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Uterine fibroids may impact fertility and the outcomes of infertility treatments negatively, depending on the fibroids' positions in the uterine wall, their sizes, and their numbers. This article reviews the available data on managing uterine fibroids in infertile patients. Subserosal fibroids do not affect fertility negatively and generally do not require treatment. It is advisable to remove submucosal fibroids before infertility treatment or in patients who have recurrent miscarriages. It is challenging to counsel infertile women with intramural fibroids because of the lack of a consensus about what should be done. The choice of treating intramural fibroids depends on the characteristics of the fibroids (such as numbers, sizes, and distances from the endometrial cavity), the reproductive history of the patient, and her willingness to wait until the appropriate time for myometrial healing before receiving infertility treatments. (J GYNECOL SURG 40:4) [ABSTRACT FROM AUTHOR]

• The total pregnancy rate of the study population was 48%. • 29% of the women had a live birth after natural conception. • The median time required to conceive naturally was 10 months. • 16% of the women had a live birth after conceiving by ART. • A worsening of pain and intestinal symptoms were observed in case of multiple IVF. Several studies have investigated reproductive outcomes following surgical treatment of colorectal endometriosis, mainly segmental colorectal resection. This study examines pregnancy and live birth rates of women with rectosigmoid endometriosis not treated by surgery. A retrospective analysis of data collected between May 2009 and January 2020 related to 215 women affected by rectosigmoid endometriosis wishing to conceive. Patients had a diagnosis of rectosigmoid endometriosis by transvaginal ultrasonography and magnetic resonance imaging enema. Patients with estimated bowel stenosis >70% at computed tomographic colonography and/or subocclusive/occlusive symptoms were excluded. During the median length of follow-up of 31 months (range 13–63 months), the total pregnancy and live birth rates of the study population were 47.9% and 45.1%, respectively. Sixty-two women had a live birth after natural conception (28.8%; 95% confidence interval [CI] 22.8–35.6%) with a median time required to conceive of 10 months (range 2–34 months). Eighty-three women underwent infertility treatments (38.6%, 95% CI 32.1–45.5%); among these, 68 patients underwent IVF either directly (n = 51) or after intrauterine insemination (IUI) failure (n = 17). Time to conception was significantly higher in women having conceived by IVF than in those having conceived naturally (P < 0.001) or by IUI (P = 0.006). In patients undergoing IVF cycles, a worsening of some pain and intestinal symptoms was observed. At median follow-up of 31 months, women with rectosigmoid endometriosis have a 48% pregnancy rate. However, these patients must be referred to centres specialized in managing endometriosis to properly assess symptoms and degree of bowel stenosis. [ABSTRACT FROM AUTHOR]

Background: Human herpervirus-8/human immunodeficiency virus negative Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disorder sustained by a pro-inflammatory condition of hypercytokinemia mostly mediated by Interleukin-6 (IL-6). According to iMCD consensus guidelines, anti-IL-6 blockade should be the first-line therapy for iMCD. However, despite the existing therapeutic alternatives, a large proportion of iMCD patients still lacks an effective therapy.Case Presentation: Here, we report two real-life iMCD cases with a different response to IL-6 blockade. The first presented patient obtained a prompt resolution of symptoms and a complete regression of adenopathies after IL-6 blockade therapy administration. Conversely, the second patient did not respond neither to Rituximab and Etoposide association nor to IL-6 blockade therapy (both Siltuximab and Tocilizumab). Furthermore, Intravenous immunoglobulin, Cyclosporine A, Sirolimus and anti-Interleukin-1 Anakinra were all attempted without any results. Since no treatment was successful, after a further confirmation of iMCD diagnosis by a second lymph node biopsy, patient has been candidate for thalidomide, cyclophosphamide and prednisone association therapy.Conclusions: The iMCD cases we reported are coherent with the evidences that IL-6 blockade is a safe and an effective therapy for iMCD. Despite this, more than half of patients do not respond to anti IL-6 drugs. In such cases, therapeutic alternatives could be represented by Sirolimus, targeting PI3K/AKT/mTOR signaling or by associations of conventional drugs such as thalidomide, cyclophosphamide and prednisone. However, the two reported iMCD cases, confirm the need to more deeply investigate iMCD pathogenesis and to better dissect the heterogeneity of the disease in order to develop novel, effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the efficacy of the etonogestrel (ENG)-releasing implant in treating patients with rectovaginal endometriosis. The study was based on the retrospective analysis of a prospectively collected database, including symptomatic women who had ultrasonographic diagnosis of rectovaginal endometriosis. Patients were follow-up at 6, 12 and 24 months from the insertion of the ENG-releasing implant. The intensity of pain symptoms was evaluated using a visual analog scale. The volume of the nodules was estimated by virtual organ computer-aided analysis. The Endometriosis Health Profile (EHP-30) was used to evaluate quality of life. Overall, 43 women were included in the study. The 2-year continuation rate for the ENG-releasing implant was 93.0%. The treatment quickly improved the intensity of non-menstrual pelvic pain, deep dyspareunia, dysmenorrhea, and dyschezia. At 6-month follow-up, there were improvements in all domains of the EHP-30 compared with baseline. Further improvements in the EHP-30 results were observed only in pain sub score at 12-month follow-up and in emotional well-being sub score at 24-month follow-up. At 6-month follow-up the volume of the rectovaginal nodules was significantly lower compared with baseline; a further decrease was observed at 12- and 24-month follow-up. The treatment was well tolerated. [ABSTRACT FROM AUTHOR]

Introduction: Nowadays, the resection of submucosal myomas is usually performed by hysteroscopy. No previous study has investigated the use of preoperative hormonal therapy before outpatient hysteroscopic myomectomy.Objective: To compare the usefulness of 3-month preoperative treatment with ulipristal acetate (UPA) before outpatient hysteroscopic myomectomy in patients with FIGO (International Federation of Gynecology and Obstetrics) type 0-1 myomas.Study Design: This prospective patient preference study included women requiring hysteroscopic resection of single FIGO type 0-1 myoma with the largest diameter <2 cm. Patients underwent either preoperative treatment with UPA (5 mg/day) for 3 months or direct surgery. Outpatient myomectomy was performed using the bipolar electrosurgical Versapoint system (Ethicon Gynecare, USA). The primary objective of the study was to compare the rate of complete resections in the 2 study groups. The secondary objective of the study was to compare the operative time and the volume of fluid infused/absorbed. The tertiary objective of the study was to assess the surgical appearance of the myomas in patients treated with UPA.Results: The study included 38 women treated with UPA and 45 women who underwent direct surgery. UPA treatment significantly decreased the volume of uterine myomas (p < 0.001). The percentage of complete resection was higher in patients treated with UPA (89.5%) than in those who underwent direct surgery (68.9%; p = 0.046). Preoperative UPA treatment decreased the operative time (p < 0.001) and the volume of fluid infused (p = 0.016), but it did not significantly affect the volume of fluid absorbed (p = 0.874). The texture of the myoma was not significantly affected by UPA treatment (p = 0.142).Conclusions: Three-month UPA treatment improves the chance of single-step complete outpatient hysteroscopic resection of single FIGO type 0-1 myoma. Future randomized studies with a larger sample size should confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

