Giovanni Scambia

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (562)2207.68 Total impact

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    ABSTRACT: To assess the prevalence of femicides in Italy over the last three years and the potential long lasting effects of these traumatic events for the children of a woman who dies a violent death. The data used in this study come from an internet search for the number of femicides occurring in Italy between 1 st January, 2012 and 31 st October, 2014. The total number of femicides was 319; the average age of murdered women was 47.50 ± 19.26. Cold arms in the form of sharp object -mostly knives- have caused the death of 102/319 women; firearms were used in 87/319 cases; asphyxiation was the chosen method in 52/319 cases. About the place where the femicides occurred, 209/319 were committed inside the victim’s house. Children of women who died a violent death were 417 with a total of 180 minors in less than three years. A total of 52/417 children were witness to the killing and, among these 30/52 were minors; in 18/417 cases, children were murdered together with their mother and among these 9/18 were minors. Long-term studies are needed to ascertain what happens to these children, to understand what are the most appropriate psychological treatments, the best decisions about the contact with their father and the best placement for these children.
    Italian Journal of Pediatrics 12/2015; 41(1). DOI:10.1186/s13052-015-0173-z · 1.52 Impact Factor
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    ABSTRACT: Background: Nowadays, laparoscopy acquired an increasing role in the management of ovarian cancer. Laparoscopic cytoreduction could represent a new frontier for selected patients after neoadjuvant chemotherapy. Objective: To assess feasibility and early complication's rate of Minimally Invasive Interval Debulking Surgery (MI-IDS) in stage III-IV EOC patients after neoadjuvant chemotherapy STUDY DESIGN: This is a Phase II multicentric study in Advanced Epithelial Ovarian Cancer women with clinical complete response after neoadjuvant chemotherapy, according to GCIG and RECIST criteria. The IRB approval was obtained and all patients signed a written informed consent to be included in the protocol. The study was registered in the with the number NCT02324595 and was named MISSION trial. For patients meeting inclusion criteria, surgical procedures started with diagnostic laparoscopy in order to confirm preoperative findings and assess surgical complexity. MI-IDS included hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, peritonectomy and bowel resection. Pelvic and/or aortic lymphadenectomy were not considered as standard procedure in these cases. Intra- and post-operative outcomes, time to restart chemotherapy, survival rate and Quality of Life data were registered. Results: From December 2013 to February 2015, of 184 AEOC patients considered eligible for interval debulking surgery, 52 (28.2%) met inclusion criteria and were enrolled in the study. For twenty-two (12%) of them standard laparotomic approach was preferred because of intra-operatory surgeon's evaluation. Finally 30 (16.3%) patients received the planned treatment of MI-IDS. Median age was 61 years (39 - 81) and median BMI was 24 Kg/m2 (range 20-31). Median numbers of NACT cycles were 4 (range 3-7). Median operative time was 285 minutes (range 124-418) and median EBL was 100 ml (range 50-200). Surgical procedures included 28 (93.3%) hysterectomy and bilateral salpingo-oophorectomy, 29 (96.6%) omentectomy, 2 (6.6 %) appendectomy, 11 (36.6%) regional peritonectomy and 1 (3.4 %) bowel resection. A residual tumor of 0 was reached in 29 patients (96.6%) and 0,5 cm in only one case (3.4%). The vast majority of patients were discharged on post-operative day 2 (range 2 - 3). No early post-operative complications were registered. Median time to restart chemotherapy was 20 days (10 - 30) and all patients successfully completed the cycles. Histological findings showed 3 (10%) complete response, 9 (30%) microscopic residual disease and 18 (60%) evidence of macroscopic residual disease. With a median follow-up of 10.5 month, 5 peritoneal and 2 lymphnodal recurrences were observed. Psychometric test revealed a moderate discomfort in the vast majority of patients (66.7%). All patients still alive. Conclusions: Minimally Invasive-IDS in patients with clinical complete response to neoadjuvant chemotherapy seems to be feasible and safe in terms of perioperative outcomes, psycho-oncological impact and survival rate. The equivalence between MIS and laparotomy needs to be confirmed with a longer follow-up and a larger number of patients.
