Risks factors for anastomotic leakage in advanced ovarian cancer: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to summarise the available evidence on the pre- and intra-operative risk factors for anastomotic leakage (AL) after bowel resection and anastomosis for ovarian cancer (OC). STUDY DESIGN: We searched online databases from Pubmed, Scopus, ScienceDirect, and Cochrane Library from inception to October 2020. Pre- and intra-operative risk factors for AL were considered as the primary outcomes. Research heterogeneity and bias were evaluated by I2 and by the Newcastle Ottawa scale, respectively. The study was registered with PROSPERO, CRD42018095225. RESULTS: The overall AL rate after OC surgery (median ± SD) was 5.3 ± 12% (277 AL on 5178 anastomoses). Thirteen non-randomised studies were included in the meta-analysis enrolling a total of 3274 patients. Pre albumin level ≤ 3 gr/dl, multiple bowel resections and primary cytoreductive surgery were associated with a significantly high risk of AL with a pooled OR of 5.29 (95% CI: 1.51-18.59), OR = 4.4 (95% CI: 1.19-16.66) and OR = 1.71 (95% CI: 1.05-2.77), respectively. Optimal cytoreduction, ASA score, ascites, and protective stoma were not associated with an increased risk of AL. CONCLUSION: Based on the best available evidence, preoperative albumin level <3 gr/dl, multiple bowel resections and primary cytoreductive surgery were associated with an increased risk for AL after bowel surgery for OC.

Endometrial scratching for infertile women undergoing a first embryo transfer: a systematic review and meta-analysis of published and unpublished data from randomized controlled trials.

OBJECTIVE: To investigate endometrial scratch injury (ESI) as an intervention to improve IVF outcome in women undergoing a first ET. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing a first fresh/frozen embryo transfer. INTERVENTION(S): We included published and unpublished data from randomized controlled trials in which the intervention group received ESI and controls received placebo or no intervention. Pooled results were expressed as relative risk (RR) with 95% confidence interval (CI). The review protocol was registered in PROSPERO to start the data extraction (CRD42018087786). MAIN OUTCOME MEASURE(S): Ongoing pregnancy/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), miscarriage rate (MR), and ectopic pregnancy rate (EPR). RESULT(S): Seven studies were included (1,354 participants). We found a nonsignificant difference between groups in terms of OPR/LBR, CPR, MR, MPR, and EPR. Subgroup analysis found that ESI on the day of oocyte retrieval (achieved by a Novak curette) reduced OPR/LBR (RR 0.31, 95% CI 0.14-0.69) and CPR (RR 0.36, 95% CI 0.18-0.71), whereas ESI during the cycle preceding ET (performed through soft devices) had no effect on OPR/LBR and CPR. No difference in the impact of ESI was observed between fresh and frozen embryo transfer. CONCLUSION(S): Current evidence does not support performing ESI with the purpose of improving the success of a first ET attempt.

Use of pre-operative imaging for symptomatic uterine myomas during pregnancy: a case report and a systematic literature review.

PURPOSE: Uterine fibroids (UFs) occur in 10% of pregnancies and may lead to severe maternal-fetal complications, mainly depending on UFs characteristics and the distance to the uterine cavity (UC). When symptomatic, UFs are managed medically. Nevertheless, in about 2% of cases, surgery becomes necessary. Entry into the UC should be avoided during myomectomy. Consequentially, pre-operative assessment of this risk could be beneficial. Ultrasonography (US) represents the gold standard for UFs assessment; however, scarce evidence has been produced to assess the role of magnetic resonance imaging (MRI). The aim of the present study was to summarize current evidence about the pre-operative use of imaging techniques for UFs during pregnancy. METHODS: A systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect and the Cochrane Library, including case reports and case series. A case report was also discussed. We collected data regarding patients, imaging assessment, UFs characteristics, surgical information, timing and modality of delivery. RESULTS: According to our search strategy, 66 articles were selected and 210 patients were included. US assessment was reported in 36 (17%) cases. MRI was reported in 10 (4.7%) cases. Only in one case, MRI was used to measure the distance between UFs and UC. CONCLUSION: US allows an adequate pre-operative evaluation of anterior, submucosal or pedunculated symptomatic UFs in pregnancy. However, compared to US, MRI may provide a more accurate evaluation of multiple, large, intramural or posterior UFs and could measure the distance between UFs and UC more accurately.

Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition.

