Giovanni Scambia

Catholic University of the Sacred Heart , Milano, Lombardy, Italy

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Publications (576)2237.04 Total impact

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    ABSTRACT: Objectives: This retrospective, multicentric study investigates quality-of-life issues and emotional distress in gynecological cancer survivors submitted to pelvic exenteration (PE). Methods: The Global Health Status scale of European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30; the EORTC QLQ-CX24 (CX24), and EORTC QLQ-OV28 questionnaires were administered at least 12 months from surgery only in women with no evidence of further recurrence after PE. Statistical analysis was performed by the analysis of variance (for repeated measures. Results: Ninety-six subjects affected by gynecological malignancies receiving PE were enrolled in the study. Anterior PE was performed in 47 patients (49%), posterior PE was performed in 29 cases (30.2%), and total PE performed in 20 women (20.8%). In 38 cases (39.6%), a definitive colostomy was performed. Urinary diversion with continent pouch was created in 11 patients. (11.5%), whereas in the remaining cases, a noncontinent pouch was reconstructed. Patients showed a significant discomfort in attitude to disease (71.5 ± 4.7), body image (48.9 ± 6.4), financial difficulties (56.2 ± 5.8), gastrointestinal symptoms (constipation, 47.8 ± 5.1; diarrhea, 62.4 ± 6.6; appetite loss, 43.6 ± 6.7), insomnia (64.5 ± 6.6), Global Health Status (64.6 ± 3.8), physical functioning (65.8 ± 4.6), role functioning (58.8 ± 5.8), and emotional functioning (67.4 ± 4.2). A higher number of ostomies (hazard rate [HR], 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of poorer Global Health Status scores. Older age (HR, 11.235; P = 0.003), vaginal/vulvar cancer (HR, 7.369; P = 0.013), total/posterior PE (HR, 7.393; P = 0.013), higher number of ostomies (HR, 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of lower body image levels. Conclusions: Long-term psycho-oncological support is strongly recommended. The reduction of ostomies seems the most effective way to improve patients' quality of life.
    No preview · Article · Jan 2016 · International Journal of Gynecological Cancer
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    ABSTRACT: The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2 modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERα expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ERα-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2 on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC.
    Preview · Article · Jan 2016 · Oncotarget
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    ABSTRACT: Introduction: The aim of this study was to identify, quantify and evaluate the use of robotic materials and operating theatre times in Telelap ALF-X robotic hysterectomy. Materials and methods: Cost analysis was performed on 81 patients who underwent a Telelap ALF-X robotic hysterectomy. Data were collected during a phase II study trial conducted at the University Hospital A. Gemelli, Catholic University, Rome. According to micro-costing technique, surgical team costs, materials and operating theatre usage were recorded during each surgical intervention. Cost data were provided by the hospital's accounting office. Probabilistic sensitivity analysis was carried out in order to test the robustness of the results by assuming an Inv-norm random variable. Results: The base case analysis showed a cost/patient of €3391.82. The new robotic device requires a low consumption of robotic materials. Sensitivity analysis showed that the most sensitive cost driver was use of the operating theatre. Conclusion: This study shows that Telelap ALF-X robotic hysterectomy is feasible and safe and could offer specific advantages in terms of cost. Copyright © 2016 John Wiley & Sons, Ltd.
    No preview · Article · Jan 2016 · International Journal of Medical Robotics and Computer Assisted Surgery
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    ABSTRACT: Objective: To investigate the feasibility of laparoscopic splenectomy in recurrent ovarian cancer (ROC) patients with isolated spleen metastasis. Methods: From February 2013 to May 2015, 8 women with an isolated platinum sensitive splenic relapse of ovarian cancer were submitted to laparoscopic splenectomy. Results: All patients underwent laparoscopic splenectomy without conversion to open approach. The median estimated blood loss (EBL) was 100 ml (50 - 200). The median operating room time was 200 minutes (80-275). No intraoperative complication occurred and no intraoperative blood transfusions were required. The median length of hospital stay was 3 days (2-5). For all patients a complete tumor resection was achieved. The median time from surgery to adjuvant chemotherapy was 16 days (14-24). After a median follow-up of 23 months (6-32), no secondary recurrence or death of disease has been observed. Conclusions: Our report shows that a laparoscopic approach to remove the spleen is feasible for selected patients with a splenic relapse of ovarian cancer when performed in tertiary referral centers by well-trained surgeons.
