Search

N-Demethylation and dehalogenation of chlorpromazine (CPZ) were compared in six psychotic inpatients and in rats orally treated for 4 weeks with a daily CPZ dose of 5.4 (mean value) and 20 mg X kg-1 body weight, respectively, by measuring drug and metabolite plasma levels by means of a gas-liquid chromatography-nitrogen/phosphorus detector method. In patients the major plasma metabolite was found to be promazine (PZ), as identified by capillary GC-MS analysis. In rats, on the contrary, PZ represented only a small proportion of the compounds detected in plasma. The mean [PZ]/[CPZ] ratio after 4 weeks of treatment was 1.64 in patients and 0.08 in rats. The relative frequency of the N-demethyl metabolites in plasma, however, was similar in the two species. The mean [N-monodemethylated CPZ]/[CPZ] and [N-didemethylated CPZ]/[CPZ] ratios after 4 weeks of treatment were 0.45 and 0.24 in patients and 0.56 and 0.25 in rats, respectively. These findings suggest that dechlorination of CPZ in psychotic patients represents an important metabolic pathway.

Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild-to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P0.0001), aspartate (P0.0001), GABA (P0.0001) and taurine (P0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage.

OBJECTIVE: To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta. METHODS: This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 340-356 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not. RESULTS: Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%; p = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively. CONCLUSION: In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury.

Background: Transversus abdominis plane (TAP) block and wound infiltration (WI) with local anesthetics are used for postoperative analgesia after cesarean section (CS), reducing the need for administration of opioids. Objective: To compare the analgesic effect of TAP block related to WI. Search strategy: MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Cochrane Library, and CINAHL were searched from inception until April 2020. Selection criteria: Randomized controlled trials (RCTs) about women who underwent TAP block or WI after CS. Data collection and analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome was cumulative opioid consumption (COC) 24 and 48 h after CS. Main results: Five RCTs, enrolling 268 women, were included. There were no significant differences between the interventions regarding COC at 24 (mean difference [MD] -1.68, 95% confidence interval [CI] -6.29 to 2.93) and 48 hours (MD 1.28, 95% CI -10.44 to 13.00). Adverse effects (relative risk [RR] 0.93, 95% CI 0.75-1.16), gastrointestinal reactions (RR 1.30, 95% CI 0.46-3.68), or mild-moderate sedation (RR 1.12, 95% CI 0.72-1.74), pain scores, satisfaction of women, and withdrawals were similar between groups. Conclusions: There might be no significant advantages selecting TAP block over WI for post-CS analgesia.

Purpose: Cancer-related cognitive impairment (CRCI) has been reported in non-central nervous system neoplasms survivors. The purpose of this study was to evaluate the perception of cognitive decrement in patients undergoing surgical and / or medical therapy for gynecological cancers. Methods: All women diagnosed with primary gynecological cancer and undergoing active medical treatment have been enrolled in a prospective study. Before starting treatment (T1) and 6 months after the end of treatment (T2), patients were interviewed to evaluate the effects of cancer treatment on perceived cognitive function (using FACT-Cog -version 3), on depression (using Beck Depression Inventory-II test) and on quality of life (using EORTC-QLQC-30). Age, education level, marital status, lifestyle, menopausal state at diagnosis, cancer type, cancer FIGO stage, treatment modality was also recorded. The differences between baseline and post-treatment results have been evaluated with Student's t test. The results have been stratified by the menopausal state at diagnosis, type of tumor (endometrial, cervical, ovarian, vulvar) disease stage and type of treatment (chemotherapy or radiotherapy). Results: Seventy-three patients were included. A significant reduction in perceived cognitive impairments was demonstrated at T2 (CogPCI: 61.35 ± 13.83 vs 55.05 ± 16.56; p < 0.05). On the contrary, a significant improvement was shown in depression state (BDII: 21.14 ± 11.23 vs 12.82 ± 12.33, p < 0.005). The menopausal state at surgery, tumor site, stage and treatment modality seem to influence the variables analyzed. Conclusion: CRCI is a true risk also in gynecological cancer survivors. The cognitive impairment does not seem to be dependent on depression state after treatment or to a menopausal condition. Assessing cognitive decline in cancer survivorship is essential for ensuring the optimum quality of life and functioning.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by hyperglycaemia with onset or first recognition during pregnancy. Risk factors include family history of diabetes, previous GDM, genetic predisposition for GDM/type 2 diabetes, insulin resistance conditions such as overweight, obesity and ethnicity. Women with GDM are at high risk for fetal macrosomia, small for gestational age, neonatal hypoglycaemia, operative delivery and caesarean delivery. The aim of this narrative review is to summarize the most recent findings of diagnosis and treatment of GDM in order to underline the importance to promote adequate prevention of this disease, especially through lifestyle interventions such as diet and physical activity. METHODS: The research was conducted using the following electronic databases, MEDLINE, EMBASE, Web of Science, Scopus, ClinicalTrial.gov, OVID and Cochrane Library, including all published randomized and non-randomized studies as well as narrative and systematic reviews. RESULTS: The lack of universally accepted criteria makes the definition of diagnosis and prognosis of this condition difficult. Early diagnosis and glucose blood level control may improve maternal and fetal short and long-term outcomes. Treatment strategies include nutritional interventions and exercise. Medical treatment can be necessary if these strategies are not effective. Moreover, novel non-pharmacologic agents such as myo-inositol seem to be effective and safe both in the prevention and the treatment of GDM. CONCLUSIONS: It is important to promote adequate prevention of GDM. Further studies are needed in order to better define the most appropriate strategies for the clinical management of women affected by GDM.