PURPOSE: Data collection in clinical trials is becoming complex, with a huge number of variables that need to be recorded, verified, and analyzed to effectively measure clinical outcomes. In this study, we used data warehouse (DW) concepts to achieve this goal. A DW was developed to accommodate data from a large clinical trial, including all the characteristics collected. We present the results related to baseline variables with the following objectives: developing a data quality (DQ) control strategy and improving outcome analysis according to the clinical trial primary end points. METHODS: Data were retrieved from the electronic case reporting forms (eCRFs) of the phase III, multicenter MCL0208 trial (ClinicalTrials.gov identifier: NCT02354313) of the Fondazione Italiana Linfomi for younger patients with untreated mantle cell lymphoma (MCL). The DW was created with a relational database management system. Recommended DQ dimensions were observed to monitor the activity of each site to handle DQ management during patient follow-up. The DQ management was applied to clinically relevant parameters that predicted progression-free survival to assess its impact. RESULTS: The DW encompassed 16 tables, which included 226 variables for 300 patients and 199,500 items of data. The tool allowed cross-comparison analysis and detected some incongruities in eCRFs, prompting queries to clinical centers. This had an impact on clinical end points, as the DQ control strategy was able to improve the prognostic stratification according to single parameters, such as tumor infiltration by flow cytometry, and even using established prognosticators, such as the MCL International Prognostic Index. CONCLUSION: The DW is a powerful tool to organize results from large phase III clinical trials and to effectively improve DQ through the application of effective engineered tools. [ABSTRACT FROM AUTHOR]

Background/aims: Ulipristal acetate ([UPA], Esmya®) is an orally active selective progesterone-receptor modulator that has been approved as preoperative treatment for uterine myomas. This systematic review aims to summarize the available data on surgical outcomes of patients undergoing myomectomy by hysteroscopy or by laparoscopy after preoperative treatment with UPA.Methods: this review was performed following PRISMA guidelines and was registered in PROSPERO (CRD42018092201). PubMed, EMBASE, and Medline databases were systematically searched electronically until March 2018 for keywords concerning this topic. There were included only peer-reviewed, English language journal articles.Results: two prospective studies and 4 retrospective studies were included. The effect of UPA on the endometrium does not increase the technical difficulty during hysteroscopic myomectomy, but it increases the chance of complete primary resection in complex hysteroscopic myomectomies. Moreover, UPA does not increase the overall technical difficulty of laparoscopic myomectomy. Contradictory results have been reported on the impact of UPA on the separation of the myoma from the myometrium and on the consistency of the myomas.Conclusion: current results support the use of UPA prior to both surgical procedures. Further studies should confirm these preliminary findings and to assess the long-term outcomes of myomectomies following UPA treatment. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic benign disease that affects women of reproductive age. Medical therapy is often the first line of management for women with endometriosis in order to ameliorate symptoms or to prevent post-surgical disease recurrence. Currently, there are several medical options for the management of patients with endometriosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of chronic inflammatory conditions, being efficacious in relieving primary dysmenorrhea. Combined oral contraceptives (COCs) and progestins, available for multiple routes of administration, are effective first-line hormonal options. In fact, several randomized controlled trials (RCTs) demonstrated that they succeed in improving pain symptoms in the majority of patients, are well tolerated and not expensive. Second-line therapy is represented by gonadotropin-releasing hormone (GnRH) agonists. Even if these drugs are efficacious in treating women not responding to COCs or progestins, they are not orally available and have a less favorable tolerability profile (needing an appropriate add-back therapy). The use of danazol is limited by the large availability of other better-tolerated hormonal drugs. Because few data are available on long-term efficacy and safety of aromatase inhibitors they should be administered only in women with symptoms refractory to other conventional therapies in a clinical research setting. Promising preliminary data have emerged from multicenter Phase III trials on elagolix, a new oral GnRH antagonist but non-inferiority RCT data are required to compare elagolix with first-line therapies for endometriosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the response to superovulation for in vitro fertilization (IVF) in patients with unilateral endometriomas with diameter ≥5cm and in the contralateral healthy ovary.Study Design: This retrospective analysis of a prospectively collected database included patients who underwent superovulation for IVF/ICSI cycles and had unoperated single unilateral endometrioma with diameter ≥5cm and healthy contralateral ovary. The primary outcome of the study was to compare the number of oocyte retrieved in the ovary with the endometrioma and the contralateral healthy ovary.Results: The total number of follicles was lower in ovaries with endometriomas (2.6±1.3) than in healthy ovaries (4.8±2.0; p<0.001). The number of codominant follicles and the total number of oocytes retrieved were lower in ovaries with endometriomas (1.5±0.9 and 2.0±1.2) than in the contralateral ovaries (3.7±1.5 and 4.2±1.7; p<0.001, respectively). The number of oocytes retrieved suitable for fertilization was lower in ovaries with endometriomas (1.5±1.1) than in the healthy ovaries (3.3±1.5; p<0.001). The total number of oocytes retrieved and the number of oocytes retrieved suitable for fertilization were lower in ovaries with endometriomas respectively in 21 (80.8%) and in 20 (76.9%) cases. The decreased responsiveness to ovarian superovulation was confirmed considering women with ultrasonographic diagnosis of deep infiltrating endometriosis. 30.8% of patients had positive HCG; the pregnancy rate was 23.1%.Conclusion: The presence of large endometriomas (≥5cm) at time of IVF significantly decreases the number of oocyte retrieved compared with the contralateral healthy ovaries. [ABSTRACT FROM AUTHOR]

Objective: To assess the usefulness of 3-month treatment with ulipristal acetate (UPA) before laparoscopic myomectomy of large uterine myomas.Study Design: This retrospective analysis of a prospectively collected database included women of reproductive age requiring laparoscopic myomectomy with the following characteristics: FIGO type 3, 4 or 5 myomas; largest diameter of the main myoma ≥10cm; number of myomas ≤3; largest diameters of the other myomas ≤5cm (second myoma) and ≤3cm (third myoma). Patients either underwent direct surgery (group S) or were treated before surgery with UPA for 3 months (group UPA).Results: The mean (±SD) intraoperative blood loss was lower in group UPA (507.1±214.9ml) than in group S (684.2±316.8; p=0.012). The total operative time was lower in group UPA (137.6±26.8min) than in group S (159.7±26.8min; p<0.001); there was no significant difference in the suturing time between the two study groups (p=0.076). Hemoglobin drop was lower in group UPA (1.1±0.5g/dl) than in group S (1.3±0.7g/dl; p=0.034). Six patients in group S and no patient in group UPA required postoperative blood transfusions (p=0.031). Complications were not different between the two groups (p=0.726). Moreover, preoperative treatment with UPA caused a significant increase in hemoglobin levels (11.9±1.6g/dl) compared with baseline (9.1±1.1g/dl; p<0.001).Conclusion: A 3-month treatment with UPA before laparoscopy for large uterine myomas decreases intraoperative blood loss, hemoglobin drop, postoperative blood transfusion and length of surgery. [ABSTRACT FROM AUTHOR]

