Searching HPV genome for methylation sites involved in molecular progression to cervical precancer.

Background: Human Papilloma Virus has been considered as the main cause for cervical cancer. In this study we investigated epigenetic changes and especially methylation of specific sites of HPV genome. The main goal was to correlate methylation status with histological grade as well as to determine its accuracy in predicting the disease severity by establishing optimum methylation cutoffs. Methods: In total, sections from 145 cases genotyped as HPV16 were obtained from formalin- fixed, paraffin-embedded tissue of cervical biopsies, conization or hysterectomy specimens. Highly accurate pyrosequencing of bisulfite converted DNA, was used to quantify the methylation percentages of UTR promoter, enhancer and 5' UTR, E6 CpGs 494, 502, 506 and E7 CpGs 765, 780, 790. The samples were separated in different groupings based on the histological outcome. Statistical analysis was performed by SAS 9.4 for Windows and methylation cutoffs were identified by MATLAB programming language. Results: The most important methylation sites were at the enhancer and especially UTR 7535 and 7553 sites. Specifically for CIN3+ (i.e. HSIL or SCC) discrimination, a balanced sensitivity vs. specificity (68.1%, 66.2% respectively) with positive predictive value (PPV) and negative predictive value (NPV) (66.2%, 68.2% respectively) was achieved for UTR 7535 methylation of 6.1% cutoff with overall accuracy 67.1%, while for UTR 7553 a sensitivity 60.9%, specificity 69.0%, PPV=65.6%, NPV=64.5% and overall accuracy=65.0% at threshold 10.1% was observed. Conclusion: Viral HPV16 genome was found methylated in NF-1 binding sites of UTR in cases with high grade disease. Methylation percentages of E6 and E7 CpG sites were elevated at the cancer group.

Placental volume at 11 to 14 gestational weeks in pregnancies complicated with fetal growth restriction and preeclampsia.

OBJECTIVE: The study aims to evaluate the predictive value of first trimester placental volume in pregnancies destined to develop fetal growth restriction (FGR) and preeclampsia (PE). METHODS: Prospective observational study including placentas from 34 FGR, 12 PE, 15 GH (gestational hypertension) pregnancies, and 265 controls. Placental volume (PV) was obtained using VOCAL technique, and a z score was calculated (z-PV). The association of PV with other first trimester variables and maternal characteristics was assessed with Spearman's correlation. RESULTS: PV increased exponentially with crown-rump length (CRL) and was unrelated to maternal factors (weight, age, parity, and smoking status) as well as first trimester uterine artery Doppler, free ß-hCG, nuchal translucency, or fetal heart rate. However, PV was positively associated with maternal height, CRL, PAPP-A, and birth weight. z-PV was a strong predictor for FGR with abnormal fetal Dopplers (AUC = 0.9472, P < 0.001). z-PV provided moderate prediction of FGR with normal fetal Dopplers (AUC = 0.8396, P < 0.001), PE (AUC = 0.8312, P < 0.001), and GH (AUC = 0.7640, P < 0.001). The addition of maternal weight, PAPP-A, ß-hCG, and uterine artery Doppler improved our models. CONCLUSION: At 11 to 14 weeks, PV is an independent predictor of pregnancy complications related to placental insufficiency, and the predictive ability is greater for FGR pregnancies with abnormal fetal Dopplers.

2017 Update on Ovarian Cancer Peritoneal Carcinomatosis Multimodal-Treatment Considerations.

Ovarian cancer peritoneal carcinomatosis requires a multimodal-treatment approach. Current treatment considerations are analyzed in this update and include the management of recurrent malignant ascites and the understanding of its pathophysiology, the role of peritoneal washing cytology in detecting peritoneal metastases, capsular invasion and ovarian cancer histologic type, interpretation of pretreatment Ca-125 levels at different time points of ovarian cancer therapeutic management, characteristics of 10-year survivors of high-grade ovarian cancer, and the role of lymphadenectomy in ovarian cancer peritoneal carcinomatosis. This update also includes current considerations on the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer peritoneal carcinomatosis as well as relevant ongoing phase III randomized controlled trial protocols.