Introduction: The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may cause a not negligible rate of adverse events, in particular vasomotor symptoms and bone mineral density loss, that may limit patients’ adherence and safety on long-term treatment. Several strategies have been suggested to improve the compliance to treatment. Areas covered: This narrative review aims to give an overview of the safety and tolerability of GnRH-a therapy and to present the different options of steroidal and non-steroidal add-back therapies in order to reduce the hypoestrogenic side effects. Expert opinion: Side effects of long term GnRH-a treatment are particularly relevant. Although it has been known the efficacy of GnRH-as for treating endometriosis-associated pain, the best schedules of therapy in terms of duration and dosages are still to be defined. The ideal treatment schedule of GnRH-a is still a matter of debate as to the optimal add-back combination.

Background: Rectal laceration without sphincter lesion during childbirth is an unusual presentation. Like all the other severe lacerations during parturition, if left undiagnosed and untreated could hesitate in serious short and long term complications. Episiotomy once considered a routine procedure in nulliparous and a safeguard against severe tissue trauma nowadays is undergoing criticism and his effectiveness reconsidered. Currently, a policy of “selective” use of episiotomy is recommended only when an impending risk of lacerations is identified. When, according to this proposal, in the absence of risk factors episiotomy is not performed and complications occur, the medicolegal implication could arise. Case: A 29-year-old primigravida was admitted with spontaneous onset of labor at 41 weeks after an uncomplicated pregnancy. During the second stage of labor a spurt of siero- hemorrhagic fluid was noted trough the anus. In absence of recognized risk factor episiotomy was not performed. A healthy 3650 grams female was born in a fair condition. Rectal examination immediately after delivery revealed a longitudinal laceration with un undamaged sphincter. The rectal tear was repaired and recovery was uneventful. Conclusions: In our as in the other cases here reviewed a severe laceration occurred unexpectedly and unpreventably in patients where, according to a selective regime, episiotomy was not performed. In this setting, if severe short and long term complications ensued, especially in nulliparous, the decision to withhold episiotomy could be a source of medicolegal issues. Therefore a detailed informed consent is necessary to offer to patients a full disclosure on the role of episiotomy, its recent indications as well as the possible complications stemming from both executing or withholding this procedure.

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 8–13% of reproductive-age women. Irregular periods, hirsutism, or infertility are the most common clinical presentations of patients affected by PCOS. This syndrome is also linked to metabolic abnormalities such as type 2 diabetes, insulin resistance and obesity. The optimal therapeutic approach is still unknown. Areas covered: This narrative review offers an overview of the literature on current and experimental pharmacological options for treating PCOS and highlights ongoing clinical trials. Several electronic databases were searched and current research registers were analyzed to the present year. The papers selected for this review were critically analyzed, and all data available were summarized, organized, and explored to derive key information. Expert opinion: The main goal of PCOS treatment is to obtain a metabolic and hormonal balance. Optimal PCOS therapy should be direct to the reproductive abnormalities and the entire spectrum of endocrine and metabolic complications that appear to have a long-term negative impact on PCOS patient health, as in post-menopausal period. The discovery of new mechanisms in PCOS pathogenesis will offer the possibility of testing new drug classes.

Objective. Evaluate the effects of carboxy-methyl-beta-glucan on cervical epithelialization and on the vaginal microbiota in patients with HPV infection or low-grade cervical preneoplastic lesion (CIN 1). Materials and Methods. Seven-hundred eighty-four women with positive HPV tests or diagnosed with CIN 1 were enrolled in a retrospective case-control study. All the recruited women performed, at baseline and after 6 months, Pap test, HPV test, evaluation of vaginal health according to the Amsel criteria, colposcopy, and punch biopsy. The study population was then divided into 2 groups in relation to the therapy performed during the follow-up period. Group A performed treatment with vaginal gel based on carboxy-methyl-beta-glucan (1 application/day for 20 days per month for 3 months). Group B was the control group. Results. The patients of group A had a significant improvement in the ectopia pattern and a greater number of cases with metaplasia in the maturation phase with a significant increase in Lugol uptake. In the experimental group, a significant improvement in the pH indices, a negative Swift test and a resolution of the leucorrhoea were observed. A negative result of the 37.1% Pap test and the 39.9% HPV test (vs. 15.2% and 16.5%, respectively) were demonstrated in the treatment group with respect to the control group. A negativization of the colposcopic pictures was observed with a reduction in the amount of CIN 1 found higher in the treatment group. Conclusions. Vaginal therapy based on carboxy-methyl-beta-glucan has been able to improve overall vaginal health; this effect seemed to positively impact the risk of persistence and progression of CIN.