Context Mirabegron, the first β 3 -adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms. Because β 3 -adrenoceptors are expressed in cardiovascular (CV) tissues, there are concerns that OAB treatment with β 3 -adrenoceptor agonists may affect the heart and vasculature. Objective To provide a summary of CV effects of β 3 -adrenoceptor agonists in clinical studies. Evidence acquisition A systematic literature search from inception until November 2014 was performed on studies in PubMed and Medline. Evidence synthesis Twenty papers, published between 1994 and 2014, were identified: mirabegron (16), solabegron (2), AK-677 (1), and BRL35135 (1). More detailed CV data from mirabegron studies were available in online regulatory documents filed with the US Food and Drug Administration and the UK National Institute for Health and Care Excellence. Conclusions The CV safety of mirabegron appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, currently first-line therapy for OAB. Patient summary In this review we looked at the cardiovascular (CV) effects of β 3 -adrenoceptor agonists used for the treatment of overactive bladder (OAB). The CV safety of mirabegron (the only clinically approved β 3 -adrenoceptor agonist) appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, the current first-line therapy for OAB. [ABSTRACT FROM AUTHOR]

Background: Traditionally, pregnancy was considered to have a positive effect on endometriosis and its painful symptoms due not only to blockage of ovulation preventing bleeding of endometriotic tissue but also to different metabolic, hormonal, immune and angiogenesis changes related to pregnancy. However, a growing literature is emerging on the role of endometriosis in affecting the development of pregnancy and its outcomes and also on the impact of pregnancy on endometriosis. The present article aims to underline the difficulty in diagnosing endometriotic lesions during pregnancy and discuss the options for the treatment of decidualized endometriosis in relation to imaging and symptomatology; to describe all the possible acute complications of pregnancy caused by pre-existing endometriosis and evaluate potential treatments of these complications; to assess whether endometriosis affects pregnancy outcome and hypothesize mechanisms to explain the underlying relationships.Methods: This systematic review is based on material searched and obtained via Pubmed and Medline between January 1950 and March 2015. Peer-reviewed, English-language journal articles examining the impact of endometriosis on pregnancy and vice versa were included in this article.Results: Changes of the endometriotic lesions may occur during pregnancy caused by the modifications of the hormonal milieu, posing a clinical dilemma due to their atypical appearance. The management of these events is actually challenging as only few cases have been described and the review of available literature evidenced a lack of formal estimates of their incidence. Acute complications of endometriosis during pregnancy, such as spontaneous hemoperitoneum, bowel and ovarian complications, represent rare but life-threatening conditions that require, in most of the cases, surgical operations to be managed. Due to the unpredictability of these complications, no specific recommendation for additional interventions to the routinely monitoring of pregnancy of women with known history of endometriosis is advisable. Even if the results of the published studies are controversial, some evidence is suggestive of an association of endometriosis with spontaneous miscarriage, preterm birth and small for gestational age babies. A correlation of endometriosis with placenta previa (odds ratio from 1.67 to 15.1 according to various studies) has been demonstrated, possibly linked to the abnormal frequency and amplitude of uterine contractions observed in women affected. Finally, there is no evidence that prophylactic surgery would prevent the negative impact of endometriosis itself on pregnancy outcome.Conclusions: Complications of endometriosis during pregnancy are rare and there is no evidence that the disease has a major detrimental effect on pregnancy outcome. Therefore, pregnant women with endometriosis can be reassured on the course of their pregnancies although the physicians should be aware of the potential increased risk of placenta previa. Current evidence does not support any modification of conventional monitoring of pregnancy in patients with endometriosis. [ABSTRACT FROM AUTHOR]

Pain is the most evident clinical manifestation of deep infiltrating endometriosis (DIE). Several hormonal and immunologic mechanisms are markedly altered in DIE compared with superficial peritoneal and ovarian endometriosis, and may explain its most aggressive behavior and the presence of severe pain symptoms. Hormonal therapies, such as combined hormonal contraceptives and progestogens, should be regarded as first-line treatment, as they are efficacious, safe, and well tolerated. Gonadotropin-releasing hormone agonists may be used in patients with symptoms persisting after the administration of first-line therapies. Scanty literature is available for danazol treatment in patients with DIE and, however, it has become less popular due to the high rates of androgenic adverse events (AEs). The partial relief of pain that often is achieved with available therapies and its recurrence after the suspension of the treatment have brought to the development of new therapies (such as aromatase inhibitors, oral GnRH antagonists) that are currently under investigation. Surgical excision of DIE should be considered in patients with pain symptoms persisting after first-line hormonal therapies. The benefits of surgery in terms of pain improvement should be always balanced with the risk of intraoperative complications and for this reason surgical cases should be referred to tertiary centers for the treatment of DIE. A multidisciplinary approach is mandatory in patients with DIE involving the bowel and/or the urinary tract. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas. Design Case-control study. Setting University teaching hospital. Patient(s) This study included patients who underwent stripping of endometriomas (diameter ≥4 cm) and were followed-up at our institution. Case subjects had second surgery for recurrent unilateral endometriomas (n = 18); control subjects had no recurrence and no second surgery (n = 18). Intervention(s) This case-control study was based on a retrospective analysis of a prospectively collected database including patients who underwent surgery for endometriomas at our institution. Main Outcome Measure(s) The primary outcome of the study was to assess the changes in antimüllerian hormone (AMH) levels in each study group and between the two study groups. The secondary outcomes of the study were to assess the changes in basal FSH, antral follicle count (AFC), and ovarian volume in each study group and between the two study groups. Result(s) In both study groups, primary surgery decreased AMH, increased basal FSH, and decreased the AFC of the operated ovary. Before second surgery, case subjects had AMH, basal FSH, and AFC similar to control subjects. After second surgery, case subjects had lower AMH, higher basal FSH, and lower AFC of the affected ovary than before surgery; the volume of the operated ovary was lower than that of the contralateral ovary. Conclusion(s) The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure. Clinical Trial Registration Number NCT02047838 . [ABSTRACT FROM AUTHOR]

Bladder endometriosis causes urinary symptoms including frequency, dysuria, cyclic haematuria and non-urinary pain symptoms. To our knowledge, the association of bladder endometriosis with urinary incontinence has not been described. We present the first case of bladder endometriosis that caused urinary symptoms including mixed urinary incontinence (MUI). A 34-year-old nulliparous woman was referred to our urogynaecology clinic with a 18-month history of urgency urinary incontinence (UUI) and stress urinary incontinence (SUI). A diagnosis of bladder endometriosis was performed on the basis of symptoms and imaging. The patient refused surgery and dienogest was prescribed. At the 12-month follow-up, all endometriosis-related symptoms and questionnaire scores had significantly improved, and there was resolution of the abnormal urodynamic findings. In reproductive-aged women suffering pain symptoms, bladder endometriosis should be considered in the differential diagnosis of urinary incontinence and treatment with dienogest may lead to improvement of both urinary and pain symptoms. [ABSTRACT FROM AUTHOR]

