Retrospective study 2005-2015 of all cases of fetal death occurred at ≥23 gestational weeks, in Friuli Venezia Giulia, Italy.

BACKGROUND: Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available. METHODS: Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks. RESULTS: The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks. CONCLUSION: The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.

The Utility of the Congenital Pulmonary Airway Malformation-Volume Ratio in the Assessment of Fetal Echogenic Lung Lesions: A Systematic Review.

Although relatively uncommon, the incidence of fetal echogenic lung lesions - a heterogeneous group of anomalies that includes congenital pulmonary airway malformations (CPAM) and bronchopulmonary sequestrations (BPS) - has increased recently. Two decades ago, the CPAM-volume ratio (CVR) was first described as a tool to predict the development of hydrops, with this outcome found to be unlikely in fetuses with CVRs of ≤1.6 cm2. Since then, no clear international consensus has evolved as to the optimal CVR thresholds for the prediction of fetal/neonatal outcomes. This systematic review aimed to assess all original research studies that reported on the predictive utility of the CVR. Potentially relevant papers were identified through searching for citations of the paper that originally described the CVR, in addition to keyword searches of electronic databases. Fifty-two original research papers were included in the final review. Of these, 34 used the CVR for descriptive purposes only, 5 assessed the validity of established thresholds in different populations, and 13 proposed new thresholds. The evidence identified in this review would suggest that a threshold much lower than 1.6 cm2 is likely to be of greater utility in most populations for many outcomes of perinatal relevance. For neonatal outcomes (mostly respiratory compromise at birth), a CVR on the initial ultrasound scan ranging from 0.5 to 1.0 cm2 appears to have the greatest predictive value. Although a number of studies concurred that 1.6 cm2 was a useful threshold for the prediction of hydrops, many others were unable to assess this due to the rarity of this complication. For this reason, thresholds as low as 0.4 cm2 may be more useful for the prediction of a broader range of fetal concerns, including mediastinal shift and fluid collections. Further large-scale studies are required to determine the true utility of this well-established index.

Could HPV-DNA test solve the dilemma about sentinel node frozen section accuracy in early stage cervical cancer? Hypothesis and rationale.

In order to reduce the surgical invasiveness in early-stage cervical-cancer treatment, the sentinel lymph-node (SLN) technique could be considered as a possible intraoperative-guidance to lymphadenectomy decision making. Unfortunately its accuracy ranges between 33.3% and 100% in different studies. Recent manuscripts suggest that HPV-DNA presence in pelvic-lymph-nodes may represent a molecular marker of micrometastases. According to this hypothesis, the rationale in proposing the HPV-DNA-test when negative frozen-section occurs is due to the expected improvement of its diagnostic-accuracy. HPV-DNA test may represent a marker able to discriminate at frozen section the false-negative from the truth-negative tests filling the gap between optimal and real frozen-section accuracy.

Limits and complications of laparoscopic myomectomy: which are the best predictors? A large cohort single-center experience.

PURPOSE: To determine whether a correlation exists between size, location, type of myomas and perioperative outcomes. METHODS: This is a observational study in women undergone to laparoscopic myomectomy (LM) because of single symptomatic myoma >4 cm in diameter. We collected data about general features, surgical outcomes, intraoperative/postoperative complications and time to return to normal activity. RESULTS: A total of 444 patients (mean age 36.7 ± 6.4 years) resulted eligible for the study. Myomas sized between 8 and 12 cm were linked to an increased amount of blood loss (significantly higher in intramural than subserosal myoma). The removal of intramural myomas >8 cm and the subserosal ones >12 cm required a significant longer surgical time. Patients returned 17.9 ± 9.5 days after surgery to their personal activities. Six cases (1.35 %) required conversion to laparotomy, and only in two cases blood transfusion was necessary. CONCLUSION: Myomas size and type represent the best predictors of surgical difficulties and possible intrapostoperative complications. Intramural myomas >8 cm and subserosal ones >12 cm should be considered as a challenging procedure. LM remains the gold standard approach because of very low perioperative complication rate and faster return to normal activity.

Update on best available options in obstetrics anaesthesia: perinatal outcomes, side effects and maternal satisfaction. Fifteen years systematic literature review.

