[Show abstract][Hide abstract] ABSTRACT: To investigate the biologic relevance and clinical implication of genes involved in multiple gene expression signatures for breast cancer prognosis, we identified 16 published gene expression signatures, and selected two genes, MAD2L1 and BUB1. These genes appeared in 5 signatures and were involved in cell-cycle regulation. We analyzed the expression of these genes in relation to tumor features and disease outcomes. In vitro experiments were also performed in two breast cancer cell lines, MDA-MB-231 and MDA-MB-468, to assess cell proliferation, migration and invasion after knocking down the expression of these genes. High expression of these genes was found to be associated with aggressive tumors and poor disease-free survival of 203 breast cancer patients in our study, and the association with survival was confirmed in an online database consisting of 914 patients. In vitro experiments demonstrated that lowering the expression of these genes by siRNAs reduced tumor cell growth and inhibited cell migration and invasion. Our investigation suggests that MAD2L1 and BUB1 may play important roles in breast cancer progression, and measuring the expression of these genes may assist the prediction of breast cancer prognosis.
PLoS ONE 08/2015; 10(8):e0136246. DOI:10.1371/journal.pone.0136246 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Morcellation of a bulky uterus after total laparoscopic hysterectomy (TLH) is a challenge for those dealing with advanced laparoscopic surgery. However, there are no laparoscopic standardized procedures available to date. We developed a laparoscopic cold knife technique with the aim of demonstrating a simple and reproducible method of sectioning and vaginal retrieval of the bulky uterus.
From June 2012 to June 2014, patients who underwent TLH for benign indication, with a uterus size over 12 gestational weeks, were prospectively admitted into the clinical study. Before specimen vaginal retrieval, uterine section was achieved by Chardonnens' cold knife with the aim of obtaining two uterus halves sectioned longitudinally and held together only by the posterior cervical wall. We performed the procedure in a containment system to avoid myometrial spillage into the abdomen.
Twenty-nine women with a bulky uterus were treated by TLH and the cold knife section technique. The uterine size ranged from 240 to 850 g (median, 460 g), and the average morcellation operative time was 11.3 minutes. All procedures were completed successfully without complications.
Our data suggest that the cold knife uterine section technique after TLH is a feasible, simple, and reproducible method of bulky uterus morcellation, even if further research is advisable to fully evaluate the advantages of this procedure.
[Show abstract][Hide abstract] ABSTRACT: Background:
The association of recombinant FSH (rFSH) plus recombinant LH (rLH) is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its efficacy has, to date, not yet been compared to that of human Menopausal Gonadotropin (hMG), the FSH + LH activity-containing urinary drug.
Eight hundred forty-eight (848) IVF patients classified as expected "poor" or "normal" responders according to antral follicle count (AFC) and basal (day 3) FSH were treated with rFSH + rLH (2:1 ratio, n = 398, Group A) or hMG (n = 450, Group B). Data were collected under real-life practice circumstances and the pregnancy rate with fresh embryos was calculated by stratifying patients according to the number of retrieved oocytes (1-2, 3-4, 5-6, 7-8, >8).
Overall, the pregnancy rate in both groups progressively improved according to the number of oocytes retrieved. When comparing patients within the same subgroup of oocyte yield, Group A and B showed a comparable outcome up to the reported highest yield (>8). When more than 8 oocytes were available, Group A had a significantly better pregnancy rate outcome. Patients' characteristics did not significantly differ between the two groups and the better outcome in the best responding patients in Group A was confirmed by a multivariable logistic regression analysis, that showed that both the use of rFSH + rLH and the total number of retrieved oocytes increased the probability of pregnancy with odd ratio (OR) of 1.628 and 1.083, respectively.
When comparing patients with the same number of retrieved oocytes under real-life circumstances, the association of rFSH + rLH results in a significantly higher pregnancy rate than hMG when more than 8 oocytes are retrieved. The reason(s) for this are unknown, but a more favorable effect on oocyte quality and/or endometrial receptivity could be involved.
[Show abstract][Hide abstract] ABSTRACT: Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.Bone Marrow Transplantation advance online publication, 11 May 2015; doi:10.1038/bmt.2015.111.
