Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study.

OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

[Use of bulking agents in urinary incontinece]. / L'utilizzo dei bulking agents nel trattamento dell'incontinenza urinaria.

Urinary incontinence consist in voluntary urine leakage. Female affected in the world are about 200 thousand. Urinary incontinence affect severely women quality of life. There are different kinds of urinary incontinence that can be treated in different ways. We can use pelvic floor rehabilitation, drug therapy, invasive and non-invasive surgical treatment. Different treatments are used for different incontinence types. Periurethral injection is the most common procedure between non-invasive surgery. The most recent bulking agents occasionally determine severe adverse reaction or complication. Frequently we can have just pain during injection and a temporary urine retention. During the latest years we used a lot of bulking agents: bovine collagen, autologous fat, carbon particles, macroplastique, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, dextranomer. Urethral injection have success in 40-90%. We can assert that macroplastique is the most efficacy and safe on the basis of literature data and of our experience data. This surgical procedure, in fact, has good percentage of success in accurately selected patients. In our experience Macroplastique can also be used in oncological patients, in elderly women, in patients with important comorbidity and with high surgical risk with good objective and subjective results.

Hormone replacement therapy after prophylactic risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A meta-analysis.

BACKGROUND: Hormone replacement therapy (HRT) has been tested in women with BRCA1 and BRCA2 mutations who underwent risk-reducing salpingo-oophorectomy (RRSO), but its effect on breast cancer (BC) risk has never been appraised using meta-analysis comparison. We performed the first meta-analysis aimed to clarify whether HRT after RRSO could negatively impact on BC risk in women carriers of BRCA1 and BRCA2 mutations. METHODS AND MATERIAL: Pubmed and Scopus databases were searched to retrieve articles written in the English language. Trials comparing RRSO with or without HRT were identified and only those trials with available BC events were included. BC risk was the main endpoint. RESULTS: Three trials with 1100 patients were included. There was not a significantly higher BC risk in BRCA1 and BRCA2 mutation carriers receiving HRT after RRSO (HR = 0.98; 95% CI 0.63-1.52). There was a slightly but not significantly, benefit in BC risk reduction in favor of estrogen alone HRT versus estrogen plus progesterone HRT formulation (OR = 0.53; 95% CI 0.25-1.15). CONCLUSION: HRT use after RRSO in BRCA 1 and BRCA2 mutation carries does not affect BC risk. Comparison of the different HRT types suggests that estrogen alone should be related to lowest BC risk.

Clonal analysis of gene loss of function and tissue-specific gene deletion in zebrafish via CRISPR/Cas9 technology.

In the last few years the development of CRISPR/Cas 9-mediated genome editing techniques has allowed the efficient generation of loss-of-function alleles in several model organisms including zebrafish. However, these methods are mainly devoted to target-specific genomic loci leading to the creation of constitutive knock-out models. On the contrary, the analysis of gene function via tissue- or cell-specific mutagenesis remains challenging in zebrafish. To circumvent this limitation, we present here a simple and versatile protocol to achieve tissue-specific gene disruption based on the Cas9 expression under the control of the Gal4/upstream activating sequence binary system. In our method, we couple Cas9 with green fluorescent protein or Cre reporter gene expression. This strategy allows us to induce somatic mutations in genetically labeled cell clones or single cells, and to follow them in vivo via reporter gene expression. Importantly, because none of the tools that we present here are restricted to zebrafish, similar approaches are readily applicable in virtually any organism where transgenesis and DNA injection are feasible.