Raf kinase inhibitor protein expression in smooth muscle tumours of the uterus: a diagnostic marker for leiomyosarcoma?

RESEARCH QUESTION: What is the expression pattern of Raf kinase inhibitory protein (RKIP) in different subtypes of leiomyoma (usual type, cellular, apoplectic or haemorrhagic leiomyoma, leiomyoma with bizarre nuclei and lipoleiomyoma) and leiomyosarcoma specimens, and what is its biological role in leiomyosarcoma cells? DESIGN: Leiomyoma and leiomyosarcoma specimens underwent immunohistochemistry staining. Leiomyosarcoma SK-LMS-1 cell line was RKIP knocked down and RKIP overexpressed, and cell viability, wound healing migration and clonogenicity assays were carried out. RESULTS: A higher immunohistochemical expression of RKIP was observed in bizarre leiomyomas, than in usual-type leiomyomas. Decreased expression was also found in cellular leiomyoma, with generally absent staining in leiomyosarcomas. Upon RKIP expression manipulation in SK-LMS-1 cell line, no major differences were observed in cell viability and migration capacity over time. RKIP knockout, however, resulted in a significant increase in the cell's ability to form colonies (P = 0.011). CONCLUSION: RKIP distinct expression pattern among leiomyoma histotype and leiomyosarcoma, and its effect on leiomyosarcoma cells on colony formation, encourages further studies of RKIP in uterine smooth muscle disorders.

Copy number variations in endometrial cancer: from biological significance to clinical utility.

The molecular basis of endometrial cancer, which is the most common malignancy of the female reproductive organs, relies not only on onset of mutations but also on copy number variations, the latter consisting of gene gains or losses. In this review, we introduce copy number variations and discuss their involvement in endometrial cancer to determine the perspectives of clinical applicability. We performed a literature analysis on PubMed of publications over the past 30 years and annotated clinical information, including histological and molecular subtypes, adopted molecular techniques for identification of copy number variations, their locations, and the genes involved. We highlight correlations between the presence of some specific copy number variations and myometrial invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, high grade, drug response, and cancer progression. In particular, type I endometrial cancer cells have few copy number variations and are mainly located in 8q and 1q, while type II, high grade, and advanced FIGO stage endometrial cancer cells are aneuploid and have a greater number of copy number variations. As expected, the higher the number of copy number variations the worse the prognosis, especially if they amplify CCNE1, ERBB2, KRAS, MYC, and PIK3CA oncogenes. Great variability in copy number and location among patients with the same endometrial cancer histological or molecular subtype emerged, making them interesting candidates to be explored for the improvement of patient stratification. Copy number variations have a role in endometrial cancer progression, and therefore their detection may be useful for more accurate prediction of prognosis. Unfortunately, only a few studies have been carried out on the role of copy number variations according to the molecular classification of endometrial cancer, and even fewer have explored the correlation with drugs. For these reasons, further studies, also using single cell RNA sequencing, are needed before reaching a clinical application.

Reproducibility of colposcopy quality indicators-A survey among members of the European Federation for Colposcopy.

INTRODUCTION: Colposcopy is an important part of the diagnostic work-up of women with an abnormal cervical screening test as it is used to guide the collection of biopsies. Although quality assurance has been used in the evaluation of screening programs, not much is known about quality indicators for the diagnostics and treatment of screen-positive women. Therefore, the European Federation for Colposcopy developed quality indicators aiming to support colposcopy practice across Europe. We performed a survey of colposcopy cases to determine if the quality indicators are understandable, relevant, and reproducible. MATERIAL AND METHODS: We conducted a survey among all members of the European Federation for Colposcopy Quality and Standards Group from November 2022 to March 2023. Members were asked to collect information on a total of 17 quality indicators for 50 women who had been newly referred for colposcopy due to an abnormal screening test between January 1, 2020 to December 31, 2021. Results were reported descriptively. RESULTS: We included data on 609 cases from 12 members across Europe. The majority of the quality indicators were either achieved or within reach of the agreed standard, often due to few countries with outlying data. One quality indicator had very low performance, although stratified results indicated that two countries had different clinical management of the patient type thereby skewing the results. In addition, discrepancies between the number of cases included in each quality indicator raised concerns regarding potential misunderstanding of the quality indicator and its objective. CONCLUSIONS: Quality indicators on colposcopy must be understandable to those collecting data, highlighting the importance of validating quality indicators before data collection.