Bone marrow transplantation 05/2015; 50(9). DOI:10.1038/bmt.2015.111 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hormonal changes during the reproductive cycle are thought to account for the variation in migraine occurrence and intensity. Although the majority of women and the specialists treating them do not consider migraine as a component of the climacteric syndrome, many women, in fact, do experience migraine during perimenopause. If a woman already suffers from migraine, the attacks often worsen during menopausal transition. Initial onset of the condition during this period is relatively rare. Women with the premenstrual syndrome (PMS) prior to entering menopause are more likely to experience, during late menopausal transition, an increased prevalence of migraine attacks. Hormone replacement therapy (HRT) can be initiated during the late premenopausal phase and the first years of postmenopause to relieve climacteric symptoms. The effect of HRT on migraine, either as a secondary effect of the therapy or as a preventive measure against perimenopausal migraine, has been variously investigated. HRT preparations should be administered continuously, without intervals, to prevent sudden estrogen deprivation and the migraine attacks that will ensue. Wide varieties of formulations, both systemic and topical, are available. Treatment with transdermal patches and estradiol-based gels is preferable to oral formulations as they maintain constant blood hormone levels. Natural menopause is associated with a lower incidence of migraine as compared with surgical menopause; data on the role of hysterectomy alone or associated with ovariectomy in changing the occurrence of migraine are till now unclear.
[Show abstract][Hide abstract] ABSTRACT: In 2014 our group published the results of a survey conducted in Piedmont, Italy, on the patterns of use and dispensing of drugs in patients requesting assistance from pharmacists for relief of a migraine attack. Epidemiological studies on migraine have consistently shown that migraine is far more common among women than men. This gender difference is also reflected in the higher percentage of women visiting a pharmacy to obtain treatment or advice for headache attacks. In this study, we further explored gender differences in healthcare-seeking behavior and use of migraine medications. The aim of the study was to determine whether women made better selective use of migraine medications and whether visiting a headache center for consultation and treatment reflected awareness of how best to manage their condition. Among the drugs usually taken for relieving head pain, there was no statistically significant difference between men and women in the routine use of NSAIDs (55.6 vs. 51.6 %) or ergot derivatives (8.7 vs. 9.3 %). Statistically significant differences emerged between men and women (27.9 vs. 35.4 %) in the use of triptans (p = 0.003; OR 1.41, 95 % CI 1.12-1.78) and in the use of combined medications (8.5 vs. 12.2 %) (p = 0.029; OR 1.49, 95 % CI 1.04-2.14) but not in the use of simple OTC non-NSAIDs. Less men than women sought professional medical care for managing migraine (65.7 vs. 72.4 %) (p = 0.003; OR 0.71, 95 % CI 0.57-0.89); more women than men sought treatment at a headache center (21.7 vs. 17.4 %) (p = 0.044; OR 1.31, 95 % CI 1.07-1.72).
[Show abstract][Hide abstract] ABSTRACT: The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.
[Show abstract][Hide abstract] ABSTRACT: Understanding the molecular mechanisms involving the initiation, progression, and metastasis of ovarian cancer is important for the prevention, detection, and treatment of ovarian cancer. In this study, two ovarian cancer cell lines, HO-8910 and its derivative HO-8910PM with highly metastatic potential, were applied to comparative genomic hybridization (CGH) analysis. We found 14 chromosome fragments with different copy numbers between the two cell lines, one (2q36.1-37.3) of which was confirmed to be one-copy loss in HO-8910PM by fluorescent in situ hybridization (FISH). Using the microarray data on gene expression profiles from these cell lines, 6 significantly expression-decreased genes located on 2q36.1-37.3 in HO-8910PM were identified. Of the 6 genes, ARL4C was identified as a novel ovarian cancer-related gene using integrated molecular and genomic analyses. ARL4C mRNA expression was validated by quantitative PCR to be markedly decreased in HO-8910PM cells, compared to that in HO-8910. Both overexpression and knockdown of ARL4C demonstrated that low ARL4C expression promotes the migration but not influences proliferation capability of ovarian cancer cells in vitro, indicating its specific role in ovarian cancer progression. Furthermore, ovarian cancer patients with medium and high expression of ARL4C mRNA had a favorable prognosis compared to those with low expression, suggesting the ARL4C could be a potential predictor for ovarian cancer prognosis.