PURPOSE: Gynaecological cancer management in older people represents a current challenge. Therefore, in the present paper, we aimed to gather all the evidence reported in the literature concerning gynecological cancers in the elderly, illustrating the state of art and the future perspectives. METHODS: We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS and Grey literature (Google Scholar; British Library) from January 1952 to May 2017, using the terms "ovarian cancer", "endometrial cancer", "cervical cancer", "gynecological cancers" combined with 'elderly', 'cancer', 'clinical trial' and 'geriatric assessment'. RESULTS: The search identified 81 citations, of which 65 were potentially relevant after initial evaluation and met the criteria for inclusion and were analyzed. We divided all included studies into three different issue: "Endometrial cancer", "Ovarian cancer" and "Cervical cancer". CONCLUSIONS: The present literature review shows that, in spite of the higher burden of comorbidities, elderly patients can also benefit from standard treatment to manage their gynecological cancers. It is important to overcome the common habit of undertreating the elderly patients because they are more fragile and with a lower life expectancy than their younger counterpart. Further trials with elderly women are warranted.

Endometrial scratch injury for women with one or more previous failed embryo transfers: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate endometrial scratch injury (ESI) as an intervention to improve IVF outcome in women with a history of ET failure. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing IVF after one or more failed ET. INTERVENTION(S): We included all randomized controlled trials of women undergoing IVF after one or more failed ET, where the intervention group received ESI and controls received placebo or no intervention. Pooled results were expressed as relative risk (RR) with a 95% confidence interval (95% CI). The review protocol was registered in PROSPERO before starting the data extraction (CRD42017082777). MAIN OUTCOME MEASURE(S): Live birth rate (LBR), clinical pregnancy rate (PR), multiple PR, miscarriage rate, ectopic pregnancy (EP) PR. RESULT(S): Ten studies were included (1,468 participants). The intervention group showed higher LBR (RR 1.38, 95% CI 1.05-1.80) and clinical PR (RR 1.34, 95% CI 1.07-1.67) in comparison to controls, without difference in terms of multiple PR, miscarriage rate, and EP PR. Double luteal ESI with pipelle was associated with the greatest effect on LBR (RR 1.54, 95% CI 1.10-2.16) and clinical PR (RR 1.30, 95% CI 1.03-1.65). The ESI was beneficial for patients with two or more previous ET failure, but not for women with a single previous failed ET. No effect was found in women undergoing frozen-thawed ET cycles. CONCLUSION(S): The ESI may improve IVF success in patients with two or more previous ET failures undergoing fresh ET. The ESI timing and technique seem to play a crucial role in determining its effect on embryo implantation.

The Role of Oxidative Stress and Membrane Transport Systems during Endometriosis: A Fresh Look at a Busy Corner.

Endometriosis is a condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to a chronic inflammatory reaction. It is one of the most widespread gynecological diseases with a 10-15% prevalence in the general female population, rising up to 30-45% in patients with infertility. Although it was first described in 1860, its etiology and pathogenesis are still unclear. It is now accepted that inflammation plays a central role in the development and progression of endometriosis. In particular, it is marked by an inflammatory process associated with the overproduction of an array of inflammatory mediators such as prostaglandins, metalloproteinases, cytokines, and chemokines. In addition, the growth and adhesion of endometrial cells in the peritoneal cavity due to reactive oxygen species (ROS) and free radicals lead to disease onset, its ensuing symptoms-among which pain and infertility. The aim of our review is to evaluate the role of oxidative stress and ROS in the pathogenesis of endometriosis and the efficacy of antioxidant therapy in the treatment and mitigation of its symptoms.

miRNA expression for early diagnosis of preeclampsia onset: hope or hype?

PURPOSE: Preeclampsia (PE) is a multi-systemic disease characterized by hypertension, proteinuria and other typical signs that can negatively affect the development of pregnancy. The outcome of the disease is strongly linked to the possibility of early diagnosis, in order to prevent the clinical manifestations. Pathogenesis is still unknown, although abnormalities of placenta development linked to angiogenesis alterations and abnormal trophoblastic invasion seem to be involved, corroborating the epigenetic theory. Basing on these elements, this review aims to summarize the possible role of miRNAs in PE onset, both as increased or decreased expression in placenta or as maternal serum markers. MATERIALS AND METHODS: We considered eligible all original articles (randomized, observational and retrospective studies), published between 2000 and 2016 in English language, about miRNA expression in placenta and maternal serum levels both in uncomplicated and PE pregnancies. RESULTS: Available data support a direct correlation between selective miRNAs high/low expression in placenta and maternal serum, although it is still unclear how these epigenetic changes may affect the development and outcomes of the disease. CONCLUSION: Future studies should aim to identify a robust panel of miRNA markers in order to predict the onset and development of PE.

Hysteroscopic Morcellation of Submucous Myomas: A Systematic Review.