    American journal of obstetrics and gynecology 11/2015; DOI:10.1016/j.ajog.2015.10.922 · 4.70 Impact Factor
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    ABSTRACT: Background: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer. Methods: In this double-blind phase 3 trial, chemotherapy-naive patients (aged 18 years or older) with International Federation of Gynecology and Obstetrics (FIGO) IIB-IV ovarian cancer and upfront debulking surgery were stratified by postoperative resection status, FIGO stage, and planned carboplatin dose. Patients were randomly assigned (2:1) via an interactive voice or web-based response system to receive six cycles of carboplatin (AUC 5 mg/mL per min or 6 mg/mL per min) and paclitaxel (175 mg/m(2)) in addition to either 200 mg of nintedanib (nintedanib group) or placebo (placebo group) twice daily on days 2-21 of every 3-week cycle for up to 120 weeks. Patients, investigators, and independent radiological reviewers were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival analysed in the intention-to-treat population. This trial is registered with, number NCT01015118. Findings: Between Dec 9, 2009, and July 27, 2011, 1503 patients were screened and 1366 randomly assigned by nine study groups in 22 countries: 911 to the nintedanib group and 455 to the placebo group. 486 (53%) of 911 patients in the nintedanib group experienced disease progression or death compared with 266 (58%) of 455 in the placebo group. Median progression-free survival was significantly longer in the nintedanib group than in the placebo group (17·2 months [95% CI 16·6-19·9] vs 16·6 months [13·9-19·1]; hazard ratio 0·84 [95% CI 0·72-0·98]; p=0·024). The most common adverse events were gastrointestinal (diarrhoea: nintedanib group 191 [21%] of 902 grade 3 and three [<1%] grade 4 vs placebo group nine [2%] of 450 grade 3 only) and haematological (neutropenia: nintedanib group 180 [20%] grade 3 and 200 (22%) grade 4 vs placebo group 90 [20%] grade 3 and 72 [16%] grade 4; thrombocytopenia: 105 [12%] and 55 [6%] vs 21 [5%] and eight [2%]; anaemia: 108 [12%] and 13 [1%] vs 26 [6%] and five [1%]). Serious adverse events were reported in 376 (42%) of 902 patients in the nintedanib group and 155 (34%) of 450 in the placebo group. 29 (3%) of 902 patients in the nintedanib group experienced serious adverse events associated with death compared with 16 (4%) of 450 in the placebo group, including 12 (1%) in the nintedanib group and six (1%) in the placebo group with a malignant neoplasm progression classified as an adverse event by the investigator. Drug-related adverse events leading to death occurred in three patients in the nintedanib group (one without diagnosis of cause; one due to non-drug-related sepsis associated with drug-related diarrhoea and renal failure; and one due to peritonitis) and in one patient in the placebo group (cause unknown). Interpretation: Nintedanib in combination with carboplatin and paclitaxel is an active first-line treatment that significantly increases progression-free survival for women with advanced ovarian cancer, but is associated with more gastrointestinal adverse events. Future studies should focus on improving patient selection and optimisation of tolerability. Funding: Boehringer Ingelheim.
    The Lancet Oncology 11/2015; DOI:10.1016/S1470-2045(15)00366-6 · 24.69 Impact Factor
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    ABSTRACT: Objective: To investigate the expression of inflammosome components (NALP-3, associated speck-like protein containing a CARD [ASC]) and their activation (caspase-1, interleukin [IL]-1β, and IL-18 secretion) in the human endometrium from fertile and women with history of recurrent pregnancy loss (RPL). Design: Experimental study. Setting: University hospital. Patient(s): Ten fertile women (control group [CTR]) and 30 women with RPL. Intervention(s): None. Main outcome measure(s): Endometrial samples were collected by hysteroscopy during the putative window of implantation and evaluated for chronic endometrial inflammation by hystopathological analysis. Inflammosome expression was analysed by immunohystochemical staining (27 RPL and 10 CTR women). The expression of NALP-3 and ASC protein was quantified by Western blot (30 RPL and 10 CTR women). Caspase-1 activation and IL-1β and IL-18 secretion was quantified by ELISA (30 RPL and 10 CTR women). Result(s): We observed a significantly increased expression of inflammasome NALP-3 and ASC protein, an increased activation of caspase-1, and increased levels of IL-1β and IL-18 in RPL endometrium compared with CTR. Conclusion(s): Abnormal activation of endometrial innate immunity by means of inflammosome, stimulated by pathogen- or damage-associated molecular patterns, may represent an additional mechanism, currently not investigated, negatively interfering with endometrial receptivity. More studies are required [1] to identify the primary trigger of endometrial inflammosome activation and its clinical impact in the occurrence of RPL; and [2] to validate the inflammosome components as a novel family of endometrial biomarkers and promising therapeutic targets in RPL.