American Journal of Translational Research 04/2015; 7(2):242-56. · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vincenzo Tullo, Fabio Valguarnera, Piero Barbanti, Pietro Cortelli, Giuliano Sette, Gianni Allais, Florindo d'Onofrio, Marcella Curone, Dario Zava, Deborha Pezzola, Chiara Benedetto, Fabio Frediani and Gennaro Bussone. Comparison of frovatriptan plus dexketoprofen (25mg or 37.5mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: A randomized study. Cephalalgia 2014; 34: 434-445. DOI: 10.1177/0333102413515342. In the published version of this article, the author names and affiliations were represented as below: Vincenzo Tullo(1), Fabio Valguarnera(2), Piero Barbanti(3), Pietro Cortelli(4), Giuliano Sette(5), Gianni Allais(6), Florindo d'Onofrio(7), Marcella Curone(1), Dario Zava(8), Deborha Pezzola(8), Chiara Benedetto(6), Fabio Frediani(9) and Gennaro Bussone(1) (1)Department of Clinical Neuroscience, National Neurological Institute Carlo Besta, Italy (2)Sestri Ponente Hospital Padre Antero Micone, Italy (3)Unit for treatment and research of headaches and pain, IRCCS San Raffaele Pisana, Italy (4)Neurological Clinic, Department of Neurological Science, University of Bologna, Italy (5)Sant'Andrea Hospital, Italy (6)Department of Gynecology and Obstetrics, Women's Headache Center, University of Turin, Italy (7)San Giuseppe Moscati Hospital, Italy (8)Istituto Luso Farmaco d'Italia, Peschiera Borromeo, Italy (9)Ospedale S. Carlo Borromeo, Italy However, the affiliation for Pietro Cortelli(4) should have been written correctly as follows: (4)Neurological Clinic, Department of Biomedical and Neuromotor Science, University of Bologna, Italy and IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy The authors apologize for this mistake.
[Show abstract][Hide abstract] ABSTRACT: To investigate efficacy and safety of a controlled ovarian stimulation (COS) protocol in which a single dose of Corifollitropin-alfa (CFα) was administered on day 4 of a GnRH-antagonist cycle.
Cohort case-control study.
One hundred twenty-two normally cycling women expected to be normal responders to COS.
In 61 patients, CFα (100-150 μg) was injected subcutaneously on day 4 of a spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control group of 61 matched women was stimulated with daily subcutaneous injections of rFSH (100-150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25 mg/day) from day 8. IVF or ICSI was performed according to the sperm characteristics, and 1-2 embryos were transferred in utero under US guidance on day 2.
Number of retrieved cumulus-oocyte complexes (COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10 weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate.
No cycle was cancelled and the mean number of retrieved COCs was comparable in patients and controls. About 60 % of CF-alfa treated women had no need of daily rFSH addition, and the mean number of injections/cycle was significantly lower in the CF-alfa group than in controls (p < 0.05). The ongoing PR/transfer was 36.8 % in CF-alfa group and 37.5 % in controls. No patient developed severe OHSS, and the incidence of moderate OHSS was similar in cases and controls.
CFα may be started on day 4 of the cycle obtaining results comparable to those of a COS using day 4-start daily rFSH, with significantly less injections and a similar risk of OHSS.
Journal of Assisted Reproduction and Genetics 01/2015; 32(3). DOI:10.1007/s10815-014-0426-6 · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Thalassemias are genetic disorders characterized by decreased synthesis of one of the globin chains. Beta-thalassemia is caused by impairment in the production of beta-globin chains leaving the excess alpha chains unstable. With better treatment approaches and improvement in chelation therapy, thalassemic patients are living longer. As a consequence, new complications and associations with other conditions including malignancy have emerged. The occurrence of malignancies in thalassemia has rarely been reported, and our review of the literature revealed only few cases. We report the first case of a thalassemic patient developing breast cancer and discuss the possibility of a link between the two disease entities. This case is intended to alert physicians of the possibility of a malignancy in thalassemia patients.