Endometriosis is an estrogen-dependent inflammatory disease defined by the growth of endometrial stroma and glands outside of the uterus. Epidemiological and clinical studies show that estrogen is essential for the growth of endometriosis. There are several molecular links between estrogen production and inflammation in endometriosis. The enzyme aromatase P450 is expressed aberrantly in endometriosis and is stimulated by prostaglandin E2, resulting in production of estrogen that induces prostaglandin E2 expression within endometriotic lesions. Furthermore, estrogen promotes the secretion of several inflammatory cytokines and growth factors, which contribute to the progression of endometriosis and stimulate estrogen production. On the basis of the local estrogen biosynthesis in endometriotic implants, nonsteroidal aromatase inhibitors have been successfully used to treat pain symptoms caused by endometriosis. These agents do not cause the disappearance of endometriosis; they cannot be considered routine treatment and should only be administered in adequately controlled clinical studies. [ABSTRACT FROM AUTHOR]

Endometriosis is an estrogen-dependent inflammatory disease defined by the growth of endometrial stroma and glands outside of the uterus. Epidemiological and clinical studies show that estrogen is essential for the growth of endometriosis. There are several molecular links between estrogen production and inflammation in endometriosis. The enzyme aromatase P450 is expressed aberrantly in endometriosis and is stimulated by prostaglandin E2, resulting in production of estrogen that induces prostaglandin E2 expression within endometriotic lesions. Furthermore, estrogen promotes the secretion of several inflammatory cytokines and growth factors, which contribute to the progression of endometriosis and stimulate estrogen production. On the basis of the local estrogen biosynthesis in endometriotic implants, nonsteroidal aromatase inhibitors have been successfully used to treat pain symptoms caused by endometriosis. These agents do not cause the disappearance of endometriosis; they cannot be considered routine treatment and should only be administered in adequately controlled clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the efficacy of norethisterone acetate (NETA; group N) or letrozole combined with NETA (group L) in treating endometriotic ovarian cysts. Study design: This patient-preference study included 20 patients in group N and 20 patients in group L. The primary aim of the study was to compare the volume of the endometriomas during and after treatment. The secondary outcome was the evaluation of the changes in pain symptoms during and after treatment. Results: After six months of treatment, the volume of the endometriomas significantly decreased compared with baseline in both study groups; it was smaller in group L than in group N (p =0.026). The rate of satisfied patients at six months of treatment was similar between the study groups (p =0.451). No significant difference was reported between the two study groups in the amelioration of pain symptoms and in the incidence of adverse events. Conclusions: Letrozole combined with NETA is more efficacious than NETA alone in reducing the volume of endometriotic cysts but in none of the 40 patients included in the study did the endometriomas disappear. The efficacy of aromatase inhibitors, however, should be balanced with the need to administer long-term treatment. [Copyright &y& Elsevier]

Abstract: Purpose: To compare the accuracy of multidetector computerized tomography enema (MDCT-e) and magnetic resonance enema (MRI-e) in determining the presence of sigmoid and rectal endometriotic nodules. Materials and methods: 260 women (32.6±4.3 years) with symptoms suggestive of rectosigmoid endometriosis underwent MDCT-e and MRI-e prior to laparoscopy. After retrograde colonic distention and injection of intravenous contrast medium, patients were scanned on a 64-row MDCT scanner. MRI-e was performed on a 1.5T magnet using an 8 channels phased array coil; intestinal distention was achieved by introducing in the rectum 250–300ml of ultrasonographic gel diluted with saline solution. Radiological findings were compared with surgical and histological results. Results: 176 women had rectosigmoid endometriosis at surgery. There was no significant difference in the accuracy of MDCT-e (98.5%) and MRI-e (96.9%) in the diagnosis of sigmoid and rectal endometriosis (p =0.248). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of MDCT-e and MRI-e were respectively 98.3%, 98.8%, 99.4%, 96.5%, 81.59, 0.02 and 97.2%, 96.4%, 98.3%, 94.1%, 26.89, 0.03. Conclusions: Both MDCT-e and MRI-e are accurate in the diagnosis of rectal and sigmoid endometriosis. [Copyright &y& Elsevier]

Pre-emptive rituximab (pRTX) might represent an effective approach for patients with follicular (FL) and mantle cell lymphoma (MCL) experiencing molecular relapse (M-rel). However, available experience is still limited. We retrospectively collected FL and MCL cases that underwent pRTX with four weekly rituximab infusions (375 mg/m) due to molecular persistence or M-rel. M-rel was assessed using nested polymerase chain reaction (PCR) and real-time quantitative PCR using the Bcl-1/IGH, Bcl-2/IGH or the immunoglobulin heavy chain rearrangement. Twenty-three occurrences of M-rel or persistence were treated in 18 patients (nine MCL and nine FL). The pRTX reinduced molecular remission (MR) in 17/23 cases (7/9 FL and 10/14 MCL). The median time to MR reinduction was 4.5 months (range 3-12), and the median duration of the first MR reinduction was 34 months (range 12-72). In five MCL cases, pRTX was used to treat subsequent M-rels, with success in four cases. No clinical relapses were seen within 2 years of successful reinduction of MR. Progression-free survival after pRTX was 64 % at a median follow-up of 6 years. pRTX was feasible and safe and effectively reinduced MR in FL and MCL patients (74 %). Prospective trials are needed to verify the clinical benefit of similar approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: The interest in using Machine-Learning (ML) techniques in clinical research is growing. We applied ML to build up a novel prognostic model from patients affected with Mantle Cell Lymphoma (MCL) enrolled in a phase III open-labeled, randomized clinical trial from the Fondazione Italiana Linfomi (FIL)—MCL0208. This is the first application of ML in a prospective clinical trial on MCL lymphoma. We applied a novel ML pipeline to a large cohort of patients for which several clinical variables have been collected at baseline, and assessed their prognostic value based on overall survival. We validated it on two independent data series provided by European MCL Network. Due to its flexibility, we believe that ML would be of tremendous help in the development of a novel MCL prognostic score aimed at re-defining risk stratification. Background: Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313). Methods: We developed a score with a clustering algorithm applied to clinical variables. The candidate score was correlated to overall survival (OS) and validated in two independent data series from the European MCL Network (NCT00209222, NCT00209209); Results: Three groups of patients were significantly discriminated: Low, Intermediate (Int), and High risk (High). Seven discriminants were identified by a feature reduction approach: albumin, Ki-67, lactate dehydrogenase, lymphocytes, platelets, bone marrow infiltration, and B-symptoms. Accordingly, patients in the Int and High groups had shorter OS rates than those in the Low and Int groups, respectively (Int→Low, HR: 3.1, 95% CI: 1.0–9.6; High→Int, HR: 2.3, 95% CI: 1.5–4.7). Based on the 7 markers, we defined the engineered MCL international prognostic index (eMIPI), which was validated and confirmed in two independent cohorts; Conclusions: We developed and validated a ML-based prognostic model for MCL. Even when currently limited to baseline predictors, our approach has high scalability potential. [ABSTRACT FROM AUTHOR]

