control group; n = 17). The following parameters were measured at baseline and 12 weeks later: (1) for evaluation of physical fitness: VO2max, muscular endurance, joint mobility and body fat; (2) for evaluation of the lipidemic profile: triglyceride, total cholesterol, HDL and LDL levels, and (3) levels of hormones associated with lactation: prolactin, estradiol, cortisol, TSH, fT3 and fT4. RESULTS: After completion of the exercise training program, comparisons between the interventional and the control group showed statistically significant mean changes in VO2max (p = 0.003), muscular endurance of the upper extremities (p < 0.001), and the abdomen (p < 0.001), flexibility (p = 0.042), and body fat (p = 0.007). There were no significant differences between the two groups in mean changes of lipid and hormone levels. CONCLUSION: Implementation of a low-impact exercise training program appears to improve physical fitness of postpartum women, while it does not seem to affect lipid levels and lactation-associated hormone levels. Hence, implementation of an exercise training program combining low-impact dance aerobic, resistance and stretching exercise is feasible in postpartum, primiparous, lactating women.

Three-dimensional versus two-dimensional ultrasound for fetal nasal bone evaluation in the second trimester.

OBJECTIVES: To compare two-dimensional with three-dimensional ultrasound evaluation of the fetal nasal bone in the second trimester. METHODS: A prospective, non-interventional study was conducted, in 55 singleton fetuses, between 18 and 24 weeks' gestation. Fetal nasal bone length was measured in the midsagittal plane by two-dimensional imaging and in the midsagittal and coronal plane with three-dimensional ultrasound. All three measurements were compared with one another using one-way repeated samples-measures ANOVA and paired samples t-test. RESULTS: The average fetal nasal bone length (mean ± SD) as determined by the three methods was 7.01 ± 0.94 mm for the two-dimensional midsagittal, 6.96 ± 1.34 mm for the three-dimensional midsagittal, and 6.98 ± 1.32 mm for the three-dimensional coronal plane; comparisons between one another were not statistically significant. Unilateral hypoplasia and bifid shape of the fetal nasal bone were detected in 8.2% and 20.4% of cases, respectively, by three-dimensional ultrasound, whereas all cases evaded detection with two-dimensional ultrasound (p < 0.001 and p = 0.001, respectively). CONCLUSIONS: Fetal nasal bone length measured with two-dimensional ultrasound does not differ significantly from three-dimensional measurements. However, three-dimensional ultrasound is superior in detecting unilateral nasal bone hypoplasia or absence and in assessing fetal nasal bone shape. Hence, fetal nasal bone examination in the second trimester should include three-dimensional ultrasound evaluation.

Obstetric and neonatal outcome after assisted fertilization and spontaneous conception: a comparative study.

PURPOSE: The widespread use of assisted reproduction technology (ART) is accompanied by concerns for potential adverse outcomes. The aim of the present study was to evaluate the impact of ART in obstetric and neonatal outcome. METHODS: Data from labor ward records from 913 consecutive births were analyzed retrospectively, and the obstetric and neonatal outcomes of pregnancies after ART were compared with those after natural conception. RESULTS: No major complications were noted after ART. A higher probability of cesarean section, lower gestational age at birth, lower birth weight and hospitalization in the Neontal Intensive Care Unit (NICU) was noted after ART, as compared with spontaneous conception. However, after exclusion of multifetal pregnancies, there was no significant difference in outcomes, except for cesarean section rates. CONCLUSIONS: The higher proportion of multiple pregnancies after ART is associated with lower gestational age at birth, lower birth weights and higher NICU hospitalization rates.

Time trends of female breast cancer mortality in Greece during 1980-2005: a population based study.

BACKGROUND: Changes in female breast cancer mortality trends have been observed in recent years in western countries. The aim of the present study was to analyse breast cancer mortality in Greece, between 1980 and 2005. METHODS: Time trends of breast cancer mortality were calculated per 100,000 women in the whole female population of Greece, in different age groups, and in different areas of the country. Mortality data and population age distribution were provided by the National Statistical Service of Greece. RESULTS: Overall, female breast cancer mortality in Greece had an increasing trend during 1980-2005. Subgroup analysis according to age showed that this increase was confined to women older than 70 years. In contrast, a mild decrease was noted after the mid-1990s in women 40-69 years old. There were no notable regional differences in breast cancer mortality. CONCLUSIONS: The increasing trend of breast cancer mortality in women aged 70 years and older could be attributed to limited use of secondary prevention methods and rare administration of systemic cytotoxic chemotherapy in these women. In contrast, implementation of these strategies could explain the recent reduction of breast cancer mortality in younger age groups.

Broad ligament leiomyosarcoma in a premenopausal nulliparous woman: case report and review of the literature.