A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding ( p < .005), easy bruising ( p = .028), fissures ( p = .008), petechiae/splinter hemorrhages ( p < .001), and bleeding/blistering or open sores ( p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum ( p = .013) and the perianal region ( p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population ( p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population ( p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Circulating miRNAs and Preeclampsia: From Implantation to Epigenetics.

In this review, we comprehensively present the literature on circulating microRNAs (miRNAs) associated with preeclampsia, a pregnancy-specific disease considered the primary reason for maternal and fetal mortality and morbidity. miRNAs are single-stranded non-coding RNAs, 20-24 nt long, which control mRNA expression. Changes in miRNA expression can induce a variation in the relative mRNA level and influence cellular homeostasis, and the strong presence of miRNAs in all body fluids has made them useful biomarkers of several diseases. Preeclampsia is a multifactorial disease, but the etiopathogenesis remains unclear. The functions of trophoblasts, including differentiation, proliferation, migration, invasion and apoptosis, are essential for a successful pregnancy. During the early stages of placental development, trophoblasts are strictly regulated by several molecular pathways; however, an imbalance in these molecular pathways can lead to severe placental lesions and pregnancy complications. We then discuss the role of miRNAs in trophoblast invasion and in the pathogenesis, diagnosis and prediction of preeclampsia. We also discuss the potential role of miRNAs from an epigenetic perspective with possible future therapeutic implications.

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia.

The HtrA serine peptidase 1 (HTRA1) is a multidomain secretory protein with serine-protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HTRA1 is normally expressed in the human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in the early phases of human placenta development. The aim of this study was to evaluate the functional role of HTRA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE). BeWo and HTR8/SVneo cells expressing HTRA1 were used as syncytiotrophoblast and cytotrophoblast models, respectively. Oxidative stress was induced by treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HTRA1 expression. In addition, HTRA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility, and invasion processes. Our main data showed that oxidative stress significantly increased HTRA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HTRA1 has a pivotal role in cell motility and invasion processes. In particular, HTRA1 overexpression increased while HTRA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. In conclusion, our results suggest an important role of HTRA1 in regulating extravillous cytotrophoblast invasion and motility during the early stage of placentation in the first trimester of gestation, suggesting a key role of this serine protease in PE onset.

High levels of hypusinated eIF5A in leiomyoma and leiomyosarcoma pathologies: a possible novel therapeutic target.

RESEARCH QUESTION: Is the hypusinated form of the eukaryotic translation initiation factor 5A (EIF5A) present in human myometrium, leiomyoma and leiomyosarcoma, and does it regulate cell proliferation and fibrosis? DESIGN: The hypusination status of eIF5A in myometrial and leiomyoma patient-matched tissues was evaluated by immunohistochemistry and Western blotting as well as in leiomyosarcoma tissues by immunohistochemistry. Myometrial, leiomyoma and leiomyosarcoma cell lines were treated with N1-guanyl-1,7-diaminoheptane (GC-7), responsible for the inhibition of the first step of eIF5A hypunization, and the proliferation rate was determined by MTT assay; fibronectin expression was analysed by Western blotting. Finally, expression of fibronectin in leiomyosarcoma tissues was detected by immunohistochemistry. RESULTS: The hypusinated form of eIF5A was present in all tissues examined, with an increasing trend of hypusinated eIF5A levels from normal myometrium to neoplastic benign leiomyoma up to neoplastic malignant leiomyosarcoma. The higher levels in leiomyoma compared with myometrium were confirmed by Western blotting (P = 0.0046). The inhibition of eIF5A hypusination, with GC-7 treatment at 100 nM, reduced the cell proliferation in myometrium (P = 0.0429), leiomyoma (P = 0.0030) and leiomyosarcoma (P = 0.0044) cell lines and reduced the expression of fibronectin in leiomyoma (P = 0.0077) and leiomyosarcoma (P = 0.0280) cells. The immunohistochemical staining of leiomyosarcoma tissue revealed that fibronectin was highly expressed in the malignant aggressive (central) part of the leiomyosarcoma lesion, where hypusinated eIF5A was also highly represented. CONCLUSIONS: These data support the hypothesis that eIF5A may be involved in the pathogenesis of myometrial benign and malignant pathologies.

