Current strategies in the diagnosis of endometrial cancer

Purpose

Endometrial cancer is the most common gynecological malignancy in developed countries. There are no uniform recommendations for endometrial cancer screening in the general population. Therefore, it is of paramount importance that the primary physician profoundly understands, and is familiar with the methods for prevention and early detection of endometrial cancer. The aim of this review is to provide the primary physician with a toolbox to reach these goals.

Methods

We performed a systemic review to summarize the current strategies to diagnose and prevent endometrial cancer. Many published articles from the last years were identified and included.

Results

A systematic review that summarizes the important subjects in the diagnosis and prevention of endometrial cancer.

Conclusion

Maintaining a high index of suspicion and obtaining endometrial biopsies from all suspected patients is the key for achieving a timely diagnosis.

     

Efficacy of dienogest in improving pain in women with endometriosis: a 12-month single-center experience

Purpose

Dienogest has recently been marketed as a medical treatment for endometriosis. Given the recent introduction on the market of Dienogest, little data are available regarding its effectiveness in routine clinical practice.

Methods

The study is an observational, single-center, cohort study. Eligible was women with a surgical diagnosis of endometriosis dating back <24 months or a clinical/instrumental diagnosis of endometriosis and endometriosis-associated pelvic pain score of at least 40 mm on a 100-mm visual analog scale (VAS) at start of treatment and who had been taking Dienogest 2 mg once daily treatment at the time of study entry for no more than 30 days, consecutively observed between September 2013 to September 2014. In accordance with routine practice, women came back for clinical assessment and evaluation of pain after 1 (V1), 3 (V2), and 12 (V3) months.

Results

A total of 132 women were enrolled in the study. A total of 21 of the enrolled patients were released from the study during follow-up due to adverse effects. The mean pelvic pain VAS score at baseline was 8.9 (SD 1.3). The corresponding values were 6.7 (SD 3.2) and 5.7 (SD 3.7) for dyspareunia and dyschezia. The mean VAS scores progressively and significantly decreased to 0.9 (SD 1.6) for pelvic pain, 1.4 (SD 2.1) for dyspareunia and 0.2 (SD 0.9) for dyschezia, respectively, 12 months after start of treatment.

Conclusion

This study confirms that in routine clinical practice, Dienogest 2 mg is an effective and well-tolerated treatment for endometriosis-related pain in women with endometriosis.

     

Dienogest Versus Leuprolide Acetate for Recurrent Pelvic Pain Following Laparoscopic Treatment of Endometriosis

Objective

To compare the efficacy and safety of dienogest (DNG) with depot leuprolide acetate (LA) in patients with recurrent pelvic pain following laparoscopic surgery for endometriosis.

Design

Prospective randomized trial.

Setting

Zagazig University hospitals, Egypt.

Patients

Two hundred and forty-two patients with recurrent pelvic pain following laparoscopic surgery for endometriosis.

Intervention

Dienogest (2 mg/day, orally) or depot LA (3.75 mg/4 weeks, intramuscularly) for 12 weeks.

Main Outcome Measures

A visual analogue scale was used to test the intensity of pain before and after the end of treatment.

Results

There was highly significant reduction in pelvic pain, back pain and dyspareunia in both groups with mean of difference in dienogest group (28.7?±?5.3, 19.0?±?4.3 and 20.0?±?3.08 mm, respectively) and in LA group (26.2?±?3.01, 19.5?±?3.01 and 17.9?±?2.9 mm, respectively). The most frequent drug-related adverse effects in dienogest group were vaginal bleeding and weight gain (64.5 and 10.8%, respectively) which were significantly higher than LA group (21.5 and 3.3%, respectively). While the most frequent drug-related adverse effects in LA group were hot flushes and vaginal dryness (46.3 and 15.7%, respectively) which were significantly higher than dienogest group (15.7 and 3.3%, respectively).

Conclusion

Daily dienogest is as effective as depot LA for relieving endometriosis-associated pelvic pain, low back pain and dyspareunia. In addition, dienogest has acceptable safety, tolerability and lower incidence of hot flushes. Thus, it may offer an effective and well-tolerated treatment in endometriosis.