    Fertility and sterility 10/2015; DOI:10.1016/j.fertnstert.2015.09.027 · 4.59 Impact Factor
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    ABSTRACT: Objective: To evaluate the feasibility of a novel laparoscopic procedure for complete eradication of diaphragmatic endometriosis (DE). Design: Retrospective multicenter study (Canadian Task Force Classification II-2). Setting: University tertiary referral centre. Patients: A consecutive series of 9 women with DE. Intervention: Laparoscopic en bloc eradication by Sugarbaker's peritonectomy including or not diaphragmatic resection for DE. All surgical procedures were performed by the same surgeon in two tertiary referral centres (Charitè University in Berlin, Germany, Catholic University of the Sacred Heart, Foundation John Paul II, Campobasso, Italy). Main outcome measures: Rate of conversion to laparotomy, perioperative outcomes, intra and post-operative complications, recurrence rate. Results: The procedures were successfully performed in all the patients laparoscopically, without conversion to laparotomy. All patients presented also, multiple endometriosic lesions nodules in the Morison's pouch, and In 3 cases a deep infiltration of the right diaphragm was observed which required partial diaphragmatic resection. In 2 women also pulmonary nodules were detected, and lung laparoscopic resection was attempted to eradicate the disease. Chest drainage was placed in 7 women, and was removed after a median time of 6 days (4-10 days). No intra or post-operative complications were recorded. To complete the diaphragmatic peritonectomy, the median operative time required was 180 minutes (90-240 minutes). Median estimate blood loss was 100 ml (50-300 ml), and median hospital stay was 10 days (5-17 days). After a median follow-up of 6 months, we observed symptomatic relief for all the study patients, without major surgery-related morbidity. In one woman a laparoscopic adhesiolysis was performed after 18 months from surgery, without signs of recurrent endometriosis. Conclusion: The laparoscopic en bloc eradication of DE, with Sugarbaker peritonectomy is highly effective in the management of symptomatic DE, with no major intra/post-operative complications, and very favourable perioperative outcomes.
    Journal of Minimally Invasive Gynecology 10/2015; DOI:10.1016/j.jmig.2015.09.020 · 1.83 Impact Factor

  • Value in Health 10/2015; DOI:10.1016/j.jval.2015.08.010 · 3.28 Impact Factor
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    ABSTRACT: Objectives: To investigate the feasibility and determine the recommended preoperative intensity modulated radiotherapy (IMRT) dose of extended field chemoradiation along with simultaneous integrated boost (SIB) dose escalation Methods: A radiation dose of 40 Gy over four weeks, 2 Gy per fraction, was delivered to the tumor and the lymphatic drainage (planning target volume, PTV3), which encompassed a volume larger than standard (common iliac lymphatic area up to its apex, in front of the L3 vertebra ), concurrently with chemotherapy (cisplatin and 5- fluorouracil). Radiation dose was escalated to the pelvis (PTV2) and to the macroscopic disease (PTV1) with the SIB-IMRT strategy. Three dose levels were planned: level 1 (PTV3: 40/2 Gy, PTV2: 40/2 Gy; PTV1: 45/2.25 Gy), level 2 (PTV3: 40/2 Gy, PTV2: 45/2.25 Gy; PTV1: 45/2.25 Gy) and level 3 (PTV3: 40/2 Gy, PTV2: 45/2.25 Gy; PTV1: 50/2.5 Gy). All treatments were delivered in 20 fractions. Patients were treated in cohorts of 3 to six per group using a phase I study design. The recommended dose was exceeded if N=2 of 6 patients in a cohort experienced dose-limiting toxicity (DLT) within 3 months from treatment. Results: 19 patients (median age: 46 years; FIGO stage IB2: 3, IIB: 10, IIIA-IIIB: 6) were enrolled. Median follow-up was 24 months (9-60 months). The most common grade 3/4 toxicity was gastrointestinal (diarrhea, mucous discharge, rectal/abdominal pain). At level 1 and 2 only one grade 3 GI toxicity per level were recorded, while at level 3 two grade 3 GI toxicity (diarrhea, emesis and nausea) were recorded. Conclusions: The SIB-IMRT technique was found feasible and safe at the recommended doses of 45 Gy to PTV1 and PTV2, and 40 Gy to PTV3 in the preoperative treatment of LACC patients. Unfortunately this complex technique was unable to safely escalate dose beyond levels already achieved with 3D-conformal radiotherapy technique given acute GI toxicity. Advances in knowledge: A phase I radiotherapy dose escalation trial with SIB-IMRT technique is proposed in cervical cancer. This complex technique is feasible and safe at the recommended doses.