• Dynamic models of nuclear fusion plant can help optimize their performance. • A model of a supercritical CO 2 power cycle developed using Modelica language. • Adequate controls have been implemented in the model aiming at real control design. • When simulating a variable load operation, the modelled system has performed well. • Modelica is a convenient tool to design control algorithms of dynamic systems. Nuclear fusion technology is one of the main valuable candidates for providing a trustable base load in low-carbon future energy scenarios, thanks to its power density, low emissions and flexibility, together with innovative power conversion systems that could improve its performance, as the supercritical CO 2 Brayton cycle. Since the nuclear plant will be required to provide variable loads, due to the fluctuating nature of renewable energies, a powerful modelling tool will be necessary to simulate different power outputs. The present paper presents a dynamic model of a supercritical CO 2 power cycle developed with Modelica, aimed at the design of control systems to adjust the power production according to the load required. Thanks to the activity of three PI controllers, the system is able to follow a variable load profile while preserving the turbomachinery inlet temperature, to avoid any possible damage of the devices. The work has shown the adequacy and potential interest of the use of Modelica in this kind of analyses. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the changes in the volume of rectovaginal endometriotic nodules infiltrating the rectum during 12-month treatment with hormonal therapies. Materials and methods: This prospective, non-randomized, self-controlled clinical trial included patients with rectovaginal endometriotic nodules infiltrating at least the muscularis propria of the rectum, who received one of the following therapies: norethisterone acetate, triptorelin and tibolone, norethisterone acetate and letrozole, desogestrel, sequential oral contraceptive pill. The volume of the nodules was determined by virtual organ computer-aided analysis (VOCAL, GE Healthcare, USA) at baseline and after 6 and 12 months of treatment. Results: Eighty-three women (90.2 %) completed the 12-month treatment. When compared with baseline values, the volume of the nodules decreased at 6-month ( p < 0.001) and 12-month treatment ( p < 0.001). After 12-month treatment, the volume of the nodules decreased in all study groups. The volume of the nodules decreased during therapy in 68 women (73.9 %) and increased in 11 women (12.0 %). Conclusion: 12-month administration of hormonal therapies reduces the volume of rectovaginal endometriotic nodules infiltrating the rectum in the majority of cases. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: This investigation describes the feasibility and outcome of vaginal paravaginal repair (VPVR) performed using the Capio™ suture-capturing device. Methods: This prospective study included 36 women with paravaginal fascial defects, symptomatic stage II to IV anterior vaginal wall prolapse, and uterine prolapse equal or more than stage 2. VPVR was performed using the Capio device. In addition, anterior colporrhaphy, posterior colporrhaphy, and vaginal hysterectomy were performed. Results: The mean time required to perform the VPVR was 12.9 min (range, 11-18 min). The median blood loss during the VPVR was 35 ml (range, 20-65 ml). There were no major intraoperative complications. At 2-year follow-up, the rate of recurrent anterior vaginal wall prolapse (stage ≥2) was 8.6%. Conclusions: VPVR performed using the Capio device is associated with minimal dissection of the tissues, blood loss, and operating time and has low recurrence rate at 2-year follow-up. [ABSTRACT FROM AUTHOR]

Background. Aromatase inhibitors have recently been proposed for the treatment of endometriosis; however, no previous study examined the effects of these agents on pain and urinary symptoms of premenopausal women with bladder endometriosis. Case. Two premenopausal patients with bladder endometriosis were treated with letrozole (2.5 mg/day), norethisterone acetate (2.5 mg/day), elemental calcium and vitamin D3 for 6 months. The double-drug regimen quickly improved pain and urinary symptoms in both patients. One patient had no significant adverse effect and continued the therapy for 14 months. The other patient developed myalgia and severe arthralgia; pain and urinary symptoms recurred few months after the interruption of the 6-month treatment and the patient underwent laparoscopic partial cystectomy. Conclusion. Aromatase inhibitors improve pain and urinary symptoms in patients with bladder endometriosis; however, severe side effects of treatment may occur. These agents should be administered only to patients who refuse surgery and fail to respond to other therapies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of treatment with vaginal danazol in improving the pain symptoms caused by rectovaginal endometriosis that persist after insertion of a levonorgestrel-releasing intrauterine device (LNG-IUD).Methods: This pilot observational study included 15 women with rectovaginal endometriosis and pain symptoms persisting after LNG-IUD insertion. Vaginal danazol (100mg per day) was self-administered for 6months. The intensity of pain symptoms and the volume of rectovaginal endometriotic nodules were evaluated.Results: Twelve women were satisfied or very satisfied with the treatment. After treatment with vaginal danazol for 3months, there was a significant decrease in the intensity of pain symptoms compared with their intensity before the administration of danazol. The intensity of pain symptoms decreased further at 6-month follow-up. The volume of the rectovaginal nodules decreased after treatment with vaginal danazol for 6months (1.7±0.8cm(3)) compared with the baseline volume (2.3±0.9cm(3); P<0.001). Adverse effects of the treatment were minimal and well tolerated.Conclusion: Although a placebo effect cannot be excluded, the results indicate that vaginal danazol decreases the severity of endometriosis-related pain symptoms after LNG-IUD insertion. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of newly diagnosed endometriosis in premenopausal women who requested a consultation with their general practitioner because of non-gynecological problems.Method: Participants in the study were invited to complete a questionnaire investigating the presence of pain symptoms and infertility. On the basis of the characteristics of these symptoms, some patients underwent gynecological examination and transvaginal ultrasound. Radiological examinations were performed when bowel or bladder endometriosis were suspected.Results: A total of 1291 women without a previous diagnosis of endometriosis were included in the study. On the basis of the symptoms, 108 women were referred to a gynecologist. After gynecological examination and transvaginal ultrasound, endometriosis was suspected in 51 women (47.2%). The diagnosis of endometriosis was confirmed by radiological investigations and/or surgery in 46 patients; the diagnosis of endometriosis was presumed in 2 other women but it was not confirmed by radiological investigations and/or surgery. The prevalence of endometriosis diagnosed by magnetic resonance imaging and/or surgery was 3.6% (46/1291).Conclusion: The prevalence of newly diagnosed symptomatic endometriosis in this study was at least 3.6%. A simple evaluation of symptoms (pain and infertility) that can be performed by a general practitioner facilitates the diagnosis of endometriosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Up to now limited attention has been given to the medical treatment of bowel endometriosis. This study evaluates the efficacy of aromatase inhibitors and norethisterone acetate in treating pain and gastrointestinal symptoms caused by bowel endometriosis. Study design: This prospective pilot study included six women with colorectal endometriosis; all women had intestinal nodules infiltrating at least the muscularis propria of the bowel and did not have a stenosis of the bowel lumen >60%; the patients suffered from pain and intestinal symptoms. The study subjects received letrozole (2.5mg/day) and norethisterone acetate (2.5mg/day) continuously for 6 months. The presence and intensity of symptoms were evaluated before starting the treatment, and after 3 and 6 months of treatment. Results: The double-drug regimen improved pain, non-menstrual pelvic pain, deep dyspareunia, dyschezia, symptoms mimicking diarrhoea-predominant irritable bowel syndrome, intestinal cramping, abdominal bloating and passage of mucus in the stools, and 67% of the patients declared that the treatment improved their gastrointestinal symptoms. Conclusions: The administration of letrozole and norethisterone acetate reduces pain and gastrointestinal symptoms of women with colorectal endometriosis, particularly when patients suffer from symptoms mimicking diarrhoea-predominant irritable bowel syndrome. [Copyright &y& Elsevier]