     

Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies

Purpose

Platelets have multiple functions and they also play an important role in malignancies. Elevated platelet count and thrombocytosis at the time of diagnosis in patients with many solid tumors correlates with prognosis and is associated with poor survival. The aim of the following report is to review the literature concerning elevated platelet count and thrombocytosis in gynecologic malignancies.

Method

A PubMed search of all English literature peer-reviewed publications was performed containing the terms elevated platelet count or thrombocytosis and vulvar cancer, cervical cancer, endometrial cancer, and ovarian cancer. All studies published until December 31, 2015, were included in the following review.

Results

A pretreatment elevated platelet count and thrombocytosis have been shown to be associated with a poor prognosis in many studies of gynecologic malignancies with the exception of vulvar carcinoma.

Conclusion

Since elevated platelet count and thrombocytosis may be prevented by blocking thrombopoietic cytokines, their assessment may, in the future, be of therapeutic significance.

     

Fertility outcome after treatment of retained products of conception: a systematic review

Background

Treatment of retained products of conception (RPOC) can be expectant, medical or operative. Surgical removal of RPOC may lead to intrauterine adhesions (IUA) and Asherman’s syndrome.

Objective

To evaluate how treatment options for RPOC affect future fertility by means of a systematic review.

Search strategy

MEDLINE, EMBASE, The Cochrane Library, and clinical trial registers were searched, and reference lists were scanned.

Selection criteria

Randomised controlled trials (RCT) comparing different treatment options for RPOC (conservative, medical or surgical treatment, including curettage and/or hysteroscopic techniques, with or without application of anti-adhesion therapy), in women of reproductive age, were eligible for inclusion.

Data collection and analysis

Reviewers independently performed data extraction and quality of evidence assessment. For dichotomous variables, results were presented as risk ratio (RR) with 95% CI.

Main results

Two studies were included. Nonsignificant differences were observed between the use of an anti-adhesion barrier gel versus no treatment after operative hysteroscopy in IUAs (RR 0.32, 95% CI 0.04 to 2.80, P value?=?0.30) and clinical pregnancy (RR 2.22, 95% CI 0.67 to 7.42, P value?=?0.19), and between hysteroscopic morcellation versus loop resection in IUAs (RR 0.86, 95% CI 0.06 to 13.12, P value?=?0.91).

Conclusion

There is insufficient evidence on how different treatment options for RPOC affect future reproductive outcomes. Results from ongoing RCTs are needed to guide clinicians towards choosing the best treatment.

     

Feasibility of hysteroscopic endometrial polypectomy using a new dual wavelengths laser system (DWLS): preliminary results of a pilot study

Purpose

Currently, endometrial polyps may be successfully treated in an outpatient setting with 5 Fr mechanical and bipolar instruments. Our aim is to evaluate the benefits of minimally invasive techniques in hysteroscopy, focusing on the use of a new dual wavelengths laser system in the treatment of endometrial polyps in an outpatient setting.

Methods

Between September 2012 and December 2014, all consecutive patients of reproductive and menopausal age with ultrasound diagnosis of endometrial polyp with maximum diameter ≤2.5 cm were eligible to participate in a prospective study. They underwent a hysteroscopic procedure with excision of the polyp using a new dual wavelengths laser system. All procedures were performed on an outpatient basis without anesthesia.

Results

Laser polypectomy was successfully performed in 219 out of 225 (97.3%). Success of surgery was not influenced by the initial location of polyp. No main complications were reported during or immediately after the procedure. 6 and 12 months follow-up with ultrasound scan did not show any persistence or recurrence of the pathology.

Conclusions

Our preliminary findings seem to support the safety and the effectiveness of the laser hysteroscopic endometrial polypectomy. However, further studies are mandatory to validate its use in daily hysteroscopic practice.

     

Implantationsversagen: Embryo,Endometrium oder beides?

Background

Despite advanced techniques in reproductive medicine, about 10% of couples treated with assisted reproductive technology (ART) experience recurrent implantation failure (RIF). Besides other general maternal factors, the role of the embryo itself and the endometrium are now discussed.

Objectives

The diagnostic possibilities to examine the embryo and the endometrium in RIF patients are reviewed and discussed.

