First-trimester and combined first- and second-trimester prediction of small-for-gestational age and late fetal growth restriction.

OBJECTIVE: To develop a first-trimester or combined first- and second-trimester screening algorithm for the prediction of small-for-gestational age (SGA) and late fetal growth restriction (FGR). METHODS: This was a retrospective study of women with singleton pregnancy, who underwent routine first-, second- and third-trimester ultrasound assessment. Late FGR was defined, at ≥ 32 weeks' gestation in the absence of congenital anomalies, as either (i) estimated fetal weight (EFW) or birth weight (BW) < 3rd centile, or (ii) EFW < 10th centile and either uterine artery mean pulsatility index (UtA-PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile. Neonates with BW < 10th centile, regardless of prenatal parameters, were defined as SGA. The predictive effectiveness of maternal and first- and second-trimester factors was tested using logistic regression and receiver-operating characteristics curve analyses. RESULTS: A total of 3520 fetuses were included (late FGR, n = 109 (3.1%); SGA, n = 292 (8.3%)). Of the late FGR cases, 56 (1.6%) fulfilled the antenatal criteria (EFW < 3rd centile or EFW < 10th centile plus abnormal UtA-PI or CPR) and were defined as prenatally detected late FGR. A first-trimester screening model (comprising conception method, smoking status, maternal height, pregnancy-associated plasma protein-A (PAPP-A) and UtA-PI) could predict 50.0% of the prenatally diagnosed and 36.7% of the overall late FGR fetuses for a 10% false-positive rate (FPR). A model combining first- and second-trimester screening parameters (conception method, smoking status, PAPP-A, second- trimester EFW, head circumference/abdominal circumference ratio and UtA-PI) could predict 78.6% of the prenatally detected, and 59.6% of the overall late FGR fetuses, for a 10% FPR (area under the curve 0.901 (95% CI, 0.856-0.947) and 0.855 (95% CI, 0.818-0.891), respectively). The prediction of SGA was suboptimal for both first-trimester and combined screening. CONCLUSIONS: A simple model combining maternal and first- and second-trimester predictors can detect 60% of fetuses that will develop late FGR, and 79% of those fetuses that will be classified prenatally as late FGR, for a 10% FPR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The utility of artificial neural networks and classification and regression trees for the prediction of endometrial cancer in postmenopausal women.

OBJECTIVE: Artificial neural networks (ANNs) and classification and regression trees (CARTs) have been previously used for the prediction of cancer in several fields. In our study, we aim to investigate the diagnostic accuracy of three different methodologies (i.e. logistic regression, ANNs and CARTs) for the prediction of endometrial cancer in postmenopausal women with vaginal bleeding or endometrial thickness ≥5 mm, as determined by ultrasound examination. STUDY DESIGN: We conducted a retrospective case-control study based on data from analysis of pathology reports of curettage specimens in postmenopausal women. METHODS: Classical regression analysis was performed in addition to ANN and CART analysis using the IBM SPSS and Matlab statistical packages. RESULTS: Overall, 178 women were enrolled. Among them, 106 women were diagnosed with carcinoma, whereas the remaining 72 women had normal histology in the final specimen. ANN analysis seems to perform better with a sensitivity of 86.8%, specificity of 83.3%, and overall accuracy (OA) of 85.4%. CART analysis did not perform well with a sensitivity of 78.3%, specificity of 76.4%, and OA of 77.5%. Regression analysis had a poorer predictive accuracy with a sensitivity of 76.4%, a specificity of 66.7%, and an OA of 72.5%. CONCLUSION: Artificial intelligence is a powerful mathematical tool that may significantly promote public health. It may be used as a non-invasive screening tool to guide clinicians involved in primary care decision making when endometrial pathology is suspected.

Low-Grade Appendiceal Mucinous Neoplasm Presenting as an Adnexal Mass.

Appendiceal tumors are rare, late diagnosed neoplasms that may not be differentiated from adnexal masses even by advanced imaging methods and other diagnostic procedures. They may be asymptomatic and remain undiagnosed until surgery. We report a case of an 80-year-old postmenopausal woman presenting with a pelvic mass and a history of weight loss. The patient underwent laparotomy which revealed an appendiceal mucocele, for which she received a full oncological procedure. The histology report showed a low-grade appendiceal mucinous neoplasm, and the patient underwent six cycles of chemotherapy. Appendiceal tumors should be kept in mind in patients with adnexal mass.

Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the diagnostic accuracy of a previously developed model for prediction of pre-eclampsia (PE) by a combination of maternal factors and biomarkers at 11-13 weeks' gestation. METHODS: This was a prospective first-trimester multicenter study of screening for PE in 8775 singleton pregnancies. A previously published algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those for the dataset used for development of the algorithm. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. With combined screening by maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor, the DR was 100% (95% CI, 80-100%) for PE < 32 weeks, 75% (95% CI, 62-85%) for PE < 37 weeks and 43% (95% CI, 35-50%) for PE ≥ 37 weeks, at a 10% FPR. These DRs were similar to the estimated rates for the dataset used for development of the model: 89% (95% CI, 79-96%) for PE < 32 weeks, 75% (95% CI, 70-80%) for PE < 37 weeks and 47% (95% CI, 44-51%) for PE ≥ 37 weeks. CONCLUSION: Assessment of a combination of maternal factors and biomarkers at 11-13 weeks provides effective first-trimester screening for preterm PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Ovarian tumors: Should the cervix be examined first?

There is a controversy regarding ovarian metastasis in early-stage adenocareinoma of the uterine cervix. The authors present the case of a 5 1-year-old woman that at the time of diagnosis was thought to suffer from a Stage II cervical carcinoma and a synchronous ovarian carcinoma, that turned out to be an ovarian metastasis from the endocervical adenocarcinoma, as attested morphologically, histochemically, and immunohistochemically. Radical hysterectomy with oophorectomy, excision of the omentum, lymph node excision, and cytological sampling of the peritoneal cavity were carried out. It is important to always bear in mind that even low-grade adenocarcinomas of the cervix can be metastatic to the ovaries. Clinicians have to be careful when managing those cases, while further investigation is needed in order to determine the exact mechanism of those metastases and the criteria needed in order to preserve the ovaries in young patients.

Role of the angiopoietin/Tie system in pregnancy (Review).

Angiopoietin-1 and -2 are endogenous ligands for the vascular endothelium-specific receptor tyrosine kinase Tie-2. The angiopoietin/Tie system plays a critical role in the regulation of endothelial cell survival and vascular maturation and stability. Apart from its well-established role in vascular morphogenesis, emerging data support the involvement of angiopoietins in inflammation and various malignancies. Previous studies have underlined the significance of several angiogenic factors in normal placental development. In addition, angiogenic imbalance is observed in pregnancy complications related to impaired placentation, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). However, there is only limited information available on the role of the angiopoietin/Tie system in the establishment of a competent feto-maternal vascular system. In this review, we present the current knowledge regarding the role of angiopoietins in normal pregnancy and pregnancy complications.

Teenage pregnancy antenatal and perinatal morbidity: results from a tertiary centre in Greece.

We present the experience of a tertiary referral hospital in Greece, evaluating obstetric and perinatal outcomes among teenage and average maternal age (AMA) women. We retrospectively assessed all singleton pregnancies during a twelve-month period (January-December 2012). A total of 1,704 cases were reviewed and divided into two groups: one of AMA mothers (20-34 years old) (1,460 women) and the other of teenage mothers (12-19 years old) (244 women). We observed significantly higher incidence rates of preterm births (p < 0.001), preterm premature rupture of the membranes (p < 0.001), gestational hypertension (p < 0.001), preeclampsia (p = 0.043) and Apgar scores < 7 at 5 min (p = 0.015) among teenage mothers. Antenatal surveillance was decreased among teenage mothers (p < 0.001), while rates of anaemia were higher (p < 0.001). Teenage pregnancy is accompanied by significant antenatal and perinatal complications that need specific obstetrical attention. Obstetricians should be aware of these complications in order to ameliorate the antenatal outcome of childbearing teenagers.

Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie-2 is altered in pregnancies complicated by preeclampsia.