The aim of this randomized, surgeon-blind, controlled study was to evaluate the role of a 7 days minimal-residue (low fibre intake) pre-operative diet compared with a mechanical bowel preparation in laparoscopic benign gynaecological surgery. This was a randomized, surgeon-blind, controlled study. The study included 83 women scheduled to undergo diagnostic or operative laparoscopy for various gynaecological benign conditions. Exclusion criteria were suspicion of malignancy, associated non-gynaecological surgical pathologies, severe endometriosis, and history of previous abdominal surgery. Study group had a total daily fibre intake inferior to 10 g for a week before the operation ( n = 42). Control group had a mechanical bowel preparation the day before the operation ( n = 41). The principal measures of outcome were the quality of bowel preparation, the acceptability of the preoperative diet and of the mechanical bowel preparation. Secondary outcomes included postoperative pain, time of ambulation, length of postoperative ileus, and length of postoperative hospital stay. The two treatment groups were comparable with respect to demographic characteristics and indications for surgery. Preoperatively, abdominal distension and overall discomfort were significantly more frequent in the control group ( P = 0.061 and 0.034 respectively). There was no significant difference in the small and large bowel preparation between the two groups. Postoperatively, no significant difference was observed between the two groups in pain, nausea, abdominal swelling, length of ileus, and of postoperative stay. This study shows that preoperative low fibre diet and mechanical bowel preparation provide similar quality of surgical field exposure. However, when compared with mechanical bowel preparation, preoperative low fibre diet may be better tolerated by the patients, thus increasing compliance. Moreover, a 7 days preoperative low fibre diet allow the patient to continue working and social activities until the day of surgery without requiring admission to the hospital or home bowel preparation on the day before surgery. [ABSTRACT FROM AUTHOR]

Objective: To determine the pregnancy rate after bowel resection for rectosigmoid endometriosis. Design: Prospective cohort study. Setting: University hospital. Patient(s): Forty-six symptomatic women with bowel endometriosis requiring colorectal resection. Intervention(s): Bowel resection by either laparoscopy or laparotomy. Main Outcome Measure(s): Pregnancy rate after surgery. Result(s): The pregnancy rate was higher in women who underwent bowel resection by laparoscopy (57.6%) than in those who underwent laparotomy (23.1%). No significant difference was observed in pregnancy rate and mode of conception between women with different fertility status before bowel resection. Women who conceived were significantly younger than those who did not conceive; only 26.7% of women aged ≥35 years conceived after bowel resection. Uterine adenomyosis was more frequently present in women who did not conceive than in those who conceived. Infertile women who conceived had a shorter length of infertility before surgery than those who did not conceive. Conclusion(s): Laparoscopic colorectal resection is less likely to impact negatively on fertility than the laparotomy approach. Previous laparotomies, age ≥35 years, uterine adenomyosis, and longer duration of infertility before surgery are associated with decreased pregnancy rate. [Copyright &y& Elsevier]

Current treatment of endometriosis is mainly based on surgery and ovarian suppressive agents. In the last 10 years, it has been demonstrated that aromatase P450, a key enzyme for estrogen biosynthesis, may have a pathogenic role in endometriosis because it is aberrantly expressed in endometriotic implants and in eutopic endometrium of women with endometriosis. Therefore, inhibition of aromatase activity may represent a new therapeutic option for endometriosis. Case reports and observational studies have shown that pain symptoms caused by endometriosis quickly improve after administration of aromatase inhibitors. Limited data are available on the long-term course of pain symptoms after completion of treatment with aromatase inhibitors; however, some recent studies suggest that symptoms may recur at short-term follow-up. A range of results are reported on the effects of aromatase inhibitors on endometriotic lesions, with some authors describing improvements and other authors reporting persistence of pelvic lesions at second-look laparoscopy after treatment. No severe adverse effect has been reported during treatment with aromatase inhibitors both in pre- and postmenopausal women. On the basis of the available data, administration of aromatase inhibitors should now be offered only to the small number of women who have severe pain despite previous surgical and hormonal therapies. Further research in the form of randomized controlled trials will be required before recommending the routine use of these agents. [ABSTRACT FROM AUTHOR]

To compare the peritoneal fluid (PF) proteome of women with and without uterine leiomyomas. PF samples were collected at laparoscopy from 14 women with uterine leiomyomas and 14 patients without leiomyomas who underwent tubal sterilization. PF samples were subjected to two-dimensional gel electrophoresis, silver stained, digitally captured, and compared by computerised analysis. Protein spots with aberrant expression in PF of women with leiomyomas were identified by liquid chromatography tandem mass spectrometry. One isoform of leucine-rich alpha-2-glycoprotein (LRGm), one immunoglobulin light chain, and one unidentified protein (pI: 5.62; M r: 51.1 kDa) had significantly higher expression in PF of women with leiomyomas. Two isoforms of fibrinogen gamma chain had decreased expression in PF of women with uterine leiomyomas. Following Bonferroni correction for multiple comparisons, the aberrant expressions of LRGm and of one isoform of fibrinogen gamma chain was confirmed. The expression of these molecules was not affected by the phase of the menstrual cycle. Uterine leiomyomas are associated with changes in proteins present within the peritoneal fluid. The physiopathological relevance of the increased expression of LRGm in PF of women with uterine leiomyomas remains unclear. [ABSTRACT FROM AUTHOR]

Objective. Endometriosis has a wide range of severity but molecular factors associated with variable extension of the disease have not been widely investigated. The present study compares the peritoneal fluid (PF) proteome of 109 women with endometriosis and different disease stage as defined by the American Society for Reproductive Medicine (ASRM). Methods. PF samples were subjected to two-dimensional gel electrophoresis; protein spots of interest were identified by liquid chromatography tandem mass spectrometry. Results. Over 470 protein spots were analyzed. One isoform of haptoglobin α chain, α-1b-glycoprotein and one unknown protein had higher expression in PF of women with ASRM stage I-II endometriosis. Four isoforms of α1-antitrypsin, three isoforms of α-1b-glycoprotein, one isoform of S100-A8 and serotransferrin had higher expression in PF of women with ASRM stage III-IV disease. Conclusions. Several protein isoforms have different expression in PF of women with ASRM stage I-II endometriosis than in those with ASRM stage III-IV disease; most of these molecules are involved in inflammation and immune response. [ABSTRACT FROM AUTHOR]

Although several radiological techniques have been used for the diagnosis of bowel endometriosis, no gold standard is currently established. We used multislice computerized tomography (CT) combined with the distention of the colon by rectal enteroclysis (MSCTe) for the diagnosis of bowel endometriosis. Following bowel preparation, pharmacological hypotonicity, retrograde colonic distention by water enteroclysis, and intravenous injection of iodinated contrast medium, a single volumetric acquisition of the abdomen is performed. MSCTe findings suggestive of bowel endometriosis are the presence of solid nodules with positive enhancement, contiguous or penetrating the colonic wall. When endometriotic lesions are detected, the degree of infiltration of the intestinal wall can be estimated; however, the depth infiltrated by nodules reaching the submucosa may be underestimated. MSCTe is well tolerated by the patients. The strength of MSCT consists in the high spatial resolution; volumetric data acquired by using thin slices provide isotropic voxels and multiplanar reconstructions have a quality comparable with that of the original axial scans. The potential of MSCTe for the diagnosis of bowel endometriosis relies on the fact that the serosal, muscular, and mucosal layers of the bowel wall can be evaluated. [ABSTRACT FROM AUTHOR]

This cross-sectional survey investigates patients’ attitudes towards the use of photos of children born following infertility treatment. Each partner of 270 infertile couples independently completed a standardized questionnaire investigating patients’ attitudes towards the presence of photos of children born following infertility treatment in fertility clinics, Internet websites, brochure, and videos. Subjects (77.4%) were pleased to provide a photo of their child to hang on the walls of the fertility centre, a lower percentage of subjects desired to exhibit the photo in the fertility centre website, brochure, and video. Among subjects wishing to hang the photo of their child in the infertility centre, 60.3% wanted the name of the child on the photo and 15.3% wanted both the name and surname of the child on the photo. If a photo is explicitly requested by a member of the fertility team, 30.9% of the subjects feel to have the duty to give it. No significant difference was observed in the desire to provide a photo of the child to hang on the walls of the fertility centre according to sex of the patient. The majority of infertile patients are pleased to exhibit a photo of their babies in the fertility centre. Members of the fertility team should avoid asking explicitly the photo because parents may feel to have the duty to give it. [ABSTRACT FROM AUTHOR]

This prospective study aims to evaluate the efficacy of multislice computed tomography combined with colon distension by water enteroclysis (MSCTe) in determining the presence and depth of bowel endometriotic lesions. Ninety-eight women with symptoms suggestive of colorectal endometriosis underwent MSCTe; locations, number of nodule/s, size of the nodule/s and depth of bowel wall infiltration were determined. Independently from the findings of MSCTe, all women underwent laparoscopy. MSCTe findings were compared with surgical and histological results. Abnormal findings suggestive of bowel endometriotic nodules were detected by MSCTe in 75 of the 76 patients with bowel endometriosis. MSCTe identified 110 (94.8%) of the 116 bowel endometriotic nodules removed at surgery; 6 nodules missed at MSCTe were located on the rectum. MSCTe correctly determined the degree of infiltration of the bowel wall in all of the 34 serosal bowel nodules identified at MSCTe. In six nodules reaching the submucosa, the depth of infiltration was underestimated by MSCTe. MSCTe had a sensitivity of 98.7%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 95.7% in identifying women with bowel endometriosis. MSCTe is effective in determining the presence and depth of bowel endometriotic lesions. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of deep dyspareunia (DD) and characteristics of sexual life in women with uterine myomas. Design: Cross-sectional survey. Setting: University hospital. Patient(s): Three hundred seven sexually active premenopausal women who underwent surgery because of uterine myomas (group M, n = 132), uterine myomas and ovarian cysts (group MC, n = 84), ovarian cysts (group C, n = 67), and tubal sterilization (group S, n = 24). Exclusion criteria were as follows: endometriosis, pelvic inflammatory disease, interstitial cystitis, and preoperative treatment with GnRH analogues. Intervention(s): Before surgery, patients underwent transvaginal ultrasound; number and characteristics of myomas were recorded. Main Outcome Measure(s): The presence and intensity of DD were determined. Patients completed a sexual-function questionnaire. Result(s): Patients included in the four groups had similar DD prevalence and DD intensity. No significant difference was observed in DD prevalence and pain intensity according to the number, position, and size of myomas. Deep dyspareunia intensity was higher in women with fundal and anterior myomas than in those with other myoma positions. No significant difference was observed in sexual function among the four study groups. Conclusion(s): Women with uterine myomas do not have increased prevalence or severity of DD; their sexual function is not impaired. [Copyright &y& Elsevier]

Abstract: Introduction: This study aimed to investigate the desired menstrual frequency of subjects without menstruation-related symptoms. Materials and Methods: The study included 270 women of reproductive age. Women with menstrual headache, dysmenorrhea, hypermenorrhea and/or premenstrual syndrome were excluded. The study subjects completed a standardized questionnaire. Results: Of the women, 75.6% declared that menstrual periods interfere with their sexual life, 28.8% preferred not having their menstrual period when at work and 48.4% reported that menstrual periods interfere with practicing sports. Given the choice, 28.5% of the women would desire amenorrhea and 27.8% would prefer a reduction in the frequency of menstrual periods. Of the 152 women desiring to reduce menstrual frequency, 73.0% declared that they would accept to use a drug to reduce menstrual frequency. Conclusions: Over 50% of women without menstruation-related symptoms would like to lessen the frequency of menstrual periods and about 50% of them would desire amenorrhea. [Copyright &y& Elsevier]

Keywords: endometriosis; epigenetic drugs; trichostatin A; valproic acid; toxicity; human endometriotic stromal cells Valproic acid and progestin inhibit lesion growth and reduce hyperalgesia in experimentally induced endometriosis in rats. Endometriosis, epigenetic drugs, trichostatin A, valproic acid, toxicity, human endometriotic stromal cells. [Extracted from the article]

