Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: A Single-Institution Experience and a Review of the Literature.

OBJECTIVES: The aim of this study was to evaluate the role of neoadjuvant chemotherapy (NACT) in advanced ovarian carcinoma patients unable to undergo a complete resection during primary debulking surgery. METHODS: From February 2005 to October 2015, all consecutive cases of advanced-stage epithelial ovarian carcinoma at the University of Bari were retrospectively recorded. Of them, patients treated with NACT were collected. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors of survival. RESULTS: Seventy-eight women with advanced-stage epithelial ovarian carcinoma were treated with NACT. On univariate analysis, age (p = 0.003), CA-125 serum level (0.001), response to NACT (p < 0.0001), stage of disease (p = 0.011) and optimal debulking surgery (p < 0.0001) were found to be important prognostic factors related to survival. However, on multivariate analysis, age, response to NACT, CA-125 serum level and optimal debulking surgery remained as independent poor prognostic factors for survival. The median overall and disease-free survival were 31 and 12 months, respectively. CONCLUSIONS: NACT does not compromise survival in patients with stage IIIC and IV ovarian cancer compared to patients treated with primary surgery. Prospective randomized trials comparing NACT to conventional treatment are needed to determine the quality of life and cost/benefit outcomes for women presenting advanced epithelial ovarian cancer.

The new robotic TELELAP ALF-X in gynecological surgery: single-center experience.

BACKGROUND: To evaluate the safety and feasibility of the new robotic TELELAP ALF-X platform in a heterogeneous series of gynecological procedures. METHODS: Between September 2013 and May 2014, 146 patients were enrolled in this Phase II study trial. Patients with presumed benign or borderline adnexal disease, and benign and early stage malignant uterine disease were prospectively included. RESULTS: Median age was 52 years (range 19-79 years), and median BMI was 23.7 (range 17.3-34.0 kg/m(2)). Sixty-two patients (32.5%) underwent mono/bilateral salpingo-oophorectomy or cyst removal (Group A), four patients (2.7%) myomectomy (Group B), 46 patients (31.5%) total hysterectomy (Group C), and 34 (23.3%) endometrial cancer staging (Group D). Median docking time was 7 min (range 3-36). Median OT was 35 min (range 17-145) in the Group A, 40 min (range 10-50) in the Group B, 133 min (range 58-320) in the Group C, and 160 min (range 69-290) in the Group D. Reduction in OT over the study period for hysterectomy (p < 0.001) and adnexal surgery (p < 0.002) was observed. We registered two laparoscopic conversion (3.2%) in the Group A and two (4.3 %) in the Group C. In the Group D, we showed one (2.9%) laparoscopic and two (5.8%) laparotomic conversions. One patient (2.17%) in the Group C was readmitted in the early postoperative period for severe vaginal bleeding. CONCLUSIONS: We report the first series of a novel robotic approach for the treatment of various gynecological conditions. When performed by experienced minimally invasive surgeons, TELELAP ALF-X is feasible and safe. Further studies are mandatory to define the benefits, advantages, and costs of this new robotic approach with respect to others minimally invasive approaches.

Learning a new robotic surgical device: Telelap Alf X in gynaecological surgery.

BACKGROUND: To assess the learning curve associated with tele-assisted surgery. METHODS: 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. RESULTS: All the participants completed the training programme with a good learning curve. CONCLUSIONS: 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.

Telelap Alf-X-Assisted Laparoscopy for Ovarian Cyst Enucleation: Report of the First 10 Cases.