Human papillomavirus (HPV) vaccination: a call for action in Italy.

Human papillomavirus (HPV) is the most common sexually transmitted infection. The implementation of primary prevention aims to reduce the burden of HPV infection and HPV-related disease. However, HPV-related diseases are still a concern, even in high-income countries. Approximately 570 000 new cervical cancer cases are diagnosed in Italy every year. Prophylactic HPV vaccines have been developed to minimize the spread of HPV. Growing evidence supports the administration of HPV vaccines (even just one dose) in reducing the prevalence of HPV infection and HPV-related disease including cancers. HPV vaccines are characterized by a high level of efficacy (>95%) in women who are naïve to HPV; however, they do not increase clearance in patients with ongoing HPV infection. With more than 200 million doses administered to date, HPV vaccines are considered to be safe and effective at preventing HPV-related infections and cancers. In this review we aim to review the current evidence regarding HPV vaccination and to describe trends in HPV vaccination coverage in Italy. In Italy, vaccination against HPV has been included in the National Immunization Plan (NIP) since 2007-2008. Using data abstracted from the Italian Ministry of Health, we analyzed changes in HPV vaccination coverage. We observed that HPV vaccines are underutilized and coverage rates are decreasing. Looking at the target population (females and males aged 11-12 years) in Italy, a decrease in coverage rates was observed. A call for action, improved HPV awareness, and education are the key elements to enhance the widespread adoption of HPV vaccination.

Maternal hemodynamics and computerized cardiotocography during labor with epidural analgesia.

PURPOSE: To analyze the mechanisms involved in the fetal heart rate (FHR) abnormalities after the epidural analgesia in labor. METHODS: A prospective unblinded single-center observational study on 55 term singleton pregnant women with spontaneous labor. All women recruited underwent serial bedside measurements of the main hemodynamic parameters using a non-invasive ultrasound system (USCOM-1A). Total vascular resistances (TVR), heart rate (HR), stroke volume (SV), cardiac output (CO) and arterial blood pressure were measured before epidural administration (T0), after 5 min 5 (T1) from epidural bolus and at the end of the first stage of labor (T2). FHR was continuously recorded through computerized cardiotocography before and after the procedure. RESULTS: The starting CO was significantly higher in a subgroup of women with low TVR than in women with high-TVR group. After the bolus of epidural analgesia in the low-TVR group there was a significant reduction in CO and then increased again at the end of the first stage, in the high-TVR group the CO increased insignificantly after the anesthesia bolus, while it increased significantly in the remaining part of the first stage of labor. On the other hand, CO was inversely correlated with the number of decelerations detected on cCTG in the 1 hour after the epidural bolus while the short-term variation was significantly lower in the group with high-TVR. CONCLUSION: Maternal hemodynamic status at the onset of labor can make a difference in fetal response to the administration of epidural analgesia.

The Role of NQO1 in Ovarian Cancer.

Ovarian cancer is one of the most dangerous gynecologic malignancies showing a high fatality rate because of late diagnosis and relapse occurrence due to chemoresistance onset. Several researchers reported that oxidative stress plays a key role in ovarian cancer occurrence, growth and development. The NAD(P)H:quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that, using NADH or NADPH as substrates to reduce quinones to hydroquinones, avoids the formation of the highly reactive semiquinones, then protecting cells against oxidative stress. In this review, we report evidence from the literature describing the effect of NQO1 on ovarian cancer onset and progression.

Gestational Diabetes Mellitus and Small-for-Gestational-Age: An Insight into the Placental Molecular Biomarkers.

Gestational diabetes mellitus (GDM) and small-for-gestational-age (SGA) are two metabolic-related diseases that could affect women during pregnancy. Considering that the chorionic villi (CVs) are crucial structures for the feto-maternal exchange, the alterations in their conformation have been linked to an imbalanced metabolic environment of placenta. In this study, a multidisciplinary approach has been carried out to describe the changes occurring in the placental CVs of GDM and SGA patients. The results revealed higher levels of superoxide dismutase 1 (SOD-1) and catalase (CAT), especially in the GDM placentae, which could be correlated with the hyperglycemic environment characteristic of this pathology. Furthermore, spectroscopy and histologic analyses revealed that both pathologies modify the placental lipid composition altering its structure. However, SGA induces lipid peroxidation and reduces collagen deposition within the CVs. Since the endocannabinoid system (ECS) is involved in placentation and different metabolic activities, the cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV-1) were analyzed. No changes have been observed either at general or specific levels in the CVs comparing control and pathological samples, suggesting the non-involvement of the cannabinoid system in these two pathologies.

