Modulation of Oxidative Stress by 17 ß-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro.

BACKGROUND/AIMS: estrogens and phytoestrogens exert hepatoprotection through mechanisms not clearly examined yet. Here, we investigated the protective effects exerted by 17ß-estradiol and genistein against oxidative stress in hepatocytes and hepatic stellate cells (HSCs) and the involvement of specific receptors and the intracellular signalling. METHODS: Huh7.5 and LX-2, alone or in co-culture with Huh7.5, were treated with 17ß-estradiol and genistein alone or in the presence of menadione and of estrogen receptors (ERs) and G protein-coupled-estrogenic-receptors (GPER) blockers. Cell viability, mitochondrial membrane potential and oxidant/antioxidant system were measured by specific kits. Western Blot was used for the analysis of Akt and p38-mitogen-activated-protein kinases (MAPK) activation and α-smooth-muscle actin expression. RESULTS: In Huh7.5, 17ß-estradiol and genistein prevented the effects of peroxidation by modulating Akt and p38MAPK activation. Similar antioxidant and protective findings were obtained in LX-2 of co-culture experiments, only. ERs and GPER blockers were able to prevent the effects of 17ß-estradiol and genistein. CONCLUSION: In Huh7.5 and LX-2, 17ß-estradiol and genistein counteract the effects of peroxidation through the involvement of ERs and GPER and by an intracellular signalling related to Akt and p38MAPK. As concerning LX-2, paracrine factors released by Huh7.5 play a key role in protection against oxidative stress.

Robotic-Assisted Conservative Excision of Retrocervical-Rectal Deep Infiltrating Endometriosis: A Case Series.

Deep infiltrating endometriosis (DIE) is a complex disease that impairs the quality of life and the fertility of women. Colorectal DIE accounts for 70% to 93% of all the intestinal endometriotic sites and frequently needs a surgical approach. However, the indications for the surgical management of this condition are still controversial. From March 2010 to June 2014, we scheduled 33 consecutive patients presenting with retrocervical-rectal DIE of any diameter not involving the mucosa nor producing rectal stenosis >50% for laparoscopic robotic-assisted nerve-sparing rectal nodulectomy (LRN). All patients were examined preoperatively, at 3 months and 6 months postoperatively, and yearly thereafter. Dysmenorrhea, dyschezia, dyspareunia, and dysuria were evaluated on a 10-point visual analog scale. Among the 33 enrolled patients, 31 (93.9%) fulfilled the selection criteria and were submitted to LRN. In 1 out of 31 available patients (3.2%), a segmental bowel resection was considered necessary for prudential purpose at the end of the nodulectomy procedure. No laparotomic conversion was performed in any case. A wide variety of associated surgical procedures were performed in 25 of 30 patients (83.3%). No intraoperative complications were observed. One grade 3b and 2 grade 1 postoperative complications were recorded. The mean larger axis of the excised nodules measured on the formalin-fixed specimen was 26.4 mm. We found significant improvements in patient symptoms at a 3-month follow-up which persisted over the time. We observed 2 (6.7%) recurrences of intestinal endometriosis and 1 (3.3%) recurrence of chronic pelvic pain without clinical and/or radiologic evidence of endometriotic lesions. The mean follow-up time was 27.6 months. We believe that LRN is feasible and safe and shows promising results in terms of radicality, anatomic recurrence rate, and pain recurrence rate for treating isolated retrocervical-rectal DIE not involving the mucosa, without limiting this procedure to nodules smaller than 3 cm.

Human Chorionic Gonadotropin Protects Vascular Endothelial Cells from Oxidative Stress by Apoptosis Inhibition, Cell Survival Signalling Activation and Mitochondrial Function Protection.