Objective: This study aimed to evaluate the risk of endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women concerning the endometrial thickness measured by stratified threshold categories used for performing subsequent endometrial sampling and histologic evaluation. Data Sources: MEDLINE, Scopus, ClinicalTrials.gov, SciELO, Embase, the Cochrane Central Register of Controlled Trials, LILACS, conference proceedings, and international controlled trials registries were searched without temporal, geographic, or language restrictions. Study Eligibility Criteria: Studies were selected if they had a crossover design evaluating the risk of atypical endometrial hyperplasia and endometrial carcinoma in postmenopausal asymptomatic women and calculated the diagnostic accuracy of transvaginal ultrasonography thresholds (at least 3.0 mm) confirmed by histopathologic diagnosis. Methods: This was a systematic review and diagnostic test accuracy meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy and Synthesizing Evidence from Diagnostic Accuracy Tests guidelines. Endometrial thickness thresholds were grouped as follows: from 3.0 to 5.9 mm; between 6.0 and 9.9 mm; between 10.0 and 13.9 mm; and ≥14.0 mm. Quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. Publication bias was quantified using the Deek funnel plot test. Coprimary outcomes were the risk of atypical endometrial hyperplasia or endometrial carcinoma according to the endometrial thickness and diagnostic accuracy of each threshold group. Results: A total of 18 studies provided the data of 10,334 women who were all included in the final analysis. Overall, at an endometrial thickness threshold of at least 3.0 mm, the risk of atypical endometrial hyperplasia or endometrial carcinoma was increased 3-fold relative to women below the cutoff (relative risk, 3.77; 95% confidence interval, 2.26–6.32; I2=74%). Similar degrees of risk were reported for thresholds between 3.0 and 5.9 mm (relative risk, 5.08; 95% confidence interval, 2.26–11.41; I2=0%), 6.0 and 9.9 mm (relative risk, 4.34; 95% confidence interval, 1.68–11.23; I2=0%), 10.0 and 13.9 mm (relative risk, 4.11; 95% confidence interval, 1.55–10.87; I2=86%), and ≥14.0 mm (relative risk, 2.53; 95% confidence interval, 1.04–6.16; I2=78%) with no significant difference among subgroups (P=.885). Regarding diagnostic accuracy, the pooled sensitivity decreased from thresholds below 5.9 mm (relative risk, 0.81; 95% confidence interval, 0.49–0.85) to above 14.0 mm (relative risk, 0.28; 95% confidence interval, 0.18–0.40). Furthermore, the specificity increased from 0.70 (95% confidence interval, 0.61–0.78) for endometrial thickness between 3.0 and 5.9 mm to 0.86 (95% confidence interval, 0.71–0.94) when the endometrial thickness is ≥14.0 mm. For 3.0 to 5.9 mm and 10.0 to 13.9 mm thresholds, the highest diagnostic odds ratios of 10 (95% confidence interval, 3–41) and 11 (95% confidence interval, 2–49), with areas under the curve of 0.81 (95% confidence interval, 0.77–0.84) and 0.82 (95% confidence interval, 0.79–0.86), respectively, were retrieved. The summary point analysis revealed that the 3.0 to 5.9 mm cutoff point was placed higher in the summary receiver operator curve space than the other subgroups, indicating increased endometrial carcinoma or atypical endometrial hyperplasia diagnosis using these cutoffs. Conclusion: Both low and high endometrial thickness thresholds in postmenopausal asymptomatic women seem equally effective in detecting endometrial carcinoma and atypical endometrial hyperplasia. However, although using a 3.0 to 5.9 mm cutoff results in a lower specificity, the offsetting improvement in sensitivity may justify using this cutoff for further endometrial evaluation in patients with suspected endometrial malignancy.

Purpose This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). Methods Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. Results Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. Conclusions TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results.

This cross-sectional study aimed to evaluate the prevalence of postpartum depression and the associated risk factors in a sample of Italian women at three months after delivery. Eighty women were screened by completing the Edinburgh Postnatal Depression Scale (EPDS). Women with a score ≥10 were evaluated as positive and other variables were detected through the administration of the Postpartum Depression Predictors Inventory. The prevalence of postpartum depression in the sample was 11.25% (EPDS score >10). A statistically significant relationship was found between the predisposition to postnatal depression and various risk factors such as prenatal depression, stressful life experiences marital problems. Furthermore, strong emotional and instrumental support from the partner and a good economic status can represent protective factors. It is essential to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account, and adequate screening programs are implemented.Impact StatementWhat is already known on this subject? Pregnancy can cause emotional stress for women with consequent development, in some cases, of mood disorders such as postpartum depression. What do the results of this study add? According to this study, women suffering from postpartum depression showed a significant tendency to anxiety and depression, low perceived support from the partner, and low socio-economic status. What are the implications of these findings for clinical practice and/or further research? It would be desirable to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account and adequate screening programs are implemented.

Histological chorioamnionitis is associated with significant adverse maternal, perinatal and long-term outcome. We performed a meta-analysis of 30 observational studies in order to clarify the association between Histological chorioamnionitis and pulmonary complications, like respiratory distress syndrome and Bronchopulmonary Dysplasia. Unadjusted data extracted from all studies showed that Histological chorioamnionitis has no effect on development of RDS (RR 0.93, 95% CI 1.08-1.67), while it increased the risk of Bronchopulmonary Dysplasia (RR 1.75, 95% CI 1.37-2.23). However, when we restricted the analysis to the studies that adjust for Gestational Age, in order to exclude the influence of prematurity, we found that HCA reduced the risk of respiratory distress syndrome (RR 0.57, CI 95% 0.35-0.93) and it did not affect the development of Bronchopulmonary Dysplasia (RR 0.99, CI 0.76-1.3). Our results confirmed a possible role of prenatal inflammation on lung maturation. However, further prospective studies with a selected population are needed, in order to clarify the role of Histological chorioamnionitis in neonatal pulmonary complications.