Hysteroscopic surgery is the actual gold standard treatment for several types of intrauterine pathologies, including submucous myomas (SMs). To date, the availability of Hysteroscopic Tissue Removal systems (HTRs) opened a new scenario. Based on these elements, the aim of this article is to review the available evidence about HTRs for the management of SMs. We included 8 papers (3 prospective studies and 5 retrospective studies). A total of 283 women underwent intrauterine morcellation of SM: 208 were treated using MyoSure and 75 using Truclear 8.0. Only 3 articles reported data about procedures performed in outpatient/office setting. Only half of the included studies included type 2 SMs. HTRs significantly reduced operative time compared to traditional resectoscopy in some studies, whereas others did not find significant differences. Despite the availability of few randomized controlled trials and the cost of the instrument, according to our systematic review, the use of HTRs seems to be a feasible surgical option in terms of operative time and complications. Nevertheless, the type of SM still remains the biggest challenge: type 0 and 1 SMs are easier to manage with respect to type 2, reflecting what already is known for the "classic" hysteroscopic myomectomy.

Anxiety and depression in patients with endometriosis: impact and management challenges.

Endometriosis is one of the most common gynecological diseases and affects ~10% of women in reproductive age. The most common clinical signs of endometriosis are menstrual irregularities, chronic pelvic pain (CPP), dysmenorrhea, dyspareunia and infertility. Symptoms of endometriosis often affect psychological and social functioning of patients. For this reason, endometriosis is considered as a disabling condition that may significantly compromise social relationships, sexuality and mental health. Considering this point, the aim of this narrative review is to elucidate the impact of anxiety and depression in the management of women with endometriosis. Psychological factors have an important role in determining the severity of symptoms, and women who suffer from endometriosis report high levels of anxiety, depression and other psychiatric disorders. In addition, endometriosis is one of the most important causes of CPP; women with endometriosis suffer from a wide range of pelvic pain such as dysmenorrhea, dyspareunia, nonmenstrual (chronic) pelvic pain, pain at ovulation, dyschezia and dysuria. Several studies have underlined the influence of CPP on quality of life and psychological well-being of women with endometriosis. Data suggest that the experience of pelvic pain is an important component of endometriosis and may significantly affect emotive functioning of affected women. It has been demonstrated that high levels of anxiety and depression can amplify the severity of pain. Further studies are needed to better understand the relationship between psychological factors and perception of pain. Treatment of endometriosis may be hormonal or surgical. Surgery is the primary treatment for more severe forms of endometriosis. There are few data in the literature about the influence of psychological factors and psychiatric comorbidities on the effectiveness of treatments. It is important to evaluate the presence of previous psychiatric diseases in order to select the most appropriate treatment for the patient.

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives.

Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2-5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50-80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms "uterine carcinosarcoma", "uterine Malignant Mixed Müllerian Tumors", "target therapies", "angiogenesis therapy", "cancer stem cell therapy", "prognostic biomarker", and "novel antibody-drug". Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

Do miRNAs Play a Role in Fetal Growth Restriction? A Fresh Look to a Busy Corner.

Placenta is the crucial organ for embryo and fetus development and plays a critical role in the development of fetal growth restriction (FGR). There are increasing evidences on the role of microRNAs (miRNAs) in a variety of pregnancy-related complications such as preeclampsia and FGR. More than 1880 miRNAs have been reported in humans and most of them are expressed in placenta. In this paper, we aimed to review the current evidence about the topic. According to retrieved data, controversial results about placental expression of miRNAs could be due (at least in part) to the different experimental methods used by different groups. Despite the fact that several authors have demonstrated a relatively easy and feasible detection of some miRNAs in maternal whole peripheral blood, costs of these tests should be reduced in order to increase cohorts and have stronger evidence. In this regard, we take the opportunity to solicit future studies on large cohort and adequate statistical power, in order to identify a panel of biomarkers on maternal peripheral blood for early diagnosis of FGR.

Safe introduction of ancillary trocars in gynecological surgery: the "yellow island" anatomical landmark.

AIM: This technical note aims to suggest a safe introduction of ancillary trocars in gynaecological surgery, in order to prevent inferior epigastric artery damage. MATERIAL OF STUDY: We performed a narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Among the different techniques, the identification of the "yellow island" as anatomical landmark seems to be a useful aid to avoid complication. This particular landmark is identified taking the lateral third of a line between the anterior superior iliac spine and the umbilicus as reference points, by a subperitoneal accumulation of adipose tissue located in that area. DISCUSSION: "Yellow island" could be considered a safe place for trocars introduction because epigastric artery never runs there, even in patients with particular anatomical variants. This technique is particularly useful in obese patients, in which "yellow island" appears to be more evident respect to lean ones. Furthermore, the use of "open" trocars insertion may reduce the possibility of epigastric artery lesions respect to "Verres needle technique". CONCLUSION: The identification of the "yellow island" anatomical landmark could be considered an useful aid for the safe introduction of ancillary trocars in gynaecological surgery. KEY WORDS: Gynaecology, Laparoscopic surgery, Trocars placement.

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation.

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.

How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin.

Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.