[Show abstract][Hide abstract] ABSTRACT: This review focuses on the possibility of improving the outcome of human IVF by studying the follicles where oocytes grow by ultrasound techniques. A comprehensive analysis of bi-dimensional (2D) and three-dimensional (3D) ultrasound (US) assessment of the follicle size and volume is presented.
Published reports from the year 1999 to 2014 analyzing the relationship between oocyte competence, IVF outcome and ultrasound assessment of the follicle size and volume have been critically analyzed.
US assessment of growing follicles has been performed mainly by 2D-US, and while overall very useful, it has been found to be of limited usefulness in predicting oocyte competence, recognize which follicles will release a mature metaphase II oocytes and decide the ideal time to trigger ovulation. In fact, a quite wide follicle size range (16-22 mm) has been reported to be associated with mature oocytes with good competence toward fertilization and embryo development. It has been also shown that smaller follicles sometimes contain mature, fertilizable oocytes. However, embryos derived from smaller follicles have probably a lower implantation potential, while follicles larger than 22 mm often contain post-mature eggs.
The study of follicular size by 2D-US is of limited usefulness in helping in the identification of follicles containing the best oocytes and in choosing the best moment to trigger ovulation. Possibly the value of US in this area will be improved by large prospective studies in which automated 3D-US will be used.
[Show abstract][Hide abstract] ABSTRACT: Objectives We investigated levels of knowledge of the effects of combined hormonal contraceptives (CHCs) on general/reproductive health and physical/psychosexual wellbeing. Methods A cross-sectional study was conducted in two university hospitals in northern Italy. Healthy current-, past- and never CHC users (n = 545; age 18-44 years) completed a self-administered questionnaire. Results Ninety-three percent of current-, 74% of past-, and 56% of never users believed they were sufficiently informed (χ(2): 67.1; p = 0.001) about the benefits and risks of CHCs. Respondents mentioned: (i) a reduced risk of ovarian (67%) and endometrial (53%) cancer; (ii) an increased risk of thrombosis (82%); (iii) an increased risk of breast cancer (45%); (iv) a decreased fertility (19%) and no influence on risk of sexually transmitted infections (48%); (v) a reduced risk of menstrual abnormalities (77%) and acne (79%); (vi) less dysmenorrhoea (83%) and more headache (56%), weight gain (74%), increased appetite (51%), leg cramps (77%), mood swings (45%), vaginal dryness (47%), and low sex drive (48%). Beliefs about diseases/conditions and symptoms were influenced by CHC use. Conclusions CHC use is linked to good knowledge of risks and benefits. Our data suggest HCPs must be proactive in providing relevant information so that women can choose their contraception with a balanced insight of side effects.
The European Journal of Contraception and Reproductive Health Care 10/2014; 20(1):1-11. DOI:10.3109/13625187.2014.961598 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bowel endometriosis affects 3-37% of patients with endometriosis, involving more frequently the rectum and the rectosigmoid junction. Severe endometriosis with bowel involvement is often refractory to standard medical therapy. For these reasons, surgery for bowel treatment is frequently needed. We report the case of a 36-year-old woman with deep endometriosis of the pelvis, triple segmental bowel involvement (recto-sigma, ileum-cecum, transverse colon) and massive endometriotic ascites with secondary Glisson's capsule inflammation, refractory to medical therapy. A laparoscopic triple segmental bowel resection and complete fertility sparing excision of pelvic endometriotic lesions was performed. At 48 months of follow-up, the woman was asymptomatic, with no evidence of recurrence of disease or ascites. Laparoscopic segmental bowel resection, including multiple section, is feasible in selected symptomatic patients with consequent improved quality of life, morbidity rates similar to those achieved by laparotomy and with a less detrimental effect on fertility.