The association between sexually transmitted infections, human papillomavirus, and cervical cytology abnormalities among women in Greece.

OBJECTIVE: To investigate the diagnosis of sexually transmitted infections (STIs) with human papillomavirus (HPV) infection and the presence of cytological changes in the cervix in a cohort of sexually active women in Greece. METHODS: Cervical cytology testing and the molecular typing of HPV and other STIs were performed for 345 sexually active women aged between 18 and 45 years (mean 33.2±7.2years) visiting a gynaecology clinic for routine cervical screening. The association of HPV and STI detection with cytological findings was investigated. RESULTS: HPV was detected in 61 women (17.7%) and STIs in 82 (23.8%). Ureaplasma spp was the most frequently detected pathogen, which was found in 63 (18.2%) women, followed by Mycoplasma spp (21 women, 25.6%) and Chlamydia trachomatis (five women, 6.1%). HPV positivity only (with no co-presence of STI) was associated with an abnormal cytology (odds ratio 6.9, p<0.001), while women who were negative for both HPV and STIs had a higher probability of a normal cytology (odds ratio 0.36, p<0.01). Sixteen out of the 63 (25.4%) women who tested positive for Ureaplasma spp, harboured a high-risk HPV type (odds ratio 2.3, p=0.02). CONCLUSIONS: In a population with a high prevalence of Ureaplasma spp, there was an association of this pathogen with high-risk HPV infection, a finding that needs further elucidation.

Falsely Elevated CA 15-3 Levels in Ovarian Sarcoidosis with Peritoneal Involvement and Ascites.

A rare case of ovarian sarcoidosis with peritoneal and omental involvement presenting as an ovarian malignancy is presented. Clinical, laboratory, and radiological evaluation of the patient revealed ascites and high levels of serum CA 125 and CA 15.3. The diagnosis of sarcoidosis was confirmed with pathology findings on tissues obtained during surgical laparotomy. Establishing the diagnosis of sarcoidosis can be treacherous and was complicated in this case by the falsely elevated biomarkers and ascites.

Counselling for smoking cessation during pregnancy reduces tobacco-specific nitrosamine (NNAL) concentrations: A randomized controlled trial.

INTRODUCTION: Smoking cessation during pregnancy is beneficial to both the mother and child. Our objective was to assess if an intensive smoking cessation intervention for pregnant women increases: a) rates of smoking cessation, and b) reduces exposure to tobacco-specific carcinogens during pregnancy. METHODS: A two-group single-blinded parallel randomized controlled trial (RCT) was conducted involving 84 pregnant smokers in either a high intensity (n=42) or minimal contact control group (n=42). Women assigned to the high intensity smoking cessation intervention group received a single 30-minute behavioural counselling session and a tailored self-help booklet. The primary outcome measures were: 7-day point prevalence abstinence measured by selfreport and urine cotinine levels, and maternal tobacco specific carcinogens nitrosamine (NNAL) urine concentrations assessed at 32 weeks of gestation. RESULTS: A significantly greater percentage of pregnant smokers quit smoking in the high intensity group compared to the low intensity control group (45.2% vs 21.4%; p=0.001). A significant decrease in urine cotinine concentrations was documented in the experimental group (-140.74 ± 361.70 ng/mL; p=0.004), with no significant decrease documented in the control group. A significant decrease in NNAL levels was also documented in the experimental group (158.17 ± 145.03 pg/mL before, 86.43 ± 112.54 pg/mL after; p=0.032) with no significant changes in the control group. CONCLUSIONS: The high intensity intervention tested resulted in significantly greater cessation rates. Intensive smoking cessation interventions can be effective in reducing fetal exposure to NNAL. This is the first trial to report on NNAL tobacco-specific carcinogen concentrations before and after an intervention for smoking cessation during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01210118. ABBREVIATIONS: 5Αs: ask, advise, asses, assist, arrange; GHQ: general health questionnaire; ANOVA: analysis of variance; RCT: randomized control trials; NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.

γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL.

BACKGROUND: γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. METHODS: Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. RESULTS: Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. CONCLUSIONS: γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state.

Stress urinary incontinence and endogenous sex steroids in postmenopausal women.

AIMS: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). METHODS: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Δ4-Androstendione (Δ4Α), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. RESULTS: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 ± 8.16 vs. 24.22 ± 8.99, P < 0.001). Furthermore, the same association was observed for serum Δ4Α (146.07 ± 52.63 vs. 159.99 ± 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. CONCLUSIONS: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121-125, 2017. © 2015 Wiley Periodicals, Inc.

The amount and duration of smoking is associated with aggravation of hormone and biochemical profile in women with PCOS.

We investigated the association between the amount and duration of smoking on biochemical, clinical parameters and the ovarian morphology in women with polycystic ovary syndrome (PCOS). That was a retrospective study. These women were divided into two groups, non-smokers (217) and smokers (92). The amount of cigarettes and duration of smoking was measured in pack-years. Both groups underwent clinical evaluation, biochemical and hormone analysis, transvaginal ultrasound and oral glucose tolerance tests (OGTT). The mean value of the number of cigarettes was 14.8 (±8.8) and the median value of pack-years in the smokers group was 4.0 (1.5-7.5). Smokers group has significantly higher free testosterone (F-T), 17-hydroxyprogesterone (17-OHP), delta 4 androstenedione (Δ4-A), T4, low-density lipoprotein (LDL), and white blood cells (WBC). During correlation of all the above parameters and pack-years, there has been significant positive correlation in F-T and Δ4-A. The participants with more pack-years showed statistically higher values of F-T and Δ4-A. There was also a significant positive correlation between total cholesterol, triglycerides, WBC and pack-years of the participants. Prolactin (PRL) has been inversely associated with pack-years. We concluded that the increase of pack-years aggravated lipid profile, WBC and decreased PRL levels, in PCOS patients.

Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan.

AIM: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). METHOD: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. RESULTS: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2=0.39) with BW1 being the strongest predictor (R2=0.37). The addition of EFW conferred significant improvement (R2=0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. CONCLUSIONS: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. Incorporating EFW enhanced the sensitivity for the detection of both conditions.

The diagnostic accuracy of E6 & 7 mRNA detection as a primary screening test for the detection of severe cervical lesions.

PURPOSE: This prospective accuracy study aimed to assess the diagnostic accuracy of nucleic acid sequence amplification (NASBA) and flow cytometry for E6/7 human papillomavirus (HPV) mRNA detection as a primary screening test compared to cytology in the triage of severe cervical intraepithelial neoplasia (CIN) lesions. METHODS: 1083 women referred to our outpatient gynecology clinics for a routine Pap test were recruited. Residual material of the Pap smears was tested by NASBA and by flow cytometry for E6/7 mRNA expression. Biopsy results were used as reference standards. The accuracy indices of both techniques and of NASBA type-16 HPV were assessed for the detection of CIN2+ lesions and were compared to cytology. RESULTS: An increased lesion severity was associated with increased positivity rates of both NASBA and flow cytometry tests (x(2), p<0.001). A positive correlation between NASBA and flow cytometry was identified when these methods were examined with the Phi coefficient (value 0.369, 95% confidence interval [95%CI] : 0.307-0.426). Furthermore, NASBA (89.7 vs 57.7%, p<0.0005) and flow cytometry (77.3 vs 57.7%, p<0.0005) exhibited higher specificity rates than cytology. However, their sensitivity rates did not exceed those of cytology (NASBA:69.8 vs 84.6%, p=0.051; flow cytometry: 69.12 vs 84.6%, p=0.043). CONCLUSIONS: Both NASBA and flow cytometry exhibited increased specificity for the triage of CIN2+ lesions. However, their relatively lower sensitivity and higher positivity rates when compared to cytology do not make them ideal for a primary screening test. Hence, the role of mRNA detection in the screening for severe cervical lesions remains to be clarified.