Homozygous C677T Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism as a Risk Factor for Endometriosis: A Retrospective Case-Control Study.

This study was conducted to evaluate the role of methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism as a risk factor for endometriosis. A retrospective case-control study was conducted from January 2020 to December 2022 on all patients attending the gynecological outpatient clinic of our institution who had performed an MTHFR polymorphisms test. Patients with endometriosis were considered cases, while those without endometriosis were considered controls. The presence of an MTHFR C677T homozygous polymorphism was defined as exposure. Risk factors for endometriosis were considered confounders in a binomial logistic regression, with endometriosis diagnosis as the dependent variable. Among the 409 included patients, 106 (25.9%) cases and 303 (74.1%) controls were identified. A higher rate of MTHFR C677T homozygous polymorphism was found in patients with endometriosis (24.5% vs. 15.8%, p = 0.0453), with an adOR of 1.889 (95% CI 1.076-3.318, p = 0.0269) at the binomial logistic regression. A history of no previous pregnancy was associated with an endometriosis diagnosis (adOR 2.191, 95% CI 1.295-3.708, p = 0.0035). An MTHFR C677T homozygous polymorphism could be considered a risk factor for endometriosis. Epigenetic modifications may be the most important mechanism explaining the observed association through the processes of altered DNA methylation and reduced activity of antioxidant systems.

Uterine fibroid vascularization: from morphological evidence to clinical implications.

Uterine fibroids are the most common cause of solid pelvic tumours, occurring in 20-30% of fertile women and presenting clinical complications that seriously affect women's health. They commonly cause severe symptoms, such as heavy, prolonged menstrual bleeding and anaemia. The study of microscopic and macroscopic vascular aspects of uterine fibroids is important for understanding the clinical manifestations of uterine fibroids, for predicting the effectiveness of alternative treatments to surgery, i.e. uterine artery embolization, for improving surgery outcomes and for carrying out a differential diagnosis with other benign conditions, e.g. adenomyosis, or malignancy, e.g. leiomyosarcoma, and to develop new therapeutic approaches. In this review, current knowledge of how the vascular network and angiogenesis are implied in the formation of uterine fibroids and in the pathogenesis of related symptoms is explored, and evidence on the role of ultrasound in evaluating fibroid vascularization is summarized. This review combines anatomical, morphological and biomolecular information related to angiogenic mechanisms with diagnostic and clinical information, highlighting the various interconnections. Uterine and fibroid vascularization need further investigation to gain a deeper understanding of the pathogenetic elements that lead to the formation of uterine fibroids and their clinical manifestations.

A clinician's dilemma: what should be communicated to women with oncogenic genital HPV and their partners regarding the risk of oral viral transmission?

Head and neck cancer, the sixth most common cancer worldwide, account for about 1 out of 20 malignant tumors. In recent years a reduction in the incidence of cervical cancer, but a concomitant major increase in the incidence of HPV-mediated oropharyngeal cancer caused by orogenital HPV transmission has been observed. Consequently, in wealthy countries oropharyngeal squamous-cell carcinomas (OPSCC) is now the most frequent HPV-related cancer, having overtaken cervical cancer. Without effective medical interventions, this incidence trend could continue for decades. As no specific precursor lesion has been consistently identified in the oral cavity and oropharynx, HPV vaccination is the logical intervention to successfully counteract also the rising incidence of OPSCCs. However, HPV vaccine uptake remains suboptimal, particularly in males, the population at higher risk of OPSCC. Alternative primary prevention measures, such as modifications in sexual behaviors, could be implemented based on knowledge of individual genital HPV status. Until recently, this information was not available at a population level, but the current gradual shift from cytology (Pap test) to primary HPV testing for cervical cancer screening is revealing the presence of oncogenic viral genotypes in millions of women. In the past, health authorities and professional organizations have not consistently recommended modifications in sexual behaviors to be adopted when a persistent high-risk HPV cervicovaginal infection was identified. However, given the above changing epidemiologic scenario and the recent availability of an immense amount of novel information on genital HPV infection, it is unclear whether patient counseling should change. The right of future partners to be informed of the risk could also be considered. However, any modification of the provided counseling should be based also on the actual likelihood of a beneficial effect on the incidence of HPV-associated oropharyngeal cancers. The risk is on one side to induce unjustified anxiety and provide ineffective instructions, on the other side to miss the opportunity to limit the spread of oral HPV infections. Thus, major health authorities and international gynecologic scientific societies should issue or update specific recommendations, also with the aim of preventing inconsistent health care professionals' behaviors.