PURPOSE: In modern obstetrics, different pharmacological and non-pharmacological options allow to obtain pain relief during labour, one of the most important goals in women satisfaction about medical care. The aim of this review is to compare all the analgesia administration schemes in terms of effectiveness in pain relief, length of labour, mode of delivery, side effects and neonatal outcomes. METHODS: A systematic literature search was conducted in electronic databases in the interval time between January 1999 and March 2013. Key search terms included: "labour analgesia", "epidural anaesthesia during labour" (excluding anaesthesia for Caesarean section), "epidural analgesia and labour outcome" and "intra-thecal analgesia". RESULTS: 10,331 patients were analysed: 5,578 patients underwent Epidural-Analgesia, 259 patients spinal analgesia, 2,724 combined spinal epidural analgesia, 322 continuous epidural infusion (CEI), 168 intermittent epidural bolus, 684 patient-controlled infusion epidural analgesia and 152 intra-venous patient-controlled epidural analgesia. We also considered 341 women who underwent patient-controlled infusion epidural analgesia in association with CEI and 103 patients who underwent patient-controlled infusion epidural analgesia in association with automatic mandatory bolus. CONCLUSION: No significant differences occurred among all the available administration schemes of neuraxial analgesia. In absence of obstetrical contraindication, neuraxial analgesia has to be considered as the gold standard in obtaining maternal pain relief during labour. The options available in the administration of analgesia should be known and evaluated together by both gynaecologists and anaesthesiologists to choose the best personalized scheme and obtain the best women satisfaction. Since it is difficult to identify comparable circumstances during labour, it is complicate to standardize drugs schemes and their combinations.

Intrauterine Morcellator Devices: The Icon of Hysteroscopic Future or Merely a Marketing Image? A Systematic Review Regarding Safety, Efficacy, Advantages, and Contraindications.

The aim of this study was to analyze all available evidence regarding the use of intrauterine morcellator (IUM), for treatment of the most prevalent intrauterine benign lesions, compared to both traditional resectoscopy and conventional outpatient operative hysteroscopy in terms of safety, efficacy, contraindications, perioperative complications, operating time, and estimated learning curve. We reported data regarding a total of 1185 patients. Concerning polypectomy and myomectomy procedures, IUM systems demonstrated a better outcome in terms of operative time and fluid deficit compared to standard surgical procedures. Complication rates in the inpatient setting were as follows: 0.02% for IUM using Truclear 8.0 (Smith & Nephew Endoscopy, Andover, Massachusetts) and 0.4% for resectoscopic hysteroscopy. No complications were described using Versapoint devices. Office polipectomy reported a total complication rate of 10.1% using Versapoint device (Ethicon Women's Health and Urology, Somerville, New Jersey) and 1.6% using Truclear 5.0 (Smith & Nephew Endoscopy). The reported recurrence rate after polypectomy was 9.8% using Versapoint device and 2.6% using Truclear 8.0. Finally, the reported intraoperative and postoperative complication rate of IUM related to removal of placental remnants using Truclear 8.0 and MyoSure (Hologic, Marlborough, Massachusetts) was 12.3%. The available evidence allows us to consider IUM devices as a safe, effective, and cost-effective tool for the removal of intrauterine lesions such as polyps, myomas (type 0 and type 1), and placental remnants. Evidence regarding Truclear 5.0 suggests that it may represent the best choice for office hysteroscopy. Further studies are needed to confirm the available evidence and to validate the long-term safety of IUM in procedures for which current data are not exhaustive (placental remnants removal).

Could Harmonic Scalpel (Ultracision®) be considered the best device in surgical treatment of vulvar cancer of patients with implanted pace-maker? Proposal and rationale.

