It is time to implement molecular classification in endometrial cancer.

A huge effort has been done in redefining endometrial cancer (EC) risk classes in the last decade. However, known prognostic factors (FIGO staging and grading, biomolecular classification and ESMO-ESGO-ESTRO risk classes stratification) are not able to predict outcomes and especially recurrences. Biomolecular classification has helped in re-classifying patients for a more appropriate adjuvant treatment and clinical studies suggest that currently used molecular classification improves the risk assessment of women with EC, however, it does not clearly explain differences in recurrence profiles. Furthermore, a lack of evidence appears in EC guidelines. Here, we summarize the main concepts why molecular classification is not enough in the management of endometrial cancer, by highlighting some promising innovative examples in scientific literature studies with a clinical potential significant impact.

Urological Complications in Radical Surgery for Cervical Cancer: A Comparative Meta-Analysis before and after LACC Trial.

BACKGROUND: After the LACC trial publication in 2018, the minimally invasive approach (MIS) has severely decreased in favor of open surgery: MIS radical hysterectomy was associated with worse oncological outcomes than open surgery, but urological complications were never extensively explored in pre- versus post-LACC eras, even if they had a great impact on post-operative QoL. The purpose of this meta-analysis is to compare functional and organic urological complication rates before and after LACC trial. METHODS: An independent search of the literature was conducted 4 years before and after the LACC trial and 50 studies were included. RESULTS: The overall rate of urologic complications was higher in pre-LACC studies while no differences were found for organic urological complications. Conversely, the overall risk of dysfunctional urological complications showed a higher rate in the pre-LACC era. This is probably related to a sudden shift to open surgery, with potential lower thermal damage to the urinary tract autonomic nervous fibers. CONCLUSIONS: This meta-analysis showed that the incidence of urological complications in radical cervical cancer surgery was higher before the LACC trial, potentially due to the shift to open surgery. Nevertheless, further studies are needed to shed light on the connection between minimally invasive surgery and urological damage.

The added value of spinal cord lesions to disability accrual in multiple sclerosis.

Spinal cord MRI is not routinely performed for multiple sclerosis (MS) monitoring. Here, we explored whether spinal cord MRI activity offers any added value over brain MRI activity for clinical outcomes prediction in MS. This is a retrospective, monocentric study including 830 MS patients who underwent longitudinal brain and spinal cord MRI [median follow-up 7 years (range: < 1-26)]. According to the presence (or absence) of MRI activity defined as at least one new T2 lesion and/or gadolinium (Gd) enhancing lesion, each scan was classified as: (i) brain MRI negative/spinal cord MRI negative; (ii) brain MRI positive/spinal cord MRI negative; (iii) brain MRI negative/spinal cord MRI positive; (iv) brain MRI positive/spinal cord MRI positive. The relationship between such patterns and clinical outcomes was explored by multivariable regression models. When compared with the presence of brain MRI activity alone: (i) Gd + lesions in the spine alone and both in the brain and in the spinal cord were associated with an increased risk of concomitant relapses (OR = 4.1, 95% CI 2.4-7.1, p < 0.001 and OR = 4.9, 95% CI 4.6-9.1, p < 0.001, respectively); (ii) new T2 lesions at both locations were associated with an increased risk of disability worsening (HR = 1.4, 95% CI = 1.0-2.1, p = 0.05). Beyond the presence of brain MRI activity, new spinal cord lesions are associated with increased risk of both relapses and disability worsening. In addition, 16.1% of patients presented asymptomatic, isolated spinal cord activity (Gd + lesions). Monitoring MS with spinal cord MRI may allow a more accurate risk stratification and treatment optimization.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

Chemo-surgical approach in vulvar leiomyosarcoma: A case report.

INTRODUCTION: Primary sarcoma of the vulva is an extremely rare entity, representing only 1%-3% of all vulvar malignant neoplasms. Among sarcomas, leiomyosarcoma (LMS) is the most prevalent histologic variant. Due to the rarity of LMS, guidelines are lacking and phase III trials have not been carried out, so clinical management is based on local clinical practice and physician experience. CASE PRESENTATION: Here, we described a case of primary LMS of the vulva and its successful management, with the adoption of neoadjuvant chemotherapy and surgery. We report a case of a 74-year-old woman with 12.5 cm vulvar LMS. The patient received three cycles of neoadjuvant chemotherapy with a partial response. Radical vulvectomy with vulvar reconstruction with V-F flap was carried out. Surgical margins were negative. Three additional cycles of adjuvant chemotherapy were delivered. RESULTS: One year after treatment, the patient was disease-free. CONCLUSION: There are no approved therapeutic protocols for this rare neoplasia. Surgery is the mainstay of treatment. However, it is not always feasible, so neoadjuvant chemotherapy was delivered for downstaging the vulvar lesion. We suppose that neoadjuvant chemotherapy has optimized the possibilities of radical surgery. Despite the anectodical nature of this case presentation, neoadjuvant chemotherapy seems a valid therapeutic option for managing patients with bulky vulvar sarcoma. Further large collaborative studies are warranted to identify the best therapeutic option for these patients.

Clinical management of hypertensive disorders in postpartum women.

Hypertensive disorders of pregnancy (HDP) could persist post-partum, or appear for the first time after delivery and could require a pharmacological treatment. It was found no evidence in literature about which therapy should be used in puerperal hypertension. The aim of this review is to determine the most effective therapy and best in terms of risk-benefit ratio for the treatment of high postpartum systemic arterial blood pressure in women with pregnancy-induced hypertension (PIH) or in those with de-novo diagnosis of hypertension in the puerperium. Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CCRCT), Embase, Medline, and PubMed were searched. The main inclusion criterion was articles regarding postnatal women with hypertension, therapeutic treatment for the management of hypertension compared with placebo or no therapy, with the exclusion of preeclampsia/eclampsia. Twenty-three studies were included. This review highlights significant evidence gaps, demonstrating that further comparative research is required, particularly to clarify postpartum antihypertensive selection. In conclusion, there is insufficient evidence to recommend a particular therapy or model of care, but calcium channel blockers, beta-blockers, alpha-blockers and angiotensin-converting enzyme inhibitors (ACEIs) appeared variably effective.

Non-invasive treatment of vulvovaginal atrophy in menopause with CO2 laser.

Genitourinary syndrome of menopause (GSM) may affect up to 90% of menopausal women, including vulvovaginal atrophy (VVA), burning, pain, bleeding, irritation, dyspareunia, anorgasmia, and urinary symptoms. Vaginal symptoms from lack of estrogens can have a significant impact on the sexual health and quality of life (QoL) in as many as 50% of postmenopausal women. Several therapeutic alternatives, both hormonal and non- hormonal, have been proposed. Microablative CO2 laser is one of the three non-surgical energy-based therapies, with Erbium:YAG laser and temperature-controlled radiofrequency (RF). Microablative CO2 laser induces morphological changes in vaginal tissues and results of several clinical trials suggest that this type of laser improves symptoms of GSM. Moreover, this treatment seems to be safe. Given the increasingly widespread use of laser CO2 as a non-hormonal alternative treatment for GSM, the authors reviewed the current published literature evaluating this therapy, to compare efficacy and safety of different protocols.

Myasthaenia gravis in pregnancy, delivery and newborn.

INTRODUCTION: Myasthaenia gravis (MG) is the most common disease of the neuromuscular junction; clinical presentation of the disease includes a variety of symptoms, the most frequent beign the only ocular muscles involvement, to the generalized myasthenic crisis with diaphragmatic impairment and respiratory insufficiency. It is most common in women between 20 ad 40 years. EVIDENCE ACQUISITION: We performed a comprehensive search of relevant studies from January1990 to Dicember 2019 to ensure all possible studies were captured. A systematic search of Pubmed databases was conducted. EVIDENCE SYNTHESIS: Pregnancy has an unpredictable and variable effect on the clinical course of MG; however, a stable disease before is likely not to relapse during pregnancy. exacerbations can still occur more often during the first trimester and the post partum period. The transplacental passage of antibodies results in a neonatal transient disease, whereas the major concern is related to foetal malformations such as fetal arthrogryposis and polyhydramnios. The overall neonatal outcome described in literature is variable, perinatal mortality in women with MG is generally the same as non affected patients, although in one study the risk of premature rupture of the membranes was higher. Treatment of MG in pregnangncy includes pyridostigmine and corticosteroids, although the latter have been associated with higher risk of cleft palate, premature rupture of the membranes and preterm delivery. These drugs appear also to be safe in breastfeeding. In MG patients spontaneous vaginal delivery should be encouraged, for surgery could cause acute worsening of myasthenic symptoms; also an accurate anesthesiological evaluation must be performed prior to both general and local anesthesia due to increased risk of complications. CONCLUSIONS: Most of the myasthenic women could have uneventful pregnancy with good obstetrical outcomes, both for mother and neonate. However, a careful planning of pregnancy and multidisciplinary team approach, composed by neurologists, obstetricians, neonatologists and anesthesiologists, is required to manage these pregnancies.

Does hysterosalpingo-foam sonography have any therapeutic effect? A systematic review.

INTRODUCTION: Tubal patency is one of the mandatory and necessary conditions to be granted in order to guarantee a good pregnancy rate. Numerous studies have been conducted to compare the various testing techniques for tubal evaluation in order to optimize the diagnostic-therapeutic process. Aim of this review is to clarify if hysterosalpingo-foam sonography could be considered as a useful tool not only in the diagnostic procedure, but also in treatment of infertility. EVIDENCE ACQUISITION: We performed a comprehensive search of relevant studies from January 2010 to December 2019 to ensure all possible studies were captured. A systematic search of PubMed databases was conducted. EVIDENCE SYNTHESIS: Over the years, increasingly less invasive approaches have been used to test tubal patency. For many years Laparoscopic with chromopertubation (DLS) has been considered the reference standard, then less invasive procedures have been introduced, such as hysterosalpingography (HSG). Sonohysterosalpingography (HyCoSy) represents a non-invasive procedure with accuracy comparable to HSG. Several studies have been made on different contrast agents that could be used on this procedure and recent studies considered hysterosalpingo-foam sonography (HyFoSy) procedure as a new technique used for the study of tubal function performed on unfertile women. Nowadays, HyFoSy is largely used in the study of tubal patency, but it is not completely clear the role of this technique as treatment of imperviousness of Fallopian tubes, leading to an increase in pregnancy rate after its use. CONCLUSIONS: As described in the literature for other procedures, similarly with HyFoSy, the tubal flushing improves the chance of an embryo implanting and establishing a spontaneous pregnancy. More prospective studies should be taken to better analyze the singular maternal risk fators, hoping to offer more complete indications to recommend HyFoSy.

Impact of early diagnosis on clinical characteristics of an Italian sample of people with multiple sclerosis recruited online.

BACKGROUND: In order to anticipate the diagnosis of Multiple Sclerosis (MS), the diagnostic criteria had been reviewed several times in the last years. OBJECTIVE: We wanted to understand whether earlier diagnoses of MS have impacted on therapeutic management of the disease. METHODS: We designed a 22-item survey posted on SMsocialnetwork, a webplatform with a medical supervision, dedicated to Italian MS patients. We collected socio-demographic data, disease and treatment-related information of 1000 patients. RESULTS: The median age at diagnosis significantly decreased over years. In the last decades the time delay between disease onset and diagnosis reduced, the disease phenotypes at diagnosis shifted from progressive form to relapsing ones and clinically isolated syndrome, the number of early treated patients increased over time. CONCLUSION: We showed, verifying a large sample of patients in a reallife setting, that the improvement of the diagnostic process allowed the anticipation of MS diagnosis over years and had a huge impact in terms of treatment approach.

A lesion topography-based approach to predict the outcomes of patients with multiple sclerosis treated with Interferon Beta.

BACKGROUND: With increasing availability of effective disease-modifying treatments for multiple sclerosis (MS), an early identification of patients who do not adequately respond to Interferon Beta (IFNB) is relevant to decide the future strategy. OBJECTIVE: To investigate the predictive role of new lesion location on the risk of breakthrough disease in IFNB-treated patients with MS. METHODS: We analysed data from 392 patients starting IFNB and regularly followed up to 5 years. Before and after one year of IFNB treatment, all patients underwent a conventional brain and spinal cord magnetic resonancer imaging (MRI) scan with the same 1.5T magnet to obtain the count and location of new MRI lesions. Relapses and MRI activity occurred in the first year of IFNB treatment (year 0-1) were included in the set of potential predictors for relapses and disability worsening in the subsequent four years (year 2-5). RESULTS: We found that 96 (24.5%) patients had relapses and/or MRI activity in the first year of IFNB treatment, while 41.6% of the patients experienced relapses and 17.8% experienced disability worsening. from year 2 to 5. The risk of relapses (year 2-5) was associated with ≥2 relapses (HR=5.65, p<0.001) and new T2-hyperintense lesions (for 2 new lesions: HR=1.96, p=0.011; for ≥3 new lesions: HR=3.55, p<0.001) in the first year of treatment. Other than male sex (HR=2.01, p=0.01) and higher EDSS score (HR=2.17, p<0.001), the risk of disability worsening (year 2-5) was associated with ≥2 relapses (HR=4.33, p<0.001) and new spinal cord or infratentorial lesions (HR=4.45,p<0.001) in the first year of treatment. CONCLUSIONS: Our findings suggest a dose-effect relationship between the lesion count and the risk of future relapses, while the occurrence of new MRI lesions in sites representing anatomical bottle-necks was better than lesion count at predicting the future risk of disability worsening despite IFNB treatment.