Pathogenic Role of the Sphingosine 1-Phosphate (S1P) Pathway in Common Gynecologic Disorders (GDs): A Possible Novel Therapeutic Target.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid, noteworthy for its involvement both in the modulation of various biological processes and in the development of many diseases. S1P signaling can be either pro or anti-inflammatory, and the sphingosine kinase (SphK)-S1P-S1P receptor (S1PR) axis is a factor in accelerating the growth of several cells, including endometriotic cells and fibrosis. Gynecologic disorders, including endometriosis, adenomyosis, and uterine fibroids are characterized by inflammation and fibrosis. S1P signaling and metabolism have been shown to be dysregulated in those disorders and they are likely implicated in their pathogenesis and pathophysiology. Enzymes responsible for inactivating S1P are the most affected by the dysregulation of S1P balanced levels, thus causing accumulation of sphingolipids within these cells and tissues. The present review highlights the past and latest evidence on the role played by the S1P pathways in common gynecologic disorders (GDs). Furthermore, it discusses potential future approaches in the regulation of this signaling pathway that could represent an innovative and promising therapeutical target, also for ovarian cancer treatment.

Evaluation of Controlled Ovarian Stimulation Protocols in Patients with Normal and Low Ovarian Reserve: Analyses of miRNAs and Selected Target Genes Involved in the Proliferation of Human Cumulus Cells and Oocyte Quality.

The oocyte and the surrounding cumulus cells (CCs) are deeply linked by a complex bidirectional cross-talk. In this light, the molecular analysis of the CCs is nowadays considered to be precious in providing information on oocyte quality. It is now clear that miRNAs play a key role in several ovarian functions, such as folliculogenesis, steroidogenesis, and ovulation. Thus, in this study, specific miRNAs, together with their target genes, were selected and investigated in CCs to assess the response of patients with normal (NR) and low (LR) ovarian reserve to two different controlled ovarian stimulation (COS) protocols, based on rFSH and hMG. Moreover, a Fourier transform infrared microspectroscopy (FTIRM) analysis was performed to evaluate DNA conformational changes in CCs and to relate them with the two COS protocols. The results evidenced a modulation of the expression of miRNAs and related target genes involved in CCs' proliferation, in vasculogenesis, angiogenesis, genomic integrity, and oocyte quality, with different effects according to the ovarian reserve of patients. Moreover, the COS protocols determined differences in DNA conformation and the methylation state. In particular, the results clearly showed that treatment with rFSH is the most appropriate in NR patients with normal ovarian reserve, while treatment with hMG appears to be the most suitable in LR patients with low ovarian reserve.

HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications.

Cervical cancer is the fourth most common cancer in women. It is the leading cause of female deaths in developing countries. Most of these cervical neoplasms are represented by squamous lesions. Cervical adenocarcinoma causes about a quarter of cervical cancers. In contrast to squamous lesions, cervical glandular disease is HPV-negative in about 15-20% of cases. HPV-negative cervical adenocarcinomas typically present in advanced stages at clinical evaluation, resulting in a poorer prognosis. The overall and disease-free survival of glandular lesions is lower than that of squamous lesions. Treatment options require definitive treatments, as fertility-sparing is not recommended. Moreover, the impact of HPV vaccination and primary HPV screening is likely to affect these lesions less; hence, the interest in this challenging topic for clinical practice. An updated review focusing on clinical and molecular characterization, prognostic factors, and therapeutic options may be helpful for properly managing such cervical lesions.

Preeclampsia Correlates with an Increase in Cannabinoid Receptor 1 Levels Leading to Macromolecular Alterations in Chorionic Villi of Term Placenta.