Vulvar cancer (VC) represents about 4% of gynecologic malignancies, its incidence increases with age and peak incidence is found between 70-79 years. In cases of locally advanced disease surgery is often required and radical vulvectomy, with or without mono-bilateral inguino-femoral lymphadenectomy, is standard management. Various devices have been implemented in gynecological surgery in an attempt to minimize or avoid frequent intra/postoperative complications linked to energy use, unfortunately the majority of these devices require monopolar or bipolar energy. Ultracision® represents a unique surgical device capable of performing both cutting and coagulation at different intensities without use of electric energy. The use of Ultracision® in the radical treatment of VC has advantages both in terms of intraoperative and postoperative complications responsible for the reduction of surgical time and blood loss, complete tissue removal according to oncological criteria, diminished desensitization of peripheral areas and reduction of wound complications. These advantages have been widely demonstrated and contribute to making Ultracision® a cost-effective option in the routine treatment of patients affected by vulvar cancer especially when considering its safety in cardiopathic patients with implanted pacemaker. If the impressive results achieved in radical vulvar surgery will be confirmed, scalpel use could be proposed as routine for surgery of the routinely in surgical approach of vulvar and perineal area, in both benign and malignant disease.

Levonorgestrel intrauterine system in adjuvant tamoxifen treatment: balance of breast risks and endometrial benefits--systematic review of literature.

Levonorgestrel intrauterine system (LNG-IUS) is used in patients with breast patients taking tamoxifen (TAM) to prevent endometrial proliferation. The benefits (on endometrium), the side effects (on breast), and the patients suitable for this treatment are not still clear. Aim of this systematic review is to define the breast risks and endometrial benefits in TAM-treated women using Mirena and to define which patients could benefit from LNG-IUS use. In all, 3 studies on LNG-IUS effects on endometrium in TAM-treated women and 4 studies on breast cancer recurrence were selected for the study. All studies described a reduction in benign endometrial pathologies among Mirena users, but controversial data showed malignant disease and breast cancer recurrence. So it is mandatory to define hormonal status before TAM treatment. In selected patients Mirena was proven to protect endometrium. Perspective clinical trials on Mirena pharmacological features are necessary to establish whether systemic levels of progesterone could increase breast cancer recurrence in such patients.

Magnetic resonance-guided focused ultrasound myomectomy: safety, efficacy, subsequent fertility and quality-of-life improvements, a systematic review.

We performed a systematic review about studies reporting data of myomectomy performed by magnetic resonance-guided focused ultrasound (MRgFUS) technique in order to define its safety, feasibility, indications, complications, and impact on uterine fibroid symptom and health-related quality of life (UFS-QOL) and fertility. Outcomes were considered according to fibroids shrinkage, nonperfused volume (NPV), NPV ratio, and uterine fibroid symptoms assessed with UFS-QOL questionnaire (baseline 3, 4, 6, and 12 months). We analyzed 38 eligible studies reporting outcomes about 2500 patients (mean age 43.67 years). The MRgFUS results a safe, efficient, and cost-effective minimal invasive technique for treatment of uterine fibroids. Increasing experience, device improvements, and availability for a larger number of patients are enhancing the outcomes, while the obstetrical ones should be more extensively explored. The MRgFUS could be considered as a minimal invasive alternative to traditional surgical or radiological procedures for the treatment of symptomatic uterine myomas improving both QOL and subsequent fertility.

Intrapartum ultrasound assessment of fetal spine position.

We investigated the role of foetal spine position in the first and second labour stages to determine the probability of OPP detection at birth and the related obstetrical implications. We conducted an observational-longitudinal cohort study on uncomplicated cephalic single foetus pregnant women at term. We evaluated the accuracy of ultrasound in predicting occiput position at birth, influence of fetal spine in occiput position during labour, labour trend, analgesia request, type of delivery, and indication to CS. The accuracy of the foetal spinal position to predict the occiput position at birth was high at the first labour stage. At the second labour stage, CS (40.3%) and operative vaginal deliveries (23.9%) occurred more frequently in OPP than in occiput anterior position (7% and 15.2%, resp.), especially in cases of the posterior spine. In concordant posterior positions labour length was greater than other ones, and analgesia request rate was 64.1% versus 14.7% for all the others. The assessment of spinal position could be useful in obstetrical management and counselling, both before and during labour. The detection of spinal position, more than OPP, is predictive of successful delivery. In concordant posterior positions, the labour length, analgesia request, operative delivery, and caesarean section rate are higher than in the other combination.

Usefulness, methods and rationale of lymph nodes HPV-DNA investigation in estimating risk of early stage cervical cancer recurrence: a systematic literature review.