Videosurgery and Other Miniinvasive Techniques / Wideochirurgia i Inne Techniki Malo Inwazyjne 09/2014; 9(3):463-7. DOI:10.5114/wiitm.2014.41617 · 1.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present case report to demonstrate a laparoscopic approach to treat interstitial cornual pregnancy in emergency. Interstitial ectopic pregnancy develops in the uterine portion of the fallopian tube, account for 2–4% of all ectopic pregnancies and have potential to cause life-threatening haemorrhage at rupture. The mortality rate for a woman diagnosed with such a pregnancy is 2–2.5%. Diagnosis of interstitial pregnancy is made by ultrasound. In this case a 32 year-old woman, Gravida 0 Parity 0 ectopic1 presented to the emergency obstetrical room complaining acute abdominal pain. There was history of 10 weeks pregnancy but no pelvic ultrasound scan was performed before the access. A Transvaginal ultrasound scan immediately performed demonstrated a gestational sac with viable foetus in the right interstitial region. Moreover there was ultrasound evidence of haemoperitoneum. She was transferred to operating room and an emergency laparoscopy surgery was performed. The postoperative course was uneventful and the patient was discharged two days after the surgery. Interstitial pregnancies present a difficult management problem with no absolute standard of care in literature. Laparoscopic technique is under study with favorable results. For our personal point of view a treatment via laparoscopy could be performed both in elective and in emergency cases.
[Show abstract][Hide abstract] ABSTRACT: Frovatriptan is a triptan characterized by a high affinity for 5-HT1B/1D receptors and a long half-life contributing to a more sustained and prolonged action than other triptans. Dexketoprofen is a nonsteroidal anti-inflammatory drug with a relatively short half-life and rapid onset of action, blocking the action of cyclo-oxygenase, which is involved in prostaglandins' production, thus reducing inflammation and pain. Both drugs have been successfully employed as monotherapies for the treatment of acute migraine attacks. The combination of these two drugs (frovatriptan 2.5 mg plus dexketoprofen 25 or 37.5 mg) has been tested in migraine sufferers, showing a rapid and good initial efficacy, with 2-h pain free rates of 51%, and a high persistence in the 48-h following the onset of pain: recurrence occurred in only 29% of attacks and sustained pain free rates were 43% at 24- and 33% at 48-h.
[Show abstract][Hide abstract] ABSTRACT: Abstract Fertility preservation programs (FPPs) based on oocyte or ovarian tissue cryostorage may be offered to women facing oncostatic treatments at risk of precocious ovarian insufficiency. The way in which FPPs are presented to patients affects their decision to join them. We studied herein 48 young women to whom a FPP was proposed, aiming at clarifying the emotional aspects involved. A psychologist attended the consultations in which the FPP was offered to patients; at the end of the talk, a questionnaire was administered and a semi-structured interview was carried out. Finally, the STAI test was administered to measure trait (TAI) and state (SAI) anxiety, both immediately after consultation, and later on, when patients returned home. We observed that the possibility to join a FPP implied important emotional aspects, and that the presence of a psychologist was helpful to integrate technical information and emotions as well as to reduce trait and state anxiety levels. Our study suggests that the presence of a psychologist during the meeting in which a FPP is offered improves communication between doctors and patients, and helps these women to get a full awareness before choosing to join the FPP.
[Show abstract][Hide abstract] ABSTRACT: Purpose
The purpose of this article is to investigate the efficacy and safety of frovatriptan plus dexketoprofen 25 or 37.5 mg (FroDex25 or FroDex37.5, respectively) compared to that of frovatriptan 2.5 mg (Frova) in menstrually related migraine (MRM).
The aim of this article is to analyze a subgroup of 76 women who treated an MRM attack in this multicenter, randomized, double-blind, parallel-group study.
The primary end-point was the proportion of patients who were pain free (PF) at two hours. Secondary end-points included pain-relief (PR) at two hours and 48 hours sustained pain free (SPF).
PF rates at two hours were 29% under Frova, 48% under FroDex25 and 64% under FroDex37.5 (p < 0.05). PR at two hours was Frova 52%, FroDex25 81% and FroDex37.5 88%, while 48 hours SPF was 18% under Frova, 30% under FroDex25 and 44% under FroDex37.5.
Combining frovatriptan+dexketoprofen produced higher PF rates at two hours compared to Frova while maintaining efficacy at 48 hours. Tolerability profiles were comparable.