This prospective single-institutional clinical trial sought to assess the safety and feasibility of laparoscopic benign ovarian cyst enucleation with a novel robotic-assisted laparoscopic system. Here we report a series of 10 patients treated using the Telelap ALF-X system in the first clinical application on patients at the Division of Gynecologic Oncology, Catholic University of the Sacred Heart of Rome. The primary inclusion criterion was the presence of monolateral ovarian cyst without a preoperative assessment suspicious for malignancy. Intraoperative data, including docking time, operative time, estimated blood loss, intraoperative and perioperative complications, and conversion to either standard laparoscopy or laparotomy, were collected. The cysts were removed with an ovary-sparing technique with respect to conservative surgical principles. The median operative time was 46.3 minutes, and patients without postoperative complications were discharged at 1 or 2 days after the procedure. Telelap ALF-X laparoscopic enucleation of benign ovarian cysts with an ovary-sparing technique is feasible, safe, and effective; however, more clinical data are needed to determine whether this approach can offer any other benefits over other minimally invasive surgical techniques.

Borderline epithelial tumors of the ovary: Experience of 55 patients.

The objective of the present study was to evaluate the clinicopathological features and the survival time estimates in patients treated for borderline ovarian tumors (BOTs). A retrospective review of all patients treated for BOTs at the University of Bari (Bari, Italy) between 1991 and 2011 was performed. Data were obtained from hospital records and gynecological oncology charts. A total of 55 patients were identified. The median age was 40 years (range, 13-79 years). The majority of the patients (85.5%) exhibited International Federation of Obstetrics and Gynecology (FIGO) stage I disease and the remainder exhibited FIGO stage II/III (7.3% in each stage). Serous histology was found in 60.0% of the cases and an elevation of the cancer antigen-125 serum level occurred in 23.6% of the cases. All patients underwent surgery and 3.7% received chemotherapy. In total, 10.9% exhibited recurrence and the median survival rate was 39 months. The median survival time and the five-year survival rate were 42 months (range, 16-84 months) and 97%, respectively. Therefore, BOTs have an excellent prognosis. Conservative surgery should be considered for patients of reproductive age who desire preservation of fertility. A long-term follow-up is highly recommended for these tumors.

Hysterosalpingo-contrast-sonography (HyCoSy) in the assessment of tubal patency in endometriosis patients.

OBJECTIVE: Tubal patency in women with endometriosis has traditionally been evaluated by laparoscopy. The aim of this study was to investigate the accuracy of hysterosalpingo-contrast-sonography (HyCoSy) in the assessment of tubal patency in these women. STUDY DESIGN: A retrospective study was conducted at Physiopathology of Human Reproduction Unit. Infertile women who underwent HyCoSy and then a laparoscopy (dye test) within 6 months from the HyCoSy were included. Tubal patency was assessed by HyCoSy and the findings were compared with the results of laparoscopy, which was considered the gold standard for assessment of tubal patency. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) and positive and negative likelihood ratios (Lh+, Lh-) were calculated including the 95% confidence interval (CI). RESULTS: A total of 1452 women underwent HyCoSy and 126 of them received a laparoscopy within 6 months from the HyCoSy. Of the 126 women, 42 (33.3%) had a diagnosis of pelvic endometriosis and 84 (66.7%) had no endometriosis. In the endometriosis population, HyCoSy showed a sensitivity, specificity, PPV, NPV, Lh+ and Lh- of 85% (95% CI 62-96), 93% (95% CI 82-97), 81% (95% CI 58-94), 94% (95% CI 84-98), 12.6 (95% CI 4.8-33) and 0.15 (95% CI 0.05-0.4) respectively. In the non-endometriosis group, HyCoSy showed a sensitivity, specificity, PPV, NPV, LR+ and LR- of 85% (95% CI 65-95), 93% (95% CI 87-96), 71% (95% CI 53-85), 97% (95% CI 92-99), 13.2 (95% CI 6.9-25) and 0.15 (95% CI 0.06-0.3) respectively. The diagnostic accuracy of HyCoSy was 91% in the endometriosis group and 92% in the non-endometriosis patients. CONCLUSIONS: HyCoSy showed high accuracy in evaluating tubal patency in infertile non-endometriosis women and in those affected by endometriosis.

Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial.