Introduction: To evaluate the feasibility of uterine arteries prophylactic occlusion balloon placement (POBP) to reduce hemorrhagic complications associated with placenta praevia. Material and methods: A retrospective analysis was carried out from January 2014 to November 2018. Only women with a diagnosis of placenta praevia and gestational age at delivery between 33 and 40 weeks were included. All women were diagnosed using transvaginal ultrasound scan (TVS) and confirmed with magnetic resonance imaging (MRI). All women underwent uterine arteries POBP before caesarean delivery (CD). All patients underwent clinical and instrumental follow-up with semestral outpatient TVS for 2 years after the surgery. Results: Forty-eight pregnant women were recruited and analyzed. 32/48 patients (66%) had positive anamnesis for previous CDs. Mean blood loss was 510 ± 222 mL. 15/48 patients (31.6%) were supported with RBC concentrate transfusion. In 10 (20.8%) cases, an intrauterine haemostatic balloon (Bakri-Balloon, Cook Medical, Spencer, USA) was used to control the intra-operative hemorrhage. Hysterectomy was performed in eight cases (16.6%). No cases of hemodynamic instability or urinary complications were reported. No postoperative complications occurred. During follow-up, no long-term complications were observed and nine patients had a successful pregnancy. Conclusions: Uterine arteries POPB is a promising technique that may be adopted in women with placenta praevia to prevent hemorrhagic complications.

Endometrial carcinoma (EC) is the most common gynecological malignancy in the world. It is mostly detected in postmenopausal women, but it can also occur in women of fertile age who need fertility-sparing therapy. An early diagnosis is the main objective for the correct management of these patients, making it possible to use a fertility-sparing treatment approach without exposing the patients to the risk of cancer progression. In this review, we discuss the role of sonography and hysteroscopy in the detection of intrauterine neoplasm in women of childbearing age.

Objective To evaluate the impact of hysteroscopy for retained products of conception (RPOC) removal on surgical and reproductive outcomes. Data Sources Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, SciELO, EMBASE, and the Cochrane Central Register of Controlled Trials at the Cochrane Library) were searched from inception to March 2020. Methods of Study Selection Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were followed. Medical Subject Headings terms and text words such as “retained products of conception,” “placental remnants,” “placenta,” and “hysteroscopy” were used for the identification of relevant studies. We included observational and randomized studies that analyzed surgical and/or reproductive outcomes of women who underwent hysteroscopic removal of RPOC. The primary outcome was the complete resection rate after 1 procedure. Tabulation, Integration, and Results Twenty out of 245 studies were applicable, with data provided for 2112 women. The pooled complete resection rate was 91% (95% confidence interval [CI], 0.83–0.96). The incomplete resection rate evaluated was 7% (95% CI, 0.03–0.14), with a complication rate of 2% (95% CI, 0.00–0.04). Out of 1478 procedures, only 12 cases (0.8%) of postsurgical intrauterine adhesions were reported. Regarding post-therapy fecundity, women attempting postoperative conception had a clinical pregnancy rate of 87% (95% CI, 0.75–0.95), with a live birth rate of 71% (95% CI, 0.60–0.81) and a pregnancy loss rate of 9% (95% CI, 0.06–0.12). Conclusion Hysteroscopy has a high rate of completely removing RPOC in a single surgical step, with low complication rates. Subsequent fecundity seems reassuring, with appropriate clinical pregnancy and live birth rates. However, standardization of approach and comparative trials of different hysteroscopic approaches are needed.

Postmenopausal bleeding (PMB) is a relevant aspect for health-care providers in clinical practice: the first objective is to rule out potential gynecological cancer. The purpose of this narrative review is to evaluate the role of office hysteroscopy in the management of PMB. Office hysteroscopy is a minimally invasive procedure allowing direct visualization of uterine pathology without the need for general anesthesia and the use of an operating room, generating cost savings and greater compliance among patients. Here, we focus on major intrauterine diseases (polyps, submucosal myomas, endometrial hyperplasia, and cancer) as causes of PMB. Office hysteroscopy appears to be safe and feasible, and could allow accurate diagnosis of intrauterine pathologies, especially that with a focal growth pattern, otherwise misdiagnosed with blinded procedures. However, studies focusing exclusively on postmenopausal women are still few, so further research, especially randomized controlled trials, is needed.

Aim Human papillomavirus (HPV) is the etiologic agent of the majority of cervical intraepithelial lesions (CIN) and cervical cancers. While prophylactic HPV vaccines prevent infections from the main high-risk HPV types associated with cervical cancer, alternative nonsurgical and nonablative therapeutics to treat HPV infection and preinvasive HPV diseases have been experimentally investigated. Therapeutic vaccines are an emerging investigational strategy. This review aims to introduce the results of the main clinical trials on the use of therapeutic vaccines for treating HPV infection and -related CIN, reporting the ongoing studies on this field. Methods Data research was conducted using MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library querying for all articles related to therapeutic vaccines for the treatment of HPV-related CIN. Selection criteria included randomized clinical trials, nonrandomized controlled studies and review articles. Results Preliminary data are available on the evaluation of therapeutic vaccines for treating cervical HPV infections and CIN. Despite having in vitro demonstrated to obtain humoral and cytotoxic responses, therapeutic vaccines have not yet clinically demonstrated consistent success; moreover, each class of therapeutic vaccines has advantages and limitations. Early clinical data are available in the literature for these compounds, except for MVA E2, which reached the phase III clinical trial status, obtaining positive clinical outcomes. Conclusion Despite promising results, to date many obstacles are still present before hypothesize an introduction in the clinical practice within the next years. Further studies will draw a definitive conclusion on the role of therapeutic vaccines in this setting.