Metastatic involvement of pelvic lymph-nodes (LNs), generally found in 0-29.3 % of early stages, is the most important prognostic factor in cervical cancer (CC). However, even in non-metastatic LNs, recurrence rate reaches 10-15 %. The role of HPV-DNA presence in pelvic LNs has been a point of debate in the last two decades. The aim of this systematic review is to collect all available data about LNs HPV-DNA detection in patients affected by early-stage CC in order to elucidate its clinical and surgical usefulness to choose the best surgical treatment, the necessity of adjuvant therapy and to estimate the overall oncological prognosis. The available data in this field results very patchy and often conflicting in the results. The high correlation between HPV-DNA genome detected in primary lesion and the one detected in LNs, as well as the high correlation between LNs metastatic involvement and HPV-DNA presence, lead to hypothesize that LNs HPV presence represents a potential risk-factor for recurrence and poor oncological prognosis. The large disparities in recurrence-rate of cases with LNs positive for HPV-DNA test and negative for metastases could be explained by the relative "inappropriateness" of PCR test to discriminate the presence of HPV-genome alone (condition necessary but not sufficient) or in association with squamous cells (condition necessary and sufficient). The use of ISH test for HPV-DNA detection in LNs, particularly if associated to CK19-assay, improve the accuracy of micro-metastasis detection, and the identification of patients with negative histology but potentially at high-risk of recurrence and poor oncological prognosis.

Endometrial surveillance in tamoxifen users: role, timing and accuracy of hysteroscopic investigation: observational longitudinal cohort study.

To determine the role, timing and indications for endometrial hysteroscopic investigation in relation to the clinical, ultrasound and histological features of the endometrium during tamoxifen (TAM) use. We performed an observational longitudinal cohort study (years 2007-2012) that investigated the endometria of 151 TAM users with hysteroscopy and histology. For all patients, gynaecological history, years of adjuvant treatment, ultrasound endometrial thickness measurement and indications for hysteroscopy were recorded. Hysteroscopic findings showed that 100% of patients referred for simple follow-up had no evidence of endometrial disease. We found a strong correlation between previous history of abnormal uterine bleeding (with or without endometrial thickening) and hysteroscopic suspicion of endometrial atypia that was confirmed by histology. Hysteroscopy had 83.3% sensitivity, 99% specificity, 83.3% positive predictive value (PPV) and 99% negative predictive value (NPV) in detecting endometrial atypia. No significant correlation was found between endometrial thickening to >5 mm without bleeding and histological atypia. Similarly, the duration of treatment was not related to endometrial thickening and histological atypia. Endometrial stromal hyperplasia was detected by histology in 70.5% of patients with endometrial thickness measurements ranging from 5 to 10 mm. In contrast, no atypia was detected when endometrial thickness was <5 mm. Ultrasound performed using a 5-mm cut-off threshold for endometrial thickness resulted in 100% sensitivity, 15% specificity, 4% PPV and 100% NPV in detecting endometrial atypia, while a 10-mm cut-off threshold resulted in 84% sensitivity, 69% specificity, 10% PPV and 99% NPV. Low-risk TAM users do not require different endometrial surveillance than the general population. Hysteroscopy could play a fundamental role in determining the endometrial status of patients before the initiation of TAM treatment and in assessing the endometrial status of patients when bleeding occurs.

Radical trachelectomy: the first step of fertility preservation in young women with cervical cancer (Review).

Radical trachelectomy (RT) can be performed vaginally or abdominally (laparotomic, laparoscopic or robotic). The aim of this systematic review was to compare all techniques in terms of surgical complications, disease recurrence and subsequent fertility/pregnancy outcomes. A total of 1293 RTs were analyzed (FIGO-stage: IA1-IIA). The most frequent surgical complications do not differ from the ones of radical hysterectomy. The recurrence risk is approximately 3% (range 0-16.8%). The majority of women conceive spontaneously: 284 pregnancies with 173 live births. The most frequent pregnancy complication was miscarriage and chorioamnionitis. RT appears to be a safe option for eligible women who intend to maintain their future pregnancy desire.

Update on raloxifene: mechanism of action, clinical efficacy, adverse effects, and contraindications.

Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in post-menopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor-positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene.