Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update

The integrity of bone tissue and its remodeling that occurs throughout life requires a coordinated activity of osteoblasts and osteoclasts. The decreased estrogen circulating level during postmenopausal transition, with a prevalence of osteoclastic activity over osteoblastic activity, represents the main cause of bone loss and osteoporosis. Osteoporosis is a chronic disease requiring long-term therapy and it is important to evaluate the efficacy and safety of treatments over several years, as the fear of health risks is a common reason for discontinuing therapy. Raloxifene is a selective estrogen receptor modulator (SERM) leading to estrogen-agonist effects in some tissues and estrogen-antagonist effects in others. Raloxifene is effective to prevent and treat postmenopausal vertebral osteoporosis, with reduction of spine fractures and, in post-hoc analyses, non-spine fractures in high-risk subjects. Moreover, raloxifene reduces the risk of invasive breast cancer and improves the levels of serum lipoprotein but with an increased risk of venous thromboembolism and fatal stroke, without significant change in the incidence of coronary events. For these reasons the overall risk-benefit profile is favorable. Therefore, when considering the use of raloxifene in a postmenopausal woman, we should take into account the osteoporosis-related individual risk and weigh the potential benefits, skeletal and extra-skeletal, against the health risks

Detection of high mobility group A2 specific mRNA in the plasma of patients affected by epithelial ovarian cancer

Ovarian cancer is the most lethal gynecological malignancy and the high mortality rate is associated with advanced-stage disease at the time of the diagnosis. In order to find new tools to make diagnosis of Epithelial Ovarian Cancer (EOC) at early stages we have analyzed the presence of specific HMGA2 mRNA in the plasma of patients affected by this neoplasm. HMGA2 overexpression represents a feature of several malignances including ovarian carcinomas. Notably, we detected HMGA2 specific mRNA in the plasma of 40 out 47 patients with EOC, but not in the plasma of healthy donors. All cases found positive for HMGA2 mRNA in the plasma showed HMGA2 protein expression in EOC tissues. Therefore, on the basis of these results, the analysis of circulating HMGA2 specific mRNA might be considered a very promising tool for the early diagnosis of EOC

Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction

To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination

Cytoreductive Surgery for Heavily Pre-Treated, Platinum-Resistant Epithelial Ovarian Carcinoma: A Two-Center Retrospective Experience

Few retrospective studies have shown a benefit in selected patients affected by heavily pre-treated, platinum-resistant ovarian carcinomas (PROCs) who have undergone cytoreduction at relapse. However, the role of tertiary and quaternary cytoreductive surgery is not fully defined. Our aim was to evaluate survival and surgical morbidity and mortality after maximal cytoreduction in this setting. We evaluated all consecutive patients undergoing cytoreduction for platinum-resistance over an 8-year period (2010–2018) in two different centers. Fifty patients (median age 52.5 years, range 34–75) were included; the median number of previous chemotherapy lines was three (range 1–7) and the median number of previous surgeries was one (range 1–4). Completeness of cytoreduction (CC = 0) was achieved in 22 patients (44%). Rates of major operative morbidity and 30-day mortality were 38% and 8%, respectively. Median follow-up was 35 months. The absence of tumor residual (CC = 0) was associated with a significantly better overall survival (OS) compared to the CC > 0 subgroup (median OS 32.9 months (95% CI 21.6–44.2) vs. 4.8 months (95% CI n.a.–9.8), hazard ratio (HR) 4.21 (95% CI 2.07–8.60), p < 0.001). Optimal cytoreduction is feasible and associated with promising OS in selected, heavily pre-treated PROCs. Further prospective studies are required to better define the role of surgery in platinum-resistant disease

Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+

Ripristino combinato dell’ecosistema vaginale con gel vaginale e schiuma esterna a base di Lactobacillus Rhamnosus: effetti nell’età fertile e nella post-menopausa

Nel periodo fertile della donna l’ecosistema vaginale è dominato da lattobacilli acidofili che garantiscono un pH acido, tossico per i batteri anaerobi. In post-menopausa i bacilli acidofili tendono a scomparire con conseguente variazione della flora batterica. Risulta evidente che per ridurre il rischio di infezioni vaginali sia necessario mantenere un fisiologico pH vaginale associato ad un equilibrio stabile tra le diverse specie di microorganismi. Nella nostra esperienza su 34 donne in età fertile e 50 donne in post-menopausa con disordine lattobacillare trattate per due mesi con un gel vaginale ed una schiuma esterna a base di Lactobacillus Rhamnosus è stato rilevato un miglioramento della sintomatologia e del Grading lattobacillare con abbassamento del pH vaginale. Il trattamento combinato si è rivelato essere un valido approccio nel ripristino dell’ecosistema vaginale inteso come ripopolamento lattobacillare e riequilibrio del pH vaginale sia per le donne in età fertile che per quelle in post-menopausa al fine di una reale prevenzione delle vaginosi batteriche