Introduction: Cervical cancer is the fourth common cancer in women worldwide. While, in the past, locally advanced stage disease was treated by pelvic radiotherapy, nowadays the National Cancer Institute strongly recommends chemoradiation protocols. Weekly cisplatin was previously the standard of care in this setting; however, the low response rate and the short median progression-free survival (PFS) of patients have led researchers to investigate combinatory regimens. Area covered: This article is based on literature searches up until April 2019, with current trial registers also analyzed. All data available on this topic has been summarized in this narrative review. Expert opinion: In recent years, it has been demonstrated that cisplatin-based doublets, and in particular, cisplatin plus paclitaxel, are superior to cisplatin as a monotherapy in terms of response rate and progression-free survival of patients with advanced cervical cancer. This double regime combined with bevacizumab is also considered the first-line option for metastatic or recurrent disease. Dose-dense paclitaxel in neo-adjuvant chemotherapy combinations is a promising option in patients with locally advanced cervical cancer. Exploration of novel biological therapies and in vitro combinations based on the use of paclitaxel is warranted.

Introduction: Colposcopy represents the second step of the diagnostic approach of cervical intraepithelial lesions. Limits of colposcopy in studying cervix are essentially related to cervical anatomy. Nowadays, endocervical courettage is the standard technique to examine endocervix. Endocervicoscopy is a new imaging technique for the diagnostic work-up of endocervix in patients with cervical intraepithelial neoplasia (CIN). Objective: To evaluate endocervicoscopy accuracy to identify and grade cervical intraepithelial lesion in comparison to other procedures employed into the diagnostic workup of cervical pathology. Methods: A total of 634 women who performed colposcopy, endocervicoscopy and cytological or histological sampling were included in a retrospective study. The agreement between the endocervicoscopic and the colposcopic impressions, minor and major changes, and between these imaging techniques and histological diagnosis was assessed for the entire cohort. χ2 test and k statistic were used in the statistical analysis. Results: The extension of the lesion resulted significantly greater at endocervicoscopy than at colposcopy. We showed a statistically significant association between colposcopy and endocervicoscopy findings. Overall, the correlation of minor or major findings between colposcopy and endocervicoscopy was statistically significant with a p value for all parameters k value (k = 0.68 [95% CI 0.64–0.73], k = 0.80 [95% CI 0.75–0.85], k = 0.78 [95% CI 0.64–0.90], respectively). The sensitivity (70.1%) and the specificity (77.0%) of endocervicoscopy for all CIN lesions were lower than colposcopy. Conclusion: Endocervicoscopy turned out to be a good method to identify and grade CIN lesions in a subset of patients where colposcopy was not satisfactory. It allowed us to overcome one of the limits of colposcopy in the evaluation of the squamo-columnar junction and to establish the real extension of the lesion into cervical cancer.

Background: Postpartum hemorrhage (PPH) is responsible for about 25% of maternal deaths worldwide. Antifibrinolytic agents, mainly tranexamic acid (TXA), have been demonstrated to reduce blood loss in patients with established PPH. Objective: The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of TXA administration in women with established primary PPH after vaginal delivery. Data sources: The search was conducted using electronic databases from inception of each database through February 2018. Review of articles also included the abstracts of all references retrieved from the search. No restrictions for language or geographic location were applied. Study design: Selection criteria included RCTs comparing the use of TXA in women with established primary PPH after vaginal delivery with control (either placebo or no treatment). Trials in women undergoing cesarean delivery and trials in prevention of PPH were excluded. The primary outcome was the incidence of hysterectomy. The summary measures were reported as summary relative risk (RR) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird. Tabulation, integration, and results: Two trials including 14,363 women with established primary PPH after vaginal delivery were analyzed. Women who received TXA soon after the diagnosis of PPH had a significantly lower incidence of hysterectomy (0.5% vs 0.8%; RR 0.63, 95% CI 0.42–0.94), compared to those who did not. The risk of thrombotic events was not increased in the TXA group. Conclusion: In women with established PPH after vaginal delivery, the use of TXA reduces the risk of hysterectomy and does not increase the risk of thrombotic events. We recommend 1 g plus a second dose of 1 g if bleeding continues after 30 min.