Materials and methods

Current, relevant research and review articles concerning embryological and endometrial factors are discussed.

Results

In addition to risk factors such as hereditary and acquired thrombophilia or anatomical abnormalities, embryonic and endometrial factors have come into focus. Nowadays, the chromosomal composition and morphological development of the embryo can be examined in more detail. Using new techniques, the properties of the endometrium for implantation can be analyzed from a genetically and immunological/infectiological perspective. Chronic endometritis and alterations of natural killer cells in the endometrium are discussed as new risk factors for RIF.

Conclusions

Couples should be educated about success rates before ART treatment. Several unsuccessful fertility treatments are not only a financial but also an extreme psychological burden. Many of the current risk factors for RIF have been studied only on the basis of a small study population. Before use in clinical routine, new diagnostic procedures should be investigated in prospective studies with a sufficient number of cases and a uniformly defined patient collective. According to the current state of knowledge, both embryonic and endometrial factors can be responsible for the development of RIF.

     

Feasibility of sentinel lymph node fluorescence detection during robotic laparoendoscopic single-site surgery in early endometrial cancer: a prospective case series

Background

In the last few decades, the introduction of technologies such as single-site surgery, robotics, and sentinel lymph node detection has reduced invasiveness in the treatment and staging of endometrial cancer patients. The goal of the present prospective cohort study is to evaluate the feasibility of lymph node fluorescence detection with robotic single-site approach in low-risk endometrial cancer.

Results

Fifteen non consecutive low-risk endometrial atypical hyperplasia (EAH) patients underwent sentinel lymph node (SLN) biopsy and total hysterectomy utilizing the Da Vinci Si Single-Site Surgical. System and Firefly 3D imaging. Indications for surgery included eight (53.3%) IA FIGO stage G1 EC, three (20%) IA FIGO stage G2 EC, and four (26.6%) EAH. Mean operative time was 155 min (range 112–175). One vaginal laceration was the only perioperative complication encountered, and all patients were discharged within 48 h of surgery.SLN was detected in 86.6% of cases; 1/29 (3.4%) SLN results were positive for isolated tumor cells (ITCs) at immunohistochemical analysis.

Conclusions

The present study demonstrates the feasibility and applicability of robotic single-site approach with SLN fluorescence detection for the staging of low-risk endometrial cancer.

     

Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis

Purpose

To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes.

Methods

A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation.

Results

Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR?=?0.48, 95% CI 0.31–0.77, P?=?0.002), but there was no significant difference in the ongoing pregnancy rate between groups.

Conclusion

Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.

     

A long-standing incomprehensible matter of obstetrics: meconium-stained amniotic fluid,a new approach to reason

Objective

We sought to determine whether meconium-stained amniotic fluid is based on chronic hypoxia or not? In case of chronic hypoxia, higher red blood cell (Rbc) count and/or total hemoglobin levels (Hgb) and/or higher fetal hemoglobin (HbF) and/or lower adult hemoglobin (HbA) levels were expected when compared with controls.

Design

Case–control study.

Setting

Obstetric unit of a tertiary ministry of health hospital.

Sample

Fifty singleton pregnancies with meconium-stained amniotic fluid and 50 singleton pregnancies with clear amniotic fluid at all stages of labor.

Methods

Umbilical cord blood samples were collected for determination of total blood parameters and hemoglobin electrophoresis.

Main outcome measures

Red blood cell count, total hemoglobin, fetal and adult hemoglobin contents (HbF and HbA).

Results

Red blood cell count, total hemoglobin, fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents were not different between meconium stained and clear amniotic fluid groups.

Conclusion

These results suggest that meconium passage may not be associated with chronic fetal hypoxia as demonstrated by similar red blood cell count, total hemoglobin values and fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents.

     

Knockdown of E-cadherin expression of endometrial epithelial cells may activate Wnt/β-catenin pathway in vitro

Purpose

E-cadherin, a transmembrane glycoprotein mediating Ca²⁺-independent homotypic cell–cell adhesion in epithelial cell, plays an essential role in metastasis. It has been postulated that E-cadherin downregulation is a crucial mechanism in the pathogenesis of endometriosis. To evaluate the effect on the cell behavior after knockdown of E-cadherin gene (CDH1) in cultured human endometrial epithelial cells (EECs) isolated from normal endometrium.