BACKGROUND: Carboplatin plus paclitaxel administered every 3 weeks is standard first-line chemotherapy for patients with advanced ovarian cancer. A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial. The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks. METHODS: We did a multicentre, randomised, phase 3 study at 67 institutions in Italy and France. Women with FIGO stage IC-IV ovarian cancer, an ECOG performance status of 2 or lower, and who had never received chemotherapy were randomly allocated in a 1:1 ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175 mg/m(2)) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m(2)) every week for 18 weeks. Randomisation was done by computer-based minimisation, stratified by centre, residual disease after surgery, and ECOG performance status. The study was not blinded. Coprimary endpoints were progression-free survival and quality of life (assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI] score), and analysis was by modified intention to treat. This report presents the final analysis. The study is registered with ClinicalTrials.gov, number NCT00660842. FINDINGS: 822 patients were enrolled into the study between Nov 20, 2008, and March 1, 2012; 12 withdrew their consent immediately after randomisation and were excluded, and 810 were eligible for analysis. 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule. After median follow-up of 22·3 months (IQR 16·2-30·9), 449 progression-free survival events were recorded. Median progression-free survival was 17·3 months (95% CI 15·2-20·2) in patients assigned to treatment every 3 weeks, versus 18·3 months (16·8-20·9) in women allocated to the weekly schedule (hazard ratio 0·96, 95% CI 0·80-1·16; p=0·66). FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p<0·0001); with treatment every 3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores remained stable. Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3-4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen. INTERPRETATION: A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer. FUNDING: None.

The use of different size-hysteroscope in office hysteroscopy: our experience.

PURPOSE: To evaluate the successful rate and patient acceptance of different-sized hysteroscope in office hysteroscopy. METHODS: We retrospectively evaluated 900 office hysteroscopy performed in ambulatory setting using three different hysteroscopes: 5 mm Hamou II (n = 300), 5 mm Bettocchi (n = 300) and 4 mm Bettocchi (n = 300). Endpoints of our study were the successful rate of hysteroscopy, the eventual side effects/complication and the pain intensity experience from the patients using visual analog scale (VAS). RESULTS: Use of 4 mm Bettocchi leads to a higher rate of successfully performed hysteroscopy (99%, n = 297) and statistically significant when compared to the 5 mm Hamou (95%, n = 285) and to the 5 mm Bettocchi (96%, n = 288) (4 mm Bettocchi vs. 5 mm Bettocchi p < 0.05; 4 mm Bettocchi vs. 5 mm Hamou II p < 0,001; 5 mm Bettocchi vs. 5 mm Hamou II ns). Moreover, the VAS score was higher using 5 mm Hamou II (5.72 ± 1.99) and statistically significant when compared to the 4 mm Bettocchi (3.06 ± 2.14) and to the 5 mm Bettocchi (4.27 ± 1.88) (A vs. B p < 0.05; A vs. C p < 0.001; B vs. C p < 0.001). CONCLUSIONS: Our result suggests that the hysteroscope size plays a pivotal role in the acceptance and for the success of office hysteroscopy.

Two cases of complete hydatidiform mole and coexistent live fetus.

The aim of this study was to report the clinical features, management, and outcome of complete hydatidiform mole with a coexisting viable fetus. Two cases are reported. In both cases ultrasound examination demonstrated a normally growing live fetus alongside a normal placenta and an additional intrauterine echogenic mass with features of hydatidiform mole. The hCG levels were significantly increased and fetal karyotypes were normal. A cesarean section performed at 28 weeks' gestation in the first case and at 26 weeks' gestation in the second one resulted in the delivery of live normal infant and two adjoining placentas in both cases. Microscopic examination of the abnormal placentas confirmed complete hydatidiform mole. The babies did well and serial maternal serum hCG levels showed a declining trend and were undetectable by a few months after delivery. Continuation of a twin pregnancy with complete hydatidiform mole (CHMF) is an acceptable option. There is, although, an increased risk of developing maternal and fetal complications. Close surveillance of an ongoing pregnancy is compulsory to detect potential early signs of complications.