Preeclampsia is a human pregnancy-specific disease characterized by abnormal placentation that usually presents with maternal hypertension and proteinuria. The main hallmark of preeclampsia, impaired trophoblast migration, and the subsequent disruption of uterine arteries remodeling lead to several molecular alterations in the placental compartments with those occurring in the chorionic villi being of the utmost importance. Given the essential role of the endocannabinoid system during preimplantation and trophoblast migration, we have combined the histological and hyperspectral imaging analyses to shed light on the involvement of two cannabinoid receptors in the macromolecular alterations related to preeclampsia. The results obtained by immunohistochemistry showed a significant increase in the protein levels of cannabinoid receptor 1 (CB1) in the preeclamptic chorionic villi. However, no changes were reported regarding transient receptor potential vanilloid 1 (TRPV-1) levels either in the bulk placental samples or chorionic villi when comparing control and preeclamptic patients. Histological analysis and Fourier-transform infrared spectroscopy (FTIRI) showed an increase in collagen deposition together with higher levels of lipid peroxidation and phosphorylated compounds in the pathological villi. Since CB1 enhancement has been described as promoting fibrosis and oxidative stress in several tissues, we proposed that the higher receptor abundance in preeclampsia could be triggering similar molecular effects in preeclamptic term placentas.

Factors influencing intraoperative blood loss and hemoglobin drop during laparoscopic myomectomy: a tailored approach is possible?

A retrospective study was conducted on patients subjected to laparoscopic myomectomy at our institution from January 2017 to December 2018 to identify predictive factors of blood loss. Two multiple regression models were run to predict intraoperative blood loss and haemoglobin drop. Predictors of an increased intraoperative blood loss and haemoglobin drop were the presence of three-four fibroids at ultrasound (+47 ml, p = .01; +0.58 g/dl, p = .05) and increased operative time (r = 0.57, p = .01; r = 0.01, p < .01), while predictors of a reduced intraoperative blood loss and haemoglobin drop were epinephrine injection (-50 ml, p < .01; -0.42 g/dl, p < .01), FIGO7 (-87 ml, p < .01; -0.85, p = .01), and FIGO6 (-35 ml, p < .01; -0.44, p = .02) fibroids at the ultrasound. Preoperative ultrasound evaluation is crucial in identifying patients at higher risk for blood loss, which could benefit from optimising haemoglobin values. The injection of diluted epinephrine could be proposed in selected high-risk patients. In the clinical practice, a tailored approach based on fibroids' ultrasonographic characteristics should be implemented to optimise preoperative Hb values and evaluate the use of diluted epinephrine in selected cases, reducing blood loss and the potential related complications.Impact statementWhat is already known on this subject? Laparoscopic myomectomy is the conservative surgical treatment of choice for symptomatic uterine fibroids. Still, it could represent a challenging procedure even for an experienced surgeon, with the risk of excessive blood loss, need of transfusions, prolonged operative time, and prolonged hospital stay. The knowledge of the predictive factors of blood loss is essential for patient preparation and surgical planning to reduce intraoperative and postoperative complications.What do the results of this study add? The results of the present study focus on the importance of presurgical evaluation to identify predictive factors of intraoperative blood loss and Hb drop such as the number of fibroids and the FIGO classification (at preoperative ultrasound), as well as intraoperative factors like operative time and the intramyometrial injection of diluted epinephrine.What are the implications of these findings for clinical practice and/or further research? A tailored approach based on the ultrasonographic characteristics of fibroids should be implemented to optimise preoperative haemoblobin levels.

Spotlight on the role of human papillomavirus vaccines.

In high income setting, the massive implementation of screening programs has reduced the incidence of cervical cancer, dramatically. However, cervical cancer still remains a major health concern, being one of the most common cause of death for cancer among women. The adoption of primary prevention through vaccination against HPV aims to reduce the prevalence of HPV-related lesions and cervical cancer. Accumulating data highlighted the cost-effectiveness of introducing HPV vaccination for adolescent and young adults. In the present review, we critically evaluated the role of vaccination against HPV, focusing much more on the role of vaccination in specific cluster of subjects (eg, post-treatment and older adults). Additionally, we evaluated the available evidence on the role of vaccination in HIV-positive subjects and in women receiving solid organs transplantation. We observed that although vaccination might be considered effective in those cluster of subjects; further evidence is needed to assess the cost-effectiveness of vaccination in these settings.