Methods

EECs were isolated from the endometrial tissues of fertile woman who underwent total hysterectomy due to cervical intraepithelial neoplasia III. CDH1 expression was knocked down by small hairpin RNA. The EECs transfected with empty vector served as control. Transwell assay was used to test EECs migration or invasion. qRT-PCR and western blot were used to detect mRNA and protein levels.

Results

The results showed that knockdown of E-cadherin expression can increase cell migration and invasion, and up-regulate mRNA and protein levels of β-catenin, cyclinD1, and c-myc.

Conclusions

Down-regulation of E-cadherin expression may activate the Wnt/β-catenin pathway in endometrial cells, which may together participate in the occurrence of endometriosis.

     

The effects of GnRH antagonist on the endometrium of normally menstruating women

Purpose

To study the effects of GnRH antagonist (ganirelix-Orgalutran®) on the endometrium of regularly menstruating women.

Materials and methods

Prospective, self-controlled study. The thirty-five volunteers were studied for two cycles: one as a control and the other, GnRH antagonist-treated cycles in which ganirelix 0.25 mg/d was given daily for 3 days, starting when the largest follicle reached 15 mm. In both cycles, serum estradiol, LH and endometrial thickness were measured when the largest follicle was ≥18 mm. Endometrial biopsy was performed on day 6 after ovulation for histological dating and morphometric study.

Results

No statistical differences between histological dating and the endometrial thickness in the control and GnRH antagonist-treated cycles. All morphometric parameters were also not different. Serum estradiol and LH levels were significantly lower in GnRH antagonist-treated cycles.

Conclusion

GnRH antagonist has no effect on the endometrium of regularly menstruating women as assessed by either histological dating or morphometric analysis.

     

Chronic Endometritis and Recurrent Pregnancy Loss

Purpose of Review

Chronic endometritis is generally an asymptomatic condition typically diagnosed by the histopathological presence of plasma cell infiltration in the endometrial stromal compartment. Emerging data suggests that chronic endometritis may be a cause of recurrent pregnancy loss (RPL).

Recent Findings

Chronic endometritis is prevalent in cases of otherwise unexplained recurrent pregnancy loss. Treatment appears to lead to improved pregnancy outcomes in subsequent pregnancies. The use of CD138 immunohistochemistry as a supplement to traditional hematoxylin and eosin staining of plasma cells increases the detection rate of chronic endometritis.

Summary

Chronic endometritis is emerging as a treatable cause of RPL.

     

Termination of pregnancy due to fetal central nervous system abnormalities performed after 24 weeks’ gestation: survey of 57 fetuses from a single medical center

Objective

Postoperative cognitive decline (POCD) is known to occur quite frequently after a cardiac surgery, especially in older population. Few studies specifically focused on its incidence and characteristics in gynecological setting.

Methods

Current opinions and future applications of POCD studies in gynecological setting have been discussed.

Result

There are still many questions and issues about POCD in gynecological setting that remain unanswered as well as numerous research fields that have not been still explored. In particular, from this article emerges the need of further studies in gynecological setting focusing on: (a) the evaluation of long-term effect of POCD (e.g. over 3 months after surgery); (b) elderly population; (c) a wide range of cognitive functions (memory, attention, concentration, orientation, etc.); (d) the evaluation of risk and protective factors for subsequent POCD development; (e) the relationships between POCD and previous psychological or neuroendocrine factors; (f) the difference on POCD outcomes between different anaesthesia and disorders.

Conclusion

Promoting studies on this topic is significant for the reduction of sociosanitary costs, mortality rates, social dependences and the likelihood of comorbidity.

     

G-CSF and stem cell therapy for the treatment of refractory thin lining in assisted reproductive technology

Purpose

The study aims to describe two promising therapeutic options for resistant “thin” endometrium in fertility treatment: granulocyte colony-stimulating factor (G-CSF) and stem cell therapy.

Methods

A review of the scientific literature related to patients with thin endometrium undergoing fertility treatment.