Introduction Endometriosis is a very common disease that affects up to 10% of the female population. The use of indocyanine green (ICG) dye has been proposed to allow the proper localization of endometriotic lesions during surgery. Our purpose is to offer an overview of near-infrared (NIR)-ICG in the surgical treatment of superficial peritoneal endometriosis and deep infiltrating endometriosis. Material and methods Electronic databases were searched, including MEDLINE, Embase, Web of Science, Scopus, ClinicalTrial.gov, OVID and Cochrane Library. The studies were identified with the use of a mesh combination of the following keywords: "indocyanine green", "endometriosis", "deep endometriosis", "robotic surgery", "laparoscopy", "ureter", "rectosigmoid" from 2000 to May 2020. All articles describing the use of ICG applied to endometriosis surgery were considered for review. Only original papers that reported specific experience data on the topic were included. Moreover, video-articles were included in the analysis. Quality and risk of bias were evaluated by two authors, respectively. Results Fifty-three studies were reviewed and reviews or comment articles not reporting original data and original articles lacking specific data on the application of ICG in patients affected by endometriosis were excluded. The quality of the 17 studies included was assessed. Eight studies suggested the usefulness of NIR-ICG as a tool in the detection of endometriosis during surgery, and one randomized controlled trial and one prospective study did not confirm the advantage of its use. Eight studies found that NIR-ICG was useful for the evaluation of vascularization in intestinal anastomoses and ureterolysis after surgery for deep infiltrating endometriosis. Conclusions NIR-ICG appears useful in the evaluation of vascularization in intestinal anastomoses after segmental resection, confirming its role even after ureterolysis for parametrial deep infiltrating endometriosis. However, its usefulness as a tool in the detection of endometriosis during surgery is inconsistent.

Objective To investigate the diagnostic accuracy of endometrial biopsy performed with hysteroscopic direct visualization using the “grasp technique” for the detection of endometrial carcinoma (EC) histology type and tumor grade. Methods A cross-sectional study including the clinical and pathology records of patients with confirmed EC who underwent definitive surgery at University of Naples was performed. The preoperative diagnosis of endometrial tumor type and grade obtained using the hysteroscopy grasp technique was correlated with the final pathology specimens. Those results were compared to the diagnostic accuracy of the biopsies collected in a cohort of patients who underwent preoperative diagnostic hysteroscopy followed by blind endometrial biopsy using the Novak curette with subsequent surgical definitive treatment at University of Pisa. Statistical analysis was based on frequency data and diagnostic agreement of the pathology results. Results A total of 129 patients were included in the final analysis. An agreement rate of 104/106 (98.1%) for endometrioid type and 15/23 (65.2%) for non-endometrioid type was obtained between preoperative hysteroscopic grasp endometrial biopsy specimens and the final pathology with a coefficient k for G1, G2 and G3 tumors of 0.928, 0.925 and 0.974, respectively. When compared to 121 patients undergoing preoperative blind Novak endometrial biopsy, the hysteroscopic grasp technique was superior in agreement rates for tumor histotype [diagnostic accuracy (0.922 vs 0.890); K value (0.705 vs 0.642)] and grade when in presence of endometrioid type EC (K Cohen 0.354 for G1, 0.263 for G2 and 0.488 for G3). Conclusions Preoperative hysteroscopic guided “grasp” endometrial biopsy provides a more accurate diagnosis of EC histology type and tumor grade when in presence of endometrioid type tumor compared to blind endometrial biopsy obtained using the Novak curette.

Endometriosis is a chronic disease characterized by the growth of endometrial-like glands and stroma outside the uterine cavity. Nowadays, the exact etiology of endometriosis is unclear and the interaction between a variety of environmental physical and chemical compounds may potentially promote the disease in women with an individual susceptibility. The first demonstration of a relation between an environmental factor and endometriosis was obtained with the chronic dietary exposure of a primate colony to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Besides the well-known dioxin's pathway of action, several papers are focusing on the role of epigenetic mechanisms, a way through which the genome responds to the environment and can lead to permanent changes in gene expression until affecting the phenotypes or cause disease. In this review, we focus on the possible role of dioxin epigenetics modification in endometriosis.

Objective. Cesarean scar pregnancy (CSP) is a rare condition that occurs when the pregnancy implants in a cesarean scar. An early diagnosis and a proper management are fundamental to prevent maternal complications. We review and discuss the different treatment employed in our unit to reduce morbidity, preserve fertility, and predict possible complications. Methods. The reported treatment has been expectant management, operative hysteroscopy approach, and intramuscular injection of 50 mg methotrexate (MTX), followed by cervical dilation and manual vacuum aspiration (D&S) with a Karman cannula under ultrasound guidance, uterine artery embolization (UAE), and manual vacuum aspiration under ultrasound guidance and uterine artery embolization before surgical laparotomic resection. Results. Complications were more frequent in women with a history of three or more cesarean section deliveries and with a myometrial thickness thinner than 2 mm. MTX and D&S treatment appear to be most effective and safe at the early age of pregnancy, while UAE and D&S are related to the highest risk of complication in any age of pregnancy. Conclusion. An appropriate preoperative diagnostic evaluation, the identification of cases at higher risk, and those eligible for a conservative treatment are fundamental to reduce complications.