OBJECTIVE: To investigate the placental expression of angiopoietin (Ang)-1, Ang-2 and their receptor, Tie-2, in preeclampsia (PE) with or without intrauterine growth restriction (IUGR). METHODS: Case-control study including placentas from 28 PE pregnancies, 30 PE-IUGR pregnancies and 40 controls. The expression status of the genes was evaluated by quantitative real-time PCR. RESULTS: In both PE and PE-IUGR groups, compared to the control group, there was significantly higher expression of Ang-2 (p < 0.001) and Tie-2 (p = 0.008) and lower expression of Ang-1 (p = 0.001). The magnitude of the difference was similar for Ang-1 for both groups, whereas the magnitude of the differences was higher for Ang-2 and Tie-2 in PE-IUGR group compared to controls. Ang-2 and Tie-2 were correlated in both PE (r = 0.8602, p < 0.001) and PE-IUGR (r = 0.6342, p < 0.001) groups. In PE-IUGR group, Ang-1 was associated to Ang-2 (r = 0.3458, p = 0.0452) and Tie-2 (r = 0.4448, p = 0.0084). Log10Ang-1 but not Ang-2 was gestational age dependent (R2 = 0.40, p < 0.001). After conversion in Multiples of the Median (MoM) log10 MoM Ang-1 was reduced in the PE group (mean = -0.8181, p < 0.001) and the PE-IUGR group (mean = -1.2583, p < 0.001) compared to control group (mean = -0.0924). DISCUSSION: We have demonstrated increased placental expression of Ang-2 and Tie-2 along with lower expression levels of Ang-1 in pregnancies with PE and PE-IUGR. CONCLUSION: The angiopoietin axis seems to be disrupted in PE pregnancies. Whether the results of this study represent the angiogenic imbalance observed in PE pregnancies or they are part of the pathophysiology of this condition has to be further investigated.

Fetal MRI: is it really helpful?

OBJECTIVE: The aim of this study is to emphasize on the diagnostic effectiveness of fetal MRI that led to increased utilization in fetal medicine as well as its value in prognosis and decision making in the modern obstetric practice. METHODS: One hundred five (n = 105) pregnant women were referred for a fetal MRI examination after a high detailed ultrasound examination revealed a fetal abnormality. Fetal MRI was performed using 1, 5 Tesla units, with T1, T2-weighted and diffusion-weighted images. The findings were analyzed in comparison to the previous ultrasound findings, according to the fetal organ affected and the value of the MRI for therapeutic decision making was addressed. A statistical analysis was performed. RESULTS: The fetal MRI provides a more accurate diagnosis compared to ultrasound examination, and when the ultrasound detects fetal anomalies, the MRI can efficiently either confirm or reject the finding, proving its high value for prenatal diagnosis and perinatal and management. The sensitivity, specificity and positive predictive value of fetal MRI as a screening tool approaches 100%. CONCLUSIONS: Despite the fact that ultrasound is the method of choice for fetal screening, MRI can add up significantly to the diagnosis and management of congenital abnormalities and the indications for MRI continue to increase as new sequences and shorter acquisition times evolve.

"7, 10 and 14-days rabeprazole-based standard triple therapies for H. pylori eradication: are they still effective? A randomized trial".

BACKGROUND & STUDY AIMS: Increasing data suggests that the efficiency of standard triple therapies of 7-10-14 days duration has fallen below the threshold for acceptability (80% cure rates in intention to treat analysis). Use of rabeprazole, a PPI less influenced by CYP2C19 gene polymorphisms is reported to lead to improved eradication rates. This study aims to re-examine the effectiveness of 7-10-14 days triple therapies based on rabeprazole in Greek patients. PATIENTS AND METHODS: 307 patients, from 2 endoscopic centers in Greece, were randomized to receive Rabeprazole 20 mg bid, Clarithromycin 500 mg bid, and Amoxycillin 1gr bid for 7-days, for 10-days or for 14-days. Cure rates were assessed by CLO-test and histology. Clarithromycin sensitivity tests were carried out in the cultured pre-treatment H.pylori strains. The success rates were calculated by both intention-to-treat (ITT) and per protocol (PP) analyses. RESULTS: The eradication rates according to ITT analyses were 74.5% (95% CI: 66.5-82.9%) for 7-days, 80.6% (95% CI: 73.2-88.2%) for 10-days and 90.2% (95% CI: 84.5-95.9%) for 14-days treatment. PP cure rates were 76% (95% CI: 68.4-85.0%) for 7-days, 83% (95% CI: 76.6-91.0%) for 10-days and 93.9% (95% CI: 86.7-973%) for 14-days treatment. Side effects were generally minor and comparable in all treatment groups. CONCLUSIONS: Both 10- and 14-days rabeprazole-based triple regimens reached eradication rates above the threshold of 80% on an intention to treat basis. In our setting, the current regimen using rabeprazole, amoxicillin and clarithromycin was well tolerated, is still effective and should continue to be recommended as first-line therapy for H. pylori eradication.