Results

Sufficient endometrial growth is fundamental for embryo implantation. Whether idiopathic or resulting from an underlying pathology, a thin endometrium of <7 mm is associated with lower probability of pregnancy; however, no specific thickness excludes the occurrence of pregnancy. We specifically reviewed two relatively new treatment options for resistant thin lining: intrauterine G-CSF and stem cell therapy. The majority of the reviewed trials showed a significant benefit for intrauterine G-CSF infusion in improving endometrial thickness and pregnancy rates. Early results of stem cell therapy trials seem promising.

Conclusions

EMT <7 mm is linked to lower probability of pregnancy in assisted reproductive technology. Intrauterine G-CSF infusion appears to be a potentially successful treatment option for resistant cases, while stem cell therapy seems to be a promising new treatment modality in severely refractory cases.

     

Cumulative live birth and surplus embryo incidence after frozen-thaw cycles in PCOS: how many oocytes do we need?

Purpose

This study aimed to evaluate the cumulative live birth rate (CLBR) and surplus embryo rate of polycystic ovarian syndrome (PCOS) patients during in vitro fertilization and embryo transfer (IVF-ET) treatment.

Methods

In this retrospective cohort study, we analyzed 1142 PCOS patients who underwent first IVF in our institution between January 2011 and December 2014. All patients were categorized into five groups according to the number of oocytes retrieved. Main outcomes include CLBR and surplus embryo rate.

Results

A strong correlation was observed between number of oocytes retrieved and CLBR as well as surplus embryo rate in PCOS patients. CLBR was elevated with the increasing number of oocytes and plateaued when oocyte number was up to ten, whereas the surplus embryo rate steadily increased in line with the increase of oocyte number. Patients transferred with frozen embryos showed higher CLBR and LBR during first ET than patients transferred with fresh embryos.

Conclusions

For PCOS patients, retrieving more than ten oocytes leads to no significant benefit to CLBR but generates surplus embryos. Thus, moderate ovarian stimulation should be reconsidered during IVF treatment.

     

Zykluscomputer und -Apps

Background

New cycle computers and fertility apps appear on the market almost daily, which promise to support women in the determination of their fertile days.

Objective and methods

In the study the credibility of cycle computers and apps was assessed according to certain criteria. The various cycle computers and apps were assessed based on the results of own published studies on this topic and publications on determination of the fertile window.

Results

For some of the cycle computers own results are available, sometimes in comparative studies. New ways of recording intravaginal temperatures and continuous temperature measurement procedures have made the development of new devices possible but objective results generated by prospective studies on effectiveness are not available. For hormone computers efficiency data reported in the literature from Europe and the USA differ, sometimes greatly but comparative prospective efficiency studies are practically completely lacking. There is a similar situation with devices for measuring resistance. With apps there are principally two different versions available on the market: calender and symptom-based apps; however, no results from good effectiveness studies are available.

Conclusion

Prospective efficiency studies must still be carried out for the majority of these developments. Otherwise the user will be consciously misled.

     

Association between ERCC2 rs13181 polymorphism and ovarian cancer risk: an updated meta-analysis with 4024 subjects

Background

Genetic variants in the excision repair cross-complimentary group 2 (ERCC2) gene may affect individual susceptibility to cancer by modulating the capability of DNA damage repair. However, the current studies concerning the association of ERCC2 rs13181 polymorphism with ovarian cancer risk provided inconsistent evidence.

Methods

This study was to quantitatively summarize the evidence from the individual studies electronically retrieved by a meta-analysis.

Results

Totally, nine eligible case–control studies with 1333 cases and 2691 controls were included for the concerned association. Overall, a significant association between ERCC2 gene rs13181 polymorphism and increased risk of ovarian cancer was revealed (CC+AC vs. AA: OR 1.44, 95% CI 1.11–1.86; CC vs. AA: OR 2.12, 95% CI 1.14–3.97). Similarly, in the subgroup analyses, such association was also evident in non-Caucasian population and hospital-based studies. Noteworthily, the recombined analysis with a significant decrease in between-heterogeneity represented a significant association of the variant with increased risk of ovarian cancer after excluding the individual study not in agreement with HWE.

Conclusion

The present study suggests that the ERCC2 gene rs13181 polymorphism might be associated with increased risk of ovarian cancer.