The role of mTOR signaling pathway in premalignant and malignant cervical lesions.

PURPOSE OF THE STUDY: Aberrant activation of the Akt/mTOR/pS6 signaling pathway has been identified in various types of cancer and is under investigation in cervical cancer. The purpose of this study was to assess the expression of the phosphorylated/activated forms of Akt (upstream molecule), 4E-BP1 and pS6 (downstream molecules) in biopsy samples of cervical low grade squamous intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions (HSIL), and squamous cell carcinoma (Ca) compared to normal cervical epithelium. MATERIAL AND METHODS: The study included 38 cases diagnosed as LSIL, 31 cases as HSIL, 29 cases as Ca, and eight control cases from normal cervix. Immunohistochemistry was used to assess the expression of pAkt, p4E-BP1 and pS6. RESULTS: Statistical analysis revealed significant differences between HSIL and Ca groups compared to controls regarding intensity, positivity, and total scores for all three molecules (p < 0.001). A trend for higher expression with increasing grade of dysplasia was demonstrated. CONCLUSION: These results strongly support the view that the mTOR signaling pathway is involved in cervical carcinogenesis.

Secondary hypoparathyroidism during pregnancy--a case report and review of the literature.

Secondary hypoparathyroidism is seldom seen during pregnancy. Usually, it presents with hypocalcemia. Even if there is no established therapeutic treatment, vitamin D or its analogues are required. In the present case, a 36-year-old, second gravida, with known hypoparathyroidism for the last ten years, was admitted in the prenatal clinic of "Aretaieion" University Hospital in Athens at her 39 weeks of pregnancy. She was treated with calcitriol and calcium and she was monitored monthly. She had a cesarian section and delivered a healthy female baby of 3,380 gr at 39 weeks and 1 day.

Gene receptor polymorphism as a risk factor for BMD deterioration in adolescent girls with anorexia nervosa.

Anorexia nervosa is a serious eating disorder that is associated with decreased bone mineral density and greater lifetime risk for fractures. This case-controlled study, analyzed single nucleotide polymorphisms of genes encoding vitamin D receptor, estrogen receptor alpha (ESR1), collagen type I and calcitonin receptor (CTR). Relationships between genotype and body mass index, cycling status and lumbar spine bone mineral density (LBMD) were determined in 40 adolescent girls with anorexia nervosa and 10 age-matched controls. The distribution of CTR-AluI genotypes differed between groups, but this polymorphism was not associated with LBMD Z-score. Distribution of ESR1-XbaI genotypes did not differ between groups, but the AA genotype was associated with decreased LBMD Z-score (≤-1) (OR = 24.79, 95% CI, 1.01-606.08). Carriers of the A allele were more likely to have decreased LBMD Z-scores compared with carriers of the G allele (OR = 4.12, 95% CI, 1.23-13.85, p = 0.022). In conclusion, our study shows that anorexic patients with wild-type genotype ESR-XbaI receptor are in greater risk for decreased BMD in relation to those with the mutated gene. Prompt recognition of these patients is crucial because early administration of the proper therapeutic treatment may contribute to the prevention of adverse sequelae on bone metabolism.

Prevalence of non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Greek women with acne: a hospital-based cross-sectional study.

AIM: To determine the prevalence and frequency of non classical congenital adrenal hyperplasia (NC-CAH) due to 21-OHD at the time of clinical presentation and at the peripubertal period in a substantial sample of Greek women with acne and to investigate the correlation of serum T, 17-OHP and DHEA-S with acne appearance at the time of clinical presentation. METHODS: One hundred and twenty-three unselected women with hyperandrogenemic symptoms were examined. After the ACTH stimulation test, 6 (4.9%) women were diagnosed with NC-CAH due to 21-OHD. RESULTS: There was not any statistical significant difference in the frequency of peripubertal acne between NC-CAH group of patients (6.4%) and patients with hyperandrogenemia of other aetiology (93%), mainly ovarian (P = 0.41). However, there was a statistical significant difference in the prevalence of acne at the time of clinical examination between the two groups (P = 0.04). Acne was present in 83.3% of women with NC-CAH vs. 41.02% of women in the hyperandrogenic group without NC-CAH. A statistically significant decrease of acne from the peripubertal time to the time of clinical examination in the group of women with hyperandrogenemia of other aetiology (-21.37%) was observed compared to women with NC-CAH (P < 0.001). CONCLUSION: We have shown that acne persists from peripubertal period to adult life in NC-CAH women whereas it tends to diminish in women with hyperandrogenemia of other aetiology. Acne is a prominent finding in women with NC-CAH. Serum concentrations of 17-OHP after ACTH stimulation (17-OHP6O ) should be investigated in women with persistent acne in adult life.