BACKGROUND/AIM: Previous reports have made it hypothetically possible that human chorionic gonadotropin (hCG) could protect against the onset of pregnancy-related pathological conditions by acting as an antioxidant. In the present study we planned to examine the effects of hCG against oxidative stress in human umbilical vein endothelial cells (HUVEC). METHODS: HUVEC were subjected to peroxidation by hydrogen peroxide. The modulation of nitric oxide (NO) release by hCG and its effects on cell viability, glutathione (GSH) levels, mitochondrial membrane potential and mitochondrial transition pore opening (MPTP) were examined by specific dyes. Endothelial and inducible NO synthase (eNOS and iNOS), Akt and extracellular -signal-regulated kinases 1/2 (ERK1/2) activation and markers of apoptosis were analyzed by Western Blot. RESULTS: In HUVEC, hCG reduced NO release by modulating eNOS and iNOS. Moreover, hCG protected HUVEC against oxidative stress by preventing GSH reduction and apoptosis, by maintaining Akt and ERK1/2 activation and by keeping mitochondrial function. CONCLUSION: The present results have for the first time shown protective effects exerted by hCG on vascular endothelial function, which would be achieved by modulation of NO release, antioxidant and antiapoptotic actions and activation of cell survival signalling. These findings could have clinical implications in the management of pregnancy-related disorders.

Osteoporosis's Menopausal Epidemiological Risk Observation (O.M.E.R.O.) study.

Osteoporosis (OP) and related fractures are well-known severe conditions affecting quality of life and life expectancy of postmenopausal women, with high economic costs in Europe. On behalf of The Italian Society of Gynecology and Obstetrics (Società Italiana di Ginecologia ed Ostetricia, SIGO), the Osteoporosis's Menopausal Epidemiological Risk Observation (O.M.E.R.O.) study, a national multicenter study on clinical risk factors of OP was organized, using FRAX® tool as a reference. Here, data from this study are presented, showing an important portion of Italian postmenopausal women affected by osteopenia/OP at high risk of fracture and the need to do prevention and/or treatment. Gynecologist can be a primary specialist in this important challenge.

Vaginal hysterectomy and multimodal anaesthesia with bipolar vessel sailing (Biclamp(®) forceps) versus conventional suture technique: quality results' analysis.

PURPOSE: The medical and economic benefits of the transvaginal approach over the abdominal and laparoscopic methods are demonstrated in many studies. Vaginal hysterectomy with bipolar vessel sailing (BiClamp(®)) represents an example of mininvasive surgery and could be a valid and cost-benefit alternative in the surgical treatment of benign gynaecologic disease. BiClamp(®) may be carried out according to Clavè's technique with a good result in postoperative pain. METHODS: Prospective randomized study (Canadian Task Force classification I). We compared the vaginal hysterectomy with salpingo-oophorectomies with BiClamp(®) and multimodal anaesthesia (group A 30 patients) with vaginal hysterectomy with salpingo-oophorectomies and spinal anaesthesia (group B 30 patients). RESULTS: The median operating time was 33.5 min for group A and 54.5 min for group B (p < 0.0001). The median blood loss was 59.25 ml in group A and 81.75 ml in group B. The median hospital stay was 1.6 ± 0.58 days for group A and 2.55 ± 0.66 days for group B. Postoperative pain was statistically different between groups in the immediate postoperatory times, at 2 and at 6 h from the surgery and at 10 p.m. (p < 0.0001). Analyses of cost-effectiveness have stated advantages in terms of costs and indirect-direct benefits but also in earlier resumption of working. CONCLUSIONS: BiClamp(®) technique with multimodal anaesthesia has advantages from surgical, anaesthesiology and economic point of view. It is a minimally invasive surgery characterised by lower morbidity, quicker surgery times and reduced costs when compared to classical vaginal hysterectomy. BiClamp(®) technique represents a new border in vaginal surgery.

Cardiovascular Risk Perception and Knowledge among Italian Women: Lessons from IGENDA Protocol.

A multicenter, cross-sectional observational study (Italian GENder Differences in Awareness of Cardiovascular risk, IGENDA study) was carried out to evaluate the perception and knowledge of cardiovascular risk among Italian women. An anonymous questionnaire was completed by 4454 women (44.3 ± 14.1 years). The 70% of respondents correctly identified cardiovascular disease (CVD) as the leading cause of death. More than half of respondents quoted cancer as the greatest current and future health problem of women of same age. Sixty percent of interviewed women considered CVD as an almost exclusively male condition. Although respondents showed a good knowledge of the major cardiovascular risk factors, the presence of cardiovascular risk factors was not associated with higher odds of identifying CVD as the biggest cause of death. Less than 10% of respondents perceived themselves as being at high CVD risk, and the increased CVD risk perception was associated with ageing, higher frequency of cardiovascular risk factors and disease, and a poorer self-rated health status. The findings of this study highlight the low perception of cardiovascular risk in Italian women and suggest an urgent need to enhance knowledge and perception of CVD risk in women as a real health problem and not just as a as a life-threatening threat.

Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis.

Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identified in silico their predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopic versus eutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology.

Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells.

Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and hypothalamus to stimulate appetite, adiposity, and growth hormone release, through activation of growth hormone secretagogue receptor (GHSR)-1a receptor. Moreover, ghrelin features several activities such as inhibition of apoptosis, regulation of differentiation, and stimulation or inhibition of proliferation of several cell types. Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities. However, the unacylated ghrelin form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any endocrine activity, is far more abundant than ghrelin in plasma, and it shares with ghrelin some of its cellular activities. In here we show that both ghrelin and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to differentiate and to fuse into multinucleated myotubes in vitro through activation of p38. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12 proliferation in growth medium. Moreover, the ectopic expression of ghrelin in C2C12 enhances differentiation and fusion of these myoblasts in differentiation medium. Finally, we show that C2C12 cells do not express GHSR-1a, but they do contain a common high-affinity binding site recognized by both acylated and des-acylated ghrelin, suggesting that the described activities on C2C12 are likely mediated by this novel, yet unidentified receptor for both ghrelin forms.

Role of HPV testing in the follow-up of women treated for cervical dysplasia.

PURPOSE: The aim of study was to investigate factors predicting persistence or relapse of disease after cervical conisation for high-grade squamous intraepithelial lesions (CIN 2 or 3). METHODS: The study involved 78 women with high-grade squamous intraepithelial lesions, conservatively treated with loop electroexcision procedure for cervical conisation and subsequent with CO(2) laser-vaporisation of the cervical bed. Histological specimens were totally included and examined by an experienced pathologist. To evaluate the efficacy of treatment, the patients were examined with colposcopy and Pap smear 4 months after surgery and with PCR to search for and genotyping of HPV, 10 months after treatment. RESULTS: During the post-treatment follow-up, the cytologic examination showed persistent/relapsing disease in six patients (7.6%). In only 1 case, the deep margin of the cone was considered positive for CIN (16%).Ten months after treatment, viral typing revealed the persistence of high-risk HPV in all of these patients. Conversely, the viral follow-up of the other 72 patients without persisting/relapsing disease after treatment disclosed low-risk HPV genotypes in 6 cases, high-risk HPV in 2 cases (2.7%), whereas 7 cases had positive margins for CIN (9.7%). The risk of persistence and relapse of CIN in the group with positive margins was not statistically significant (P = 0.87), whereas it was in the group with HR-HPV positive (P = 0.000048). CONCLUSION: HPV testing is the most sensitive mean of identifying persistence or relapse early and is therefore capable of optimising follow-up after the treatment of high-grade CIN.

Minilaparotomy in spinal anaesthesia: a surgical choice in treatment of benign gynaecologic disease.

PURPOSE: Minilaparotomic access in spinal anaesthesia represents an example of mininvasive surgery and could be a valid cost-benefit alternative in the surgical treatment of benign gynaecologic diseases. METHODS: The study is a randomized study. We analyzed a consecutive series of 80 patients treated for benign gynaecological diseases with spinal (group A) or with general anaesthesia (group B). RESULTS: The median length of incision was 5 cm. The average operating time was 40.5 +/- 9.39 min, without differences between groups. The average hospital stay was 0.71 days shorter (p < or = 0.0001) and the postoperative pain was lower at 2 and 6 h from the surgery and at 10 p.m. in the group A (p < or = 0.0001). CONCLUSIONS: Minilaparotomy in spinal anaesthesia carries advantages from economic point of view with reduction of length of stay in hospital which is an important parameter for the evaluation of the quality of surgical treatments.

Peritoneal psammocarcinoma diagnosed by a Papanicolau smear: a case report.