Angiopoietin-2 primes infection-induced preterm delivery.

Current knowledge on the participation of angiopoietin-2 (Ang-2) in the inflammatory process and on the importance of bacterial endotoxins (LPS) in the induction of preterm delivery (PTD) led us to investigate the role of Ang-2/LPS interplay in the pathogenesis of PTD. At a first stage, Ang-2 was measured at the end of the first trimester of pregnancy in the serum of 50 women who delivered prematurely; of 88 women well-matched for age and parity who delivered full-term; and of 20 non-pregnant healthy women. Ang-2 was greater in pregnant than in non-pregnant women. The time until delivery was shorter among those with Ang-2 greater than 4 ng/ml (odds ratio for delivery until week 34; p: 0.040). To further investigate the role of Ang-2 for PTD, an experimental model of PTD induced by the intraperitoneal injection of LPS in mice was used. Ang-2 was administered intraperitoneally before LPS on day 14 of pregnancy. When Ang-2 was administered before the LPS diluent, all mice delivered full-term. However, administration of Ang-2 prior LPS accelerated further the time until delivery. Sacrifice experiments showed that the effect of Ang-2 was accompanied by decrease of the penetration of Evans Blue in the embryos and by increase of its penetration in maternal tissues. In parallel, the concentration of tumour necrosis factor-alpha in the maternal circulation, in fetal tissues and in the placentas was significantly decreased. Results indicate that Ang-2 accelerated the phenomena of PTD induced by LPS. This is related with deprivation of fetal perfusion.

Fetal volume at 11-14 gestational weeks: reference ranges and association with first trimester biochemical and biophysical markers.

AIMS: To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11-14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters. METHODS: Prospective observational study on 240 fetuses at 11-14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided Analysis. Pearson correlation coefficient (cc) and regression analysis were used. RESULTS: FV increased exponentially with crown rump length and was unrelated to maternal weight (cc=-0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76), smoking status (t-test, P=0.149) and mode of conception (t-test, P=0.8). Z-scores (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=-0.026, P=0.733), log10 multiples of the median (MoM) free beta human chorionic gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was significantly positively correlated with log10 MoM pregnancy associated plasma protein-A (PAPP-A; regression coefficient=1.420976, R2=0.0957, P<0.0001). CONCLUSIONS: FV is strongly related to PAPP-A even after adjustment for crown rump length with a mechanism unrelated to placental perfusion. FV is independent of the vast majority of first trimester parameters; hence, it is a promising marker of early fetal growth.

mRNA and DNA detection of human papillomaviruses in women of all ages attending two colposcopy clinics.

OBJECTIVE: HPV infection is a common finding, especially in young women while the majority of infections are cleared within a short time interval. The aim of this study was to examine the efficacy of HPV DNA and mRNA testing in a population attending colposcopy units of two University hospitals. METHODS: 1173 liquid based cervical samples from two colposcopy clinics were tested for HPV DNA positivity using a commercial typing kit and HPV E6/E7 mRNA positivity with a flow cytometry based commercial kit. Statistic measures were calculated for both molecular tests and morphological cytology and colposcopy diagnosis according to histology results. RESULTS: HPV DNA, high-risk HPV DNA, HPV16 or 18 DNA and HPV mRNA was detected in 55.5%, 50.6%, 20.1% and 29.7% of the cervical smears respectively. Concordance between the DNA and the mRNA test was 71.6% with their differences being statistically significant. Both tests' positivity increased significantly as lesion grade progressed and both displayed higher positivity rates in samples from women under 30 years old. mRNA testing displayed similar NPV, slightly lower sensitivity but significantly higher specificity and PPV than DNA testing, except only when DNA positivity for either HPV16 or 18 was used. CONCLUSIONS: Overall mRNA testing displayed higher clinical efficacy than DNA testing, either when used as a reflex test or as an ancillary test combined with morphology. Due to enhanced specificity of mRNA testing and its comparable sensitivity in ages under 25 or 30 years old, induction of mRNA testing in young women could be feasible if a randomized trial verifies these results.