Practising obstetrics in the 17th century: François Mauriceau (1637-1709).

In 17th century France, the practice of obstetrics passed from female midwives to medical men called accoucheurs. François Mauriceau, a prominent French obstetrician of the 17th century urged the need of an organised obstetrical education, emphasising anatomy. He invented the semi-recumbent or 'French' birthing position, the 'tire-tête' forceps, the 'Mauriceau manoeuvre' in breech delivery, and provided one of the first epidemiological analyses in obstetrics contributing enormously to the development of this specialty. His best-seller, Traité des maladies des femmes grosses revolutionised the practice of obstetrics.

Corticotropin-releasing hormone and progesterone plasma levels association with the onset and progression of labor.

UNLABELLED: PURPOSE OF LNVESTIGATION: To examine the relationship between maternal plasma progesterone along with corticotropin- releasing hormone (CRH) plasma levels and the progression of labor. MATERIALS AND METHODS: Maternal serum CRH and progesterone were measured during the latent phase of labor, active labor, and 24 hours postpartum in women who went into spontaneous labor and delivered vaginally at term. Progesterone (P) levels in women delivered by an elective cesarean section at term were also measured as baseline. RESULTS: Mean maternal plasma P was 18% higher in the active phase than in the latent phase of labor (p < 0.01), and declined significantly by 24 hours postpartum (p < 0.001). Mean level of serum CRH was 24% higher in the active phase than in the latent phase of labor (p < 0.01), and subsequently declined significantly by 24 hours postpartum (p < 0.001). CONCLUSIONS: As labor progresses, P and CRH increase and subsequently decrease precipitously in the immediate postpartal period. P levels tend to drop in women who are in early labor compared with non-laboring full-term women.

Mediators of chronic inflammation in polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is an endocrine disorder affecting 5-10% of reproductive-age women. Hyperandrogenemia, which characterizes the syndrome, stimulates the maturation of adipocytes and favors central obesity. The linking hub between obesity and other metabolic manifestations of the syndrome seems to be chronic low-grade inflammation. We discuss the most reliable current data regarding the role of inflammatory mediators in PCOS, with particular focus on the genetic mechanisms implicated. C-reactive protein levels are 96% higher in PCOS patients than in healthy controls. Patients with the -308A polymorphism of the tumor necrosis factor-α gene have elevated androgens in comparison with carriers of the -308G. Interleukin 18 (IL-18) is elevated in lean patients, with a further rise in the presence of obesity and insulin resistance. Polymorphisms of the IL-1a, IL-1b and IL-6 genes have also been associated with PCOS. Plasminogen activator inhibitor-1 levels are positively associated with the syndrome, and carriers of the 4G allele of the 4G/5G polymorphism are at risk of developing PCOS. Other mediators discussed include adhesion molecules, osteoprotegerin, asymmetric dimethylarginine, homocysteine and advanced glycation end-products. The elucidation of the pathogenetic mechanisms implicated in PCOS and their connection with low-grade inflammation may in the future offer the opportunity for the formulation of novel therapeutic strategies and individualized therapy for these patients.

Fetuin A concentration in the second trimester amniotic fluid of fetuses with trisomy 21 appears to be lower: phenotypic considerations.

OBJECTIVE: We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. METHODS: 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The median concentration of fetuin A in amniotic fluid of trisomy 21 pregnancies (5.3 ng/ml) was statistically significantly lower (P value = 0.008) compared with that in euploid pregnancies (6.8 ng/mL). CONCLUSION: Lower levels of fetuin A in trisomy 21 may indicate an association with altered metabolic pathways in this early stage that could potentially be associated with features of the syndrome, such as growth restriction or impaired osteogenesis.

Management of hematocolpos in adolescents with transverse vaginal septum.