Leiomyosarcomas of the broad ligament of the uterus are extremely rare tumors. Most of the time they are diagnosed in older women and despite radical surgical treatment prognosis is dismal. We present a rare case of a 38-year-old nulligravida presenting with a large, firm mass, fixed in the pelvis. After enucleation of the tumor, histological examination revealed the presence of a broad ligament leiomyosarcoma, leading to total abdominal hysterectomy and bilateral salpingo-ophorectomy three weeks later. Management options and cases reported in the literature are reviewed.

Long-term follow-up after cervical cancer treatment and subsequent successful surrogate pregnancy.

Preservation of fertility is a major concern for premenopausal women after diagnosis of cervical cancer. Successful surrogate pregnancy after treatment for cervical cancer has very rarely been reported. In the present report, a case of successful surrogate pregnancy after radical hysterectomy, lymphadenectomy and ovarian transposition for cervical cancer, followed by radiation therapy, is presented. After stimulation of the transposed ovaries using the short gonadotrophin-releasing hormone (GnRH) analogue protocol, four oocytes were retrieved transabdominally from the genetic mother. IVF followed and two embryos were transferred to the surrogate mother, leading to an uneventful singleton pregnancy, and ultimately normal vaginal delivery of a healthy female infant at term. The unique aspect in this case is the long-lasting favourable outcome for both genetic mother and child, observed during 8.5 years of follow-up, the longest follow-up period reported to date in such cases.

ERBB2 (HER2) protein expression in uterine sarcomas.

PURPOSE: Multiple clinical trials in recent years have shown that breast cancer patients with primary tumors overexpressing ERBB2 can be effectively treated with specific forms of modern anti-ERBB2-targeted therapy. The aim of the present study was to analyze the expression of the ERBB2 (HER2) protein in uterine sarcomas, in order to investigate the possibility of applying this treatment modality in uterine sarcomas. METHODS: The expression of ERBB2 has been analyzed immunohistochemically in formalin-fixed paraffin-embedded primary uterine sarcomas (n = 11). RESULTS: Using a semi-quantitative immunohistochemical score, we found that ERBB2 expression was very weak in the majority of tumors, with only three sarcomas showing moderate ERBB2 expression. Published studies evaluating the same issue in small numbers of uterine sarcomas reached similar findings. CONCLUSION: Overall, ERBB2 expression appears to be weak in uterine sarcomas. However, targeted treatment might still be feasible in a subgroup of patients with uterine sarcomas overexpressing ERBB2.

Virilizing ovarian hilus (Leydig) cell tumor with concurrent contralateral hilus cell hyperplasia: a rare diagnosis.

Ovarian hilus or Leydig cell tumor and ovarian hilus cell hyperplasia are rare clinical entities, causing virilization in both pre- and postmenopausal women. Differentiation between these two conditions is not always straightforward; the former is usually unilateral appearing as a single, grossly visible, circumscribed mass of hilus cells, while the latter is usually bilateral, appearing as diffuse microscopic aggregates of hilus cells. We report herein an extremely rare case of ovarian hilus or Leydig cell tumor, presenting concurrently with contralateral ovarian hilus cell hyperplasia in a postmenopausal woman with virilization. To the best of our knowledge, only four such cases have been previously reported in the literature. Ovarian hilus cell tumors and hilus hyperplasia almost always have benign biological behavior, thus making bilateral salpingo-oophorectomy an appropriate and sufficient therapeutic approach.

A unique case of palatinate tonsil metastasis from endometrial cancer.

Metastases from malignancies of the female genital tract to the tonsils have never been reported. A case of a 55-year-old woman presenting with a palatinate tonsil tumour two and half years after primary diagnosis of endometrioid endometrial adenocarcinoma (FIGO Stage IB, G2) and six months after local disease recurrence is presented. The tonsillar malignancy was poorly differentiated and tumour cells were immunohistochemically positive to LMW keratin and EMA, and negative to HMW keratin and LCA, strongly suggesting a possible endometrial origin of the tumour. Metastatic disease was treated with systemic chemotherapy, but the patient soon succumbed due to rapid disease progression. In conclusion, a unique case of a palatinate tonsil tumour as the first metastatic site in an endometrial cancer patient is reported.

A rare case of renal cell carcinoma metastasizing to the uterine cervix.

Metastatic tumors to the uterine cervix originating from malignancies in other organs are very rare. A case of a 45-year-old white woman presenting with vaginal bleeding, due to renal cell carcinoma metastasizing to the cervix, is reported. The patient had been treated four years and five months earlier due to two primary malignancies: colon adenocarcinoma and renal cell carcinoma. After D&C, microscopic examination and immunohistochemical staining showed that the tumor was metastatic, originating from the renal cell carcinoma. Radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node resection followed, and postoperatively the patient received targeted therapy with sutinib malate. The possibility of metastasis from another primary should be considered in the differential diagnosis of tumors of the uterine cervix in order to plan optimal management.