Increased nuchal translucency and short femur length as possible early signs of osteogenesis imperfecta type III.

OBJECTIVE: this paper reports an association between an increased Nuchal Translucency (NT) and Osteogenesis Imperfecta (OI), a type of skeletal dysplasia. Measurement of fetal NT at 10-14 weeks of gestation is a sensitive and effective screening method for chromosomal abnormalities. METHODS: a 35-year- old Caucasian woman in her fourth pregnancy was referred to our clinic for an ultrasound scan at 12 weeks of gestation, that confirmed increased Nuchal Translucency. Chorionic villi sampling was performed, showing a normal karyotype. The patient was evaluated by a team of experienced ultra sonographers for pregnancy follow-up at our Department, that is a tertiary center. RESULTS: in our case the ultrasound scan at 12 week of gestation revealed only an increased NT (3 mm). Cytogenetic analysis on chorionic villi demonstrated a normal male karyotype. US follow-up, performed every 3-4 weeks, confirmed normal anthropometric parameters except for shortening of both femurs, but at 23 weeks an incorrect attitude of the feet was revealed. A clinical and radiographic diagnosis of OI type III was made only at birth, and through follow-up continuing to date. DISCUSSION: NT screening was successful for chromosomal abnormalities at 11-14 weeks of gestation. An increased NT thickness is also associated with numerous fetal anomalies and genetic syndromes in a chromosomally normal fetus. In our case there were no sonographic signs of imperfect osteogenesis in the first trimester, although there was an increased NT with a normal karyotype. CONCLUSION: currently, in literature, there are not other cases of OI type III associated with an increased NT. Our report is the first to suggest an association between an increased nuchal translucency, short femur length and osteogenesis imperfecta type III.

Regulation of the expression of CLU isoforms in endometrial proliferative diseases.

Clusterin (CLU) is a nearly ubiquitous multifunctional protein synthesized in different functionally divergent isoforms, sCLU and nCLU, playing a crucial role by keeping a balance between cell proliferation and death. Studying in vivo CLU expression we found a higher mRNA expression both in neoplastic and hyperplastic tissues in comparison to normal endometria; in particular, by RT-qPCR we demonstrated an increase of the specific sCLU isoform in the neoplastic and hyperplastic endometrial diseases. On the contrary, no CLU increase was detected at the protein level. The CLU gene transcriptional activity was upregulated in the hyperplastic and neoplastic tissues, indicating the existence of a fine post-trans-criptional regulation of CLU expression possibly responsible for the protein decrease in the malignant disease. A specific CLU immunoreactivity was present in all the endometrial glandular cells in comparison to the other cellular compartments where CLU immunoreactivity was lower or absent. In conclusion, our results suggest the existence of a complex regulatory mechanism of CLU gene expression during the progression from normal to malignant cells, possibly contributing to endometrial carcinogenesis. Moreover, the specific alteration of the sCLU:nCLU ratio associated with the pathological stage, suggests a possible usage of CLU as molecular biomarker for the diagnosis/prognosis of endometrial proliferative diseases.

Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO--the MIMOSA study.

PURPOSE: To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response. RESULTS: Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35 U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti-anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response. CONCLUSION: Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS.

Using a 16-French resectoscope as an alternative device in the treatment of uterine lesions: a randomized controlled trial.

