RE: Universal tumor DNA BRCA1/2 testing of ovarian cancer: prescreening PARPi treatment and genetic predisposition

BRCA1/2 mutations play a predictive role in ovarian cancer risk evaluation. Moreover , patients are today being tested for BRCA1/2 mutations to select a tailored therapy too , because they could benefit from a treatment with PARP inhibitors (PARPi).Therefore in ovarian carcinomas (OCs), BRCA1/2 mutation testing is an important step in planning the correct therapeutic strategy in association with chemotherapy and anti VEGF agents. We read with great interest the paper submitted by Vos et al (1) which investigates the role of universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as prescreen for PARPi treatment and cancer predisposition. With the approach described by the authors, both hereditary and somatic aberrations affecting DNA BRCA1/2 could be quickly and correctly detected with tumor BRCA1/2 smMIP-based next generation sequence testing

Progesterone therapy in endometrial cancer

We read with interest the paper “All-cause mortality in young women with endometrial cancer receiving progesterone therapy” by Maria P. Ruiz et al (1). The authors reported that the use of primary progesterone therapy increased significantly from 2004 to 2014 and that utilization was less frequent in older women, white women, and women with unfavorable grading and substaging. Moreover, the authors note, “its use was associated with decreased survival, particularly in women with stage IB tumors“. The results of this large study deserve some critical considerations. Given the demographic and clinical characteristics of the population, it appears that relatively few women were treated with primary progesterone therapy compared to primary hysterectomy. This trend is likely to generate contradictory bias. While oral progesterone therapy has remained largely unmodified over the past 10 years, surgery has undoubtedly improved greatly in terms of oncological outcomes and safety, thanks to better surgeons, expertise and improved technology (laparoscopy, robot assisted surgery). Moreover, the use of progesterone-releasing intrauterine devices has largely increased in the last 10 years in early endometrial cancer. Unfortunately, we don't know how many women were treated with oral or intrauterine progesterone, nor do we know the type and timing of surgical approach in women who underwent primary hysterectomy. We don't know the criteria used to select candidates for surgery, immediately or after primary progesterone therapy. We don't know how many women receiving primary progesterone therapy were also treated with resective hysteroscopy and how many received hysterectomy after primary progesterone therapy. Likewise we have no information about pharmaceutical selections (dosing, progestional agents, treatment interruptions and changes). According to recent data, the absence of such information undermines reliability of study results. (2, 3). This is not a small thing since some studies suggest ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT that the levonorgestrel intrauterine device could be superior to oral progestogens in the control of endometrial cancer and complex atypical hyperplasia (4). And we have to consider that use of progesterone delivering intrauterine device was rapidly increasing in the last years for neoplastic disorders in young patients. But above all, the study does not associate unfavorable survival data, in women treated with primary progesterone therapy, with the possible presence of risk factors for cardiovascular, thromboembolic and metabolic events. This greatly limits the validity of the authors’ conclusions, especially considering the small sample sizes. According to the above comments, it seems hard to state that primary progesterone therapy is less safe and less effective than primary hysterectomy in women with early endometrial cancer