    The British journal of radiology 09/2015; 88(1055):20150385. DOI:10.1259/bjr.20150385 · 2.03 Impact Factor
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    ABSTRACT: Background: Minilaparoscopy is an attractive approach for hysterectomy due to advantages such as reduced morbidities and enhanced cosmesis. However, it has not been popularized due to the lack of suitable instruments and high technical demand. We aim to highlight the first case of laparoscopic hysterectomy performed with percutaneous instruments (The Percuvance™ System, Teleflex Incorporated,USA) that represents a significant advance in minimally invasive surgery. Methods: The basis of the system is a less than 3 mm diameter shaft that, when connected to an introducer tool tip, can be inserted percutaneously through the skin. The introducer tool tip can then be exchanged outside the body for a wide variety of 5 mm interchangeable surgical tool tips. The shaft is sufficiently strong to hold structures, and surgeons can use its interchangeable tool tips to grasp, cut and manipulate tissue. We used a 3-dimensional high-definition 10-mm flexible tip endoscope (ENDOEYE FLEX 3D, Olympus Winter & IBE GMBH, Hamburg - Germany). A 53-year-old, multiparous patient with endometrial endometroid cancer grading 1, Fédération Internationale de Gynécologie et d'Obstétrique stage IA. Informed consent for abdominal or laparoscopic was obtained from the patients in accordance with the local legislation. Moreover patient firmed an informed consent to use image and video of the procedure. IRB aproval was not required for this kind of procedure. The patient was hysteroscopically diagnosed with endometrial cancer after removal of an endometrial polip adnexectomy. Once referred to our center, a surgical staging was planned including total hysterectomy, bilateral adnexectomy. Laparoscopy with two lateral percutaneous and one soprapubic 3mm instruments was believed to be feasible to achieve it. Results: The operation was performed successfully with no intraoperative or postoperative complication. Operative time was 80minutes overall, and blood loss was 50 mL. The pathology report confirm endometrial endometroid cancer grading 1, Fédération Internationale de Gynécologie et d'Obstétrique stage IA. The patient was discharged on day 1. After 2 months, no late complication and recurrence was detected. Conclusion: Percutaneous total hysterectomy is technically feasible and the use of this novel devices permit to surgeons to mantein the standard setting. Further studies are mandatory to define the benefits, advantages, and costs of this novel approach with respect to others minimally invasive approaches.
    Journal of Minimally Invasive Gynecology 09/2015; DOI:10.1016/j.jmig.2015.09.004 · 1.83 Impact Factor
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    ABSTRACT: we investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT). 84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2) was finally calculated. At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001). Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor) to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029). At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037) emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019), and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037) survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis. polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC.