    No preview · Article · Jan 2016 · Journal of Minimally Invasive Gynecology
  • Anna Fagotti · Federica Perelli · Luigi Pedone · Giovanni Scambia
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    ABSTRACT: Minimally invasive surgery (MIS) currently is performed to stage and treat ovarian cancer at different stages of disease; however, the higher level of evidence from existing studies is IIB. Despite the absence of randomized controlled trials, MIS represents a safe and adequate procedure for treating and staging early ovarian cancer, and its use has increased significantly in clinical practice. Major concerns are related to minimizing tumor disruption or dissemination, removing the adnexal mass intact, adequate retroperitoneal staging, and fertility-sparing surgery for young patients. The main goal for patients with advanced ovarian cancer is to determine the best therapeutic strategy by evaluating the risks and benefits of primary debulking surgery versus neoadjuvant chemotherapy followed by interval debulking surgery. The use of staging laparoscopy in patients with advanced epithelial ovarian cancer appears to be the most researched and accepted approach. Regarding other types and stages of ovarian cancer, although the evidence is very promising, clinical trials performed by expert gynecologic oncology surgeons in referral centers are still needed to prove the efficacy of such an approach in these patients. In particular, MIS has provided an opportunity to remove localized recurrences, with both retroperitoneal and intraperitoneal diffusion.
    No preview · Article · Jan 2016 · Current Treatment Options in Oncology
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    ABSTRACT: Background: The aim of the present study was to evaluate the efficacy of tertiary and quaternary cytoreduction in recurrent ovarian cancer patients. Patients and Methods: Between January 1997 and December 2014, 53 patients were submitted to cytoreductive surgery for second and third ovarian cancer recurrence at our Unit. Results: Median age at first diagnosis was 48 years (range= 20-69). Forty-six patients (86.8%) underwent tertiary cytoreduction. At the time of surgery, isolated and diffuse disease was observed in 48 (90.6%) and 5 (9.4%) patients, respectively. Complete and optimal cytoreduction was obtained in 41 (77.5%) and in 1 (1.9%) patients, respectively. We did not observe any statistically significant survival differences according to residual tumor. Patients with TFI > 12 months showed longer PFS (38 vs. 7 months, p< 0.002) than those with TFI < 12 months. In 18 of these patients a third recurrence was observed. In 12 patients (66.7%) a complete quaternary cytoreduction was performed. Longer PFS (16 vs. 21 months; p= 0.032) and OS (152 vs. 116 months; p= 0.015) in patients submitted to cytoreduction with respect to those treated with chemotherapy were observed. Conclusion: Our data suggest that selected ovarian cancer patients who develop a secondary and tertiary recurrence may benefit from additional cytoreductive attempts. The benefit seems to be greater in patients with TFI > 12 months showing a single-site recurrence disease, in which complete cytoreduction is achievable. Further studies are required to better-define the role of tertiary and quaternary cytoreduction in recurrent ovarian cancer patients.
    No preview · Article · Dec 2015 · Anticancer research
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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.
    No preview · Article · Dec 2015 · Italian Journal of Pediatrics
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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.
    No preview · Article · Nov 2015 · American journal of obstetrics and gynecology
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    ABSTRACT: Due to their high prevalence and related morbidity, uterine myomas constitute a group of gynecological pathologies largely studied in all clinical, diagnostic, and therapeutic aspects. They have been widely evaluated with a large series of imaging techniques. In fact, ultrasound (also saline infusion sonohysterography) and magnetic resonance imaging (MRI) are considered the optimal methods to assess uterine fibroids in terms of number, volume, echostructure, location, relation with endometrial cavity and uterine layers, vascularization, and differential diagnosis with other benign (adenomyosis) and malignant myometrial pathologies. Nevertheless, further studies are required to fill some gaps such as the absence of a common and sharable sonographic terminology and methodology to scan the myometrium, as well as imaging parameters for differentiation of typical myomas from smooth tumors of unknown malignant potential (STUMP) and leiomyosarcomas.
    No preview · Article · Nov 2015 · Best practice & research. Clinical obstetrics & gynaecology
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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.