OBJECTIVE: To compare a 16-French resectoscope with a 22-French resectoscope and a 15-French hysteroscope for the treatment of uterine cavity lesions. METHODS: This was a prospective, randomized study of women with endometrial polyps or submucous myomas treated with a 16-French resectoscope, a traditional 22-French resectoscope, or a 15-French hysteroscope. The operating time, volume of distension medium delivered, discharge time, and patient discomfort by visual analog scale were recorded. Data were compared by one-way and two-way analysis of variance as appropriate. RESULTS: Four hundred one women were included in the analysis. All four parameters showed lower values in the 16-French resectoscope group (142 women) compared with the 15-French hysteroscope group (132 women; P<.01). The mean operating time was 10.87±2.87 minutes in the 22-French group (127 women), 8.33±2.94 minutes in the 16-French group, and 17.11±6.86 minutes in the 15-French group. The mean volume of distension medium delivered was 1,043±230 mL in the 22-French group, 991±442 mL in the 16-French group, and 1,489±566 mL in the 15-French group. The mean discharge time was 1.99±0.72 hours in the 22-French group, 1.08±0.18 hours in the 16-French group, and 1.89±0.68 hours in the 15-French group. Finally, the mean visual analog scale scores were 2.10±0.97 in the 22-French group, 1.93±1.03 in the 16-French group, and 4.00±1.61 in the 15-French group. An analysis of patients subdivided according to the lesion size (less than 1.5 cm and more than 1.5 cm in diameter) showed similar results. CONCLUSION: The new 16-French resectoscope is effective for the "see and treat" approach for both small (less than 1.5 cm diameter) and large (more than 1.5 cm diameter) uterine lesions.

Correlation between ultrasound diagnosis and autopsy findings of fetal malformations.

OBJECTIVE: to compare ultrasound (US) and autopsy findings of fetal malformations in second trimester terminations of pregnancy to evaluate the degree of agreement between US and fetal autopsy. METHODS: in this study, all second trimester termination of pregnancy between 2003-2010 were considered. US and autopsy findings were compared and all cases were classified into five categories according to the degree of agreement between US and pathology (A1: full agreement between US and autopsy; A2: autopsy confirmed all US findings but revealed additional anomalies 'rarely detectable' prenatally; B: autopsy demonstrated all US findings but revealed additional anomalies 'detectable' prenatally; C: US findings were only partially demonstrated at fetal autopsy; D: total disagreement between US and autopsy). RESULTS: 144 cases were selected. In 49% of cases there was total agreement between US and autopsy diagnosis (A1). In 22% of cases additional information were about anomalies 'not detectable' by US (A2). In 12% of cases autopsy provided additional information about anomalies not observed but 'detectable' by US (B). In 13% of cases some anomalies revealed at US, such as valve insufficiencies, pericardial and pleural effusions, were not verified at autopsy (C). Total lack of agreement was noted only in 4% of cases (D). Main areas of disagreement concerned cardiovascular, CNS and complex malformations. The degree of agreement was higher if malformations were diagnosed in a tertiary center. CONCLUSIONS: this study shows an overall high degree of agreement between definitive US and autopsy findings in second trimester termination of pregnancy for fetal malformations. Autopsy reveals to be the best tool to diagnose malformations and often showed other abnormalities of clinical importance not detected by US, but sometimes also US could provide additional information about functional anomalies because US is a dynamic examination.

Mitochondrial DNA content and mass increase in progression from normal to hyperplastic to cancer endometrium.

BACKGROUND: An increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1α signalling pathway was previously reported in type I endometrial cancer. The aim of this study has been to evaluate if mtDNA content and the citrate synthase (CS) activity, an enzyme marker of mitochondrial mass, increase in progression from control endometrium to hyperplasia to type I endometrial carcinoma. RESULTS: Given that no statistically significant change in mtDNA content and CS activity in endometrium taken from different phases of the menstrual cycle or in menopause was found, these samples were used as control. Our research shows, for the first time, that mtDNA content and citrate synthase activity increase in hyperplastic endometrium compared to control tissues, even if their levels remain lower compared to cancer tissue. In particular, mtDNA content increases seem to precede increases in CS activity. No statistically significant change in mtDNA content and in CS activity was found in relation to different histopathological conditions such as grade, myometrial invasion and stage. CONCLUSION: MtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma.

