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Objective To evaluate the misdiagnosis between endometrial biopsy and definitive surgical pathology and to assess whether the failure in recognizing preoperatively high-risk endometrial carcinoma (EC) can impact oncological outcomes. Study design A retrospective study was conducted to evaluate patients with EC diagnosed by preoperative endometrial biopsy who subsequently underwent surgical staging between 2006 and 2013 at our institution. In patients with a surgical diagnosis of high-risk EC, histotype and grade change between the endometrial biopsy and surgical specimen (discordance diagnosis) were evaluated and correlated to survival outcomes. Cox's regression model for multivariable analysis was used to evaluate the effect of several variables (age, stage, discordance in diagnosis, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy) on the survival rate. Results Data from 447 patients were reviewed. Among 109 women with surgical diagnosis of high-risk EC, 35 (32.1%) were preoperatively misdiagnosed. Of these 35 women, 24 (68.6%) cases were upgraded to grade 3, and 11 (3.4%) were upgraded to serous or clear cell type in the definitive specimen. The 5-year overall survival (OS; 70.2 vs. 86.8%; p =0.029), disease-specific survival (DSS; 72.5 vs. 88.2%; p =0.039) and recurrence free survival (RFS; 62.6 vs. 82.5%; p =0.024) were significantly lower in the high-risk EC patients who were preoperatively undiagnosed in the endometrial biopsy compared with patients with an appropriate preoperative histological diagnosis. Controlling for age, stage, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy, multivariable analysis revealed that discordance in diagnosis was associated with poorer survival outcomes. Conclusion Failure to recognize preoperatively high-risk ECs is associated with worse outcomes.

Objective The objective of this study is to compare ovarian function and surgical outcomes between patients affected by benign uterine pathologies submitted to total laparoscopic hysterectomy (TLH) plus salpingectomy and women in which standard TLH with adnexal preservation was performed. Methods We retrospectively compared data of 79 patients who underwent TLH plus bilateral salpingectomy (group A), with those of 79 women treated by standard TLH without adnexectomy (sTLH) (group B). Ovarian reserve modification, expressed as the difference between 3months post-operative and pre-operative values of Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Antral Follicle Count (AFC), mean ovarian diameters and Peak Systolic Velocity (PSV), was recorded for each patient. For each surgical procedure, operative time, variation of hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were recorded as secondary outcomes. Results According to our post-hoc analysis , this equivalence study resulted to have a statistical power of 96.8%. Significant difference was not observed between groups with respect to ΔAMH ( p = 0.35 ), ΔFSH ( p = 0.15 ), ΔAFC ( p = 0.09 ), Δ mean ovarian diameters ( p = 0.57 ) and ΔPSV ( p = 0.61 ). In addition, secondary outcomes such as operative time ( p = 0.79 ), ΔHb ( p = 0.41 ), postoperative hospital stay ( p = 0.16 ), postoperative return to normal activity ( p = 0.11 ) and complication rate also did not show any significant difference. Conclusions The addition of bilateral salpingectomy to TLH for prevention of ovarian cancer in women who do not carry a BRCA1/2 mutations do not show negative effects on the ovarian function. In addition, no perioperative complications are related to the salpingectomy step in TLH.

A novel anion exchange membrane adsorber is presented which shows excellent impurity removal under different buffer conductivities ranging from 2 to 27 mS/cm. The membrane utilizes a primary amine ligand (polyallylamine) and was designed specifically to bind impurities at high salt concentrations. Studies with DNA, endotoxin, and virus spiked into buffer at varying salt conditions were done, resulting in clearance of >3, 4, and 4 LRV, respectively, with negligible change on increasing salt up to 27 mS/cm conductivities. Verification of virus removal in mAb feedstocks is also shown. The data are compared with other membrane adsorbers and a conventional resin which utilize traditional chemistries to demonstrate improved purification performance with the primary amine ligand. Additional data on scale-up of the membrane adsorber device is discussed. A stacked flat-sheet design was implemented to ensure linear scale-up of performance using bovine serum albumin (BSA) as a model. The linearly scalable device, coupled with the highly effective membrane for virus, DNA, and endotoxin removal, represents a step forward in polishing technology for the purification of monoclonal antibodies and recombinant proteins.

