Emanuele Ancona

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 postmenopausal 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. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to identify the mechanism of action of raloxifene, treat the adverse effects of raloxifene, prescribe raloxifene for patients with osteoporosis, to prevent estrogen receptor–positive breast cancer, as effective therapy in women with osteoporosis and concomitant increased levels of plasma cholesterol, and select the appropriate patients for raloxifene treatment using the patient’s medical history and risk of thromboembolism.

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.

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

PurposeIn 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.MethodsA 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”.Results10,331 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.ConclusionNo 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.

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.

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.

Fertility preservation in young women with cervical cancer: an oncologic dilemma or a new conception of fertility sparing surgery?

We have read with great interest the article by Hwang et al. showing the optimal results after lateral (1.5 cm above the iliac crest) ovarian transposition (OT) in order to preserve fertility after...

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.

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).

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.

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.