BACKGROUND: Serous psammocarcinoma is a rare variant of epithelial neoplasia that can arise from the ovaries or peritoneum. It is characterized by massive psammoma body formation, invasiveness and low grade cytologic features. CASE: A 70-year-old woman was admitted to our hospital; a bimanual examination with cervicovaginal smear was performed. The smears revealed neoplastic cells with psammoma bodies; afterward, endocervical curettage revealed microaggregates of epithelial neoplastic cells with psammoma bodies. Computed tomography of the abdomen showed a diffuse peritoneal carcinosis with left ovarian calcification. An exploratory laparotomy was carried out. Final pathologic findings showed peritoneal serous psammocarcinoma with ovarian implants. CONCLUSION: Our report suggests that a Pap smear can play a role in the detection of peritoneal psammocarcinoma and underlines the significance of psammoma bodies as a cytologic marker of this rare tumor.

Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.

Ghrelin is an acyl-peptide gastric hormone acting on the pituitary and hypothalamus to stimulate growth hormone (GH) release, adiposity, and appetite. Ghrelin endocrine activities are entirely dependent on its acylation and are mediated by GH secretagogue (GHS) receptor (GHSR)-1a, a G protein-coupled receptor mostly expressed in the pituitary and hypothalamus, previously identified as the receptor for a group of synthetic molecules featuring GH secretagogue (GHS) activity. Des-acyl ghrelin, which is far more abundant than ghrelin, does not bind GHSR-1a, is devoid of any endocrine activity, and its function is currently unknown. Ghrelin, which is expressed in heart, albeit at a much lower level than in the stomach, also exerts a cardio protective effect through an unknown mechanism, independent of GH release. Here we show that both ghrelin and des-acyl ghrelin inhibit apoptosis of primary adult and H9c2 cardiomyocytes and endothelial cells in vitro through activation of extracellular signal-regulated kinase-1/2 and Akt serine kinases. In addition, ghrelin and des-acyl ghrelin recognize common high affinity binding sites on H9c2 cardiomyocytes, which do not express GHSR-1a. Finally, both MK-0677 and hexarelin, a nonpeptidyl and a peptidyl synthetic GHS, respectively, recognize the common ghrelin and des-acyl ghrelin binding sites, inhibit cell death, and activate MAPK and Akt.These findings provide the first evidence that, independent of its acylation, ghrelin gene product may act as a survival factor directly on the cardiovascular system through binding to a novel, yet to be identified receptor, which is distinct from GHSR-1a.

IGENDA protocol: gender differences in awareness, knowledge and perception of cardiovascular risk: an Italian multicenter study.

AIMS: Recent reports evidenced gender differences in the knowledge, perception and awareness of cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs). Despite the number of high-quality trials that attempted to establish the efficacy of different preventive interventions on CVDs, in the Italian scenario the differences by gender in awareness, knowledge and perception of CVD have not been addressed yet. So, the aims of this cross-sectional, observational and multicenter study will be to evaluate the gender differences in the awareness and perception of CVD risk, to assess the knowledge of CVD symptoms and preventive behaviors/barriers in men and women participating in this study, and to provide a national primary care approach for gender-oriented cardiovascular prevention strategies and therapy. METHODS: A self-administered questionnaire will be completed by 5000 consecutive Italian women and men aged 18-70 years. Moreover, a health questionnaire will be completed by the physicians. RESULTS: The present study will be the largest to be conducted in Italy, and probably in the European countries, to comprehensively demonstrate the current level of the knowledge, awareness and perception of CVRFs and CVD in both men and women. CONCLUSION: The present project could shed new light on the knowledge, awareness and perception of CVRFs and CVDs. If substantial differences will be detected by gender, the findings of this study may contribute to ultimately provide a new gender-oriented primary care approach inside the Italian healthcare system related to cardiovascular prevention and therapy strategies.

Intracoronary genistein acutely increases coronary blood flow in anesthetized pigs through beta-adrenergic mediated nitric oxide release and estrogenic receptors.