The contribution of three-dimensional power Doppler imaging in the preoperative assessment of breast tumors: a preliminary report.

Purpose. The aim of this study was to determine the value of 3D and 3D Power Doppler sonography in the detection of tumor malignancy in breast lesions and to find new diagnostic criteria for differential diagnosis. Methods. One hundred and twenty five women with clinically or mammographically suspicious findings were referred for 3D Power Doppler ultrasound prior to surgery. Histological diagnosis was conducted after surgery and compared with ultrasound findings. Sonographic criteria used for breast cancer diagnosis were based on a system that included morphological characteristics and criteria of the vascular pattern of a breast mass by Power Doppler imaging. Results. Seventy-two lesions were histopathologically diagnosed as benign and 53 tumors as malignant. Three-dimensional ultrasound identified 49 out of 53 histologically confirmed breast cancers resulting in a sensitivity of 92.4% and a specificity of 86.1% in diagnosing breast malignancy (PPV: 0.83, NPV:0.94). Conclusions. 3D ultrasonography is a valuable tool in identifying preoperatively the possibility of a tumor to be malignant.

Amniotic fluid interleukin-18 at mid-trimester genetic amniocentesis: relationship to intraamniotic microbial invasion and preterm delivery.

OBJECTIVE: To determine the value of amniotic fluid interleukin-18 (AF IL-18) in the diagnosis of microbial invasion of the amniotic cavity and prediction of preterm delivery (PTD). DESIGN: Analysis of the results of AF collected prospectively following genetic amniocentesis between February 2006 and September 2007. SETTING: A tertiary referral centre for fetal medicine. METHODS: Following amniocentesis, a sample of amniotic fluid was transferred to the laboratory for aerobic and anaerobic bacterial cultures, Ureaplasma urealyticum culture and IL-18 assays. All women who delivered preterm (<37 weeks of gestation) formed the study group. The control group consisted of the two subsequent women who also underwent amniocentesis during the same time period and delivered a normal neonate at term, matched for maternal age, parity and indication for amniocentesis. MAIN OUTCOME MEASURES: The relationship between AF IL-18 levels and the risk of both microbial invasion of the amniotic cavity and PTD. RESULTS: Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The preterm delivery group had significantly higher concentrations of IL-18 (median=609 pg/ml, interquartile range: 445.7-782.7) compared to controls (median=322.1 pg/ml, interquartile range: 277.7-414.4), (P<0.001). IL-18 level was also significantly higher (P<0.001) in cases with positive amniotic fluid cultures (median=697.7, interquartile range: 609.0-847.2) compared to those with negative ones (median=330.9 pg/ml, interquartile range: 235.2-440.8). CONCLUSIONS: Elevated mid-trimester concentrations of AF IL-18 can identify women at risk for intraamniotic infection and spontaneous PTD.

The role of three-dimensional imaging in the investigation of IUD malposition.