SAR interferometry based on Permanent Scatterers (PS-InSAR(TM)) is used here to study the present crustal mobility of a large area of NW Italy, in the Piemonte region. Thirty-eight satellite scenes (ERS SAR), taken from May 1992 to January 2001, were analysed for detecting more than 2million PS on the study area. Continuous velocity surface maps (Iso-Kinematic Maps: IKM) were obtained from geo-statistical and spatial cluster techniques (Hot Spot analysis) of PS ''short-period'' data, to identify relative ground motions and to compare them with ''long-period'' tectonic mobility trends, i.e. those inferred at regional scale over geological times (some million years). The comparison was made by individuation of homogeneous kinematic areas, represented in the IKM, and characterization of the boundaries between them (Iso-Kinematic Boundaries: IKB). The IKB were used as tools to asses if the PS-InSAR data on present-day crustal mobility could fit with the distribution of real tectonic structures or field geological elements. IKM were drawn for uplifting geological sectors of Piemonte (Maritime Alps, Gran Paradiso, Langhe) where moderate to very low seismicity is recorded, and gravitational instabilities of rock mass on mountain slopes are widespread. The land sectors have been chosen in order to test the suitability of IKM in very different geo-morphological conditions. Different types of correspondence between the IKM and the geological kinematic trend were found:-a first type in which the kinematic trend of short-period (a decade of years, i.e. the PS-InSAR detection time span) is in agreement with a long-period tectonic trend (some million years) and seem to be driven by well known faults subparallel to the IKB. These kinematic trends can be hidden by the slope movement due to gravitational instabilities; -a second type in which the kinematic trend of short-period does not strictly correspond to the long-period trend, but can be considered as minor-order, uplifting-subsidence cycles, even if in contrast with the long-period kinematic trend. Alternatively, the short-period kinematic trends could reflect the action of deep-seated geological forces or structures, not yet known or inferable (at least with the recorded PS-InSAR velocities) on the basis of the available geological data and models. Lingua abstractEnglish

Objective: To study the bone metabolism in postmenopausal women who have been treated with gonadotropin-releasing hormone agonist (GnRH-a) and tibolone. Design: Prospective, open, controlled clinical trial. Setting: Department of Gynecology and Obstetrics, University of Catanzaro, Catanzaro, Italy. Patient(s): One hundred twenty perimenopausal women with symptomatic uterine leiomyomas (groups A and B), and 40 healthy control women who underwent a normal spontaneous menopause (group C). Intervention(s): Treatment for 12 months with leuprolide acetate plus tibolone (group A) or hysterectomy with bilateral oophorectomy (group B). Main Outcome Measure(s): Lumbar spine bone mineral density (BMD) and bone turnover markers at entry into the study, after medical treatment (only group A), and 12 months after discontinuation medical treatment (group A) or after surgery (group B). The same parameters were noted in healthy women before and 12 months after menopause (retrospective control group, group C). Result(s): At the women's entry into the study, no significant difference in BMD and bone turnover markers was detected between groups A and B. In group A, no significant variation in BMD or bone turnover markers was observed 12 months after medical treatment in comparison with baseline. At 12 months after discontinuation of treatment (in women who had achieved menopause) and after surgery, we observed a statistically significant decrease in BMD and in bone turnover markers in both groups in comparison with baseline. At 12 months after they became menopausal, we also observed a statistically significant reduction in BMD and in bone turnover markers in control group C. At the same 12-month follow-up visit, a statistically significant difference in BMD and in bone turnover markers was detected when comparing groups A and B with group C. Conclusion(s): Women previously treated with GnRH-a and tibolone similar to women who are menopausal as a result of surgery, have higher bone loss after menopause.

To evaluate whether tibolone modifies the effectiveness of gonadotropin-releasing hormone (GnRH) analog administered before laparoscopic myomectomy.Prospective, randomized, open, placebo-controlled clinical trial (Canadian Task Force classification I).University-affiliated hospital.Sixty-six women with symptomatic leiomyomas.Patients received 2 months of treatment with GnRH analog and iron plus tibolone (group A) or placebo (group B); group C received only iron. Laparoscopic myomectomy was performed after medical treatment.Uterine volume, number and volume of leiomyomas, echogenicity and volume of the largest leiomyomas, hematologic values, and myoma-related symptoms were evaluated at baseline, 1 week before, and 1 week after surgery. We observed significant (p0.05) reductions in uterine and leiomyomata volume, myoma-related symptoms, and improvement in hematologic values before surgery in groups A and B, without significant difference between groups compared with baseline values and group C. Operating time and blood loss were significantly (p0.05) lower in groups A and B, without significant difference compared with group C. After surgery, significant numbers of women in group C had worsening of hematologic values (p0.05).Adding tibolone to the GnRH analog regimen before laparoscopic myomectomy does not modify the effectiveness of GnRH analog administered alone.

Objective(s) : To evaluate the effects of two doses of medroxyprogesterone acetate (MPA) on uterine leiomyoma sizes and on uterine bleeding pattern in postmenopausal women treated with oral hormone replacement therapy (HRT). Study design : Thirty natural postmenopausal women affected by uterine leiomyomas were enrolled and treated with oral micronized estradiol (E 2 ) at dose of 2 mg per day, and randomized to receive in association MPA at dose of 2.5 mg daily (group A) or of 5 mg daily (group B). At the beginning of the study and after 1 year of treatment, uterine leiomyomata dimensions were measured using transvaginal ultrasonography (TV-USG). The subjects were instructed to note on a daily dairy the number and severity of abnormal uterine bleeding (AUB) episodes. Results : After 1 year of therapy, a significant changes in mean uterine leiomyomas size was observed in the group treated with higher dose of MPA. No significant differences in uterine bleeding were detected between the two groups. Conclusion(s) : In postmenopausal women with uterine leiomyomas, it is necessary to use the minimal efficacious dose of progestin during HRT because of a higher risk to increase the tumors dimensions.