    No preview · Article · Nov 2015 · The Lancet Oncology
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    ABSTRACT: Study design: To compare the surgical and clinical outcomes of patients affected by early stage endometrial cancer treated using the TELELAP ALF-X platform versus conventional laparoscopic surgery. Design: Single-institutional retrospective cohort study (Canadian Task Force classification II-2). Setting: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy. Patients: The study involved 89 patients affected by early stage endometrial cancer who underwent elective surgical staging between October 2013 to September 2014. Among them, 43 underwent Telelap ALF-X staging (48.3%) (ALF-X group), and 46 underwent conventional laparoscopic staging (51.7%) (Laparoscopic group). Interventions: All selected patients underwent laparoscopic staging with radical hysterectomy (Class A sec Querleu-Morrow), bilateral salpingo-oophorectomy and pelvic lymphadenectomy, if required. Patients in which lymphadenectomy was not required were collected into a subgroup named Group 1; the patients who underwent a pelvic lymphadenectomy were included in Group 2 for each type of surgical approach. Measurements and main results: In Groups 1 and 2 of the ALF-X staging, the median operative times (OTs) were 128 min (range 69-260 min) and 193 min (range 129-290 min) respectively. In Groups 1 and 2 of the Laparoscopic staging, the median operative times (OTs) were 82 min (range 25-180 min) and 104 min (range 36-160 min), respectively. The difference between ALF-X OT and LPS OT was statistically significant for both group (p-value .000). In Group 1 of the ALF-X staging, one conversion to standard laparoscopy occurred (2.3%); instead in Group 2, 2 conversions to laparotomy (4.7%) occurred (p-value .234). No conversion to laparotomy was recorded in the Laparoscopic staging. The post-operative complications recorded included one pelvic hematoma (2.3%) in the ALF-X group (Group 1) and one subocclusion and one pulmonary edema (4.3%) in the Laparoscopic one (Group 1). Conclusion: Basing on operative outcomes and complication rates, our results suggest that the Telelap ALF-X approach is feasible and safe in endometrial cancer staging. However further studies are needed to definitively assess the role of Telelap ALF-X early stage endometrial cancer staging.
    No preview · Article · Nov 2015 · Journal of Minimally Invasive Gynecology
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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.
    Full-text · Article · Oct 2015 · Fertility and sterility
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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.
    No preview · Article · Oct 2015 · Journal of Minimally Invasive Gynecology
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    ABSTRACT: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases.
    Full-text · Article · Oct 2015 · Value in Health
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    ABSTRACT: Objective: We present a very rare case of focal metastasis of endometrial cancer to the small bowel entirely managed laparoscopically. Methods: A 58 year-old patient with a FIGO I B G2 N0 stage endometrial cancer was found to have a vaginal cuff recurrence and an isolated distant metastasis to the small bowel 13 months after primary treatment. In this video we show a fully laparoscopic management mainly focusing on the small bowel resection with intracorporal anastomosis. A laparoscopic partial colpectomy was also performed. Results: Operative time was 180 min. Intraoperative blood loss was less than 100 cc. The operation was performed successfully with no intra-operative complications. Pathological finding showed recurrent disease in the vaginal cuff and in the resected small bowel segment with free resection margins in both specimens and three mesenteric local nodes negative for metastasis. Patient was discharged on day three and 26 days later started adjuvant chemotherapy. After a 16 months follow-up period, the patient is still disease free and in good general conditions. Conclusion: This case shows a successful laparoscopic management of a case of recurrent endometrial cancer requiring complex surgical procedures.
    No preview · Article · Sep 2015 · Journal of Minimally Invasive Gynecology
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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.
    No preview · Article · Sep 2015 · The British journal of radiology
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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.
    No preview · Article · Sep 2015 · Journal of Minimally Invasive Gynecology
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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.
    Preview · Article · Sep 2015 · PLoS ONE
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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.
    Full-text · Article · Sep 2015 · American Journal Of Reproductive Immunology
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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.
    Full-text · Article · Aug 2015 · Expert Review of Molecular Diagnostics

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  • 1982-2016
    • 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
  • 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
  • 1994-2015
    • Università Cattolica del Sacro Cuore
      Milano, Lombardy, 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
  • 2009-2013
    • Columbus-Gemelli University Hospital
      Roma, Latium, Italy
  • 2011
    • The American University of Rome
      Roma, Latium, 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
  • 2004
    • Università degli Studi di Siena
      • Department of Molecular & Developmental Medicine
      Siena, Tuscany, Italy
  • 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