    PLoS ONE 09/2015; 10(9):e0136654. DOI:10.1371/journal.pone.0136654 · 3.23 Impact Factor
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    ABSTRACT: Problem: A threefold higher prevalence of antinuclear antibodies (ANA) has been reported in patients with recurrent pregnancy loss (RPL). Nevertheless, the role of ANA in reproductive failure is still unclear. The aim of this study was to investigate the role of ANA during early pregnancy in vivo. Method of study: We used pregnant mice treated with immunoglobulin G (IgG) obtained from normal healthy subjects (NHS); ANA(+) sera of patients with RPL; and ANA(+) sera from women with uncomplicated pregnancies (HW). Placental immunohistochemical/immunofluorescence staining was performed to detect complement and immune complex deposition. ELISA was performed to evaluate complement levels. Results: ANA(+) IgG from RPL women significantly increased embryo resorption rate, reduced C3, and increased C3a serum levels compared to NHS IgG or ANA(+) -HW IgG. Increased C3 deposition and increased immune complex staining in placental tissues from mice treated with ANA(+) -RPL IgG fraction compared to NHS- and ANA(+) -HW-IgG-treated mice were found. Conclusion: ANA(+) IgG injection in mice is able to induce fetal resorption and complement activation. The presence on placental tissues of immune complexes and complement fragments suggests the complement activation as a possible mechanism of placental damage.
    American Journal Of Reproductive Immunology 09/2015; DOI:10.1111/aji.12429 · 2.44 Impact Factor
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    ABSTRACT: Massive parallel sequencing (MPS) is the new frontier for molecular diagnostics. Twenty-four papers regarding BRCA analysis were considered for reviewing all pipelines evaluated in this field. Proposed here is an integrated MPS workflow able to successfully identify BRCA1/2 mutational status on 212 Italian ovarian cancer patients. The review of literature data is reported. The pipeline can be routinely used as robust molecular diagnostic strategy, being highly sensitive and specific. Literature data report that efforts are being made in order to fully translate MPS-based BRCA1/2 gene assay into routine clinical diagnostics. However, this study highlights the need of an integrated MPS BRCA1/2 molecular workflow fulfilling the standardized requirements needed in the routine clinical laboratory practice.
    Expert Review of Molecular Diagnostics 08/2015; 15(10). DOI:10.1586/14737159.2015.1081059 · 3.52 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the impact of aromatase inhibitor (AI) treatment on vertebral morphology by vertebral fracture assessment in postmenopausal women with early-stage breast cancer. A clinical cross-sectional study was conducted. A group of 156 postmenopausal women with breast cancer (mean [SD] age, 60.4 [10.1] y; mean [SD] time since menopause, 11.7 [9.2] y) was included in the study. Eighty-two women received AI treatment, whereas 74 women did not. Women underwent extensive medical history check and risk factor assessment together with vertebral morphology and bone mineral density (BMD) evaluation. In the studied population, the prevalence of vertebral fractures identified by vertebral fracture assessment was 16.6%. Multivariate analysis showed that AI treatment was significantly associated with vertebral fractures (adjusted P < 0.04). Women receiving AI treatment had a higher prevalence of vertebral fractures than women not treated with AIs (25.6% vs 4%). The risk of vertebral fractures in women treated with AIs was significantly higher than in non-AI-treated women (adjusted odds ratio, 4.7; P < 0.005). Vertebral fractures of the highest grade were identified at the lumbar spine. Women treated with AIs had a significantly lower BMD than women not treated with AIs (P < 0.01). Reduction of BMD was significantly associated with length of therapy, whereas there was no association between length of treatment and risk of vertebral fractures. AI treatment severely impacts vertebral morphology. Our study demonstrates a high prevalence of asymptomatic vertebral fractures in women treated with AIs.