Human placental lactogen and color Doppler in predicting expulsion of retained adherent placenta: a new clinical observation.

PURPOSE: To present a new clinical observation made in three cases of retained adherent placenta, a rare obstetrical complication, associated with potentially life-threatening hemorrhage. METHODS: Three consecutive cases of retained adherent placenta are presented. RESULTS: Diagnosis of placenta increta in two and placenta percreta in one case was established with ultrasound and MRI. Methotrexate 50 mg i.v. (300 mg total dose) and follinic acid 0.1 mg/kg were administered on alternating days, over 12 days. On follow-up, placental perfusion on color Doppler was present up to the point when circulating hPL levels were no longer detectable; this was followed in all cases by spontaneous placental expulsion within 10 days. CONCLUSIONS: The observation that both color Doppler and human placental lactogen can be used to monitor response to therapy and predict placental expulsion should be evaluated in future cases of retained adherent placenta.

Hormone therapy for postmenopausal breast cancer survivors: a survey among obstetrician-gynaecologists.

PURPOSE OF INVESTIGATION: To investigate the attitude of Greek obstetrician-gynaecologists towards prescription of hormone therapy to postmenopausal breast cancer survivors. METHODS: An anonymous questionnaire was sent to members of the Hellenic Society of Obstetrics and Gynaecology with a hypothetical case and a series of relevant questions. RESULTS: Three hundred valid answers were received. Hormone therapy would be prescribed to a breast cancer survivor by only 8%; 80% of these would prefer tibolone. In contrast, 92% would not prescribe hormone therapy; 97% would do so due to the risk of disease recurrence; 70% would not prescribe any alternative therapy, 21% would prescribe CNS-active compounds and 7% SERMs. CONCLUSIONS: The vast majority of Greek obstetrician-gynaecologists would not prescribe hormone therapy for menopausal symptoms in breast cancer survivors due to the theoretical risk of disease recurrence. Among those who would not prescribe hormone therapy, 21% would opt to CNS-active compounds.

Apert syndrome: the current role of prenatal ultrasound and genetic analysis in diagnosis and counselling.

Apert syndrome is a rare congenital malformation syndrome characterized by the triad of cutaneous and progressive bony syndactyly, midfacial hypoplasia and craniosynostosis. Two missense mutations of the gene encoding the fibroblast growth factor receptor 2 (FGFR2) have been implicated in most cases. We report a case of Apert syndrome detected on prenatal ultrasound. Postnatal genetic analysis showed, for the first time, that the previously reported P253R mutation of the FGFR2 gene is also prevalent in southeast Europe. After prenatal sonographic detection of anomalies suggestive of Apert syndrome, parents should be counselled about prognosis and risk of recurrence, and the option of amniocentesis should be offered.

KIT protein expression in uterine sarcomas: an immunohistochemical study and review of the literature.

PURPOSE: The aim of the present study was to investigate the possibility of treating uterine sarcomas with imatinib mesylate. Imatinib mesylate, a selective tyrosine kinase inhibitor, is very efficient against mesenchymal tumors of the gastrointestinal tract, known as GISTs. Imatinib mesylate acts against a tyrosine kinase encoded by the KIT gene in GISTs, and is more effective in tumors expressing this protein. METHODS: Expression of KIT was analyzed immunohistochemically (n = 12) in formalin-fixed paraffin-embedded primary uterine sarcomas. RESULTS: Using a semi-quantitative immunohistochemical score we found that KIT expression was very weak in the majority of tumors, while none of the uterine sarcomas tested showed strong expression. Overall, published studies addressing this issue in small series of uterine sarcomas yielded similar results. CONCLUSION: Current data suggest that it is unlikely that imatinib mesylate could be used effectively as a single agent in patients with uterine sarcomas.

The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation.