The diagnostic accuracy of two methods for E6&7 mRNA detection in women with minor cytological abnormalities.

OBJECTIVE: To examine the diagnostic accuracy of nucleic acid sequence based amplification (NASBA) and flow cytometry for E6&7 human papillomavirus (HPV) mRNA detection in the triage of minor cytological abnormalities. DESIGN: Prospective diagnostic accuracy study. SETTING: Gynecology outpatient clinics of a university hospital. POPULATION: 472 women with low-grade squamous intraepithelial lesion (LSIL) or atypical squamous cells of undetermined significance (ASCUS). METHODS: Residual material of the liquid-based smears was tested by NASBA and by flow cytometry for E6&E7 mRNA expression. Histological diagnosis was used as reference standard. MAIN OUTCOME MEASURES: Accuracy indices of the two techniques and of type 16-specific NASBA for the detection of cervical intraepithelial neoplasia (CIN) 2+ and CIN3+, accuracy indices at age >35 years, correlation between NASBA and flow, comparison between integrated and episomal high-risk HPV infection for risk of CIN2+. RESULTS: Both tests showed increased positivity rates with increasing severity of the lesion (p < 0.05, chi-squared test for trend). There was a positive correlation between NASBA and flow results (phi coefficient = 0.325). NASBA-positive cases were more likely to have CIN2+ than were NASBA-negative/DNA-positive for types 16, 18, 31, 33, 45 (25/73 vs. 4/52, p= 0.0004; Fisher's exact test). In the LSIL group the NASBA accuracy indices for CIN3+ were: sensitivity 75%, specificity 78.7% and positivity rate 20.8%, and for flow 77.8%, 64.5% and 35.9%, respectively. CONCLUSIONS: NASBA has favorable specificity and positivity rates for triaging LSIL prior to colposcopy. A relatively low sensitivity warrants cytological surveillance of the NASBA-negative LSILs. Flow cytometry does not perform as well overall.

Design and study protocol of the maternal smoking cessation during pregnancy study, (M-SCOPE).

BACKGROUND: Maternal smoking is the most significant cause of preventable complications during pregnancy, with smoking cessation during pregnancy shown to increase birth weight and reduce preterm birth among pregnant women who quit smoking. Taking into account the fact that the number of women who smoke in Greece has increased steadily throughout the previous decade and that the prevalence of smoking among Greek females is one of the highest in the world, smoking cessation should be a top priority among Greek health care professionals. METHODS/DESIGN: The Maternal Smoking Cessation during Pregnancy Study (M-SCOPE), is a Randomized Control Trial (RCT) that aims to test whether offering Greek pregnant smokers a high intensity intervention increases smoking cessation during the third trimester of pregnancy, when compared to a low intensity intervention. Prospective participants will be pregnant smokers of more than 5 cigarettes per week, recruited up to the second trimester of pregnancy. Urine samples for biomarker analysis of cotinine will be collected at three time points: at baseline, at around the 32nd week of gestation and at six months post partum. The control group/low intensity intervention will include: brief advice for 5 minutes and a short leaflet, while the experimental group/intensive intervention will include: 30 minutes of individualized cognitive-behavioural intervention provided by a trained health professional and a self-help manual especially tailored for smoking cessation during pregnancy, while counselling will be based on the ''5 As.'' After childbirth, the infants' birth weight, gestational age and any other health related complications during pregnancy will be recorded. A six months post-partum a follow up will be performed in order to re-assess the quitters smoking status. DISCUSSION: If offering pregnant smokers a high intensity intervention for smoking cessation increases the rate of smoking cessation in comparison to a usual care low intensity intervention in Greek pregnant smokers, such a scheme if beneficial could be implemented successfully within clinical practice in Greece. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01210118.