    Menopause (New York, N.Y.) 08/2015; DOI:10.1097/GME.0000000000000515 · 3.36 Impact Factor
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    ABSTRACT: To evaluate the impact of obesity on the outcomes of surgical treatment for endometrial cancer (EC) in general and comparing laparoscopic vs. open abdominal approach. Retrospective case-control study DESIGN: Classification: Canadian Task Force II-1 SETTING: Obstetrics and Gynecology Department, University of Insubria, Varese; Catholic University of the Sacred Heart, Rome, Italy; International School of Surgical Anatomy, Sacred Heart Hospital, Negrar; Sant'Orsola-Malpighi Hospital, Bologna (Italy). Data of consecutive patients who underwent surgery for EC in four centers were reviewed. Univariate and multivariable analysis were performed. Adjustment for potential selection bias in surgical approach was made using propensity score (PS) matching. Laparoscopic or open surgical treatment for endometrial cancer. A total of 1,266 patients were included: 764 by laparoscopy and 502 by open surgery. Three-hundred-ninety-one (30.9%) patients were obese: 238 (18.8%), 89 (7%), and 64 (5.1%) women were obese class I, II and III, respectively. The total number of complications, risk of wound complications, and venous thromboembolic events were higher among obese vs. non-obese women. Blood transfusions, incidence/severity of post-operative complications, and post-operative hospital stay were significantly higher in the open surgery group compared to laparoscopy, irrespectively of obesity. These differences remained significant both after multivariable and PS-matched analysis. The percentage of patients who received lymphadenectomy declined significantly for BMI>40 both for laparoscopy and open surgery. Conversions from initially-intended minimally-invasive approach to open surgery were between 1.1% and 2.2% for women with BMI<40, but they increased when BMI was >40 (8.6%; p=.05). PS analysis showed that obese women in the laparoscopic group had a lower complication rate, shorter hospital stay, and higher likelihood of receiving lymphadenectomy. Laparoscopy for EC retains its advantages over open surgery, even in obese patients. However, operating an obese subject, can be challenging per se, regardless of the surgical approach, especially in case of morbid adiposity. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.
    Journal of Minimally Invasive Gynecology 08/2015; DOI:10.1016/j.jmig.2015.08.007 · 1.83 Impact Factor
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    ABSTRACT: The past five years have yielded substantial developments in the management of advanced ovarian cancer. Initial promise shown by anti-angiogenic agents has translated into positive phase III trials in the front-line and recurrent settings. Nevertheless, several questions remain unanswered, including the most appropriate timing for initiation of anti-angiogenic therapy and patient selection for the various treatment approaches. This review article summarises the key results (including final overall survival data), from five pivotal phase III trials of bevacizumab, highlights emerging data with new maintenance strategies and considers unanswered questions and ongoing research to address uncertainties in treatment duration, re-exposure to bevacizumab in bevacizumab-pretreated patients and the potential integration of anti-angiogenic therapy into neoadjuvant treatment regimens.
    Critical reviews in oncology/hematology 08/2015; DOI:10.1016/j.critrevonc.2015.08.017 · 4.03 Impact Factor
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    ABSTRACT: Hypoxia selects the most aggressive and drug-resistant clones in solid malignancies. One of the pivotal transcription factors induced by hypoxia is Hif-1α. However, in serous ovarian cancer (SEOC), Hif-1α expression is not a prognostic biomarker. This study aims to assess the hypothesis that the serine-threonine kinase Nek6 functions as a downstream effector cooperating with Hif-1α in driving ovarian cancer aggressiveness. Nek6 was overexpressed and Hif-1α was silenced in A2780 cells. Nek6 was also stably silenced in Hey cells. The dependence of Nek6 expression on Hif-1α was assayed as a function of hypoxic growth conditions. Nek6 interaction with the cytoskeletal gateway of drug resistance was investigated with far western blot. The co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts was quantified with qPCR in two cohorts of SEOC patients (346 locally treated patients and 344 from the TCGA dataset). Nek6 expression is induced by hypoxia in a Hif-1α dependent fashion. Nek6 directly interacts with GBP-1, thus being a component of the cytoskeletal gateway of drug resistance. Nek6 overexpression increases and silencing decreases the anchorage-independent growth of cultured cells. In SEOC patients, NEK6 expression is significantly correlated with HIF1A. Co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts identifies a subset of SEOC patients characterized by poor outcome and drug resistance. This study demonstrates the functional relevance of Nek6 in the context of the adaptive response to hypoxia in SEOC. This finding may help identify a sub-population of patients at high risk of relapse to standard first-line chemotherapy.