Various studies have suggested that the phytoestrogen genistein has beneficial cardioprotective and vascular effects. However, there has been scarce information regarding the primary effect of genistein on coronary blood flow and its mechanisms including estrogen receptors, autonomic nervous system, and nitric oxide (NO). The present study was planned to determine the primary effect of genistein on coronary blood flow and the mechanisms involved. In anesthetized pigs, changes in left anterior descending coronary artery caused by intracoronary infusion of genistein at constant heart rate and arterial pressure were assessed using ultrasound flowmeters. In 25 pigs, genistein infused at 0.075 mg/min increased coronary blood flow by about 16.3%. This response was graded in a further five pigs by increasing the infused dose of the genistein between 0.007 and 0.147 mg/min. In the 25 pigs, blockade of cholinergic receptors (iv atropine; five pigs) and alpha-adrenergic receptors (iv phentolamine; five pigs) did not abolish the coronary response to genistein, whose effects were prevented by blockade of beta(2)-adrenergic receptors (iv butoxamine; five pigs), nitric oxide synthase (intracoronary N(omega)-nitro-L-arginine methyl ester; five pigs) and estrogenic receptors (ERs; ERalpha/ERbeta; intracoronary fulvestrant; five pigs). In porcine aortic endothelial cells, genistein induced the phosphorylation of endothelial nitric oxide synthase and NO production through ERK 1/2, Akt, and p38 MAPK pathways, which was prevented by the concomitant treatment by butoxamine and fulvestrant. In conclusion, genistein primarily caused coronary vasodilation the mechanism of which involved ERalpha/ERbeta and the release of NO through vasodilatory beta(2)-adrenoreceptor effects.

Interaction between inflammation and angiogenesis during different stages of cervical carcinogenesis.

OBJECTIVE: The primary aim of this study was to investigate the role of angiogenesis and inflammatory cell response in cervical carcinogenesis. METHODS: Formalin-fixed tissue specimens from 58 uterine cervical specimens (8 CIN1, 14 CIN2, 28 CIN3, and 8 SCC), representing the different stages of cervical carcinogenesis, were immunohistochemically analyzed. Normal cervical tissue specimens were also included as controls. The present study assessed the expression of CD31 and CD105 to evaluate microvessel density (MVD), the macrophage marker CD68 and the panleukocyte marker CD45. In addition, expression of iNOS (inducible Nitric Oxide Synthase) was also evaluated. RESULTS: MVD, measured by either CD31 or CD105, increased along the continuum from normal epithelium to squamous cell carcinoma, and a significant correlation between the CD105-MVD and the CD31-MVD was observed (r=0.8735; p<0.0001). Furthermore, the number of infiltrating macrophages was significantly associated with progression to malignancy. Interestingly, there was a close positive correlation between macrophage counts and CD105-MVD (r=0.7525; p<0.0001). In striking contrast to the other angiogenic and inflammatory markers tested, iNOS expression was significantly reduced as cervical lesion grade progressed from low to high. CONCLUSIONS: Our findings demonstrated a positive correlation between neovascularity and macrophage counts, whereas iNOS expression displayed an inverse relationship with macrophage density and tumor progression. Low iNOS expression may modify the function of tumor-infiltrating macrophages toward a malignant phenotype that promotes tumor progression rather than an anti-tumor response.

Long-term outcome of hysteroscopic endometrial ablation without endometrial preparation.

OBJECTIVE: To describe the three-step hysteroscopic endometrial ablation (EA) technique without endometrial preparation, and its long-term outcomes. STUDY DESIGN: Four hundred and thirty-eight premenopausal women with menorrhagia or menometrorrhagia underwent three-step hysteroscopic EA, which consists of rollerball ablation of the fundus and cornual regions, a cutting loop endomyometrial resection of the rest of the cavity, and rollerball redessication of the whole pre-ablated uterine cavity. The main outcome measures were menstrual status, level of satisfaction with the procedure, and the need for repeat ablation or hysterectomy. Questionnaires were completed for 385 women (87.9%) with a mean follow-up of 48.2 months. RESULTS: One hundred and eighty-four responders (47.8%) reported amenorrhea; 177 (46%) had light to normal flow. One patient (0.3%) underwent repeat ablation and 20 (5.2%) underwent hysterectomy: 15 (3.9%) because of endometrial ablation failure and 5 (1.3%) because of indications unrelated to the ablation (three cases of atypical endometrial hyperplasia and two cases of fibroids). Two hundred and ninety-two patients (75.8%) were very satisfied, and 78 (20.3%) satisfied with the results. No major complications occurred and three women (0.8%) became pregnant during the follow-up period. CONCLUSIONS: EA is safe and effective means of treating of menorrhagia and menometrorrhagia in premenopausal women, and helps avoid hysterectomy in 95% of patients suffering from heavy bleeding, with or without uterine fibroids. Women should be informed that the procedure is not contraceptive and that pregnancy is possible after treatment.