AIM: The aim of this study was to underline the significance of premenarcheal gynecological examination in patients with transverse vaginal septum that could possibly be complicated with endometriosis. DESIGN: Retrospective study including the period between January 2008 and December 2010. SETTING: Second Department of Obstetrics and Gynecology. PATIENTS: We searched our databases regarding cases of hematocolpos caused by transverse vaginal septum. MAIN OUTCOME: Among the patients presented with hematocolpos we identified 4 cases caused by transverse vaginal septum. RESULTS: We present the management of these cases regarding diagnosis, differential diagnosis, and treatment. The mean age of the patients was 13.1 years. All patients presented in our department with hypogastric abdominal pain and hematocolpos. No problems in adrenarche or thelarche were mentioned. The U/S and MRI revealed a normal cystic in the upper part of the vagina--hematocolpos varying from 42 × 26 × 30 to 73 × 55 × 32 mm. Three of the patients had an upper transverse vaginal septum while one had a middle transverse vaginal septum. Only one patient had a concomitant anomaly of the urinary system (ectopic kidney). In our patients, after laparoscopic examination 3 out of 4 patients had findings of endometriosis (2/3 with stage I-minimal endometriosis and 1/3 with stage II-mild endometriosis). CONCLUSION: Physicians should be aware of transverse vaginal septum in the differential diagnosis of hematocolpos with abdominal pain and primary amenorrhea in the early adolescent years. Early diagnosis could be based on premenarcheal gynecological examination and could lead to correct management in order to avoid the complications of endometriosis (dysmenorrhea or infertility).

The implication of second-trimester amniotic fluid TNF-alpha, cytochrome C and cell death nucleosomes in the prediction of preterm labor and/or premature rupture of membranes.

AIM: The multifactorial pathway leading to preterm labor possibly includes the implication of apoptosis. This study aimed to clarify the role of amniotic fluid apoptotic molecules (TNF-alpha, cytochrome C and cell death nucleosomes) at midtrimester as possible predictors of preterm labor (PTL) and/or premature rupture of membranes (PROM). METHOD: In this case-control study, comprising 360 women undergoing genetic amniocentesis and out of whom 38 delivered preterm and 18 out of the latter after PROM, the above apoptotic molecules were determined by ELISA. The 38 cases with PTL and 18 cases with PROM were matched for age with 38 and 18 respective controls delivering at term, and the levels of apoptotic molecules were compared. RESULTS: Cell death nucleosome levels were found to be significantly associated with preterm delivery. Specifically, for every unit increase in nucleosomes, women were on average 0.2% more likely to deliver preterm (OR: 1.002, CI: 1.0-1.003, p = 0.018). In contrast, such an association was not found concerning the other two apoptotic molecules (TNF-a and Cytochrome C). CONCLUSION: Second-trimester amniotic fluid cell death nucleosomes' levels are significantly associated with preterm delivery and could possibly serve as predicting markers.

Laparoscopic management of large ovarian cysts.

The aim of this study was to describe a new technique for laparoscopic removal of large ovarian cystic masses. The authors performed a retrospective study during the period January 2008 to December 2009 in the Second Department of Obstetrics and Gynecology of Aretaieion University Hospital; 19 women with large ovarian cysts were included in the study. During the study period, 53 women underwent laparoscopic excision of ovarian cysts. Among them, 19 had very large complex ovarian cysts with a mean diameter of 8.4 cm. The mean age of the patients was 32.1 years. Ultrasound examination revealed findings suggestive of benign disease in all patients. In 8 out of 19 patients CA-125 levels were elevated, ranging from 40.5 to 194.7 IU/mL. A 5-mm suprapubic trocar was directly inserted into the cyst and fluid contents aspirated, so the decompressed cyst could fit in a 5-cm laparoscopic bag. The cyst wall was carefully detached from the healthy ovarian tissue and placed in the bag without any spillage. The remaining cyst wall was removed from the peritoneal cavity with the laparoscopic bag. The mean operative time was 45 minutes. No operative or postoperative complications were noted. There was no conversion to laparotomy. Mean hospital stay was 1 day. Pathology revealed 7 endometriomas, 3 mucinous cystadenomas, 3 serous cystadenomas, 3 serous cysts, and 3 teratomas. Direct trocar insertion within the ovarian cyst followed by aspiration of the fluid contents is a safe and feasible method for the laparoscopic management of large ovarian cysts.