    American Journal of Cancer Research 08/2015; 5(6):1862-77. DOI:10.1158/1538-7445.AM2015-4327 · 4.17 Impact Factor
  • Anna Capozzi · Giovanni Scambia · Alfredo Pontecorvi · Stefano Lello ·
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    ABSTRACT: Prolactin (PRL) is a hormone, mainly secreted by lactotroph cells of the anterior pituitary gland. Recent studies have shown it may also be produced by many extrapituitary cells. Its well-recognized PRL plays an important role in lactation during pregnancy, but it is involved in other biological functions such as angiogenesis, immunoregulation and osmoregulation. Hyperprolactinemia is a typical condition producing reproductive dysfunction in both sexes, resulting in hypogonadism, infertility and galactorrhea. It may be also asymptomatic. Lactotroph adenomas (prolactinoma) is one of the most common cause of PRL excess, representing approximately 40% of all pituitary tumors. Several other conditions should be excluded before a clear diagnosis of hyperprolactinemia is made. Hyperprolactinemia may be secondary to pharmacological or pathological interruption of hypothalamic–pituitary dopaminergic pathways or idiopathic. Stress, renal failure or hypothyroidism are other frequent conditions to exclude in patients with hyperprolactinemia. We will review biochemical characteristics and physiological functions of that hormone. Clinical and pharmacological approach to hyperprolactinemia will also be discussed.
    Gynecological Endocrinology 07/2015; 31(7). DOI:10.3109/09513590.2015.1017810 · 1.33 Impact Factor
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    ABSTRACT: Pelvic organ prolapse occurs in 50% of parous women. Laparoscopic sacrocolpopexy (LSCP) is a common surgical procedure for restoring pelvic anatomy and function. The aim of this study is to evaluate surgical anatomy and anatomical modifications induced by standardized LSCP. Ten fresh female cadavers underwent LSCP, six subsequently underwent standard anatomical dissection, and four had sagittal anatomical dissection. Four cadavers were used as control subjects; two of them underwent standard anatomical dissection, and two had sagittal anatomical dissection. Vesicovaginal space dissection resulted in an arrow-shaped space limited by the trigone and vesical branches of the uterine artery. Rectovaginal space dissection resulted in an inverted V-shaped space marked by the utero-sacral and rectovaginal ligaments, the cranial end of the perineal body and the levator ani muscle. Exposing the longitudinal vertebral ligament through a peritoneal and presacral fascia incision along the medial border of the right common iliac artery allowed the identification and the preservation of the right hypogastric nerve. The anterior mesh stretched across the proximal half of the anterior vaginal wall, and the cervix towards the sacral promontory provided excellent cervix suspension and anterior-vaginal wall support with a concomitant stretch of the pubocervical fascia. The median angle formed by the axis of the infra-levatorial vagina with the axis of the supra-levatorial vagina changed from 142° to 171° and determined the linearization-ventralization of the vaginal canal. LSCP can be performed in a nerve-sparing, standardized fashion, providing excellent apical suspension and anterior vaginal wall support. Neurourol. Urodynam. 9999:1-6, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Neurourology and Urodynamics 07/2015; DOI:10.1002/nau.22806 · 2.87 Impact Factor
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    ABSTRACT: Male gender is a risk factor for medulloblastoma (MB), being also a negative predictor for clinical outcome. This study sought to assess sex differences in tumor biological features and hormone receptor profiles in a cohort of MB patients. Sixty-four MBs and 5 normal cerebella were included in the study. Cell proliferation (Ki67), apoptosis (cleaved caspase-3) and microvessel density (CD31) were evaluated in tumors by immunohistochemistry. Tissues were analyzed for Estrogen Receptor α (ERα), ERβ1, ERβ2, ERβ5 and Androgen Receptor (AR) expression. Results demonstrated sex-specific features in MBs, with tumors from females exhibiting a higher apoptosis/proliferation ratio along with a decreased tumor vascularization compared to males. MBs were negative for ERα and AR, while expressing ERβ isoforms at similar levels between sexes. Altogether these findings indicate that signaling mechanisms that control cell turnover and angiogenesis are more efficiently operating in females compared to males. The lack of sex differences in the hormone receptor profiles suggests that circulating estrogens could be the major determinants of the sexual dimorphism observed in MB features. Here we give molecular support to epidemiological data showing gender differences in MB incidence and outcome, completely defining the hormone receptor profile of the tumors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 07/2015; DOI:10.1111/his.12770 · 3.45 Impact Factor