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET).

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Ulipristal acetate versus leuprolide acetate for uterine fibroids.

BACKGROUND: The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. METHODS: In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%. RESULTS: Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate). CONCLUSIONS: Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.).

Follicular loss in endoscopic surgery for ovarian endometriosis: quantitative and qualitative observations.

OBJECTIVE: To identify a possible marker of follicular depletion in relation to some histologic parameters of endometriotic cysts. DESIGN: Prospective study. SETTING: Università Cattolica del Sacro Cuore, Operative Division of Endocrinological Gynecology. PATIENT(S): Seventy-seven patients (aged 20-40 years) with endometrioma. INTERVENTION(S): Patients underwent laparoscopic surgery for ovarian endometriosis. MAIN OUTCOME MEASURE(S): After excision of the cyst wall, involuntarily removed follicles were correlated with age at surgery and with intrinsic histologic parameters of the specimen (thickness and composition of capsule; size of cyst). RESULT(S): There was a statistically significant relationship between patient age and number of follicles in the histologic section, a statistically significant inverse relationship between size of cyst and number of follicles, and no significant correlation between thickness of the capsule and number of follicles. Fibroblastic-type capsule, most frequently found in younger patients, was associated with removal of a significantly higher number of follicles. CONCLUSION(S): Our study suggests that patient age and cyst dimension are related to the histologic composition of the capsule, which is a marker of the aggressiveness of the cyst itself.

Carcinosarcoma of the ovary: analysis of 13 cases and review of the literature.

OBJECTIVES: The aim of this study was to evaluate our experience with patients affected by ovarian carcinosarcoma. PATIENTS AND METHODS: During a 16-year period, data on 13 patients with ovarian carcinosarcoma were collected. They were obtained from hospital charts and follow-up visits. Survival curves were estimated by the Kaplan-Meier method and compared using the log-rank test. All tests were two-tailed with p values < 0.05 considered significant. RESULTS: Our study was conducted on 13 patients with ovarian carcinosarcoma referred to our unit, during an observation time of about 16 years (March 1994 to October 2010). An improved survival was observed in patients treated with optimal cytoreductive surgery with residual tumors <2 cm (30 vs. 5 months; p = 0.042). All patients underwent adjuvant chemotherapy based on the combination of cisplatin, epirubicin and ifosfamide (PEI) and taxol and carboplatin (TAX-CBDCA) regimen. Overall survival of the patient population was 17 months. CONCLUSIONS: Similarly to data published in the literature, we observed that malignant mixed mullerian ovarian tumors are very aggressive and are usually diagnosed at an advanced age and at an advanced stage of disease. Therefore, due to the rarity of the tumor we would like to add our series to those already published in the literature, although our treatment recommendations are actually based upon retrospective studies with a small patient population.

Changes in the management and outcome of central nervous system involvement from ovarian cancer since 1994.

OBJECTIVE: To identify differences in the management and outcome of patients with central nervous system metastases from epithelial ovarian cancer. METHODS: The clinical and pathologic characteristics, treatment, and outcome of 23 patients with brain metastases from epithelial ovarian cancer who were treated during 1982-1994 were compared with those of 20 patients treated during 1995-2010 at the same center. RESULTS: No differences were found in terms of primary tumor characteristics, time interval from ovarian cancer diagnosis to brain involvement diagnosis, sites of metastasis, and presence of extracranial disease. The main difference between the 2 groups was the therapeutic approach. During 1982-1994, most patients received radiotherapy only, whereas most patients during 1995-2010 underwent surgical resection followed by radiotherapy and/or chemotherapy. The duration of survival during 1982-1994 was 5 months, which was significantly shorter than the duration of survival (18 months) during 1995-2010. CONCLUSION: An aggressive multimodal treatment approach might prolong the survival of patients with brain involvement from ovarian cancer.