Niraparib in ovarian cancer. results to date and clinical potential

Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened

Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection

Background: Over recent years, a growing interest has developed in microbiota and in the concept of maintaining a special balance between Lactobacillus and other bacteria species in order to promote women's well-being. The aim of our study was to confirm that vaginal Lactobacilli long-lasting implementation in women with HPV-infections and concomitant bacterial vaginosis or vaginitis might be able to help in solving the viral infection, by re-establishing the original eubiosis.Methods: A total of 117 women affected by bacterial vaginosis or vaginitis with concomitant HPV-infections were enrolled at Department of Gynecological Obstetrics and Urological Sciences, La Sapienza University, Rome, Italy between February 2015 and March 2016. Women were randomized in two groups, standard treatment (metronidazole 500 mg twice a day for 7 days or fluconazole 150 mg orally once a day for 2 consecutive days) plus short-term (3 months) vaginal Lactobacillus implementation (group 1, short probiotics treatment protocol group, n = 60) versus the same standard treatment plus long-lasting (6 months) vaginal Lactobacillus rhamnosus BMX 54 administration (group 2, treatment group, n = 57).Results: After a median follow up of 14 months (range 9-30 months) the chance to solve HPV-related cytological anomalies was twice higher in probiotic long-term users (group 2) versus short probiotics implementation group (group 1) (79.4% vs 37.5%, p = 0.041). Moreover, a total HPV-clearance was shown in 11.6% of short schedule probiotics implementation patients compared to a percentage of 31.2% in vaginal Lactobacilli long term users (p = 0.044), assessed as negative HPV-DNA test documented at the end of the study period.Conclusions: The consistent percentage of clearance of PAP-smear abnormalities and HPV-clearance obtained in long-term treatment group has been interestingly high and encouraging. Obviously, larger and randomized studies are warranted to confirm these encouraging results, but we believe that eubiosis re-establishment is the key to tackle effectively even HPV-infection

Environmental contaminants exposure and preterm birth: a systematic review

Preterm birth is an obstetric condition associated with a high risk of infant mortality and morbidities in both the neonatal period and later in life, which has also a significant public health impact because it carries an important societal economic burden. As in many cases the etiology is unknown, it is important to identify environmental factors that may be involved in the occurrence of this condition. In this review, we report all the studies published in PubMed and Scopus databases from January 1992 to January 2019, accessible as full-text articles, written in English, including clinical studies, original studies, and reviews. We excluded articles not written in English, duplicates, considering inappropriate populations and/or exposures or irrelevant outcomes and patients with known risk factors for preterm birth (PTB). The aim of this article is to identify and summarize the studies that examine environmental toxicants exposure associated with preterm birth. This knowledge will strengthen the possibility to develop strategies to reduce the exposure to these toxicants and apply clinical measures for preterm birth prevention

Intestinal endometriosis without evident pelvic foci treated with gonadotropin-releasing hormone agonist

[No abstract available

D-mannose: a promising support for acute urinary tract infections in women. A pilot study

Urinary tract infections still represent a significant bother for women and result in high costs to the health system. D-mannose is a simple sugar; it seems able to hinder bacteria adhesion to the urothelium. The present study aimed to determine whether D-mannose alone is effective in treating acute urinary tract infections in women and its possible utility in the management of recurrences

The age-adjusted Charlson comorbidity index as a predictor of survival in surgically treated vulvar cancer patients

OBJECTIVE: To evaluate the impact of age-adjusted Charlson comorbidity index (ACCI) in predicting disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) among surgically treated patients with vulvar carcinoma. The secondary aim is to evaluate its impact as a predictor of the pattern of recurrence. METHODS: We retrospectively evaluated data of patients that underwent surgical treatment for vulvar cancer from 1998 to 2016. ACCI at the time of primary surgery was evaluated and patients were classified as low (ACCI 0-1), intermediate (ACCI 2-3), and high risk (>3). DFS, OS and CSS were analyzed using the Kaplan-Meir and the Cox proportional hazard models. Logistic regression model was used to assess predictors of distant and local recurrence. RESULTS: Seventy-eight patients were included in the study. Twelve were classified as low, 36 as intermediate, and 30 as high risk according to their ACCI. Using multivariate analysis, ACCI class was an independent predictor of worse DFS (hazard ratio [HR]=3.04; 95% confidence interval [CI]=1.54-5.99; p<0.001), OS (HR=5.25; 95% CI=1.63-16.89; p=0.005) and CSS (HR=3.79; 95% CI=1.13-12.78; p=0.03). Positive nodal status (odds ratio=8.46; 95% CI=2.13-33.58; p=0.002) was the only parameter correlated with distant recurrence at logistic regression. CONCLUSION: ACCI could be a useful tool in predicting prognosis in surgically treated vulvar cancer patients. Prospective multicenter trials assessing the role of ACCI in vulvar cancer patients are warranted