OBJECTIVES: The aim of this study was to present a systematic review of the use of three-dimensional ultrasound for the detection and evaluation of intrauterine device malposition in a patient of our department. BACKGROUND: Transvaginal sonography failed to detect IUD misplacement in about 9% of cases. Whereas the three-dimensional ultrasound (3D), a new emerging technology, that could provide precise evaluation of IUD malposition. METHODS: The data were extracted from the literature using computerised Medline system. The use-effectiveness and acceptance of three-dimensional imaging in the detection of IUD malposition was examined as an alternative method to two-dimensional ultrasound. RESULTS: Three-dimensional ultrasound was more accurate than two-dimensional for the identifying IUD device. Three-dimensional technique enables assessment of IUD length in the longitudinal section synchronically with imaging arms of the device. Examination with 2D ultrasound is limited to transverse views of the shaft. The arms or other smaller parts cannot be investigated completely because of the frontal view of an IUD is rarely presented. CONCLUSION: Three-dimensional ultrasound is a new and promising imaging tool which provides much better view of the endometrial cavity. This is especially useful in uterus examination and in the detection of IUDs because structures that are not located in one single plane can be imaged simultaneously. Three-dimensional ultrasound is considered to be more secure and safer diagnostic technique to determine the location of IUDs than hysteroscopic evaluation (Fig. 2, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

Imperforate hymen with hematocolpometra combined with elevated Ca125.

In the present case, ultrasound examination ruled out the presence of hematosalpinx or other gynecological tumors. This was of great importance to the surgical intervention, especially for avoiding laparotomy. Dilatation of the vagina and uterus, due to imperforate hymen with retrograde menstruation should be considered in the differential diagnosis of abdominal pain in premenarchal girls (Fig. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

Uterine prolapse in pregnancy: a rare condition an obstetrician should be familiar with.

Uterine prolapse complicating pregnancy is a rare event. Early recognition is essential in order to avoid possible maternal and fetal risks. We report the case of a 37-year-old pregnant woman who presented to the antenatal outpatient clinic with uterine prolapse at 31(+1) weeks of gestation. Sonographic examination revealed an enlarged fibromatous uterus. She was conservatively treated on an inpatient basis. Two weeks later she underwent an emergency cesarean section because of preterm uterine contractions. A live male neonate weighing 1,900 g was delivered. We believe that conservative management with bed rest, followed by an elective cesarean section, may ensure an uncomplicated gestation and an uneventful delivery.

Screening for pre-eclampsia by oxidative stress markers and uteroplacental blood flow.

Recent evidence suggests that the oxidative stress is an important factor in the pathophysiology of pre-eclampsia. The purpose of this study was to evaluate the possible relationship between increased resistance at the Doppler assessment of the uterine arteries between 20-23 gestational weeks and biochemical markers of oxidative stress, with the development of pre-eclampsia and/or growth restricted infants. This was a prospective study of 34 pregnant women with normal uteroplacental flow and 30 women with abnormal uterine arteries Doppler analysis (mean PI >or= 1.60) during the transvaginal assessment of the uterine arteries at the routine anomaly scan. Blood samples were obtained in order to assess the plasma oxidative stress, namely malondialdehyde (MDA) and uric acid levels. The MDA was significantly higher in the group of women with abnormal uterine arteries Dopplers. This group is at increased risk for the development of pre-eclampsia. The uric acid levels did not differ significantly between the two groups of women. There was no significant difference regarding the sensitivity or the specificity of the uterine arteries Doppler examination in detecting pre-eclampsia in comparison to the combination of oxidative stress and Doppler's. Our study provides additional evidence regarding the role of oxidative stress in the pathophysiology of pre-eclampsia. Whether antioxidant supplementation in the group of women with abnormal uterine Doppler's is effective in reducing the incidence of the disease remains to be established.

Herpes simplex Virus Esophagitis in an Immunocompetent Patient with Ebstein-Barr Virus Infection.

Epstein-Barr virus infectious mononucleosis can cause transient immune deficiency which may predispose to reactivation of latent herpes simplex virus (HSV) infection in the immunocompetent host. We report the case of a 15-year-old male who presented with severe odynophagia and herpes labialis during the course of Epstein-Barr virus infectious mononucleosis that had been diagnosed ten days before. Esophagoscopy revealed extensive ulcerations with distinct borders and whitish exudates at the mid and distal esophagus. Polymerase chain reaction detected HSV-1 DNA in the biopsy specimens. The patient was treated with intravenous acyclovir. The symptoms resolved rapidly within 3 days, in accordance with improved endoscopic findings.