Introduction To evaluate the feasibility and safety of robotic hysterectomy in the "transgender male/non-conforming" population and the short and long-term surgical outcomes of robotic surgery in these patients. Materials and methods A retrospective analysis was carried out from February 2016 to January 2018. Twenty female transgender patients with a previous psychiatric diagnosis of gender dysphoria who did not present genital pathologies were included in the study. The robotic hysterectomies were performed from June 2016 to March 2018 using a Da Vinci Xi Robot (Intuitive Surgical, Sunnyvale, CA, USA). Results No intraoperative or postoperative complications were recorded. The median duration of the intervention was of 90 minutes, including docking which lasted 16 minutes, while the median stay in the operating room was of 140 minutes. The median time of duration of intervention was of 90 minutes. The median blood loss was about 90 ml with a percentage decrease in hemoglobin between pre- and post-operative of about 8%. Postoperative pain was assessed using the VAS scale in the immediate postoperative period, on the first and second day, resulting of 3 and 2, respectively. The pathological examination of surgical specimens confirmed the absence of malignancy. Conclusions The robotic approach represents a feasible, safe, and effective surgical option for hysterectomy for "transgender male" affected by gender dysphoria.

BACKGROUND: Postpartum hemorrhage (PPH) is responsible for about 25% of maternal deaths worldwide. Antifibrinolytic agents, mainly tranexamic acid, have been demonstrated to reduce maternal blood loss and need for transfusion requirements at delivery in some settings. OBJECTIVE: The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of tranexamic acid for the prevention of PPH after vaginal delivery. DATA SOURCES: The search was conducted using electronic databases from the inception of each database through February 2018. Review of articles also included the abstracts of all references retrieved from the search. No restrictions for language or geographic location were applied. STUDY DESIGN: Selection criteria included RCTs comparing the prophylactic use of tranexamic acid after vaginal delivery with control (either placebo or no treatment). Trials in women undergoing cesarean delivery and trials in women with established PPH were excluded. The primary outcome was the incidence of primary PPH. The summary measures were reported as summary relative risk (RR) with 95% confidence interval (CI) using the random-effects model of DerSimonian and Laird. TABULATION, INTEGRATION, AND RESULTS: Four RCTs, including 4671 participants, evaluating tranexamic acid usually 1 g intravenous (IV) within 10 min after vaginal delivery in addition to oxytocin, cord traction, and uterine massage, at or near term for prevention of primary PPH, defined mostly as blood loss ≥500 mL in the first 24 h following delivery, were analyzed. Women who received prophylactic tranexamic acid after vaginal delivery had a significantly lower incidence of primary PPH (8.7 versus 11.4%; RR 0.61, 95% CI 0.41-0.91) and lower mean blood loss mean difference (MD) -84.74 mL, 95% CI -109.76 to -59.72). The risk of thrombotic events was not increased in the tranexamic acid group. CONCLUSIONS: Prophylactic tranexamic acid 1 g IV within 10 min after vaginal delivery reduces the risk of primary PPH.

Ovarian borderline tumors (OBT) are tumors with an intermediate grade of malignancy whose diagnosis is purely based on morphological criteria. They usually occur in young women (under 40 years) and are characterized by a cellular proliferation with slight nuclear atypia and lacking stromal invasion with a destructive pattern. Aim of this study was to explore the immunohistochemical expression of Ki67 proliferative index in OBT and to correlate it with known clinicopathologic prognostic factors in patients older than 40 years.Twenty cases of OBTdiagnosed in the period ranging from 2016 to 2018 were retrieved. Each specimen was taken from hysterectomy or adnexectomy surgery. Immunohistochemical studies were performed on the most representative sample of the tumor. Positive signal was nuclear and it was evaluated by three independent pathologists.Ki67 Labelling Index (L.I.) value ranged from 2% to 40%, with an average value of 14% and a median of 10%. Higher Ki67 L.I. was observed in patients older than 40 years (pvalue = 0.0194) and in those with tumors with a maximum diameter ≥ 10 cm (pvalue = 0.0547). Furthermore, a direct correlation was evident between tumor size value and Ki67 L.I. (p value0.0001, r = 0.7745). Hitherto no known prognostic factor correlated with high Ki67 L.I.Overall, OBT are tumors with greater risk of evolution at a more advanced age and when they are greater in size. The assessment of Ki67 could be a valid support in the diagnosis of a more aggressive tumor. Further studies are needed to assess possible correlation with data concerning recurrences rate, that in our cases were not available.

Introduction Prolonged length of labor is associated with increased maternal and neonatal complications. Therefore, great attention has been given to interventions aimed at reducing the length of labor. One such intervention is the peanut ball, a large elongated exercise ball placed between a woman’s legs during labor. Objective The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess the effect of the use of peanut ball in reducing length of labor. Study Design Data sources: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library were searched from inception until January 2019. Selection criteria: Selection criteria included RCTs of laboring women with singleton gestations in cephalic presentation at term (≥37weeks) who were randomized to either use of peanut ball or control group (no peanut ball). Data Collection and Analysis: Four trials with 648 nulliparous and multiparous women in spontaneous or induced labor were identified and included. 330 women were randomized to the intervention (peanut ball between the knees during labor) and 318 women to the control. Summary measures were reported as mean difference (MD) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird. The primary outcome was total length of labor. PROSPERO Registration Number: CRD42018082438 Results Total length of labor was 79 min shorter in the peanut ball group, but this was not significant (MD −79.1 min, 95% CI −204.9, 46.7). Peanut ball use showed trends toward higher incidence of spontaneous vaginal deliveries (RR 1.1, 95% CI 1.0, 1.2) and lower incidence of cesarean deliveries (RR 0.8, 95% CI 0.6, 1.0). Conclusions Peanut ball use was not associated with a significant decrease in total length of labor. Since there were trends toward reductions in length of labor, an increased incidence in spontaneous vaginal deliveries, and lower incidence of cesarean deliveries, more research is needed.

Epithelial ovarian cancer (EOC) is the predominant type of ovarian cancer (OC). The 5-year survival of patients has improved over the last three decades, although the overall cure rate of OC if about 30%. Despite high response rates after initial chemotherapy, most patients with advanced ovarian cancer ultimately develop the recurrent disease because of resistance to chemotherapy. A proper early diagnosis and treatment of patients with ovarian cancer are urgently needed. Nowadays the diagnosis is performed by means of clinical symptoms and signs, often indicators of a disease already at an advanced stage, tumor markers (CA125 and HE4), transvaginal ultrasonography and imaging, very useful in distinguishing adnexal masses. Understand the nature of an adnexal mass is the primary point to begin the diagnosis of OC. Validated different model to approach and characterize adnexal pathology preoperatively are described, such as the International Ovarian Tumor Analysis (IOTA) and the Assessment of Different NEoplasias in the AdneXa (ADNEX) model. New tumor markers, such as PRSS8, FOLR1, KLK6/7, GSTT1, and miRNAs, are getting ahead and are worth noting for early detection of ovarian cancer. Despite the development of numerous ultrasound models for the diagnosis of adnexal masses and the analysis of different tumor markers, the early diagnosis of ovarian cancer is still difficult to practice. Moreover, identifying genetic risk alleles, such as germline BRCA1 and BRCA2 mutations, for ovarian cancer has had a significant impact on disease prevention strategies.

Trabectedin is a marine-derivate antitumor drug with a relevant cytotoxic activity and good safety profile. It has been investigated for the treatment of solid diseases, including ovarian cancer (OC), breast cancer, and soft-tissue sarcoma. In 2009, results from the pivotal trial OVA-301 led the European Medicines Agency (EMA) to the approval of trabectedin in combination with PEGylated liposomal doxorubicin for the treatment of platinum-sensitive recurrent OC; further studies revealed an additional benefit also in the subgroup of patients with partially platinum-sensitive disease and in those with a BRCA-mutated status. Additionally, trabectedin demonstrated to prolong the time interval to the subsequent chemotherapy line. Recently, the improved understanding of the antitumor action exerted by trabectedin paved the way to new investigational trials exploring its combination with targeted therapies.

Ovarian cancer is considered the leading cause of death among gynecologic neoplasias. Breast metastases from primary ovarian cancer have been reported in only 0.03-0.6% of all breast cancers. A 38-year-old female, multipara, affected by advanced ovarian cancer and undergone a total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and pelvic peritonectomy two years earlier, was discovered to have a breast metastasis. She underwent a quadrantectomy (QSI) with an open biopsy of nodularity attached to the pectoral muscle fascia: on definitive histological characterization the breast lesions showed a high-grade invasive carcinoma, with papillary serum differentiation, and the immunohistochemistry study of breast lesion showed positivity for cytokeratin 7 and an extensive positivity for Wilm's tumor (WT)-1 and paired box 8 (PAX8). These aspects are indicative of mammary metastasis from carcinoma of ovarian origin. Despite their rarity, metastases to breast from ovarian cancer should be considered possible because their recognition and differentiation compared to primary tumors are crucial for prognosis. Future clinical studies on MOCB should be performed to discover new specific markers for a more accurate histopathological diagnosis and to establish the real need of surgical treatment.

Study Objectives To describe and demonstrate a technique for laparoscopic removal of a perforating intrauterine device (IUD) during pregnancy, and to provide tips to facilitate safe laparoscopic surgery during pregnancy. Design Video presentation of the technique for laparoscopic removal of a perforating IUD in a pregnant woman. Setting Department of Neuroscience, Reproductive Sciences, and Dentistry, University of Naples Federico II, Naples, Italy. Intervention A 30-year-old woman, gravida 3, para 2, with a copper T IUD (Nova T 380; Bayer, Leverkusen, Germany) perforating the left adnexa presented to the emergency room complaining of left lower quadrant pain. The patient had the IUD inserted by her gynecologist 3 months before the onset of the symptoms. Ultrasound revealed a 6-week intrauterine pregnancy with the presence of fetal cardiac activity along with the IUD perforating the left adnexa. The patient returned at 11 weeks of gestation complaining of worsening abdominal pain and excruciating left lower quadrant pain. She was scheduled for laparoscopic excision of the perforating IUD 1 , 2 , 3 . Considering her pregnancy, laparoscopy under regional anesthesia was performed in the minimal Trendelenburg position at 12 degrees, through open laparoscopic access [4] . Intra-abdominal pressure of 8 mmHg and ultrasound energy to cut and coagulate, avoiding monopolar/bipolar energy owing to the presence of a copper IUD, were used. The IUD and tube were extracted in an endobag through umbilical access, under a 5-mm, 0-degree telescope in left lateral access [5] . The procedure was carried out uneventfully, and the IUD was removed. Fetal viability was confirmed after the procedure. At the time of this report, the patient was in the 23rd week of gestation, and the pregnancy was progressing without any problems. Conclusion Laparoscopic removal of perforated IUD during pregnancy under regional anesthesia is a feasible and safe option that should be considered when needed.