Inter-alpha-trypsin inhibitors (ITIs) are protease inhibitors stabilizing the extracellular matrix. ITIs consist of one light (bikunin) and two heavy chains (ITIHs). We have recently characterized ITIH5, a novel member of the ITIH gene family, and showed that its messenger RNA is lost in a high proportion of breast tumours. In the present study, an ITIH5-specific polyclonal antibody was generated, validated with western blot and used for immunohistochemical analysis on a tissue microarray; ITIH5 was strongly expressed in epithelial cells of normal breast (n=11/15), while it was lost or strongly reduced in 42% (92/217) of invasive breast cancers. ITIH5 expression in invasive carcinomas was associated with positive expression of oestrogen receptor (P=0.008) and histological grade (P=0.024). Correlation of ITIH5 expression with clinical outcome revealed that patients with primary tumours retaining abundant ITIH5 expression had longer recurrence-free survival (RFS; P=0.037) and overall survival (OS; P=0.044), compared to those with reduced expression (mean RFS: 102 vs 78 months; mean OS: 120 vs 105 months). Methylation-specific PCR analysis frequently showed strong methylation of the ITIH5 promoter in primary breast tumours (41%, n=109) and breast cancer cell lines (n=6). Methylation was significantly associated with mRNA loss (P<0.001; n=39), and ITIH5 expression was induced after treatment of tumour cell lines with the demethylating agent 5-aza-2'-deoxycytidine. Moreover, ITIH5 promoter methylation was significantly associated with reduced OS (P=0.008). The cellular function of ITIH5 was evaluated by forced expression of a full-length ITIH5 complementary DNA in the breast cancer cell line MDA-MB-231, which does not endogenously express ITIH5. ITIH5-expressing clones showed a 40% reduced proliferation rate compared to mock-transfected cells. Overall, these data show that promoter methylation-mediated loss of ITIH5 expression is associated with unfavourable outcome in breast cancer patients, and thus ITIH5 could be used as a prognostic marker, although this marker is not multivariate independent due to its close association with ER expression. Our data indicate that ITIH5 is a candidate class II tumour suppressor gene and could be involved in tumour progression, invasion and metastasis, as its absence is associated with increased proliferation rates and a prognostic value indicating poor clinical outcome.

Fetal abdominal subcutaneous tissue thickness measured by ultrasound at term is associated with birth weight and mode of delivery.

PURPOSE: To determine if measurement of fetal abdominal subcutaneous tissue thickness (FASTT) at term can predict birth weight, mode of delivery and perinatal outcome. METHODS: A prospective study with 352 normal, singleton pregnancies in the vertex presentation examined with real-time ultrasound at 37-39 weeks' gestation. RESULTS: FASTT was positively correlated with birth weight (Pearson's, r = 0.784, p < 0.001). Fetuses with low FASTT were more likely to be delivered through normal vaginal delivery (7.8 +/- 0.1 mm), while higher FASTT was correlated with operative vaginal delivery (7.9 +/- 0.2 mm) and cesarean section (8.6 +/- 0.3 mm) (ANOVA, p = 0.034). In contrast, FASTT was not correlated with intrapartum CTG, labor duration and Apgar scores. CONCLUSIONS: In normal pregnancies, FASTT at term is positively associated with birth weight. With increasing FASTT the likelihood of operative vaginal and cesarean delivery increases. FASTT is not associated with perinatal outcome.

Prenatal management and postnatal separation of omphalopagus and craniopagus conjoined twins.

Two cases of prenatally diagnosed conjoined twins are presented: a set of omphalopagus twins sharing a common liver, and a set of craniopagus with involvement limited to the skull. In both cases, prenatal diagnosis allowed accurate planning of pre- and postnatal management. Prenatal management involved serial imaging and counseling with participation of different specialists according to imaging findings. In the rare case of conjoined twins, an interdisciplinary approach is required, with feto-maternal specialists playing a pivotal role in co-ordinating teamwork and planning successive stages of management.

Nuchal cord detected by ultrasound at term is associated with mode of delivery and perinatal outcome.

OBJECTIVES: To evaluate the clinical relevance of nuchal cord in normal, vertex, singleton pregnancies at term, and its effect on mode of delivery and perinatal outcome. STUDY DESIGN: Prospective study with 352 normal, singleton pregnancies, with fetuses in the vertex presentation, examined with real-time ultrasound at 37-39 weeks. Health care workers at labour and delivery blinded to previous detection of nuchal cord. RESULTS: Fetuses of nulliparous women with a nuchal cord were more likely to be delivered with operative vaginal or caesarean delivery (n = 153, p < 0.0001). This was not the case with higher parity (n = 199, p = 0.07). There was no difference between nuchal cord (n = 144) and control groups (n = 208) in amniotic fluid quantity at 37-39 weeks (p = 0.554) or intrapartum CTG (p = 0.9). On the other hand, nuchal cord group had lower Apgar scores at 1 and 5 min (p = 0.001 and 0.027 respectively); this difference remained significant when adjusted for birth weight (p = 0.001 and 0.016), but disappeared when adjusted for mode of delivery (p = 0.048 and 0.319). CONCLUSIONS: Nuchal cord in normal pregnancies at term is associated with increased rate of operative vaginal and caesarean delivery in nulliparae. The presence of a nuchal cord results in slightly lower Apgar scores at 1 and 5 min, mainly as a consequence of higher operative delivery rates.