Abstract: Objective: Alterations of the p53 gene have been widely suggested to be relevant to the development of endometrial carcinoma. However, contradictory results have been reported when immunohistochemical determination of p53 expression has been correlated with stage and histological features of the tumours. Study design: Pathology findings were reviewed and p53 immunoperoxidase staining was performed in 240 cases of endometrial carcinoma. Results: Uterine papillary serous adenocarcinomas showed significantly higher p53 overexpression than uterine endometrioid adenocarcinomas (100.0% versus 61.0%, p <0.005). p53 overexpression was significantly higher in the secretory variant (85.7%) than in the typical endometrioid carcinoma (60.0%) (p <0.05). p53 expression did not differ between early (stage I) and advanced (stage II–IV) carcinomas. Likewise, no difference was observed in p53 expression among different architectural grades. The incidence of metastasis to lymph nodes was similar in p53 positive (13.7%) and in p53 negative tumours (12.5%). Conclusion: In the present series, p53 immunostaining did not differ between cases with different FIGO stages or histologic characteristics of the tumours. No simple relationship exists between the immunohistochemical determination of p53 expression and the biological aggressiveness of endometrial carcinomas. [Copyright &y& Elsevier]

Abstract: Myasthenia gravis (MG) often affects women in the second and third decades of life, overlapping with the childbearing years. The course of the disease is unpredictable during pregnancy; however, worsening of symptoms occurs more likely during the first trimester and postpartum. MG can be well managed during pregnancy with relatively safe and effective therapies. Anticholinesterase drugs are the mainstay of treatment, when MG symptoms are not satisfactorily controlled, corticosteroids, azathioprine and in some cases cyclosporin A can be used. Until information is available regarding safety, mycophenolate mofetil should be discontinued before pregnancy. Pregnancy should be avoided in women treated with methotrexate because of the risk of causing typical malformations. Plasmapheresis and intravenous immunoglobulins have been successfully used in the treatment of MG crisis during pregnancy. Caesarean section is recommended only for obstetric reasons; forceps delivery and vacuum extraction are sometimes required. Epidural anesthesia is advised to reduce physical and emotional stress. MG during pregnancy can lead to serious life-threatening conditions, including respiratory insufficiency; therefore, intensive checkups by a gynaecologist and a neurologist are necessary. Women with myasthenia gravis should not be discouraged from conceiving; however, they should discuss their plan for pregnancy with their neurologist and their gynaecologist. [Copyright &y& Elsevier]

Abstract: Objective:: Previous studies did not establish a clear correlation between the presence of endometriosis and the values of body mass index (BMI). Study design:: The BMI of 366 women with endometriosis was compared to that of 248 controls undergoing laparoscopy because of benign gynaecological conditions. Significant differences at univariate analyses were confirmed by using Analysis of covariance (ANCOVA) to control for potential confounding variables. Results:: BMI was significantly lower in women with endometriosis than in controls (p &#60;0.001); this difference was confirmed when the analysis was restricted to subjects with normal BMI (18.50–24.99kg/m2) (p =0.002). 4.8% of control subjects and no woman with endometriosis were obese. No significant difference was observed in the BMI of women with mild (revised classification of the American Fertility Society, rAFS I–II) and severe endometriosis (rAFS III–IV). Conclusion:: Women with endometriosis have lower BMI and are less frequently obese than control subjects. Further studies should investigate the physiopathological basis of decreased BMI in women with endometriosis. [Copyright &y& Elsevier]

Objective: Two-dimensional gel electrophoresis is a powerful method for identifying post-translationally modified molecules in biological fluids. We examined the presence and expression of vitamin D binding protein (DBP) in the peritoneal fluid (PF) and plasma (PL) of women with endometriosis. Methods: PL and PF samples were obtained from 36 women with untreated mild endometriosis (revised classification of the American Fertility Society [rAFS] stage I¿II), 52 women with untreated severe endometriosis (rAFS stage III¿IV), 17 women with endometriosis treated with the oral contraceptive (OC), and 40 controls (infertility, n = 23; tubal sterilization, n = 12; pelvic pain, n = 5). PF and PL samples were analyzed by quantitative, high-resolution 2-dimensional gel electrophoresis. Results: The expression of one DBP isoform (DBPE) in the PF of patients with untreated endometriosis was significantly lower than in the control group (P <.05). The levels of PF DBPE in patients with endometriosis using OC were significantly higher than in women with untreated endometriosis (P <.05). No significant difference was observed in PL DBPE expression between women with and without endometriosis, while it was significantly increased in patients with endometriosis using OC (P <.05). DBP expression was not correlated with the stage of endometriosis (rAFS classification) or the phase of the menstrual cycle. Conclusion: The decreased level of DBPE in the PF but not in PL of women with untreated endometriosis suggests that this molecule may be relevant in the pathogenesis of this disease. [Copyright &y& Elsevier]

Objective: To estimate the expression of haptoglobin (Hp) ? chain isoforms in the peritoneal fluid (PF) and plasma (PL) of women with and without endometriosis. Design: Cross-sectional study. Setting: University hospital. Patient(s): Seventy-two patients with endometriosis and 35 controls. Intervention(s): Peritoneal fluid and PL samples were subjected to two-dimensional gel electrophoresis, silver stained, digitally captured, and compared by semiquantitative computerized analysis. Main Outcome Measure(s): Expression of Hp ? chain isoforms. Result(s): No significant difference was observed in the frequency of expression of the Hp ? chain isoforms between the two groups. One ? chain isoform (Hp?E; molecular weight, 38.40 ± 0.94 kD; and isoelectric point, 5.63 ± 0.17) had significantly higher expression in both the PF and PL of women with endometriosis than in the PF and PL of controls. No significant difference was observed in Hp?E expression between women with mild (revised American Fertility Society [rAFS], stage I–II) and severe (rAFS, stage III–IV) endometriosis. In the control group, Hp?E expression was correlated with the phase of the menstrual cycle. Conclusion(s): Women with endometriosis have higher PF and PL levels of Hp?E. Further investigation should be aimed at producing antibodies against the Hp?E-specific epitopes to determine whether its measurement may improve the clinical diagnosis of endometriosis. [Copyright &y& Elsevier]

Objective: To characterize sexual function among women with endometriosis and deep dyspareunia (DD). Design: Cross-sectional survey. Setting: University teaching hospital. Patient(s): Three-hundred nine women undergoing surgery because of infertility, pelvic pain, or adnexal masses. Three groups of patients with DD were created: women with deep infiltrating endometriosis of the uterosacral ligament (group U), women with endometriosis without uterosacral ligament lesions (group E), and controls (group C). Intervention(s): Laparoscopy. Main outcome measure(s): Sexual function questionnaire. Result(s): The prevalence of DD since the first intercourse was significantly higher among women with endometriosis than in controls (P=.029). When group U was compared with group E and C, the pain score was higher, the number of intercourses per week was reduced, the orgasm was less satisfying, and the patients felt less relaxed and fulfilled after sex. No significant difference was observed in pain score and coital frequency between subjects with monolateral and bilateral lesions of the uterosacral ligament. Conclusion(s): Among subjects with DD, those with deep infiltrating endometriosis of the uterosacral ligament have the most severe impairment of sexual function; the presence of bilateral lesions does not influence the severity of the symptoms. Women with endometriosis have frequently suffered DD during their entire sex lives. [Copyright &y& Elsevier]

Presents a letter to the editor regarding octanoylated and monoctanoylated ghrelin levels in cord blood.