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    ABSTRACT: To assess the learning curve associated with tele-assisted surgery. We performed a training box-based study, describing speed and accuracy in volunteers performing basic and complex laparoscopic tasks, to assess performance and in the skill acquisition of inexperienced users, using the Telelap Alf X system. Ten surgeons in gynaecology who had never received formal instruction on this new surgical device, completed four modules during a consecutive 3 day training programme. All the participants completed the training programme with a good learning curve. Use of the TELELAP Alf X advanced surgical robotic system is associated with a rapid learning curve among experienced surgeons. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    International Journal of Medical Robotics and Computer Assisted Surgery 06/2015; DOI:10.1002/rcs.1672 · 1.53 Impact Factor
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    ABSTRACT: Mutations in the KCNQ2 gene, encoding for voltage-gated Kv7.2K(+) channel subunits, are responsible for early-onset epileptic diseases with widely-diverging phenotypic presentation, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy. In the present study, Kv7.2 BFNS-causing mutations (W344R, L351F, L351V, Y362C, and R553Q) have been investigated for their ability to interfere with calmodulin (CaM) binding and CaM-induced channel regulation. To this aim, semi-quantitative (Far-Western blotting) and quantitative (Surface Plasmon Resonance and dansylated CaM fluorescence) biochemical assays have been performed to investigate the interaction of CaM with wild-type or mutant Kv7.2 C-terminal fragments encompassing the CaM-binding domain; in parallel, mutation-induced changes in CaM-dependent Kv7.2 or Kv7.2/Kv7.3 current regulation were investigated by patch-clamp recordings in CHO cells co-expressing Kv7.2 or Kv7.2/Kv7.3 channels and CaM or CaM1234 (a CaM isoform unable to bind Ca(2+)). The results obtained suggest that each BFNS-causing mutation prompts specific biochemical and/or functional consequences; these range from slight alterations in CaM affinity which did not translate into functional changes (L351V), to a significant reduction in the affinity and functional modulation by CaM (L351F, Y362C or R553Q), to a complete functional loss without significant alteration in CaM affinity (W344R). CaM overexpression increased Kv7.2 an Kv7.2/Kv7.3 current levels, and partially (R553Q) or fully (L351F) restored normal channel function, providing a rationale pathogenetic mechanism for mutation-induced channel dysfunction in BFNS, and highlighting the potentiation of CaM-dependent Kv7.2 modulation as a potential therapeutic approach for Kv7.2-related epilepsies. Copyright © 2015. Published by Elsevier B.V.
    Biochimica et Biophysica Acta 06/2015; 1852(9). DOI:10.1016/j.bbadis.2015.06.012 · 4.66 Impact Factor

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  • 2015
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 2009-2015
    • Policlinico Universitario Agostino Gemelli
      Roma, Latium, Italy
    • Università degli studi di Cassino e del Lazio Meridionale
      • Department of Sports Science and Health
      Cassino, Latium, Italy
  • 1988-2015
    • The Catholic University of America
      Washington, Washington, D.C., United States
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
    • University of Ferrara
      Ferrare, Emilia-Romagna, Italy
  • 1982-2015
    • Catholic University of the Sacred Heart
      • • School of Obstetrics and Gynecology
      • • School of Oncology
      • • Institute of Clinical Obstetrics and Gynecology
      • • Institute of Neurology
      Milano, Lombardy, Italy
  • 2014
    • Charité Universitätsmedizin Berlin
      • Department of Gynecology
      Berlín, Berlin, Germany
  • 2009-2013
    • Columbus-Gemelli University Hospital
      Roma, Latium, Italy
  • 1994-2013
    • Università Cattolica del Sacro Cuore
      Milano, Lombardy, Italy
  • 2002-2010
    • Sapienza University of Rome
      • Department of Experimental Medicine
      Roma, Latium, Italy
  • 2008
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 2007
    • Belcolle Hospital, Viterbo
      Viterbo, Latium, Italy
  • 2006
    • Gynecologic Oncology Group
      Buffalo, New York, United States
  • 2003
    • Centro Cardiologico Monzino
      Milano, Lombardy, Italy
  • 2001
    • Thomas Jefferson University
      • Department of Pathology, Anatomy & Cell Biology
      Filadelfia, Pennsylvania, United States
    • Università degli Studi dell'Insubria
      Varese, Lombardy, Italy
  • 1986-1987
    • Università degli studi di Cagliari
      Cagliari, Sardinia, Italy