Female genital mutilation in Greece.

The number of migrants and refugees with a female genital mutilation (FGM) living in Greece is rising. This study explores the characteristics and psychosexual issues of women with FGM who were examined in the 2nd Department of Obstetrics and Gynecology, University of Athens Medical School, Greece during the year 2009. The women were asked to fill out an anonymous questionnaire asking for demographic data, obstetric history, current complaints, and psychosexual problems. The results are presented and discussed, as FGM is a new reality for Greece. Healthcare providers have to familiarize themselves with issues related to FGM and improve their skills in transcultural care, so as to manage and support women with FGM adequately.

The impact of HPV diagnosis on women's sexual and mental health: preliminary findings.

PURPOSE OF INVESTIGATION: The objective of the present study was to demonstrate the impact of HPV diagnosis on sexual function and mental health of Greek women. METHODS: The study population included 51 patients who proceeded to the gynecological outpatient clinic of "Aretaieion" Hospital, Athens, during 2008-2009. The participants were asked to complete a questionnaire regarding demographic characteristics, knowledge on HPV, gynecological and sexual history, as well as questions regarding their mental and sexual health after the diagnosis. RESULTS: Mean age of the participants was 36 years and mean age of their first Pap smear test was 24.4 years. Mean age of HPV diagnosis was 34 years and mean number of sexual partners was four. Regarding mental health, the majority experienced anxiety after the HPV diagnosis as well as fear regarding their health in the future. Nearly half of the women experienced guilt and anger and some of them distress, shame, diminution of self-esteem and stigmatization. Diminution in the level of sexual interest and desire and decrease in sexual intercourse frequency were quite often reported. CONCLUSION: Except for the important physical impact of HPV infection, its diagnosis seems to trigger several negative feelings and reduce sexual desire.

Uterine tamponade balloon for the management of massive hemorrhage during cesarean section due to placenta previa/increta.

OBJECTIVE: Uterine tamponade with the Bakri catheter is effectively used as a treatment in postpartum hemorrhage and as a means to prevent fertility. CASE: We present a case of a 40-year-old pregnant woman who had a massive hemorrhage during cesarean section who was successfully treated with a tamponade balloon. Furthermore, we comment on a similar technique--Logothetopoulos pack--which was first developed and used in our department in the early years of the previous century. CONCLUSION: A conservative technique such as the Bakri catheter is an alternative intermediate step to control postpartum hemorrhage when pharmaceutical methods fail and before proceeding to obstetric hysterectomy.

Isolated sigmoid colon metastasis from a primary fallopian tube carcinoma: a case report.

Isolated metastasis of primary fallopian tube carcinoma (PFTC) is extremely rare. We describe a case of a 41-year-old asymptomatic woman who was referred three years after the initial treatment for PFTC due to elevated sertum CA-125 levels. The abdominal and pelvic CT scans revealed a pelvic mass near the top of the vaginal vault. On surgery, a sigmoid colon tumour was found and a sigmoidectomy was performed. On histopathology the tumour involved the bowel wall from serosa to submucosa, without involvement of the underlying mucosa. Immunohistochemical staining was positive for cytokeratin 7 and negative for cytokeratin 20, and the tumour was determined to be a metastatic müllerian neoplasm, consistent with the initial PFTC. Although this is the first reported case of colon metastasis of PFTC, the possibility of such an unusual site of metastasis should be kept in mind, as PFTC may recur as isolated bowel lesions even in the absence of peritoneal disease.

Maternal serum levels of TNF-alpha and IL-6 long after delivery in preeclamptic and normotensive pregnant women.