Prolactin induces regional vasoconstriction through the beta2-adrenergic and nitric oxide mechanisms.

Prolactin has been associated with many effects and has been implicated in the pathogenesis of pregnancy-related hypertensive disorders, although little is known about its vascular effects. The present study was designed to determine the primary effect of prolactin on regional vascular beds and the mechanisms involved. In 37 anesthetized pigs, the infusion of 0.17 mug/kg min of prolactin at constant heart rate and arterial pressure decreased coronary, mesenteric, renal, and iliac blood flow. This response was graded in further five pigs by increasing the infused dose of the hormone between 0.017 and 1 mug/kg min. In 22 of the 37 pigs, blockade of cholinergic receptors (five pigs) and of alpha-adrenoceptors (five pigs) did not affect the prolactin-induced vascular response, which was abolished by blockade of beta(2)-adrenoceptors (five pigs) and by blockade of vascular nitric oxide (NO) synthase (seven pigs). In 15 of the 37 pigs the increases in measured blood flows caused by iv infusion of isoproterenol (five pigs) and by intraarterial administration of acetylcholine (five pigs) and of sodium nitroprusside (five pigs) were significantly reduced by infusion of prolactin. Moreover, the treatment of porcine aortic endothelial cells by prolactin caused a reduction of NO production and of the phosphorylation of ERK, Akt, and p38, which was prevented by the concomitant treatment by the beta(2)-adrenergic agonist albuterol. The present study showed that iv infusion of prolactin primarily caused coronary, mesenteric, renal, and iliac vasoconstriction. These effects were brought about by the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the NO intracellular pathway.

Diacylglycerol kinase is required for HGF-induced invasiveness and anchorage-independent growth of MDA-MB-231 breast cancer cells.

BACKGROUND: Estrogen receptor (ER)-negative breast cancers have a worse prognosis than ER-positive cancers, being more aggressive and overexposed to stimuli leading to their progression. Hepatocyte growth factor (HGF) has been associated with proliferation, migration and invasion of tumor cells, and several tumors, including those of breast cancer, produce HGF and overexpress its receptor. Diacylglycerol kinases (Dgks), which phosphorylate diacylglycerol to phosphatidic acid, are key regulators of cell signaling. Our research was focused on their role in HGF-induced invasion of MDA-MB-231 cells, a model of ER-negative breast cancer. MATERIALS AND METHODS: Dgk activity was evaluated with a kinase assay, MDA-MB-231 cell invasion via culturing of cells in matrigel-coated transwells, and anchorage-independent growth was assessed using a soft agar assay. RESULTS: HGF induces Dgk activation in MDA-MB-231 cells that is required for cell invasiveness. Moreover, Dgks are involved in MDA-MB-231 anchorage-independent growth. CONCLUSION: Dgks could be a target for ER-negative breast cancer therapy.

Intraoperative radiotherapy in gynaecological and genito-urinary malignancies: focus on endometrial, cervical, renal, bladder and prostate cancers.

Intraoperative radiotherapy (IORT) refers to the delivery of a single radiation dose to a limited volume of tissue during a surgical procedure. A literature review was performed to analyze the role of IORT in gynaecological and genito-urinary cancer including endometrial, cervical, renal, bladder and prostate cancers.Literature search was performed by Pubmed and Scopus, using the words "intraoperative radiotherapy/IORT", "gynaecological cancer", "uterine/endometrial cancer", "cervical/cervix cancer", "renal/kidney cancer", "bladder cancer" and "prostate cancer". Forty-seven articles were selected from the search databases, analyzed and briefly described.Literature data show that IORT has been used to optimize local control rate in genito-urinary tumours mainly in retrospective studies. The results suggest that IORT could be advantageous in the setting of locally advanced and recurrent disease although further prospective trials are needed to confirm this findings.