Cervical length changes from the first to second trimester of pregnancy, and prediction of preterm birth by first-trimester sonographic cervical measurement.

OBJECTIVES: The purpose of this study was to examine the evolution of cervical length from the first to second trimester of pregnancy and the value of first-trimester cervical measurement in the prediction of preterm delivery. METHODS: We conducted a longitudinal prospective study. Cervical length was measured by transvaginal sonography at 11 to 14 weeks (Cx1), 16 to 19 weeks (Cx2), and 20 to 24 weeks (Cx3). RESULTS: Eight hundred singleton pregnancies were studied. The median cervical lengths were 33 mm for Cx1 and 31 mm for Cx2 and Cx3. Significant independent predictors for cervical length were maternal weight, height, and history of cervical surgery for Cx1, maternal height, history of cervical surgery, and history of preterm delivery for Cx2, and history of cervical surgery, history of first-trimester miscarriage, and history of spontaneous preterm delivery for Cx3. Mean cervical length shortening was 2.36 mm between Cx1 and Cx3. In the subgroups of women with previous cervical surgery and history of previous preterm birth, cervical shortening was significantly more prominent. The median Cx1 was significantly shorter in the women who subsequently delivered preterm; Cx1 predicted preterm delivery before 34 weeks (odds ratio, 0.746; 95% confidence interval, 0.649-0.869) and preterm delivery before 32 weeks (odds ratio, 0.734; 95% confidence interval, 0.637-0.912). CONCLUSIONS: Cervical length in the first trimester depends on maternal characteristics and a history of cervical surgery. The cervix exhibits minimal changes from 11 to 24 weeks for most women, although the shortening is more prominent in women with a history of cervical surgery or preterm delivery. First-trimester cervical length measurement can predict preterm delivery.

Office hysteroscopy: current trends and potential applications: a critical review.

Office hysteroscopy is an excellent method of identifying and treating intracavitary uterine lesions. It has become easy to learn and perform; as an aid of modern technological applications, it is safe, accurate, provides immediate results under direct visualisation, and offers the additional benefit of histological confirmation and the discomfort of patients is minimal. We applied an extended literature search to explore the special features and details of the technique itself, as it evolved since it first appeared 30 years back. Our initial goal was to examine potential changes/improvements of the modality, in terms of the instrumentation used and the technique itself, the indications of use, its incorporation in daily practice, and patients' and clinicians' acceptability.

Immunological factors and their role in the genesis and development of endometriosis.

The article presents an overview of immunological factors and their role in the genesis and development of endometriosis, with emphasis on inflammatory cytokines and growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women with retrograde menstruation suffer the disease. Development of endometriosis seems to be a complex process, facilitated by several factors, including quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies, upregulated during development of endometriosis, seem useful in the development of a non-surgical diagnostic tool. In this review work, the immune role in endometriosis is examined through the role of immunological factors in the genesis and development of the disease. Furthermore, it could be concluded that, although endometriosis can be treated using hormonal suppression, there is a need today for non-hormonal drugs, probably to modulate immune function, in order to confront the disease and alleviate pain or infertility without inhibition of ovulation.

Ultrasonographic evaluation of a uterine malignant melanoma presenting as a large pelvic mass.

The uterus is an extremely rare location for a primary or metastatic melanoma. We describe the ultrasonographic appearance of a malignant melanoma of the uterus presenting clinically as a large mass in a 78-year-old woman. Transabdominal sonography revealed a solid uterine mass measuring 13 x 11.5 x 8.5 cm with inhomogeneous echotexture and bright internal echoes. The tumor showed a diffuse spread inside the uterine corpus, and the endometrium was not demonstrated ultrasonographically.