AIM: To evaluate maternal TNF-alpha and IL-6 plasma levels in normotensive pregnant women, women with preeclampsia, and to examine the temporal changes in their levels from the antepartum to the postpartum period correlated with the regression of preeclampsia. METHOD: A prospective study was performed in the 2nd Department of Obstetrics and Gynecology, University of Athens. Blood samples were obtained: (1) antepartum at the time of clinical diagnosis of the syndrome, 2. 12-14 weeks postpartum. RESULTS: No statistically significant differences were found in IL-6 levels, whereas a difference was found in TNF-alpha levels between preeclamptic and controls in antepartum period (0.80 pg/ml versus 0.60 pg/ml, P : .04). Long after delivery, TNF-alpha levels were significantly higher in preeclamptic compared to normotensive controls (0.86 pg/ml versus 0.60 pg/ml, P : .004). No difference was observed in TNF-alpha before and after delivery in both groups. No difference was noticed in IL-6 levels in women of normotensive group long after delivery compared to that before delivery. Long after delivery IL-6 levels were statistically significant higher in preeclamptic women compared to normal controls (3.53 ± 0.52 pg/ml versus 1.69 ± 0.48 pg/ml, P : .02). CONCLUSION: Preeclamptic women remain under a status of increased inflammatory stress up to 12-14 weeks postpartum despite the fact that all the other signs of preeclampsia are resolved.

Fibronectin plasma levels in gynecological cancers.

PURPOSE: Fibronectin (FBN) is involved in the motility and migration of malignant cells. The purpose of this study was to investigate FBN plasma levels in gynecological cancers patients and in healthy women. METHODS: The study took place between 1998 and 2003. One hundred women with histologically diagnosed cancer of gynecological organs (cervix, ovary, endometrium, breast) formed the study group (group A), whereas the control group (group B) consisted of 100 healthy women. FBN plasma levels were measured with the radial immunodiffusion method. RESULTS: The average age of group A patients was 42.08 years (range 33-77), and of group B it was 41.1 years (range 32-65). Both groups were compared with the Student's-t test. The median plasma value of FBN in all gynecological malignancies was 258.4 mg/l (standard deviation/SD 163.9, p=0.0066, t-statistics: 2.768, (t95): 1.984, 95% CI: 225.4-290.9). The plasma levels were significantly elevated when compared to the control group (median=213 mg/l). The distribution of values showed a statistically important "tail" in high plasma levels (FBN >400 mg/l). Plasma levels of FBN were more increased in breast and cervical malignancies when compared to ovarian and endometrial cancers. CONCLUSION: FBN plasma levels were significantly increased in the total of group A patients, but not significantly increased in the endometrial and ovarian subgroup. Whether or not FBN could reliably be a marker for gynecological cancers should be confirmed in studies with larger number of patients.

Progestin may modify the effect of low-dose hormone therapy on mammographic breast density.

OBJECTIVES: To evaluate the effect on breast density of two low-dose hormone therapy regimens identical in their estrogen component but different in the progestin. METHODS: A total of 81 non-hysterectomized postmenopausal women were allocated either to 17beta-estradiol 1 mg and norethisterone acetate 0.5 mg (E2/NETA, n = 43) or to 17beta-estradiol 1 mg and drospirenone 2 mg (E2/DRSP, n = 38). Treatment was continuous and lasted 12 months. The main outcomes were the changes in breast density according to the Wolfe classification between baseline and 12-month mammograms. RESULTS: Involution of the fibroglandular tissue was not seen in either of the treatment groups. Under E2/NETA, breast density increased in seven women (16.3%). In contrast, only three women (7.9%) exhibited a density increase under E2/DRSP. CONCLUSIONS: Although hormone therapy appears to suspend breast involution, it does not increase breast density in the majority of treated women. Progestins differing in pharmacological properties may have a variable impact on breast density.

Clinical parameters linked with malignancy in endometrial polyps.

AIM: To investigate the association of different clinical parameters with the histological diagnosis and the prevalence of premalignant and malignant endometrial polyps. METHOD: The study included 516 cases from January 2002 to December 2006. Possible risk factors such as age, menopause status, abnormal bleeding, obesity, hypertension, diabetes mellitus, hormone therapy, use of tamoxifen and size of polyp were investigated in relation to their association with the malignant potential of endometrial polyps. RESULTS: All cases of endometrial polyps underwent hysteroscopic resection; 96.9% of the cases were benign, 1.2% premalignant and 1.9% malignant. Premalignant and malignant endometrial polyps were significantly associated with advanced age (>60 years), menopause, obesity and diabetes. The malignant polyps were analyzed to eight endometrioid, one serous and one clear cell carcinoma. CONCLUSION: The prevalence of premalignant and malignant endometrial polyps is very low. Advanced age, menopause, obesity and diabetes increase the risk of endometrial polyp malignancy.